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https://www.readbyqxmd.com/read/28813024/advances-in-understanding-of-penile-carcinogenesis-the-search-for-actionable-targets
#1
REVIEW
Juan Chipollini, Sharon Chaing, Mounsif Azizi, Laura C Kidd, Patricia Kim, Philippe E Spiess
Penile cancer (PeCa) is a rare malignancy with potentially devastating effects. Squamous cell carcinoma is the most common variant with distinct precancerous lesions before development into invasive disease. Involvement of the inguinal lymph nodes is the most important prognostic factor in PeCa, and once disease is present outside the groin, prognosis is poor. Metastatic PeCa is challenging to treat and often requires multidisciplinary approaches in management. Due to its rarity, molecular understanding of the disease continues to be limited with most studies based on small, single center series...
August 16, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28813003/self-assessment-of-antimicrobial-stewardship-in-primary-care-self-reported-practice-using-the-target-primary-care-self-assessment-tool
#2
Rebecca Owens, Leah Ffion Jones, Michael Moore, Dirk Pilat, Cliodna McNulty
Multifaceted antimicrobial stewardship (AMS) interventions including: antibiotic guidance, reviews of antibiotic use using audits, education, patient facing materials, and self-assessment, are successful in improving antimicrobial use. We aimed to measure the self-reported AMS activity of staff completing a self-assessment tool (SAT). The Royal College of General Practitioners (RCGP)/Public Health England (PHE) SAT enables participants considering an AMS eLearning course to answer 12 short questions about their AMS activities...
August 16, 2017: Antibiotics
https://www.readbyqxmd.com/read/28812994/organ-organ-crosstalk-and-alcoholic-liver-disease
#3
REVIEW
Lauren G Poole, Christine E Dolin, Gavin E Arteel
Alcohol consumption is a common custom worldwide, and the toxic effects of alcohol on several target organs are well-understood. Given the poor prognosis of treating clinically-relevant alcoholic liver disease (ALD) (i.e., alcoholic hepatitis (AH) and cirrhosis), additional research is required to develop more effective therapies. While the stages of ALD have been well-characterized, targeted therapies to prevent or reverse this process in humans are still needed. Better understanding of risk factors and mechanisms underlying disease progression can lead to the development of rational therapies to prevent or reverse ALD in the clinic...
August 16, 2017: Biomolecules
https://www.readbyqxmd.com/read/28812304/management-of-castration-resistant-taxane-resistant-prostate-cancer
#4
Tomasz M Beer
Metastatic castration-resistant prostate cancer that is progressing despite docetaxel chemotherapy is difficult to treat and often aggressive. If not previously used, modern androgen signaling inhibitors have established clinical activity in this setting. Cabazitaxel and radium-223 have also been shown to extend survival in appropriately selected patients. Carboplatin-containing chemotherapy regimens have not been studied in randomized trials with a survival endpoint, but they have demonstrated activity in phase II trials and are occasionally considered in the post-docetaxel setting...
August 15, 2017: Oncology (Williston Park, NY)
https://www.readbyqxmd.com/read/28812022/histopathologic-differences-between-jewish-and-arab-population-in-israel-at-first-time-presentation-with-bladder-cancer
#5
Ofir Avitan, Zaher Bahouth, Sarel Halachmi, Sagi Shprits, Ismail Masarwa, Edmond Sabo, Boaz Moskovitz, Ofer Nativ
BACKGROUND: Pathology of urothelial carcinoma may vary in different populations at diagnosis. Our aim was to evaluate the histopathologic differences between Jewish and Arab patients in Israel at first diagnosis of urothelial cancer. PATIENTS AND METHODS: We retrospectively collected data of all patients with confirmed urothelial cancer, treated at our department between January 2010 and January 2015. We examined the distribution of the histopathologic data among the studied populations...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28811579/cxcl12-enhances-angiogenesis-through-cxcr7-activation-in-human-umbilical-vein-endothelial-cells
#6
Min Zhang, Lisha Qiu, Yanyan Zhang, Dongsheng Xu, Jialin C Zheng, Li Jiang
