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https://www.readbyqxmd.com/read/28829366/understanding-resistance-mechanisms-and-expanding-the-therapeutic-utility-of-parp-inhibitors
#1
REVIEW
Joline S J Lim, David S P Tan
Poly-(ADP-ribose) polymerase (PARP) inhibitors act through synthetic lethality in cells with defects in homologous recombination (HR) DNA repair caused by molecular aberrations such as BRCA mutations, and is approved for treatment in ovarian cancer, with promising clinical activity against other HR defective tumors including breast and prostate cancers. Three PARP inhibitors have been FDA approved, while another two have shown promising activity and are in late stage development. Nonetheless, both primary and secondary resistance to PARP inhibition have led to treatment failure, and the development of predictive biomarkers and the ability to identify and overcome mechanisms of resistance is vital for optimization of its clinical utility...
August 22, 2017: Cancers
https://www.readbyqxmd.com/read/28817104/national-and-subnational-population-based-incidence-of-cancer-in-thailand-assessing-cancers-with-the-highest-burdens
#2
Shama Virani, Surichai Bilheem, Wasan Chansaard, Imjai Chitapanarux, Karnchana Daoprasert, Somsak Khuanchana, Atit Leklob, Donsuk Pongnikorn, Laura S Rozek, Surattaya Siriarechakul, Krittika Suwanrungruang, Sukit Tassanasunthornwong, Patravoot Vatanasapt, Hutcha Sriplung
In Thailand, five cancer types-breast, cervical, colorectal, liver and lung cancer-contribute to over half of the cancer burden. The magnitude of these cancers must be quantified over time to assess previous health policies and highlight future trajectories for targeted prevention efforts. We provide a comprehensive assessment of these five cancers nationally and subnationally, with trend analysis, projections, and number of cases expected for the year 2025 using cancer registry data. We found that breast (average annual percent change (AAPC): 3...
August 17, 2017: Cancers
https://www.readbyqxmd.com/read/28805682/alk-in-non-small-cell-lung-cancer-nsclc-pathobiology-epidemiology-detection-from-tumor-tissue-and-algorithm-diagnosis-in-a-daily-practice
#3
REVIEW
Paul Hofman
Patients with advanced-stage non-small cell lung carcinoma (NSCLC) harboring an ALK rearrangement, detected from a tissue sample, can benefit from targeted ALK inhibitor treatment. Several increasingly effective ALK inhibitors are now available for treatment of patients. However, despite an initial favorable response to treatment, in most cases relapse or progression occurs due to resistance mechanisms mainly caused by mutations in the tyrosine kinase domain of ALK. The detection of an ALK rearrangement is pivotal and can be done using different methods, which have variable sensitivity and specificity depending, in particular, on the quality and quantity of the patient's sample...
August 12, 2017: Cancers
https://www.readbyqxmd.com/read/28805673/alk-status-assessment-with-liquid-biopsies-of-lung-cancer-patients
#4
REVIEW
Paul Hofman
Patients with advanced stage non-small cell lung carcinoma (NSCLC) harboring an anaplastic lymphoma kinase ALK gene rearrangement, detected from a tissue sample, can benefit from targeted ALK inhibitor treatment. However, while treatment is initially effective in most cases, relapse or progression occurs due to different resistance mechanisms including mutations in the tyrosine kinase domain of echinoderm microtubule-associated protein-like 4 (EML44)-ALK. The liquid biopsy concept has recently radically changed the clinical care of NSCLC patients, in particular for those harboring an epidermal growth factor receptor (EGFR) gene mutation...
August 12, 2017: Cancers
https://www.readbyqxmd.com/read/28796150/the-role-of-cancer-derived-exosomes-in-tumorigenicity-epithelial-to-mesenchymal-transition
#5
REVIEW
Robert H Blackwell, Kimberly E Foreman, Gopal N Gupta
Epithelial-to-mesenchymal transition (EMT) is a process by which epithelial cells lose their basement membrane interaction and acquire a more migratory, mesenchymal phenotype. EMT has been implicated in cancer cell progression, as cells transform and increase motility and invasiveness, induce angiogenesis, and metastasize. Exosomes are 30-100 nm membrane-bound vesicles that are formed and excreted by all cell types and released into the extracellular environment. Exosomal contents include DNA, mRNA, miRNA, as well as transmembrane- and membrane-bound proteins derived from their host cell contents...
