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Cancer pathways

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https://read.qxmd.com/read/30786019/identification-of-a-new-inhibitor-of-kras-pde%C3%AE-interaction-targeting-kras-mutant-non-small-cell-lung-cancer
#1
Elaine Lai-Han Leung, Lian Xiang Luo, Ying Li, Zhong-Qiu Liu, Lan Lan Li, Dan Feng Shi, Ying Xie, Min Huang, Lin Lin Lu, Fu Gang Duan, Ju Min Huang, Xing Xing Fan, Zhong Wen Yuan, Jian Ding, Xiao Jun Yao, David C Ward, Liang Liu
Oncogenic KRAS is considered a promising target for anti-cancer therapy. However, direct pharmacological strategies targeting KRAS-driven cancers remained unavailable. The prenyl-binding protein PDEδ, a transporter of KRAS, has been identified as a potential target for pharmacological inhibitor by selectively binding to its prenyl-binding pocket, impairing oncogenic KRAS signaling pathway. Here, we discovered a novel PDEδ inhibitor (E)-N'-((3-(tert-butyl)-2-hydroxy-6,7,8,9-tetrahydrodibenzo[b,dfuran-1-yl)methylene)-2,4-dihydroxybenzohydrazide(NHTD) by using a high-throughput docking-based virtual screening approach...
February 20, 2019: International Journal of Cancer. Journal International du Cancer
https://read.qxmd.com/read/30785889/early-stage-serrated-adenocarcinomas-are-divided-into-several-molecularly-distinct-subtypes
#2
Daiki Hirano, Yuji Urabe, Shinji Tanaka, Koki Nakamura, Yuki Ninomiya, Ryo Yuge, Ryohei Hayashi, Shiro Oka, Yasuhiko Kitadai, Fumio Shimamoto, Koji Arihiro, Kazuaki Chayama
Serrated adenocarcinoma (SAC) is considered the end stage of the serrated neoplasia pathway. Although SAC prognosis is not widely recognized, the serrated pathway-associated subtype consistently exhibits unfavorable prognosis in genetic studies. Herein, we classified molecularly distinct subtypes of serrated adenocarcinomas and clarified their associated clinicopathological characteristics and genetic changes. We examined 38 early-stage colorectal SACs. Of these, 24 were classified into three molecularly distinct groups by colon cancer subtyping (CCS)...
2019: PloS One
https://read.qxmd.com/read/30785867/isoform-specific-ras-signaling-is-growth-factor-dependent
#3
Fiona E Hood, Bertram Klinger, Anna U Newlaczyl, Anja Sieber, Mathurin Dorel, Simon P Oliver, Judy M Coulson, Nils Blüthgen, Ian A Prior
HRAS, NRAS and KRAS isoforms are almost identical proteins that are ubiquitously expressed and activate a common set of effectors. In vivo studies have revealed that they are not biologically redundant; however, the isoform-specificity of Ras signaling remains poorly understood. Using a novel panel of isogenic SW48 cell lines endogenously expressing wild type or G12V mutated activated Ras isoforms we have performed a detailed characterization of endogenous isoform-specific mutant Ras signaling. We find that despite displaying significant Ras activation, the downstream outputs of oncogenic Ras mutants are minimal in the absence of growth factor inputs...
February 20, 2019: Molecular Biology of the Cell
https://read.qxmd.com/read/30785478/kaempferol-suppresses-human-gastric-cancer-snu-216-cell-proliferation-promotes-cell-autophagy-but-has-no-influence-on-cell-apoptosis
#4
Fan Zhang, Cuimei Ma
Gastric cancer remains a serious threat to human health worldwide. Kaempferol is a plant-derived flavonoid compound with a wide range of pharmacological activities. This study aimed to investigate the effects of kaempferol on gastric cancer SNU-216 cell proliferation, apoptosis, and autophagy, as well as underlying potential mechanisms. Viability, proliferation, and apoptosis of SNU-216 cells after kaempferol treatment were evaluated using cell counting kit-8 assay, 5-btomo-2'-deoxyuridine incorporation assay, and annexin V-FITC/PI staining, respectively...
