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https://www.readbyqxmd.com/read/28640862/a-biosystems-approach-to-identify-the-molecular-signaling-mechanisms-of-tmem30a-during-tumor-migration
#1
Jiao Wang, Qian Wang, Dongfang Lu, Fangfang Zhou, Dong Wang, Ruili Feng, Kai Wang, Robert Molday, Jiang Xie, Tieqiao Wen
Understanding the molecular mechanisms underlying cell migration, which plays an important role in tumor growth and progression, is critical for the development of novel tumor therapeutics. Overexpression of transmembrane protein 30A (TMEM30A) has been shown to initiate tumor cell migration, however, the molecular mechanisms through which this takes place have not yet been reported. Thus, we propose the integration of computational and experimental approaches by first predicting potential signaling networks regulated by TMEM30A using a) computational biology methods, b) our previous mass spectrometry results of the TMEM30A complex in mouse tissue, and c) a number of migration-related genes manually collected from the literature, and subsequently performing molecular biology experiments including the in vitro scratch assay and real-time quantitative polymerase chain reaction (qPCR) to validate the reliability of the predicted network...
2017: PloS One
https://www.readbyqxmd.com/read/28640835/bilateral-blockade-of-mek-and-pi3k-mediated-pathways-downstream-of-mutant-kras-as-a-treatment-approach-for-peritoneal-mucinous-malignancies
#2
Murali R Kuracha, Peter Thomas, Brian W Loggie, Venkatesh Govindarajan
Mucinous colorectal adenocarcinomas (MCAs) are clinically and morphologically distinct from nonmucinous colorectal cancers (CRCs), show a distinct spectrum of genetic alterations (higher KRAS mutations, lower p53, high MUC2), exhibit more aggressive behavior (more prone to peritoneal dissemination and lymph node involvement) and are associated with poorer response to chemotherapy with limited treatment options. Here, we report the effectiveness of combinatorial targeting of two KRAS-mediated parallel pathways in reducing MUC2 production and mucinous tumor growth in vitro and in vivo...
2017: PloS One
https://www.readbyqxmd.com/read/28636984/whether-low-dose-metronomic-oral-cyclophosphamide-improves-the-response-to-docetaxel-in-first-line-treatment-of-non-triple-negative-metastatic-breast-cancer
#3
Jian Zhang, Leiping Wang, Zhonghua Wang, Biyun Wang, Jun Cao, Fangfang Lv, Sheng Zhang, Zhimin Shao, Xichun Hu
Oral metronomic chemotherapy may target tumor cells indirectly via antiangiogenic activity, restoration of anticancer immune response, or induction of tumor dormancy. We initiated the single-center, randomized, open-label, phase II study to determine whether the addition of metronomic cyclophosphamide to docetaxel (T) (w/o trastuzumab) improves overall response rate (ORR) as first-line treatment among patients with non-triple-negative metastatic breast cancer (MBC). Eligible patients with previously untreated non-triple-negative MBC were randomly assigned (1:1) to receive 3-weekly cycles of Metro-TC (T 75mg/m2, d1 plus oral cyclophosphamide 50 mg daily) or T alone...
June 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28636942/extensive-proliferation-of-human-cancer-cells-with-ever-shorter-telomeres
#4
Rebecca A Dagg, Hilda A Pickett, Axel A Neumann, Christine E Napier, Jeremy D Henson, Erdahl T Teber, Jonathan W Arthur, C Patrick Reynolds, Jayne Murray, Michelle Haber, Alexander P Sobinoff, Loretta M S Lau, Roger R Reddel
Acquisition of replicative immortality is currently regarded as essential for malignant transformation. This is achieved by activating a telomere lengthening mechanism (TLM), either telomerase or alternative lengthening of telomeres, to counter normal telomere attrition. However, a substantial proportion of some cancer types, including glioblastomas, liposarcomas, retinoblastomas, and osteosarcomas, are reportedly TLM-negative. As serial samples of human tumors cannot usually be obtained to monitor telomere length changes, it has previously been impossible to determine whether tumors are truly TLM-deficient, there is a previously unrecognized TLM, or the assay results are false-negative...
June 20, 2017: Cell Reports
https://www.readbyqxmd.com/read/28636555/overcoming-resistance-to-targeted-therapy-with-immunotherapy-and-combination-therapy-for-metastatic-melanoma
#5
REVIEW
Hilary R Keller, Xin Zhang, Li Li, Helmut Schaider, James W Wells
Resistance to targeted therapy is an ongoing problem for the successful treatment of Stage IV metastatic melanoma. For many patients, the use of targeted therapies, such as BRAF kinase inhibitors, were initially promising yet resistance inevitably occurred. Even after combining BRAF kinase inhibitors with MEK pathway inhibitors to offset re-activation of the MAP kinase pathway, resistance is still documented. Similarly, outcomes with immune checkpoint inhibitors as monotherapy were optimistic for some patients without relapse or progression, yet the majority of patients undergoing monotherapy have progressive disease...
