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https://www.readbyqxmd.com/read/28742795/cancer-associated-fibroblasts-promote-bone-invasion-in-oral-squamous-cell-carcinoma
#1
A A Elmusrati, A E Pilborough, S A Khurram, D W Lambert
BACKGROUND: The molecular mechanisms involved in the invasion of bone by oral squamous cell carcinomas (OSCC) are poorly understood, and little is known about the role of cancer-associated fibroblasts (CAF), the presence of which confers a poor prognosis. METHODS: Clinicopathological data from 277 OSCC cases involving bone resections were reviewed, and 32 cases thoroughly analysed histologically. Immunohistochemistry was used to examine αSMA, RANKL and OPG. Western blotting and qPCR were used to assess myofibroblast (CAF-like) differentiation, RANKL and OPG expression in vitro, and RANKL secretion was analysed by ELISA...
July 25, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28742207/socs3-overexpression-enhances-adm-resistance-in-bladder-cancer-t24-cells
#2
M-Z Li, D-H Lai, H-B Zhao, Z Chen, Q-X Huang, J Situ
OBJECTIVE: JAK-STAT3 signaling pathway widely participates in cell proliferation and apoptosis. Suppressor of cytokine signaling 3 (SOCS3) is a negative regulator of JAK-STAT3. SOCS3 downregulation is associated with drug resistance in breast cancer and leukemia. However, its role in bladder cancer drug resistance is still unclear. This study established ADM resistant bladder cancer cell model to investigate the role of SOCS3-JAK/STAT3 signaling pathway ADM resistance. MATERIALS AND METHODS: ADM drug resistant cell line T24/ADM was established...
July 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28741923/codelivery-of-trichosanthin-and-albendazole-by-nano-self-assembly-for-overcoming-tumor-multidrug-resistance-and-metastasis
#3
Yisi Tang, Jianming Liang, Aihua Wu, Yingzhi Chen, Pengfei Zhao, Tingting Lin, Meng Zhang, Qin Xu, Jianxin Wang, Yongzhuo Huang
Multidrug resistance (MDR) and metastasis are the major obstacles in cancer chemotherapy. Nanotechnology-based combination therapy is a useful strategy. Recently, the combination of biologics and small drugs has attracted much attention in cancer therapy. Yet, the treatment outcomes are often compromised by the different pharmacokinetics profiles of the co-administered drugs, thus leading to inconsistent drug uptake and suboptimal drug combination at the tumor sites. Nanotechnology-based codelivery offers a promising method to address this problem, which is well demonstrated in the use of small drugs combination...
July 25, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28741662/molecular-breakdown-a-comprehensive-view-of-anaplastic-lymphoma-kinase-alk-rearranged-non-small-cell-lung-cancer
#4
Ka-Won Noh, Mi-Sook Lee, Seung Eun Lee, Ji-Young Song, Hyun-Tae Shin, Yu Jin Kim, Doo Yi Oh, Kyungsoo Jung, Minjung Sung, Mingi Kim, Sungbin An, Joungho Han, Young Mog Shim, Jae Ill Zo, Jhingook Kim, Woong-Yang Park, Se-Hoon Lee, Yoon-La Choi
Most anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancers (NSCLCs) show good clinical response to ALK inhibitors. However, some ALK-rearranged NSCLC patients show various primary responses with unknown reasons. Previous studies focused on the clinical aspects of ALK fusions in small cohorts, or were conducted in vitro and/or in vivo to investigate the function of ALK. One of the suggested theories describes how Echinoderm microtubule-associated protein-like 4 (EML4)-ALK variants play a role towards different sensitivities in ALK inhibitors...
July 25, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28741521/hypoxia-inducible-factors-master-regulators-of-cancer-progression
#5
REVIEW
Luana Schito, Gregg L Semenza
Intratumoral hypoxia (reduced O2 availability) is a common finding in human cancer and leads to increased activity of hypoxia-inducible factors (HIFs), which regulate the expression of genes that contribute to angiogenesis, metabolic reprogramming, extracellular matrix remodeling, epithelial-mesenchymal transition, motility, invasion, metastasis, cancer stem cell maintenance, immune evasion, and resistance to chemotherapy and radiation therapy. Conventional anticancer therapies target well-oxygenated and proliferating cancer cells, whereas there are no approved therapies that target hypoxic cancer cells, despite growing clinical and experimental evidence indicating that intratumoral hypoxia is a critical microenvironmental factor driving cancer progression...
