Immunology

Aging (Aging-US)

Aging-US published this research paper in Volume 14, Issue 17, entitled, "Fetal programming: in utero exposure to acrylamide leads to intergenerational disrupted ovarian function and accelerated ovarian aging" by researchers from the Department of Zoology, College of Science, King Saud University, Riyadh, Saudi Arabia, Department of Biochemistry, College of Science, King Saud University, Riyadh, Saudi Arabia, Department of Botany and Microbiology, College of Science, King Saud University, Riyadh, Saudi Arabia.

DOI - https://doi.org/10.18632/aging.204269

Corresponding authors - Abdel Halim Harrath - hharrath@ksu.edu.sa 

Abstract

In this study we investigated the effects of multigenerational exposures to acrylamide (ACR) on ovarian function. Fifty-day-old Wistar albino female rats were divided into the control and ACR-treated groups (2.5, 10, and 20 mg/kg/day) from day 6 of pregnancy until delivery. The obtained females of the first (AF1) and second generation (AF2) were euthanized at 4 weeks of age, and plasma and ovary samples were collected. We found that in utero multigenerational exposure to ACR reduced fertility and ovarian function in AF1 through inducing histopathological changes as evidenced by the appearance of cysts and degenerating follicles, oocyte vacuolization, and pyknosis in granulosa cells. TMR red positive cells confirmed by TUNEL assay were mostly detected in the stroma of the treated groups. Estradiol and IGF-1 concentrations significantly decreased as a result of decreased CYP19 gene and its protein expression. However, ACR exposure in AF2 led to early ovarian aging as evidenced by high estradiol and progesterone levels among all treated groups compared to control group, corresponding to the upregulation of the CYP19 gene and protein expression. The apoptotic cells of the stroma were greatly detected compared to that in the control group, whereas no significant difference was reported in ESR1 and ESR2 gene expression. This study confirms the developmental adverse effects of ACR on ovarian function and fertility in at least two consecutive generations. It emphasizes the need for more effective strategies during pregnancy, such as eating healthy foods and avoiding consumption of ACR-rich products, including fried foods and coffee.

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Keywords - aging, acrylamide, transgeneration, apoptosis, female fertility, ovary aging

About Aging-US

Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways.

Please visit our website at https://www.Aging-US.com​​ and connect with us:

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Facebook - https://www.facebook.com/AgingUS/
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Trending With Impact: Effects of Multigenerational Exposures to Acrylamide on Ovarian Function

Oncotarget

Oncotarget published this research paper on September 14, 2022 in Volume 13, entitled, "Site of analysis matters - Ongoing complete response to Nivolumab in a patient with HIV/HPV related metastatic anal cancer and MLH1 mutation" by researchers from Dr. Senckenbergisches Institut für Pathologie, Universitätsklinikum Frankfurt, Frankfurt 60590, Germany; Universitäres Centrum für Tumorerkrankungen (UCT), Universitätsklinikum Frankfurt, Frankfurt 60590, Germany; Klinik für Allgemein- und Viszeralchirurgie, Universitätsklinikum Frankfurt, Frankfurt 60590, Germany; Institut für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Frankfurt, Frankfurt 60590, Germany; Klinik für Strahlentherapie und Onkologie, Universitätsklinikum Frankfurt, Frankfurt 60590, Germany; Medizinische Klinik 1, Schwerpunkte Gastroenterologie und Hepatologie, Universitätsklinikum Frankfurt, Frankfurt 60590, Germany; Centrum für Hämatologie und Onkologie, Frankfurt 60389, Germany.

DOI - https://doi.org/10.18632/oncotarget.28274

Correspondence to - Oliver Waidmann - oliver.waidmann@kgu.de

Abstract

Anal cancer is a rare disease with increasing incidence. In patients with locally recurrent or metastatic disease which cannot be treated with chemoradiotherapy or salvage surgery systemic first-line chemotherapy with carboplatin and paclitaxel is standard of care. For patients who progress after first-line therapy and are still eligible for second-line therapy Programmed cell death protein 1 (PD-1) antibodies are potential therapeutic options. However, prediction of response to immunotherapy is still challenging including anal cancer. We report here to our knowledge the first anal cancer case with microsatellite instability (MSI) due to MLH1 mutation and a deep and ongoing response to Nivolumab treatment. Namely, thorough analysis of the primary tumor as well as metastatic sites by next generation sequencing (NGS) revealed that MSI was formally only found in the metastatic sites but not in the primary tumor. Concomitantly, tumor mutational burden (TMB) was higher in the metastatic site than in the primary tumor. Therefore, we conclude that all anal cancer patients should be tested for MSI and whenever possible molecular analysis should be performed rather from metastatic sites than from the primary tumor.

