The potential of the incorporated collagen microspheres in alginate hydrogel as an engineered three-dimensional microenvironment to attenuate apoptosis in human pancreatic islets

xlomafota13 shared this article with you from Inoreader The potential of the incorporated collagen microspheres in alginate hydrogel as an engineered three-dimensional microenvironment to attenuate apoptosis in human pancreatic islets Via histochem Acta Histochem. 2021 Aug 24;123(7):151775. doi: 10.1016/j.acthis.2021.151775. Online ahead of print. ABSTRACT BACKGROUND: Tissue engineering is considered as a promising tool for remodeling the native cells microenvironment. In the present study, the effect of alginate hydrogel and collagen microspheres integrated with extracellular matrix components were evaluated in the decrement of apoptosis in human pancreatic islets. MATERIALS/METHODS: For three-dimensional cultur e, the islets were encapsulated in collagen microspheres, containing laminin and collagen IV and embedded in alginate scaffold for one week. After that the islets were examined in terms of viability, apoptosis, genes and proteins expression including BAX, BCL2, active caspase-3, and insulin. Moreover, the islets function was evaluated through glucose-induced insulin and C-peptide secretion assay. In order to evaluate the structure of the scaffolds and the morphology of the pancreatic islets in three-dimensional microenvironments, we performed scanning electron microscopy. RESULTS: Our findings showed that the designed hydrogel scaffolds significantly improved the islets viability using the reduction of activated caspase-3 and TUNEL positive cells. CONCLUSIONS: The reconstruction of the destructed matrix with alginate hydrogels and collagen microspheres might be an effective step to promote the culture of the islets. PMID:34450327 | DOI:10.1016/j.acthis.2021.151775 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

BMP2 downregulates urokinase-type plasminogen activator via p38 MAPK: Implications in C2C12 cells myogenic differentiation

xlomafota13 shared this article with you from Inoreader BMP2 downregulates urokinase-type plasminogen activator via p38 MAPK: Implications in C2C12 cells myogenic differentiation Via histochem Acta Histochem. 2021 Aug 23;123(6):151774. doi: 10.1016/j.acthis.2021.151774. Online ahead of print. ABSTRACT Bone morphogenetic protein (BMP)2 strongly affects the differentiation program of myoblast cells by inhibiting myogenesis and inducing osteogenic differentiation. In turn, extracellular matrix (ECM) proteinases, such as urokinase-type plasminogen activator (uPA), can influence the fate of muscle stem cells by participating in ECM reorganization. Although both BMP2 an d uPA have antagonistic roles in muscles cells differentiation, no connection between them has been elucidated so far. This study aims to determine whether BMP2 regulates uPA expression in the myogenic C2C12 cell line and its impact on muscle cell fate differentiation. Our results showed that BMP2 did not modify C2C12 cell proliferation in a growth medium or myogenic differentiation medium. Although BMP2 inhibited myogenesis and induced osteogenesis, these effects were achieved with different doses of BMP2. Low concentrations of BMP2 blocked myogenesis, while a higher concentration was needed to induce osteogenesis. Reduced uPA expression was noticed alongside myogenic inhibition at low concentrations of BMP2. BMP2 activated p38 MAPK signaling to inhibit uPA activity. Furthermore, ectopic human uPA expression reduced BMP2's ability to inhibit the myogenic differentiation of C2C12 cells. In conclusion, BMP2 inhibits uPA expression through p38 MAPK and in vitro myogenesis at non-osteo genic concentrations, while uPA ectopic expression prevents BMP2 from inhibiting myogenesis in C2C12 cells. PMID:34450502 | DOI:10.1016/j.acthis.2021.151774 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Catamnesis after a single intervention for tinnitus patients in a specialized clinic