June 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28635565/prostate-cancer-stem-cells-from-theory-to-practice
#6
Jan Adamowicz, Katayoon Pakravan, Babak Bakhshinejad, Tomasz Drewa, Sadegh Babashah
None of the generally accepted theories on prostate cancer development can fully explain many distinguishing features of the disease, such as intratumoral heterogeneity, metastatic growth, drug resistance and tumor relapse. Prostate stem cells are a heterogeneous and small subpopulation of self-renewing cells which can actively proliferate in response to changes in the androgen level and give rise to all the cell lineages that build the prostate epithelium. According to the cancer stem cell hypothesis, prostate cancer could be a stem cell disease...
February 7, 2017: Scandinavian Journal of Urology
https://www.readbyqxmd.com/read/28634910/the-complex-biology-of-the-aryl-hydrocarbon-receptor-and-its-role-in-the-pituitary-gland
#7
REVIEW
Robert Formosa, Josanne Vassallo
The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor best known for its ability to mediate the effects of environmental toxins such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD or dioxin), polycyclic aromatic hydrocarbons (PAHs), benzene, and polychlorinated biphenyls (PCBs) through the initiation of transcription of a number of metabolically active enzymes. Therefore, the AHR has been studied mostly in the context of xenobiotic signaling. However, several studies have shown that the AHR is constitutively active and plays an important role in general cell physiology, independently of its activity as a xenobiotic receptor and in the absence of exogenous ligands...
June 20, 2017: Hormones & Cancer
https://www.readbyqxmd.com/read/28634583/circular-rnas-biogenesis-function-and-role-in-human-diseases
#8
REVIEW
John Greene, Anne-Marie Baird, Lauren Brady, Marvin Lim, Steven G Gray, Raymond McDermott, Stephen P Finn
Circular RNAs (circRNAs) are currently classed as non-coding RNA (ncRNA) that, unlike linear RNAs, form covalently closed continuous loops and act as gene regulators in mammals. They were originally thought to represent errors in splicing and considered to be of low abundance, however, there is now an increased appreciation of their important function in gene regulation. circRNAs are differentially generated by backsplicing of exons or from lariat introns. Unlike linear RNA, the 3' and 5' ends normally present in an RNA molecule have been joined together by covalent bonds leading to circularization...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/28634489/a-study-of-patients-with-primary-mediastinal-germ-cell-tumors-treated-using-multimodal-therapy
#9
Yutaro Tanaka, Takehiko Okamura, Takashi Nagai, Daichi Kobayashi, Takahiro Kobayashi, Hidetoshi Akita, Yoshinobu Moritoki, Takahiro Yasui
OBJECTIVES: Primary mediastinal germ cell tumors (PMGCTs) are rare, which often makes them difficult to treat. Herein, we examined patients with PMGCTs who underwent multimodal treatment. METHODS: We examined 6 patients (median age: 25 years, range: 19-27 years) with PMGCTs who underwent multimodal treatment between April 2001 and March 2015. Three patients had seminomas, 2 patients had yolk sac tumors, and 1 patient had choriocarcinoma. The median observation period was 32...
2017: Advances in Urology
https://www.readbyqxmd.com/read/28634226/phostine-pst3-1a-targets-mgat5-and-inhibits-glioblastoma-initiating-cell-invasiveness-and-proliferation
#10
Zahra Hassani, Ali Saleh, Soumaya Turpault, Salim Khiati, Willy Morelle, Jacques Vignon, Jean-Philippe Hugnot, Emmanuelle Uro-Coste, Philippe Legrand, Marcel Delaforge, Séverine Loiseau, Ludovic Clarion, Marc Lecouvey, Jean-Noël Volle, David Virieux, Jean-Luc Pirat, Hugues Duffau, Norbert Bakalara
Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor and accounts for a significant proportion of all primary brain tumors. Median survival after treatment is around 15 months. Remodeling of N-glycans by the N-acetylglucosamine glycosyltransferase (MGAT5) regulates tumoral development. Here, perturbation of MGAT5 enzymatic activity by the small-molecule inhibitor 3-Hydroxy-4,5-bis-benzyloxy-6-benzyloxymethyl-2-phenyl2-oxo-2λ5-[1,2]oxaphosphinane (PST3.1a) restrains GBM growth. In cell based assays it is demonstrated that PST3...