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Keywords - anal cancer, microsatellite instability, immunotherapy, high-throughput nucleotide sequencing, nivolumab

About Oncotarget

Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed.

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Trending With Impact: HIV/HPV-Related Metastatic Colorectal Cancer Response to Nivolumab

Teach Me in 10

In this Teach Me In 10 episode Petra Gerhards, regional marketing manager for Thermo Fisher Scientific , shares information on the main challenges of MOSH/MOAH and how to overcome these for more successful analysis. 

MOSH/MOAH Analysis Without the Usual Struggles With Petra Gerhards

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In this episode we are joined by Shane O’Neill, director of scientific affairs at EKF Diagnostics. Shane provides an introduction to the glycated albumin (GA) test for intermediate-term glycemic control in diabetic patients. 

The GA test is now FDA-cleared and available for use in the United States. It was developed by Asahi-Kasei Pharma of Japan (Lucica® brand) and is a standardized and well-evidenced method for determining glycated albumin levels in the serum.

Shane will also describe why glycemic control is important and discuss the value of the test for glycemic monitoring, outlining its clinical utility and how it compares to other markers of glycemic control, such as hemoglobin A1C and fructosamine. 
EKF Diagnostics distributes the test in the United States.

Lucica® Glycated Albumin-L test for diabetes: Comparisons and Clinical Utility With Shane O’Neill

Oncotarget published this research paper on August 16, 2022 in Volume 13, entitled, "Combined epigenetic and immunotherapy for blastic and classical mantle cell lymphoma" by researchers from Department of Medicine, Pennsylvania State University College of Medicine and Penn State Hershey Cancer Institute, Hershey, PA; Department of Hematology/Oncology, Penn State Hershey Cancer Institute, Hershey, PA; BayCare Medical Group, Cassidy Cancer Center, Winter Haven, FL; Division of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY; Developmental Therapeutics Branch, Center for Cancer Research, NCI, NIH, Bethesda, MD; Department of Pharmacology, University of Virginia, Charlottesville, VA; Department of Public Health Sciences, The Pennsylvania State University College of Medicine, Hershey, PA; Department of Medicine/Hematology-Oncology, UVA Cancer Center, Charlottesville, VA; Department of Anatomic Pathology, Pennsylvania State University College of Medicine, Hershey, PA; Department of Medicine and Cancer Center, University of Arizona College of Medicine, Tucson, AZ; Department of Medicine, Oregon Health and Science University, Portland, OR; Beverly Hills Cancer Center, Beverly Hills, CA.

DOI - https://www.oncotarget.com/article/28258/text/

Correspondence to - Francis R. LeBlanc - francis.leblanc@cchmc.org

Abstract

Classical MCL (cMCL) constitutes 6–8% of all B cell NHL. Despite recent advances, MCL is incurable except with allogeneic stem cell transplant. Blastic mantle cell lymphoma (bMCL) is a rarer subtype of cMCL associated with an aggressive clinical course and poor treatment response, frequent relapse and poor outcomes. We treated 13 bMCL patients with combined epigenetic and immunotherapy treatment consisting of vorinostat, cladribine and rituximab (SCR). We report an increased OS greater than 40 months with several patients maintaining durable remissions without relapse for longer than 5 years. This is remarkably better then current treatment regimens which in bMCL range from 14.5-24 months with conventional chemotherapy regimens. We demonstrate that the G/A870 CCND1 polymorphism is predictive of blastic disease, nuclear localization of cyclinD1 and response to SCR therapy. The major resistance mechanisms to SCR therapy are loss of CD20 expression and evasion of treatment by sanctuary in the CNS. These data indicate that administration of epigenetic agents improves efficacy of anti-CD20 immunotherapies. This approach is promising in the treatment of MCL and potentially other previously treated refractory cancers.

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Keywords - epigenetics, blastic mantle cell lymphoma, cladribine

About Oncotarget

Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed.

To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:

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Combined Epigenetic and Immunotherapy for Mantle Cell Lymphoma

View the latest research on aging in Volume 14, Issue 15.
https://www.aging-us.com/issue/v14i15

Research Paper (Cover): “Profiles of behavioral, social and psychological well-being in old age and their association with mobility-limitation-free survival”
https://doi.org/10.18632/aging.204182

Editorial: “Sex difference in epigenomic instability during human aging”
https://doi.org/10.18632/aging.204199

Editorial: “NAD+ to assess health in aging humans”
https://doi.org/10.18632/aging.204220

Editorial: “T cell senescence by N-glycan branching”
https://doi.org/10.18632/aging.204239

Research Paper: “mtDNA variability determines spontaneous joint aging damage in a conplastic mouse model”
https://doi.org/10.18632/aging.204153

