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https://www.readbyqxmd.com/read/29240881/nrf2-promotes-mutant-k-ras-p53-driven-pancreatic-carcinogenesis
#1
Shin Hamada, Keiko Taguchi, Atsushi Masamune, Masayuki Yamamoto, Tooru Shimosegawa
The Keap1-Nrf2 system contributes to the maintenance of homeostasis by regulating oxidative stress responses in normal tissues and organs, and is exploited in various cancers for proliferation, survival and acquisition of therapy resistance. Pancreatic cancer remains one of the intractable cancers, despite the improved clinical outcomes of other types of cancer, due to its invasive and refractory nature to therapeutic intervention. The current study aimed to clarify the contribution of Nrf2 to pancreatic carcinogenesis using a pancreas-specific mutant K-ras and p53 (KPC) mouse model...
June 1, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/29238973/demethylzeylasteral-zst93-inhibits-cell-growth-and-enhances-cell-chemosensitivity-to-gemcitabine-in-human-pancreatic-cancer-cells-via-apoptotic-and-autophagic-pathways
#2
Feng Wang, Xiaodong Tian, Zhengkui Zhang, Yongsu Ma, Xuehai Xie, Jian Liang, Chunxin Yang, Yinmo Yang
The overall 5-year survival rate of patients with human pancreatic cancer remains less than 8% because of its aggressive growth, early metastasis, and resistance to conventional chemoradiotherapy. It is essential to develop innovative and effective therapeutic agents to improve its prognosis. Demethylzeylasteral (ZST93) is a novel triterpenoid monomer extracted from the xylem of Tripterygium roots. This study aimed to assess the effects of ZST93 on cell proliferation and its role in the chemosensitivity to gemcitabine in human pancreatic cancer cells...
December 14, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29238879/the-small-vesicular-culprits-the-investigation-of-extracellular-vesicles-as-new-targets-for-cancer-treatment
#3
REVIEW
Fumihiko Urabe, Nobuyoshi Kosaka, Yusuke Yoshioka, Shin Egawa, Takahiro Ochiya
Extracellular vesicles (EVs) are membranous vesicles released from almost all type of cells including cancer cells. EVs transfer their components, such as microRNAs (miRNAs), messenger RNAs, lipids and proteins, from one cell to another, affecting the target cells. Emerging evidence suggests that reciprocal interactions between cancer cells and the cells in their microenvironment via EVs drive disease progression and therapy resistance. Therefore, understanding the roles of EVs in cancer biology will provide us with new opportunities to treat patients...
December 13, 2017: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/29238073/stage-dependent-therapeutic-efficacy-in-pi3k-mtor-driven-squamous-cell-carcinoma-of-the-skin
#4
Charbel Darido, Smitha R Georgy, Carleen Cullinane, Darren D Partridge, Rachael Walker, Seema Srivastava, Suraya Roslan, Marina R Carpinelli, Sebastian Dworkin, Richard B Pearson, Stephen M Jane
Cutaneous squamous cell carcinoma (SCC) is a recurrent cancer that is prevalent in predisposed subjects such as immunosuppressed patients and patients being treated for other malignancies. Model systems to trial therapies at different stages of SCC development are lacking, therefore precluding efficient therapeutic interventions. Here, we have disrupted the expression of the tumor suppressor GRHL3 to induce loss of PTEN and activation of the PI3K/mTOR signaling pathway in mice and human skin, promoting aggressive SCC development...
December 13, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29237805/preclinical-evaluation-of-scc244-glumetinib-a-novel-potent-and-highly-selective-inhibitor-of-c-met-in-met-dependent-cancer-models
#5
Jing Ai, Yi Chen, Xia Peng, Yinchun Ji, Yong Xi, Yanyan Shen, Xinying Yang, Yi Su, Yi-Ming Sun, Yinglei Gao, Yuchi Ma, Bing Xiong, Jingkang Shen, Jian Ding, Meiyu Geng
Because the receptor tyrosine kinase c-Met plays a critical role in tumor growth, metastasis, tumor angiogenesis and drug resistance, the c-Met axis represents an attractive therapeutic target. Herein, we report the first preclinical characterization of SCC244, a novel, potent and highly selective inhibitor of c-Met kinase. SCC244 showed subnanomolar potency against c-Met kinase activity and high selectivity versus 312 other tested protein kinases, making it one of the most selective c-Met inhibitors described to date...
