Epigenetic approaches for cervical neoplasia screening (Review)

xlomafota13 shared this article with you from Inoreader Epigenetic approaches for cervical neoplasia screening (Review) Via Experimental and therapeutic medicine Exp Ther Med. 2021 Dec;22(6):1481. doi: 10.3892/etm.2021.10916. Epub 2021 Oct 25. ABSTRACT Human papillomavirus (HPV) infection is the leading cause of cervical cancer. The Papanicolaou cytology test is the usually employed type of screening for this infection; however, its sensibility is limited. Only a small percentage of women infected with high-risk HPV develop cervical cancer with an array of genetic and epigenetic modifications. Thus, it is necessary to develop rapid, reproducible and minimally invasive technologies for screening. DNA methylation has gained attention as an alternative method for molecular diagnosis and prognosis in HPV infection. The aim of the present review was to highlight the potential of DNA methylation in cervical neoplasia screening for clinical applications. It was observed that the methylation human and viral genes was correlated with high-grade lesions and cancer. Methylation biomarkers have shown a goo d capacity to discriminate between high-grade lesions with a transformative potential and cervical cancer, being able to detect these modifications at an early stage. With further research, the epigenetic profiles and subtypes of the tumors could be elaborated, which would aid in therapy selection by opening avenues in personalized precision medicine. Response to therapy could also be evaluated through such methods and the accessibility of liquid biopsies would allow a constant monitoring of the patient's status without invasive sampling techniques. PMID:34765022 | PMC:PMC8576616 | DOI:10.3892/etm.2021.10916 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Heat-induced antigen retrieval in fluorescence in situ hybridization: An effective approach enhancing signal intensity in poor-quality FFPE sections

xlomafota13 shared this article with you from Inoreader Heat-induced antigen retrieval in fluorescence <em>in situ</em> hybridization: An effective approach enhancing signal intensity in poor-quality FFPE sections Via Experimental and therapeutic medicine Exp Ther Med. 2021 Dec;22(6):1480. doi: 10.3892/etm.2021.10915. Epub 2021 Oct 25. ABSTRACT Fluorescence in situ hybridization (FISH) serves as an ancillary tool for assessing chromosomal abnormalities and is important in differential diagnoses and treatment decisions. In clinical practice, pathologists encounter unsatisfactory formalin-fixed paraffin-embedded (FFPE) sections exhibiting weak fluorescence signals, mostly due to inappropriate tissue processing or preservation, leading to interpretation difficulties. For the present study, FFPE samples for which conventional FISH failed were collected. Instead of a pretreatment step using a commercial kit, heat-induced antigen retrieval (HIAR) was introduced using either citrate buffer or Tris-EDTA buffer, while the subsequent experimental workflow remained unchanged. After HIAR-assisted FISH, the hybridization efficiency and signal intensity were markedly enhanced and no difference in signal adequacy was observed when comparing the effect of the two AR solutions. The present study demonstrated that HIAR is a reliable tool for FISH, particularly for poor-quality FFPE sections yielding weak or no fluorescence signals in the conventional analysis. PMID:34765021 | PMC:PMC8576618 | DOI:10.3892/etm.2021.10915 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Multiple functions of the DEAD-box RNA helicase, DDX5 (p68), make DDX5 a superior oncogenic biomarker and target for targeted cancer therapy

xlomafota13 shared this article with you from Inoreader Multiple functions of the DEAD-box RNA helicase, DDX5 (p68), make DDX5 a superior oncogenic biomarker and target for targeted cancer therapy Via American Journal of Cancer Research Am J Cancer Res. 2021 Oct 15;11(10):5190-5213. eCollection 2021. ABSTRACT DDX5 (p68) is a well-known multifunctional DEAD-box RNA helicase and a transcription cofactor. Since its initial discovery more than three decades ago, DDX5 is gradually recognized as a potential biomarker and target for the treatment of various cancer types. Studies over the years significantly expanded our understanding of the functional diversity of DDX5 in various cancer types and extended our knowledge of its Mechanism of Action (MOA). This provides a rationale for the development of novel cancer therapeutics by using DDX5 as a biomarker and a therapeutic target. However, while most of the published studies have found DDX5 to be an oncogenic target and a cancer treatment-resistant biomarker, a few studies have reported that in certain scenarios, DDX5 may act as a tumor suppressor. After careful review of all the available relevant studies in the literature, we found that the multiple functions of DDX5 make it both a superior independent oncogenic biomarker and target for targeted cancer therapy. In this article, we will summarize the relevant studies on DDX5 in literature with a careful analysis and discussion of any inconsistencies encountered, and then provide our conclusions with respect to understanding the MOA of FL118, a novel small molecule. We hope that such a review will stimulate further discussion on this topic and assist in developing better strategies to treat cancer by using DDX5 as both an oncogenic biomarker and therapeutic target. PMID:34765320 | PMC:PMC8569338 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Sensitization of breast cancer to Herceptin by redox active nanoparticles