xlomafota13 shared this article with you from Inoreader Catamnesis after a single intervention for tinnitus patients in a specialized clinic Via hno HNO. 2021 Aug 27. doi: 10.1007/s00106-021-01103-3. Online ahead of print. ABSTRACT BACKGROUND: Patients suffering from tinnitus require individualized clarification (counseling), sometimes going beyond the scope of the field of ENT and the initiation of specific interventions. AIM: To investigate if patients who had a specific neurotological assessment including a psychosomatic medical history follow the recommendations provided to them. In addition, it should be exami ned whether compliance with the treatment suggestions has led to any psychological improvement in the suffering from tinnitus, evaluated by psychological tests. MATERIAL AND METHOD: In295 out of 699 patients audiological tests were evaluated using the mini-questionnaire (TF 12) according to Hiller and Goebel and the German language version of the Hospitality Anxiety and Depression Scale (HADS) at 2 points in time with an interval of a least 6 months. The group of those who followed the recommendations were compared to the group of those who did not follow the recommendations. RESULTS: A total of 180 patients (64.5%) followed at least 1 of the recommendations made to them. Patients who followed at least one recommendation benefited significantly more than the whole group in the TF 12 and in both HADS categories compared to the group that did not follow the recommendations. CONCLUSION: In addition to counseling it was shown that the implementation of a specific measu re has a positive effect, detectable for the Progressive Muscle Relaxation (PMR). Specific for ENT, a hearing aid can initiate an improvement even if no statistically significant difference to the comparison group was found. PMID:34453187 | DOI:10.1007/s00106-021-01103-3 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Do people living with HIV face more secondary cancers than general population: From the French CANCERVIH network

xlomafota13 shared this article with you from Inoreader Do people living with HIV face more secondary cancers than general population: From the French CANCERVIH network Via Association française pour l'étude du cancer Bull Cancer. 2021 Aug 24:S0007-4551(21)00282-4. doi: 10.1016/j.bulcan.2021.01.026. Online ahead of print. ABSTRACT INTRODUCTION: People living with HIV (PLWHIV) are at a higher risk of cancer compared to the general population. With improved cancer treatments and the increased life expectancy of PLWHIV, the incidence of second cancers is also expected to increase. METHODS: We reviewed the cases of PLWHIV with cancer that have been presented to the CANCERVIH national multidisciplinary board since 2014. We included all cases with a history of cancer, and studied the incidence and types of second cancers. RESULTS: In total, 719 cases were reviewed, out of which 94 (13%) had a history of at least one cancer. For the first primary cancers, 46 (49%) were AIDS-defining cancers (ADCs) and 48 (51%) were non-AIDS-defining cancers (NADCs). Kaposi sarcoma (33%) and NHL (15%) occurred most frequently as first cancers. Among the first ca ncers that were ADCs, 15% of the second cancers were NHL, 11% anal canal cancers, 9% bladder and 9% Hodgkin lymphomas. Among the first cancers that were NADCs, 38% of the second cancers were lung cancers, 8% bladder, 8% head and neck and 8% NHL. DISCUSSION: With the aging of PLWHIV, the incidence of second and subsequent cancers is expected to increase in this population. Immuno-virological control should be maintained. Increased surveillance, early prevention and screening programs should be offered to all PLWHIV, including those with an undetectable HIV viral load and/or immune restoration. PMID:34452700 | DOI:10.1016/j.bulcan.2021.01.026 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Regression of nevi, vitiligo-like depigmentation and halo phenomenon may indicate response to immunotherapy and targeted therapy in melanoma

