Deepa S Mandlik, Satish K Mandlik
The most common tumor linked with elevated death rates is considered the hepatocellular carcinoma (HCC), sometimes called the malignant hepatoma. The initiation and progression of HCC are triggered by multiple factors like long term alcohol consumption, metabolic disorders, fatty liver disease, hepatitis B and C infection, age, and oxidative stress. Sorafenib is the merely US Food and Drug Administration (FDA)-approved drug used to treat HCC. Several treatment methods are available for HCC therapy such as chemotherapy, immunotherapy and adjuvant therapy but they often lead to several side effects...
October 19, 2020: Nutrition and Cancer
Shengqi He, Dongqing Hu, Haixia Feng, Ye Xue, Jin Jin, Xiaoyan Wang
Aim: PD-1 inhibitors have a leading role among immunotherapy while its efficacy on colorectal cancer (CRC) patients did not reach consensus and the small sample size remains as a limitation. Therefore, we undertook a meta-analysis on the effects of the monotherapy anti-PD-1 inhibitors in treating metastatic colorectal cancer (mCRC). Materials & methods: We searched databases to identify studies on efficacy of anti-PD-1 inhibitor on CRC. Objectives were objective response rate, progression-free survival rate, disease control rate and overall survival rate with their 95% CI...
October 19, 2020: Journal of Comparative Effectiveness Research
Xinyuan Zhang, Chelsea F Mariano, Yuta Ando, Keyue Shen
T lymphocytes are the central coordinator and executor of many immune functions. The activation and function of T lymphocytes are mediated through the engagement of cell surface receptors and regulated by a myriad of intracellular signaling network. Bioengineering tools, including imaging modalities and fluorescent probes, have been developed and employed to elucidate the cellular events throughout the functional lifespan of T cells. A better understanding of these events can broaden our knowledge in the immune systems biology, as well as accelerate the development of effective diagnostics and immunotherapies...
October 19, 2020: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
Maria Lia Scribano
The COVID-19 pandemic has created a public health emergency. In this context, there are major concerns for patients with inflammatory bowel disease (IBD), particularly for those treated with immunomodulators, biologics, and Janus Kinase inhibitors. Infection susceptibility is, in fact, one of the reported risks for immunotherapy drugs. This review provides the existing evidence from worldwide case series describing: (a) the risk for the SARS-CoV-2 infection and (b) the risk of a severe infection outcome in patients with IBD treated with immunotherapy...
October 19, 2020: Digestive Diseases and Sciences
Antonio B Ward, Adam B Keeton, Xi Chen, Tyler E Mattox, Alex B Coley, Yulia Y Maxuitenko, Donald J Buchsbaum, Troy D Randall, Gang Zhou, Gary A Piazza
Approximately 30% of human cancers harbor a gain-in-function mutation in the RAS gene, resulting in constitutive activation of the RAS protein to stimulate downstream signaling, including the RAS-mitogen activated protein kinase pathway that drives cancer cells to proliferate and metastasize. RAS-driven oncogenesis also promotes immune evasion by increasing the expression of programmed cell death ligand-1, reducing the expression of major histocompatibility complex molecules that present antigens to T-lymphocytes and altering the expression of cytokines that promote the differentiation and accumulation of immune suppressive cell types such as myeloid-derived suppressor cells, regulatory T-cells, and cancer-associated fibroblasts...
September 2020: MedComm
Katia Abarca, Emma Rey-Jurado, Natalia Muñoz-Durango, Yaneisi Vázquez, Jorge A Soto, Nicolás M S Gálvez, Javier Valdés-Ferrada, Carolina Iturriaga, Marcela Urzúa, Arturo Borzutzky, Jaime Cerda, Luis Villarroel, Victoria Madrid, Pablo A González, José V González-Aramundiz, Susan M Bueno, Alexis M Kalergis
Background: Respiratory syncytial virus (RSV) is responsible for most respiratory tract infections and hospitalizations in infants and represents a significant economic burden for public health. The development of a safe, effective, and affordable vaccine is a priority for the WHO. Methods: We conducted a double-blinded, escalating-dose phase 1 clinical trial in healthy males aged 18-50 years to evaluate safety, tolerability, and immunogenicity of a recombinant Mycobacterium bovis BCG vaccine expressing the nucleoprotein of RSV (rBCG-N-hRSV)...
October 2020: EClinicalMedicine
Runlei Yang, Qian Dong, Huibin Xu, XueHui Gao, Ziyue Zhao, Jianchun Qin, Chuan Chen, Duqiang Luo
Phomoxanthone A and B (PXA and PXB) are xanthone dimers and isolated from the endophytic fungus Phomopsis sp. By254. The results demonstrated that PXB and PXA are noncompetitive inhibitors of SHP2 and PTP1B and competitive inhibitors of SHP1. Molecular docking studies showed that PXB and PXA interact with conserved domains of protein tyrosine phosphatases such as the β5-β6 loop, WPD loop, P loop, and Q loop. PXA and PXB could significantly inhibit the cell proliferation in MCF7 cells. Our results indicated that these two compounds do not efficiently inhibit PTP1B and SHP2 activity...