December 13, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29237381/targeting-fgfr-with-bgj398-in-breast-cancer-effect-on-tumor-growth-and-metastasis
#6
Ana Sahores, Maria May, Gonzalo Sequeira, Cynthia Fuentes, Britta Jacobsen, Claudia Lanari, Caroline Ana Lamb
BACKGROUND: Endocrine resistance and metastatic dissemination comprise major clinical challenges for breast cancer treatment. The fibroblast growth factor receptor family (FGFR) consists of four tyrosine kinase transmembrane receptors, involved in key biological processes. Genomic alterations in FGFR have been identified in advanced breast cancer and thus, FGFR are an attractive therapeutic target. However, the efficacy of FGFR inhibitors on in vivo tumor growth is still controversial...
December 13, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/29236940/polyclonal-rb1-mutations-and-acquired-resistance-to-cdk-4-6-inhibitors-in-patients-with-metastatic-breast-cancer
#7
R Condorelli, L Spring, J O'Shaughnessy, L Lacroix, C Bailleux, V Scott, J Dubois, R J Nagy, R B Lanman, A J Iafrate, F Andre, A Bardia
Background: While deregulation of the cyclin D1-CDK4/6-retinoblastoma pathway is common in hormone receptor positive (HR+) breast cancer, Rb is usually intact in HR+ breast cancer, and targeted CDK 4/6 inhibitors that act upstream of Rb, are routinely being utilized in clinical practice. However, factors that can lead to clinical resistance to CDK 4/6 inhibitors are not known. Patients and methods: We identified patients who had pre and post genotyping in tissue and peripheral blood samples after receiving CDK 4/6 inhibitors...
December 11, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29236476/oxygen-self-produced-nanoplatform-for-relieving-hypoxia-and-breaking-resistance-to-sonodynamic-treatment-of-pancreatic-cancer
#8
Jie Chen, Honglin Luo, Yan Liu, Wei Zhang, Hongxue Li, Tao Luo, Kun Zhang, Yongxiang Zhao, Junjie Liu
Hypoxia as one characteristic hallmark of solid tumors has been demonstrated to involve in cancer metastasis and progression, induce severe resistance to oxygen-dependent therapies and hamper the transportation of theranostic agents. To address these issues, an oxygen self-produced sonodynamic therapy (SDT) nanoplatform involving modified fluorocarbon (FC) chains-mediated oxygen delivery protocol has been established to realize highly-efficient SDT against hypoxic pancreatic cancer. In this nanoplatform, mesopores and FC chains of FC chains-functionalized hollow mesoporous organosilica nanoparticles (FHMONs) carriers can provide sufficient storage capacity and binding sites for sonosensitizers (IR780) and oxygen, respectively...
December 13, 2017: ACS Nano
https://www.readbyqxmd.com/read/29236311/mir-221-negatively-regulates-inflammation-and-insulin-sensitivity-in-white-adipose-tissue-by-repression-of-sirtuin-1-sirt1
#9
Jie Peng, Yuanfei Zhou, Zhao Deng, Hong Zhang, Yinghui Wu, Tongxing Song, Yang Yang, Hongkui Wei, Jian Peng
It is well known that obesity-induced white adipose tissue inflammation is an important reason for insulin-resistance and type 2 diabetes mellitus. Sirtuin-1 (SIRT1) is an important regulator of inflammtion response pathways in white adipose tissue. Here, we found that miR-221 negatively regulated SIRT1 in white adipose tissue during inflammation and HFD-induced obesity. MiR-221 is a putative oncogene which has been found overexpressed in a number of human tumors. Recently, it has also found that miR-221 was increased in obese adipose tissue and may be involved in inflammation and insulin-resistance...
December 13, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29236227/loss-of-vascular-expression-of-nucleoside-triphosphate-diphosphohydrolase-1-cd39-in-hypertension
#10
Charlotte Roy, Julie Tabiasco, Antoine Caillon, Yves Delneste, Jean Merot, Julie Favre, Anne Laure Guihot, Ludovic Martin, Daniele C Nascimento, Bernhard Ryffel, Simon C Robson, Jean Sévigny, Daniel Henrion, Gilles Kauffenstein
Ectonucleoside triphosphate diphosphohydrolase-1, the major vascular/immune ectonucleotidase, exerts anti-thrombotic and immunomodulatory actions by hydrolyzing extracellular nucleotides (danger signals). Hypertension is characterized by vascular wall remodeling, endothelial dysfunction, and immune infiltration. Here our aim was to investigate the impact of arterial hypertension on CD39 expression and activity in mice. Arterial expression of CD39 was determined by reverse transcription quantitative real-time PCR in experimental models of hypertension, including angiotensin II (AngII)-treated mice (1 mg/kg/day, 21 days), deoxycorticosterone acetate-salt mice (1% salt and uninephrectomy, 21 days), and spontaneously hypertensive rats...
