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https://www.readbyqxmd.com/read/29318591/immune-checkpoint-molecules-in-acute-myeloid-leukaemia-managing-the-double-edged-sword
#1
REVIEW
Willemijn Hobo, Tim J A Hutten, Nicolaas P M Schaap, Harry Dolstra
New immunotherapeutic interventions have revolutionized cancer treatment. The immune responsiveness of acute myeloid leukaemia (AML) was first demonstrated by allogeneic stem cell transplantation. In addition, milder immunotherapeutic approaches are exploited. However, the long-term efficacy of these therapies is hampered by various immune resistance and editing mechanisms. In this regard, co-inhibitory signalling pathways have been shown to play a crucial role. Via up-regulation of inhibitory checkpoints, tumour-reactive T cell and Natural Killer cell responses can be strongly impeded...
January 9, 2018: British Journal of Haematology
https://www.readbyqxmd.com/read/29311762/anti-inflammatory-cellular-targets-on-neutrophils-elucidated-using-a-novel-cell-migration-model-and-confocal-microscopy-a-clinical-supplementation-study
#2
T Smith, L Engelbrecht, C Smith
Background: In vivo studies have shown grape seed-derived polyphenols (GSP) to benefit in recovery from muscle injury by modulation of neutrophil infiltration into damaged tissue, thereby reducing secondary damage, as well as by facilitating an early anti-inflammatory macrophage phenotype shift. The current study aimed to provide data in this context from human models and to elucidate specific molecular targets of GSP.Using a placebo-controlled, double-blind study design, eighteen normally healthy volunteers between the ages of 18-35 years old (13 female and 5 male) were orally supplemented with 140 mg/day of GSP for 2 weeks...
2018: Journal of Inflammation
https://www.readbyqxmd.com/read/29289361/the-pathobiology-of-primary-testicular-diffuse-large-b-cell-lymphoma-implications-for-novel-therapies
#3
REVIEW
David D W Twa, Anja Mottok, Kerry J Savage, Christian Steidl
Primary testicular lymphomas (PTL) are the most prevalent type of testicular cancer arising in men over the age of 60. PTL accounts for approximately 1-2% of all non-Hodgkin lymphomas and most present with localized disease but despite this, outcome is poor. The majority of cases represent an extranodal manifestation of diffuse large B-cell lymphoma (DLBCL), known as primary testicular DLBCL (PT-DLBCL). Gene expression profiling has established that over 75% of PT-DLBCLs resemble the activated B-cell-like (ABC) or non-germinal center subtype of nodal DLBCL...
December 20, 2017: Blood Reviews
https://www.readbyqxmd.com/read/29259349/are-fusion-transcripts-in-relapsed-metastatic-head-and-neck-cancer-patients-predictive-of-response-to-anti-egfr-therapies
#4
Paolo Bossi, Marco Siano, Cristiana Bergamini, Maria Cossu Rocca, Andrea P Sponghini, Marco Giannoccaro, Luca Tonella, Alessandro Paoli, Edoardo Marchesi, Federica Perrone, Silvana Pilotti, Laura D Locati, Silvana Canevari, Lisa Licitra, Loris De Cecco
Prediction of benefit from combined chemotherapy and the antiepidermal growth factor receptor cetuximab is a not yet solved question in head and neck squamous cell carcinoma (HNSCC). In a selected series of 14 long progression-free survival (PFS) and 26 short PFS patients by whole gene and microRNA expression analysis, we developed a model potentially predictive of cetuximab sensitivity. To better decipher the "omics" profile of our patients, we detected transcript fusions by RNA-seq through a Pan-Cancer panel targeting 1385 cancer genes...
2017: Disease Markers
https://www.readbyqxmd.com/read/29245066/immuno-biological-comparison-of-hepatic-stellate-cells-in-a-reverted-and-activated-state
#5
Mehdi Najar, Hussein Fayyad-Kazan, Wissam H Faour, Adil El Taghdouini, Gordana Raicevic, Leo A van Grunsven, Mustapha Najimi, Etienne Sokal, Laurence Lagneaux
Human hepatic stellate cells (HSCs) demonstrated great immunological plasticity with important consequences for liver cell therapy. Activated HSCs (aHSCs) are in vitro reverted (rHSCs) to a quiescent-like phenotype with potential benefit to reduce liver fibrosis. The goal of this study is to establish and compare the immunological profile of activated and in vitro reverted HSCs and to investigate the impact of inflammatory priming on the immunobiology of both HSCs populations. The distribution of inflammatory primed activated and reverted HSCs across the different phases of the cell cycle is assessed by flow cytometry...
