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https://www.readbyqxmd.com/read/28327183/modeling-multi-mutation-and-drug-resistance-analysis-of-some-case-studies
#1
Mitra Shojania Feizabadi
BACKGROUND: Drug-induced resistance is one the major obstacles that may lead to therapeutic failure during cancer treatment. Different genetic alterations occur when tumor cells divide. Among new generations of tumor cells, some may express intrinsic resistance to a specific chemotherapeutic agent. Also, some tumor cells may carry a gene that can develop resistance induced by the therapeutic drug. The methods by which the therapeutic approaches need to be revised in the occurrence of drug induced resistance is still being explored...
March 21, 2017: Theoretical Biology & Medical Modelling
https://www.readbyqxmd.com/read/28326803/when-is-an-alveolar-type-2-cell-an-alveolar-type-2-cell-a-conundrum-for-lung-stem-cell-biology-and-regenerative-medicine
#2
Michael F Beers, Yuben Moodley
Generating mature, differentiated, adult lung cells from pluripotent cells such as induced pluripotent cells (iPS) and embryonic stem cells (ES) offers the hope of both generating disease specific in vitro models and creating definitive and personalized therapies for a host of debilitating lung parenchymal and airway diseases. With the goal of advancing lung regenerative medicine, several groups have developed and reported on protocols utilizing either defined media, co-culture with mesenchymal components, or sequential treatments mimicking lung development, to obtain distal lung epithelial cells from stem cell precursors...
March 22, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28326039/estrone-sulfate-transport-and-steroid-sulfatase-activity-in-colorectal-cancer-implications-for-hormone-replacement-therapy
#3
Lorna C Gilligan, Ali Gondal, Vivien Tang, Maryam T Hussain, Anastasia Arvaniti, Anne-Marie Hewitt, Paul A Foster
Hormone replacement therapy (HRT) affects the incidence and potential progression of colorectal cancer (CRC). As HRT primarily consists of estrone sulfate (E1S), understanding whether this conjugated estrogen is transported and metabolized in CRC will define its potential effect in this malignancy. Here, we show that a panel of CRC cell lines (Colo205, Caco2, HCT116, HT-29) have steroid sulfatase (STS) activity, and thus can hydrolyze E1S. STS activity is significantly higher in CRC cell lysate, suggesting the importance of E1S transport in intracellular STS substrate availability...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28325301/increased-expression-of-laminin-subunit-alpha-1-chain-by-dcas9-vp160
#4
Arnaud Perrin, Joël Rousseau, Jacques P Tremblay
Laminin-111 protein complex links the extracellular matrix to integrin α7β1 in sarcolemma, thus replacing in dystrophic muscles links normally insured by the dystrophin complex. Laminin-111 injection in mdx mouse stabilized sarcolemma, restored serum creatine kinase to wild-type levels, and protected muscles from exercised-induced damages. These results suggested that increased laminin-111 is a potential therapy for DMD. Laminin subunit beta 1 and laminin subunit gamma 1 are expressed in adult human muscle, but laminin subunit alpha 1 (LAMA1) gene is expressed only during embryogenesis...
March 17, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28325291/systemic-rala-inos-nanoparticles-a-potent-gene-therapy-for-metastatic-breast-cancer-coupled-as-a-biomarker-of-treatment
#5
Cian M McCrudden, John W McBride, Joanne McCaffrey, Ahlam A Ali, Nicholas J Dunne, Vicky L Kett, Jonathan A Coulter, Tracy Robson, Helen O McCarthy
This study aimed to determine the therapeutic benefit of a nanoparticular formulation for the delivery of inducible nitric oxide synthase (iNOS) gene therapy in a model of breast cancer metastasis. Nanoparticles comprising a cationic peptide vector, RALA, and plasmid DNA were formulated and characterized using a range of physiochemical analyses. Nanoparticles complexed using iNOS plasmids and RALA approximated 60 nm in diameter with a charge of 25 mV. A vector neutralization assay, performed to determine the immunogenicity of nanoparticles in immunocompetent C57BL/6 mice, revealed that no vector neutralization was evident...
