Cell-free DNA and preoperative chemoradiotherapy for rectal cancer: a systematic review

Abstract

Background

Preoperative chemoradiotherapy is the standard of care for patients with locally advanced rectal cancer, yet valid circulating biomarkers are lacking. We aimed at systematically reviewing the literature of cell-free DNA and locally advanced rectal cancer.

Methods

A systematic literature search was performed. We retrieved papers reporting a correlation between a clinical outcome and cell-free DNA for patients receiving chemoradiotherapy for locally advanced rectal cancer.

Results

We included nine studies of a total of 615 patients. Only single-arm studies were identified, analyzing either the total level of cell-free DNA or tumor-specific DNA. Despite differences in the methodology and outcomes, eight of the nine studies showed a correlation between cell-free DNA and a clinical outcome.

Conclusions

Cell-free DNA might hold prognostic and predictive information for patients with locally advanced rectal cancer receiving preoperative chemoradiotherapy; although, firm conclusions are limited by the heterogeneity in this field.

https://ift.tt/2PcIJRE

Succeeding in New Cardiac Bundles: Lessons from History, Directions for the Future

No abstract available

https://ift.tt/2QxmI1C

GROmaρs: a GROMACS-based toolset to analyse density maps derived from molecular dynamics simulations

We introduce a computational toolset, named GROmaρs, to obtain and compare time-averaged density maps from molecular dynamics (MD) simulations. GROmaρs efficiently computes density maps, by fast multi-Gaussian spreading of atomic densities onto a 3-dimensional grid. It complements existing map-based tools by enabling spatial inspection of atomic average localization during the simulations. Most importantly, it allows the comparison between computed and reference maps (e.g. experimental), through calculation of difference maps, and local and time-resolved global correlation.

https://ift.tt/2ACiuij

Highly efficient protein-free membrane fusion: a giant vesicle study

Membrane fusion is a ubiquitous process in biology and is a prerequisite for many intracellular delivery protocols relying on the use of liposomes as drug carriers. Here, we investigate in detail the process of membrane fusion and the role of opposite charges in a protein-free lipid system based on cationic liposomes (LUVs) and anionic giant unilamellar vesicles (GUVs) composed of different palmitoyloleoylphosphatidylcholine:palmitoyloleoylphosphatidylglycerol (POPC:POPG) molar ratios. By using a set of optical microscopy- and microfluidics-based methods, we show that liposomes strongly dock to GUVs of pure POPC or low POPG fraction (up to 10 mol%), in a process mainly associated with hemifusion and membrane tension increase, commonly leading to GUV rupture.

https://ift.tt/2ACiuPl

Visualization of Dynamic Sub-microsecond Changes in Membrane Potential

Direct observation of rapid membrane potential changes is critical to understand how complex neurological systems function. This knowledge is especially important when stimulation is achieved through an external stimulus meant to mimic a naturally-occurring process. To enable exploration of this dynamic space, we developed an all-optical method for observing rapid changes in membrane potential at temporal resolutions of 25 ns. By applying a single 600 ns electric pulse, we observe sub-microsecond, continuous membrane charging and discharging dynamics.

https://ift.tt/2TWH7PP

Interplay between membrane curvature and cholesterol: Role of palmitoylated caveolin-1

Caveolin-1 (cav-1) is an important player in cell signaling and endocytosis that has been shown to co-localize with cholesterol-rich membrane domains. Experimental studies with varying cav-1 constructs have suggested that it can induce both cholesterol clustering and membrane curvature. Here, we probe the molecular origin of membrane curvature and cholesterol clustering by cav-1 using coarse-grain molecular dynamics simulations. We have performed a series of simulations of a functionally important cav-1 construct, comprising of the membrane interacting domains and a C-terminal palmitoyl tail.

https://ift.tt/2U3u133

Organ Preservation Protocols in T4 Laryngeal Cancer: a Review of the Literature

Abstract

Population-based studies indicate that chemoradiation has become the most popular treatment for advanced laryngeal cancers; however, by extrapolating trial results to the general population, several issues have emerged, such as reduced overall survival, non-functional laryngeal preservation, and poor response to treatment. Although included in these trials, T4 laryngeal and hypopharyngeal cancers with cartilage invasion formed a small percentage of these patients and questions over whether they were appropriately staged remain unanswered. Literature on the use of chemoradiation in this set of patients, including the challenges, treatment considerations, and factors predicting response to treatment and outcomes, was reviewed. Current evidence indicates that all patients of T4 laryngeal and hypopharyngeal cancer are not suitable candidates for organ preservation; this modality should be offered only to select patients with good performance status and access to rehabilitative care and regular follow-up in order to achieve good results.

https://ift.tt/2AIQmKq

Assessing the effects of long-term osteoporosis treatment by using conventional spine radiographs: results from a pilot study in a sub-cohort of a large randomized controlled trial

Abstract

Objective

To evaluate the clinical applicability of a software tool developed to extract bone textural information from conventional lumbar spine radiographs, and to test it in a subset of postmenopausal women treated for osteoporosis with the fully human monoclonal antibody denosumab.

Methods

The software was developed based on the principles of a fractal model using pixel grey-level variations together with a specific machine-learning algorithm. The obtained dimensionless parameter, termed bone structure value (BSV), was then tested and compared to bone mineral density (BMD) in a sub-cohort of postmenopausal women with osteoporosis who were treated with the monoclonal antibody denosumab, within the framework of a large randomized controlled trial and its open-label extension phase.

Results

After 3 years and after 8 years of treatment with denosumab, mean lumbar spine BMD as well as mean lumbar BSV were significantly higher compared to study entry (one-way repeated measures ANOVA for DXA: F = 108.2, p < 0.00001; and for BSV: F = 84.3, p < 0.00001). The overall increase in DXA-derived lumbar spine BMD at year 8 was + 42% (mean ± SD; 0.725 ± 0.038 g/cm² to 1.031 ± 0.092 g/cm²; p < 0.0001), and the overall increase of BSV was 255% (mean ± SD; 0.076 ± 0.022 to 0.270 ± 0.09, p < 0.0001). Overall, BMD and BSV were significantly correlated (R = 0.51; p < 0.0001).

Conclusions

This pilot study provides evidence that lumbar spine BSV as obtained from conventional radiographs constitutes a useful means for the assessment of bone-specific treatment effects in postmenopausal women with osteoporosis.

https://ift.tt/2PbAbuh

Survivorship issues in older breast cancer survivors

Abstract

Purpose

Almost half of breast cancer survivors are aged ≥ 65 years and the proportion is likely to increase due to the aging of the population. The objectives of this article were to review studies of health outcomes among older breast cancer survivors ≥ 65 years to identify gaps in the published literature and offer suggestions for future research.

Methods

The present review is based upon bibliographic searches in PubMed and CINAHL and relevant search terms. Articles published in English from January 1, 1970 through October 1, 2018 were identified using the following MeSH search terms and Boolean algebra commands.

Results

This review has revealed that older breast cancer survivors cope with health issues related to cancer treatment and the aging process, including comorbidities, osteoporosis, symptoms, physical functioning, cognitive functioning, nutrition, and physical activity.

Conclusions

Additional research is needed to examine therapeutic interventions to address the health conditions older breast cancer survivors are coping with. Particular focus of further research should be on the nutritional status and physical activity levels of older breast cancer survivors. Individualized nutrition plans and tailored physical activity programs for older survivors are needed that meet people where they are and that form habits.

https://ift.tt/2BKI3Qb

Demystifying biosimilars: development, regulation and clinical use

Future Oncology, Ahead of Print.


https://ift.tt/2DUo0A8

Hydration requirements in patients receiving highly emetogenic chemotherapy

Future Oncology, Ahead of Print.


https://ift.tt/2QwV9sk

Monthly News Roundup - November 2018

FDA Approves Truxima as the First Biosimilar to Rituxan In November, the U.S. Food and Drug Administration (FDA) approved Truxima (rituximab-abbs) injection from Celltrion as the first biosimilar to Rituxan (rituximab) for the treatment of adult...

https://ift.tt/2DUMrNP

Clinical validity of HPV circulating tumor DNA in advanced anal carcinoma: an ancillary study to the Epitopes-HPV02 trial

Purpose: Human papillomavirus (HPV) is found in 90% of squamous cell carcinomas of the anal canal (SCCA). We investigated the clinical validity of HPV circulating tumor DNA (ctDNA) detection in patients enrolled in the Epitopes-HPV02 trial which demonstrated the efficacy of docetaxel, cisplatin and 5FU as first-line chemotherapy (CT) in advanced SCCA. Experimental Design: According to the protocol, serum samples were collected before CT and on completion of CT. HPV16 ctDNA was quantified by ddPCR and correlated with prospectively registered patient characteristics and outcomes. A landmark was set at the time of CT completion for post-CT progression-free survival (PFS) analyses. Results: Among 57 patients with HPV16-related advanced SCCA, HPV ctDNA was detected in 91.1% (95% CI 81.1 to 96.2) of baseline samples. Baseline HPV ctDNA levels were not associated with any patient characteristics; baseline ctDNA level below the cut-off obtained by AUC (area under the curve) was associated with a longer PFS (HR=2.1, p=0.04). Among the 36 patients who completed 5 months of CT, residual HPV ctDNA was detected after CT in 38.9% of patients. Residual HPV ctDNA detected at CT completion was associated with shorter post-CT PFS (median PFS 3.4 months vs not reached; HR=5.5, p<0.001) and a reduction of one-year overall survival rate (OR=7.0, p=0.02). Conclusions: This prospective study in advanced SCCA demonstrated a significant prognostic impact of HPV ctDNA level before first-line CT and HPV ctDNA negativity after CT completion. With a limited cost and short turnaround, this assay is a promising tool to optimize the therapeutic management of SCCA.

https://ift.tt/2E7hSWj

Expression of MT4-MMP, EGFR and RB in triple negative breast cancer strongly sensitizes tumors to erlotinib and palbociclib combination therapy

Purpose: Here, we investigated the clinical relevance of an unprecedented combination of three biomarkers in triple-negative breast cancer (TNBC), both in human samples and in patient-derived xenografts of TNBC (PDX-TNBC): epidermal growth factor receptor (EGFR), its recently identified partner (MT4-MMP) and retinoblastoma protein (RB). Experimental design: Immunohistochemistry (IHC) analyses were conducted on human and PDX-TNBC samples to evaluate the production of the three biomarkers. The sensitivity of cancer cells expressing or not MT4-MMP to anti-EGFR (E: erlotinib) or anti-CDK4/6 inhibitor (P: palbociclib) was evaluated, in vitro in 2D and 3D proliferation assays and, in vivo using xenografts and PDX-TNBC displaying different RB, MT4-MMP and EGFR status after single (E or P) or combined (E+P) treatments. Results: EGFR and MT4-MMP were co-expressed in >70% of TNBC samples and PDX-TNBC, among which approximately 60% maintained RB expression. Notably, approximately 50% of all TNBC and PDX-TNBC expressed the three biomarkers. Single E and P treatments drastically reduced the in vitro proliferation of cells expressing EGFR and MT4-MMP when compared to control cells. Both TNBC xenografts and PDX expressing MT4-MMP, EGFR and RB but not PDX-TNBC with RB-loss were sensitive to E and P with an additive effect of combination therapy. Moreover, this combination was efficient in another PDX-TNBC expressing the three biomarkers and resistant to E alone. Conclusion. We defined a new association of three biomarkers (MT4-MMP/EGFR/RB) expressed together in 50% of TNBC and demonstrated its usefulness to predict the TNBC response to anti-EGFR and anti-CDK4/6 drugs used in single or combined therapy.

https://ift.tt/2SkJ8ne

Depression induced neuropeptide Y secretion promotes prostate cancer growth by recruiting myeloid cells

