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Programmed cell death

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https://www.readbyqxmd.com/read/28732383/radiation-alters-pd-l1-nkg2d-ligand-levels-in-lung-cancer-cells-and-leads-to-immune-escape-from-nk-cell-cytotoxicity-via-il-6-mek-erk-signaling-pathway
#1
Ming Jing Shen, Li Jun Xu, Li Yang, Ying Tsai, Peter C Keng, Yongbing Chen, Soo Ok Lee, Yuhchyau Chen
We investigated whether radiation influences the susceptibility of non-small cell lung cancer (NSCLC) cells to NK cell mediated cytotoxicity. We found radiation treatment increased expression of programmed cell death ligand 1 (PD-L1), but decreased NK group 2, member D (NKG2D) ligand expressions in A549 and H157 NSCLC cells. Both types of changes would have protected tumor cells from the cytotoxic action of NK cells. Consistently, we detected similar alteration in these molecules in radioresistant A549R26-1 and H157R24-1 subline cells...
July 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28730266/-malignant-melanoma-current-status
#2
REVIEW
J K Winkler, K Buder-Bakhaya, A Dimitrakopoulou-Strauss, A Enk, J C Hassel
CLINICAL ISSUE: The incidence of malignant melanoma is continuously increasing. The prognosis of metastatic disease is still limited. STANDARD TREATMENT: Until a few years ago palliative chemotherapy with a limited response rate was the standard treatment for metastatic melanoma. TREATMENT INNOVATIONS: Immunotherapy and targeted therapy provide new treatment options. Immune checkpoint inhibitors have significantly improved the prognosis. DIAGNOSTIC WORK-UP: Regional lymph node sonography, computed tomography (CT) of the neck, chest and abdomen and brain magnetic resonance imaging (MRI) are routinely used...
July 20, 2017: Der Radiologe
https://www.readbyqxmd.com/read/28730140/current-advances-in-checkpoint-inhibitors-lessons-from-non-central-nervous-system-cancers-and-potential-for-glioblastoma
#3
REVIEW
Natasha Lakin, Robert Rulach, Stefan Nowicki, Kathreena M Kurian
The adaptive immune system depends on the sequence of antigen presentation, activation, and then inhibition to mount a proportionate response to a threat. Tumors evade the immune response partly by suppressing T-cell activity using immune checkpoints. The use of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death 1 (PD-1), and programmed cell death ligand 1 (PD-L1) antibodies counteract this suppression, thereby enhancing the antitumor activity of the immune system. This approach has proven efficacy in melanoma, renal cancer, and lung cancer...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28729873/ageratum-enation-virus-infection-induces-programmed-cell-death-and-alters-metabolite-biosynthesis-in-papaver-somniferum
#4
Ashish Srivastava, Lalit Agrawal, Rashmi Raj, Meraj Jaidi, Shri K Raj, Swati Gupta, Ritu Dixit, Poonam C Singh, Tusha Tripathi, Om P Sidhu, Brahma N Singh, Sudhir Shukla, Puneet S Chauhan, Susheel Kumar
A previously unknown disease which causes severe vein thickening and inward leaf curl was observed in a number of opium poppy (Papaver somniferum L.) plants. The sequence analysis of full-length viral genome and associated betasatellite reveals the occurrence of Ageratum enation virus (AEV) and Ageratum leaf curl betasatellite (ALCB), respectively. Co-infiltration of cloned agroinfectious DNAs of AEV and ALCB induces the leaf curl and vein thickening symptoms as were observed naturally. Infectivity assay confirmed this complex as the cause of disease and also satisfied the Koch's postulates...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28729821/optimized-model-of-cerebral-ischemia-in-situ-for-the-long-lasting-assessment-of-hippocampal-cell-death
#5
Oksana Rybachuk, Olga Kopach, Volodymyr Krotov, Nana Voitenko, Tatyana Pivneva
Among all the brain, the hippocampus is the most susceptible region to ischemic lesion, with the highest vulnerability of CA1 pyramidal neurons to ischemic damage. This damage may cause either prompt neuronal death (within hours) or with a delayed appearance (over days), providing a window for applying potential therapies to reduce or prevent ischemic impairments. However, the time course when ischemic damage turns to neuronal death strictly depends on experimental modeling of cerebral ischemia and, up to now, studies were predominantly focused on a short time-window-from hours to up to a few days post-lesion...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28729608/programmed-death-one-homolog-maintains-the-pool-size-of-regulatory-t-cells-by-promoting-their-differentiation-and-stability