xlomafota13 shared this article with you from Inoreader Regression of nevi, vitiligo-like depigmentation and halo phenomenon may indicate response to immunotherapy and targeted therapy in melanoma Via Melanoma Research - Published Ahead-of-Print We present two patients with stage IV melanoma, the first with BRAF wild-type melanoma with multiple visceral metastases treated with immunotherapy (pembrolizumab) and the second with BRAFV600E melanoma with subcutaneous and lymph nodes metastasis treated with BRAF and MEK-inhibitors (dabrafenib/trametinib). Already a fter the second cycle of immunotherapy, the first patient developed a diffuse regression of nevi, perceptible only with the use of dermoscopy and 3 months later a clinically evident poliosis of the eyebrows. The second patient, treated with dabrafenib/trametinib, developed small areas of leukoderma on his chest and white halos around nevi with a dermoscopic globular or structureless pattern. Both observations are suggestive for an immune reaction against melanocytic cells, which is further supported by the complete response to systemic therapy in both patients. It has been demonstrated that the development of vitiligo-like depigmentation during immunotherapy is associated with a better prognosis; in our patient, the phenomenon of poliosis appeared much later than the dermoscopic presence of regression among his nevi, suggesting that the latter may be an early sign (along with vitiligo-like phenomena) of good response to immunotherapy. On the other hand, the development of halo nev i and leukoderma during treatment with BRAF/MEK-inhibitors, suggests that not only immunotherapy but also targeted therapy may induce an immunologic response against melanoma and nevi, again indicative of a favorable prognosis. More data are needed to confirm these findings; however, they indicate that dermatologists should be involved in the follow-up of patients with melanoma, both in studies and clinical practice. Received 23 May 2021 Accepted 24 July 2021 Correspondence to Eleonora Farinazzo, MD, Department of Medicine, Surgery and Health Sciences, University of Trieste, Piazza dell'Ospitale 1, 34125, Trieste, Italy, Tel: +39 040 3992056; e-mail: farinazzo.eleonora@gmail.com Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Nivolumab exposure in a hemodialysis patient with metastatic melanoma

xlomafota13 shared this article with you from Inoreader Nivolumab exposure in a hemodialysis patient with metastatic melanoma Via Melanoma Research - Published Ahead-of-Print The effect of intermittent hemodialysis (IHD) on nivolumab serum concentrations in patients with severe renal impairment is largely unknown. Here, we present a 79-year-old patient with metastatic melanoma and end-stage renal disease on IHD three times a week, treated with 480 mg nivolumab every 4 weeks. A serum trough concentration of nivolumab was determined before the start of the third cycle, and two samples were taken immediately before and after a hemodialysis session during this cycle. All nivolumab serum concentrations were within a similar range as those previously measured among patients without renal insufficiency, after a comparable duration of nivolumab treatment. Therefore, we conclude that IHD does not influence nivolumab exposure. Furthermore, nivolumab treatment was continued without complications and appears to be well tolerated for patients on IHD. Received 22 March 2021 Accepted 24 July 2021 Correspondence to Robin van Geel, PharmD, PhD, Department of Clinical Pharmacy & Toxicology, Maastricht University Medical Center, P. Debyelaan 25, 6229 HX the Netherlands, Tel: +0031 043 3871881; e-mail: robin.van.geel@mumc.nl Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Expression of the cancer stem cell marker OCT4 is associated with worse prognosis and survival in cutaneous melanoma

xlomafota13 shared this article with you from Inoreader Expression of the cancer stem cell marker OCT4 is associated with worse prognosis and survival in cutaneous melanoma Via Melanoma Research - Published Ahead-of-Print Cutaneous melanoma has an aggressive clinical presentation, showing rapid rate of growth and metastatic dissemination due to the permanence of cancer stem cells. The present study was to evaluate the expression of the self-renewal regulatory factor and the clinical significance of the transcription factor OCT4 in me lanoma. Melanoma tissues were stained by immunohistochemistry and the correlation between the expression of this marker was determined through clinical–pathological variables and survival outcomes. Positive expression of nuclear and cytoplasmic OCT4 was observed in 49% and 41.2% of cases, respectively. The positive expression of nuclear OCT4 in melanoma was significantly associated with prognostic factors, such as Breslow depth, Clark's level, ulceration and metastasis. Survival of patients was 56% compared to positive nuclear OCT4 expression and 94.2% when compared to the low expression of the gene. Nuclear OCT4 positive genotype indicated aggressive tumor behavior with a worse clinical outcome, which indicates OCT4 as a useful biomarker in the prognosis of melanoma. Received 10 November 2020 Accepted 1 July 2021 Correspondence to Kleber Santiago Freitas e Silva, PhD, Department of Medicine, Anápolis University Center, UniEvangélica, Avenida Universitária, Km 3,5 - Cidade Universitária, CEP 75083-515 Anápolis, Goiás, Brazil, Tel: +55 (62) 99924 5983; e-mail: smallbinho@hotmail.com Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