Purpose: Psychological depression has been shown to dysregulate the immune system and promote tumor progression. The aim of this study is to investigate how psychological depression alters the immune profiles in prostate cancer. Experimental Design: We used a murine model of depression in Myc-CaP tumor bearing immune competent FVB mice and Hi-myc mice presenting with spontaneous prostate cancer. Transwell migration and co-culture assays were used to evaluate myeloid cell trafficking and cytokine profile changes evoked by Myc-CaP cells that had been treated with norepinephrine (NE), a major elevated neurotransmitter in depression. Chemoattractant which correlated with immune cell infiltration was screened by RNA-seq. The chemoattractant and immune cell infiltration were further confirmed using clinical samples of prostate cancer patients with high score of psychological depression. Results: Psychological depression predominantly promoted tumor-associated macrophage (TAM) intra-tumor infiltrations which resulted from spleen and circulating monocytic myeloid-derived suppressor cell (Mo-MDSC) mobilization. Neuropeptide Y (NPY) released from NE-treated Myc-CaP cells promotes macrophage trafficking and IL-6 releasing which activates STAT3 signaling pathway in prostate cancer cells. Clinical specimens from prostate cancer patients with higher score of depression revealed higher CD68+ TAM infiltration and stronger NPY and IL-6 expression. Conclusions: Depression promotes myeloid cell infiltration and increases IL-6 levels by a sympathetic-NPY signal. Sympathetic-NPY inhibition may be a promising strategy for prostate cancer patients with high score of psychological depression.

https://ift.tt/2SprcrH

NRF2 through RPS6 activation is related to anti-HER2 drug resistance in HER2-amplified gastric cancer

Purpose: Despite the clinical advantage of the combination of trastuzumab and platinum-based chemotherapy in HER2-amplified tumors, resistance will eventually develop. The identification of molecular mechanisms related to primary and acquired resistance is needed. Experimental Design: We generated lapatinib- and trastuzumab-resistant clones deriving from two different HER2-amplified GC cell lines. Molecular changes such as protein expression and gene expression profile were evaluated to detect alterations which could be related to resistance. Functional studies in vitro were corroborated in vivo. The translational relevance of our findings was verified in a patient cohort. Results: We found RPS6 activation and NRF2 to be related to anti-HER2 drug resistance. RPS6 or NRF2 inhibition with siRNA reduced viability and resistance to anti-HER2 drugs. In knockdown cells for RPS6, a decrease of NRF2 expression was demonstrated, suggesting a potential link between these two proteins. The use of a PI3K/TORC1/TORC2 inhibitor, tested in vitro and in vivo, inhibited pRPS6 and NRF2 expression and caused cell and tumor growth reduction, in antiHER2 resistant models. In a cohort of HER2-amplified patients treated with trastuzumab and chemotherapy, a high level of NRF2 at baseline corresponds with worse progression-free survival (PFS). Conclusions: NRF2 through PI3K/AKT/mTOR/RPS6 pathway could be a potential effector of resistance to anti-HER2 drugs in our models. RPS6 inhibition decreases NRF2 expression and restores sensitivity in HER2-amplified gastric cancer in vitro and in vivo. High NRF2 expression in gastric cancer patients predicts resistance to treatment. RPS6 and NRF2 inhibition could prevent resistance to anti-HER2 drugs.

https://ift.tt/2E8hc2G

ZW25 Active in HER2-positive Cancers [News in Brief]

Patients treated with novel anti-HER2 therapy had high response rate, few serious side effects.

https://ift.tt/2So2DeO

Antiviral- and Antitumor-Specific T-cell Immunity Is WDFY4-Dependent [Research Watch]

WDFY4 is required for classic dendritic cell–mediated cross-presentation of tumor and viral antigens.

https://ift.tt/2E7hJlJ

JARID2 Is a Tumor Suppressor in Myeloid Neoplasms [Research Watch]

JARID2 recruits PRC2 to repress the self-renewal of multipotent progenitor cells.

https://ift.tt/2SmSIWx

CHAF1B Suppresses Myeloid Differentiation to Promote Leukemogenesis [Research Watch]

Heterozygous CHAF1B expression is sufficient for normal hematopoiesis but induces AML cell differentiation.

https://ift.tt/2E7hI19

IFN-r-induced IFIT5 promotes epithelial-to-mesenchymal transition in prostate cancer via microRNA processing

Interferon-γ (IFNγ), a potent cytokine known to modulate tumor immunity and tumoricidal effects, is highly elevated in prostate cancer (PCa) patients after radiation. In this study, we demonstrate that IFNγ can induce epithelial-to-mesenchymal transition (EMT) in PCa cells via the JAK-STAT signaling pathway, leading to the transcription of IFN-stimulated genes (ISG) such as interferon-induced tetratricopeptide repeat 5 (IFIT5). We unveil a new function of IFIT5 complex in degrading precursor microRNAs (pre-miRNA) that include pre-miR-363 from the miR-106a-363 cluster as well as pre-miR-101 and pre-miR-128, who share a similar 5'-end structure with pre-miR-363. These suppressive miRNAs exerted a similar function by targeting EMT transcription factors in PCa cells. Depletion of IFIT5 decreased IFNγ-induced cell invasiveness in vitro and lung metastasis in vivo. IFIT5 was highly elevated in high-grade PCa and its expression inversely correlated with these suppressive miRNAs. Altogether, this study unveils a pro-metastatic role of the IFNγ pathway via a new mechanism of action, which raises concerns about its clinical application.

https://ift.tt/2FS1fj8

Efficient Homologous Recombination in Mice Using Long Single Stranded DNA and CRISPR Cas9 Nickase

The CRISPR/Cas9 nickase mutant is less prone to off-target double-strand (ds)DNA breaks than wild-type Cas9 because to produce dsDNA cleavage it requires two guide RNAs to target the nickase to nearby opposing strands. Like wild-type Cas9 lesions, these staggered lesions are repaired by either non-homologous end joining or, if a repair template is provided, by homologous recombination (HR). Here, we report very efficient (up to 100%) recovery of heterozygous insertions in Mus musculus produced by long (>300 nt), single-stranded DNA donor template-guided repair of paired-nickase lesions.

https://ift.tt/2DSNOg8

Teva Recalls Two Blood Pressure Medications

FRIDAY, Nov. 30, 2018 -- All lots of amlodipine/valsartan and amlodipine/valsartan/hydrochlorothiazide combination blood pressure tablets have been recalled by Teva Pharmaceuticals due to higher-than-acceptable levels of a chemical that may cause...

https://ift.tt/2P8ZSvz

Family Functioning Does Not Impact Family Dinner, Diet Link

FRIDAY, Nov. 30, 2018 -- Among adolescents and young adults, family dinner frequency is associated with healthful dietary intake, regardless of family functioning, according to a study published online Nov. 21 in JAMA Network Open. Kathryn Walton,...

https://ift.tt/2zBWLaD

Limiting Social Media May Improve Psychological Well-Being

FRIDAY, Nov. 30, 2018 -- Limiting social media use to 30 minutes per day may lead to significant improvement in well-being, according to a study published in the December issue of the Journal of Social and Clinical Psychology. Melissa G. Hunt,...

https://ift.tt/2zzkzfn

Case Description Can Reliably Define Acute Flaccid Myelitis

FRIDAY, Nov. 30, 2018 -- A case description can reliably define patients with acute flaccid myelitis (AFM), according to a study published online Nov. 30 in JAMA Pediatrics. Matthew J. Elrick, M.D., Ph.D., from the Johns Hopkins University School of...

https://ift.tt/2Pch5Ex

Presence of Antiphospholipid Antibodies Tied to First-Time MI

FRIDAY, Nov. 30, 2018 -- There is a strong and independent association between the presence of antiphospholipid antibodies (aPLs) and first-time myocardial infarction (MI), according to a research letter published recently in the Annals of Internal...

https://ift.tt/2zwfJiL

Risk stratification in early breast cancer in premenopausal and postmenopausal women: integrating genomic assays with clinicopathological features

Purpose of review There is growing consensus that genomic assays provide useful complementary information to clinicopathological features in oestrogen receptor-positive breast cancers. Here, ongoing research with multigene tests used for postmenopausal breast cancer and new emerging prognostic and predictive markers for pre and postmenopausal women are summarised. Recent findings Results of the TAILORx trial have shown that women with an intermediate risk score do not benefit from adjuvant chemotherapy. Prosgina has been further investigated in a contemporary patient population in postmenopausal women and its use has been extended for premenopausal women. The EndoPredict was extensively used in decision-impact studies showing that its use can potentially reduce the need for adjuvant chemotherapy. Several new genomic assays have been developed, with some of them showing promising use for women with early oestrogen receptor-positive breast cancer. Summary New areas of research for prediction of recurrence and risk stratification involve the development of immune gene signatures that carry modest but significant prognostic value. The recent expansion of high-throughput technology platforms including circulating tumour DNA/RNA and microRNA offer new opportunities to improve prediction models, particularly in women with oestrogen receptor-negative disease and premenopausal women. Genomic assays have clearly improved prognostication of early oestrogen receptor-positive breast cancer but it is clear that standard clinicopathological parameters are still very important when identifying patient for adjuvant chemotherapy.

https://ift.tt/2SkSYFC

Editorial introductions

No abstract available

https://ift.tt/2E5Rf41

Epidermal growth factor receptor tyrosine kinase inhibitors in advanced nonsmall cell lung cancer: what is the preferred first-line therapy?

Purpose of review Epidermal growth factor receptor (EGFR) mt+ nonsmall cell lung cancer (NSCLC) were the first molecularly described NSCLC with an established 'targeted' therapy inhibiting mutated EGFR [EGFR tyrosine kinase inhibitor (TKI)]. EGFR TKI of first and second generation have led to an unprecedented improvement in objective response rate, progression-free survival (PFS) and overall survival (OS) compared with chemotherapy with a significantly reduced toxicity and improved quality of life. Fast elucidation of the most frequent resistance mechanism against first and second-generation TKI, T790M, led to the approval of the third-generation TKI osimertinib in second line. Recent findings Recently, the FLAURA study showed an impressive PFS benefit and immature OS data for osimertinib against solely first-generation TKI's. Also, the ARCHER study comparing dacomitinib against first-generation TKI showed a PFS and also OS benefit. Two studies combining EGFR TKI and antiangiogenesis showed PFS but no OS benefit. Lately, the combination of TKI and chemotherapy has seen a revival with the NEJ009 study, resulting in an impressive median OS of 55 months. Summary Therefore, potentially four different therapeutic options are available in first-line therapy of EGFR mt+ NSCLC, first, second, third generation, TKI + antiangiogenic agent and TKI + chemotherapy. The purpose of the review is to help to guide physicians to decide in their treatment choice and discuss potential directions of research.

https://ift.tt/2SlY9Fj

Impact of ovarian function suppression in premenopausal women with estrogen receptor-positive early breast cancer

Purpose of review This manuscript aims at providing an updated overview on the role of adding ovarian function suppression to tamoxifen or an aromatase inhibitor as adjuvant endocrine therapy in premenopausal women with estrogen receptor-positive early breast cancer. Recent findings Until recently, tamoxifen alone was the only recommended adjuvant treatment option for premenopausal women with estrogen receptor-positive disease. However, recent important evidence has contributed to significantly modify the endocrine treatment landscape in this setting. Summary With the only exception of patients with low-risk clinical-pathological features characterized by excellent survival outcomes with tamoxifen alone, the use of ovarian function suppression is to be considered standard of care for most of premenopausal women with estrogen receptor-positive disease. Regarding the choice of its best partner as endocrine agent, the available data suggest that the higher the risk of disease recurrence the larger benefit can be observed with a more profound estrogen deprivation that can be obtained with ovarian function suppression and an aromatase inhibitor as compared to ovarian function suppression and tamoxifen. Despite the significant improvement in our understanding on the role of ovarian function suppression in this setting, several unanswered questions remain and further research efforts are needed in the field.

https://ift.tt/2E6oJ23

Treatment of anaplastic lymphoma kinase-positive non-small cell lung cancer: update and perspectives