#6
Qi Wang, Jianwei He, Dallas B Flies, Liqun Luo, Lieping Chen
Programmed death one homolog (PD-1H) is an immunoglobulin superfamily molecule and primarily acts as a coinhibitor in the initiation of T cell response to antigens. Here, we report that genetic ablation of PD-1H in mice blocks the differentiation of naive T cells to Foxp3(+) inducible Treg cells (iTreg) with a significant decrease of iTreg in lymphoid organs. This effect of PD-1H is highly specific for iTreg because both naturally generated iTreg in gut-related tissues and in vitro induced iTreg by TGF-β were decreased whereas the genesis of natural Treg (nTreg) remains normal...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28729419/the-exocyst-is-required-for-photoreceptor-ciliogenesis-and-retinal-development
#7
Glenn P Lobo, Diana Fulmer, Lilong Guo, Xiaofeng Zuo, Yujing Dang, Seok-Hyung Kim, Yanhui Su, Kola George, Elisabeth Obert, Ben Fogelgren, Deepak Nihalani, Russell A Norris, Bärbel Rohrer, Joshua H Lipschutz
We previously have shown that the highly-conserved eight-protein exocyst trafficking complex is required for ciliogenesis in kidney tubule cells. We hypothesized here that ciliogenic programs are conserved across organs and species. To determine if renal primary ciliogenic programs are conserved in the eye, and to characterize the function and mechanisms by which the exocyst regulates eye development in zebrafish, we focused on exoc5, a central component of the exocyst complex, by analyzing both exoc5 zebrafish mutants, and photoreceptor-specific Exoc5 knockout mice...
July 20, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28728976/effect-of-alkylaminophenols-on-growth-inhibition-and-apoptosis-of-bone-cancer-cells
#8
Phuong Doan, Tien Nguyen, Olli Yli-Harja, Nuno R Candeias, Meenakshisundaram Kandhavelu
In this work, we report the anticancer properties of a series of 11 chemically synthesized alkylaminophenols against human osteosarcoma U2OS tumor cell line. Several assays including cytotoxicity, inhibitor kinetic study, cell migration, Annexin-V/PI double staining, reactive oxygen species (ROS) and caspase 3/7 assays were conducted on this cell line. Cytotoxic 2-((3,4-dihydroquinolin-1(2H)-yl)(p-tolyl)methyl)phenol was determined to have an IC50 value of 36.6μM against U2OS cells and it also inhibits the cell growth in time-dependent manner...
July 17, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28728868/pdl1-expression-in-desmoplastic-melanoma-is-associated-with-tumor-aggressiveness-and-progression
#9
Stefan Kraft, Maria-Teresa Fernandez-Figueras, Nina A Richarz, Keith T Flaherty, Mai P Hoang
BACKGROUND: The prognostic role of programmed death ligand 1 (PDL1), CD8, and forkhead box p3 (FoxP3) expression in desmoplastic melanomas is unclear. METHODS: We correlated PDL1, p53, and Ki-67 expression with CD8(+) and FoxP3(+) immune infiltrates with clinicopathologic variables and patient outcomes in a series of 66 desmoplastic melanomas. RESULTS: Tumoral PDL1 expression (≥25%), which was seen in 21% of patients (14 of 66), significantly correlated with mixed histology, tumor thickness, mitoses, recurrence, and metastasis...
July 17, 2017: Journal of the American Academy of Dermatology
https://www.readbyqxmd.com/read/28728856/achaete-scute-complex-homologue-2-accelerates-the-development-of-sj%C3%A3-gren-s-syndrome-like-disease-in-the-nod-shiltj-mouse
#10
Sung-Min Kim, Jeong-Eun Kwon, Jin-Sil Park, Hyeon-Beom Seo, Kyung-Ah Jung, Young-Mee Moon, Jennifer Lee, Seung-Ki Kwok, Mi-La Cho, Sung-Hwan Park
Achaete-scute complex homologue 2 (Ascl2) has been reported to induce the differentiation and activation of follicular helper T (TFH) cells, which are essential for development of Sjögren's syndrome (SS). This study examined whether Ascl2 plays a role in the development of SS. NOD/ShiLtJ mice were injected with an Ascl2-overexpression vector, and the infiltration of lymphocytes into salivary and lacrimal glands was assessed. The expression of inflammatory cytokines and chemoattractants for T or B cells was measured...