December 12, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29222272/signaling-pathways-and-immune-evasion-mechanisms-in-classical-hodgkin-lymphoma
#6
REVIEW
W Robert Liu, Margaret A Shipp
Classical Hodgkin lymphoma (cHL) is an unusual B-cell-derived malignancy in which rare malignant Hodgkin and Reed-Sternberg (HRS) cells are surrounded by an extensive but ineffective inflammatory/immune cell infiltrate. This striking feature suggests that malignant HRS cells escape immunosurveillance and interact with immune cells in the cancer microenvironment for survival and growth. We previously found that cHLs have a genetic basis for immune evasion: near-uniform copy number alterations of chromosome 9p24...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29209572/trial-watch-immunostimulatory-monoclonal-antibodies-for-oncological-indications
#7
REVIEW
Mariona Cabo, Rienk Offringa, Laurence Zitvogel, Guido Kroemer, Aura Muntasell, Lorenzo Galluzzi
The goal of cancer immunotherapy is to establish new or boost pre-existing anticancer immune responses that eradicate malignant cells while generating immunological memory to prevent disease relapse. Over the past few years, immunomodulatory monoclonal antibodies (mAbs) that block co-inhibitory receptors on immune effectors cells - such as cytotoxic T lymphocyte-associated protein 4 (CTLA4), programmed cell death 1 (PDCD1, best known as PD-1) - or their ligands - such as CD274 (best known as PD-L1) - have proven very successful in this sense...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29167175/signaling-pathways-and-immune-evasion-mechanisms-in-classical-hodgkin-lymphoma
#8
REVIEW
W Robert Liu, Margaret A Shipp
Classical Hodgkin lymphoma (cHL) is an unusual B-cell-derived malignancy in which rare malignant Hodgkin and Reed-Sternberg (HRS) cells are surrounded by an extensive but ineffective inflammatory/immune cell infiltrate. This striking feature suggests that malignant HRS cells escape immunosurveillance and interact with immune cells in the cancer microenvironment for survival and growth. We previously found that cHLs have a genetic basis for immune evasion: near-uniform copy number alterations of chromosome 9p24...
November 23, 2017: Blood
https://www.readbyqxmd.com/read/29158190/prevalence-of-microsatellite-instability-in-intraductal-papillary-mucinous-neoplasms-of-the-pancreas
#9
R M Lupinacci, A Goloudina, O Buhard, J B Bachet, R Maréchal, P Demetter, J Cros, A Bardier-Dupas, A Collura, P Cervera, A Scriva, S Dumont, P Hammel, A Sauvanet, C Louvet, J-R Delpéro, F Paye, J-C Vaillant, T André, J Closset, J-F Emile, J-L Van Laethem, V Jonchère, I Abd Alsamad, M Antoine, A Rodenas, J F Fléjou, N Dusetti, J Iovanna, A Duval, M Svrcek
Microsatellite instability (MSI) due to mismatch repair deficiency (dMMR) is detected in a small proportion of pancreatic ductal adenocarcinomas (PDACs). dMMR and MSI have been associated with responses of metastatic tumors, including PDACs, to immune checkpoint inhibitor therapy. We performed immunohistochemical analyses of a 445 PDAC specimens, collected from consecutive patients at multiple centers, to identify those with dMMR, based on loss of mismatch repair proteins MLH1, MSH2, MSH6, and/or PMS2. We detected dMMR in 1...
November 17, 2017: Gastroenterology
https://www.readbyqxmd.com/read/29124538/effect-of-acorus-calamus-l-polysaccharide-on-cd274-and-cd326-expression-by-lewis-lung-carcinoma-cells-in-mice
#10
K A Lopatina, E A Safonova, K V Nevskaya, M N Stakheeva, A M Gur'ev, E P Zueva, T G Razina, E N Amosova, S G Krylov, M V Belousov
Tumor cells can maintain their growth via immunosuppression and escape from host antitumor immunity by controlling the PD-1/PD-L1 system. Expression of PD-L1 (CD274) is an inhibitory signal for T cells, while the increase in CD326 expression in the tumor tissue correlates with metastasis development. The experimental preparation on the basis of α(1,2)-L-rhamno-α(1,4)-D-galactopyranosyluronan from Acorus calamus L. produces an antitumor effect: it reduces tumor node size and the number and area of metastases after transplantation of Lewis lung carcinoma...
November 10, 2017: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/29113654/the-role-of-intestinal-bacteria-in-the-development-and-progression-of-gastrointestinal-tract-neoplasms
#11
REVIEW
Kosuke Mima, Shuji Ogino, Shigeki Nakagawa, Hiroshi Sawayama, Koichi Kinoshita, Ryuichi Krashima, Takatsugu Ishimoto, Katsunori Imai, Masaaki Iwatsuki, Daisuke Hashimoto, Yoshifumi Baba, Yasuo Sakamoto, Yo-Ichi Yamashita, Naoya Yoshida, Akira Chikamoto, Takatoshi Ishiko, Hideo Baba
More than 100 trillion microorganisms inhabit the human intestinal tract and play important roles in health conditions and diseases, including cancer. Accumulating evidence demonstrates that specific bacteria and bacterial dysbiosis in the gastrointestinal tract can potentiate the development and progression of gastrointestinal tract neoplasms by damaging DNA, activating oncogenic signaling pathways, producing tumor-promoting metabolites such as secondary bile acids, and suppressing antitumor immunity. Other bacterial species have been shown to produce short-chain fatty acids such as butyrate, which can suppress inflammation and carcinogenesis in the gastrointestinal tract...