Purpose of review We describe recent developments in the rapidly evolving field of anaplastic lymphoma kinase-targeting agents. Recent findings Five targeted drugs are currently available in the clinic via regular approval or named patient programs, including crizotinib, ceritinib, alectinib, brigatinib and lorlatinib. Further drugs are tested in clinical trials. This review summarizes published data, together with drug-specific information on dosing and toxicity. Moreover, we discuss different clinical scenarios and potential treatment options in patients with tumor progression, based on current literature and our own experience. Summary Patients with metastatic, anaplastic lymphoma kinase-rearranged nonsmall cell lung cancer should be managed by interdisciplinary expert teams. New drugs with enhanced brain activity are available, and some patients may benefit from local therapies.

https://ift.tt/2SjRbRh

Biomarkers for immune checkpoint inhibitors in advanced nonsmall cell lung cancer

Purpose of review Immune checkpoint inhibitors have been established as a new class of anticancer drugs for patients with advanced nonsmall cell lung cancer. Predictive biomarkers might help to select those patients who will derive the greatest benefit from these expensive drugs. This review summarizes the current status of predictive biomarkers for immune checkpoint inhibitors in advanced nonsmall cell lung cancer. Recent finding Programmed death ligand 1 (PD-L1) staining on tumor cells and immune cells has been studied as a predictive biomarker for immune checkpoint inhibitors. Higher PD-L1 levels appeared to be associated with greater benefit from these drugs in many studies, although such an association was absent in some studies. Tumor mutational load was associated with benefit from the combination of nivolumab plus ipilimumab. Immune checkpoint inhibitors combined with first-line chemotherapy improved survival compared to chemotherapy alone. These improvements were clinically relevant also in patients with PD-L1 expression in less than 1% of tumor cells. Summary PD-L1 expression on tumor and immune cells and tumor mutational load allow better selection of patients for treatment with immune checkpoint inhibitors as single agents. The role of PD-L1 for the selection of patients for chemoimmuntherapy remains to be seen.

https://ift.tt/2E7dc2I

Immunotherapy in patients with early stage resectable nonsmall cell lung cancer

Purpose of review 'Early-stage' nonsmall cell lung cancer (NSCLC) refers to stage I and stage II disease, and selected cases of stage IIIA disease where complete tumor resection is feasible. Surgery is the standard treatment for early NSCLC, but the overall 5-year survival remains below 50%. The addition of adjuvant cisplatin-based chemotherapy to surgery improved 5-year survival rates by 5–10%, but no significant therapeutic innovation has been established thereafter. We review recent and ongoing studies looking how immunotherapy may improve the outcome of these patients. Recent findings Antigen-specific immunotherapy (cancer vaccination) did not fulfill its promise in a large phase III randomized trial in completely resected early-stage NSCLC. Over the past few years, immunotherapy with immune checkpoint inhibition (ICI) has led to remarkable progress in nononcogene addicted metastatic NSCLC. We review ongoing clinical investigations that want to translate these benefits to earlier stages of NSCLC. Both adjuvant and neoadjuvant large randomized controlled trials with ICI are ongoing. Summary Although from a mechanistic perspective the neoadjuvant administration may be preferred, it is crucial that both adjuvant and neoadjuvant trials are recruited as planned, to have a balanced view how ICI therapy may ultimately improve cure rates in these patients.

https://ift.tt/2Sl6x7V

Escalation and de-escalation in HER2 positive early breast cancer

Purpose of review Current standard for HER2+ early breast cancer patients includes chemotherapy and trastuzumab for 1 year. The purpose of this article is to review available evidence on escalated treatment strategies for high-risk patients and de-escalated treatments for patients at low risk of relapse or high risk of cardiac toxicity. Recent findings Recent results have led to the approval of two adjuvant escalated treatment strategies: pertuzumab and trastuzumab combined with chemotherapy for up to 1 year for high-risk patients; extension of adjuvant anti-HER2 treatment with 1 year of neratinib. However, these treatments are associated with increased costs and toxicity, therefore careful patients' selection is highly required. With regard to de-escalated treatments, the anthracycline-free regimen of adjuvant paclitaxel and 1 year trastuzumab has entered clinical practice for early-stage patients. One year of trastuzumab remains the standard; however, shorter trastuzumab could be an option for low-risk patients and in case of increased risk of cardiotoxocity. Chemotherapy-free regimens are attractive but deserve further evaluation. Summary There have been advances in treatment individualization for HER2+ early breast cancer patients. Integration of promising biomarkers into risk classification will further help progressing in the field.

https://ift.tt/2E6WJLN

Role of immunotherapy in stage III nonsmall cell lung cancer

Purpose of review Despite aggressive treatment based on definitive chemoradiotherapy, 5-year overall survival in unresectable stage III nonsmall cell lung cancer remains poor (15–20%). The novel immunotherapy based on immune checkpoint inhibitors (ICIs) presents as the therapeutic 'Holly Grail' in lung cancer treatment. Recent findings Preclinical models provide evidence of immunotherapy–radiotherapy (IM-RT) synergy. The exposure to ionizing radiation turns tumor in an in-situ vaccine, primes the innate immune system, increases immunotherapy efficacy by overcoming the immunosuppressive microenvironment of immune-resistant tumors and promotes a systemic, out-of-field antitumor T-cell-mediated response called abscopal effect. The immunomodulatory and abscopal effects of radiotherapy can be further enhanced by combining with systemic immunotherapies. The phase III START trial proved that liposomal vaccine – tecemotide (L-BLP25) administered as maintenance therapy after concurrent chemoradiotherapy (CRT) in LA-NSCLC prolongs survival. In the phase III PACIFIC trial consolidation with durvalumab, an anti-PDL-1 antibody, was associated with survival benefit in patients diagnosed with LA-NSCLC who responded to concurrent chemoradiotherapy. Summary PACIFIC trial results are expected to definitely establish durvalumab as standard consolidation strategy in LA-NSCLC. Many clinical trials are ongoing in the field of immunoradiotherapy in LA-NSCLC to define the optimal conditions for this therapeutic combination.

https://ift.tt/2SkyM6L

Revisiting tumor patterns and penetrance in germline TP53 mutation carriers: temporal phases of Li–Fraumeni syndrome Erratum

No abstract available

https://ift.tt/2E7yai2

Down-regulation of microRNA-21 inhibits cell proliferation and invasion of high-invasion liver cancer stem cells

OBJECTIVE: Cancer stem cells (CSCs) play critical roles in tumorigenesis, tumor recurrence and metastasis. This study aims to investigate the effects of small interfere microRNA-21 RNA (miR-21 RNAi) on cell proliferation, invasive ability of high-invasion liver cancer stem cells (H-ILCSCs), HCCLM3 and HL-7702 cells.

MATERIALS AND METHODS: pLVX-shRNA2 lentiviral vector system was established, packaged and transfected into H-ILCSCs, HCCLM3 and HL-7702 cells. Cell counting kit-8 (CCK-8) assay was performed to observe cell viabilities of cells. Transwell assay was conducted to evaluate the invasion potential of H-ILCSCs, HCCLM3 and HL-7702 cells. Quantitative PCR (qPCR) assay was used to examine the miR-21 levels in different cell lines.

RESULTS: pLVX-anti-miR21 lentiviral vector system was successfully established. miR-21 levels were down-regulated in anti-miR-21 gene steady expression cell lines compared to untreated cells (p<0.05). miR-21 levels were significantly lower in H-ILCSC2-LV-anti-miR-21 group compared to HCCLM3-anti-miR-21 and HL7702-anti-miR-21 (p<0.05). miR-21 inhibition significantly decreased cell proliferation and invasion compared to untreated cells (p<0.05). Cell proliferation and invasive ability of H-ILCSC2-LV-anti-miR-21 group were significantly higher compared to HCCLM3-anti-miR-21 and HL7702-anti-miR-21 (p<0.05). There were even not effects of miR-21 RNAi treatment on the cell proliferation and invasion of HL-7702 cells.

CONCLUSIONS: The down-regulation of miR-21 significantly inhibited the cell proliferation and invasion abilities of H-ILCSCs and HCCLM3 cells, and illustrated higher effects on H-ILCSCs.

L'articolo Down-regulation of microRNA-21 inhibits cell proliferation and invasion of high-invasion liver cancer stem cells sembra essere il primo su European Review.

https://ift.tt/2KKoREX

MiR-98-5p regulates myocardial differentiation of mesenchymal stem cells by targeting TBX5

OBJECTIVE: This study aims to investigate whether miR-98-5p can participate in the myocardial differentiation of bone marrow mesenchymal stem cells (MSCs) by regulating TBX5.

MATERIALS AND METHODS: In this study, we first identified the MSCs that were isolated from rat bone marrow samples. Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was performed to detect mRNA expressions of cardiac-related genes, including brain natriuretic peptide (BNP), α-actinin, and Islet-1. The binding site of miR-98-5p and TBX5 was detected by dual-luciferase report gene assay. In addition, co-transfection of miR-98-5p mimics and TBX5 overexpression plasmids was conducted to assess whether miR-98-5p could regulate myocardial differentiation by targeting TBX5.

RESULTS: Overexpression of TBX5 or knockdown of miR-98-5p promoted myocardial differentiation of BMSCs. The mRNA expressions of α-actinin and Islet-1 were significantly increased after the miR-98-5p knockdown. Dual-luciferase report gene assay showed that miR-98-5p could bind to TBX5, which was further verified by qRT-PCR. Additionally, TBX5 overexpression reversed the inhibitory effect of miR-98-5p on regulating the mRNA expressions of α-actinin and Islet-1.

CONCLUSIONS: MiR-98-5p can inhibit the differentiation of rat MSCs into cardiomyocytes through targeting TBX5.

L'articolo MiR-98-5p regulates myocardial differentiation of mesenchymal stem cells by targeting TBX5 sembra essere il primo su European Review.

https://ift.tt/2BItfkU

MicroRNA-7-5p regulates osteogenic differentiation of hMSCs via targeting CMKLR1

OBJECTIVE: To investigate the function of microRNA-7-5p in human mesenchymal stem cells (hMSCs) and its underlying potential mechanism in osteogenic differentiation.

PATIENTS AND METHODS: Expression levels of osteogenic genes (ALP, RUNX2), microRNA-7-5p and CMKLR1 in hMSCs were detected by quantitative real time-polymerase chain reaction (qRT-PCR). After transfection of microRNA-7-5p mimics or inhibitor, the effect of microRNA-7-5p on osteogenic differentiation of hMSCs was detected by Alizarin red staining, ALP activity determination and Western blot, respectively. The potential target gene of microRNA-7-5p was predicted online and further verified by luciferase reporter gene assay. Rescue experiments were conducted to explore whether the effect of microRNA-7-5p on osteogenic differentiation of hMSCs could be reversed by CMKLR1.

RESULTS: Expression levels of ALP, RUNX2 and microRNA-7-5p were gradually elevated with the prolongation of osteogenic differentiation, whereas CMKLR1 was reduced. Overexpression of microRNA-7-5p increased levels of ALP and RUNX2. The amount of calcified nodules was increased after microRNA-7-5p overexpression. CMKLR1 was the target gene of microRNA-7-5p. The effect of microRNA-7-5p on osteogenic differentiation of hMSCs could be reversed by CMKLR1.

CONCLUSIONS: MicroRNA-7-5p promotes osteogenic differentiation of hMSCs via targeting CMKLR1.

L'articolo MicroRNA-7-5p regulates osteogenic differentiation of hMSCs via targeting CMKLR1 sembra essere il primo su European Review.

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MiR-216a-3p promotes differentiation of BMMSCs into ACE II cells via Wnt/β-catenin pathway

OBJECTIVE: To explore whether miR-216a-3p could promote differentiation of bone marrow mesenchymal stem cells (BMMSCs) into type II alveolar epithelial cells (ACE II) via Wnt/β-catenin pathway, thereby alleviating neonatal respiratory distress syndrome (NRDS).