March 17, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28322181/epithelial-mesenchymal-and-hybrid-epithelial-mesenchymal-phenotypes-and-their-clinical-relevance-in-cancer-metastasis
#6
Minal Garg
Cancer metastasis occurs through local invasion of circulating tumour cells (CTCs), intravasation, transportation to distant sites, and their extravasation followed by colonisation at secondary sites. Epithelial-mesenchymal transition (EMT) is a normal developmental phenomenon, but its aberrant activation confers tumour cells with enhanced cell motility, metastatic properties, resistant to therapies and cancer stem cell (CSC) phenotype in epithelium-derived carcinoma. Experimental studies from various research papers have been reviewed to determine the factors, which interlink cancer stemness and cellular plasticity with EMT...
March 21, 2017: Expert Reviews in Molecular Medicine
https://www.readbyqxmd.com/read/28320896/estrogen-maintains-mitochondrial-content-and-function-in-the-right-ventricle-of-rats-with-pulmonary-hypertension
#7
Aiping Liu, Jennifer Philip, Kalyan C Vinnakota, Francoise Van den Bergh, Diana M Tabima, Timothy Hacker, Daniel A Beard, Naomi C Chesler
The typical cause of death in pulmonary hypertension (PH) is right ventricular (RV) failure, with females showing better survival rates than males. Recently, metabolic shift and mitochondrial dysfunction have been demonstrated in RV failure secondary to PH In light of evidence showing that estrogen protects mitochondrial function and biogenesis in noncardiovascular systems, we hypothesized that the mechanism by which estrogen preserves RV function is via protection of mitochondrial content and oxidative capacity in PH We used a well-established model of PH (Sugen+Hypoxia) in ovariectomized female rats with/without estrogen treatment...
March 2017: Physiological Reports
https://www.readbyqxmd.com/read/28319113/combinatorial-crispr-cas9-screens-for-de-novo-mapping-of-genetic-interactions
#8
John Paul Shen, Dongxin Zhao, Roman Sasik, Jens Luebeck, Amanda Birmingham, Ana Bojorquez-Gomez, Katherine Licon, Kristin Klepper, Daniel Pekin, Alex N Beckett, Kyle Salinas Sanchez, Alex Thomas, Chih-Chung Kuo, Dan Du, Assen Roguev, Nathan E Lewis, Aaron N Chang, Jason F Kreisberg, Nevan Krogan, Lei Qi, Trey Ideker, Prashant Mali
We developed a systematic approach to map human genetic networks by combinatorial CRISPR-Cas9 perturbations coupled to robust analysis of growth kinetics. We targeted all pairs of 73 cancer genes with dual guide RNAs in three cell lines, comprising 141,912 tests of interaction. Numerous therapeutically relevant interactions were identified, and these patterns replicated with combinatorial drugs at 75% precision. From these results, we anticipate that cellular context will be critical to synthetic-lethal therapies...
March 20, 2017: Nature Methods
https://www.readbyqxmd.com/read/28319041/practical-use-of-a-plastic-scintillator-for-quality-assurance-of-electron-beam-therapy
#9
Katsunori Yogo, Yuya Tatsuno, Masato Tsuneda, Yuki Aono, Daiki Mochizuki, Yoshiki Fujisawa, Akihiro Matsushita, Minoru Ishigami, Hiromichi Ishiyama, Kazushige Hayakawa
Quality assurance (QA) of the clinical electron beam is essential for performing accurate and safe radiation therapy. However, with advances in radiation therapy, QA tends to be labor-intensive and time consuming. Here, we propose the practical use of a tissue-equivalent plastic scintillator for quick and easy QA of clinical electron beams. This tool enabled us to verify simultaneously the constancy of output, beam quality, depth and lateral dose profiles during monthly QAs at lower doses of irradiation (small MUs)...
March 20, 2017: Physics in Medicine and Biology
https://www.readbyqxmd.com/read/28318761/the-bone-marrow-microenvironment-home-of-the-leukemic-blasts
#10
REVIEW
Manar S Shafat, Bruno Gnaneswaran, Kristian M Bowles, Stuart A Rushworth
Acute Myeloid Leukaemia (AML) is a genetically, biologically and clinically heterogeneous set of diseases, which are characterised by an increased growth of abnormal myeloid progenitor cells within the bone marrow (BM). Ex-vivo AML exhibits a high level of spontaneous apoptosis. Furthermore, relapse for patients achieving remission occurs from minimal residual disease harboured within the BM microenvironment. Taken together, these observations illustrate the importance of the BM microenvironment in sustaining AML...