December 2017: Surgical Oncology
https://www.readbyqxmd.com/read/29108360/prediction-of-radio-responsiveness-with-immune-profiling-in-patients-with-rectal-cancer
#12
In Ja Park, Soyeon An, Sang-Yeob Kim, Hye Min Lim, Seung-Mo Hong, Mi-Ju Kim, Yun Jae Kim, Chang Sik Yu
We evaluate whether the tumor immune infiltrate (TIL) could be used for prediction of responsiveness to preoperative chemoradiotherapy (PCRT) in rectal cancers. Using formalin-fixed paraffin-embedded slides of pretreatment biopsies, co-stain for CD4, CD8, CD274 (PD-L1), FOXP3, cytokeratin, and DAPI was performed with Opal multi staining kit (Perkin-Elmer, Waltham, MA). Multispectral imaging and digital analysis to visualize and quantify specific immune infiltrates were performed using the Vectra imaging system (Perkin-Elmer)...
October 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29048660/canonical-and-non-canonical-wnt-signaling-in-cancer-stem-cells-and-their-niches-cellular-heterogeneity-omics-reprogramming-targeted-therapy-and-tumor-plasticity-review
#13
Masaru Katoh
Cancer stem cells (CSCs), which have the potential for self-renewal, differentiation and de-differentiation, undergo epigenetic, epithelial-mesenchymal, immunological and metabolic reprogramming to adapt to the tumor microenvironment and survive host defense or therapeutic insults. Intra-tumor heterogeneity and cancer-cell plasticity give rise to therapeutic resistance and recurrence through clonal replacement and reactivation of dormant CSCs, respectively. WNT signaling cascades cross-talk with the FGF, Notch, Hedgehog and TGFβ/BMP signaling cascades and regulate expression of functional CSC markers, such as CD44, CD133 (PROM1), EPCAM and LGR5 (GPR49)...
September 19, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29038297/tumor-pdcd1lg2-pd-l2-expression-and-the-lymphocytic-reaction-to-colorectal-cancer
#14
Yohei Masugi, Reiko Nishihara, Tsuyoshi Hamada, Mingyang Song, Annacarolina da Silva, Keisuke Kosumi, Mancang Gu, Yan Shi, Wanwan Li, Li Liu, Daniel Nevo, Kentaro Inamura, Yin Cao, Xiaoyun Liao, Katsuhiko Nosho, Andrew T Chan, Marios Giannakis, Adam J Bass, F Stephen Hodi, Gordon J Freeman, Scott J Rodig, Charles S Fuchs, Zhi Rong Qian, Jonathan A Nowak, Shuji Ogino
Expression of the immune checkpoint ligand CD274 (programmed cell death 1 ligand 1, PD-L1, from gene CD274) contributes to suppression of antitumor T cell-mediated immune response in various tumor types. However, the role of PDCD1LG2 (PD-L2, CD273, from gene PDCD1LG2) in the tumor microenvironment remains unclear. We hypothesized that tumor PDCD1LG2 expression might be inversely associated with lymphocytic reactions to colorectal cancer. We examined tumor PDCD1LG2 expression by IHC in 823 colon and rectal carcinoma cases within two U...
November 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28991373/novel-enriched-pathways-in-superficial-malignant-peripheral-nerve-sheath-tumors-mpnst-and-spindle-desmoplastic-melanomas-sdm
#15
George Jour, Nicole K Andeen, Rami Al -Rohil, Phyu P Aung, Meenakshi Mehrotra, Dzifa Duose, Benjamin Hoch, Zolt Argenyi, Rajyalakshmi Luthra, Ignacio I Wistuba, Victor G Prieto
Superficial malignant peripheral nerve sheath tumor (MPNST) is a rare, soft tissue neoplasm that shares morphological features and some molecular events with spindle and desmoplastic melanoma (SDM). Herein we sought to identify molecular targets for therapy using targeted RNA/DNA sequencing and gene expression of key immunological players. DNA and RNA from formalin-fixed, paraffin-embedded (FFPE) tissue were extracted and processed. Massive high-throughput deep parallel sequencing was performed using the Oncomine comprehensive panel enabling detection of relevant SNVs, CNVs, gene fusions, and indels from 143 unique genes on the Ion torrent sequencer for clinical trial research programs...