December 2016: Trends in Cancer
https://www.readbyqxmd.com/read/28741507/mtor-signaling-confers-resistance-to-targeted-cancer-drugs
#6
REVIEW
Yakir Guri, Michael N Hall
Cancer is a complex disease and a leading cause of death worldwide. Extensive research over decades has led to the development of therapies that target cancer-specific signaling pathways. However, the clinical benefits of such drugs are at best transient due to tumors displaying intrinsic or adaptive resistance. The underlying compensatory pathways that allow cancer cells to circumvent a drug blockade are poorly understood. We review here recent studies suggesting that mammalian TOR (mTOR) signaling is a major compensatory pathway conferring resistance to many cancer drugs...
November 2016: Trends in Cancer
https://www.readbyqxmd.com/read/28741495/adaptive-stress-responses-during-tumor-metastasis-and-dormancy
#7
REVIEW
Daniela Senft, Ze'ev A Ronai
To survive inhospitable environments, tumor cells are forced to remodel their signaling pathways by altering transcription, translation, and post-translational modifications. This adaptation is regulated in a spatial and temporal manner and gives rise to individual tumor cells with distinct gene expression and metabolic signatures. Such phenotypic heterogeneity is the result of tumor cell plasticity, which-together with the genetic background of the tumor-determines whether cells resist environmental stress, enter dormancy, or metastasize...
August 2016: Trends in Cancer
https://www.readbyqxmd.com/read/28741274/cyclin-dependent-kinase-4-6-inhibitors-in-breast-cancer-palbociclib-ribociclib-and-abemaciclib
#8
REVIEW
Dorota Kwapisz
PURPOSE: The cyclin D-cyclin dependent kinase (CDK) 4/6-inhibitor of CDK4 (INK4)-retinoblastoma (Rb) pathway plays a crucial role in cell cycle progression and its dysregulation is an important contributor to endocrine therapy resistance. CDK4/6 inhibitors trigger cell cycle arrest in Rb protein (pRb)-competent cells. Recent years have seen the development of selective CDK4/6 inhibitors, which have delivered promising results of efficacy and manageable safety profiles. The main objective of this review is to discuss preclinical and clinical data to date, and ongoing clinical trials with palbociclib, ribociclib, and abemaciclib in breast cancer...
July 24, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28741098/regulation-of-paclitaxel-activity-by-microtubule-associated-proteins-in-cancer-chemotherapy
#9
REVIEW
Xingjuan Shi, Xiaoou Sun
Microtubules, highly dynamic components of the cytoskeleton, participate in diverse cellular activities such as mitosis, cell migration, and intracellular trafficking. Dysregulation of microtubule dynamics contributes to the development of serious diseases, including cancer. The dynamic properties and functions of microtubule network are regulated by microtubule-associated proteins. Paclitaxel, an anti-microtubule agent of the taxane family, has shown a success in clinical treatment of many cancer patients...
July 24, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28740606/structure-guided-strategy-for-the-development-of-potent-bivalent-erk-inhibitors
#10
Bernhard C Lechtenberg, Peter D Mace, E Hampton Sessions, Robert Williamson, Romain Stalder, Yann Wallez, Gregory P Roth, Stefan J Riedl, Elena B Pasquale
ERK is the effector kinase of the RAS-RAF-MEK-ERK signaling cascade, which promotes cell transformation and malignancy in many cancers and is thus a major drug target in oncology. Kinase inhibitors targeting RAF or MEK are already used for the treatment of certain cancers, such as melanoma. Although the initial response to these drugs can be dramatic, development of drug resistance is a major challenge, even with combination therapies targeting both RAF and MEK. Importantly, most resistance mechanisms still rely on activation of the downstream effector kinase ERK, making it a promising target for drug development efforts...