COVID-19 vaccination mimicking lymph-node progression in a patient with melanoma: a case report

xlomafota13 shared this article with you from Inoreader COVID-19 vaccination mimicking lymph-node progression in a patient with melanoma: a case report Via Melanoma Research - Published Ahead-of-Print COVID-19 vaccination has been rapidly implemented among patients with cancer. We present the case of a patient with high-risk resected cutaneous melanoma, who was a candidate for adjuvant treatment, with postsurgery 18-fluorodeoxyglucose (FDG) PET/computed tomography (CT) scan showing positive axillary lymph nodes after COV ID-19 vaccination. This report presents a 50-year-old man with a history of stage IIA cutaneous melanoma. During follow-up, the patient experienced subcutaneous and lymph-node disease progression, documented with 18FDG PET/CT scan. The patient underwent laparoscopic left para-aortic lymphadenectomy and excision of subcutaneous lesion. Histologic examination showed presence of melanoma metastases in 2 lymph nodes out of total 17 excised and neoplastic emboli to the subcutaneous tissue. In view of starting adjuvant nivolumab, the patient underwent CT scan restaging, with evidence of suspect centimetric periaortic and paracaval lymph nodes, which were deemed worthy of 18FDG PET investigation. The 18FDG PET/CT was negative for abdominal hypercaptation, but showed left axillary pathologic lymph nodes. The medical history of the patient revealed that he had received intramuscular Moderna COVID-19 mRNA vaccine in the left deltoid, one week before 18FDG PET examination. Since the patient' s clinical examination was negative and suspecting postvaccination false-positive adenopathy, bilateral axillary ultrasound was performed, excluding the presence of pathologic lymph nodes. The patient has started adjuvant treatment with nivolumab, which is currently ongoing. This case demonstrates unexpected findings in response to COVID-19 vaccination in a patient with melanoma. In this specific case, the detection of 18FDG PET hypercaptation could significantly change the patient's management. With growing evidence about the pattern and occurrence of adenopathies after mRNA COVID-19 vaccination, recommendations for scheduling and interpretation of 18FDG PET/CT scans among cancer patients will be implemented, in order to reduce equivocal findings and improve outcomes. Received 12 May 2021 Accepted 3 July 2021 Correspondence to Alice Indini, MD, Medical Oncology Unit, Department of Internal Medicine, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, via Francesco Sforza 35, 20122 Milano, Italy, Tel: +39 0255032660; fax: +39 0255032659; e-mail: alice.indini@gmail.com Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Aseptic cystitis induced by nivolumab and ipilimumab combination for metastatic melanoma

xlomafota13 shared this article with you from Inoreader Aseptic cystitis induced by nivolumab and ipilimumab combination for metastatic melanoma Via Melanoma Research - Published Ahead-of-Print Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced melanoma. Combination of ICI with ipilimumab cytotoxic T-lymphocyte antigen-4 and nivolumab [anti-programmed cell death-1 (PD-1)] improves tumoral response compared to anti-PD1 monotherapy in melanoma patients, but is associated with more seve re and multiple immune-related adverse events. We report the first case of aseptic cystitis induced by ipilimumab and nivolumab combination in a 61-year-old melanoma patient. She described after two infusions, diarrhea, pollakiuria, intense bladder pain, urinary urgency, and nocturia. Repeated negative urine culture tests led to perform cystoscopy. Mucosal bladder biopsies showed lymphocytic T-cells infiltration in intraepithelial and in subepithelial connective tissue, which were consistent with the diagnosis of immune-related aseptic cystitis. Aseptic cystitis is a rare and poorly known side-effect related to ICI. Only four other cases with anti-PD1 monotherapy were found in literature, only in Japanese patients. It simulates bacterial cystitis with negative urinary tests, and is often associated with atypical symptoms like diarrhea, which may delay the diagnosis. Oral steroids appear to be the most efficient therapeutic options. Received 4 May 2021 Accepted 28 June 2021 Correspondence to Sorilla Prey, MD, PhD, Service de Dermatologie, Groupe hospitalier Saint André, 1, rue Jean Burguet, F-33000 Bordeaux, France, Tel: +33 5 56 79 47 05; fax: +33 5 56 79 49 75; e-mail: sorilla.prey@chu-bordeaux.fr Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Metastatic acral melanoma treatment outcomes: a systematic review and meta-analysis