February 14, 2019: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://read.qxmd.com/read/30785332/circular-rna-expression-in-exosomes-derived-from-breast-cancer-cells-and-patients
#5
Jinyan Wang, Qian Zhang, Siying Zhou, Hanzi Xu, Dandan Wang, Jifeng Feng, Jianhua Zhao, Shanliang Zhong
AIM: We aimed to explore the roles of circular RNAs (circRNAs) in breast cancer (BCa). MATERIALS & METHODS: RNA was extracted from exosomes and BCa cells and analyzed using the RNA sequencing technique or microarray. RESULTS: Compared with controls, 1147 and 1195 circRNAs were dysregulated in exosomes from metastatic and localized BCa patients, respectively. A total of 480 dysregulated circRNAs were found in metastatic patients compared with localized patients, and these dysregulated circRNAs were enriched in eight pathways...
February 20, 2019: Epigenomics
https://read.qxmd.com/read/30785305/exploration-of-n5-cair-mutase-novel-inhibitors-from-pyrococcus-horikoshii-ot3-a-computational-study
#6
Guru Raj Rao Ravi, Jayashree Biswal, Sureka Kanagarajan, Jeyaraman Jeyakanthan
In bacterial and archaeal purine biosynthetic pathways, sixth step involves utilization of enzyme PurE, catalyzing the translation of aminoimidazole ribonucleotide to 4-carboxy-5-aminoimidazole ribonucleotide (CAIR) with carbon dioxide. The formation of CAIR takes place through an unstable intermediate N5-CAIR, played by two enzymes-N5-CAIR synthetase (PurK) and N5-CAIR mutase (PurE) that further catalyzes the reaction of N5-CAIR to CAIR. In this study, N5-CAIR mutase (PH0320) from Pyrococcus horikoshii OT3 (PurE) was considered...
February 20, 2019: Journal of Computational Biology: a Journal of Computational Molecular Cell Biology
https://read.qxmd.com/read/30785126/antitumor-activity-of-asiaticoside-against-multiple-myeloma-drug-resistant-cancer-cells-is-mediated-by-autophagy-induction-activation-of-effector-caspases-and-inhibition-of-cell-migration-invasion-and-stat-3-signaling-pathway
#7
Li Yingchun, Wang Huihan, Zhang Rong, Zhang Guojun, Yang Ying, Liu Zhuogang
BACKGROUND Accumulating evidence suggests that plant-derived molecules may prove extremely beneficial in the development of chemotherapy for deadly cancer types. Multiple myeloma is a rare and incurable type of cancers. Very little research has been directed towards the development of chemotherapy for the management of multiple myeloma. Here, the anticancer effects of a plant-derived triterpenoid, Asiaticoside, were examined against the drug-resistant myeloma cell line KM3/BTZ. MATERIAL AND METHODS Cell viability was determined by CCK-8 assay and autophagy was checked by transmission electron microscopy...
February 20, 2019: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://read.qxmd.com/read/30785020/novel-2-4-disubstituted-quinazolines-as-cytotoxic-agents-and-jak2-inhibitors-synthesis-in-vitro-evaluation-and-molecular-dynamics-studies
#8
Siva Jyothi Buggana, Mani Chandrika Paturi, Harathi Perka, Deepak Reddy Gade, Rajendra Prasad Vvs
Recent studies reported the involvement of JAK2/STAT3 pathway in various solid tumours including breast, ovarian, prostate and lung cancers. Clinical literature also reported the lowered burden in breast and ovarian cancers by targeting JAK2 pathway. In this study, a series of novel 2,4-disubstituted quinazolines (2a-2 j and 3a-3 j) were synthesized and were evaluated for their cytotoxicity against human breast cancer (MDA-MB-231) and ovarian cancer (SK-O-V3) cell lines using MTT assay. Moderate to good in vitro cytotoxic potentials of the newly synthesized molecules were reported against selected human cancer cell lines...