October 13, 2020: ACS Omega
Xiaodan Yao, Jaffer A Ajani, Shumei Song
Peritoneal metastases occur in 55-60% of patients with gastric cancer (GC) and are associated with a 2% 5-year overall survival rate. There are limited treatment options for these patients, and no targeted therapy or immunotherapy is available. Rational therapeutic targets remain to be found. In this review, we present the published literature and our own recent experience in molecular biology to identify important molecules and signaling pathways as well as cellular immunity involved in the peritoneal metastasis of GC...
2020: Translational Gastroenterology and Hepatology
Taymeyah Al-Toubah, Mauro Cives, Jonathan Strosberg
Neuroendocrine tumors (NETs) and neuroendocrine carcinomas (NECs) are a heterogeneous family of neoplasms. Well-differentiated tumors are often slow growing and characterized by low tumor mutational burden. Poorly differentiated NECs are aggressive, with an increased mutational burden and higher propensity to express PD-L1. While the therapeutic landscape for neuroendocrine neoplasms (NENs) has evolved substantially over the past decade, immunotherapy has been unexplored in NENs until recently. Checkpoint inhibitors such as anti-PD-1 and anti-CTLA-4 agents, bi-specific tumor-targeting antibodies, and chimeric antigen receptor (CAR) T-cell therapy are examples of treatments that have demonstrated efficacy in other cancers and have recently been investigated in NENs...
2020: Translational Gastroenterology and Hepatology
Andre Luiz Pitanga Bastos De Souza
Although researchers have been trying to harness the immune system for over 100 years, the advent of immune checkpoint blockers (ICB) marks an era of significant clinical outcomes in various metastatic solid tumors, characterized by complete and durable responses. ICBs are monoclonal antibodies that target either of a pair of transmembrane molecules in tumors or T-cells involved in immune evasion. Currently 2 ICBs targeting the checkpoint program death 1 (PD-1), nivolumab and pembrolizumab, and one cytotoxic lymphocyte antigen-4 (CTLA-4) inhibitor (ipilimumab) are approved in gastrointestinal malignancies...
2020: Translational Gastroenterology and Hepatology
William R Hartman, Aaron S Hess, Joseph P Connor
Background: SARS-CoV-2 and its associated disease, COVID-19, has infected over seven million people world-wide, including two million people in the United States. While many people recover from the virus uneventfully, a subset of patients will require hospital admission, some with intensive care needs including intubation, and mechanical ventilation. To date there is no cure and no vaccine is available. Passive immunotherapy by the transfusion of convalescent plasma donated by COVID-19 recovered patients might be an effective option to combat the virus, especially if used early in the course of disease...
2020: Translational medicine communications
Katarina Kalavska, Silvia Schmidtova, Michal Chovanec, Michal Mego
Testicular germ cell tumors (TGCTs) are malignancies with very high curative potential even in metastatic settings, mainly due to the introduction of cisplatin in the treatment of this disease. However, in a group of patients with cisplatin-refractory disease or with progressive disease despite high-dose salvage chemotherapy treatment, the prognosis is typically dismal. The triple combination of gemcitabine, oxaliplatin, and paclitaxel (GOP) has reasonable efficacy and is considered to be standard care for this group of patients...
2020: Frontiers in Oncology
Kai Kang, Fucun Xie, Jinzhu Mao, Yi Bai, Xiang Wang
Background: Melanoma is highly immunogenic and therefore suitable for immunotherapy, but the efficacy is limited by response rate. In several types of tumor, tumor mutation burden (TMB) and immune infiltration have been reported to predict the response to immunotherapy, although each has its limitations. In the current study, we aimed to explore the association of TMB with immune infiltration and prognosis in cutaneous melanoma. Methods: The data of cutaneous melanoma used for analyses was downloaded from The Cancer Genome Atlas (TCGA) database...
2020: Frontiers in Oncology
Olivier Humbert, David Chardin
When evaluating metastatic tumor response to systemic therapies, dissociated response is defined as the coexistence of responding and non-responding lesions within the same patient. Although commonly observed on interim whole-body imaging, the current response criteria in solid cancer do not consider this evolutive pattern, which is, by default, assimilated to progression. With targeted therapies and chemotherapies, dissociated response is observed with different frequencies, depending on the primary cancer type, treatment, and imaging modality...
