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https://www.readbyqxmd.com/read/28928472/a-high-conductance-chemo-optogenetic-system-based-on-the-vertebrate-channel-trpa1b
#1
Pui-Ying Lam, Suresh K Mendu, Robert W Mills, Baohui Zheng, Hugo Padilla, David J Milan, Bimal N Desai, Randall T Peterson
Optogenetics is a powerful research approach that allows localized optical modulation of selected cells within an animal via the expression of genetically encoded photo-excitable ion channels. Commonly used optogenetic techniques rely on the expression of microbial opsin variants, which have many excellent features but suffer from various degrees of blue spectral overlap and limited channel conductance. Here, we expand the optogenetics toolbox in the form of a tunable, high-conductance vertebrate cation channel, zTrpa1b, coupled with photo-activated channel ligands, such as optovin and 4g6...
September 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28895245/genetic-evolution-of-glioblastoma-stem-like-cells-from-primary-to-recurrent-tumor
#2
Francesca Orzan, Francesca De Bacco, Giovanni Crisafulli, Serena Pellegatta, Benedetta Mussolin, Giulia Siravegna, Antonio D'Ambrosio, Paolo M Comoglio, Gaetano Finocchiaro, Carla Boccaccio
Glioblastoma (GBM) is a lethal tumor that displays remarkable genetic heterogeneity. It is also known that GBM contains a cell hierarchy driven by stem-like cells (GSCs), responsible for tumor generation, therapeutic resistance and relapse. An important and still open issue is whether phylogenetically related GSCs can be found in matched primary and recurrent GBMs, and reflect tumor genetic evolution under therapeutic pressure. To address this, we analyzed the mutational profile of GSCs isolated from either human primary GBMs (primary GSCs) or their matched tumors recurring after surgery and chemo-radiotherapy (recurrent GSCs)...
September 12, 2017: Stem Cells
https://www.readbyqxmd.com/read/28852532/an-unusual-neck-tumor-in-a-young-pregnant-woman-challenge-diagnosis-and-response-to-treatment
#3
Juan F Arango, Juan C López, Virginia Arrazubi, Silvia Cisneros, Angel Rodríguez, Aitor Zabala, Purificación Martinez Del Prado
We report the case of a 19-year-old woman 33 weeks pregnant who presented a painful mass of progressive growth in the neck, having also dysphonia and dyspnea. Physical examination revealed a primary laryngeal tumor. A neuroendocrine small-cell carcinoma was diagnosed after histopathology, immunohistochemistry and genetic studies. Chemo-radiotherapy with a cisplatin-etoposide schedule was administered. Despite obtaining a complete response, the patient relapsed and finally survived 35 months with successive cisplatin-based treatments...
August 2017: Oxford Medical Case Reports
https://www.readbyqxmd.com/read/28837152/lysosomotropism-depends-on-glucose-a-chloroquine-resistance-mechanism
#4
Laura E Gallagher, Ohood A Radhi, Mahmud O Abdullah, Anthony G McCluskey, Marie Boyd, Edmond Y W Chan
There has been long-standing interest in targeting pro-survival autophagy as a combinational cancer therapeutic strategy. Clinical trials are in progress testing chloroquine (CQ) or its derivatives in combination with chemo- or radiotherapy for solid and haematological cancers. Although CQ has shown efficacy in preclinical models, its mechanism of action remains equivocal. Here, we tested how effectively CQ sensitises metastatic breast cancer cells to further stress conditions such as ionising irradiation, doxorubicin, PI3K-Akt inhibition and serum withdrawal...
August 24, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28832261/prospects-and-progress-of-immunotherapy-for-bladder-cancer
#5
Martin Boegemann, Ahmet Murat Aydin, Aditya Bagrodia, Laura-Maria Krabbe
With recent advances in immunooncology and the introduction of checkpoint inhibitors into clinical practice for many cancers, the treatment landscape of urothelial carcinoma has changed dramatically and will continue to change further. Currently, a number of compounds and combinations are under investigation in numerous clinical trials and various clinical scenarios for bladder cancer. Areas covered: In this review, the authors provide an overview of the history and rationale for immunotherapy in bladder cancer...
August 23, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28804127/discovery-of-novel-drug-sensitivities-in-t-pll-by-high-throughput-ex-vivo-drug-testing-and-mutation-profiling
#6
E I Andersson, S Pützer, B Yadav, O Dufva, S Khan, L He, L Sellner, A Schrader, G Crispatzu, M Oleś, H Zhang, S Adnan-Awad, S Lagström, D Bellanger, J P Mpindi, S Eldfors, T Pemovska, P Pietarinen, A Lauhio, K Tomska, C Cuesta-Mateos, E Faber, S Koschmieder, T H Brümmendorf, S Kytölä, E-R Savolainen, T Siitonen, P Ellonen, O Kallioniemi, K Wennerberg, W Ding, M-H Stern, W Huber, S Anders, J Tang, T Aittokallio, T Zenz, M Herling, S Mustjoki
T-cell prolymphocytic leukemia (T-PLL) is a rare and aggressive neoplasm of mature T-cells with an urgent need for rationally designed therapies to address its notoriously chemo-refractory behavior. The median survival of T-PLL patients is <2 years and clinical trials are difficult to execute. Here we systematically explored the diversity of drug responses in T-PLL patient samples using an ex vivo drug sensitivity and resistance testing platform and correlated the findings with somatic mutations and gene expression profiles...
