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https://www.readbyqxmd.com/read/28614736/nanoparticle-mediated-knockdown-of-dna-repair-sensitizes-cells-to-radiotherapy-and-extends-survival-in-a-genetic-mouse-model-of-glioblastoma
#1
Forrest M Kievit, Kui Wang, Tatsuya Ozawa, Aria W Tarudji, John R Silber, Eric C Holland, Richard G Ellenbogen, Miqin Zhang
Glioblastoma (GBM) remains incurable, and recurrent tumors that rarely respond to standard-of-care radiation and chemo-therapies. Therefore, strategies that enhance the effects of these therapies should provide significant benefits to GBM patients. We have developed a nanoparticle delivery vehicle that can stably bind and protect nucleic acids for specific delivery into brain tumor cells. These nanoparticles can deliver therapeutic siRNAs to sensitize GBM cells to radiotherapy and improve GBM treatment via systemic administration...
June 11, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/28606997/hpv-e7-induces-chemotherapy-mediated-tumor-suppression-by-ceramide-dependent-mitophagy
#2
Raquela J Thomas, Natalia Oleinik, Shanmugam Panneer Selvam, Silvia G Vaena, Mohammed Dany, Rose N Nganga, Ryan Depalma, Kyla D Baron, Jisun Kim, Zdzislaw M Szulc, Besim Ogretmen
Human papillomavirus (HPV) infection is linked to improved survival in response to chemo-radiotherapy for patients with oropharynx head and neck squamous cell carcinoma (HNSCC). However, mechanisms involved in increased HNSCC cell death by HPV signaling in response to therapy are largely unknown. Here, using molecular, pharmacologic and genetic tools, we show that HPV early protein 7 (E7) enhances ceramide-mediated lethal mitophagy in response to chemotherapy-induced cellular stress in HPV-positive HNSCC cells by selectively targeting retinoblastoma protein (RB)...
June 12, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28568899/winding-back-wnt-signalling-potential-therapeutic-targets-for-treating-gastric-cancers
#3
REVIEW
Dustin J Flanagan, Elizabeth Vincan, Toby J Phesse
Gastric cancer persists as a frequent and deadly disease that claims over 700,000 lives annually. Gastric cancer is a multifactorial disease that is genetically, cytologically and architecturally more heterogeneous than other gastrointestinal cancers, making it therapeutically challenging. As such, and largely attributed to late-stage diagnosis, gastric cancer patients show only partial response to standard chemo and targeted molecular therapies, highlighting an urgency to develop new targeted therapies for this disease...
June 1, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28541182/chemotactic-network-responses-to-live-bacteria-show-independence-of-phagocytosis-from-chemo-receptor-sensing
#4
Netra Pal Meena, Alan R Kimmel
Aspects of innate immunity derive from characteristics inherent to phagocytes, including chemotaxis toward and engulfment of unicellular organisms or cell debris. Ligand chemotaxis has been biochemically investigated using mammalian and model systems, but precision of chemotaxis towards ligands being actively secreted by live bacteria is not well studied, nor has there been systematic analyses of interrelationships between chemotaxis and phagocytosis. The genetic/molecular model Dictyostelium and mammalian phagocytes share mechanistic pathways for chemotaxis and phagocytosis; Dictyostelium chemotax toward bacteria and phagocytose them as food sources...
May 25, 2017: ELife
https://www.readbyqxmd.com/read/28540598/parp-inhibitors-in-prostate-cancer
#5
REVIEW
Praveen Ramakrishnan Geethakumari, Matthew J Schiewer, Karen E Knudsen, Wm Kevin Kelly
The genomic landscape of metastatic prostate cancer (mPCa) reveals that up to 90% of patients harbor actionable mutations and >20% have somatic DNA repair gene defects (DRD). This provides the therapeutic rationale of PARP inhibition (PARPi) to achieve "synthetic lethality" in treating this fatal disease. Clinical trials with PARP inhibitors have shown significant response rates up to 88% for PCa patients having DRD like BRCA1/2 or ATM mutations. The FDA has awarded "breakthrough designation" to develop the PARPi olaparib in treating this subset of metastatic PCa patients...