2020: Frontiers in Oncology
Maria Levitin, Joel Ofori, Woo Jae Shin, Jiayi Huang, Mackenzie Daly, Dengfeng Cao, Russell Pachynski
Renal cell carcinoma (RCC) comprises 4.2% of all new cancer cases in the United States and 30% of cases are metastatic (mRCC) at diagnosis. Brain metastatic RCC historically has poor prognosis, but the development of immune checkpoint inhibitors has revolutionized their care and may be successfully combined with SBRT to improve prognosis. Here, we present a case of a patient with mRCC who had brain metastases treated with concurrent immune checkpoint inhibitors and SBRT. He continues to survive with good functional status years following his initial diagnosis...
2020: Frontiers in Oncology
Giuseppe Schepisi, Vincenza Conteduca, Chiara Casadei, Giorgia Gurioli, Lorena Rossi, Valentina Gallà, Maria Concetta Cursano, Nicole Brighi, Cristian Lolli, Cecilia Menna, Alberto Farolfi, Salvatore Luca Burgio, Amelia Altavilla, Giovanni Martinelli, Ugo De Giorgi
Currently, renal cell carcinoma is characterized by encouraging benefits from immunotherapy that have led to significant results in treatment outcome. The approval of nivolumab primarily as second-line monotherapy and, more recently, the approval of new combination therapies as first-line treatment have confirmed the importance of immunotherapy in this type of tumor. In this context, the chimeric antigen receptor (CAR)-T represents a further step forward in the field of immunotherapy. Initially tested on hematological malignancies, this new therapeutic approach is also becoming a topic of great interest for solid tumors...
2020: Frontiers in Oncology
Daiki Ikarashi, Shigehisa Kitano, Kazuyuki Ishida, Tetsuya Nakatsura, Hitoshi Shimodate, Takashi Tsuyukubo, Daichi Tamura, Renpei Kato, Tamotsu Sugai, Wataru Obara
Treatment options as second-line therapy for advanced ureteral carcinoma are limited, and patients experiencing recurrence after first-line cisplatin-based chemotherapy have a poor prognosis. Recently, the programmed death-1 (PD-1) inhibitor pembrolizumab provided a better survival benefit with a complete response rate (9.2%) for chemoresistatant urothelial carcinoma. However, the dynamic changes of the cancer microenvironment about the cases of complete response are still unknown. We herein report a case of a 57-year-old man who had been diagnosed with localized, non-muscle-invasive bladder cancer (pT1N0M0, high grade), for which he underwent transurethral resection of the bladder cancer twice...
2020: Frontiers in Oncology
Graziana Digiacomo, Claudia Fumarola, Silvia La Monica, Mara A Bonelli, Daniele Cretella, Roberta Alfieri, Andrea Cavazzoni, Maricla Galetti, Patrizia Bertolini, Gabriele Missale, Pier Giorgio Petronini
Advanced hepatocarcinoma (HCC) is an aggressive malignancy with poor prognosis and limited treatment options. Alterations of the cyclin D-CDK4/6-Rb pathway occur frequently in HCC, providing the rationale for its targeting at least in a molecular subset of HCC. In a panel of HCC cell lines, we investigated whether the CDK4/6 inhibitor palbociclib might improve the efficacy of regorafenib, a powerful multi-kinase inhibitor approved as second-line treatment for advanced HCC after sorafenib failure and currently under clinical investigation as first-line therapy in combination with immunotherapy...
2020: Frontiers in Oncology
Qiyao Zhang, Xiao Yu, Qingyuan Zheng, Yuting He, Wenzhi Guo
Hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world with a very poor prognosis. Immunotyping is of great significance for predicting HCC outcomes and guiding immunotherapy. Therefore, we sought to establish a reliable prognostic model for HBV-related HCC based on immune scores. We identified immune-related modules of The Cancer Genome Atlas LIHC and GSE14520 data sets through weighted gene co-expression network analysis and evaluated HCC through a non-negative matrix factorization algorithm...
2020: Frontiers in Oncology
Luochengling Xiang, Xiao Fu, Xiao Wang, Wenyuan Li, Xiaoqiang Zheng, Kejun Nan, Tao Tian
Objectives: The Kirsten Rat Sarcoma ( KRAS ) mutation is the commonest oncogenic drive mutation in lung adenocarcinoma (LUAD) and immunotherapy may be quite promising for KRAS -mutant LUAD. While the effects of tumor mutation burden (TMB) and copy number alteration (CNA) are poorly understood in this illness, our study aimed to explore the roles TMB and CNA play in the prediction of response to immune checkpoint inhibitor (ICI) therapy in advanced KRAS -mutant LUAD. Methods: Mutation and clinical data were downloaded from cBioPortal...
2020: Frontiers in Oncology
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