MATERIALS AND METHODS: BMMSCs were directionally differentiated into ACE II cells. Expressions of ACE II cell-specific transcription factors Occludin, KGF, CK18, SpA, SpB, and SpC were detected at the different time points after cell differentiation. Enzyme-linked immunosorbent assay (ELISA) was applied to detect inflammatory factors in the culture medium, including interleukin-1 (IL-1), interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α), and Interferon-α (INF-α). After overexpression or knockdown of miR-216a-3p in BMMSCs, expressions of ACE II cell-specific transcription factors and inflammatory factors were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) and Western blot. Rescue experiments were carried out after DKK-1 treatment in BMMSCs.

RESULTS: Expressions of ACE II cell-specific transcription factors Occludin, KGF, CK18, SpA, SpB, and SpC were elevated with the prolongation of cell differentiation. Overexpression of miR-216a-3p elevated levels of pro-inflammatory factors (IL-1, TNF-α, and INF-α) and reduced anti-inflammatory factor (IL-10). Expressions of ACE II cell-specific transcription factors Occludin, KGF, CK18, SpA, SpB, and SpC were remarkably increased at 7 d and 14 d compared to those detected at 1 d. Overexpression of miR-216a-3p in BMMSCs downregulated Wnt3a expression. The regulatory effect of miR-216a-3p on BMMSCs differentiation was partially reversed by DKK-1 treatment.

CONCLUSIONS: Knockdown of miR-216a-3p induces differentiation of BMMSCs into ACE II cells through Wnt/β-catenin pathway, thereby alleviating NRDS.

L'articolo MiR-216a-3p promotes differentiation of BMMSCs into ACE II cells via Wnt/β-catenin pathway sembra essere il primo su European Review.

https://ift.tt/2BLeMVD

Isolated Fetal Cardiac Abnormalities: Are They Really Isolated?

AJP Rep 2018; 08: e355-e358
DOI: 10.1055/s-0038-1675349

Objective To determine the rate of unsuspected noncardiac abnormalities in newborns suspected to have isolated cardiac abnormalities in the second trimester. Study Design A review of the ultrasound database from the Weill Cornell Medical Center identified fetuses with a suspected cardiac abnormality from January 2006 to November 2016. Cases with prenatally suspected noncardiac structural abnormalities, abnormal fetal or neonatal karyotype or microarray, and those who delivered at an outside institution or underwent abortion were excluded. Neonatal records were reviewed to confirm prenatal findings and to identify anomalies not suspected in the second trimester. Results Sixty-eight live births met the inclusion criteria. Five newborns (7.4%) had major abnormalities not identified in the second trimester. Three newborns had an imperforate anus. One newborn had left hydronephrosis and absent right lung, and one had hemifacial microsomia and fused ribs. All five newborns with unsuspected anomalies were in the group with suspected conotruncal anomalies, with a 11.9% rate of unsuspected anomalies versus 0% in those with nonconotruncal cardiac anomalies (p = 0.15). Conclusion Patients with a suspected isolated fetal cardiac anomaly on ultrasound should be aware of the possibility of other major structural abnormalities, especially in cases of conotruncal cardiac anomalies.
[...]

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Article in Thieme eJournals:
Table of contents  |  Abstract  |  open access Full text

https://ift.tt/2PcObE8

Preventive effects of combinative natural foods produced by elite crop varieties rich in anticancer effects on N‐nitrosodiethylamine‐induced hepatocellular carcinoma in rats

In this paper, the pure natural food combinations Diet I and Diet II, which were mainly produced by elite crop varieties rich in anticancer effects (ACEs) with different mixture ratios, prevented N‐nitrosodiethylamine‐induced hepatocarcinogenesis in rats effectively, the low‐grade hepatic dysplasia incidence was 20% for Diet II and 40% for Diet I, and the apparent hepatocellular carcinoma (HCC) rates of both were 0, while the apparent HCC rate of the control diet treatment rats was 90% (P<0.01). This study indicated excellent prospects of daily dietary for cancer prevention and the importance of discovery and creation of ACEs‐rich crop varieties.

Abstract

The World Cancer Research Fund International has released 32 anticancer effects (ACEs) that targeted every stage of cancer processes. Thus, we designed two formulas of natural food combination Diet I and Diet II, mainly produced by elite crop varieties rich in ACEs with different mixture ratios, and evaluated their cancer preventive effects on N‐nitrosodiethylamine (NDEA)‐induced hepatocarcinogenesis. After 20 weeks of dietary intervention, Diet I and Diet II reduced incidence, size, and number of hepatic nodules (p < 0.01) and prevented hepatic tumor formation in NDEA‐induced hepatocarcinogenesis rats. Low‐grade hepatic dysplasia incidence was 20% for Diet II and 40% for Diet I, and apparent hepatocellular carcinomas (HCC) rates were both 0, while 90% HCC in control diet treatment group (p < 0.01). Diet I and Diet II ameliorated abnormal liver function enzymes, reduced serum alpha fetal protein, tumor‐specific growth factor, dickkopf‐related protein 1, tumor necrosis factor‐alpha and interleukin‐6 levels, regulated hepatic phase I and II xenobiotic‐metabolizing enzymes, enhanced antioxidant capacity, suppressed NDEA‐initiated oxidative DNA damage, and induced apoptosis coupled to down‐regulation of proinflammatory, invasion, and angiogenesis markers. Daily intake of combination diet produced from ACEs‐rich elite crop varieties can effectively prevent or delay occurrence and development of NDEA‐induced hepatocarcinogenesis in rats.

https://ift.tt/2P6tHNv

Perceptions of college students in consuming whole grain foods made with Brewers’ Spent Grain

Reclaiming Brewers' Spent Grains (BSG), the leftover grains from beer production, as a potential human food source is an opportunity for reducing food waste. Six focus groups were conducted using 37 college students to determine their consumption of whole grains, perceptions of whole grains versus refined grains and interest in or barriers related to consuming and purchasing foods made with BSG. Thirteen themes emerged from focus group discussions, and we concluded most participants were open to tasting BSG foods; however, consumers need further education on BSG sensory attributes.

Abstract

One‐third of all food produced for human consumption is wasted producing landfill accumulation and greenhouse gas emissions. Brewers' Spent Grains (BSGs) are the leftover grains from beer production, and each year approximately 30 million tons of BSG is generated globally by the brewing industry. Reclaiming BSG as a potential human food source is an opportunity for reducing food waste in the food supply chain. Six focus groups were conducted using 37 college students to determine their consumption of whole grains, perceptions of whole grains versus refined grains, and interest in or barriers related to consuming and purchasing foods made with BSG. Focus groups were transcribed verbatim and analyzed using constant comparative analysis to identify themes and discover relationships among the study aims. Thirteen themes emerged from focus group discussions with Concept of Health, Sensory, and Experience with BSG representing the top three discussed. Participants believed whole grains are healthier and contain more nutrients than refined grains. Most participants enjoyed the BSG foods provided; however, some noted a darker appearance and lingering fiber particles or aftertaste. Findings indicate participants who are hereditary whole grain consumers are acculturated to whole grain sensory attributes and nutritional benefits and would be more receptive to consuming BSG foods in future studies. We concluded most focus group participants were open to tasting BSG foods, but hereditary whole grain consumers should be the target consumer audience, and educating consumers on sensory attributes, potential health benefits, and environmental benefits is necessary to overcome the barriers associated with BSG.

https://ift.tt/2zyW0Pu

FDA Warns About Rare But Serious Risks of Stroke and Blood Vessel Wall Tears with Multiple Sclerosis Drug Lemtrada (alemtuzumab)

Audience: Consumer, Health Professional, Pharmacy The U.S. Food and Drug Administration (FDA) is warning that rare but serious cases of stroke and tears in the lining of arteries in the head and neck have occurred in patients with multiple sclerosis...

https://ift.tt/2FNH9Xb

FDA Warns That Symptoms of a Serious Condition Affecting the Blood Cells Are Not Being Recognized with the Leukemia Medicine Idhifa (enasidenib)

Audience: Consumer, Health Professional, Pharmacy The U.S. Food and Drug Administration (FDA) is warning that signs and symptoms of a life-threatening side effect called differentiation syndrome are not being recognized in patients receiving the...

https://ift.tt/2PbekTL

Simon’s hemorrhages in a case of a fatal construction site accident as the result of body hyperextension in the upside-down position – a possible reconstruction of the injury mechanism

Abstract

An accident occurred at a construction site and a 27-year-old worker was fatally injured. Equipped with personal protective equipment (helmet and a safety belt), he was standing on an 8-meter-high platform holding a large hose that was attached to a pipe connected to a concrete pump truck. Whilst in use the pipe broke and the hose sent the man flying with force, knocking down the platform railing. Autopsy examination showed that man fell to the ground landing on his head. Prominent Simon's hemorrhages were noted on the L5-S1 and L4-L5 intervertebral discs. When the hose threw the man from the platform, for one brief moment he was suspended in the air, with the safety belt tied firmly to his waist. Simon's hemorrhages most probably emerged at that moment, due to forceful hyperextension and traction of the body in the upside-down position. A relatively unexpected appearance of Simon's hemorrhages contributed to the reconstruction of the injury mechanism.

https://ift.tt/2DTM32a

FDA Warns That Symptoms of a Serious Condition Affecting the Blood Cells Are Not Being Recognized with the Leukemia Medicine Idhifa (enasidenib)

Audience: Consumer, Health Professional, Pharmacy The U.S. Food and Drug Administration (FDA) is warning that signs and symptoms of a life-threatening side effect called differentiation syndrome are not being recognized in patients receiving the...

https://ift.tt/2PbekTL

FDA Warns About Rare But Serious Risks of Stroke and Blood Vessel Wall Tears with Multiple Sclerosis Drug Lemtrada (alemtuzumab)

Audience: Consumer, Health Professional, Pharmacy The U.S. Food and Drug Administration (FDA) is warning that rare but serious cases of stroke and tears in the lining of arteries in the head and neck have occurred in patients with multiple sclerosis...

https://ift.tt/2FNH9Xb

Effects of deep brain stimulation on the primary motor cortex: Insights from transcranial magnetic stimulation studies

Movement disorders are characterized by hyperkinetic or hypokinetic movements. Abnormal neuronal activities in the cortex and other regions related to disturbances in the basal ganglia nuclei is a major cause of many movement disorders (Lang and Lozano, 1998a; Lozano and Lipsman, 2013). Modulation of disordered circuits within basal ganglia-thalamo-cortical pathways is a critical therapeutic strategy in various movement disorders. Although a pharmacological approach to correct disordered circuits is useful, potential exposure of all neurons in the brain to a drug may make the therapy less attractive in some patient populations (Lang and Lozano, 1998b).

https://ift.tt/2rgUcWN

Opportunities to Improve Detection and Treatment of Depression among Patients with Breast Cancer Treated in an Integrated Delivery System

Patients with cancer commonly experience depression. If not addressed, depression can lead to reduced quality of life and survival.

https://ift.tt/2SnM3vr

Non-malignant pain symptom subgroups in nursing home residents

Despite many nursing home residents experiencing pain, research about the multidimensional nature of non-malignant pain in these residents is scant.

https://ift.tt/2E9pibm

The effect of residential aged care size, ownership model and multi-chain affiliation on resident comfort and symptom management at the end of life

In most resource-rich countries, a large and growing proportion of older adults with complex needs will die while in a Residential Aged Care (RAC) facility.

https://ift.tt/2SmzaBD

Clinically-oriented Contour Evaluation using Dosimetric Indices Generated from Automated Knowledge-based Planning