Research Paper: “Senolytic drugs relieve pain by reducing peripheral nociceptive signaling without modifying joint tissue damage in spontaneous osteoarthritis”
​​https://doi.org/10.18632/aging.204204

Research Paper: “Ascorbic acid induces salivary gland function through TET2/acetylcholine receptor signaling in aging SAMP1/Klotho (-/-) mice”
https://doi.org/10.18632/aging.204213

Research Paper: “Regulation of microglial activation in stroke in aged mice: a translational study”
https://doi.org/10.18632/aging.204216

Research Paper: “PDCD10 promotes the aggressive behaviors of pituitary adenomas by up-regulating CXCR2 and activating downstream AKT/ERK signaling”
https://doi.org/10.18632/aging.204206

Research Paper: “Influence of cardiovascular risk burden on pulmonary function trajectory: role of physical and social activities”
https://doi.org/10.18632/aging.204201

Research Paper: “miRNA-338-3p inhibits the migration, invasion and proliferation of human lung adenocarcinoma cells by targeting MAP3K2”
https://doi.org/10.18632/aging.204198

Research Paper: “Serial neurocognitive changes following transcatheter aortic valve replacement: comparison between low and intermediate-high risk groups”
https://doi.org/10.18632/aging.204202

Research Paper: “MAB21L1 promotes survival of lens epithelial cells through control of αB-crystallin and ATR/CHK1/p53 pathway”
https://doi.org/10.18632/aging.204203

Research Paper: “Interleukin-17D promotes lung cancer progression by inducing tumor-associated macrophage infiltration via the p38 MAPK signaling pathway”
​​https://doi.org/10.18632/aging.204208

Research Paper: “A signature constructed with mitophagy-related genes to predict the prognosis and therapy response for breast cancer”
https://doi.org/10.18632/aging.204209

Research Paper: “Artemisia argyi exhibits anti-aging effects through decreasing the senescence in aging stem cells”
https://doi.org/10.18632/aging.204210

Research Paper: “SIAH1-mediated RPS3 ubiquitination contributes to chemosensitivity in epithelial ovarian cancer”
https://doi.org/10.18632/aging.204211

Research Paper: “CBXs-related prognostic gene signature correlates with immune microenvironment in gastric cancer”
https://doi.org/10.18632/aging.204214

Research Paper: “Targeting circRNA-MAP4K2 for the treatment of diabetes-induced retinal vascular dysfunction”
https://doi.org/10.18632/aging.204215

Research Paper: “The comprehensive expression and functional analysis of m6A modification “readers” in hepatocellular carcinoma”
https://doi.org/10.18632/aging.204217

Research Paper: “Establishing and validating an ADCP-related prognostic signature in pancreatic ductal adenocarcinoma”
https://doi.org/10.18632/aging.204221

Research Paper: “SAAL1, a novel oncogene, is associated with prognosis and immunotherapy in multiple types of cancer”
https://doi.org/10.18632/aging.204224

Research Paper: “Comprehensive pan-cancer analysis reveals the prognostic value and immunological role of SPIB”
https://doi.org/10.18632/aging.204225

Research Paper: “Clinical outcomes and potential therapies prediction of subgroups based on a ferroptosis-related long non-coding RNA signature for gastric cancer”
https://doi.org/10.18632/aging.204227

About Aging-US

Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways.

Please visit our website at https://www.Aging-US.com​​ and connect with us:

SoundCloud - https://soundcloud.com/Aging-Us
Facebook - https://www.facebook.com/AgingUS/
Twitter - https://twitter.com/AgingJrnl
Instagram - https://www.instagram.com/agingjrnl/
YouTube - https://www.youtube.com/agingus​
LinkedIn - https://www.linkedin.com/company/aging/

Table of Contents: Volume 14, Issue 15

Oncotarget published this research paper on August 3, 2022 in Volume 13, entitled, "Glypican-3 (GPC3) is associated with MCPyV-negative status and impaired outcome in Merkel cell carcinoma" by researchers from SOTIO Biotech Inc., Cambridge, MA; Department of Dermatology, University Hospital of Tours, France.

DOI - https://doi.org/10.18632/oncotarget.28260

Correspondence to - Glen J. Weiss - weiss@sotio.com, and Mahtab Samimi - mahtab.samimi@univ-tours.fr
Abstract

Introduction: Merkel cell carcinoma (MCC) is an aggressive skin cancer, related to the Merkel Cell Polyomavirus (MCPyV) in 80% of cases. Immune checkpoint inhibitors provide sustained benefit in about 50% of MCC patients with advanced disease. Glypican-3 (GPC3) is an oncofetal tumor antigen that is an attractive target for chimeric antigen receptor T cell therapy due to its highly restricted expression on normal tissue and high prevalence in several solid tumors. GPC3 is known to be expressed in MCC but its association with tumor characteristics or prognosis has not been reported. We investigated MCC GPC3 expression by immunohistochemistry (IHC) and its association with tumor characteristics, MCPyV status, and patient outcome.