Angiogenesis is the process by which new vessels form from existing vascular networks. Human umbilical vein endothelial cells (HUVECs) may contribute to the study of vascular repair and angiogenesis. The chemokine CXCL12 regulates multiple cell functions, including angiogenesis, mainly through its receptor CXCR4. In contrast to CXCL12/CXCR4, few studies have described roles for CXCR7 in vascular biology, and the downstream mechanism of CXCR7 in angiogenesis remains unclear. The results of the present study showed that CXCL12 dose-dependently enhanced angiogenesis in chorioallantoic membranes (CAMs) and HUVECs...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28811572/inhibition-of-connexin-hemichannels-alleviates-non-alcoholic-steatohepatitis-in-mice
#7
Joost Willebrords, Bruno Cogliati, Isabel Veloso Alves Pereira, Tereza Cristina da Silva, Sara Crespo Yanguas, Michaël Maes, Veronica Mollica Govoni, Andressa Lima, Daniele Aparecida Felisbino, Elke Decrock, Marina Sayuri Nogueira, Inar Alves de Castro, Isabelle Leclercq, Luc Leybaert, Robim Marcelino Rodrigues, Mathieu Vinken
While gap junctions mediate intercellular communication and support liver homeostasis, connexin hemichannels are preferentially opened by pathological stimuli, including inflammation and oxidative stress. The latter are essential features of non-alcoholic steatohepatitis. In this study, it was investigated whether connexin32 and connexin43 hemichannels play a role in non-alcoholic steatohepatitis. Mice were fed a choline-deficient high-fat diet or normal diet for 8 weeks. Thereafter, TAT-Gap24 or TAT-Gap19, specific inhibitors of hemichannels composed of connexin32 and connexin43, respectively, were administered for 2 weeks...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28811550/application-of-galangin-an-active-component-of-alpinia-officinarum-hance-zingiberaceae-for-use-in-drug-eluting-stents
#8
Jung-Jin Lee, Ji-Hye Lee, Nam-Hui Yim, Joo-Hui Han, Jin Yeul Ma
In clinical pathology, stent interposition is used to treat vascular disease but can lead to restenosis. Drug-eluting stents (DES) are most commonly used to suppress restenosis but can also have side effects. Therefore, we investigated the anti-proliferative effect and its possible target in vitro and in vivo. We found that Alpinia officinarum Hance (AO) extract efficiently inhibited VSMC proliferation by arresting the transition from the G0/G1 to the S phase via the up-regulation of p27(KIP1) expression. Galangin (GA) was determined to be a significant component of this extract, with the same anti-proliferative activity as the raw extract...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28811537/prognostic-significance-and-function-of-mammalian-target-of-rapamycin-in-tongue-squamous-cell-carcinoma
#9
Shau-Hsuan Li, Chih-Yen Chien, Wan-Ting Huang, Sheng-Dean Luo, Yan-Ye Su, Wan-Yu Tien, Ya-Chun Lan, Chang-Han Chen
Despite improvement in preoperative imaging, surgical technique, and adjuvant therapy, the prognosis of patients with tongue squamous cell carcinoma (SCC) is still unsatisfactory. The mammalian target of rapamycin (mTOR) play a key role in the regulation of tumor cell proliferation and survival. However, the significance of mTOR on the prognosis of tongue SCC remains largely undefined. In the present study, immunohistochemistry was performed to evaluate the expression of phosphorylated mTOR (p-mTOR) in 160 surgically resected tongue SCC, and correlated with survival...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28811522/the-lichen-secondary-metabolite-atranorin-suppresses-lung-cancer-cell-motility-and-tumorigenesis
#10
Rui Zhou, Yi Yang, So-Yeon Park, Thanh Thi Nguyen, Young-Woo Seo, Kyung Hwa Lee, Jae Hyuk Lee, Kyung Keun Kim, Jae-Seoun Hur, Hangun Kim
Lichens are symbiotic organisms that produce various secondary metabolites. Here, different lichen extracts were examined to identify secondary metabolites with anti-migratory activity against human lung cancer cells. Everniastrum vexans had the most potent inhibitory activity, and atranorin was identified as an active subcomponent of this extract. Atranorin suppressed β-catenin-mediated TOPFLASH activity by inhibiting the nuclear import of β-catenin and downregulating β-catenin/LEF and c-jun/AP-1 downstream target genes such as CD44, cyclin-D1 and c-myc...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28811496/genome-wide-expression-differences-in-anti-vegf-and-dexamethasone-treatment-of-inflammatory-angiogenesis-in-the-rat-cornea
#11
Pierfrancesco Mirabelli, Anthony Mukwaya, Anton Lennikov, Maria Xeroudaki, Beatrice Peebo, Mira Schaupper, Neil Lagali
