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https://www.readbyqxmd.com/read/28735448/inhibitory-effects-of-andrographolide-on-activated-macrophages-and-adjuvant-induced-arthritis
#1
Swati Gupta, Kamla Prasad Mishra, Shashi Bala Singh, Lilly Ganju
Andrographolide, a diterpenoid lactone obtained from plant Andrographis paniculata, is used in South Asian countries to relieve various inflammatory symptoms. To study the effects of this agent, the impact of andrographolide on production of inflammatory mediators were delineated in mouse peritoneal macrophages (PMϕ). Inflammatory mediators like nitric oxide (NO), tumor necrosis factor (TNF)-α, interleukin-6 and related molecular mechanisms of andrographolide-mediated inhibition of enzymes/transcription factors were studied...
July 22, 2017: Inflammopharmacology
https://www.readbyqxmd.com/read/28735378/a-phase-i-ii-trial-and-pharmacokinetic-study-of-mithramycin-in-children-and-adults-with-refractory-ewing-sarcoma-and-ews-fli1-fusion-transcript
#2
Patrick J Grohar, John Glod, Cody J Peer, Tristan M Sissung, Fernanda I Arnaldez, Lauren Long, William D Figg, Patricia Whitcomb, Lee J Helman, Brigitte C Widemann
PURPOSE: In a preclinical drug screen, mithramycin was identified as a potent inhibitor of the Ewing sarcoma EWS-FLI1 transcription factor. We conducted a phase I/II trial to determine the dose-limiting toxicities (DLT), maximum tolerated dose (MTD), and pharmacokinetics (PK) of mithramycin in children with refractory solid tumors, and the activity in children and adults with refractory Ewing sarcoma. PATIENTS AND METHODS: Mithramycin was administered intravenously over 6 h once daily for 7 days for 28 day cycles...
July 22, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28735175/cancer-cell-membrane-coated-biomimetic-platform-for-tumor-targeted-photodynamic-therapy-and-hypoxia-amplified-bioreductive-therapy
#3
Shi-Ying Li, Hong Cheng, Wen-Xiu Qiu, Lu Zhang, Shuang-Shuang Wan, Jing-Yue Zeng, Xian-Zheng Zhang
Modulating tumor microenvironment to amplify the therapeutic efficiency would be a novel strategy for effective cancer treatment. In this work, based on the TPZ-loaded porphyrinic metal organic framework PCN-224 (PCN stands for porous coordination network), a cancer cell membrane-coated nanoplatform (TPZ@PCN@Mem) was fabricated for tumor targeted PDT and the successively resulting hypoxia-amplified bioreductive therapy. After administration, TPZ@PCN@Mem exhibited the selective accumulation and long-term retention at tumor tissue due to the immune escape and homologous targeting endowed by the cancer membrane coating...
July 18, 2017: Biomaterials
https://www.readbyqxmd.com/read/28734833/transforming-growth-factor-beta-promotes-liver-tumorigenesis-in-mice-via-upregulation-of-snail
#4
Hyuk Moon, Hye-Lim Ju, Sook In Chung, Kyung Joo Cho, Jung Woo Eun, Suk Woo Nam, Kwang-Hyub Han, Diego F Calvisi, Simon Weonsang Ro
BACKGROUND & AIMS: Transforming growth factor beta (TGFB) suppresses early stages of tumorigenesis, but also contributes to migration and metastasis of cancer cells. A large number of human tumors contain mutations that inactivate its receptors, or downstream proteins such as Smad transcription factors, indicating that the TGFB signaling pathway prevents tumor growth. We investigated the effects of TGFB inhibition on liver tumorigenesis in mice. METHODS: C57BL/6 mice received hydrodynamic tail injections of transposons encoding HRAS(G12V) and a short hairpin RNA (shRNA) to downregulate p53, or those encoding HRAS(G12V) and MYC, or those encoding HRAS(G12V) and TAZ(S89), to induce liver tumor formation; mice were also given injections of transposons encoding SMAD7 or shRNA against SMAD2, SMAD3, SMAD4, or SNAI1 (Snail), with or without ectopic expression of Snail...
July 19, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28734226/inhibition-of-prb-pathway-differentially-modulates-apoptosis-in-esophageal-cancer-cells
#5
Rossana C Soletti, Deborah Biasoli, Nathassya A L V Rodrigues, João M A Delou, Renata Maciel, Vera L A Chagas, Rodrigo A P Martins, Stevens K Rehen, Helena L Borges
Esophageal cancer is the sixth most common cause of cancer-related death worldwide. Current chemotherapy regimens include a combination of 5-fluorouracil (5-FU) and cisplatin, but more efficient therapy strategies are needed to increase 5-year survival. Alterations in the signaling pathway of the tumor suppressor gene Rb-1, which encodes a phosphoprotein (pRB) that negatively regulates the G1/S transition of the cell cycle, are present in 70% of all tumors, but its role in esophageal cancer is still unclear...