January 21, 2019: Computational Biology and Chemistry
https://read.qxmd.com/read/30785018/resveratrol-exerts-dose-dependent-anti-fibrotic-or-pro-fibrotic-effects-in-kidneys-a-potential-risk-to-individuals-with-impaired-kidney-function
#9
Shuyun Liu, Meng Zhao, Yijie Zhou, Chengshi Wang, Yujia Yuan, Lan Li, William Bresette, Younan Chen, Jingqiu Cheng, Yanrong Lu, Jingping Liu
BACKGROUND: Renal fibrosis is the pathological feature of chronic kidney disease (CKD) which leads to end-stage renal disease (ESRD) and renal failure. Resveratrol [3,5,4'-trihydroxy-trans-stilbene (RSV)] has shown benefits for metabolic diseases and anti-cancer therapy, but its potential risk on renal health has not been fully evaluated. PURPOSE: To investigate the global effects of RSV on renal fibrosis in human tubular epithelial cell (TEC) line HK-2, and in mice with unilateral ureteral obstruction (UUO)...
December 17, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://read.qxmd.com/read/30784933/linc00152-facilitates-tumorigenesis-in-esophageal-squamous-cell-carcinoma-via-mir-153-3p-fyn-axis
#10
Donglei Liu, Min Gao, Kai Wu, Dengyan Zhu, Yang Yang, Song Zhao
Long non-coding RNAs (LncRNAs) have been found to be associated with the biological behaviors of human cancers. LINC00152 is reported as an oncogene in many kinds of malignancies. However, the functions and mechanisms of LINC00152 involved in esophageal squamous cell carcinoma (ESCC) remain elusive. Our results revealed that LINC00152 expression was up-regulated in ESCC, and correlated with advanced TNM stage, lymph node metastasis, and poor prognosis of ESCC patients. Functionally, LINC00152 knockdown suppressed proliferation, decreased colony forming ability, and induced apoptosis in ESCC cells...
February 19, 2019: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://read.qxmd.com/read/30784916/ribociclib-a-selective-cyclin-d-kinase-4-6-inhibitor-inhibits-proliferation-and-induces-apoptosis-of-human-cervical-cancer-in-vitro-and-in-vivo
#11
Yudi Xiong, Tianqi Li, Ganiou Assani, Huan Ling, Qian Zhou, Yangyang Zeng, Fuxiang Zhou, Yunfeng Zhou
Cervical cancer remains one of the main factors leading to tumor-related death worldwide. Many strategies of cancer treatment such as chemotherapy are developed and used nowadays. However, for the cancer chemotherapy resistance, reduction of the limitation of cancer chemotherapy efficacy is one of the aims of several oncology teams. Moreover, the cyclin-dependent kinase 4/6-cyclin D-retinoblastoma protein-E2F pathway is an important mechanism for cell cycle control and its dysregulation is one of the key factors for cancers development including cervical cancer...
February 18, 2019: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://read.qxmd.com/read/30784915/network-pharmacology-based-identi%C3%AF-cation-of-caveolin-1-as-a-key-target-of-oldenlandia-diffusa-to-suppress-breast-cancer-metastasis
#12
Bowen Yang, Neng Wang, Shengqi Wang, Xiong Li, Yifeng Zheng, Min Li, Juxian Song, Fengxue Zhang, Wenjie Mei, Yi Lin, Zhiyu Wang
BACKGROUND: Breast cancer remains the most common female malignancy and metastasis is the leading cause of death in breast cancer patients. Oldenlandia diffusa has been empirically and extensively used as an adjuvant therapy for metastatic breast cancer patients in Traditional Chinese Medicine (TCM) with proven efficacy. However, its anti-metastasis mechanism has been poorly revealed. METHODS: Multiple molecular biology experiments as well as network pharmacology, bioinformatics analysis were conducted to investigate the anti-metastasis mechanism of Oldenlandia diffusa in breast cancer...