August 10, 2017: Cancers
https://www.readbyqxmd.com/read/28792442/complex-determinants-of-epithelial-mesenchymal-phenotypic-plasticity-in-ovarian-cancer
#6
REVIEW
Yuliya Klymenko, Oleg Kim, M Sharon Stack
Unlike most epithelial malignancies which metastasize hematogenously, metastasis of epithelial ovarian cancer (EOC) occurs primarily via transcoelomic dissemination, characterized by exfoliation of cells from the primary tumor, avoidance of detachment-induced cell death (anoikis), movement throughout the peritoneal cavity as individual cells and multi-cellular aggregates (MCAs), adhesion to and disruption of the mesothelial lining of the peritoneum, and submesothelial matrix anchoring and proliferation to generate widely disseminated metastases...
August 9, 2017: Cancers
https://www.readbyqxmd.com/read/28786923/secondary-intracranial-tumors-following-radiotherapy-for-pituitary-adenomas-a-systematic-review
#7
REVIEW
Ryuya Yamanaka, Eisuke Abe, Toshiteru Sato, Azusa Hayano, Yasuo Takashima
Pituitary adenomas are often treated with radiotherapy for the management of tumor progression or recurrence. Despite the improvement in cure rates, patients treated by radiotherapy are at risk of development of secondary malignancies. We conducted a comprehensive literature review of the secondary intracranial tumors that occurred following radiotherapy to pituitary adenomas to obtain clinicopathological characteristics. The analysis included 48 neuroepithelial tumors, 37 meningiomas, and 52 sarcomas which were published between 1959-2017, although data is missing regarding overall survival and type of irradiation in a significant proportion of the reports...
August 8, 2017: Cancers
https://www.readbyqxmd.com/read/28783103/significance-of-micrornas-in-androgen-signaling-and-prostate-cancer-progression
#8
REVIEW
Ken-Ichi Takayama, Aya Misawa, Satoshi Inoue
The androgen receptor (AR) plays important roles in prostate cancer development and prostate tumor growth. After binding to androgens, AR functions as a nuclear receptor and translocates to the nucleus to bind to specific AR-binding sites (ARBSs). AR regulates epigenetic factor recruitments to activate its downstream signaling. Although androgen deprivation therapy (ADT) is initially useful for prostate cancer patients, most patients eventually show resistance with hormone-refractory prostate cancers (HRPCs) or castration-resistant prostate cancers (CRPCs)...
August 7, 2017: Cancers
https://www.readbyqxmd.com/read/28771186/epithelial-to-mesenchymal-transition-and-micrornas-in-lung-cancer
#9
REVIEW
Antoine Legras, Nicolas Pécuchet, Sandrine Imbeaud, Karine Pallier, Audrey Didelot, Hélène Roussel, Laure Gibault, Elizabeth Fabre, Françoise Le Pimpec-Barthes, Pierre Laurent-Puig, Hélène Blons
Despite major advances, non-small cell lung cancer (NSCLC) remains the major cause of cancer-related death in developed countries. Metastasis and drug resistance are the main factors contributing to relapse and death. Epithelial-to-mesenchymal transition (EMT) is a complex molecular and cellular process involved in tissue remodelling that was extensively studied as an actor of tumour progression, metastasis and drug resistance in many cancer types and in lung cancers. Here we described with an emphasis on NSCLC how the changes in signalling pathways, transcription factors expression or microRNAs that occur in cancer promote EMT...
August 3, 2017: Cancers
https://www.readbyqxmd.com/read/28771164/crosstalk-between-microrna-and-dna-methylation-offers-potential-biomarkers-and-targeted-therapies-in-alk-positive-lymphomas
#10
REVIEW
Coralie Hoareau-Aveilla, Fabienne Meggetto
The discovery of microRNA (miRNA) has provided new and powerful tools for studying the mechanism, diagnosis and treatment of human cancers. The down-regulation of tumor suppressive miRNA by hypermethylation of CpG island (CpG is shorthand for 5'-C-phosphate-G-3', that is, cytosine and guanine separated by only one phosphate) is emerging as a common hallmark of cancer and appears to be involved in drug resistance. This review discusses the role of miRNA and DNA methylation in drug resistance mechanisms and highlights their potential as anti-cancer therapies in Anaplastic Lymphoma Kinase (ALK)-positive lymphomas...
