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Clinical and Translational Medicine

Terry A Jacot, Meredith R Clark, Oluwatosin E Adedipe, Susan Godbout, Abby G Peele, Susan Ju, Jill L Schwartz, Andrea R Thurman, Gustavo F Doncel
BACKGROUND: Adherence is critical for successful topical, vaginally delivered anti-retroviral (ARV)-based HIV pre-exposure prophylaxis (PrEP). Quantitating systemic or tissue ARV levels through LC-MS/MS is currently viewed as the most reliable measure of adherence. However, for placebo-controlled trials, this is a high cost analysis that measures adherence only in the drug treatment group. A desirable marker of adherence is one that is measured in both placebo and drug treatment groups using a simple on-site clinical laboratory test, which allows necessary interventions for supporting participant adherence...
November 7, 2018: Clinical and Translational Medicine
Yong Zhang
Cell toxicity may result in organ dysfunction and cause severe health problem. Recent studies revealed many toxicants may induced the over production of Nitric oxide, reactive oxygen species and the subsequent oxidative stress, cause cell toxicity. Mitochondrion dysfunction maybe the subsequent consequence of oxidative stress and has been recognized as another contributing factor in cell toxicity. Besides, oxidative products induced by some toxicants may also produce the compounds that damage cell DNA, leading to toxicity...
October 29, 2018: Clinical and Translational Medicine
Debarati Ghosh, Saikat Nandi, Sonali Bhattacharjee
Combination therapy is increasingly becoming the cornerstone of current day antitumor therapy. Glioblastoma multiforme is an aggressive brain tumor with a dismal median survival post diagnosis and a high rate of disease recurrence. The poor prognosis can be attributed to unique treatment limitations, which include the infiltrative nature of tumor cells, failure of anti-glioma drugs to cross the blood-brain barrier, tumor heterogeneity and the highly metastatic and angiogenic nature of the tumor making cells resistant to chemotherapy...
October 16, 2018: Clinical and Translational Medicine
Jun Gong, Andrew Hendifar, Richard Tuli, Jeremy Chuang, May Cho, Vincent Chung, Daneng Li, Ravi Salgia
Immune checkpoint inhibitors have demonstrated broad single-agent antitumor activity and a favorable safety profile that render them attractive agents to combine with other systemic anticancer therapies. Pancreatic cancer has been fairly resistant to monotherapy blockade of programmed cell death protein 1 receptor, programmed death ligand 1, and cytotoxic T-lymphocyte associated protein 4. However, there is a growing body of preclinical evidence to support the rational combination of checkpoint inhibitors and various systemic therapies in pancreatic cancer...
October 8, 2018: Clinical and Translational Medicine
Naasson Tuyiringire, Deusdedit Tusubira, Jean-Pierre Munyampundu, Casim Umba Tolo, Claude M Muvunyi, Patrick Engeu Ogwang
Human tuberculosis (TB) is amongst the oldest and deadliest human bacterial diseases that pose major health, social and economic burden at a global level. Current regimens for TB treatment are lengthy, expensive and ineffective to emerging drug resistant strains. Thus, there is an urgent need for identification and development of novel TB drugs and drug regimens with comprehensive and specific mechanisms of action. Many medicinal plants are traditionally used for TB treatment. While some of their phytochemical composition has been elucidated, their mechanisms of action are not well understood...
October 1, 2018: Clinical and Translational Medicine
Hans Raskov, Kasper Nørskov Kragh, Thomas Bjarnsholt, Mahdi Alamili, Ismail Gögenur
BACKGROUND: Research in the field of relation between microbes and colorectal carcinogenesis has gained increasing interest in past years. Recently, link between microbial biofilm and carcinogenesis in colon was demonstrated by several authors indicating that biofilm not only is a key player in carcinogenesis, but also may contribute to the understanding of side-specific colon cancer-right sided colon cancer versus left sided. In this article, we briefly highlight the major findings of the research of biofilm and carcinogenesis and demonstrate our findings of colonic cancer tissue and colonic polyp examined for biofilm...
September 17, 2018: Clinical and Translational Medicine
Christopher D Phillips, Pornpatcharin Wongsaisri, Thein Htut, Terry Grossman
The Editor-in-Chief is retracting this article because the authors have not obtained consent to publish from the patient whose details are described in this case report. The article has been removed to protect the patient's privacy. Terry Grossman has stated that he was not an author on this article. Christopher Phillips, Pornpatcharin Wongsaisri and Thein Htut did not reply to correspondence about this retraction.