June 20, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28634046/tumor-antigen-prame-is-up-regulated-by-mzf1-in-cooperation-with-dna-hypomethylation-in-melanoma-cells
#11
Yong-Kyu Lee, Ui-Hyun Park, Eun-Joo Kim, Jin-Taek Hwang, Ji-Cheon Jeong, Soo-Jong Um
Elevated expression of preferentially expressed antigen in melanoma (PRAME) has been implicated in disease progression in a variety of cancers. However, the mechanisms underlying the transcriptional regulation of PRAME remain largely unexplored. Initially, we observed that PRAME was elevated in proportion to the malignant potential of melanoma cells. From the in silico prediction of PRAME gene structure, we identified the putative myeloid zinc finger 1 (MZF1) binding sites, which overlap with a CpG-rich region located in the first intron...
June 17, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28633655/inhibition-of-mmp-2-and-mmp-9-decreases-cellular-migration-and-angiogenesis-in-in-vitro-models-of-retinoblastoma
#12
Anderson H Webb, Bradley T Gao, Zachary K Goldsmith, Andrew S Irvine, Nabil Saleh, Ryan P Lee, Justin B Lendermon, Rajini Bheemreddy, Qiuhua Zhang, Rachel C Brennan, Dianna Johnson, Jena J Steinle, Matthew W Wilson, Vanessa M Morales-Tirado
BACKGROUND: Retinoblastoma (Rb) is the most common primary intraocular tumor in children. Local treatment of the intraocular disease is usually effective if diagnosed early; however advanced Rb can metastasize through routes that involve invasion of the choroid, sclera and optic nerve or more broadly via the ocular vasculature. Metastatic Rb patients have very high mortality rates. While current therapy for Rb is directed toward blocking tumor cell division and tumor growth, there are no specific treatments targeted to block Rb metastasis...
June 20, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28633645/generation-of-populations-of-antigen-specific-cytotoxic-t-cells-using-dcs-transfected-with-dna-construct-encoding-her2-neu-tumor-antigen-epitopes
#13
Maria Kuznetsova, Julia Lopatnikova, Julia Khantakova, Rinat Maksyutov, Amir Maksyutov, Sergey Sennikov
BACKGROUND: Recent fundamental and clinical studies have confirmed the effectiveness of utilizing the potential of the immune system to remove tumor cells disseminated in a patient's body. Cytotoxic T lymphocytes (CTLs) are considered the main effectors in cell-mediated antitumor immunity. Approaches based on antigen presentation to CTLs by dendritic cells (DCs) are currently being intensively studied, because DCs are more efficient in tumor antigen presentation to T cells through their initiation of strong specific antitumor immune responses than other types of antigen-presenting cells...
June 20, 2017: BMC Immunology
https://www.readbyqxmd.com/read/28633632/antagonizing-mir-455-3p-inhibits-chemoresistance-and-aggressiveness-in-esophageal-squamous-cell-carcinoma
#14
Aibin Liu, Jinrong Zhu, Geyan Wu, Lixue Cao, Zhanyao Tan, Shuxia Zhang, Lili Jiang, Jueheng Wu, Mengfeng Li, Libing Song, Jun Li
BACKGROUND: The plasticity of cancer stem cells (CSCs)/tumor-initiating cells (T-ICs) suggests that multiple CSC/T-IC subpopulations exist within a tumor and that multiple oncogenic pathways collaborate to maintain the CSC/T-IC state. Here, we aimed to identify potential therapeutic targets that concomitantly regulate multiple T-IC subpopulations and CSC/T-IC-associated pathways. METHODS: A chemoresistant patient-derived xenograft (PDX) model of human esophageal squamous cell carcinoma (ESCC) was employed to identify microRNAs that contribute to ESCC aggressiveness...
June 21, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28633434/psip1-p75-promotes-tumorigenicity-in-breast-cancer-cells-by-promoting-the-transcription-of-cell-cycle-genes
#15
Deepak K Singh, Omid Gholamalamdari, Mahdieh Jadaliha, Xiao Ling Li, Yo-Chuen Lin, Yang Zhang, Shuomeng Guang, Seyedsasan Hashemikhabir, Saumya Tiwari, Yuelin J Zhu, Abid Khan, Anu Thomas, Arindam Chakraborty, Virgilia Macias, Andre K Balla, Rohit Bhargava, Sarath Chandra Janga, Jian Ma, Supriya G Prasanth, Ashish Lal, Kannanganattu V Prasanth
Breast cancer (BC) is a highly heterogeneous disease, both at the pathological and molecular level, and several chromatin-associated proteins play crucial roles in breast cancer initiation and progression. Here, we demonstrate the role of PSIP1 (PC4 and SF2 interacting protein)/p75 (LEDGF) in breast cancer progression. PSIP1/p75, previously identified as a chromatin-adaptor protein, is found to be upregulated in basal-like/triple negative breast cancer (TNBC) patient samples and cell lines. Immunohistochemistry in tissue arrays showed elevated levels of PSIP1 in metastatic invasive ductal carcinoma...
