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https://www.readbyqxmd.com/read/29691234/drug-induced-senescent-multiple-myeloma-cells-elicit-nk-cell-proliferation-by-direct-or-exosome-mediated-il-15-trans-presentation
#1
Cristiana Borrelli, Biancamaria Ricci, Elisabetta Vulpis, Cinzia Fionda, Maria Rosaria Ricciardi, Maria Teresa Petrucci, Laura Masuelli, Agnese Peri, Marco Cippitelli, Alessandra Zingoni, Angela Santoni, Alessandra Soriani
Treatment of multiple myeloma (MM) cells with sub-lethal doses of genotoxic drugs leads to senescence and results in increased NK cell recognition and effector functions. Herein we demonstrated that doxorubicin- and melphalan-treated senescent cells display increased expression of IL15, a cytokine involved in NK cell activation, proliferation, and maturation. IL15 up-regulation was evident at the mRNA and protein level, both in MM cell lines and malignant plasma cells (PCs) from patients' bone marrow (BM) aspirates...
April 24, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29690889/effect-of-colorectal-cancer-derived-extracellular-vesicles-on-the-immunophenotype-and-cytokine-secretion-profile-of-monocytes-and-macrophages
#2
Ineta Popēna, Artūrs Ābols, Līga Saulīte, Kārlis Pleiko, Elīna Zandberga, Kaspars Jēkabsons, Edgars Endzeliņš, Alicia Llorente, Aija Linē, Una Riekstiņa
BACKGROUND: Macrophages are one of the most important players in the tumor microenvironment. The polarization status of tumor associated macrophages into a pro-inflammatory type M1 or anti-inflammatory type M2 may influence cancer progression and patient survival. Extracellular vesicles (EVs) are membrane-bound vesicles containing different biomolecules that are involved in cell to cell signal transfer. Accumulating evidence suggests that cancer-derived EVs are taken up by macrophages and modulate their phenotype and cytokine profile...
April 24, 2018: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/29690614/cytokine-expression-and-macrophage-localization-in-xenograft-and-allograft-tumor-models-stimulated-with-lipopolysaccharide
#3
Junko Masuda, Tsukasa Shigehiro, Takuma Matsumoto, Ayano Satoh, Akifumi Mizutani, Chiho Umemura, Shoki Saito, Mayumi Kijihira, Eiji Takayama, Akimasa Seno, Hiroshi Murakami, Masaharu Seno
T cell-deficient mice such as nude mice are often used to generate tumor xenograft for the development of anticancer agents. However, the functionality of the other immune cells including macrophages, dendritic cells (DCs), and myeloid-derived suppressor cells (MDSCs) in the xenograft are largely unknown. Macrophages and dendritic cells (DCs) acquire functionally distinct properties in response to various environmental stimuli; the interaction of these cells with MDSCs in tumor microenvironments regulates cancer progression...
April 23, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29689559/molecular-regulation-of-bone-metastasis-pathogenesis
#4
Meng-Yu Wu, Chia-Jung Li, Giou-Teng Yiang, Yeung-Leung Cheng, Andy Po-Yi Tsai, Yueh-Tseng Hou, Yu-Chieh Ho, Ming-Feng Hou, Pei-Yi Chu
Distant metastases are the major cause of mortality in cancer patients. Bone metastases may cause bone fractures, local pain, hypercalcemia, bone marrow aplasia, and spinal cord compression. Therefore, the management of bone metastases is important in cancer treatment. Normal bone remodeling is regulated by osteoprotegerin ligand (OPGL), receptor activator of NF-κB ligand (RANKL), parathyroid hormone-related protein (PTHrP), and other cytokines. In the tumor microenvironment, tumor cells induce a vicious cycle that promotes osteoblastic and osteolytic lesions...
April 18, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29689411/radiolabeled-polyoxometalate-clusters-kidney-dysfunction-evaluation-and-tumor-diagnosis-by-positron-emission-tomography-imaging
#5
Dalong Ni, Dawei Jiang, Hyung-Jun Im, Hector F Valdovinos, Bo Yu, Shreya Goel, Todd E Barnhart, Peng Huang, Weibo Cai
Radiolabeled nanoprobes for positron emission tomography (PET) imaging has received special attention over the past decade, allowing for sensitive, non-invasive, and quantitative detection of different diseases. The rapidly renal clearable nanomaterials normally suffer from a low accumulation in the tumor through the enhanced permeability and retention (EPR) effect due to the rapidly reduced concentration in the blood circulation after renal clearance. It is highly important to design radiolabeled nanomaterials which can meet the balance between the rapid renal clearance and strong EPR effect within a suitable timescale...
