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https://www.readbyqxmd.com/read/28641053/the-discovery-and-development-of-romidepsin-for-the-treatment-of-t-cell-lymphoma
#1
Piotr Smolewski, Tadeusz Robak
Romidepsin is a potent and selective inhibitor of histone deacetylases (HDCAi). It is also the only bicyclic inhibitor to undergo clinical assessment and is considered a promising drug for the treatment of T-cell lymphomas. The cellular action of romidepsin results in enhanced histone acetylation, as well as the acetylation of other nuclear or cytoplasmic proteins, influencing cell cycle, apoptosis, and angiogenesis. In phase II studies involving patients with relapsed or refractory of cutaneous T-cell lymphoma (CTCL) and peripheral T-cell lymphoma (PTCL), romidepsin produced overall response rates (ORR) of 34-35% and 25-38%, with complete response (CR) rates of 6% and 15-18%, respectively...
June 22, 2017: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/28641031/treatment-options-for-nonalcoholic-steatohepatitis-a-safety-evaluation
#2
Danny Issa, Julia Wattacheril, Arun J Sanyal
Introduction There is an urgent as yet unmet need to develop highly effective and safe therapeutics for nonalcoholic fatty liver disease (NAFLD). The remarkable progress in understanding NAFLD pathogenesis allowed the identification of injury pathways which may be recruited as therapy targets. Areas covered This article reviews the safety and tolerability data of the NAFLD therapies and explains the mechanistic basis for each of the established and investigational drugs. Treatment targets include: weight loss, anti-metabolic agents such as lipid lowering and anti-diabetic drugs, inflammation, fibrosis and others such as targeting gut microbiota, immune modulation and apoptosis...
June 22, 2017: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/28637104/-treatment-options-in-non-alcoholic-fatty-liver-disease
#3
REVIEW
Won Kim
The prevalence of non-alcoholic fatty liver disease (NAFLD) has sharply increased over the past several decades in Korea. In most cases of NAFLD, metabolic stress and cellular apoptosis are often driven by metabolic abnormality, eventually leading to inflammation and fibrosis . Along with a dramatic surge in the obesity epidemic, 10-20% of NAFLD patients ultimately progress to non-alcoholic steatohepatitis (NASH), a precursor to cirrhosis and hepatocellular carcinoma, as well as multi-organ systemic diseases...
June 25, 2017: Korean Journal of Gastroenterology, Taehan Sohwagi Hakhoe Chi
https://www.readbyqxmd.com/read/28636992/acetylsalicylic-acid-inhibits-the-growth-of-melanoma-tumors-via-sox2-dependent-paf-r-independent-signaling-pathway
#4
Anita Thyagarajan, Jeremiah Saylae, Ravi P Sahu
Acquired resistance to standard therapies remains a serious challenge, requiring novel therapeutic approaches that incorporate potential factors involved in tumor resistance. As cancers including melanoma express inflammatory cyclooxygenases generating prostaglandins implicated in tumor growth, we investigated mechanism of anti-inflammatory drug, acetylsalicylic acid (ASA) which has been shown to inhibit various tumor types, however, its effects against highly aggressive melanoma model are unclear. Given our reports that an activation of platelet-activating factor-receptor (PAF-R) augments the growth and impede efficacies of therapeutic agents in experimental melanoma, we also sought to determine if PAF-R mediates anti-melanoma activity of ASA...
June 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28636807/targeting-protein-for-xenopus-kinesin-like-protein-2-knockdown-enhances-radiation-sensitivity-of-human-lung-squamous-carcinoma-cell
#5
Jie Yang, Feng Gao, Xinjian Xu, Yuxiang Wang, Shuchai Zhu
Targeting protein for Xenopus kinesin-like protein 2 (TPX2) has been demonstrated to be associated with the tumorigenesis of many cancers. In the present study, we investigated the role and preliminary mechanism of TPX2 in the resistance of lung squamous carcinoma to radiation therapy. The results showed that SK-MES-1R and NCI-H226R cells were more resistant to X-ray irradiation than the parental cells (SK-MES-1 and NCI-H226). Moreover, TPX2 was upregulated in the radioresistant cells compared with the parental cells...