August 3, 2017: Cancers
https://www.readbyqxmd.com/read/28763012/performance-of-a-rt-pcr-assay-in-comparison-to-fish-and-immunohistochemistry-for-the-detection-of-alk-in-non-small-cell-lung-cancer
#11
David R Hout, Brock L Schweitzer, Kasey Lawrence, Stephan W Morris, Tracy Tucker, Rosetta Mazzola, Rachel Skelton, Frank McMahon, John Handshoe, Mary Lesperance, Aly Karsan, David L Saltman
Patients with lung cancers harboring an activating anaplastic lymphoma kinase (ALK) rearrangement respond favorably to ALK inhibitor therapy. Fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) are validated and widely used screening tests for ALK rearrangements but both methods have limitations. The ALK RGQ RT-PCR Kit (RT-PCR) is a single tube quantitative real-time PCR assay for high throughput and automated interpretation of ALK expression. In this study, we performed a direct comparison of formalin-fixed paraffin-embedded (FFPE) lung cancer specimens using all three ALK detection methods...
August 1, 2017: Cancers
https://www.readbyqxmd.com/read/28758926/emt-met-at-the-crossroad-of-stemness-regeneration-and-oncogenesis-the-ying-yang-equilibrium-recapitulated-in-cell-spheroids
#12
REVIEW
Elvira Forte, Isotta Chimenti, Paolo Rosa, Francesco Angelini, Francesca Pagano, Antonella Calogero, Alessandro Giacomello, Elisa Messina
The epithelial-to-mesenchymal transition (EMT) is an essential trans-differentiation process, which plays a critical role in embryonic development, wound healing, tissue regeneration, organ fibrosis, and cancer progression. It is the fundamental mechanism by which epithelial cells lose many of their characteristics while acquiring features typical of mesenchymal cells, such as migratory capacity and invasiveness. Depending on the contest, EMT is complemented and balanced by the reverse process, the mesenchymal-to-epithelial transition (MET)...
July 29, 2017: Cancers
https://www.readbyqxmd.com/read/28788063/localization-of-vegf-to-vascular-ecm-is-an-important-aspect-of-tumor-angiogenesis
#13
Weon-Kyoo You, William B Stallcup
Our research has identified several examples in which reduced VEGF-A binding to deficient vascular extracellular matrix leads to deficits in tumor vascularization and tumor growth: (1) germline ablation of collagen VI in the stroma of intracranial B16F10 melanomas; (2) knockdown of the Tks5 scaffolding protein in MDA-MB-231 mammary tumor cells; (3) germline ablation of NG2 proteoglycan in the stroma of MMTV-PyMT mammary tumors; and (4) myeloid-specific ablation of NG2 in the stroma of intracranial B16F10 melanomas...
July 28, 2017: Cancers
https://www.readbyqxmd.com/read/28737696/targeting-platelets-for-the-treatment-of-cancer
#14
REVIEW
Omar Elaskalani, Michael C Berndt, Marco Falasca, Pat Metharom
The majority of cancer-associated mortality results from the ability of tumour cells to metastasise leading to multifunctional organ failure and death. Disseminated tumour cells in the blood circulation are faced with major challenges such as rheological shear stresses and cell-mediated cytotoxicity mediated by natural killer cells. Nevertheless, circulating tumour cells with metastatic ability appear equipped to exploit host cells to aid their survival. Despite the long interest in targeting tumour-associated host cells such as platelets for cancer treatment, the clinical benefit of this strategy is still under question...
July 22, 2017: Cancers
https://www.readbyqxmd.com/read/28753978/seed-in-soil-pancreatic-cancer-influenced-by-tumor-microenvironment
#15
REVIEW
Huey-Jen Lin, Jiayuh Lin
Pancreatic ductal adenocarcinoma is a fatal malignancy with a five-year survival rate lower than 7%, and most patients dying within six months of diagnosis. The factors that contribute to the aggressiveness of the disease include, but are not limited to: late diagnosis, prompt metastasis to adjacent vital organs, poor response, and resistance to anticancer treatments. This malignancy is uniquely associated with desmoplastic stroma that accounts for 80% of tumor mass. Understanding the biology of stroma can aid the discovery of innovative strategies for eradicating this lethal cancer in the future...
