Ritika Tiwari, Nishat Manzar, Bushra Ateeq
Despite the current advances in the treatment for prostate cancer, the patients often develop resistance to the conventional therapeutic interventions. Therapy-induced drug resistance and tumor progression have been associated with cellular plasticity acquired due to reprogramming at the molecular and phenotypic levels. The plasticity of the tumor cells is mainly governed by two factors: cell-intrinsic and cell-extrinsic. The cell-intrinsic factors involve alteration in the genetic or epigenetic regulators, while cell-extrinsic factors include microenvironmental cues and drug-induced selective pressure...
2020: Frontiers in Molecular Biosciences
Jia-En Wu, Yi-Ying Wu, Chia-Hao Tung, Yao-Tsung Tsai, Hsuan-Yu Chen, Yuh-Ling Chen, Tse-Ming Hong
The loss of cancer-cell junctions and escape from the primary-tumor microenvironment are hallmarks of metastasis. A tight-junction protein, Claudin 1 (CLDN1), is a metastasis suppressor in lung adenocarcinoma. However, as a metastasis suppressor, the underlying molecular mechanisms of CLDN1 has not been well studied. Methods: The signaling pathway regulated by CLDN1 was analyzed by Metacore software and validated by immunoblots. The effect of the CLDN1-EPHB6-ERK-SLUG axis on the formation of cancer stem-like cells, drug resistance and metastasis were evaluated by sphere assay, aldefluor assay, flow cytometry, migration assay, cytotoxicity, soft agar assay, immunoprecipitation assay and xenograft experiments...
2020: Theranostics
Tianzhi Huang, Xiao Song, Dandan Xu, Deanna Tiek, Anshika Goenka, Bingli Wu, Namratha Sastry, Bo Hu, Shi-Yuan Cheng
Over the past few decades, substantial evidence has convincingly revealed the existence of cancer stem cells (CSCs) as a minor subpopulation in cancers, contributing to an aberrantly high degree of cellular heterogeneity within the tumor. CSCs are functionally defined by their abilities of self-renewal and differentiation, often in response to cues from their microenvironment. Biological phenotypes of CSCs are regulated by the integrated transcriptional, post-transcriptional, metabolic, and epigenetic regulatory networks...
2020: Theranostics
Enyuan Shang, Trang T T Nguyen, Chang Shu, Mike-Andrew Westhoff, Georg Karpel-Massler, Markus D Siegelin
Apoptotic resistance remains a hallmark of glioblastoma (GBM), the most common primary brain tumor in adults, and a better understanding of this process may result in more efficient treatments. By utilizing chromatin immunoprecipitation with next-generation sequencing (CHIP-seq), we discovered that GBMs harbor a super enhancer around the Mcl-1 locus, a gene that has been known to confer cell death resistance in GBM. We utilized THZ1, a known super-enhancer blocker, and BH3-mimetics, including ABT263, WEHI-539, and ABT199...
August 1, 2020: Cancers
Callum J O'Kane, Rachel Weild, Edel M Hyland
Anti-microbial resistance (AMR) is currently one of the most serious threats to global human health and, appropriately, research to tackle AMR garnishes significant investment and extensive attention from the scientific community. However, most of this effort focuses on antibiotics, and research into anti-fungal resistance (AFR) is vastly under-represented in comparison. Given the growing number of vulnerable, immunocompromised individuals, as well as the positive impact global warming has on fungal growth, there is an immediate urgency to tackle fungal disease, and the disturbing rise in AFR...
July 30, 2020: Journal of Fungi (Basel, Switzerland)
Ana Rita Cardoso, João Lobo, Vera Miranda-Gonçalves, Rui Henrique, Carmen Jerónimo
Testicular germ cell tumors (TGCTs) are heterogeneous neoplasms mostly affecting young-adult men. Despite high survival rates, some patients with disseminated disease acquire cisplatin resistance, entailing the need for less toxic therapies. Epigenetic alterations constitute an important feature of TGCTs, which are also implicated in resistance mechanism(s). These alterations might be used as potential targets to design epigenetic drugs. To date, several compounds have been explored and evaluated regarding therapeutic efficacy, making use of pre-clinical studies with in vitro and in vivo models, and some have already been explored in clinical trials...
August 4, 2020: Epigenetics: Official Journal of the DNA Methylation Society
Tasnim Zahan, Plabon K Das, Syeda F Akter, Rowshanul Habib, Md Habibur Rahman, Md Rezaul Karim, Farhadul Islam
BACKGROUND: Chemo resistance is a vital problem in cancer therapy where cancer cells develop mechanisms to encounter the effect of chemo therapeutics, resulting in cancer recurrence. In addition, chemotherapy-resistant lead to the formation of a more aggressive form of cancer cells, which in turn contribute to the poor survival of patients with cancer. OBJECTIVE: In this review, we aimed to provide an overview of how the therapy resistance property evolves in cancer cells, contributing factors and their role in cancer chemo resistance, and exemplified the problems of some available therapies...