Geometric indices commonly-used for contour evaluation lack clinical context, while dosimetric indices from manual planning can introduce confounding variation. We evaluated inter-resident contour variation using automated knowledge-based planning to objectively generate plans and subsequent dosimetric indices. Amidst substantial inter-resident contour variation, there were weak and inconsistent correlations between geometric and dosimetric indices, highlighting the unreliability of using geometric indices for contour evaluation. Whenever possible, automatically-generated dosimetric indices should be used for radiotherapy contour evaluation studies.

https://ift.tt/2Q5KHsn

Long-Term Pulmonary Outcomes of a Feasibility Study of Inverse-Planned, Multibeam Intensity-Modulated Radiation Therapy (IMRT) in Node-Positive Breast Cancer Patients Receiving Regional Nodal Irradiation

Multi-beam IMRT increases the dosimetric coverage of targeted tissues while minimizing volumes of adjacent organs receiving high doses of RT, however exposes a greater volume of lung to low doses of RT, raising concern about radiation pneumonitis (RP). Our pilot study evaluated the dosimetric feasibility of inverse-planned, multibeam IMRT and incidence of RP. Coverage of targeted tissues was comprehensive, with low rates of grade 3 RP (.96%) and high 5-year locoregional recurrence-free survival (93.2%).

https://ift.tt/2Q6OrtK

A Roberts Syndrome individual with differential genotoxin sensitivity and a DNA damage response defect

Roberts Syndrome (RBS) is a rare recessively-transmitted developmental disorder characterized by growth retardation, craniofacial abnormalities and truncation of limbs. All affected individuals to date have mutations in the ESCO2 (Establishment of cohesion 2) gene, a key regulator of the cohesin complex, which is involved in sister chromatid cohesion and DNA double-strand break (dsb) repair. Here we characterize DNA damage responses (DDRs) for the first time in a RBS-affected family.

https://ift.tt/2RpJXuR

Worse Outcomes for Head and Neck Rhabdomyosarcoma Secondary to Reduced-dose Cyclophosphamide

Efforts to reduce late morbidity in head and neck rhabdomyosarcoma include proton therapy and reduced-doses of cyclophosphamide. We show that both the dose-intensity and cumulative cyclophosphamide dose seem to play a significant role in achieving local control for patients with head and neck rhabdomyosarcoma treated with definitive irradiation using either photons or protons.

https://ift.tt/2Rs8YFY

Automated Text Message Reminders Improve Radiation Therapy Compliance

Protraction of radiation therapy courses can lead to lower cancer control and cancer-specific survival rates. The requirement for daily, consecutive radiation treatments coupled with the complexities of multi-modality cancer care and quality assurance can occasionally lead to missed patient appointments or clinical inefficiency. To determine if an automated text messaging (SMS) platform could improve patient compliance with scheduled radiation therapy delivery we created an automated SMS platform to send daily reminders of radiation therapy appointments.

https://ift.tt/2Q8V0fl

Erratum Regarding “Emerging Concepts in Hematopoietic Stem Cell Transplantation–Associated Renal Thrombotic Microangiopathy and Prospects for New Treatments” (Am J Kidney Dis. 2018;72[6]:857-865)

In the Narrative Review entitled "Emerging Concepts in Hematopoietic Stem Cell Transplantation–Associated Renal Thrombotic Microangiopathy and Prospects for New Treatments" that appeared in the December 2018 issue of AJKD (Wanchoo et al, volume 72, issue 6, pages 857-865), there was an error in how Figure 2 was credited. The penultimate sentence of the Figure 2 legend should have read "Artwork created by D. Maizels, Zoobotanica Scientific Illustration, based on Figure 4 of Jodele et al7. Original image © 2014 Elsevier Ltd; adapted with permission." In addition, the last line of the Acknowledgements should have read "Figure 2 artwork adapted from Jodele et al7 by Debbie Maizels, Zoobotanica Scientific Illustration."

https://ift.tt/2E6yuNM

Purification of H3 and H4 Histone Proteins and the Quantification of Acetylated Histone Marks in Cells and Brain Tissue

The purpose of this article is to provide a comprehensive, systematic guide to the efficient purification of histones H3 and H4 and the quantification of acetylated histone residues.

https://ift.tt/2BK7DF7

Crystal Structure of the N-terminal Domain of Ryanodine Receptor from Plutella xylostella

In this article, we describe the protocols of protein expression, purification, crystallization and structure determination of the N-terminal domain of ryanodine receptor from diamondback moth (Plutella xylostella).

https://ift.tt/2KKTmdY

Analysis of β-Amyloid-induced Abnormalities on Fibrin Clot Structure by Spectroscopy and Scanning Electron Microscopy

Presented here are two methods that can be used individually or in combination to analyze the effect of beta-amyloid on fibrin clot structure. Included is a protocol for creating an in vitro fibrin clot, followed by clot turbidity and scanning electron microscopy methods.

https://ift.tt/2BK7zoR

Rational design of an improved photo-activatable intein for the production of head-to-tail cyclized peptides

Journal Name: Biological Chemistry
Issue: Ahead of print


https://ift.tt/2PfXWSk

Differential involvement of TAK1, RIPK1 and NF-κB signaling in Smac mimetic-induced cell death in breast cancer cells

Journal Name: Biological Chemistry
Issue: Ahead of print


https://ift.tt/2zIaSLR

Large-scale Production of Recombinant RNAs on a Circular Scaffold Using a Viroid-derived System in Escherichia coli

Here, we present a protocol to produce large amounts of recombinant RNA in Escherichia coli by co-expressing a chimeric RNA that contains the RNA of interest in a viroid scaffold and a plant tRNA ligase. The main product is a circular molecule that facilitates purification to homogeneity.

https://ift.tt/2U0T5be

Measuring Liver Mitochondrial Oxygen Consumption and Proton Leak Kinetics to Estimate Mitochondrial Respiration in Holstein Dairy Cattle

Here, we share methods for measuring mitochondrial oxygen consumption, a defining concept of nutritional energetics, and proton leak, the primary cause of inefficiency in mitochondrial generation of ATP. These results can account for 30% of the energy lost in nutrient utilization to help evaluate mitochondrial function.

https://ift.tt/2AEGNvY

A Wind Tunnel for Odor Mediated Insect Behavioural Assays

Here, we describe the construction and use of a wind tunnel for odor mediated behavioural assays with insects. The wind tunnel design facilitates the release of odor sources by several methods, with and without visual stimuli. Wind tunnel experiments are important methods to identify behaviorally active volatile chemicals.

https://ift.tt/2TZSMgF

Bone Indices on CT Scan Predict Fracture Risk in Older Adults

FRIDAY, Nov. 30, 2018 -- High-resolution peripheral quantitative computed tomography (HR-pQCT) indices improve prediction of fracture beyond bone mineral density and Fracture Risk Assessment Tool (FRAX) scores in older adults, according to a study...

https://ift.tt/2E8v6Cj

Increase Seen in Amphetamine, Opioid Use in Pregnant Women

FRIDAY, Nov. 30, 2018 -- The incidence of amphetamine and opioid use has increased among pregnant women, especially in rural counties, according to a study published online Nov. 29 in the American Journal of Public Health. Lindsay K. Admon, M.D.,...

https://ift.tt/2SiTeoD

For Teen Girls, Depression May Predict Subsequent Alcohol Use

FRIDAY, Nov. 30, 2018 -- For adolescent girls, depression, but not anxiety, predicts future alcohol use, according to a study published online Nov. 25 in Alcoholism: Clinical and Experimental Research. Jessica L. Schleider, Ph.D., from the Stony...

https://ift.tt/2E6bT3U

Care for Chronic Kidney Disease Varies Across VA Facilities

FRIDAY, Nov. 30, 2018 -- For veterans with diabetes and concomitant chronic kidney disease (CKD), CKD care, including ordering laboratory tests and scheduling nephrology referrals, varies considerably by facility, according to a study published...

https://ift.tt/2Spc7q9

Results of Pediatric Genomic Epilepsy Tests Often Reclassified

FRIDAY, Nov. 30, 2018 -- The interpretation of genomic epilepsy tests has evolved rapidly in the last five years, and genetic variants identified in pediatric patients are often reclassified, according to research published online Nov. 5 in JAMA...

https://ift.tt/2E8v3X9

Rotating Night Shift Work, Lifestyle Factors Linked to T2DM

FRIDAY, Nov. 30, 2018 -- Both rotating night shift work and unhealthy lifestyle are associated with an increased risk for type 2 diabetes among female nurses, with a significant additive interaction, according to a study published online Nov. 21 in...

https://ift.tt/2Spc6m5

Burnout, Satisfaction Vary With Age, Sex Among Neurologists

FRIDAY, Nov. 30, 2018 -- Burnout, career satisfaction, and well-being vary by age and sex among neurologists, according to a study published online Nov. 15 in Neurology. Kathrin LaFaver, M.D., from the University of Louisville in Kentucky, and...

https://ift.tt/2E8v2T5

Higher Cardiovascular Risk Seen With Psoriatic Arthritis

FRIDAY, Nov. 30, 2018 -- Cardiovascular risk should be carefully evaluated in patients with psoriatic arthritis, according to a study published online Nov. 5 in the International Journal of Rheumatic Diseases. Rubén Queiro, M.D., Ph.D., from...

https://ift.tt/2SpclgZ

Hypnotherapy Beats Education for Relief of IBS Symptoms

FRIDAY, Nov. 30, 2018 -- For patients with irritable bowel syndrome (IBS), individual and group hypnotherapy are more effective than educational supportive therapy in relieving symptoms, according to a study published online Nov. 22 in The Lancet...

https://ift.tt/2E8uZGT

Several Risk Factors More Strongly Linked to MI in Women

FRIDAY, Nov. 30, 2018 -- The incidence of myocardial infarction (MI) is higher in men than women, but several risk factors are more strongly linked to MI in women, according to a study published online Nov. 7 in The BMJ. Elizabeth R.C. Millett,...

https://ift.tt/2Spc2ml

Ethanol-Induced Cervical Sympathetic Ganglion Block Applications for Promoting Canine Inferior Alveolar Nerve Regeneration Using an Artificial Nerve

We evaluated the effect of cervical sympathetic ganglion block on nerve repair using artificial nerve conduits. Male beagle dogs were each implanted with an artificial nerve across a 10-mm gap in the left inferior alveolar nerve; left cervical sympathetic ganglion was blocked by injecting 99.5% ethanol via lateral thoracotomy.

https://ift.tt/2DV0oLF

Eye Tracking During Visually Situated Language Comprehension: Flexibility and Limitations in Uncovering Visual Context Effects

The present article reviews an eye-tracking methodology for studies on language comprehension. To obtain reliable data, key steps of the protocol must be followed. Among these are the correct set-up of the eye tracker (e.g., ensuring good quality of the eye and head images) and accurate calibration.

https://ift.tt/2QuZix8

Nitrogen-dependent induction of atrazine degradation pathway in Pseudomonas sp. strain AKN5

Abstract

Soil isolate Pseudomonas sp. strain AKN5 degrades atrazine as the sole source of nitrogen. The strain showed expeditious growth on medium containing citrate as the carbon source and ammonium chloride as the nitrogen source as compared to citrate plus atrazine or cyanuric acid. Biochemical and nitrogen-source dependent enzyme induction studies revealed that atrazine is metabolized through hydrolytic pathway and has two segments: the upper segment converts atrazine to cyanuric acid while the lower segment metabolizes cyanuric acid to CO₂ and ammonia. Bioinformatics and co-transcriptional analyses suggest that atzA, atzB and atzC were transcribed as three independent transcripts while atzDEF were found to be transcribed as a single polycistronic mRNA indicating operonic arrangement. Transcriptional analysis showed inducible expression of atzA/B/C/DEF from atrazine grown cells while cyanuric acid grown cells showed significantly higher expression of atzDEF. Interestingly, growth profiles and enzyme activity measurements suggests that strain utilizes a simple nitrogen source (ammonium chloride) over the complex (atrazine or cyanuric acid) when grown on dual nitrogen source. These results suggest that atrazine degradation genes were up-regulated in the presence oAf atrazine but repressed in the presence of simple nitrogen source like ammonium chloride.