July 13, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28740406/conventional-real-time-pcr-based-detection-of-t790m-using-tumor-tissue-or-blood-in-patients-with-egfr-tki-resistant-nsclc
#11
Ya-Lan Wu, Rui-Zhan Tong, Yan Zhang, Bin-Bin Hu, Ke Zheng, Zhen-Yu Ding, Feng Peng, You-Ling Gong, Yong-Mei Liu, You Lu
Blood biopsy has many advantages over tissue biopsy for diagnosing acquired T790M mutation in patients with non-small-cell lung cancer, such as being less risky and painful. New techniques with high sensitivity (eg, droplet digital PCR) show promising results during blood biopsy, but the positive rates of identification are still quite unclear. Whether there are other factors, except technology, affecting the results of blood biopsy is unclear. In this study, we used conventional amplification refractory mutation system to detect tumor tissue or blood for T790M mutation in patients clinically resistant to tyrosine kinase inhibitors...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28740365/spotlight-on-ceritinib-in-the-treatment-of-alk-nsclc-design-development-and-place-in-therapy
#12
REVIEW
Mariacarmela Santarpia, Maria Grazia Daffinà, Alessandro D'Aveni, Grazia Marabello, Alessia Liguori, Elisa Giovannetti, Niki Karachaliou, Maria Gonzalez Cao, Rafael Rosell, Giuseppe Altavilla
The identification of echinoderm microtubule-associated protein-like 4 (EML4) and anaplastic lymphoma kinase (ALK) fusion gene in non-small cell lung cancer (NSCLC) has radically changed the treatment of a subset of patients harboring this oncogenic driver. Crizotinib was the first ALK tyrosine kinase inhibitor to receive fast approval and is currently indicated as the first-line therapy for advanced, ALK-positive NSCLC patients. However, despite crizotinib's efficacy, patients almost invariably progress, with the central nervous system being one of the most common sites of relapse...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28739698/highly-eribulin-resistant-kbv20c-oral-cancer-cells-can-be-sensitized-by-co-treatment-with-the-third-generation-p-glycoprotein-inhibitor-elacridar-at-a-low-dose
#13
Yujin Park, Ji-Yeon Son, Byung-Mu Lee, Hyung Sik Kim, Sungpil Yoon
BACKGROUND/AIM: Eribulin mesylate, also called Halaven® (HAL), was recently developed as a microtubule-targeting drug and is used in the clinic for resistant or metastatic cancer. Previously, we showed that P-glycoprotein (P-gp)-overexpressing KBV20C oral cancer cells are highly resistant to HAL compared to sensitive KB cells. This qualitative study was designed to identify specific P-gp inhibitors that increase the sensitivity of highly resistant cancer cells to HAL. MATERIALS AND METHODS: In order to identify functional P-gp inhibitors, HAL-treated KBV20C cells were co-treated with P-gp inhibitors, verapamil, elacridar, cyclosporine A, mitotane, piperine, fumagillin, curcumin, indomethacin, probenecid, sulindac, tesmilifene, and C-4...
August 2017: Anticancer Research
https://www.readbyqxmd.com/read/28739680/bdnf-an-oncogene-or-tumor-suppressor
#14
REVIEW
Daniel P Radin, Parth Patel
Neurotrophins are a family of growth factors that are vital to the proper development of the central nervous system. Their effects on cells are governed by the expression and activation of the tyrosine kinase receptors TrkA, TrkB and TrkC. TrkB has been immensely implicated in mediating neuronal migration, development and differentiation. It has also been shown to protect several neuronal cell types from an array of cytotoxic stressors after activation by its conjugate ligand brain-derived neurotrophic factor (BDNF)...
August 2017: Anticancer Research
https://www.readbyqxmd.com/read/28739368/andrographolide-induces-oxidative-stress-dependent-cell-death-in-unicellular-protozoan-parasite-trypanosoma-brucei
#15
Malabika Banerjee, Debaprasad Parai, Pranab Dhar, Manab Roy, Rajib Barik, Subrata Chattopadhyay, Samir Kumar Mukherjee
African sleeping sickness is a parasitic disease in humans and livestock caused by Trypanosoma brucei throughout sub-Saharan Africa. Absence of appropriate vaccines and prevalence of drug resistance proclaim that a new way of therapeutic interventions is essential against African trypanosomiasis. In the present study, we have looked into the effect of andrographolide (andro), a diterpenoid lactone from Andrographis paiculata on Trypanosoma brucei PRA 380. Although andro has been recognized as a promosing anti-cancer drug, its usefulness against Trypanosoma spp remained unexplored...