December 13, 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/29236132/brentuximab-vedotin-maintenance-following-chemotherapy-without-irradiation-for-primary-intracranial-embryonal-carcinoma-in-down-syndrome
#11
Mohammad H Abu Arja, Suzanne E Conley, Violeta Salceda, Fahd Al-Sufiani, Daniel R Boué, Jonathan L Finlay
BACKGROUND: Germ cell tumors (GCT) are the most common central nervous system (CNS) tumors in individuals with Down syndrome. Patients with Down syndrome treated with CNS irradiation are at increased risk of developing cerebrovascular complications such as moyamoya disease. Embryonal carcinoma components are recognized to be more resistant to conventional chemotherapy and radiotherapy and confer a very poor prognosis. CD30 is a member of the tumor necrosis factor-receptor superfamily...
December 13, 2017: Child's Nervous System: ChNS: Official Journal of the International Society for Pediatric Neurosurgery
https://www.readbyqxmd.com/read/29236030/the-tumor-suppressor-p53-in-mucosal-melanoma-of-the-head-and-neck
#12
REVIEW
Marie Kristin Fritsche, Andreas Knopf
Despite worldwide prevention programs, the incidence for cutaneous melanoma is continuously increasing. Mucosal melanoma (MM) represents a rare but highly aggressive phenotype of common melanoma with predilection in the sinonasal system. Far away from ultraviolet sun exposure, the molecular mechanisms underlying tumorigenesis and the highly aggressive clinical behavior are poorly understood. In many solid malignomas of the head and neck region, p53 tumor suppressor functions as oncogene due to p53 protein stabilizing mutation...
December 13, 2017: Genes
https://www.readbyqxmd.com/read/29235656/nonalcoholic-fatty-liver-disease-in-patients-with-psoriasis-a-consequence-of-systemic-inflammatory-burden
#13
REVIEW
R B Prussick, L Miele
Patients with psoriasis are at an increased risk for nonalcoholic fatty liver disease (NAFLD) compared to the general population. However, the pathophysiology underlying this comorbidity and elucidation of effective treatment strategies are unclear. This review provides insights into the possible role of chronic, low-grade inflammation in the pathogenesis of NAFLD in patients with psoriasis. Both conditions are associated with increased levels of pro-inflammatory adipokines (such as tumor necrosis factor-α and interleukin-6), and hepatokines, and decreased levels of adiponectin, an anti-inflammatory adipokine...
December 13, 2017: British Journal of Dermatology
https://www.readbyqxmd.com/read/29234674/microrna-in-glioblastoma-an-overview
#14
REVIEW
Barbara Banelli, Alessandra Forlani, Giorgio Allemanni, Anna Morabito, Maria Pia Pistillo, Massimo Romani
Glioblastoma is the most aggressive brain tumor and, even with the current multimodal therapy, is an invariably lethal cancer with a life expectancy that depends on the tumor subtype but, even in the most favorable cases, rarely exceeds 2 years. Epigenetic factors play an important role in gliomagenesis, are strong predictors of outcome, and are important determinants for the resistance to radio- and chemotherapy. The latest addition to the epigenetic machinery is the noncoding RNA (ncRNA), that is, RNA molecules that are not translated into a protein and that exert their function by base pairing with other nucleic acids in a reversible and nonmutational mode...
2017: International Journal of Genomics
https://www.readbyqxmd.com/read/29234663/reconstruction-with-iliac-pedestal-cup-and-proximal-femur-tumor-prosthesis-after-wide-resection-of-chondrosarcoma-10-year-follow-up-results
#15
Diogo Lino Moura, Rúben Fonseca, João Freitas, António Figueiredo, José Casanova
Chondrosarcoma is a malignant cartilage-forming neoplasm. It is difficult to treat because of resistance to both chemotherapy and radiation, making wide local excision the only treatment. This report presents an active, 43 year-old man who was diagnosed with recurrent clear cell chondrosarcoma of the proximal left femur, previously reconstructed with a total hip prosthesis, extending to the weight-bearing dome of the acetabulum. Cancer staging study revealed no signs of tumor dissemination at distance. Given the excellent functional status of the patient, the authors performed a Enneking-Dunham type periacetabular pelvic resection and resected en bloc, with the total hip prosthesis including 22 cm of the femur and a portion of the hip abductor apparatus...