February 20, 2019: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://read.qxmd.com/read/30784907/sinomenine-inhibits-proliferation-migration-invasion-and-promotes-apoptosis-of-prostate-cancer-cells-by-regulation-of-mir-23a
#13
Feng Xu, Qi Li, Zhiyu Wang, Xiangming Cao
Background Prostate cancer is an extremely common disease in males, and the mortality of prostate cancer has been rising year by year. Sinomenine has been reported to exhibit anti-tumor effect on various cancers, but the function of Sinomenine in prostate cancer remains unclear. The study aimed to explore the effect of Sinomenine on proliferation, apoptosis, migration and invasion in prostate cancer cells. Methods PC3 cells were stimulated by different concentrations of Sinomenine, then cell proliferation, migration, invasion and apoptosis were examined by CCK-8, BrdU, Transwell and flow cytometry, respectively...
February 18, 2019: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://read.qxmd.com/read/30784885/synthesis-in-vitro-and-in-vivo-biological-evaluation-of-substituted-3-5-imidazo-2-1-b-thiazolylmethylene-2-indolinones-as-new-potent-anticancer-agents
#14
Rita Morigi, Alessandra Locatelli, Alberto Leoni, Mirella Rambaldi, Roberta Bortolozzi, Elena Mattiuzzo, Roberto Ronca, Federica Maccarinelli, Ernest Hamel, Ruoli Bai, Andrea Brancale, Giampietro Viola
A small library of 3-(5-imidazo[2,1-b]thiazolylmethylene)-2-indolinones has been synthesized and screened according to protocols available at the National Cancer Institute (NCI). Some derivatives were potent antiproliferative agents, showing GI50 values in the nanomolar range. Remarkably, when most active compounds against leukemia cells were tested in human peripheral blood lymphocytes from healthy donors, were 100-200 times less cytotoxic. Some compounds, selected by the Biological Evaluation Committee of NCI, were examined to determine tubulin assembly inhibition...
January 26, 2019: European Journal of Medicinal Chemistry
https://read.qxmd.com/read/30784848/negotiating-jurisdictional-boundaries-in-response-to-new-genetic-possibilities-in-breast-cancer-care-the-creation-of-an-oncogenetic-taskscape
#15
Sarah Wright, Mary Porteous, Diane Stirling, Oliver Young, Charlie Gourley, Nina Hallowell
Changes in the nature and structure of healthcare pathways have implications for healthcare professionals' jurisdictional boundaries. The introduction of treatment focused BRCA1 and 2 genetic testing (TFGT) for newly diagnosed patients with breast cancer offers a contemporary example of pathway change brought about by technological advancements in gene testing and clinical evidence, and reflects the cultural shift towards genomics. Forming part of an ethnographically informed study of patient and practitioner experiences of TFGT at a UK teaching hospital, this paper focuses on the impact of a proposal to pilot a mainstreamed TFGT pathway on healthcare professionals' negotiations of professional jurisdiction...
February 13, 2019: Social Science & Medicine
https://read.qxmd.com/read/30784801/metabolic-response-of-bacteria-to-elevated-concentrations-of-glyphosate-based-herbicide
#16
Mara Grube, Uldis Kalnenieks, Olga Muter
Glyphosate-based herbicides (GBHs) are the most widespread commonly used broad-spectrum herbicides that contaminate soils and waters, are toxic to bacteria, plants and animals, and have been classified as 'probably carcinogenic to humans' by the International Agency for Research on Cancer in 2015. Particular soil bacteria and fungi can degrade GBHs, hence, search for new GBH-degrading strains or microbial consortia, effective under specific growth conditions and local environment, seems to be a promising solution for bio-remediation of glyphosate-contaminated environment...