https://ift.tt/2Rlz7pL

Calcium ion induces outer membrane fusion of Deinococcus grandis spheroplasts to generate giant spheroplasts with multiple cytoplasms

Abstract

Generally, enlarged spheroplasts of the Gram-negative bacterium Deinococcus grandis contain a single cytoplasm and a large periplasmic space. Enlargement of D. grandis spheroplasts requires the presence of divalent cation Ca²⁺ or Mg²⁺. In this study, we elucidated the effects of concentrations of these divalent cations on the enlargement of spheroplasts. We compared the cell sizes of the spheroplasts at five different concentrations (16.2, 62, 100, 200, and 333 mM) of CaCl₂ or MgCl₂. At the lowest concentration (16.2 mM) of CaCl₂ or MgCl₂, the inner membrane of D. grandis spheroplasts collapsed and the spheroplasts did not enlarge. At the highest concentration (333 mM) of CaCl₂ or MgCl₂, enlargement was inhibited. At 200 mM of CaCl₂, the outer membranes of D. grandis spheroplasts were fused repeatedly, but the inner membranes were not fused. Thus, at 200 mM of CaCl₂, giant cells that have multiple cytoplasms were observed and were ≥ 500 μm in diameter. However, cell fusions were not observed in any concentrations of MgCl₂. This indicates that Ca²⁺ induces lipopolysaccharide dehydration more strongly than Mg²⁺ and outer membranes may be fused by hydrophobic bonding. Our findings show the different functions of Ca²⁺ and Mg²⁺ on the outer membrane stability.

https://ift.tt/2Q6NaD6

Design of a Study Assessing Disease Behaviour During the Peri-Diagnostic Period in Patients with Interstitial Lung Disease: The STARLINER Study

Abstract

Background/Objectives

This study will aim to characterise disease behaviour during the peri-diagnostic period in patients with suspected interstitial lung disease (ILD), including idiopathic pulmonary fibrosis (IPF), using daily home spirometry and accelerometry. Additionally, this study will aim to increase collaboration between secondary and tertiary centres using a digital collaboration platform.

Methods

The STARLINER study (NCT03261037) will enrol approximately 180 symptomatic patients aged 50 years or more with radiological evidence of ILD/IPF from community and tertiary centres in Canada and Europe. Approximately two-thirds of sites will be community centres. Patients will be followed during pre-diagnosis (inclusion to diagnosis; up to a maximum of 12 months) and post-diagnosis (diagnosis to treatment initiation; up to a maximum of 6 months). The study will be facilitated by a digital ecosystem consisting of the devices used for home-based assessments and a digital collaboration platform enabling communication between community and tertiary centres, and between clinicians and patients.

Planned Outcomes

The primary endpoint will be time-adjusted semi-annual change in forced vital capacity (FVC; in millilitres) during the peri-diagnostic period. Physical functional capacity and patient-reported outcomes (PROs) will also be assessed. FVC and physical functional capacity will be measured using daily home spirometry and accelerometry, and at site visits using spirometry and the 6-min walk test. PROs will be assessed prior to, or during, site visits and will always be completed in the same order.

Conclusions

Findings from this study may help to facilitate the early and accurate diagnosis of ILDs by increasing knowledge about disease progression, enabling collaboration between community and tertiary centres and improving communication between clinicians and patients.

Trial Registration Number

NCT03261037.

Funding

F. Hoffmann-La Roche, Ltd., Basel, Switzerland.

Plain Language Summary

Plain language summary available for this article.

https://ift.tt/2U1EhZY

Emergency Department Sepsis Care: Could It Matter Who Is in the Ambulance?

Annals of the American Thoracic Society, Volume 15, Issue 12, Page 1398-1400, December 2018.


https://ift.tt/2Q5hbTB

Chronic Asthma and Bronchitis without Persistent Airflow Limitation May Have Been Misclassified as Chronic Obstructive Pulmonary Disease Using Administrative Data

Annals of the American Thoracic Society, Volume 15, Issue 12, Page 1496-1497, December 2018.


https://ift.tt/2RkRivS

Occupational Exposures and Computed Tomographic Imaging Characteristics in the SPIROMICS Cohort

Annals of the American Thoracic Society, Volume 15, Issue 12, Page 1411-1419, December 2018.


https://ift.tt/2Q5AhZZ

Progressive Massive Fibrosis Resurgence Identified in U.S. Coal Miners Filing for Black Lung Benefits, 1970–2016

Annals of the American Thoracic Society, Volume 15, Issue 12, Page 1420-1426, December 2018.


https://ift.tt/2RrcP5S

Dying Patient and Family Contributions to Nurse Distress in the ICU

Annals of the American Thoracic Society, Volume 15, Issue 12, Page 1459-1464, December 2018.


https://ift.tt/2Q12Fwh

Risk Factors for Post-Traumatic Stress Disorder Symptoms in Surrogate Decision-Makers of Patients with Chronic Critical Illness

Annals of the American Thoracic Society, Volume 15, Issue 12, Page 1451-1458, December 2018.


https://ift.tt/2RnvOhJ

Addressing Gender Inequality in Our Disciplines: Report from the Association of Pulmonary, Critical Care, and Sleep Division Chiefs

Annals of the American Thoracic Society, Volume 15, Issue 12, Page 1382-1390, December 2018.


https://ift.tt/2Q2Ext7

Lung Cancer Screening in a Safety-Net Hospital: Implications of Screening a Real-World Population versus the National Lung Screening Trial

Annals of the American Thoracic Society, Volume 15, Issue 12, Page 1493-1495, December 2018.


https://ift.tt/2RmOvlG

The Burden of Silicosis in Michigan: 1988–2016

Annals of the American Thoracic Society, Volume 15, Issue 12, Page 1404-1410, December 2018.


https://ift.tt/2Q4NZwh

Prehospital Care and Emergency Department Door-to-Antibiotic Time in Sepsis

Annals of the American Thoracic Society, Volume 15, Issue 12, Page 1443-1450, December 2018.


https://ift.tt/2RnvJdV

Progressive Massive Fibrosis and Coal Mine Dust Lung Disease: The Continued Resurgence of a Preventable Disease

Annals of the American Thoracic Society, Volume 15, Issue 12, Page 1394-1396, December 2018.


https://ift.tt/2Q6LZna

A Man with Severe Pulmonary Hypertension and Right Ventricular Failure

Annals of the American Thoracic Society, Volume 15, Issue 12, Page 1472-1476, December 2018.


https://ift.tt/2RnvFeb

Sarcoidosis-associated Hospitalizations in the United States, 2002 to 2012

Annals of the American Thoracic Society, Volume 15, Issue 12, Page 1490-1493, December 2018.


https://ift.tt/2Q5hcH9

Occupational Exposure to Vapor, Gas, Dust, and Fumes, and Emphysema and Small Airways Disease: A New Role for Imaging with Computed Tomography

Annals of the American Thoracic Society, Volume 15, Issue 12, Page 1393-1394, December 2018.


https://ift.tt/2RpZtXN

Structural and Functional Lung Impairment in Primary Ciliary Dyskinesia. Assessment with Magnetic Resonance Imaging and Multiple Breath Washout in Comparison to Spirometry

Annals of the American Thoracic Society, Volume 15, Issue 12, Page 1434-1442, December 2018.


https://ift.tt/2Q6djC2

Upper Airway Narrowing during Central Apnea in Obese Adolescents

Annals of the American Thoracic Society, Volume 15, Issue 12, Page 1465-1471, December 2018.


https://ift.tt/2RoaKaR

Optimizing Home Oxygen Therapy. An Official American Thoracic Society Workshop Report

Annals of the American Thoracic Society, Volume 15, Issue 12, Page 1369-1381, December 2018.


https://ift.tt/2Q6dcq6

Imaging Lung Function Abnormalities in Primary Ciliary Dyskinesia Using Hyperpolarized Gas Ventilation MRI

Annals of the American Thoracic Society, Volume 15, Issue 12, Page 1487-1490, December 2018.


https://ift.tt/2Rq4qjg

A Young Man with Fevers and an Invasive Mediastinal Mass

Annals of the American Thoracic Society, Volume 15, Issue 12, Page 1477-1482, December 2018.


https://ift.tt/2Q20WXw

Genomic Test Helps Identify Thyroid Nodules That Don’t Require Surgery

The test measures genomic changes in thyroid biopsy samples and generates a score based on how strongly each change is associated with thyroid cancer. A study showed the test accurately identified samples that, after surgery, were found to be benign.

https://ift.tt/2Pbznpg

Therapeutic Targeting of Vascular Remodeling and Right Heart Failure in Pulmonary Arterial Hypertension with a HIF-2α Inhibitor

American Journal of Respiratory and Critical Care Medicine, Volume 198, Issue 11, Page 1423-1434, December 1, 2018.


https://ift.tt/2RpxjMx

Erratum: At the Root: Defining and Halting Progression of Early Chronic Obstructive Pulmonary Disease

American Journal of Respiratory and Critical Care Medicine, Volume 198, Issue 11, Page 1463-1463, December 1, 2018.


https://ift.tt/2Q9vtD2

End-of-Life Strategies among Patients with Advanced Chronic Obstructive Pulmonary Disease

American Journal of Respiratory and Critical Care Medicine, Volume 198, Issue 11, Page 1389-1396, December 1, 2018.


https://ift.tt/2RnrSxt

Poor Agreement and Imprecision of Respiratory Rate Measurements in Children in a Low-Income Setting

American Journal of Respiratory and Critical Care Medicine, Volume 198, Issue 11, Page 1462-1463, December 1, 2018.


https://ift.tt/2Q2B79L

Controlling for Obesity in Obstructive Sleep Apnea. Results from Dynamic Magnetic Resonance Imaging

American Journal of Respiratory and Critical Care Medicine, Volume 198, Issue 11, Page 1365-1366, December 1, 2018.


https://ift.tt/2Rwq6tS

Lung Function through the PRISm. Spreading Light or Creating Confusion?

American Journal of Respiratory and Critical Care Medicine, Volume 198, Issue 11, Page 1358-1360, December 1, 2018.


https://ift.tt/2Q3Q4s1

Ontogeny and Biology of Human Small Airway Epithelial Club Cells

American Journal of Respiratory and Critical Care Medicine, Volume 198, Issue 11, Page 1375-1388, December 1, 2018.


https://ift.tt/2Rwq4lK

Exacerbation of COPD

American Journal of Respiratory and Critical Care Medicine, Volume 198, Issue 11, Page P21-P22, December 1, 2018.


https://ift.tt/2Q9vt60

Palliative Care for Chronic Obstructive Pulmonary Disease. Signs of Progress, but Still a Long Way to Go

American Journal of Respiratory and Critical Care Medicine, Volume 198, Issue 11, Page 1356-1358, December 1, 2018.


https://ift.tt/2Rrkame

The Course of Lung Function in Middle-aged Heavy Smokers: Incidence and Time to Early Onset of Chronic Obstructive Pulmonary Disease

American Journal of Respiratory and Critical Care Medicine, Volume 198, Issue 11, Page 1449-1451, December 1, 2018.


https://ift.tt/2Q1IWfO

Cigarette Smoking Acutely Decreases Serum Levels of the Chronic Obstructive Pulmonary Disease Biomarker sRAGE

American Journal of Respiratory and Critical Care Medicine, Volume 198, Issue 11, Page 1456-1458, December 1, 2018.


https://ift.tt/2RpVv1l

The Medical Perspective on a Disease Life Cycle. Sepsis in the Realm of Implementation Science

American Journal of Respiratory and Critical Care Medicine, Volume 198, Issue 11, Page 1360-1361, December 1, 2018.


https://ift.tt/2Q3wHzu

Mucin Concentrations and Peripheral Airway Obstruction in Chronic Obstructive Pulmonary Disease