Angiogenesis as a pathological process in the eye can lead to blindness. In the cornea, suppression of angiogenesis by anti-VEGF treatment is only partially effective while steroids, although effective in treating inflammation and angiogenesis, have broad activity leading to undesirable side effects. In this study, genome-wide expression was investigated in a suture-induced corneal neovascularization model in rats, to investigate factors differentially targeted by dexamethasone and anti-Vegf. Topical treatment with either rat-specific anti-Vegf, dexamethasone, or normal goat IgG (sham) was given to sutured corneas for 48 hours, after which in vivo imaging, tissue processing for RNA microarray, and immunofluorescence were performed...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28811488/deregulation-of-zpr1-causes-respiratory-failure-in-spinal-muscular-atrophy
#12
Naresh K Genabai, Annapoorna Kannan, Saif Ahmad, Xiaoting Jiang, Kanchan Bhatia, Laxman Gangwani
Spinal muscular atrophy (SMA) is caused by the low levels of survival motor neuron (SMN) protein and is characterized by motor neuron degeneration and muscle atrophy. Respiratory failure causes death in SMA but the underlying molecular mechanism is unknown. The zinc finger protein ZPR1 interacts with SMN. ZPR1 is down regulated in SMA patients. We report that ZPR1 functions downstream of SMN to regulate HoxA5 levels in phrenic motor neurons that control respiration. Spatiotemporal inactivation of Zpr1 gene in motor neurons down-regulates HoxA5 and causes defects in the function of phrenic motor neurons that results in respiratory failure and perinatal lethality in mice...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28811486/detecting-human-melanoma-cell-re-differentiation-following-braf-or-heat-shock-protein-90-inhibition-using-photoacoustic-and-magnetic-resonance-imaging
#13
Anant Shah, Teresa Delgado-Goni, Teresa Casals Galobart, Slawomir Wantuch, Yann Jamin, Martin O Leach, Simon P Robinson, Jeffrey Bamber, Mounia Beloueche-Babari
Targeted therapies specific to the BRAF-MEK-ERK signaling pathway have shown great promise in the treatment of malignant melanoma in the last few years, with these drugs now commonly used in clinic. Melanoma cells treated using these agents are known to exhibit increased levels of melanin pigment and tyrosinase activity. In this study we assessed the potential of non-invasive imaging approaches (photoacoustic imaging (PAI) and magnetic resonance imaging (MRI)) to detect melanin induction in SKMEL28 human melanoma cells, following inhibition of Hsp90 and BRAF signaling using 17-AAG and vemurafenib, respectively...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28811384/loss-of-spdef-and-gain-of-tgfbi-activity-after-androgen-deprivation-therapy-promote-emt-and-bone-metastasis-of-prostate-cancer
#14
Wei-Yu Chen, Yuan-Chin Tsai, Hsiu-Lien Yeh, Florent Suau, Kuo-Ching Jiang, Ai-Ning Shao, Jiaoti Huang, Yen-Nien Liu
Androgen deprivation therapy (ADT) targeting the androgen receptor (AR) is a standard therapeutic regimen for treating prostate cancer. However, most tumors progress to metastatic castration-resistant prostate cancer after ADT. We identified the type 1, 2, and 4 collagen-binding protein transforming growth factor-β (TGFβ)-induced protein (TGFBI) as an important factor in the epithelial-to-mesenchymal transition (EMT) and malignant progression of prostate cancer. In prostate cancer cell lines, AR signaling stimulated the activity of the transcription factor SPDEF, which repressed the expression of TGFBI ADT, AR antagonism, or overexpression of TGFBI inhibited the activity of SPDEF and enhanced the proliferation rates of prostate cancer cells...
August 15, 2017: Science Signaling
https://www.readbyqxmd.com/read/28811345/inhibitors-of-the-histone-methyltransferases-ezh2-1-induce-a-potent-antiviral-state-and-suppress-infection-by-diverse-viral-pathogens
#15
Jesse H Arbuckle, Paul J Gardina, David N Gordon, Heather D Hickman, Jonathan W Yewdell, Theodore C Pierson, Timothy G Myers, Thomas M Kristie
Epigenetic regulation is based on a network of complexes that modulate the chromatin character and structure of the genome to impact gene expression, cell fate, and development. Thus, epigenetic modulators represent novel therapeutic targets used to treat a range of diseases, including malignancies. Infectious pathogens such as herpesviruses are also regulated by cellular epigenetic machinery, and epigenetic therapeutics represent a novel approach used to control infection, persistence, and the resulting recurrent disease...