February 20, 2019: Ecotoxicology and Environmental Safety
https://read.qxmd.com/read/30784602/whole-organ-genomic-characterization-of-mucosal-field-effects-initiating-bladder-carcinogenesis
#17
Tadeusz Majewski, Hui Yao, Jolanta Bondaruk, Woonbok Chung, Sangkyou Lee, June Goo Lee, Shizhen Zhang, David Cogdell, Guoliang Yang, Woonyoung Choi, Colin Dinney, H Barton Grossman, Christopher Logothetis, Steven E Scherer, Charles C Guo, Li Zhang, Peng Wei, John N Weinstein, Jean-Pierre Issa, Keith Baggerly, David J McConkey, Bogdan Czerniak
We used whole-organ mapping to study the locoregional molecular changes in a human bladder containing multifocal cancer. Widespread DNA methylation changes were identified in the entire mucosa, representing the initial field effect. The field effect was associated with subclonal low-allele frequency mutations and a small number of DNA copy alterations. A founder mutation in the RNA splicing gene, ACIN1, was identified in normal mucosa and expanded clonally with an additional 21 mutations in progression to carcinoma...
February 19, 2019: Cell Reports
https://read.qxmd.com/read/30784599/absence-of-cytosolic-2-cys-prx-subtypes-i-and-ii-exacerbates-tnf-%C3%AE-induced-apoptosis-via-different-routes
#18
Sunmi Lee, Joo Young Lee, Eun Woo Lee, Sujin Park, Dong Hoon Kang, Chengchun Min, Doo Jae Lee, Dongmin Kang, Jaewhan Song, Jongbum Kwon, Sang Won Kang
There are abundant peroxiredoxin (Prx) enzymes, but an increase of cellular H2 O2 level always happens in apoptotic cells. Here, we show that cellular H2 O2 switches different apoptosis pathways depending on which type of Prx enzyme is absent. TNF-α-induced H2 O2 burst preferentially activates the DNA damage-dependent apoptosis pathway in the absence of PrxI. By contrast, the same H2 O2 burst stimulates the RIPK1-dependent apoptosis pathway in the absence of PrxII by inducing the destruction of cIAP1 in caveolar membrane...
February 19, 2019: Cell Reports
https://read.qxmd.com/read/30784360/the-jak-stat3-and-nf-%C3%AE%C2%BAb-signaling-pathways-regulate-cancer-stem-cell-properties-in-anaplastic-thyroid-cancer-cells
#19
Ken Shiraiwa, Michiko Matsuse, Yuka Nakazawa, Tomoo Ogi, Keiji Suzuki, Vladimir A Saenko, Shuhang Xu, Kazuo Umezawa, Shunichi Yamashita, Kazuhiro Tsukamoto, Norisato Mitsutake
<b>Background:</b> Anaplastic thyroid carcinoma (ATC) is still one of the most aggressive cancers, and a therapy with a new concept needs to be developed. Recently, the research of cancer stem cells (CSCs) has been progressed, and CSCs have been suggested to be responsible for metastasis, recurrence, and therapy resistance. In ATC-CSCs, aldehyde dehydrogenase (ALDH) activity is the most reliable marker to enrich the CSCs; however, it itself is just a marker and is not involved in CSC properties...
February 20, 2019: Thyroid: Official Journal of the American Thyroid Association
https://read.qxmd.com/read/30784357/insights-from-molecular-dynamics-simulations-and-steered-molecular-dynamics-simulations-to-exploit-new-trends-of-the-interaction-between-hif-1%C3%AE-and-p300
#20
Zhengfei Yu, Ye Liu, Jingxuan Zhu, Jiarui Han, Xiaopian Tian, Weiwei Han, Li Zhao
Hypoxia-inducible factor-1 (HIF-1) is a transcription factor that plays an important role in the expression of genes, whose function is exerted through protein-protein interactions (PPIs), such as the transcriptional co-activator (CREB)-binding protein (CBP) and p300. Under hypoxic conditions, HIF-1is stabilized and translocated to CBP or p300, leading to the hypoxic response cascade. Furthermore, the PPI between HIF and p300/CBP is a potential cancer target for their role in the hypoxic response. In this study, molecular dynamics (MD) simulation was used to explore the conformational change for the p300 binding to one subunit of HIF-1 and HIF-1α...
February 20, 2019: Journal of Biomolecular Structure & Dynamics
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