October 9, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28977839/genetic-defects-of-the-irf1-mediated-major-histocompatibility-complex-class-i-antigen-presentation-pathway-occur-prevalently-in-the-jak2-gene-in-non-small-cell-lung-cancer
#16
Tao Shen, Zhengming Chen, Zhizhuang Joe Zhao, Jie Wu
Recognition of major histocompatibility complex (MHC) class I antigens on tumor cells by cytotoxic T cells is involved in T cell-mediated tumor immune surveillance and immune checkpoint therapy. The interferon-γ (IFNγ)-IRF1 signaling pathway regulates MHC class I antigen presentation. To examine genetic defects of the IFNγ-IRF1 pathway in non-small cell lung cancer (NSCLC), we analyzed The Cancer Genome Atlas (TCGA) lung adenocarcinoma (LuAd) and lung squamous cell carcinoma (LuSc) data. Loss-of-function (LOF) genetic alterations of the IFNγ-IRF1 pathway genes (IFNGR1, IFNGR2, JAK1, JAK2, STAT1, IRF1) were found in 64 (6...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28932563/a-systematic-and-genome-wide-correlation-meta-analysis-of-pd-l1-expression-and-targetable-nsclc-driver-genes
#17
Jin Li, Yaoqi Chen, Xiaoshun Shi, Xiaobing Le, Fenglan Feng, Jingyi Chen, Chengzhi Zhou, Yusong Chen, Shuai Wen, Haikang Zeng, Allen M Chen, Yu Zhang
BACKGROUND: Studies have shown that the ligand of programmed cell death protein 1 (B7-H1, CD274 or PD-L1) is related to lung cancer driver genes. Although studies have examined the association between lung cancer driver gene mutations or expression and PD-L1 expression, the present studies have not been mined the correlation systematically and genome-widely. METHODS: All relevant published PD-L1 articles with driver genes data and the RNA-seq dataset from The Cancer Genome Atlas (TCGA) were analyzed...
August 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28928286/hpv-integration-in-hnscc-correlates-with-survival-outcomes-immune-response-signatures-and-candidate-drivers
#18
Lada A Koneva, Yanxiao Zhang, Shama Virani, Pelle B Hall, Jonathan B McHugh, Douglas B Chepeha, Gregory Wolf, Thomas E Carey, Laura S Rozek, Maureen A Sartor
The incidence of human papillomavirus (HPV)-related oropharynx cancer has steadily increased over the past two decades, and now represents a majority of oropharyngeal cancer cases. Integration of the HPV genome into the host genome is a common event during carcinogenesis that has clinically-relevant effects if the viral early genes are transcribed. Understanding the impact of HPV integration on clinical outcomes of head and neck squamous cell carcinoma (HNSCC) is critical for implementing de-escalated treatment approaches for HPV-positive HNSCC patients...
September 19, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28927758/evaluation-of-proinflammatory-and-immunosuppressive-cytokines-in-blood-and-bone-marrow-of-healthy-hematopoietic-stem-cell-donors
#19
Wojciech Fidyk, Iwona Mitrus, Agnieszka Ciomber, Andrzej Smagur, Agata Chwieduk, Magdalena Głowala-Kosińska, Sebastian Giebel
INTRODUCTION: Cytokine composition of bone marrow microenvironment in comparison to blood is poorly explored. The goal of this study was to investigate the levels of cytokines present in peripheral blood and bone marrow of healthy hematopoietic stem cells donors. The data obtained on this subject with addition to cytometric analysis can provide new insight into the hematopoietic stem cells microenvironment. METHODOLOGY: Study consisted of cytokine concentration analysis performed by ELISA tests of peripheral blood of healthy peripheral blood stem cells donors and bone marrow of healthy bone marrow donors...
September 15, 2017: Cytokine
https://www.readbyqxmd.com/read/28925087/relationship-of-tumor-pd-l1-cd274-expression-with-lower-mortality-in-lung-high-grade-neuroendocrine-tumor
#20
Kentaro Inamura, Yusuke Yokouchi, Maki Kobayashi, Hironori Ninomiya, Rie Sakakibara, Makoto Nishio, Sakae Okumura, Yuichi Ishikawa
Programmed death-ligand 1 (PD-L1) promotes immunosuppression by binding to PD-1 on T lymphocytes. Although tumor PD-L1 expression is a potential predictive marker of clinical response to anti-PD-1/PD-L1 therapy, little is known about its association with clinicopathological features, including prognosis, in high-grade neuroendocrine tumors (HGNETs), including small-cell lung carcinoma (SCLC) and large-cell neuroendocrine carcinoma (LCNEC), of the lung. We immunohistochemically examined the membranous of expression of PD-L1 in 115 consecutive surgical cases of lung HGNET (74 SCLC cases and 41 LCNEC cases)...
October 2017: Cancer Medicine
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