June 21, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28636534/novel-tropolones-induce-the-unfolded-protein-response-pathway-and-apoptosis-in-multiple-myeloma-cells
#6
Staci L Haney, Cheryl Allen, Michelle L Varney, Kaitlyn M Dykstra, Eric R Falcone, Sean H Colligan, Qiang Hu, Alyssa M Aldridge, Dennis L Wright, Andrew J Wiemer, Sarah A Holstein
Tropolones are small organic compounds with metal-directing moieties. Tropolones inhibit the proliferation of cancer cell lines, possibly through their effects on metalloenzymes such as select histone deacetylases (HDACs). Pan-HDAC inhibitors are therapeutically beneficial in the treatment of multiple myeloma, however there is interest in the use of more selective HDAC inhibitor therapy to minimize adverse side effects. We hypothesized that tropolones might have anti-myeloma activities. To this end, a series of novel α-substituted tropolones were evaluated for effects on multiple myeloma cells...
June 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28636149/photocatalytic-interaction-of-aminophylline-riboflavin-leads-to-ros-mediated-dna-damage-and-cell-death-a-novel-phototherapeutic-mechanism-for-cancer
#7
Saniyya Khan, Imrana Naseem
The accompanied tissue devastation and systemic toxicity of chemotherapy has shifted the quest for having an effective and palliative cancer therapy towards photodynamic therapy (PDT). Riboflavin (Rf), an essential micronutrient is emerging as a potent tool of PDT, due to its excellent photosensitizing properties. It can be used as an efficient adjuvant for various anticancer drugs. The hemolytic and proteolytic effect of photoilluminated aminophylline (Am), a xanthine derivative, and Rf is well documented in literature...
June 21, 2017: IUBMB Life
https://www.readbyqxmd.com/read/28635653/virtual-screening-against-phosphoglycerate-kinase-1-in-quest-of-novel-apoptosis-inhibitors
#8
Jie Xia, Bo Feng, Qianhang Shao, Yuhe Yuan, Xiang Simon Wang, Naihong Chen, Song Wu
Inhibition of apoptosis is a potential therapy to treat human diseases such as neurodegenerative disorders (e.g., Parkinson's disease), stroke, and sepsis. Due to the lack of druggable targets, it remains a major challenge to discover apoptosis inhibitors. The recent repositioning of a marketed drug (i.e., terazosin) as an anti-apoptotic agent uncovered a novel target (i.e., human phosphoglycerate kinase 1 (hPgk1)). In this study, we developed a virtual screening (VS) pipeline based on the X-ray structure of Pgk1/terazosin complex and applied it to a screening campaign for potential anti-apoptotic agents...
June 21, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28634214/effects-of-microrna-146a-on-the-proliferation-and-apoptosis-of-human-osteochondrocytes-by-targeting-traf6-through-the-nf-%C3%AE%C2%BAb-signalling-pathway
#9
Camilla West, Michael McDermott
MicroRNAs are important cellular mediators of mRNA degradation and translation repression, which in turn can have an impact on various processes and, if their function is perturbed, can cause disease. Here, we summarise the recent manuscript by Zhong et al., which explores microRNA-146a and how it may play an indirect yet vital role in the proliferation of osteoarthritis (OA) chondrocytes. The data presented by the authors could have important implications for future OA therapies.
June 20, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28633979/zerumbone-modulates-cd1d-expression-and-lipid-antigen-presentation-pathway-in-breast-cancer-cells
#10
Ritis K Shyanti, Anuradha Sehrawat, Shivendra V Singh, J P N Mishra, Rana P Singh
Natural Killer T (NKT) cells based cancer immunotherapy is an evolving area of cancer therapy, but tumors escape from this treatment modality by altering CD1d expression and its antigen presentation pathway. Here, we have studied the relation of CD1d expression in various breast cancer cell lines to their viability and progression. We observed a novel phenomenon that CD1d expression level increases with the progressive stage of the cancer. A small molecule, zerumbone (ZER) caused down-regulation of CD1d that was accompanied by breast cancer cell growth in vitro...