November 2017: Revista Brasileira de Ortopedia
https://www.readbyqxmd.com/read/29234486/jnk-signaling-a-multiplexing-hub-in-programmed-cell-death
#16
REVIEW
Danny N Dhanasekaran, E Premkumar Reddy
Jun N-terminal kinases or JNKs have been shown to be involved in a wide array of signaling events underlying tumorigenesis and tumor progression. Through its interaction with a diverse set of signaling proteins and adaptors, JNKs regulate cell proliferation, invasive migration, therapy resistance, and programmed cell death. JNKs have been shown to play a role in apoptotic as well as non-apoptotic programmed cell death mechanisms including those of necroptosis, ferroptosis, pyroptosis, and autophagy. Most of the tumorigenic regulatory functions of JNKs can be related to their ability to module cell death via these programmed cell death mechanisms...
September 2017: Genes & Cancer
https://www.readbyqxmd.com/read/29234441/euphorbia-kansui-attenuates-insulin-resistance-in-obese-human-subjects-and-high-fat-diet-induced-obese-mice
#17
Seung-Wook Lee, Hyun-Young Na, Mi Hyeon Seol, Mia Kim, Byung-Cheol Lee
Background: Obesity is a main cause of insulin resistance (IR), metabolic syndrome, and fatty liver diseases. This study evaluated Euphorbia kansui radix (Euphorbia) as a potential treatment option for obesity and obesity-induced IR in obese human and high-fat diet- (HFD-) induced obese mice. Methods: In the human study, we analyzed the body weight change of 14 patients who took a single dose of 6 g of Euphorbia powder. In the animal study, male mice were divided into three groups: normal chow, HFD, and Euphorbia (high-fat diet and 100 mg/Kg Euphorbia once per week)...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/29234359/subtle-inflammation-a-possible-mechanism-of-future-cardiovascular-risk-in-obese-children
#18
Watchareewan Sontichai, Prapai Dejkhamron, Peraphan Pothacharoen, Prachya Kongtaweelert, Kevalee Unachak, Nuthapong Ukarapol
Purpose: The risk of cardiovascular disease (CVD) has been shown to be associated with systemic inflammation in obese adults with metabolic syndrome (MetS). The aims of this study were to evaluate the prevalence of MetS and its relation to inflammatory markers in obese Thai children. Methods: A cross-sectional study was conducted. Children with history of endogenous obesity, chronic diseases, drug ingestion, and any acute illness within 2 weeks prior to enrollment were excluded...
November 2017: Korean Journal of Pediatrics
https://www.readbyqxmd.com/read/29234250/are-we-ready-to-use-esr1-mutations-in-clinical-practice
#19
REVIEW
Rinath Jeselsohn
The recurrent ligand-binding domain ESR1 mutations are an important mechanism of endocrine resistance in estrogen receptor-positive (ER+) metastatic breast cancer. These mutations evolve under the selective pressure of endocrine treatments and are rarely found in treatment-naïve ER+ breast cancers. Preclinical studies showed that these mutations lead to ligand-independent activity facilitating resistance to aromatase inhibitors and relative resistance to tamoxifen and fulvestrant. Retrospective analyses of ESR1 mutations in baseline plasma circulating tumor DNA from clinical trials suggest that these mutations are prognostic of poor overall survival and predictive of resistance to aromatase inhibitors in metastatic disease...
October 2017: Breast Care
https://www.readbyqxmd.com/read/29234247/pi3k-mtor-inhibitors-in-the-treatment-of-luminal-breast-cancer-why-when-and-to-whom
#20
REVIEW
Francesco Schettini, Giuseppe Buono, Meghana V Trivedi, Sabino De Placido, Grazia Arpino, Mario Giuliano
Estrogen receptor (ER) signaling represents the main driver of tumor growth and survival in luminal breast cancer (BC). Despite the efficacy of endocrine agents, many patients with luminal BC do not respond to endocrine therapy and many others develop endocrine resistance over time, due to the activation of escape pathways such as the PI3K/AKT/mTOR signaling. Several clinical trials have demonstrated the efficacy of mTOR and PI3K inhibitors in overcoming endocrine resistance in hormone receptor-positive human epidermal growth factor receptor 2 (HER2)-negative metastatic BC (MBC) patients...
October 2017: Breast Care
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