xlomafota13 shared this article with you from Inoreader Sensitization of breast cancer to Herceptin by redox active nanoparticles Via American Journal of Cancer Research Am J Cancer Res. 2021 Oct 15;11(10):4884-4899. eCollection 2021. ABSTRACT Herceptin-resistant tumor relapse remains a major clinical issue responsible for the poor prognosis of HER2+ breast cancer. Understanding the underlying mechanisms and finding a therapeutic solution are of paramount urgency to improve the patient management. Here we report that anticancer redox active cerium oxide nanoparticles (CONPs) can potently sensitize the cancer cells to the cytotoxicity of Herceptin. By comparing between Herceptin-sensitive and Herceptin-resistant human breast cancer cell lines under normoxic as well as hypoxic culture conditions, we found that in the presence of CONPs, Herceptin can kill the Herceptin-resistant cells equally effectively as it kills the Herceptin-sensitive cells under the hypoxic, but not normoxic, culture conditions by inhibiting the cell viability, survival and proliferation. Signaling analysis reveals that u nder the normoxic conditions, the levels of hypoxia induced factor 1α as well as vascular endothelial growth factor are higher in the Herceptin-resistant cells than that in the Herceptin-sensitive cells and are strongly induced once the culture is switched to the hypoxic conditions, which can be potently suppressed by CONPs. Treatment with CONPs plus Herceptin significantly slows down the primary tumor growth and lung metastasis of the Herceptin-resistant cells in a xenograft mouse model of orthotopic breast cancer through inhibiting the cell proliferation and survival as well as tumor angiogenesis. These results shed new lights on the mechanisms underlying the Herceptin resistance of the HER2+ breast cancer and provide insights into introducing CONPs-like agents to Herceptin-based therapy to improve treatment outcomes. PMID:34765298 | PMC:PMC8569362 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Clinical impact of postoperative prognostic nutritional index in colorectal cancer patients undergoing adjuvant chemotherapy

xlomafota13 shared this article with you from Inoreader Clinical impact of postoperative prognostic nutritional index in colorectal cancer patients undergoing adjuvant chemotherapy Via American Journal of Cancer Research Am J Cancer Res. 2021 Oct 15;11(10):4947-4955. eCollection 2021. ABSTRACT Preoperative Prognostic Nutritional Index (PNI) could be a crucial factor for the prognosis of colorectal cancer (CRC). However, the clinical impact of postoperative PNI is still unclear, and there have been no reports on the significance of postoperative PNI in patients undergoing adjuvant chemotherapy (AC). We retrospectively analysed 227 consecutive patients who underwent AC after radical surgery for high-risk stage II or stage III CRC. PNI value was calculated before radical surgery and before the introduction of AC. In our study, patients with a low PNI value before surgery showed significantly poorer long-term outcomes than those with a high PNI value. Next, we divided the patients into four groups: patients with a high PNI value before surgery and remained after surgery (Group High-High), a high PNI value before surgery but decreased after surgery (Group H igh-Low), a low PNI value before surgery but recovered after surgery (Group Low-High), and a low PNI value but did not recover after surgery (Group Low-Low). Although the patients in Group Low-Low showed significantly poorer long-term outcomes than those in Group High-High, the prognosis of patients in Group Low-High was the same as that of patients in Group High-High. In addition, in patients with recurrence after AC, those with a high PNI value at the time of recurrence showed a significantly better survival after recurrence than patients with a low PNI value. Postoperative PNI value could be a prognostic biomarker for CRC patients undergoing AC. Even though the PNI value was low before the surgery, recovery of PNI value by the introduction of AC could improve the prognosis of CRC patients. PMID:34765302 | PMC:PMC8569341 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Effect of exercise on peritoneal microenvironment and progression of ovarian cancer