June 17, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28632792/identification-of-cell-proliferation-immune-response-and-cell-migration-as-critical-pathways-in-a-prognostic-signature-for-her2-er%C3%AE-breast-cancer
#16
Jeffrey C Liu, Miriam Zacksenhouse, Andrea Eisen, Sharon Nofech-Mozes, Eldad Zacksenhaus
BACKGROUND: Multi-gene prognostic signatures derived from primary tumor biopsies can guide clinicians in designing an appropriate course of treatment. Identifying genes and pathways most essential to a signature performance may facilitate clinical application, provide insights into cancer progression, and uncover potentially new therapeutic targets. We previously developed a 17-gene prognostic signature (HTICS) for HER2+:ERα- breast cancer patients, using genes that are differentially expressed in tumor initiating cells (TICs) versus non-TICs from MMTV-Her2/neu mammary tumors...
2017: PloS One
https://www.readbyqxmd.com/read/28632753/mait-cells-launch-a-rapid-robust-and-distinct-hyperinflammatory-response-to-bacterial-superantigens-and-quickly-acquire-an-anergic-phenotype-that-impedes-their-cognate-antimicrobial-function-defining-a-novel-mechanism-of-superantigen-induced-immunopathology
#17
Christopher R Shaler, Joshua Choi, Patrick T Rudak, Arash Memarnejadian, Peter A Szabo, Mauro E Tun-Abraham, Jamie Rossjohn, Alexandra J Corbett, James McCluskey, John K McCormick, Olivier Lantz, Roberto Hernandez-Alejandro, S M Mansour Haeryfar
Superantigens (SAgs) are potent exotoxins secreted by Staphylococcus aureus and Streptococcus pyogenes. They target a large fraction of T cell pools to set in motion a "cytokine storm" with severe and sometimes life-threatening consequences typically encountered in toxic shock syndrome (TSS). Given the rapidity with which TSS develops, designing timely and truly targeted therapies for this syndrome requires identification of key mediators of the cytokine storm's initial wave. Equally important, early host responses to SAgs can be accompanied or followed by a state of immunosuppression, which in turn jeopardizes the host's ability to combat and clear infections...
June 2017: PLoS Biology
https://www.readbyqxmd.com/read/28631775/-innovations-in-the-treatment-of-ovarian-cancer-analysis-of-the-therapeutic-development-from-platinum-to-immunotherapy
#18
Gesuino Angius, Pierangela Sepe, Anselmo Papa, Silverio Tomao, Federica Tomao
Ovarian cancer is the seventh most common cancer in women. The therapeutic approach provides for an appropriate integration between surgery and chemotherapy. Surgery is an important step for diagnosis, staging and therapy, aiming at the complete cytoreduction of all macroscopic visible disease. At the moment, adjuvant and first-line chemotherapy has as a standard the carboplatin-paclitaxel combination. Further, the addition of bevacizumab in the advanced stage (IIIB-IV) is strongly recommended. Despite the initial effectiveness, however, 70-80% of patients develop relapsed disease within the first two years and require subsequent treatment lines that have palliative, rather than curative purposes and that seek to reach a chronic state for the disease...
June 2017: Recenti Progressi in Medicina
https://www.readbyqxmd.com/read/28631712/-the-molecular-mechanisms-and-morphological-manifestations-of-leiomyoma-reduction-induced-by-selective-progesterone-receptor-modulators
#19
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/28631654/composite-lymphoma-with-coexistence-of-diffuse-large-b-cell-lymphoma-and-anaplastic-large-cell-lymphoma-diagnostic-pitfalls
#20
Meyyappa Devan Rajagopal, Rakhee Kar, Debdatta Basu, Sunu Lazar Cyriac
Composite lymphoma is a rare tumor composed of two or more distinct lymphomas in the same topographic site or tissue. Several combinations of B-cell non-Hodgkin lymphoma (NHL), T-cell NHL, and Hodgkin lymphoma can occur with different prognoses and treatments. The coexistence of a B-cell NHL and a T-cell NHL is unusual. The exact etiology of composite lymphoma is unknown; however, few mechanisms have been proposed to explain its pathogenesis. The chemotherapeutic protocols are heterogeneous but are essentially targeted against the high-grade component...
April 2017: Indian Journal of Pathology & Microbiology
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