September 14, 2018: Clinical and Translational Medicine
Barbara Lohman-Payne, Benjamin Gabriel, Sangshin Park, Dalton Wamalwa, Elizabeth Maleche-Obimbo, Carey Farquhar, Rose Kerubo Bosire, Grace John-Stewart
BACKGROUND: In low and middle income countries, human immunodeficiency virus (HIV) exposed, uninfected (HEU) infants demonstrate higher morbidity and mortality than their unexposed counterparts. To determine possible immune correlates of this effect, we investigated the impact of in utero HIV exposure on the uninfected neonatal immune milieu and maternal factors mediating these abnormalities in a cohort of vaginally delivered mother-infants. Samples of delivery and cord blood plasma were selected from 22 Kenyan HIV-infected women and their HIV exposed uninfected (HEU) infants drawn from the pre-ARV era, while 19 Kenyan HIV-uninfected (HU) women and their infants were selected from a control cohort...
September 10, 2018: Clinical and Translational Medicine
Weilong Chen, Yuanyuan Qin, Suling Liu
Chemotherapy resistance of breast cancer poses a great challenge to the survival of patients. During breast cancer treatment, the development of intrinsic and acquired drug resistance tends to further induce adverse prognosis, such as metastasis. In recent years, the progress of research on cytokine-modulated tumor microenvironment and breast cancer stem cells (BCSCs) has shed light on defining the mechanisms of drug resistance gradually. In this review, we have discussed cytokine regulation on breast cancer chemoresistance...
September 3, 2018: Clinical and Translational Medicine
Monique R Anderson, Michelle L Pleet, Yoshimi Enose-Akahata, James Erickson, Maria Chiara Monaco, Yao Akpamagbo, Ashley Velluci, Yuetsu Tanaka, Shila Azodi, Ben Lepene, Jennifer Jones, Fatah Kashanchi, Steven Jacobson
BACKGROUND: HTLV-1 infects over 20 million people worldwide and causes a progressive neuroinflammatory disorder in a subset of infected individuals called HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). The detection of HTLV-1 specific T cells in the cerebrospinal fluid (CSF) suggests this disease is immunopathologically mediated and that it may be driven by viral antigens. Exosomes are microvesicles originating from the endosomal compartment that are shed into the extracellular space by various cell types...
August 27, 2018: Clinical and Translational Medicine
Johan Malm, Yutaka Sugihara, Marcell Szasz, Ho Jeong Kwon, Henrik Lindberg, Roger Appelqvist, György Marko-Varga
We present the Cancer Moonshot clinical project located at the European center in Lund. Here, tissue and blood samples have been collected and stored in a large-scale biobank. Multiple clinical centers around the world are participating and tissue and blood samples are sent to the European Cancer Moonshot Lund Center that acts as the clinical hub. Our center has been developed to generate and build large-scale biostorage archives of patient melanoma samples, which is then combined with a histopathological capability to characterize the patient tumours...
August 20, 2018: Clinical and Translational Medicine
Oleg Dobrokhotov, Mikhail Samsonov, Masahiro Sokabe, Hiroaki Hirata
Yes-associated protein (YAP) and its paralog WW domain containing transcription regulator 1 (TAZ) are important regulators of multiple cellular functions such as proliferation, differentiation, and survival. On the tissue level, YAP/TAZ are essential for embryonic development, organ size control and regeneration, while their deregulation leads to carcinogenesis or other diseases. As an underlying principle for YAP/TAZ-mediated regulation of biological functions, a growing body of research reveals that YAP/TAZ play a central role in delivering information of mechanical environments surrounding cells to the nucleus transcriptional machinery...
August 13, 2018: Clinical and Translational Medicine
Yutaka Sugihara, Daniel Rivas, Johan Malm, Marcell Szasz, HoJeong Kwon, Bo Baldetorp, Håkan Olsson, Christian Ingvar, Melinda Rezeli, Thomas E Fehniger, György Marko-Varga
BACKGROUND: Currently, only a limited number of molecular biomarkers for malignant melanoma exist. This is the case for both diagnosing the disease, staging, and efficiently measuring the response to therapy by tracing the progression of disease development and drug impact. There is a great need to identify novel landmarks of disease progression and alterations. METHODS: Matrix-assisted laser desorption ionisation mass spectrometry imaging (MALDI-MSI) has been developed within our group to study drug localisation within micro-environmental tissue compartments...
August 6, 2018: Clinical and Translational Medicine
Furong Yan, Hong Zhao, Yiming Zeng
The prevention, diagnosis and targeted therapies of cancer are important in cancer controlling and treatment. The present challenge about cancer biomarker still remains in identifying the special biomarkers for predicting cancer risk and assessing patient's response during anticancer treatment. Lipidomics, in simple definition is the quantification of all lipids in a confined biological entity. Lipids play roles in membrane structure, energy storage, and signal transduction as well as in human cancers. Previous researches indicated that lipids may serve as a promising biomarker in the early diagnoses and individualized treatment of cancer...