xlomafota13 shared this article with you from Inoreader Metastatic acral melanoma treatment outcomes: a systematic review and meta-analysis Via Melanoma Research - Published Ahead-of-Print Acral melanomas are a unique subset of melanomas occurring on the palms, soles, and nails. There is poor prognosis with surgery alone and no specific guidelines for the treatment of metastatic acral melanoma. This meta-analysis explored the systemic therapy outcomes for metastatic acral melanoma. Medline, Pubmed, EMBA SE, and the grey literature were searched from 2010 to August 2020 for studies specifying the treatment outcome of metastatic acral melanoma. Studies were assessed by two investigators. A random-effects meta-analysis was performed and pooled Kaplan–Meier curves for progression-free survival and overall survival were created. Critical appraisal was performed using the Newcastle-Ottawa Scale. Nineteen nonrandomized studies were included, comprising 646 patients with acral melanomas and 1609 patients with nonacral melanomas treated with systemic therapy including chemotherapy, KIT-targeted drugs, as well as anti-CTLA-4 and anti-PD-1 checkpoint inhibitor therapy. Thirteen studies included Kaplan–Meier curves for progression-free survival or overall survival and 11 studies reported treatment responses. Patients with acral melanomas had worse prognosis than nonacral cutaneous melanoma (acral overall survival: median 15 months, 95% CI, 13.7–16.3 months; nonacral cutaneous: median 24 months, 95% CI, 22.6–25.4 months, P  View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Clinical implications of alpha, beta, and gamma HPV infection in juvenile onset recurrent respiratory papillomatosis

xlomafota13 shared this article with you from Inoreader Clinical implications of alpha, beta, and gamma HPV infection in juvenile onset recurrent respiratory papillomatosis Via http://link.springer.com/journal/405,European archives of oto-rhino-laryngology,The European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino Eur Arch Otorhinolaryngol. 2021 Aug 28. doi: 10.1007/s00405-021-07040-9. Online ahead of print. ABSTRACT PURPOSE: The aim of our study was to evaluate the prevalence of different HPV genera-alpha, beta and gamma-in Juvenile onset Recurrent Respiratory Papillomatosis (JoRRP) and examine the association of type and genus-specific viral features with the clinical outcome of disease. METHODS: This retrospective observational study included consecutive patients with JoRRP who were treated in a referral centre between October 2000 and October 2020. All patients underwent cold excision and laser vaporisation of papillomatous lesions. Samples were analysed for the presence of 120 viral genotypes (22 alpha-HPV, 46 beta-HPV, 52 gamma-HPV) using a highly sensitive multiplex genotyping assay. RESULTS: Twenty patients with JoRRP, aged 0.3-11 years, were included, with a median follow-up of 13.5 years. All samples were HPV DNA positive: 20 (100%) for alpha-HPV DNA; 7 (35%) for beta-HPV DNA; 0 for gamma-HPV DNA. Three groups were defined according to the number of infections: seven cases (35%) with HPV mono-infection; ten cases (50%) with HPV double-infection; three cases (15%) with ≥ 3 HPV infections. At diagnosis, patients with ≥ 3 HPV infections reported higher median Derkay's score than those with mono-infection (21 vs 14, P = 0.018). Number of HPV infections was also associated with clinical outcomes, with an average of 0.5 surgical procedures/year in patients with mono-infection, 1.2 for double-infection, 2.6 for ≥ 3 infections (P = 0.006). CONCLUSION: Despite the small sample size, these preliminary data support an association between the number of different alpha and beta HPV co-infections and the clinical severity of the disease. PMID:34453571 | DOI:10.1007/s00405-021-07040-9 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.