June 2017: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/28510097/ago-austria-recommendation-on-screening-and-diagnosis-of-lynch-syndrome-ls
#6
Alain G Zeimet, Harald Mori, Edgar Petru, Stephan Polterauer, Alexander Reinthaller, Christian Schauer, Tonja Scholl-Firon, Christian Singer, Katharina Wimmer, Johannes Zschocke, Christian Marth
PURPOSE: This manuscript reports the consensus recommendations on screening and diagnosis of Lynch syndrome (LS) in patients with endometrial or ovarian cancer as well as on possible preventive measures in effectively LS-diagnosed women. The recommendations are issued by the Austrian Arbeitsgemeinschaft für Gynäkologische Onkologie (AGO) of the Österreichischen Gesellschaft für Gynäkologie und Geburtshilfe (OEGGG) after consultation of the most recent and relevant literature and following deliberation by the Genetic Task-Force convoked May, 2015 by the AGO Council...
May 16, 2017: Archives of Gynecology and Obstetrics
https://www.readbyqxmd.com/read/28477336/rad51-as-a-potential-surrogate-marker-for-dna-repair-capacity-in-solid-malignancies
#7
REVIEW
Mariam Gachechiladze, Josef Škarda, Alex Soltermann, Markus Joerger
Targeting deficient mechanisms of cellular DNA repair still represents the basis for the treatment of the majority of solid tumors, and increased DNA repair capacity is a hallmark mechanism of resistance not only to DNA-damaging treatments such as cytotoxic drugs and radiotherapy, but also to small molecule targeted drugs such as inhibitors of poly-ADP ribose polymerase (PARP). Hence, there is substantial medical need for potent and convenient biomarkers of individual response to DNA-targeted treatment in personalized cancer care...
May 6, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28475867/dna-damage-in-stem-cells
#8
REVIEW
Ilio Vitale, Gwenola Manic, Ruggero De Maria, Guido Kroemer, Lorenzo Galluzzi
Both embryonic and adult stem cells are endowed with a superior capacity to prevent the accumulation of genetic lesions, repair them, or avoid their propagation to daughter cells, which would be particularly detrimental to the whole organism. Inducible pluripotent stem cells also display a robust DNA damage response, but the stability of their genome is often conditioned by the mutational history of the cell population of origin, which constitutes an obstacle to clinical applications. Cancer stem cells are particularly tolerant to DNA damage and fail to undergo senescence or regulated cell death upon accumulation of genetic lesions...
May 4, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28462918/targeting-hdac3-new-partner-protein-of-akt-in-the-reversal-of-chemo-resistance-in-acute-myeloid-leukemia-via-dna-damage-response
#9
Jun Long, W Y Fang, Li Chang, W H Gao, Yan Shen, M Y Jia, Y X Zhang, Y Wang, H B Dou, W J Zhang, J Zhu, A B Liang, J M Li, J Hu
Resistance to cytotoxic chemotherapy drugs remains as the major cause of treatment failure in acute myeloid leukemia. Histone deacetylases are important regulators to maintain chromatin structure and control DNA damage; nevertheless, how each HDAC regulates genome stability remains unclear, especially under genome stress conditions. Here, we identified a mechanism by which HDAC3 regulates DNA damage repair and mediates resistance to chemotherapy drugs. In addition to inducing DNA damage, chemotherapy drugs trigger upregulation of HDAC3 expression in leukemia cells...
May 2, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28427401/ki-67-protein-expression-and-tumor-associated-inflammatory-cells-macrophages-and-mast-cells-in-canine-colorectal-carcinoma
#10
M Woldemeskel, I Hawkins, L Whittington
BACKGROUND: Ki67 index, tumor associated macrophages (TAMs) and mast cells (MCs) are associated with malignancies in animal and human neoplasms including colorectal carcinomas (CRC). This has not been assessed in canine CRC. Given similar genetic abnormalities between human and canine CRC, we assessed Ki-67 and mitotic indices, TAMs and MC count (MCC) in canine CRC (n = 17). TAMs and MCC were compared with those in adenomas (n = 13) and control (n = 9). RESULTS: Ki-67 index in CRC (17...