July 30, 2018: Clinical and Translational Medicine
Heather E Brassil, Anthony P Salvatore
BACKGROUND: Purpose of this study is to investigate the presence and frequency of post-traumatic stress disorder (PTSD) symptoms in post-concussed (PC) athletes compared to a group of healthy control (HC) athletes. RESEARCH DESIGN AND METHOD: A pre and post-test group design was used to compare a post-concussed group to a matched healthy control group of athletes. An archival database which included PC (n = 62) and HC (n = 62) participants matched on age, years of education and gender who completed a test battery at baseline and post injury, The test battery was comprised of a neurocognitive assessment, self-reported symptom inventory and PTSD symptom questionnaire...
July 23, 2018: Clinical and Translational Medicine
Paige M Glumac, Aaron M LeBeau
Despite the abundant ongoing research efforts, cancer remains one of the most challenging diseases to treat globally. Due to the heterogenous nature of cancer, one of the major clinical challenges in therapeutic development is the cancer's ability to develop resistance. It has been hypothesized that cancer stem cells are the cause for this resistance, and targeting them will lead to tumor regression. A pentaspan transmembrane glycoprotein, CD133 has been suggested to mark cancer stem cells in various tumor types, however, the accuracy of CD133 as a cancer stem cell biomarker has been highly controversial...
July 9, 2018: Clinical and Translational Medicine
Mahin Khatami
Maintenance of health involves a synchronized network of catabolic and anabolic signals among organs/tissues/cells that requires differential bioenergetics from mitochondria and glycolysis (biological laws or biorhythms). We defined biological circadian rhythms as Yin (tumoricidal) and Yang (tumorigenic) arms of acute inflammation (effective immunity) involving immune and non-immune systems. Role of pathogens in altering immunity and inducing diseases and cancer has been documented for over a century. However, in 1955s decision makers in cancer/medical establishment allowed public (current baby boomers) to consume million doses of virus-contaminated polio vaccines...
July 2, 2018: Clinical and Translational Medicine
Trushil Shah, Shanshan Qin, Mona Vashi, Dan N Predescu, Niranjan Jeganathan, Cristina Bardita, Balaji Ganesh, Salvatore diBartolo, Louis F Fogg, Robert A Balk, Sanda A Predescu
BACKGROUND: Pulmonary endothelial cells' (ECs) injury and apoptotic death are necessary and sufficient for the pathogenesis of the acute respiratory distress syndrome (ARDS), regardless of epithelial damage. Interaction of dysfunctional ECs with circulatory extracellular vesicles (EVs) holds therapeutic promise in ARDS. However, the presence in the blood of long-term ARDS survivors of EVs with a distinct phenotype compared to the EVs of non-surviving patients is not reported. With a multidisciplinary translational approach, we studied EVs from the blood of 33 patients with moderate-to-severe ARDS...
June 22, 2018: Clinical and Translational Medicine
Satoshi Fukuda, Perenlei Enkhbaatar, Christina Nelson, Robert A Cox, Marla R Wolfson, Thomas H Shaffer, Robert O Williams, Soraya Hengsawas Surasarang, Sahakijpijarn Sawittree, Galina Florova, Andrey A Komissarov, Kathleen Koenig, Krishna Sarva, Harrison T Ndetan, Karan P Singh, Steven Idell
BACKGROUND: Airway fibrin casts are clinically important complications of severe inhalational smoke-induced acute lung injury (ISIALI) for which reliable evidence-based therapy is lacking. Nebulized anticoagulants or a tissue plasminogen activator; tPA, has been advocated, but airway bleeding is a known and lethal potential complication. We posited that nebulized delivery of single chain urokinase plasminogen activator, scuPA, is well-tolerated and improves physiologic outcomes in ISIALI...
June 18, 2018: Clinical and Translational Medicine
Lillian Truong, Yun-Min Zheng, Tengyao Song, Yi Tang, Yong-Xiao Wang
BACKGROUND: Human Yippee-like-4 (YPEL4) is a member of the YPEL gene family. This family has been characterized as the first highly conserved family of genes coding for proteins that contain putative zinc-finger-like metal-binding domains, known as the Yippee domain. The YPEL family proteins are located at the centrosome adjacent to the nucleolus during interphase and mitotic apparatus during mitosis. Due to its subcellular localization, it is believed that YPEL4 may have an important role in the cell cycle and proliferation...
June 11, 2018: Clinical and Translational Medicine
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