July 19, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28734166/naturally-occurring-immunomodulators-with-antitumor-activity-an-insight-on-their-mechanisms-of-action
#6
REVIEW
Shimaa Ibrahim Abdelmonym Mohamed, Ibrahim Jantan, Md Areeful Haque
Natural products with immunomodulatory activity are widely used in treatment of many diseases including autoimmune diseases, inflammatory disorders in addition to cancer. They gained a great interest in the last decades as therapeutic agents since they provide inexpensive and less toxic products than the synthetic chemotherapeutic agents. Immunomodulators are the agents that have the ability to boost or suppress the host defense response that can be used as a prophylaxis as well as in combination with other therapeutic modalities...
July 19, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28734136/the-good-and-bad-of-targeting-cancer-associated-extracellular-matrix
#7
REVIEW
Sabina Sangaletti, Claudia Chiodoni, Claudio Tripodo, Mario P Colombo
The maintenance of tissue homeostasis requires extracellular matrix (ECM) remodeling. Immune cells actively participate in regenerating damaged tissues contributing to ECM deposition and shaping. Dysregulated ECM deposition characterizes fibrotic diseases and cancer stromatogenesis, where a chronic inflammatory state sustains the ECM increase. In cancer, the ECM fosters several steps of tumor progression, providing pro-survival and proliferative signals, promoting tumor cell dissemination via collagen fibers or acting as a barrier to impede drug diffusion...
July 19, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28733709/il-4-blockade-alters-the-tumor-microenvironment-and-augments-the-response-to-cancer-immunotherapy-in-a-mouse-model
#8
Shuku-Ei Ito, Hidekazu Shirota, Yuki Kasahara, Ken Saijo, Chikashi Ishioka
Recent findings show that immune cells constitute a large fraction of the tumor microenvironment and that they modulate tumor progression. Clinical data indicate that chronic inflammation is present at tumor sites and that IL-4, in particular, is upregulated. Thus, we tested whether IL-4 neutralization would affect tumor immunity. Current results demonstrate that the administration of a neutralizing antibody against IL-4 enhances anti-tumor immunity and delays tumor progression. IL-4 blockade also alters inflammation in the tumor microenvironment, reducing the generation of both immunosuppressive M2 macrophages and myeloid-derived suppressor cells, and enhancing tumor-specific cytotoxic T lymphocytes...
July 21, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28733702/anti-invasive-effects-of-cxcr4-and-fak-inhibitors-in-non-small-cell-lung-carcinomas-with-mutually-inactivated-p53-and-pten-tumor-suppressors
#9
Miodrag Dragoj, Jasna Bankovic, Evangelia Sereti, Sofija Jovanovic Stojanov, Konstantinos Dimas, Milica Pesic, Tijana Stankovic
Non-small cell lung carcinoma (NSCLC) is the most common type of lung cancer. At the time of diagnosis, a large percentage of NSCLC patients have already developed metastasis, responsible for extremely high mortality rates. CXCR4 receptor and focal adhesion kinase (FAK) are known to regulate such invasive cancer behavior. Their expression is downregulated by p53 and PTEN tumor suppressors which are commonly co-inactivated in NSCLC patients and contribute to metastasis. Therefore, targeting CXCR4 or FAK seems to be a promising strategy in suppressing metastatic spread of p53/PTEN deficient NSCLCs...
July 22, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28733631/vgll4-selectively-represses-yap-dependent-gene-induction-and-tumorigenic-phenotypes-in-breast-cancer
#10
Yinglong Zhang, He Shen, Henry G Withers, Nuo Yang, Kayla E Denson, Ashley L Mussell, Alexander Truskinovsky, Qingyu Fan, Irwin H Gelman, Costa Frangou, Jianmin Zhang
Members of the mammalian Vestigial-like (VGLL) family of transcriptional cofactors activate genes in response to a wide variety of environmental cues. Recently, VGLL proteins have been proposed to regulate key signaling networks involved in cancer development and progression. However, the biological and clinical significance of VGLL dysregulation in human breast cancer pathogenesis remains unknown. Here, we report that diminished VGLL4 expression, but not VGLL1-3, correlated with both shorter relapse-free survival and shorter disease-specific survival of cancer patients with different molecular subtypes of breast cancer...