Methods: The GC33 antibody clone was validated for GPC3 IHC staining of tumor specimens in comparison to an established GPC3 IHC antibody. An MCC tissue microarray was stained for GPC3 by IHC using GC33 antibody. Association of GPC3+ IHC with baseline characteristics, MCPyV status (qPCR) and outcome (death from MCC/recurrence) were assessed.

Results: Forty-two of 62 samples (67.7%) were GPC3+. GPC3 expression was more frequently observed in females (p = 0.048) and MCPyV-negative tumors (p = 0.021). By multivariate analysis, GPC3 expression was associated with increased death from disease (CSS) (hazard ratio [HR] 4.05, 95% CI 1.06–15.43), together with advanced age (HR 4.85, 95% CI 1.39–16.9) and male gender (HR 4.64, 95% CI 1.31–16.41).

Conclusions: GPC3 expression is frequent in MCC tumors, especially MCPyV-negative cases, and is associated with increased risk of death. High prevalence of surface GPC3 makes it a putative drug target.

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Press release - https://www.oncotarget.com/news/pr/oncotarget-glypican-gpc-is-associated-with-mcpyv-negative-status-and-impaired-outcome-in-merkel-cell-carcinoma/

Keywords - Merkel cell carcinoma, glypican-3, Merkel cell polyomavirus, outcome

About Oncotarget

Oncotarget is a peer-reviewed, open access biomedical journal covering research on all aspects of oncology.

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Trending With Impact: GPC3 Associated With MCPyV-negative Status and Impaired Outcome in Merkel Cell Carcinoma

Oncotarget published this trending research paper on July 28, 2022 in Volume 13, entitled, "Chemoradiation-induced alteration of programmed death-ligand 1, CD8+ tumor-infiltrating lymphocytes and mucin expression in rectal cancer" by researchers from the Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD; Division of Biostatistics and Bioinformatics, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD; Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD.

DOI - https://doi.org/10.18632/oncotarget.28255

Correspondence to - Marina Baretti - mbarett1@jh.edu

Abstract

Introduction: DNA damage and resulting neoantigen formation is considered a mechanism for synergy between radiotherapy and PD-1/PD-L1 pathway inhibition to induce antitumor immune response. We investigated neoadjuvant chemoradiotherapy (nCRT)-induced changes in CD8+ tumor infiltrating lymphocyte, PD-L1 and mucin expression in rectal cancer patients.

Materials and Methods: Tumor samples of rectal adenocarcinoma patients undergoing resection between 2008-2014 with (n = 62) or without (n = 17) nCRT treatment were collected. Sections were stained with CD8 and PD-L1 antibodies for immunohistochemistry. The prevalence of CD8+ cells was recorded in the tumor, interface tumor and background rectal side. Image analysis was used to determine the density of CD8+ lymphocytes. The percentage of PD-L1 expression was manually counted in tumor cells (TC), tumor stroma (TS) and the invasive front (IF). Mucin expression was determined as the percentage of the mucin area in the whole tumor area.

Results: PD-L1 expression on TCs was identified in 7.6% (6/79) of nCRT specimens (p = 0.33) and in none of the non-nCRT patients. Median densities of CD8+ infiltrating T lymphocytes did not differ significantly between the two groups. Mucin expression was significantly higher in the nCRT cohort (p = 0.02). Higher neutrophil to lymphocytes ratio (NLR) after nCRT was associated with worse outcome (HR = 1.04, 95% CI = 1.00–1.08).

Conclusions: nCRT exposure was associated with a non-significant difference in PD-L1 expression in rectal adenocarcinoma patients, possibly due to sample size limitations. Further mechanistic investigations and comprehensive immune analysis are needed to understand nCRT-induced immunologic shift in rectal cancer and to expand the applicability of checkpoint inhibitors in this setting.

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Press release - https://www.oncotarget.com/news/pr/oncotarget-chemoradiation-induced-alteration-of-programmed-death-ligand-cd-tumor-infiltrating-lymphocytes-and-mucin-expression-in-rectal-cancer/

Keywords - programmed death ligand 1, tumor-infiltrating lymphocytes, immune checkpoints, colorectal cancer, neoadjuvant chemoradiotherapy

About Oncotarget

Oncotarget is a peer-reviewed, open access biomedical journal covering research on all aspects of oncology.

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