March 12, 2017: Blood Reviews
https://www.readbyqxmd.com/read/28318287/findings-from-a-couple-based-open-trial-for-adult-anorexia-nervosa
#11
Donald H Baucom, Jennifer S Kirby, Melanie S Fischer, Brian R Baucom, Robert Hamer, Cynthia M Bulik
Adult anorexia nervosa (AN) often is persistent, significantly erodes quality of life for both the patient and loved ones, and carries high medical and psychiatric comorbidity. Whereas individual psychotherapy for adult AN leads to improvement in some patients, recent findings indicate that the magnitude of improvement is limited: Only a small percentage of individuals fully recover and dropout rates are high. Thus, it is important to build upon current interventions to improve treatment response. We present results from an open trial of a couple-based intervention for adult anorexia nervosa as an adjunct treatment to standard multidisciplinary care...
March 20, 2017: Journal of Family Psychology: JFP
https://www.readbyqxmd.com/read/28315426/vascular-patterning-in-human-heterotopic-ossification
#12
Margaret Cocks, Aditya Mohan, Carolyn A Meyers, Catherine Ding, Benjamin Levi, Edward McCarthy, Aaron W James
Heterotopic ossification (HO, also termed myositis ossificans) is the formation of extra-skeletal bone in muscle and soft tissues. HO is a tissue repair process gone awry, and is a common complication of surgery and traumatic injury. Medical strategies to prevent and treat HO fall well short of addressing the clinical need. Better characterization of the tissues supporting HO is critical to identifying therapies directed against this common and sometimes devastating condition. The physiologic processes of osteogenesis and angiogenesis are highly coupled and interdependent...
March 14, 2017: Human Pathology
https://www.readbyqxmd.com/read/28306354/bronchiectasis-phenotyping-a-complex-disease
#13
James D Chalmers
Bronchiectasis is a long-neglected disease currently experiencing a surge in interest. It is a highly complex condition with numerous aetiologies, co-morbidities and a heterogeneous disease presentation and clinical course. The past few years have seen major advances in our understanding of the disease, primarily through large real-life cohort studies. The main outcomes of interest in bronchiectasis are symptoms, exacerbations, treatment response, disease progression and death. We are now more able to identify clearly the radiological, clinical, microbiological and inflammatory contributors to these outcomes...
March 15, 2017: COPD
https://www.readbyqxmd.com/read/28302866/genomic-profiling-of-patient-derived-xenografts-for-lung-cancer-identifies-b2m-inactivation-impairing-immunorecognition
#14
Carolina Pereira, Pol Gimenez-Xavier, Eva Pros, Maria J Pajares, Massimo Moro, Antonio Gomez, Alejandro Navarro, Enric Condom, Sebastian Moran, Gonzalo Gomez-Lopez, Osvaldo Graña, Miriam Rubio-Camarillo, Alex Martinez-Martí, Jun Yokota, Julian Carretero, Jose M Galbis, Ernest Nadal, David Pisano, Gabriella Sozzi, Enriqueta Felip, Luis M Montuenga, Luca Roz, Alberto Villanueva, Montse Sanchez-Cespedes
Purpose: We aimed to maximize the performance of detecting genetic alterations in lung cancer using high-throughput sequencing for patient-derived xenografts (PDXs).Experimental Design: We undertook an integrated RNA and whole-exome sequencing of 14 PDXs. We focused on the genetic and functional analysis of β2-microglobulin (B2M), a component of the HLA class-I complex.Results: We identified alterations in genes involved in various functions, such as B2M involved in immunosurveillance. We extended the mutational analysis of B2M to about 230 lung cancers...
March 16, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28300784/the-molecular-basis-of-toxins-interactions-with-intracellular-signaling-via-discrete-portals
#15
REVIEW
Adi Lahiani, Ephraim Yavin, Philip Lazarovici
An understanding of the molecular mechanisms by which microbial, plant or animal-secreted toxins exert their action provides the most important element for assessment of human health risks and opens new insights into therapies addressing a plethora of pathologies, ranging from neurological disorders to cancer, using toxinomimetic agents. Recently, molecular and cellular biology dissecting tools have provided a wealth of information on the action of these diverse toxins, yet, an integrated framework to explain their selective toxicity is still lacking...