July 17, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28728840/antitumor-effect-of-the-integrin-%C3%AE-4-signaling-inhibitor-jk273-in-non-small-cell-lung-cancer-nci-h460%C3%A2-cells
#11
Lu Thien Nhan, Ganganna Bogonda, Pham Thuy Trang, Vo Anh Van, Lu Thien Phuc, Thi Nguyen Huong-Giang, Thi Nguyen My-Nuong, Huynh Phuong Nguyen, Truong Ngoc Tuyen, Lee Jongkook
Lung cancer accounts for the highest death rate among cancers worldwide, with most patients being diagnosed with non-small cell lung cancer (NSCLC), urging more effective therapies. We report that JK273, a pyrrolo[2,3-d]pyrimidine analog, which inhibits α4 integrin signaling, showed a selective cytotoxic effect against HCI-H460 NSCLC cells, with an IC50 of 0.98 ± 0.15 μM, but showed less sensitivity to fibroblasts with a sensitivity index (SI) greater than 30. This effect was attributed to cell cycle arrest at S phase by JK273 treatment, resulting in the apoptosis of NCI-H460 cells, further confirmed by exposing phosphatidylserine and morphological changes...
July 17, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28728544/cladosporol-a-triggers-apoptosis-sensitivity-by-ros-mediated-autophagic-flux-in-human-breast-cancer-cells
#12
Mytre Koul, Ashok Kumar, Ramesh Deshidi, Vishal Sharma, Rachna D Singh, Jasvinder Singh, Parduman Raj Sharma, Bhawal Ali Shah, Sundeep Jaglan, Shashank Singh
BACKGROUND: Endophytes have proven to be an invaluable resource of chemically diverse secondary metabolites that act as excellent lead compounds for anticancer drug discovery. Here we report the promising cytotoxic effects of Cladosporol A (HPLC purified >98%) isolated from endophytic fungus Cladosporium cladosporioides collected from Datura innoxia. Cladosporol A was subjected to in vitro cytotoxicity assay against NCI60 panel of human cancer cells using MTT assay. We further investigated the molecular mechanism(s) of Cladosporol A induced cell death in human breast (MCF-7) cancer cells...
July 20, 2017: BMC Cell Biology
https://www.readbyqxmd.com/read/28727766/clinical-implications-of-the-novel-cytokine-il-38-expressed-in-lung-adenocarcinoma-possible-association-with-pd-l1-expression
#13
Kazuki Takada, Tatsuro Okamoto, Masaki Tominaga, Koji Teraishi, Takaki Akamine, Shinkichi Takamori, Masakazu Katsura, Gouji Toyokawa, Fumihiro Shoji, Masaki Okamoto, Yoshinao Oda, Tomoaki Hoshino, Yoshihiko Maehara
Interleukin (IL)-38, a novel member of the IL-1 cytokine family, is homologous to IL-1 receptor antagonist (IL-1Ra) and IL-36Ra, and has been reported to act as an antagonist. IL-38 expression is found in tonsil, placenta, and spleen, and recent studies suggest an association between IL-38 and autoimmune diseases. However, whether IL-38 plays a role in carcinogenesis or cancer growth is unclear. In the present study, we identified increases in IL-38 expression by immunohistochemistry in multiple types of cancer cells...
2017: PloS One
https://www.readbyqxmd.com/read/28726391/tumor-associated-mutations-in-caspase-6-negatively-impact-catalytic-efficiency
#14
Kevin B Dagbay, Maureen E Hill, Elizabeth Barrett, Jeanne A Hardy
Unregulated, particularly suppressed programmed cell death is one of the distinguishing features of many cancer cells. The cysteine protease caspase-6, one of the executioners of apoptotic cell death, plays a crucial role in regulation of apoptosis. Several CASP6 gene somatic mutations in tumor tissues have been reported. This work explores the effect of CASP6 tumor-associated mutations on the catalytic efficiency and structure of caspase-6. In general, these mutations showed decreased overall catalytic turnover...