July 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28733556/transmembrane-tnf-%C3%AE-promotes-activation-induced-cell-death-by-forward-and-reverse-signaling
#11
Meng Zhang, Jing Wang, Lingwei Jia, Jin Huang, Cheng He, Fuqing Hu, Lifei Yuan, Guihua Wang, Mingxia Yu, Zhuoya Li
Secretory tumor necrosis factor-alpha (sTNF-α) is known to mediate activation- induced cell death (AICD). However, the role of tmTNF-α in AICD is still obscure. Here, we demonstrated that tmTNF-α expression significantly increased accompanied with enhanced apoptosis during AICD in Jurkat and primary human T cells. Knockdown or enhancement of tmTNF-α expression in activated T cells suppressed or promoted AICD, respectively. Treatment of activated T cells with exogenous tmTNF-α significantly augmented AICD, indicating that tmTNF-α as an effector molecule mediates AICD...
July 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28733529/immunotherapy-of-wap-tnp-mice-with-early-stage-mammary-gland-tumors
#12
Michael Bruns, Wolfgang Deppert
The SV40 transgenic BALB/c mouse based WAP-T/WAP-TNP model for triple-negative breast cancer allows the analysis of parameters influencing immunotherapeutic approaches. Except for WAP-TNP tumors expressing the immune-dominant LCMV NP-epitope within SV40 T-antigen (T-AgNP) which is not expressed by T-Ag of WAP-T tumors, the tumors are extremely similar. Comparative anti-PD1/PD-L1 immunotherapy of WAP-T and WAP-TNP mice supported the hypothesis that the immunogenicity of tumor antigen T-cell epitopes strongly influences the success of immune checkpoint blockade therapy, with highly immunogenic T-cell epitopes favoring rapid CTL exhaustion...
June 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28733522/abi3-a-component-of-the-wave2-complex-is-potentially-regulated-by-pi3k-akt-pathway
#13
Lais Moraes, Nilson I T Zanchin, Janete M Cerutti
We previously reported that ABI3 expression is lost in follicular thyroid carcinomas and its restoration significantly inhibited cell growth, invasiveness, migration, and reduced tumor growth in vivo. The mechanistic basis by which ABI3 exerts its tumor suppressive effects is not fully understood. In this study, we show that ABI3 is a phosphoprotein. Using proteomic array analysis, we showed that ABI3 modulated distinct cancer-related pathways in thyroid cancer cells. The KEA analysis found that PI3K substrates were enriched and forced expression of ABI3 markedly decreased the phosphorylation of AKT and the downstream-targeted protein pGSK3β...
June 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28733521/overexpression-of-chd1l-is-associated-with-poor-survival-and-aggressive-tumor-biology-in-esophageal-carcinoma
#14
Ze-Han Liu, Qi Zhang, Yi-Jie Ding, Ying-Hui Ren, Hui-Peng Yang, Qing Xi, Ying-Nan Cheng, Guo-Lin Miao, Hong-Kun Liu, Cai-Xia Li, Wen-Qiang Yan, Yan Li, Zhenyi Xue, Lijuan Zhang, Xin-Ye Li, Chen-Long Zhao, Yurong Da, Xian-Zhong Wu, Jun-Qiang Chen, Rongxin Zhang, Zhi-Gang Li
Esophageal carcinoma (EC) is a malignancy with high metastatic potential. Chromosomal helicase/ATPase DNA binding protein 1-like (CHD1L) gene is a newly identified oncogene located at Chr1q21, and it is amplified in many solid tumors. However, the status of CHD1L protein expression in EC and its clinical significance is uncertain. This study was designed to investigate the significance of CHD1L expression in human EC and its biological function in EC cells. The expression of CHD1L was examined by immunohistochemistry in 191 surgically resected ECs...
June 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28733519/long-noncoding-rna-ab073614-promotes-the-malignance-of-glioma-by-activating-wnt-%C3%AE-catenin-signaling-through-downregulating-sox7
#15
Yuqian Li, Gang Zhu, Wen Zeng, Jiancai Wang, Zhihong Li, Bao Wang, Bo Tian, Dan Lu, Xingye Zhang, Guodong Gao, Lihong Li
Long noncoding RNA (lncRNA) AB073614 has recently shown to be aberrantly increased and identified as a poor prognostic biomarker in human glioma. However, the potential mechanisms remain unknown. This study demonstrated that AB073614 expression was significantly upregulated in both glioma tissues and cell lines, and glioma patients with high AB073614 expression had lower overall survival rates. Importantly, silencing AB073614 expression remarkably inhibited U251 cell proliferation, migration, and invasion in vitro, as well as suppressed tumor formation in vivo...