xlomafota13 shared this article with you from Inoreader Effect of exercise on peritoneal microenvironment and progression of ovarian cancer Via American Journal of Cancer Research Am J Cancer Res. 2021 Oct 15;11(10):5045-5062. eCollection 2021. ABSTRACT Ovarian cancer is one of the deadliest gynecological malignancies and lacks treatments that do not significantly impact patient health-related quality of life. Exercise has been associated with reduced cancer risk and improved clinical outcomes; however the underlying molecular mechanisms are unknown. In this study, we utilized a treadmill-running exercise model to investigate the effects of exercise on high-grade serous ovarian carcinoma (HGSOC) progression and chemotherapy outcomes. We found that treadmill-running suppressed peritoneal colonization of tumors in a syngeneic mouse ovarian cancer model. Acute exercise stimulated the production of CCL2 and IL-15 in the peritoneal microenvironment while downregulating CCL22, VEGF, and CCL12. Using a co-culture model, we demonstrated the role of CCL2 in mediating the activity of peritoneal cells to inhibit cancer cel l viability. We showed that the activation of M1 macrophages may contribute to the exercise-induced changes in the peritoneal microenvironment. We identified that chronic exercise modulates gene expression of intraperitoneal fat tissues related to lipid formation, thermogenesis, browning, and inflammation, which can contribute to inhibiting the colonization of metastatic ovarian cancer. Treadmill running also lowered blood urea nitrogen levels and reduced incidence of neutropenia and thrombocytopenia during chemotherapy in a mouse model, suggesting the potential beneficial effects of exercise in improving chemotherapy outcomes. Our data provided new insights into the acute and chronic effects of physical activity on ovarian cancer at the molecular and in vivo levels. PMID:34765311 | PMC:PMC8569339 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Dickkopf-1 promotes angiogenesis by upregulating VEGF receptor 2-mediated mTOR/p70S6K signaling in hepatocellular carcinoma

xlomafota13 shared this article with you from Inoreader Dickkopf-1 promotes angiogenesis by upregulating VEGF receptor 2-mediated mTOR/p70S6K signaling in hepatocellular carcinoma Via American Journal of Cancer Research Am J Cancer Res. 2021 Oct 15;11(10):4788-4806. eCollection 2021. ABSTRACT The expression of Dickkopf-1 (DKK1), a negative regulator of the Wnt/β-catenin signaling pathway, is upregulated in hepatocellular carcinoma (HCC). Here, we investigated the tumorigenic and angiogenic potential of DKK1 in HCC. Stable cell lines were established using the clustered regularly interspaced short palindromic repeats (CRISPR)-associated nuclease 9 (CRISPR/Cas9)-based DKK1 knock-out system in Hep3B cells and the tetracycline-based DKK1 inducible system in Huh7 cells. Multicellular tumor spheroids (MCTSs) were cultured using Hep3B stable cells. We also employed xenografts generated using Hep3B stable cells and transgenic mouse models established using hydrodynamic tail vein injection. The angiogenic potential increased in HUVECs treated with CM from Huh7 stable cells with high DKK1 expression and Hep3B wild-type cells. DKK1 accelerated the downstream mo lecules of vascular endothelial growth factor receptor 2 (VEGFR2)-mediated mTOR/p70 S6 kinase (p70S6K) signaling. MCTSs generated using Hep3B wild-type cells promoted compact spheroid formation and increased the expression of CD31 and epithelial-mesenchymal transition (EMT) markers, and increased the VEGFR2-mediated mTOR/p70S6K signaling, compared to the controls (all P<0.01). Xenograft tumors generated using Hep3B cells with DKK1 knock-out (n=10) exhibited slower growth than, the controls (n=10) and the expression of Ki-67, VEGFR2, CD31 and EMT markers decreased (all P<0.05). In addition, forced DKK1 expression with HRAS in transgenic mouse livers (n=5) resulted in the formation of more tumors and increased expression of downstream molecules of VEGFR2-mediated mTOR/p70S6K signaling pathway as well as Ki67, CD31 and EMT markers (P<0.05), compared to that of the controls (n=5). Our findings indicate that DKK1 facilitates angiogenesis and tumorigenesis by upregulating VEGFR2-mediated mTOR/p70S6K signaling in HCC. PMID:34765293 | PMC:PMC8569356 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