July 30, 2020: Anti-cancer Agents in Medicinal Chemistry
Haruhito Totani, Keiko Shinjo, Miho Suzuki, Keisuke Katsushima, Shoko Mase, Ayako Masaki, Asahi Ito, Masaki Ri, Shigeru Kusumoto, Hirokazu Komatsu, Takashi Ishida, Hiroshi Inagaki, Shinsuke Iida, Yutaka Kondo
Adult T-cell leukemia/lymphoma (ATL) is an aggressive T-cell neoplasm. While ATL cells in peripheral blood (PB-ATL) are sensitive to anti-CC chemokine receptor 4 treatment, non-PB-ATLs, including lymph node ATLs (LN-ATLs), are more aggressive and resistant. We examined characteristic cytokines and growth factors that allow non-PB-ATLs to proliferate and invade compared with PB-ATLs. Protein array analysis revealed hepatocyte growth factor (HGF) and C-C motif chemokine 2 (CCL2) were significantly upregulated in non-PB-ATLs compared with PB-ATLs...
August 4, 2020: Oncogene
John W Wiley, Ye Zong, Gen Zheng, Shengtao Zhu, Shuangsong Hong
BACKGROUND: Chronic stress is associated with activation of the HPA axis, elevation in pro-inflammatory cytokines, decrease in intestinal epithelial cell tight junction (TJ) proteins, and enhanced visceral pain. It is unknown whether epigenetic regulatory pathways play a role in chronic stress-induced intestinal barrier dysfunction and visceral hyperalgesia. METHODS: Young adult male rats were subjected to water avoidance stress ± H3K9 methylation inhibitors or siRNAs...
August 2, 2020: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
Massimo Petretich, Emmanuel H Demont, Paola Grandi
Cancer and inflammation are strongly interconnected processes. Chronic inflammatory pathologies can be at the heart of tumor development; similarly, tumor-elicited inflammation is a consequence of many cancers. The mechanistic interdependence between cancer and inflammatory pathologies points toward common protein effectors which represent potential shared targets for pharmacological intervention. Epigenetic mechanisms often drive resistance to cancer therapy and immunomodulatory strategies. The bromodomain and extraterminal domain (BET) proteins are epigenetic adapters which play a major role in controlling cell proliferation and the production of inflammatory mediators...
July 30, 2020: Current Opinion in Chemical Biology
Landi Luo, Xiangxiang Kong, Zean Gao, Yan Zheng, Yunqiang Yang, Xiong Li, Danni Yang, Yupeng Geng, Yongping Yang
BACKGROUND: Alternanthera philoxeroides (alligator weed) is a highly invasive alien plant that has continuously and successfully expanded from the tropical to the temperate regions of China via asexual reproduction. During this process, the continuous decrease in temperature has been a key limiting environmental factor. RESULTS: In this study, we provide a comprehensive analysis of the cold tolerance of alligator weed via transcriptomics. The transcriptomic differences between the southernmost population and the northernmost population of China were compared at different time points of cold treatments...
August 2, 2020: BMC Genomics
Samuele Ambrosini, Shafeeq A Mohammed, Thomas F Lüscher, Sarah Costantino, Francesco Paneni
Epigenetic processing takes centre stage in cardiometabolic diseases (obesity, metabolic syndrome, type 2 diabetes, hypertension), where it participates in adiposity, inflammation, endothelial dysfunction, vascular insulin resistance and atherosclerosis. Epigenetic modifications, defined as heritable changes in gene expression that do not entail mutation in the DNA sequence, are mainly induced by environmental stimuli (stress, pollution, cigarette smoking) and are gaining considerable interest due to their causal role in cardiovascular disease, and their amenability to pharmacological intervention...
August 1, 2020: High Blood Pressure & Cardiovascular Prevention: the Official Journal of the Italian Society of Hypertension
Victoria Katie Xie, Jie He, Keping Xie
Pancreatic cancer is a lethal disease with limited treatment options for cure. A high degree of intrinsic and acquired therapeutic resistance may result from cellular alterations in genes and proteins involved in drug transportation and metabolism, or from the influences of cancer microenvironment. Mechanistic basis for therapeutic resistance remains unclear and should profoundly impact our ability to understand pancreatic cancer pathogenesis and its effective clinical management. Recent evidences have indicated the importance of epigenetic changes in pancreatic cancer, including posttranslational modifications of proteins...