August 15, 2017: MBio
https://www.readbyqxmd.com/read/28811247/pharmacological-analysis-of-poecilotheria-spider-venoms-in-mice-provides-clues-for-human-treatment
#16
Alexander Andreev-Andrievskiy, Anfisa Popova, Evgeniia Lagereva, Daniil Osipov, Antonina Berkut, Eugene Grishin, Alexander Vassilevski
Bites of tiger spiders belonging to Poecilotheria genus cause moderate to severe pain and long-lasting local or generalized muscle cramps in humans. Bites occur in regions of the spiders' natural habitat, India and Sri Lanka, but the popularity of these colorful tarantulas as pets leads to reports of envenomation cases worldwide. Treatment is predominantly symptomatic and often inadequate since there is almost no clinical or toxicology research data available, and physicians outside India or Sri Lanka typically have no experience in treating such cases...
August 12, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28811128/a-newly-synthesized-ligustrazine-stilbene-derivative-inhibits-pdgf-bb-induced-vascular-smooth-muscle-cell-phenotypic-switch-and-proliferation-via-delaying-cell-cycle-progression
#17
Chunlian Peng, Siming Zhang, Haixin Liu, Yanxiao Jiao, Guifa Su, Yan Zhu
Vascular Smooth muscle cells (VSMCs) possess remarkable phenotype plasticity that allows it to rapidly adapt to fluctuating environmental cues, including the period of development and progression of vascular diseases such as atherosclerosis and restenosis subsequent to vein grafting or coronary intervention. Although VSMC phenotypic switch is an attractive target, there is no effective drug so far. Using rat aortic VSMCs, we investigate the effects of Ligustrazine and its synthetic derivatives on platelet-derived growth factor-BB (PDGF-BB) induced proliferation and phenotypic switch by a cell image-based screening of 60 Ligustrazine stilbene derivatives...
August 12, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28811106/questiomycin-a-stimulates-sorafenib-induced-cell-death-via-suppression-of-glucose-regulated-protein-78
#18
Kayo Machihara, Hidenori Tanaka, Yoshihiro Hayashi, Ichiro Murakami, Takushi Namba
Hepatocellular carcinoma (HCC) is one of the most difficult cancers to treat owing to the lack of effective chemotherapeutic methods. Sorafenib, the first-line and only available treatment for HCC, extends patient overall survival by several months, with a response rate below 10%. Thus, the identification of an agent that enhances the anticancer effect of sorafenib is critical for the development of therapeutic options for HCC. Endoplasmic reticulum (ER) stress response is one of the methods of sorafenib-induced cell death...
August 12, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28811097/type-i-collagen-promotes-primary-cilia-growth-through-down-regulating-hdac6-mediated-autophagy-in-confluent-mouse-embryo-fibroblast-3t3-l1-cells
#19
Qian Xu, Weiwei Liu, Xiaoling Liu, Wuxiyar Otkur, Toshihiko Hayashi, Masayuki Yamato, Hitomi Fujisaki, Shunji Hattori, Shin-Ichi Tashiro, Takashi Ikejima
Primary cilia are microtubule-based organelles that extend from nearly all vertebrate cells. Abnormal ciliogenesis and cilia length are suggested to be associated with hypertension and obesity as well as diseases such as Meckel-Gruber syndrome. Extracellular matrix (ECM), comprising cellular microenvironment, influences cell shape and proliferation. However, influence of ECM on cilia biogenesis has not been well studied. In this study we examined the effects of type I collagen (col I), the major component of ECM, on primary cilia growth...
August 12, 2017: Journal of Bioscience and Bioengineering
https://www.readbyqxmd.com/read/28811086/proteomic-profiling-of-the-antifungal-drug-response-of-aspergillus-fumigatus-to-voriconazole
#20
Nansalmaa Amarsaikhan, Daniela Albrecht-Eckardt, Christoph Sasse, Gerhard H Braus, Zumrut B Ogel, Olaf Kniemeyer
Antifungal resistance is an emerging problem and one of the reasons for treatment failure of invasive aspergillosis (IA). Voriconazole has become a standard therapeutic for the treatment of this often fatal infection. We studied the differentially expressed proteins as a response of Aspergillus fumigatus to voriconazole by employing the two-dimensional difference gel electrophoresis (DIGE) technique. Due to addition of drug, a total of 135 differentially synthesized proteins were identified by MALDI-TOF/TOF-mass spectrometry...
August 5, 2017: International Journal of Medical Microbiology: IJMM
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