July 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28733349/constitutive-ido1-expression-in-human-tumors-is-driven-by-cyclooxygenase-2-and-mediates-intrinsic-immune-resistance
#16
Marc Hennequart, Luc Pilotte, Stefania Cane, Delia Hoffmann, Vincent Stroobant, Etienne De Plaen, Benoît J Van den Eynde
Tumors use various mechanisms to avoid immune destruction. Cyclooxygenase-2 (COX-2) expression may be a driver of immune suppression in melanoma, but the mechanisms involved remain elusive. Here, we show that COX-2 expression drives constitutive expression of indoleamine 2,3-dioxygenase 1 (IDO1) in human tumor cells. IDO1 is an immunosuppressive enzyme that degrades tryptophan. In a series of seven human tumor lines, constitutive IDO1 expression depends on COX-2 and prostaglandin E2 (PGE2), which, upon autocrine signaling through the EP receptor, activates IDO1 via the PKC and PI3K pathways...
July 21, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28733032/pilose-antler-polypeptides-potentiates-osteoblast-differentiation-and-inhibits-osteoclastogenesis-via-manipulating-the-nf-%C3%AE%C2%BAb-pathway
#17
Guangwang Liu, Chao Ma, Peian Wang, Peiying Zhang, Xinhua Qu, Shen Liu, Zanjing Zhai, Degang Yu, Juan Gao, Jun Liang, Weixiang Dai, Lindong Zhou, Mengjiao Xia, Huilin Yang
Bones are inflexible yet ever-changing metabolic organs, and bone homeostasis is maintained through two delicately regulated processes: bone construction and bone reabsorption. An imbalance in bone metabolism is linked to most orthopedic diseases, including osteoporosis and rheumatoid arthritis. Importantly, tumor necrosis factor-α (TNF-α) blocks osteoblast differentiation and stimulates osteoclast formation, resulting in delayed deposition of new bone and accelerated bone resorption, especially in rheumatoid arthritis patients with inflammatory conditions...
July 18, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28732393/microrna-30a-suppresses-tumor-progression-by-blocking-ras-raf-mek-erk-signaling-pathway-in-hepatocellular-carcinoma
#18
Kun Zhou, Xiaoyu Luo, Yu Wang, Dachun Cao, Gang Sun
Emerging reports suggest microRNAs (miRNAs) play a vital role in the progression of malignant tumors. MiR-30a is downregulated in a variety of cancers and acts as a tumor suppressing gene. However, the molecular mechanisms of miRNA-30a in hepatocellular carcinoma (HCC) are still unclear. Hereby, in this study, we detected that miR-30a expression was significantly down-regulated in both HCC tissues compared with adjacent non-cancerous liver tissues, and we also observed that miR-30a expression was lower in HCC cell lines than that of normal controls...
July 17, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28732361/morusin-inhibits-cell-proliferation-and-tumor-growth-by-downregulating-c-myc-in-human-gastric-cancer
#19
Feng Wang, Dunke Zhang, Jingxin Mao, Xiao-Xue Ke, Rui Zhang, Chao Yin, Ning Gao, Hongjuan Cui
Morusin is a pure extract from the root bark of Morus australis (Moraceae). In recent years, morusin has been reported to exhibit anti-tumor biological activity in some types of human cancers through different mechanisms. Here, we attempted to investigate the inhibitory effect and mechanism of morusin on gastric cancer. Morusin markedly inhibited gastric cancer cell proliferation by down-regulating CDKs and Cyclins, such as CDK2, CDK4, Cyclin D1 and Cyclin E1. Additionally, morusin suppressed tumor growth in vitro and in vivo...
July 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28732288/lncrna-hotair-alleviates-rheumatoid-arthritis-by-targeting-mir-138-and-inactivating-nf-%C3%AE%C2%BAb-pathway
#20
Hong-Ju Zhang, Qiao-Feng Wei, Shu-Jun Wang, Hong-Jie Zhang, Xiu-Ying Zhang, Qin Geng, Yan-Hui Cui, Xiu-Hua Wang
Rheumatoid arthritis (RA) is a chronic and autoimmune-mediated inflammatory disease. We aimed to investigate the regulation of lncRNA HOTAIR in LPS-treated chondrocytes and RA mouse. Our results showed that HOTAIR expression was significantly reduced in LPS-treated chondrocytes. The HOTAIR was then over-expressed in chondrocytes by transfecting recombinant lentivirus carrying sequences encoding HOTAIR. The LPS-induced reduction of cell proliferation rate and production of two inflammatory factors interleukin (IL)-17, IL-23 were markedly inhibited...
July 18, 2017: International Immunopharmacology
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