The past, present and future of conversion therapy for liver cancer

xlomafota13 shared this article with you from Inoreader The past, present and future of conversion therapy for liver cancer Via American Journal of Cancer Research Am J Cancer Res. 2021 Oct 15;11(10):4711-4724. eCollection 2021. ABSTRACT Primary liver cancer is one of the world's most common malignant tumors, as well as the malignant tumor with the third highest mortality rate in China. Most Chinese patients with liver cancer already have intermediate or advanced stage disease at initial diagnosis and have lost the opportunity for surgery. Following recent advances in treatments for advanced liver cancer, the associated treatment efficacy and response rates have continuously improved. As a result, the application of preoperative treatments can lead to tumor downstaging in a high proportion of patients and consequently provide initially ineligible patients with opportunities for surgical intervention, representing a breakthrough treatment strategy for liver cancer. Since conversion study is still in its infancy, there remain controversies in terms of patient selection, choice of treatment method, and postoperative management. In this review, we collect and summarize current evidence and clinical experience of conversion therapy, highlight remaining problems and challenges and provide a foundation for further research and development of HCC treatment in clinical practice. PMID:34765289 | PMC:PMC8569342 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

The effects of endovascular clot retrieval and thrombolysis on dysphagia in an Australian quaternary hospital: A retrospective review

xlomafota13 shared this article with you from Inoreader The effects of endovascular clot retrieval and thrombolysis on dysphagia in an Australian quaternary hospital: A retrospective review Via Traditional dysphagia therapy Int J Lang Commun Disord. 2021 Nov 12. doi: 10.1111/1460-6984.12681. Online ahead of print. ABSTRACT Dysphagia (impaired swallowing) is known to contribute to decreased quality of life, and increased length of hospital stay and mortality post-stroke. Despite the advancements in stroke treatment with the introduction of thrombolysis and endovascular clot retrieval (ECR), patients continue to present with high rates of dysphagia. Speech and language therapists and stroke teams should consider the presence of haemorrhagic transformation, success of reperfusion and presence of communication deficits as risk factors for dysphagia post-ECR and/or thrombolysis. PURPOSE: To establish incidence rates and patterns of dysphagia following the administration of reperfusion therapies in acute ischaemic stroke management. METHOD: A retrospective review of 193 patients admitted with acute ischaemic stroke to a quaternary stroke unit in Australia over a three year period was completed. Clinical information extracted included demographics, type (thrombolysis and/or endovascular clot retrieval) and success of reperfusion therapy, and the progression of dysphagia and related factors. RESULTS: Over half of all patients treated with reperfusion therapies presented with dysphagia on initial assessment by speech-language pathology (SLP). The type of reperfusion therapy administered was not significantly correlated with the presence of dysphagia. Dysphagia on initial assessment was significantly correlated with the presence of aphasia on initial assessment, the presence of haemorrhagic transformation, and the success of reperfusion. Increased rates of enteral feeding were also found in this study compared to figures reported in literature. CONCLUSION: This study identified ongoing high rates of dysphagia amongst this patient population regardless of treatment type, demonstrating the need for ongoing SLP management post s troke. Further research is required in this area to develop an evidence-base for SLPs and the wider medical team and to inform clinical practice guidelines. WHAT THIS PAPER ADDS: What is already known on the subject Stroke is one of the leading causes of disability and death internationally. Dysphagia (impaired swallowing), a common sequalae of stroke, is known to contribute to decreased quality of life, increased length of hospital stay and mortality. With advancements in technology, treatments for acute ischaemic stroke (endovascular clot retrieval and thrombolysis) are increasing in popularity. However, limited research exists exploring the impact of these therapies on dysphagia. What this paper adds Despite the advancements in stroke treatment, patients continue to present with high rates of dysphagia. Dysphagia following thrombolysis and/or ECR was found to be significantly correlated to the presence of aphasia, haemorrhagic transformation, and the success of reperfusion (regardless of treatment type). Additionally, increased rates of enteral feeding were found amongst this patient population compared to figures reported in the literature for patients following traditional stroke management. Clinical implications of this study Speech-language pathologists and the wider medical team should consider dysphagia as an ongoing consequence of stroke following reperfusion therapies, with consideration for success of reperfusion and adverse outcomes i.e., haemorrhagic transformation. Further research is required to provide an evidence-base and specific guidelines for the management of dysphagia post reperfusion therapies, including use of enteral feeding. PMID:34767286 | DOI:10.1111/1460-6984.12681 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