August 14, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28771790/motoneuron-activity-is-required-for-enhancements-in-functional-recovery-after-peripheral-nerve-injury-in-exercised-female-mice
#7
Poonam B Jaiswal, Jack K Tung, Robert E Gross, Arthur W English
Inhibitory luminopsins (iLMO2) integrate opto- and chemo-genetic approaches and allow for cell-type specific inhibition of neuronal activity. When exposed to a Renilla luciferase substrate, Coelenterazine (CTZ), iLMO2 generates bioluminescence-mediated activation of its amino-terminal halorhodopsin, resulting in neuronal inhibition. Moderate daily exercise in the form of interval treadmill-training (IT) applied following a peripheral nerve injury results in enhanced motor axon regeneration and muscle fiber reinnervation in female mice...
August 3, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/28767419/b-lymphoblastic-leukemia-lymphoma-new-insights-into-genetics-molecular-aberrations-subclassification-and-targeted-therapy
#8
Xiaohui Zhang, Prerna Rastogi, Bijal Shah, Ling Zhang
B lymphoblastic leukemia/lymphoma (B-ALL) is a clonal hematopoietic stem cell neoplasm derived from B-cell progenitors, which mostly occurs in children and adolescents and is regarded as one of top leading causes of death related to malignancies in this population. Despite the majority of patients with B-ALL have fairly good response to conventional chemotherapeutic interventions followed by hematopoietic stem cell transplant for the last decades, a subpopulation of patients show chemo-resistance and a high relapse rate...
July 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28766096/inhibiting-erk-mnk-eif4e-broadly-sensitizes-ovarian-cancer-response-to-chemotherapy
#9
S Liu, J Zha, M Lei
PURPOSE: To investigate whether ERK/MNK/eIF4E contributes chemoresistance in ovarian cancer. METHODS: The phosphorylated levels of Erk, Mnk, and eIF4E were systematically analyzed in ovarian cancer patients before and after chemotherapy, and ovarian cancer cells exposed to short- and long-term chemo-agent treatment. The roles of Erk/Mnk/eIF4E were investigated using pharmacological and genetic approaches. RESULTS: Increased phosphorylation levels of ERK, Mnk1, and eIF4E were observed in ovarian cancer cell exposed to chemotherapeutic agents, and paclitaxel-resistant SK-OV-3-r cells, and is a common response of ovarian cancer patients undergoing chemotherapy...
August 1, 2017: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/28710492/nek1-kinase-domain-structure-and-its-dynamic-protein-interactome-after-exposure-to-cisplatin
#10
Talita D Melo-Hanchuk, Priscila Ferreira Slepicka, Gabriela Vaz Meirelles, Fernanda Luisa Basei, Diogo Ventura Lovato, Daniela Campos Granato, Bianca Alves Pauletti, Romenia Ramos Domingues, Adriana Franco Paes Leme, Alessandra Luiza Pelegrini, Guido Lenz, Stefan Knapp, Jonathan M Elkins, Jörg Kobarg
NEK family kinases are serine/threonine kinases that have been functionally implicated in the regulation of the disjunction of the centrosome, the assembly of the mitotic spindle, the function of the primary cilium and the DNA damage response. NEK1 shows pleiotropic functions and has been found to be mutated in cancer cells, ciliopathies such as the polycystic kidney disease, as well as in the genetic diseases short-rib thoracic dysplasia, Mohr-syndrome and amyotrophic lateral sclerosis. NEK1 is essential for the ionizing radiation DNA damage response and priming of the ATR kinase and of Rad54 through phosphorylation...
July 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28690659/chronic-myeloid-leukemia-with-a-complex-variant-ph-translocation-that-develops-in-breast-carcinoma-postchemotherapy-a-rare-but-treatable-entity
#11
Gargi Tikku, Monica Jain, Pragya Shukla
We report a case of chronic myeloid leukemia (CML) that developed after postoperative chemotherapy with cyclophosphamide, doxorubicin and 5-fluorouracil (CAF) for breast cancer. A 55-year-old woman was diagnosed with invasive ductal carcinoma which was treated with a modified radical mastectomy followed by six cycles of CAF chemotherapy. Nine years later, she developed CML and locoregional recurrence. Her breast recurrence showed strong estrogen receptor, weak progesterone receptor and strong human epidermal growth factor 2 (score 3+) expression...
June 2017: Journal of Breast Cancer
https://www.readbyqxmd.com/read/28662901/sonic-hedgehog-pathway-inhibition-normalizes-desmoplastic-tumor-microenvironment-to-improve-chemo-and-nanotherapy
#12
Fotios Mpekris, Panagiotis Papageorgis, Christiana Polydorou, Chrysovalantis Voutouri, Maria Kalli, Athanassios P Pirentis, Triantafyllos Stylianopoulos
Targeting the rich extracellular matrix of desmoplastic tumors has been successfully shown to normalize collagen and hyaluronan levels and re-engineer intratumoral mechanical forces, improving tumor perfusion and chemotherapy. As far as targeting the abundant cancer-associated fibroblasts (CAFs) in desmoplastic tumors is concerned, while both pharmacologic inhibition of the sonic-hedgehog pathway and genetic depletion of fibroblasts have been employed in pancreatic cancers, the results between the two methods have been contradictory...
September 10, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
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
#13
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 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
#14
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)...
August 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28568899/winding-back-wnt-signalling-potential-therapeutic-targets-for-treating-gastric-cancers
#15
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-chemoreceptor-sensing
#16
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
#17
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
#18
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...
July 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
#19
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...
October 1, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28475867/dna-damage-in-stem-cells
#20
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
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