April 12, 2018: Biomaterials
https://www.readbyqxmd.com/read/29689279/hepatitis-b-virus-x-protein-elevates-parkin-mediated-mitophagy-through-lon-peptidase-in-starvation
#6
Xiao-Yun Huang, Dan Li, Zhi-Xin Chen, Yue-Hong Huang, Wen-Yu Gao, Bi-Yun Zheng, Xiao-Zhong Wang
Hepatocellular Carcinoma (HCC) is the fifth most prevalent cancer worldwide. Specially, Hepatitis B viurs X protein (HBx) is a leading factor in the progression of Hepatitis B viurs-related HCC. Nutrient-deprived tumor microenvironment also contributes to tumor development. However, the role of HBx in nutrient-deprived HCC has received little investigation. Here, we show that HBx elevates PINK1-Parkin mediating mitophagy in starvation. HBx not only increases the PINK1/Parkin gene expression but also accelerates Parkin recruitment to partial mitochondria...
April 21, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29688859/patient-derived-xenograft-models-in-musculoskeletal-malignancies
#7
REVIEW
Wan Lu, Tu Chao, Chen Ruiqi, Su Juan, Li Zhihong
Successful oncological drug development for bone and soft tissue sarcoma is grossly stagnating. A major obstacle in this process is the lack of appropriate animal models recapitulating the complexity and heterogeneity of musculoskeletal malignancies, resulting in poor efficiency in translating the findings of basic research to clinical applications. In recent years, patient-derived xenograft (PDX) models generated by directly engrafting patient-derived tumor fragments into immunocompromised mice have recaptured the attention of many researchers due to their properties of retaining the principle histopathology, biological behaviors, and molecular and genetic characteristics of the original tumor, showing promising future in both basic and clinical studies of bone and soft tissue sarcoma...
April 23, 2018: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29688262/t-cells-isolated-from-patients-with-checkpoint-inhibitor-resistant-melanoma-are-functional-and-can-mediate-tumor-regression
#8
R Andersen, T H Borch, A Draghi, A Gokuldass, M A H Rana, M Pedersen, M Nielsen, P Kongsted, J W Kjeldsen, M C W Westergaard, H D Radic, C A Chamberlain, L R Hölmich, H W Hendel, M S Larsen, Ö Met, I M Svane, M Donia
Background: The majority of patients with metastatic melanoma obtain only short-term or no benefit at all from checkpoint inhibitor (CPI) immunotherapy. In this study, we investigated whether the immune system of patients progressing following CPI treatment was able to generate functional tumor-specific immune responses. Materials and methods: Tumor-infiltrating lymphocytes (TILs) were isolated and expanded from metastatic melanoma lesions which progressed during or after anti-PD-1 and anti-CTLA-4 treatment...
April 24, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29688063/evaluation-of-a-novel-biocompatible-magnetic-nanomedicine-based-on-beta-cyclodextrin-loaded-doxorubicin-curcumin-for-overcoming-chemoresistance-in-breast-cancer
#9
Roghayeh Rastegar, Hamid Akbari Javar, Mehdi Khoobi, Poua Dehghan Kelishadi, Gholam Hossein Yousefi, Mahmoud Doosti, Mohammad Hossien Ghahremani, Ahmad Sharif Tabrizi, Fatemeh Imanparast, Elham Gholibeglu, Mahdi Gholami
Codelivery of chemo-sensitizers with chemotherapeutics using combo nanomedicine is a promising platform for overcoming chemoresistance in breast cancer. However, tumor accumulation of nano-carriers based on enhanced permeability and retention (EPR) effect is confounded by heterogeneity in tumor microenvironment. Adsorption of protein corona on surface of nanoparticle boost up clearance by reticulo-endothelial system. In this study, a surface functionalized magnetic nanocomposite (NC) for codelivery of doxorubicin (DOX) and curcumin (CUR) is developed...