The stroma in oral potentially malignant disorders: An overlooked denominator?

xlomafota13 shared this article with you from Inoreader Message: Review Tumori Jan-Feb 2018;104(1):9-14. doi: 10.5301/tj.5000673. Significance of stroma in biology of oral squamous cell carcinoma Vanja Vucicevic Boras 1 2, Aleksandra Fucic 3, Mihajlo Virag 4 5, Dragana Gabric 1, Igor Blivajs 4, Cedna Tomasovic-Loncaric 6, Zoran Rakusic 7 8, Vesna Bisof 7 9, Nicolas Le Novere 10, Danko Velimir Vrdoljak 11 Affiliations collapse Affiliations 11 Department of Oral Medicine, School of Dentistry, University of Zagreb, Zagreb - Croatia. 22 Dental Department, Clinical Hospital Centre "Zagreb", Zagreb - Croatia. 33 Independent Researcher, Institute for Medical Research and Occupational Health, Zagreb - Croatia. 44 Department of Oral and Maxillofacial Surgery, Clinical Hospital Centre "Dubrava", Zagreb - Croatia. 55 Department of Maxillofacial Surgery and Dentistry, Medical Faculty, University of Zagreb, Zagreb - Croatia. 66 Department of Pathology, Clinical Hospital Centre Dubrava, Zagreb - Croatia. 77 Department of Oncology, Clinical Hospital Centre "Zagreb", Zagreb - Croatia. 88 Department of Clinical Oncology, Medical Faculty, University of Zagreb, Zagreb - Croatia. 99 Department for Nuclear Medicine and Oncology, Medical Faculty, University of Osijek, Osijek - Croatia. 1010 Biomathematics, Babraham Institute, Cambridge - UK. 1111 Department for Oncoplastic and Reconstructive Surgery, Clinic for Tumours, Clinical Hospital Centre "Sisters of Mercy", Zagreb - Croatia. PMID: 28885677 DOI: 10.5301/tj.5000673 Abstract The worldwide annual incidence of oral squamous cell carcinoma (OSCC) is over 300,000 cases with a mortality rate of 48%. This cancer type accounts for 90% of all oral cancers, with the highest incidence in men over 50 years of age. A significantly increased risk of developing OSCC exists among smokers and people who consume alcohol daily. OSCC is an aggressive cancer that metastasizes rapidly. Despite the development of new therapies in the treatment of OSCC, no significant increase in 5-year survival has been recorded in the past decades. The latest research suggests focus should be put on examining tumor stroma activation within OSCC, as the stroma may contain cells that can produce signal molecules and a microenvironment crucial for the development of metastases. The aim of this review is to provide an insight into the factors that activate OSCC stroma and hence faciliate neoplastic progression. It is based on the currently available data on the role and interaction between metal loproteinases, cytokines, growth factors, hypoxia factor and extracellular adhesion proteins in the stroma of OSCC and neoplastic cells. Their interplay is additionally presented using the Systems Biology Graphical Notation in order to sublimate the collected knowledge and enable the more efficient recognition of possible new biomarkers in the diagnostics and follow-up of OSCC or in finding new therapeutic targets. Keywords: Biomarker; Cytokines; Estrogen receptor; OSCC; Stroma androgen receptor. The stroma in oral potentially malignant disorders: An overlooked denominator? Via Head & Neck View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.