July 21, 2017: Acta Tropica
https://www.readbyqxmd.com/read/28739118/single-cell-based-automated-quantification-of-therapy-response-of-invasive-cancer-spheroids-in-organotypic-3d-culture
#16
Cornelia Veelken, Gert-Jan Bakker, David Drell, Peter Friedl
Organotypic in vitro culture of 3D spheroids in extracellular matrix represent a promising cancer therapy prediction model for personalized medicine screens, due to their controlled experimental conditions and physiological similarities to in vivo models. As in tumors in vivo, 3D invasion cultures identify intratumor heterogeneity of growth, invasion and apoptosis induction by cytotoxic therapy. We here combine in vitro 3D spheroid invasion culture with irradiation and automated nucleus-based segmentation for single cell analysis to quantify growth, survival, apoptosis and invasion response during experimental radiation therapy...
July 21, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28738967/-recent-advances-in-association-of-estrogen-and-non-small-cell-lung-cancer
#17
Xiaosheng Ding, Chuanhao Tang, Zhijie Wang, Jun Liang
Lung cancer, of which approximately 85% are non-small cell lung cancer (NSCLC), is one of the most prevalent cancers and the most leading cause of cancer mortality. Despite recent improvements in its treatment, the prognosis remains dismal. Previous studies have clearly proved that estrogen and estrogen receptors (ER) are involve in the pathogenesis and development of lung cancer. More and more evidences showed antiestrogen therapy may reverse the drug-resistance of platinum based chemotherapy in NSCLC patients and can enhance curative effect of epidermal growth factor receptor tyrosine kinase inhibitor...
July 20, 2017: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
https://www.readbyqxmd.com/read/28738876/enterolactone-has-stronger-effects-than-enterodiol-on-ovarian-cancer
#18
Huidi Liu, Jianrui Liu, Siwen Wang, Zheng Zeng, Ting Li, Yongfang Liu, Emilio Mastriani, Qing-Hai Li, Hong-Xia Bao, Yu-Jie Zhou, Xiaoyu Wang, Sijing Hu, Shan Gao, Yingying Qi, Zhihang Shen, Hongyue Wang, Miao Yu, Tingting Gao, Randal N Johnston, Shu-Lin Liu
BACKGROUND: Ovarian cancer is one of the three leading gynecological malignancies, characterized by insidious growth, highly frequent metastasis, and quick development of drug resistance. As a result, this disease has low 5-year survival rates. Estrogen receptor inhibitors were commonly used for the treatment, but only 7% to 18% of patients respond to anti-estrogen therapies. Therefore, more effective therapies to inhibit estrogen-related tumors are urgently needed. Recently, phytoestrogens, such as lignans with estrogen-like biological activities, have attracted attention for their potential effects in the prevention or treatment of estrogen-related diseases...
July 24, 2017: Journal of Ovarian Research
https://www.readbyqxmd.com/read/28738771/fumitremorgins-and-relatives-from-tremorgenic-compounds-to-valuable-anti-cancer-drugs
#19
Wolf-Rainer Abraham
BACKGROUND: Fumitremorgins are mycotoxins but can also inhibit cancer cells and reverse their drug resistance. OBJECTIVE: The bioactivity of prenylated cyclo-Trp-Pro dipeptides and their derivatives concerning their application in anti-cancer therapies will be discussed. METHOD: Reports on the discovery and assessment of this class of fungal compounds are compiled from literature using Google Scholar and PubMed. The bioactivities of the natural compounds are discussed with the aim of their improvement for cancer therapy...
July 24, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28738540/regulatory-players-of-dna-damage-repair-mechanisms-role-in-cancer-chemoresistance
#20
REVIEW
Kunnathur Murugesan Sakthivel, Sreedharan Hariharan
DNA damaging agents are most common in chemotherapeutic molecules that act against cancer. However, cancer cells possess inherent biological features to overcome DNA damages by activating various distinct repair mechanisms and pathways. Importantly, various oncogenes, cancer stem cells (CSCs), hypoxic environment, transcription factors and bystander signaling that are activated in the cancer cells influence DNA repair, thereby effectively repairing the DNA damage. Repaired cancer cells often become more resistance to further therapy and results in disease recurrence...
July 20, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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