American Journal of Respiratory and Critical Care Medicine, Volume 198, Issue 11, Page 1453-1456, December 1, 2018.


https://ift.tt/2RlvCQ9

Acute Respiratory Distress Syndrome Potentially Caused by Respiratory Syncytial Virus and a Diatom

American Journal of Respiratory and Critical Care Medicine, Volume 198, Issue 11, Page 1447-1448, December 1, 2018.


https://ift.tt/2Q83uUh

Longitudinal Phenotypes and Mortality in Preserved Ratio Impaired Spirometry in the COPDGene Study

American Journal of Respiratory and Critical Care Medicine, Volume 198, Issue 11, Page 1397-1405, December 1, 2018.


https://ift.tt/2Rkb2Q6

Organ Function Assessment, Prevention, and Outcomes in Critically Ill Patients with Sepsis

American Journal of Respiratory and Critical Care Medicine, Volume 198, Issue 11, Page 1444-1446, December 1, 2018.


https://ift.tt/2Q43F2S

What’s HIF Got to Do with It? HIF-2 Inhibition and Pulmonary Hypertension

American Journal of Respiratory and Critical Care Medicine, Volume 198, Issue 11, Page 1363-1365, December 1, 2018.


https://ift.tt/2RvkK2o

Concerns over Airway Pressure Release Ventilation Management in Children with Acute Respiratory Distress Syndrome

American Journal of Respiratory and Critical Care Medicine, Volume 198, Issue 11, Page 1458-1459, December 1, 2018.


https://ift.tt/2Q2B1Pr

Mortality Changes Associated with Mandated Public Reporting for Sepsis. The Results of the New York State Initiative

American Journal of Respiratory and Critical Care Medicine, Volume 198, Issue 11, Page 1406-1412, December 1, 2018.


https://ift.tt/2Rpxfwh

The Impact of Real-World Particulate Matter Air Pollution on the Airways of Susceptible Individuals

American Journal of Respiratory and Critical Care Medicine, Volume 198, Issue 11, Page 1362-1363, December 1, 2018.


https://ift.tt/2Q5etxp

LncRNA-UCA1 promotes PD development by upregulating SNCA

OBJECTIVE: The study aims to investigate whether Long non-coding RNA (LncRNA)-UCA1 can regulate the progression of Parkinson's disease (PD) by mediating a-synuclein (SNCA) expression.

MATERIALS AND METHODS: PD mouse model was first constructed by intraperitoneal injection of MPTP. SH-SY5Y cells were treated with MPP+ for inducing in vitro PD model. Expression levels of lncRNA-UCA1 and SNCA in brain tissues extracted from PD mice and MPP+-induced SH-SY5Y cells were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Protein expression of SNCA was accessed by Western blot. After transfection of pcDNA-NC+DMSO, pcDNA-UCA1+DMSO, pcDNA-NC+α-amantin or pcDNA-UCA1+α-amanitin in SH-SY5Y cells, SNCA expression was detected. Cell viability and SNCA expression were determined after UCA1 overexpression or knockdown in SH-SY5Y cells. Neuronal apoptosis in MPP+-induced SH-SY5Y cells was detected by flow cytometry after the UCA1 knockdown.

RESULTS: UCA1 and SNCA were highly expressed in brain tissues extracted from PD mice and MPP+-induced SH-SY5Y cells. UCA1 overexpression remarkably upregulated mRNA and protein expressions of SNCA in SH-SY5Y cells. Higher viability was seen after the UCA1 knockdown in MPP+-induced SH-SY5Y cells. UCA1 knockdown remarkably inhibited caspase-3 activity and decreased MPP+-induced neuronal apoptosis in SH-SY5Y cells.

CONCLUSIONS: LncRNA-UCA1 promotes the occurrence and progression of PD by upregulating SNCA expression.

L'articolo LncRNA-UCA1 promotes PD development by upregulating SNCA sembra essere il primo su European Review.

https://ift.tt/2zxGRhF

MiR-940 regulates angiogenesis after cerebral infarction through VEGF

OBJECTIVE: The aim of this study was to investigate whether miR-490 was involved in the regulation of angiogenesis after cerebral infarction by regulating vascular endothelial growth factor (VEGF) expression.

MATERIALS AND METHODS: Sprague Dawley (SD) rats were used to establish a middle cerebral artery infarction model. Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was used to detect the expression levels of miR-940 in serum and brain tissues at 1, 3, and 7 days after cerebral infarction. Meanwhile, miR-940 expression in brain microvascular endothelial cells (BMECs) after Oxygen-Glucose Deprivation (OGD) for 2, 4, 6 hours was measured by qRT-PCR, respectively. The cells were transfected with miR-940 mimics/inhibitor to achieve miR-940 overexpression or inhibition. Subsequently, the angiogenesis and proliferation ability of the cells was evaluated by 5-ethynyl-2′-deoxyuridine (EDU) assay. Besides, the mRNA and protein expression levels of VEGF after miR-940 transfection were detected by Western blot and qRT-PCR, respectively. Finally, recovery experiment was used to determine whether miR-940 affected angiogenesis and proliferation of BMECs by regulating VEGF expression.

RESULTS: The expression level of miR-940 in serum and brain tissues of rats was markedly decreased at 1, 3, and 7 days after cerebral infarction, which was then recovered on the 7th day. After 2, 4, and 6 hours of glucose and oxygen deprivation in BMECs, the expression level of miR-940 was significantly decreased. However, it was evidently recovered after 6 hours. After miR-940 over-expression in BMECs, the angiogenesis and proliferation of BMECs were remarkably inhibited. Conversely, miR-940 inhibitor transfection could significantly promote the formation of luminal cells and the proliferation of BMECs. QRT-PCR results showed that miR-940 overexpression down-regulated the expression level of VEGF, and the same findings were observed at the protein level. Further studies revealed that VEGF could reverse the inhibitory effect of miR-940 on lumen formation and cell proliferation in BMECs.

CONCLUSIONS: The expression of miR-940 was downregulated in cerebral infarction. The low expression of miR-940 could promote the angiogenesis ability of cerebral microvascular endothelial cells after cerebral infarction, which might be resulted from the inhibitory effect of miR-940 on VEGF.

L'articolo MiR-940 regulates angiogenesis after cerebral infarction through VEGF sembra essere il primo su European Review.

https://ift.tt/2Pb5Egv

Cancers, Vol. 10, Pages 479: Helicobacter pylori Infection-Induced Hepatoma-Derived Growth Factor Regulates the Differentiation of Human Mesenchymal Stem Cells to Myofibroblast-Like Cells

Cancers, Vol. 10, Pages 479: Helicobacter pylori Infection-Induced Hepatoma-Derived Growth Factor Regulates the Differentiation of Human Mesenchymal Stem Cells to Myofibroblast-Like Cells

Cancers doi: 10.3390/cancers10120479

Authors: Chung-Jung Liu Yao-Kuang Wang Fu-Chen Kuo Wen-Hung Hsu Fang-Jung Yu Shuchen Hsieh Ming-Hong Tai Deng-Chyang Wu Chao-Hung Kuo

Hepatoma-derived growth factor (HDGF) plays a critical role in tumor cell proliferation, anti-apoptosis, VEGF expression, lymph node metastasis and poor prognosis in human gastric cancer. Gastric cancer, as one of the most prevalent cancers worldwide, is the second leading cause of cancer-related mortality in the world for the prognosis of gastric cancer is generally poor, especially in patients with advanced stage. Helicobacter pylori (H. pylori) infection causes the chronic inflammation of stomach as well as the development of gastric cancer, with a three to six-fold increased risk of gastric cancer. Carcinoma-associated fibroblasts (CAFs) are myofibroblasts in tumor microenvironment, which possess various abilities to promote the progression of cancer by stimulating neoangiogenesis, proliferation, migration, invasion and therapy resistance of tumor cell. Mesenchymal stem cells (MSCs) are reported to promote tumor malignance through differentiation of MSCs toward CAFs. In the present study, we demonstrated that H. pylori infection promotes HDGF expression in human gastric cancer cells. HBMMSCs treated with HDGF assume properties of CAF-like myofibroblastic phenotypes, including expression of myofibroblast markers (α-smooth muscle actin (α-SMA), procollagen α1, tropomyoson I, desmin, fibroblast activation protein (FAP)), and fibroblast markers (prolyl-4-hydroxylase A1 (PHA1) and fibroblast specific protein-1 (FSP-1)/S100A4). HDGF recruits HBMMSCs, and then HBMMSCs further contributes to cell survival and invasive motility in human gastric cancer cells. Treatment of HDGF neutralizing antibody (HDGF-NAb) and serum significantly inhibit HDGF-regulated differentiation and recruitment of HBMMSCs. These findings suggest that HDGF might play a critical role in gastric cancer progress through stimulation of HBMMSCs differentiation to myofibroblast-like cells.

https://ift.tt/2DWiRYe

When It Comes to Alternaria, Instant CARMA’s Gonna Get You

American Journal of Respiratory Cell and Molecular Biology, Volume 59, Issue 6, Page 657-658, December 2018.


https://ift.tt/2SkpWWQ

Lanosterol Synthase Regulates Human Rhinovirus Replication in Human Bronchial Epithelial Cells

American Journal of Respiratory Cell and Molecular Biology, Volume 59, Issue 6, Page 713-722, December 2018.


https://ift.tt/2E6LYJj

December Highlights/Papers by Junior Investigators/NIH News

American Journal of Respiratory Cell and Molecular Biology, Volume 59, Issue 6, Page vi-vi, December 2018.


https://ift.tt/2Smlqai

Influenza in Smokers: More than Just a Cause of Symptom Exacerbations?

American Journal of Respiratory Cell and Molecular Biology, Volume 59, Issue 6, Page 670-671, December 2018.


https://ift.tt/2E8hnLN

Targeting Intracellular Ion Homeostasis for the Control of Respiratory Syncytial Virus

American Journal of Respiratory Cell and Molecular Biology, Volume 59, Issue 6, Page 733-744, December 2018.


https://ift.tt/2Sk956f

Impact of Cigarette Smoke Exposure on the Lung Fibroblastic Response after Influenza Pneumonia

American Journal of Respiratory Cell and Molecular Biology, Volume 59, Issue 6, Page 770-781, December 2018.


https://ift.tt/2E632ze

Could Immunotherapy Sink Its Teeth into Lymphangioleiomyomatosis?