June 17, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28633062/blue-light-induced-reactive-oxygen-species-from-flavin-mononucleotide-and-flavin-adenine-dinucleotide-on-lethality-of-hela-cells
#11
Ming-Yeh Yang, Chih-Jui Chang, Liang-Yü Chen
Photodynamic therapy (PDT) is a safe and non-invasive treatment for cancers and microbial infections. Various photosensitizers and light sources have been developed for clinical cancer therapies. Flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) are the cofactor of enzymes and are used as photosensitizers in this study. Targeting hypoxia and light-triggering reactive oxygen species (ROS) are experimental strategies for poisoning tumor cells in vitro. HeLa cells are committed to apoptosis when treated with FMN or FAD and exposed to visible blue light (the maximum emitted wavelength of blue light is 462nm)...
June 13, 2017: Journal of Photochemistry and Photobiology. B, Biology
https://www.readbyqxmd.com/read/28631712/-the-molecular-mechanisms-and-morphological-manifestations-of-leiomyoma-reduction-induced-by-selective-progesterone-receptor-modulators
#12
T A Demura, Z V Revazova, E A Kogan, L V Adamyan
AIM: to investigate the molecular mechanisms and morphological substrate of reduced uterine leiomyoma in patients receiving the selective progesterone receptor modulator (SPRM) ulipristal acetate for 3 months, by estimating the immunohistochemical expression of the markers steroid receptor coactivator 1 (SRC-1), nuclear receptor corepressor 1 (NCoR-1), ER, PgR, Ki-67, p16, TGF-β, and VEGF in tumor tissue. SUBJECTS AND METHODS: The investigation enrolled 75 women with uterine leiomyoma, menorrhagias, and anemia...
2017: Arkhiv Patologii
https://www.readbyqxmd.com/read/28631574/microrna-125a-5p-plays-a-role-as-a-tumor-suppressor-in-lung-carcinoma-cells-by-directly-targeting-stat3
#13
Lou Zhong, Siyuan Sun, Jiahai Shi, Fei Cao, Xiao Han, Zhong Chen
Increasing evidence supports that the dysregulation of microRNA expression plays an important role in the process of tumor occurrence and development. Studies have found that mir-125a-5p expression was downregulated in a variety of tumors, but the effects and mechanism of mir-125a-5p in lung cancer are still unclear. The aim of this study is to detect the expression of mir-125a-5p in lung cancer tissues and lung cancer cell lines and to explore the effects of mir-125a-5p on the biological characteristics of lung cancer cells; thus, this study aims to provide new methods and new strategies for the treatment of lung cancer...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28631570/the-effect-of-rcan1-on-the-biological-behaviors-of-small-cell-lung-cancer
#14
Ningqiang Ma, Weiwei Shen, Hailin Pang, Ning Zhang, Hong Shi, Jianlin Wang, Helong Zhang
Bone is the third most common site of cancer metastasis. In total, 30%-40% of lung cancer cases can develop skeletal metastasis for which no effective therapy in clinic is available. RCAN1 (regulator of calcineurin 1) is an important regulator in angiogenesis which is vital to tumor growth. In this study, we investigated the changes of biological behaviors in SBC-5 and SBC-3 cells after the RCAN1 expression level was changed. Briefly, overexpression of RCAN1 significantly attenuated their malignancy, including decreased ability of proliferation, colony formation, migration, invasion, and bone adherence...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28631569/insulin-induced-enhancement-of-mcf-7-breast-cancer-cell-response-to-5-fluorouracil-and-cyclophosphamide
#15
Siddarth Agrawal, Mateusz Łuc, Piotr Ziółkowski, Anil Kumar Agrawal, Ewa Pielka, Kinga Walaszek, Krzysztof Zduniak, Marta Woźniak
The study was designed to evaluate the potential use of insulin for cancer-specific treatment. Insulin-induced sensitivity of MCF-7 breast cancer cells to chemotherapeutic agents 5-fluorouracil and cyclophosphamide was evaluated. To investigate and establish the possible mechanisms of this phenomenon, we assessed cell proliferation, induction of apoptosis, activation of apoptotic and autophagic pathways, expression of glucose transporters 1 and 3, formation of reactive oxygen species, and wound-healing assay...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28631557/bispecific-antibody-suppresses-osteosarcoma-aggressiveness-through-regulation-of-nf-%C3%AE%C2%BAb-signaling-pathway