July 11, 2020: Cytokine & Growth Factor Reviews
Elisabeth Pérez-Ruiz, Ignacio Melero, Joanna Kopecka, Ana Bela Sarmento-Ribeiro, Marilina García-Aranda, Javier De Las Rivas
Cancer is one of the main public health problems in the world. Systemic therapies such as chemotherapy and more recently target therapies as well as immunotherapy have improved the prognosis of this large group of complex malignant diseases. However, the frequent emergence of multidrug resistance (MDR) mechanisms is one of the major impediments towards curative treatment of cancer. While several mechanisms of drug chemoresistance are well defined, resistance to immunotherapy is still insufficiently unclear due to the complexity of the immune response and its dependence on the host...
July 15, 2020: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
Maolin Ge, Dan Li, Zhi Qiao, Yan Sun, Ting Kang, Shouhai Zhu, Shifen Wang, Hua Xiao, Chunjun Zhao, Shuhong Shen, Zhenshu Xu, Han Liu
MLL undergoes multiple distinct chromosomal translocations to yield aggressive leukemia with dismal outcomes. Besides their well-established role in leukemogenesis, MLL fusions also possess latent tumor-suppressive activity, which can be exploited as effective cancer treatment strategies using pharmacological means such as proteasome inhibitors (PIs). Here, using MLL-rearranged xenografts and MLL leukemic cells as models, we show that wild-type MLL is indispensable for the latent tumor-suppressive activity of MLL fusions...
July 30, 2020: Oncogene
John M Atack, Chengying Guo, Thomas Litfin, Long Yang, Patrick J Blackall, Yaoqi Zhou, Michael P Jennings
N 6 -Adenine DNA methyltransferases associated with some Type I and Type III restriction-modification (R-M) systems are able to undergo phase variation, randomly switching expression ON or OFF by varying the length of locus-encoded simple sequence repeats (SSRs). This variation of methyltransferase expression results in genome-wide methylation differences and global changes in gene expression. These epigenetic regulatory systems are called phasevarions, phase-variable regulons, and are widespread in bacteria...
July 28, 2020: MSystems
Kezhou Zhu, Victoria Xie, Suyun Huang
As a unique subpopulation of cancer cells, cancer stem cells (CSCs) acquire the resistance to conventional therapies and appear to be the prime cause of cancer recurrence. Like their normal counterparts, CSCs can renew themselves and generate differentiated progenies. Cancer stem cells are distinguished among heterogenous cancer cells by molecular markers and their capacity of efficiently forming new tumors composed of diverse and heterogenous cancer cells. Tumor heterogeneity can be inter- or intra-tumor, molecularly resulting from the accumulation of genetic and non-genetic alterations...
2020: Advances in Cancer Research
Stanislav Filip, Veronika Vymetalkova, Jiri Petera, Ludmila Vodickova, Ondrej Kubecek, Stanislav John, Filip Cecka, Marketa Krupova, Monika Manethova, Klara Cervena, Pavel Vodicka
Colorectal cancer (CRC) remains a serious health problem worldwide. Approximately half of patients will develop distant metastasis after CRC resection, usually with very poor prognosis afterwards. Because patient performance after distant metastasis surgery remains very heterogeneous, ranging from death within 2 years to a long-term cure, there is a clinical need for a precise risk stratification of patients to aid pre- and post-operative decisions. Furthermore, around 20% of identified CRC cases are at IV stage disease, known as a metastatic CRC (mCRC)...
July 24, 2020: International Journal of Molecular Sciences
Abdul Q Khan, Fareed Ahmad, Syed Shadab Raza, Lubna Zarif, Kodappully S Siveen, Gulab Sher, Maha Victor Agha, Khalid Rashid, Michal Kulinski, Joerg Buddenkotte, Shahab Uddin, Martin Steinhoff
Skin, the largest organ of human body, is vital for the existence and survival of human beings. Further, developmental and physiological mechanisms associated with cutaneous biology are vital for homeostasis as their deregulations converge towards pathogenesis of a number of skin diseases, including cancer. It has now been well accepted that most of the transcribed human genome lacks protein translational potential and has been termed as non-coding RNAs (nc-RNAs), which includes circular RNA (circRNA), small nuclear RNA (snRNA), small nucleolar RNA (snoRNA), micro RNA (miRNA), long noncoding RNA (lncRNA), and piwi-interacting RNA (piRNAs)...
July 24, 2020: Seminars in Cancer Biology
Ian J Groves, John H Sinclair, Mark R Wills
Although the ubiquitous human herpesviruses (HHVs) are rarely associated with serious disease of the healthy host, primary infection and reactivation in immunocompromised individuals can lead to significant morbidity and, in some cases, mortality. Effective drugs are available for clinical treatment, however resistance is on the rise such that new anti-viral targets, as well as novel clinical treatment strategies, are required. A promising area of development and pre-clinical research is that of inhibitors of epigenetic modifying proteins that control both cellular functions and the viral life cycle...
2020: Frontiers in Cellular and Infection Microbiology
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