American Journal of Respiratory Cell and Molecular Biology, Volume 59, Issue 6, Page 663-665, December 2018.


https://ift.tt/2Sml9Ei

Chronic Cigarette Smoke Exposure Subdues PP2A Activity by Enhancing Expression of the Oncogene CIP2A

American Journal of Respiratory Cell and Molecular Biology, Volume 59, Issue 6, Page 695-705, December 2018.


https://ift.tt/2E6wxRG

Neutrophils and Bacterial Coinfection: Aiding and Abetting

American Journal of Respiratory Cell and Molecular Biology, Volume 59, Issue 6, Page 668-669, December 2018.


https://ift.tt/2SjNkUg

CARMA3 Mediates Allergic Lung Inflammation in Response to Alternaria alternata

American Journal of Respiratory Cell and Molecular Biology, Volume 59, Issue 6, Page 684-694, December 2018.


https://ift.tt/2E9F0Dw

PP2A as a New Player in Chronic Obstructive Pulmonary Disease

American Journal of Respiratory Cell and Molecular Biology, Volume 59, Issue 6, Page 659-660, December 2018.


https://ift.tt/2Sn1Gn0

Immune Checkpoint Ligand PD-L1 Is Upregulated in Pulmonary Lymphangioleiomyomatosis

American Journal of Respiratory Cell and Molecular Biology, Volume 59, Issue 6, Page 723-732, December 2018.


https://ift.tt/2E7Cgqi

A Nonhospitable Host: Targeting Cellular Factors as an Antiviral Strategy for Respiratory Viruses

American Journal of Respiratory Cell and Molecular Biology, Volume 59, Issue 6, Page 666-667, December 2018.


https://ift.tt/2Sml0ke

Induced Pluripotent Stem Cells for Primary Ciliary Dyskinesia Modeling and Personalized Medicine

American Journal of Respiratory Cell and Molecular Biology, Volume 59, Issue 6, Page 672-683, December 2018.


https://ift.tt/2E5nFvl

Ager-CreERT2: A New Genetic Tool for Studying Lung Alveolar Development, Homeostasis, and Repair

American Journal of Respiratory Cell and Molecular Biology, Volume 59, Issue 6, Page 706-712, December 2018.


https://ift.tt/2Srw2EX

Alveolar Micromechanics in Bleomycin-induced Lung Injury

American Journal of Respiratory Cell and Molecular Biology, Volume 59, Issue 6, Page 757-769, December 2018.


https://ift.tt/2E7C5v8

The Neutrophilic Response to Pseudomonas Damages the Airway Barrier, Promoting Infection by Klebsiella pneumoniae

American Journal of Respiratory Cell and Molecular Biology, Volume 59, Issue 6, Page 745-756, December 2018.


https://ift.tt/2Smkqmy

A New “Age”r for Lung Research Arrives: Genetic Targeting of Alveolar Type 1 Epithelial Cells

American Journal of Respiratory Cell and Molecular Biology, Volume 59, Issue 6, Page 661-662, December 2018.


https://ift.tt/2E6oOTo

LncRNA ZNF667-AS1 inhibits inflammatory response and promotes recovery of spinal cord injury via suppressing JAK-STAT pathway

OBJECTIVE: The aim of this study was to explore the role of lncRNA ZNF667-AS1 in the recovery of spinal cord injury (SCI), and to investigate its underlying mechanism.

MATERIALS AND METHODS: Mice were randomly assigned to the SCI group, the sham group and the lncRNA ZNF667-AS1 group, with 10 mice in each group. With Infinite Horizon device at a dose of 80 Kdyn, mice in the SCI group and the lncRNA ZNF667-AS1 group experienced SCI by an acute hit on the C5 spinous process. Before animal procedures, mice in the lncRNA ZNF667-AS1 group were additionally injected with overexpression lentivirus of lncRNA ZNF667-AS1. On the contrary, mice in the sham group only received laminectomy. After successful construction of the SCI model in mice, grip strength was accessed. LncRNA ZNF667-AS1 expression in spinal cord tissues before and after SCI was detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR), respectively. Meanwhile, the protein expression levels of relative genes in Janus Kinase-signal transducer and activator of transcription (JAK-STAT) pathway were detected by Western blot.

RESULTS: Grip strength of forelimb in the SCI group recovered significantly slower than that of the sham group. With the prolongation of SCI, the expression of lncRNA ZNF667-AS1 was gradually decreased. However, the expression levels of JAK2, STAT3 and iNOS were upregulated in a time-dependent manner. In addition, mice in the lncRNA ZNF667-AS1 group presented remarkable grip strength recovery of forelimb after SCI.

CONCLUSIONS: LncRNA ZNF667-AS expression is gradually downregulated after SCI. Meanwhile, it inhibits the inflammatory response and promotes SCI recovery via suppressing the JAK-STAT pathway.

L'articolo LncRNA ZNF667-AS1 inhibits inflammatory response and promotes recovery of spinal cord injury via suppressing JAK-STAT pathway sembra essere il primo su European Review.

https://ift.tt/2rfSGo5

DUSP1 promotes senescence of retinoblastoma cell line SO-Rb5 cells by activating AKT signaling pathway

OBJECTIVE: Retinoblastoma seriously threats to human health and life. Molecular targeted therapy of retinoblastoma supplies the direction of research in the future. This study aims to investigate the impact of DUSP1 on human retinoblastoma SO-Rb5 cell senescence.

MATERIALS AND METHODS: Angiotensin II (AGII) was used to induce human retinoblastoma SO-Rb5 cell senescence model. DUSP1 over-expression plasmid and small interfere RNA (siRNA) were transfected into SO-Rb5 cells by Lipofectamine. Dual specificity phosphatase 1 (DUSP1), p53, p16, and protein kinase B (Akt) signaling expressions were detected with Western blot assay. SH-6 was applied to inhibit Akt signaling in SO-Rb5 cells. Cell senescence was evaluated by using β-galactosidase test.

RESULTS: DUSP1 level increased in SO-Rb5 cells induced by AGII. Senescence protein p53 and p16 significantly upregulated in SO-Rb5 cell senescence model, together with β-galactosidase staining. DUSP1 plasmid transfection significantly enhanced DUSP expression, triggered SO-Rb5 cell senescence, and inhibited Akt signaling activation. DUSP1 siRNA exhibited the opposite effects. SH-6 significantly increased SO-Rb5 cell senescence induced by AGII through inhibiting Akt signaling.

CONCLUSIONS: DUSP1 facilitated human retinoblastoma SO-Rb5 cell senescence induced by AGII through inhibiting Akt signaling pathway.

L'articolo DUSP1 promotes senescence of retinoblastoma cell line SO-Rb5 cells by activating AKT signaling pathway sembra essere il primo su European Review.

https://ift.tt/2FT33Iv

Expression of lamin A/C protein in degenerated human intervertebral disc

OBJECTIVE: This study aimed to evaluate the expression characteristics of lamin A/C proteins in intervertebral disc degeneration (IVD) specimens from patients with different degeneration grades. Lamin A/C proteins have been shown to result in age-related changes in the osteoarticular system. However, the expression characteristics of these nuclear proteins in degenerated human IVD tissues have not been explored previously.

PATIENTS AND METHODS: Degenerated human IVD tissues were obtained during spinal surgery. Articular cartilage samples after total knee replacement surgery were used as controls. Sections of these tissues were stained with hematoxylin and eosin, Masson, safranin O, and immunostained using lamin A/C antibody. Western blot was performed to evaluate lamin A/C expression in IVD tissues. Lamin A/C expression was analyzed based on different degeneration grades.

RESULTS: In patients with IVD degeneration, mild or moderate degenerative discs contained high amounts of lamin A/C proteins. Lamin A/C expression was primarily localized in the nuclear envelope of IVD cells, and associated with apoptosis in cell nuclei, as determined by immunostaining and TUNEL assay.

CONCLUSIONS: This paper is the first to report that lamin A/C proteins are present in IVD tissues and its expression may be related to disc degeneration.

L'articolo Expression of lamin A/C protein in degenerated human intervertebral disc sembra essere il primo su European Review.

https://ift.tt/2rcChkb

HGF alleviates renal interstitial fibrosis via inhibiting the TGF-β1/SMAD pathway

OBJECTIVE: To study the role of HGF (stem cell growth factor) in renal interstitial fibrosis and to explore its underlying mechanism.

MATERIALS AND METHODS: A unilateral ureteral obstruction (UUO) mouse model was first constructed, and kidney samples of mice were then collected. Fibrosis-related indicators in UUO mice kidney were detected by Western blot. The mRNA and protein levels of HGF in UUO mice were detected by quantitative Real-time-polymerase chain reaction (qRT-PCR) and Western blot, respectively. The HGF overexpression mouse model was established by using UUO mice. For in vitro experiments, fibrosis-related indicators and the expression of HGF were detected in transforming growth factor-β1 (TGF-β1)-induced NRK-52E cells. Finally, a p-SMAD3 knockdown mouse model was established to confirm whether p-SMAD3 was involved in HGF-regulated renal interstitial fibrosis.

RESULTS: The expression levels of HGF and α-SMA (α-smooth muscle actin) were both significantly increased in UUO mice, while E-cadherin expression was significantly decreased, which were consistent with results of in vitro experiments. Overexpression of HGF remarkably decreased the protein and mRNA levels of α-SMA in fibrotic NRK-52E cells. After overexpression of HGF in UUO mice, α-SMA was remarkably downregulated, whereas E-cadherin was significantly upregulated. Further, results also demonstrated that HGF was upregulated and α-SMA was downregulated after p-SMAD3 knockdown in UUO mice.

CONCLUSIONS: HGF is highly expressed during renal interstitial fibrosis, which may suppress renal interstitial fibrosis by inhibiting the TGF-β1/SMAD signaling pathway.

L'articolo HGF alleviates renal interstitial fibrosis via inhibiting the TGF-β1/SMAD pathway sembra essere il primo su European Review.

https://ift.tt/2FRWNAI

Downregulation of miR-1294 associates with prognosis and tumor progression in epithelial ovarian cancer

OBJECTIVE: Increasing evidence has revealed that microRNAs (miRNAs) act as key players in the regulation of tumor growth and metastasis in epithelial ovarian cancer (EOC). However, the clinical role and functional effects of miR-1294 in EOC remain unknown.

PATIENTS AND METHODS: We examined the expression of miR-1294 in 69 cases of EOC tissues and cell lines by quantitative Real-time polymerase chain reaction (qRT-PCR). The associations of miR-1294 expression with clinicopathologic features and overall survival of EOC patients were analyzed. Biological functional effects of miR-1294 expression on cell growth were analyzed using Cell Counting Kit-8 (CCK8) assays and flow cytometry assays in vitro.

RESULTS: In the present study, we identified that miR-1294 expression was lower in 76 specimens of EOC compared to adjacent normal tissues. Lower miR-1294 expression was related to FIGO stage, lymph node metastasis and shorter overall survival rate in EOC patients. Multivariate Cox analysis demonstrated that miR-1294 expression was an independent prognostic indicator of EOC patients. Gain function assays showed that miR-1294 overexpression inhibited cell proliferation and cell cycle progression in EOC.

CONCLUSIONS: Our results indicated that miR-1294 acted as a prognostic biomarker and potential target of EOC treatment.

L'articolo Downregulation of miR-1294 associates with prognosis and tumor progression in epithelial ovarian cancer sembra essere il primo su European Review.

https://ift.tt/2rcxOOz

High levels of long non-coding RNA DICER1-AS1 are associated with poor clinical prognosis in patients with osteosarcoma

OBJECTIVE: Long noncoding RNA DICER1-AS1 (DICER1-AS1) has been reported to be upregulated in osteosarcoma cells and to serve as a tumor promoter. However, the clinical significance of DICER1-AS1 in osteosarcoma remains unclear. The aim of this study was to investigate the association of DICER1-AS1 expression with prognosis of osteosarcoma.

PATIENTS AND METHODS: The expression of DICER1-AS1 was measured in 214 osteosarcoma samples and normal bone samples by using Real-time PCR. The correlations between DICER1-AS1 expression and clinical features were statistically analyzed. Overall survival (OS) and disease-free survival (DFS) were examined using Kaplan-Meier curves. Multivariate analyses were performed to analyze the prognostic significance of DICER1-AS1 expression.

RESULTS: It was found that the expression levels of DICER1-AS1 in osteosarcoma tissues were significantly higher than those in corresponding noncancerous bone tissues (p < 0.01). Higher DICER1-AS1 had significant association with clinical stage (p = 0.005) and distant metastasis (p = 0.000). Kaplan-Meier survival analysis showed that patients with high DICER1-AS1 expression had a shorter OS and DFS compared with the low DICER1-AS1 expression group (p = 0.007 and p < 0.0001). In a multivariate Cox model, our results showed that DICER1-AS1 expression was an independent poor prognostic factor for both 5-year OS (HR = 3.236, 95% CI: 1.148-5.347; p = 0.004) and 5-year DFS (HR = 3.935, 95% CI: 1.556-6.349; p = 0.001).

CONCLUSIONS: DICER1-AS1 is up-regulated in osteosarcoma and may serve as a potential prognostic biomarker for osteosarcoma.

L'articolo High levels of long non-coding RNA DICER1-AS1 are associated with poor clinical prognosis in patients with osteosarcoma sembra essere il primo su European Review.

https://ift.tt/2FOV6nz