July 20, 2017: Biochemistry
https://www.readbyqxmd.com/read/28725488/generation-and-analysis-of-spheroids-from-human-primary-skin-myofibroblasts-an-experimental-system-to-study-myofibroblasts-deactivation
#15
Giuseppina Granato, Maria R Ruocco, Antonino Iaccarino, Stefania Masone, Gaetano Calì, Angelica Avagliano, Valentina Russo, Claudio Bellevicine, Gaetano Di Spigna, Giuseppe Fiume, Stefania Montagnani, Alessandro Arcucci
Myofibroblasts are activated fibroblasts involved in tissue repair and cancer. They are characterized by de novo expression of α-smooth muscle actin (α-SMA), immunoregulatory phenotype and paracrine interaction with normal and tumorigenic cells leading to cell proliferation. At the end of wound-healing myofibroblasts undergo apoptotic cell death, whereas in vitro-activated fibroblasts are also subjected to a programmed necrosis-like cell death, termed nemosis, associated with cyclooxygenase-2 (COX-2) expression induction and inflammatory response...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28724891/hypoxia-inducible-factor-1-alpha-is-involved-in-rip-induced-necroptosis-caused-by-in-vitro-and-in-vivo-ischemic-brain-injury
#16
Xiao-Sa Yang, Tai-Long Yi, Sai Zhang, Zhong-Wei Xu, Ze-Qi Yu, Hong-Tao Sun, Cheng Yang, Yue Tu, Shi-Xiang Cheng
Necroptosis, a novel type of programmed cell death, is involved in stroke-induced ischemic brain injury. Although studies have sought to explore the mechanisms of necroptosis, its signaling pathway has not yet to be completely elucidated. Thus, we used oxygen-glucose deprivation (OGD) and middle cerebral artery occlusion (MCAO) models mimicking ischemic stroke (IS) conditions to investigate mechanisms of necroptosis. We found that OGD and MCAO induced cell death, local brain ischemia and neurological deficit, while zVAD-fmk (zVAD, an apoptotic inhibitor), GSK'872 (a receptor interacting protein kinase-3 (RIP3) inhibitor), and combined treatment alleviated cell death and ischemic brain injury...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28723489/immunotherapy-for-renal-cancer-sequencing-and-combinations
#17
REVIEW
Grant D Stewart, Maria De Santis, Bernard Escudier, Thomas Powles, Guru Sonpavde
CONTEXT: Current therapy for renal cell carcinoma (RCC) generally consists of the sequential administration of single agent therapy. Given the advent of T-cell checkpoint inhibitors, the role of combinations including these agents is being intensely interrogated. OBJECTIVE: To evaluate ongoing trials of combinations including immunotherapy and sequencing of agents to treat RCC. EVIDENCE ACQUISITION: Recent data and ongoing trials were analyzed to evaluate the direction of research in this arena...
December 15, 2016: European Urology Focus
https://www.readbyqxmd.com/read/28722673/expression-and-clinical-association-of-programmed-cell-death-1-programmed-death-ligand-1-and-cd8-lymphocytes-in-primary-sarcomas-is-subtype-dependent
#18
Anke E M van Erp, Yvonne M H Versleijen-Jonkers, Melissa H S Hillebrandt-Roeffen, Laurens van Houdt, Mark A J Gorris, Laura S van Dam, Thomas Mentzel, Marije E Weidema, C Dilara Savci-Heijink, Ingrid M E Desar, Hans H M Merks, Max M van Noesel, Janet Shipley, Winette T A van der Graaf, Uta E Flucke, Friederike A G Meyer-Wentrup
In order to explore the potential of immune checkpoint blockade in sarcoma, we investigated expression and clinical relevance of programmed cell death-1 (PD-1), programmed death ligand-1 (PD-L1) and CD8 in tumors of 208 sarcoma patients. Primary untreated osteosarcoma (n = 46), Ewing sarcoma (n = 32), alveolar rhabdomyosarcoma (n = 20), embryonal rhabdomyosarcoma (n = 77), synovial sarcoma (n = 22) and desmoplastic small round cell tumors (DSRCT) (n = 11) were examined immunohistochemically. PD-L1 expression was predominantly detected in alveolar and embryonal rhabdomyosarcomas (15% and 16%, respectively)...
July 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28722656/corrupting-the-dna-damage-response-a-critical-role-for-rad52-in-tumor-cell-survival
#19
Rachel Lieberman, Ming You
The DNA damage response enables cells to survive, maintain genome integrity, and to safeguard the transmission of high-fidelity genetic information. Upon sensing DNA damage, cells respond by activating this multi-faceted DNA damage response leading to restoration of the cell, senescence, programmed cell death, or genomic instability if the cell survives without proper repair. However, unlike normal cells, cancer cells maintain a marked level of genomic instability. Because of this enhanced propensity to accumulate DNA damage, tumor cells rely on homologous recombination repair as a means of protection from the lethal effect of both spontaneous and therapy-induced double-strand breaks (DSBs) in DNA...
July 15, 2017: Aging
https://www.readbyqxmd.com/read/28721883/patterns-of-care-for-patients-with-early-stage-glottic-cancer-undergoing-definitive-radiation-therapy-a-national-cancer-database-analysis
#20
William A Stokes, Diana Abbott, Andy Phan, David Raben, Ryan M Lanning, Sana D Karam
PURPOSE: To characterize practice patterns, including temporal trends, in fractionation schedules among patients in the United States undergoing definitive radiation therapy for early-stage glottic cancer and to compare overall survival outcomes between fractionation schedules. METHODS AND MATERIALS: We queried the National Cancer Database for patients with TisN0M0, T1N0M0, or T2N0M0 squamous cell carcinoma of the glottic larynx diagnosed between 2004 and 2012 and undergoing definitive radiation therapy...
August 1, 2017: International Journal of Radiation Oncology, Biology, Physics
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