March 16, 2017: Toxins
https://www.readbyqxmd.com/read/28299797/processes-that-inform-multicultural-supervision-a-meta-analysis
#16
Nilou B Tohidian, Karen Mui-Teng Quek
As the fields of counseling and psychotherapy have become more cognizant that individuals, couples, and families bring with them a myriad of diversity factors into therapy, multicultural competency has also become a crucial component in the development of clinicians during clinical supervision and training. We employed a qualitative meta-analysis to provide a detailed and comprehensive description of similar themes identified in primary qualitative studies that have investigated supervisory practices with an emphasis on diversity...
March 16, 2017: Journal of Marital and Family Therapy
https://www.readbyqxmd.com/read/28298930/predicting-the-remaining-lifespan-and-cultivation-related-loss-of-osteogenic-capacity-of-bone-marrow-multipotential-stromal-cells-applicable-across-a-broad-donor-age-range
#17
Sarah M Churchman, Sally A Boxall, Dennis McGonagle, Elena A Jones
Background and Objectives. Culture expanded multipotential stromal cells (MSCs) have considerable potential for bone regeneration therapy but their wider use is constrained by the lack of simple and predictive assays of functional potency. Extended passaging leads to loss of multipotency but speed of decline depends on MSC donor age. The aim of this study was to develop an assay predictive of MSC culture longevity applicable to a broad donor age range. Materials and Methods. Bone marrow (BM, n = 7) was obtained from a diverse range (2-72 years) of healthy donors...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28298263/a-proof-of-principle-simulation-for-closed-loop-control-based-on-preexisting-experimental-thalamic-dbs-enhanced-instrumental-learning
#18
Ching-Fu Wang, Shih-Hung Yang, Sheng-Huang Lin, Po-Chuan Chen, Yu-Chun Lo, Han-Chi Pan, Hsin-Yi Lai, Lun-De Liao, Hui-Ching Lin, Hsu-Yan Chen, Wei-Chen Huang, Wun-Jhu Huang, You-Yin Chen
Deep brain stimulation (DBS) has been applied as an effective therapy for treating Parkinson's disease or essential tremor. Several open-loop DBS control strategies have been developed for clinical experiments, but they are limited by short battery life and inefficient therapy. Therefore, many closed-loop DBS control systems have been designed to tackle these problems by automatically adjusting the stimulation parameters via feedback from neural signals, which has been reported to reduce the power consumption...
February 24, 2017: Brain Stimulation
https://www.readbyqxmd.com/read/28295436/a-systematic-review-of-gay-lesbian-and-bisexual-research-samples-in-couple-and-family-therapy-journals
#19
Erica E Hartwell, Julianne M Serovich, Sandra J Reed, Danielle Boisvert, Teresa Falbo
The purpose of this study is to review samples from research on gay, lesbian, and bisexual (GLB) issues and to evaluate the suitability of this body of research to support affirmative and evidence-based practice with GLB clients. The authors systematically reviewed the sampling methodology and sample composition of GLB-related research. All original, quantitative articles focusing on GLB issues published in couple and family therapy (CFT)-related journals since 1975 were coded (n = 153). Results suggest that within the GLB literature base there is some evidence of heterocentrism as well as neglect of issues of class, race, and gender...
March 11, 2017: Journal of Marital and Family Therapy
https://www.readbyqxmd.com/read/28295431/relational-family-therapy-as-an-aid-toward-resolving-the-trauma-of-sexual-abuse-in-childhood-in-the-process-of-separation-in-the-couple-relationship
#20
Tanja Repič Slavič, Christian Gostečnik
Relational family therapy (RFT) is a psycho-organic therapeutic approach that combines intrapsychic dynamics with interpersonal mechanisms and a systemic perspective. This integrative model is based on the assumption that the repetitive patterns of relationships in early childhood repeat in adulthood. It often happens that a sexually abused individual will later unconsciously be attracted to someone with whom they will relive the abusive atmosphere and dynamics from childhood. The purpose of this contribution is to present the RFT approach for dealing with sexual abuse...
March 13, 2017: Journal of Marital and Family Therapy
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