April 20, 2017: BMC Veterinary Research
https://www.readbyqxmd.com/read/28419303/tumor-microtubes-convey-resistance-to-surgical-lesions-and-chemotherapy-in-gliomas
#11
Sophie Weil, Matthias Osswald, Gergely Solecki, Julia Grosch, Erik Jung, Dieter Lemke, Miriam Ratliff, Daniel Hänggi, Wolfgang Wick, Frank Winkler
Background: Primary and adaptive resistance against chemo- and radiotherapy, and local recurrence after surgery limit the benefits from these standard treatments in glioma patients. Recently we found that glioma cells can extend ultra-long membrane protrusions, "tumor microtubes" (TMs), for brain invasion, proliferation, and interconnection of single cells to a syncytium that is resistant to radiotherapy. We wondered whether TMs also convey resistance to the other two standard treatment modalities...
April 17, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28391030/metformin-triggers-autophagy-to-attenuate-drug-induced-apoptosis-in-nsclc-cells-with-minor-effects-on-tumors-of-diabetic-patients
#12
Zhiguang Xiao, Silvia Gaertner, Alicia Morresi-Hauf, Rebecca Genzel, Thomas Duell, Axel Ullrich, Pjotr G Knyazev
The biologic plausibility of an association between type 2 diabetes mellitus (T2D) and lung cancer has received increasing attention, but the results of investigations remain largely inconclusive. In the present study we investigated the influence of the anti-diabetic drug metformin on the cytotoxic effects of EGFR targeted therapy and chemotherapy in 7 non-small cell lung cancer (NSCLC) cell lines and a cohort of lung cancer patients with/without T2D. In vitro cell viability assays indicated that metformin didn't potentiate the growth inhibitory effects of erlotinib at different doses in cell lines that are of distinct genetic background...
May 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28386641/mathematical-deconvolution-uncovers-the-genetic-regulatory-signal-of-cancer-cellular-heterogeneity-on-resistance-to-paclitaxel
#13
Ian Morilla, Juan A Ranea
Drug resistance remains a major problem in combating malignancies, resulting critical the resistance to paclitaxel used in the treatment of many different cancers. Elucidating the cellular heterogeneity composition of tumours may be relevant to designing more effective treatment strategies on drug resistance. In particular, such heterogeneity correlates with the measurement of gene expression below the population level. However, experimental assays capturing differential response are limited and cannot discern the variation in gene expression specific to different cellular types in tumour populations...
April 6, 2017: Molecular Genetics and Genomics: MGG
https://www.readbyqxmd.com/read/28385379/specific-gene-expression-profiles-are-associated-with-a-pathologic-complete-response-to-neoadjuvant-therapy-in-esophageal-adenocarcinoma
#14
Patrick J McLaren, Anthony P Barnes, Willy Z Terrell, Gina M Vaccaro, Jack Wiedrick, John G Hunter, James P Dolan
BACKGROUND: Predicting treatment response to chemo-radiotherapy (CRT) in esophageal cancer remains an unrealized goal despite studies linking constellations of genes to prognosis. We aimed to determine if specific expression profiles are associated with pathologic complete response (pCR) after neoadjuvant CRT. METHODS: Eleven genes previously associated with esophageal cancer prognosis were identified. Esophageal adenocarcinoma (EAC) patients treated with neoadjuvant CRT and esophagectomy were included...
March 27, 2017: American Journal of Surgery
https://www.readbyqxmd.com/read/28306358/the-genetics-of-gastroesophageal-adenocarcinoma-and-the-use-of-circulating-cell-free-dna-for-disease-detection-and-monitoring
#15
REVIEW
Mark R Openshaw, Catherine J Richards, David S Guttery, Jacqueline A Shaw, Anne L Thomas
Gastroesophageal adenocarcinoma (GOA) is a frequently occurring cancer worldwide with a poor clinical outcome. Adenocarcinomas of the esophagus and gastroesophageal junction have shown a recent increase in frequency, therefore there is need to increase our understanding of GOA in order to improve our ability to detect, monitor and treat the disease. Areas covered: The authors discuss the current classification of GOA in the context of recent changes in incidence. The authors also discuss developments in the understanding of disease biology and recent discoveries from whole genome and whole exome sequencing, and studies in immunotherapy...