April 24, 2018: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/29687231/the-binding-of-an-anti-pd-1-antibody-to-fc%C3%AE-r%C3%AE-has-a-profound-impact-on-its-biological-functions
#10
Tong Zhang, Xiaomin Song, Lanlan Xu, Jie Ma, Yanjuan Zhang, Wenfeng Gong, Yilu Zhang, Xiaosui Zhou, Zuobai Wang, Yali Wang, Yingdi Shi, Huichen Bai, Ning Liu, Xiaolong Yang, Xinxin Cui, Yanping Cao, Qi Liu, Jing Song, Yucheng Li, Zhiyu Tang, Mingming Guo, Lai Wang, Kang Li
Antibodies targeting PD-1 have been demonstrated durable anti-cancer activity in certain cancer types. However, the anti-PD-1 antibodies are less or not efficacious in many situations, which might be attributed to co-expression of multiple inhibitory receptors or presence of immunosuppressive cells in the tumor microenvironment. Most of the anti-PD-1 antibodies used in clinical studies are of IgG4 isotype with the S228P mutation (IgG4S228P ). The functional impact by the interaction of anti-PD-1 IgG4S228P antibody with Fc gamma receptors (FcγRs) is poorly understood...
April 23, 2018: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29686906/postmastectomy-radiation-therapy-are-we-ready-to-individualize-radiation
#11
REVIEW
Ashlyn S Everett, Drexell Hunter Boggs, Jennifer F De Los Santos
Contemporary recommendations for postmastectomy radiation have undergone a shift in thinking away from simple stage based recommendations (one size fits all) to a system that considers both tumor biology and host factors. While surgical staging has traditionally dictated indications for postmastectomy radiation therapy (PMRT), our current understanding of tumor biology, host, immunoprofiles, and tumor microenvironment may direct a more personalized approach to radiation. Understanding the interaction of these variables may permit individualization of adjuvant therapy aimed at appropriate escalation and deescalation, including recommendations for PMRT...
2018: International Journal of Breast Cancer
https://www.readbyqxmd.com/read/29686682/targeting-cytosolic-nucleic-acid-sensing-pathways-for-cancer-immunotherapies
#12
REVIEW
Sandra Iurescia, Daniela Fioretti, Monica Rinaldi
The innate immune system provides the first line of defense against pathogen infection though also influences pathways involved in cancer immunosurveillance. The innate immune system relies on a limited set of germ line-encoded sensors termed pattern recognition receptors (PRRs), signaling proteins and immune response factors. Cytosolic receptors mediate recognition of danger damage-associated molecular patterns (DAMPs) signals. Once activated, these sensors trigger multiple signaling cascades, converging on the production of type I interferons and proinflammatory cytokines...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29686671/notch-signaling-in-macrophages-in-the-context-of-cancer-immunity
#13
REVIEW
Tanapat Palaga, Wipawee Wongchana, Patipark Kueanjinda
Macrophages play both tumor-suppressing and tumor-promoting roles depending on the microenvironment. Tumor-associated macrophages (TAMs) are often associated with poor prognosis in most, but not all cancer. Understanding how macrophages become TAMs and how TAMs interact with tumor cells and shape the outcome of cancer is one of the key areas of interest in cancer therapy research. Notch signaling is involved in macrophage activation and its effector functions. Notch signaling has been indicated to play roles in the regulation of macrophage activation in pro-inflammatory and wound-healing processes...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29686425/understanding-the-tumor-immune-microenvironment-time-for-effective-therapy
#14
REVIEW
Mikhail Binnewies, Edward W Roberts, Kelly Kersten, Vincent Chan, Douglas F Fearon, Miriam Merad, Lisa M Coussens, Dmitry I Gabrilovich, Suzanne Ostrand-Rosenberg, Catherine C Hedrick, Robert H Vonderheide, Mikael J Pittet, Rakesh K Jain, Weiping Zou, T Kevin Howcroft, Elisa C Woodhouse, Robert A Weinberg, Matthew F Krummel
The clinical successes in immunotherapy have been both astounding and at the same time unsatisfactory. Countless patients with varied tumor types have seen pronounced clinical response with immunotherapeutic intervention; however, many more patients have experienced minimal or no clinical benefit when provided the same treatment. As technology has advanced, so has the understanding of the complexity and diversity of the immune context of the tumor microenvironment and its influence on response to therapy. It has been possible to identify different subclasses of immune environment that have an influence on tumor initiation and response and therapy; by parsing the unique classes and subclasses of tumor immune microenvironment (TIME) that exist within a patient's tumor, the ability to predict and guide immunotherapeutic responsiveness will improve, and new therapeutic targets will be revealed...