July 21, 2017: Cancers
https://www.readbyqxmd.com/read/28718816/complex-dna-damage-a-route-to-radiation-induced-genomic-instability-and-carcinogenesis
#16
REVIEW
Ifigeneia V Mavragani, Zacharenia Nikitaki, Maria P Souli, Asef Aziz, Somaira Nowsheen, Khaled Aziz, Emmy Rogakou, Alexandros G Georgakilas
Cellular effects of ionizing radiation (IR) are of great variety and level, but they are mainly damaging since radiation can perturb all important components of the cell, from the membrane to the nucleus, due to alteration of different biological molecules ranging from lipids to proteins or DNA. Regarding DNA damage, which is the main focus of this review, as well as its repair, all current knowledge indicates that IR-induced DNA damage is always more complex than the corresponding endogenous damage resulting from endogenous oxidative stress...
July 18, 2017: Cancers
https://www.readbyqxmd.com/read/28718815/regional-delivery-of-chimeric-antigen-receptor-car-t-cells-for-cancer-therapy
#17
REVIEW
Praveen Sridhar, Fabio Petrocca
Chimeric Antigen Receptor (CAR) T-cells are T-cells with recombinant receptors targeted to tumor antigens. CAR-T cell therapy has emerged as a mode of immunotherapy and is now being extensively explored in hematologic cancer. In contrast, CAR-T cell use in solid tumors has been hampered by multiple obstacles. Several approaches have been taken to circumvent these obstacles, including the regional delivery of CAR-T cells. Regional CAR-T cell delivery can theoretically compensate for poor T-cell trafficking and tumor antigen specificity while avoiding systemic toxicity associated with intravenous delivery...
July 18, 2017: Cancers
https://www.readbyqxmd.com/read/28704962/sirt3-oncogene-and-tumor-suppressor-in-cancer
#18
REVIEW
Margalida Torrens-Mas, Jordi Oliver, Pilar Roca, Jorge Sastre-Serra
Sirtuin 3 (SIRT3), the major deacetylase in mitochondria, plays a crucial role in modulating oxygen reactive species (ROS) and limiting the oxidative damage in cellular components. SIRT3 targets different enzymes which regulate mitochondrial metabolism and participate in ROS detoxification, such as the complexes of the respiratory chain, the isocitrate dehydrogenase, or the manganese superoxide dismutase. Thus, SIRT3 activity is essential in maintaining mitochondria homeostasis and has recently received great attention, as it is considered a fidelity protein for mitochondrial function...
July 12, 2017: Cancers
https://www.readbyqxmd.com/read/28704919/the-role-of-radiation-induced-injury-on-lung-cancer
#19
Stephanie Puukila, Christopher Thome, Antone L Brooks, Gayle Woloschak, Douglas R Boreham
This manuscript evaluates the role of cell killing, tissue disorganization, and tissue damage on the induction of lung cancer following low dose rate radiation exposures from internally deposited radioactive materials. Beagle dogs were exposed by inhalation to (90)Y, (91)Y, (144)Ce, or (90)Sr in fused clay particles. Dogs lived out their life span with complete pathology conducted at the time of death. The radiation dose per cell turnover was characterized and related to the cause of death for each animal. Large doses per cell turnover resulted in acute death from lung damage with extensive cell killing, tissue disorganization, chronic inflammatory disease, fibrosis, and pneumonitis...
July 12, 2017: Cancers
https://www.readbyqxmd.com/read/28696382/phosphoinositide-3-kinase-dependent-signalling-pathways-in-cutaneous-squamous-cell-carcinomas
#20
REVIEW
Joanna M Janus, Ryan F L O'Shaughnessy, Catherine A Harwood, Tania Maffucci
Cutaneous squamous cell carcinoma (cSCC) derives from keratinocytes in the epidermis and accounts for 15-20% of all cutaneous malignancies. Although it is usually curable by surgery, 5% of these tumours metastasise leading to poor prognosis mostly because of a lack of therapies and validated biomarkers. As the incidence rate is rising worldwide it has become increasingly important to better understand the mechanisms involved in cSCC development and progression in order to develop therapeutic strategies. Here we discuss some of the evidence indicating that activation of phosphoinositide 3-kinases (PI3Ks)-dependent signalling pathways (in particular the PI3Ks targets Akt and mTOR) has a key role in cSCC...
July 11, 2017: Cancers
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