#16
Gui-Hua Yu, Ai-Min Li, Xiang Li, Zhong Yang, Hao Peng
Osteosarcoma is one of the most lethal malignancies, and the prognosis remains dismal due to the paucity of effective therapeutic targets. Bmi-1 and TRIM-14 are associated with the initiation and progression of osteosarcoma, which could promote angiogenesis, invasion, and apoptotic resistance in bone cancer tissue. In this study, we constructed a bispecific antibody of BsAbBmi/TRIM targeting Bmi-1 and TRIM-14 and investigated the therapeutic value in bone carcinoma cells and xenograft mice. Our results showed that Bmi-1 and TRIM-14 expression levels were markedly upregulated correlated with nuclear factor-κB nuclear translocation in bone cancer cells and clinical carcinoma tissues...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28631441/genetic-landscape-and-deregulated-pathways-in-b-cell-lymphoid-malignancies
#17
R Rosenquist, S Beà, M-Q Du, B Nadel, Q Pan-Hammarström
With the introduction of next-generation sequencing, the genetic landscape of the complex group of B-cell lymphoid malignancies has rapidly been unravelled in recent years. This has provided important information about recurrent genetic events and identified key pathways deregulated in each lymphoma subtype. In parallel, there has been intense search and development of novel types of targeted therapy that 'hit' central mechanisms in lymphoma pathobiology, such as BTK, PI3K or BCL2 inhibitors. In this review, we will outline the current view of the genetic landscape of selected entities: follicular lymphoma, diffuse large B-cell lymphoma, mantle cell lymphoma, chronic lymphocytic leukaemia and marginal zone lymphoma...
June 20, 2017: Journal of Internal Medicine
https://www.readbyqxmd.com/read/28630005/transgenerational-effects-of-proton-beam-irradiation-on-caenorhabditis-elegans-germline-apoptosis
#18
Hyemin Min, Minhee Sung, Miseol Son, Ichiro Kawasaki, Yhong-Hee Shims
When treating cancer using radiation therapy, it is critical to increase patient survival rates and to reduce side effects. In this respect, proton beam radiation treatment performs better than other radiation treatments because of its high target specificity. However, complications still remain after proton beam radiation treatment. Among them, the risk to progeny after irradiation of their parents is a major concern. In this study, we analyzed the transgenerational effects of proton beam irradiation using the model organism Caenorhabditis...
June 16, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28629741/establishment-of-an-ideal-time-window-model-in-hypothermic-targeted-temperature-management-after-traumatic-brain-injury-in-rats
#19
Wan-Yong Zhao, Shao-Bo Chen, Jing-Jing Wang, Chao Xu, Ming-Liang Zhao, Hua-Jiang Dong, Hai-Qian Liang, Xiao-Hong Li, Yue Tu, Sai Zhang, Chong Chen, Hong-Tao Sun
Although hypothermic-targeted temperature management (HTTM) holds great potential for the treatment of traumatic brain injury (TBI), translation of the efficacy of hypothermia from animal models to TBI patientshas no entire consistency. This study aimed to find an ideal time window model in experimental rats which was more in accordance with clinical practice through the delayed HTTM intervention. Sprague-Dawley rats were subjected to unilateral cortical contusion injury and received therapeutic hypothermia at 15 mins, 2 hours, 4 hours respectively after TBI...
June 16, 2017: Brain Research
https://www.readbyqxmd.com/read/28629523/significance-of-erythropoietin-receptor-antagonist-emp9-in-cancers
#20
Yoshiko Yasuda, Mitsugu Fujita
We have clarified that cancer cells express their own erythropoietin (Epo) and its receptor (EpoR) mRNA levels, and the respective proteins, which are under the control of Epo-EpoR signaling. Then we explored to inhibit the Epo-EpoR signaling with an EpoR antagonist Epo mimetic peptide 9 (EMP9) that is a derivative of an Epo-mimicking peptide EMP1. In the study of the cancer cell lines in vitro, rhEpo accelerated the cancer cell growth, whereas the EMP9 inhibited the cell growth along with the inhibition of STAT5 tyrosine phosphorylation...
2017: Vitamins and Hormones
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