April 23, 2018: Nature Medicine
https://www.readbyqxmd.com/read/29686060/complex-role-of-nk-cells-in-regulation-of-oncolytic-virus-bortezomib-therapy
#15
Yangjin Kim, Ji Young Yoo, Tae Jin Lee, Joseph Liu, Jianhua Yu, Michael A Caligiuri, Balveen Kaur, Avner Friedman
In the present work, we investigated the role of natural killer (NK) cells in combination therapy with oncolytic virus (OV) and bortezomib, a proteasome inhibitor. NK cells display rapid and potent immunity to metastatic and hematological cancers, and they overcome immunosuppressive effects of tumor microenvironment. We developed a mathematical model to address the question of how the density of NK cells affects the growth of the tumor. We found that the antitumor efficacy increases when the endogenous NKs are depleted and also when exogenous NK cells are injected into the tumor...
April 23, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29686035/a-peek-into-cancer-associated-fibroblasts-origins-functions-and-translational-impact
#16
REVIEW
Valerie S LeBleu, Raghu Kalluri
In malignant tumors, cancer cells adapt to grow within their host tissue. As a cancer progresses, an accompanying host stromal response evolves within and around the nascent tumor. Among the host stromal constituents associated with the tumor are cancer-associated fibroblasts, a highly abundant and heterogeneous population of cells of mesenchymal lineage. Although it is known that fibroblasts are present from the tumor's inception to the end-stage metastatic spread, their precise functional role in cancer is not fully understood...
April 19, 2018: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/29685462/aldh1-and-tumor-infiltrating-lymphocytes-as-predictors-for-neoadjuvant-chemotherapy-response-in-breast-cancer
#17
Anbok Lee, Kyu Yeoun Won, Sung-Jig Lim, Sun Young Cho, Sang-Ah Han, SaeGwang Park, Jeong-Yoon Song
Many studies have reported that Aldehyde dehydrogenase 1 (ALDH1) and tumor-infiltrating lymphocytes (TIL) are related to breast cancer prognosis. However, the clinical significance of ALDH1 and tumor-infiltrating immune cells in breast cancer has not been fully investigated in patients who received neoadjuvant chemotherapy (NAC). We studied the significance of the expression of ALDH1 and the population of TIL for predicting the prognosis and chemotherapeutic response of patients with breast cancer who had received NAC...
April 18, 2018: Pathology, Research and Practice
https://www.readbyqxmd.com/read/29685424/immunotherapy-for-the-treatment-of-hodgkin-lymphoma-an-evolving-paradigm
#18
REVIEW
Steven M Bair, Anthony Mato, Jakub Svoboda
Classical Hodgkin lymphoma (cHL) is one of the most common lymphomas in the Western world. Although most patients are cured with standard first-line therapy, up to 20% of patients will have relapsed or refractory disease. Although the conventional approach to treatment has consisted of chemotherapy, radiation, and for those who relapse, autologous or allogeneic transplantation, newer approaches have become available in recent years, including immunoconjugates and checkpoint inhibitors. These approaches have shown significant efficacy in clinical trials and might be associated with fewer long-term toxicities compared with conventional therapies...
March 31, 2018: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29685197/klf4-signalling-in-carcinogenesis-and-epigenetic-regulation-of-htert
#19
Suresh Singh Yadav, Rohini Ravindran Nair, Pramod Kumar Yadava
Gene expression is crucial and tightly regulated to steer the development, differentiation, proliferation and even apoptosis of a cell. Each cell and tissue type shows a unique repertoire of transcription factors. Tissue micro-environmental regulation of epigenetic signature of a gene has been documented in many cases. Epigenetic factors play a significant role in the regulation of gene expression. KLF4 is a well-known transcription factor regulating the expression of several genes including hTERT. KLF4 functions both as a tumor suppressor and oncogene depending on cell type...
June 2018: Medical Hypotheses
https://www.readbyqxmd.com/read/29685122/treatment-of-pancreatic-ductal-adenocarcinoma-with-tumor-antigen-specific-targeted-delivery-of-paclitaxel-loaded-plga-nanoparticles
#20
Shu-Ta Wu, Anthony J Fowler, Corey B Garmon, Adam B Fessler, Joshua D Ogle, Kajal R Grover, Bailey C Allen, Chandra D Williams, Ru Zhou, Mahboubeh Yazdanifar, Craig A Ogle, Pinku Mukherjee
BACKGROUND: Pancreatic ductal adenocarcinoma (PDA) remains the most aggressive cancers with a 5-year survival below 10%. Systemic delivery of chemotherapy drugs has severe side effects in patients with PDA and does not significantly improve overall survival rate. It is highly desirable to advance the therapeutic efficacy of chemotherapeutic drugs by targeting their delivery and increasing accumulation at the tumor site. MUC1 is a membrane-tethered glycoprotein that is aberrantly overexpressed in > 80% of PDA thus making it an attractive antigenic target...
April 23, 2018: BMC Cancer
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