May 2017: Expert Review of Molecular Diagnostics
https://www.readbyqxmd.com/read/28302031/hif1a-is-overexpressed-in-medulloblastoma-and-its-inhibition-reduces-proliferation-and-increases-epas1-and-atg16l1-methylation
#16
Gustavo Alencastro Veiga Cruzeiro, Maristella Bergamo Dos Reis, Vanessa Silva Silveira, Régia Caroline Peixoto Lira, Carlos Gilberto Carlotti, Luciano Neder, Ricardo Santos Oliveira, José Andres Yunes, Silvia Regina Brandalise, Simone Aguiar, Agda Karina Eterovic, Luiz Gonzaga Tone, Carlos Alberto Scrideli, Elvis Terci Valera
BACKGROUND: Genetic and epigenetic modifications are closely related to tumor initiation and progression and can provide guidance for understanding tumor functioning, potentially leading to the discovery of new therapies. Studies have associated hypoxia-related genes to tumor progression and chemo/radioresistance in brain tumors. Information on the expression profile of hypoxia-related genes in pediatric medulloblastoma, although scarce, may reveal relevant information that could support treatment decisions...
March 15, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28273854/overexpression-of-transforming-acidic-coiled-coil%C3%A2-containing-protein-3-reflects-malignant-characteristics-and-poor-prognosis-of-glioma
#17
Ying Sun, Yu Tian, Guang-Zhi Wang, Shi-Hong Zhao, Bo Han, Yong-Li Li, Chuan-Lu Jiang
Gliomas are malignant primary brain tumors with poor prognosis. Recently, research was indicative of a tight connection between tumor malignancy and genetic alterations. Here, we propose an oncogenic implication of transforming acidic coiled-coil-containing protein 3 (TACC3) in gliomas. By comprehensively analyzing the Chinese glioma genome atlas (CGGA) and publicly available data, we demonstrated that TACC3 were overexpressed along with glioma grade and served as an independent negative prognostic biomarker for glioma patients...
March 4, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28239999/glioblastoma-multiforme-a-review-of-its-epidemiology-and-pathogenesis-through-clinical-presentation-and-treatment
#18
Farina Hanif, Kanza Muzaffar, Kahkashan Perveen, Saima M Malhi, Shabana U Simjee
Glioblastoma multiforme (GBM) is one of the most malignant types of central nervous system tumors. Despite advances in treatment modalities it remains largely incurable. The objective of our review is to provide a holistic picture of GBM epidemiology, etiology, pathogenesis, clinical findings and treatment. A literature search was conducted for GBM at PubMed and Google Scholar, with relevant key words like glioblastoma multiforme, pathogenesis, signs and symptoms, treatment etc., and papers published until 2015 were reviewed...
January 1, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/28238718/towards-therapeutic-advances-in-melanoma-management-an-overview
#19
REVIEW
Swarnendra Singh, Atif Zafar, Saman Khan, Imrana Naseem
Melanoma is one of the most aggressive types of skin cancer with rapidly increasing incidence rate. The disease is largely considered incurable and the patients diagnosed with metastatic melanoma have a survival of not more than five years. Despite of the recent advances in anti-melanoma chemo- and immunotherapies, the available drugs are relatively toxic and responsive to only a limited subset of lesions. Currently, topical pharmacotherapy is demonstrated as an effective approach for the treatment of various skin cancers...
April 1, 2017: Life Sciences
https://www.readbyqxmd.com/read/28223669/-diagnosis-and-treatment-of-hboc-syndrome-by-a-breast-surgical-oncologist
#20
Kumiko Kida, Michiko Murai, Hideko Yamauchi
Of all breast cancer cases, 5-10% occur because of inherited germline mutation. For hereditary breast and ovarian cancer (HBOC)syndrome, congenital knowledge and strategies for breast cancer treatment and risk reduction are necessary. Regarding the surgical procedure for the cancer site, the ipsilateral breast tumor recurrence rate following breast-conserving surgery in breast cancers with BRCA1/2 mutation is not significantly higher than that in sporadic breast cancers. In addition, prognosis did not differ according to surgical methods...
February 2017: Gan to Kagaku Ryoho. Cancer & Chemotherapy
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