In The Name Of God
The Books That Authored And Translated by
12 DNA Methylation status of key cell cycle regulators such as CDKNA2/p16 and CCNA1 correlates with treatment response to doxorubicin and 5-fluorouracil in locally advanced breast tumors Clinical Cancer Research, October 21, 2014
13 The contribution of unimproved water and toilet facilities to pregnancy-related mortality in Afghanistan: analysis of the Afghan Mortality Survey Tropical Medicine & International Health, October 21, 2014
17 Simultaneous changes of magnetic resonance diffusion-weighted imaging and pathological microstructure in locally advanced cervical cancer caused by neoadjuvant chemotherapy Journal of Magnetic Resonance Imaging, October 21, 2014
18 Morphological and immunohistochemical pattern of tubo-ovarian dysplasia and serous tubal intraepithelial carcinoma European Journal of Obstetrics & Gynecology and Reproductive Biology, October 21, 2014
4 Updated interim efficacy analysis and long-term safety of abiraterone acetate in metastatic castration-resistant prostate cancer patients without prior chemotherapy (COU-AA-302) Full Text European Urology, October 21, 2014
7 Resistance training reduces disability in prostate cancer survivors on androgen deprivation therapy: evidence from a randomized controlled trial Archives of Physical Medicine and Rehabilitation, October 21, 2014
15 Intracytoplasmic morphologically selected sperm injection results in improved clinical outcomes in couples with previous ICSI failures or male factor infertility: A meta-analysis European Journal of Obstetrics & Gynecology and Reproductive Biology, October 21, 2014
17 Depression of HspA2 in human testis is associated with spermatogenic impairment and fertilization rate in ICSI treatment for azoospermic individuals Journal of Assisted Reproduction and Genetics, October 21, 2014
Urology news Oct.20.2014
Raf kinase inhibitor protein (RKIP) deficiency decreases latency of tumorigenesis and increases metastasis in a murine genetic model of prostate cancer
June Escara-Wilke1, Jill M. Keller1, Kathleen M. Woods Ignatoski1,†, Gregory Shelley1, Atsushi Mizokami2, Jian Zhang3, Miranda L Yeung4, Kam C. Yeung4 andEvan T. Keller1,*
18 OCT 2014/DOI: 10.1002/pros.22915.
Raf kinase inhibitor protein (RKIP) has been shown to act as a metastasis suppressor gene in multiple models of cancer. Loss of RKIP expression promotes invasion and metastasis in cell transplantation animal models. However, it is unknown if RKIP expression can impact the progression of cancer in an autochthonous model of cancer. The goal of this study was to determine if loss of RKIP expression in a genetic mouse model of prostate cancer (PCa) impacts metastasis.
Endogenous RKIP expression was measured in the primary tumors and metastases of transgenic adenocarcinoma of the mouse prostate (TRAMP+) mice. RKIP knockout mice (RKIP−/−) were crossbred with (TRAMP+) mice to create RKIP−/−TRAMP+ mice. Mice were euthanized at 10, 20, and 30 weeks for evaluation of primary and metastatic tumor development. To determine if loss of RKIP alone promotes metastasis, RKIP was knocked down in the low metastatic LNCaP prostate cancer cell line.
Endogenous RKIP expression decreased in TRAMP+ mice as tumors progressed. Primary tumors developed earlier in RKIP−/−TRAMP+ compared to TRAMP+ mice. At 30 weeks of age, distant metastases were identified only the RKIP−/−TRAMP+ mice. While prostate epithelial cell proliferation rates were higher at 10 and 20 weeks in RKIP−/−TRAMP+ compared to TRAMP+ mice, by 30 weeks there was no difference. Apoptosis rates in both groups were similar at all timepoints. Decreased RKIP expression did not impact the metastatic rate of LNCaP in an orthotopic PCa model.
These results demonstrate that loss of RKIP decreases latency of tumor development and promotes distant metastasis in the TRAMP mouse model in the context of a pro-metastatic background; but loss of RKIP alone is insufficient to promote metastasis. These findings suggest that in addition to its known metastasis suppressor activity, RKIP may promote tumor progression through enhancing tumor initiation. Prostate © 2014 Wiley Periodicals, Inc.
Rachid Safi1, Erik R. Nelson1, Satish K. Chitneni2, Katherine J. Franz3, Daniel J. George4, Michael R. Zalutsky2, and Donald P. McDonnell1,*1Department of Pharmacology and Cancer Biology, Duke University, Durham, North Carolina. 2Department of Radiology, Duke University, Durham, North Carolina. 3Department of Chemistry, Duke University, Durham, North Carolina. 4Divisions of Medical Oncology and Urology, Duke University, Durham, North Carolina.
Previously published reports indicate that serum copper levels are elevated in patients with prostate cancer and that increased copper uptake can be used as a means to image prostate tumors. It is unclear, however, to what extent copper is required for prostate cancer cell function as we observed only modest effects of chelation strategies on the growth of these cells in vitro.
With the goal of exploiting prostate cancer cell proclivity for copper uptake, we developed a “conditional lethal” screen to identify compounds whose cytotoxic actions were manifested in a copper-dependent manner. Emerging from this screen was a series of dithiocarbamates, which, when complexed with copper, induced reactive oxygen species–dependent apoptosis of malignant, but not normal, prostate cells. One of the dithiocarbamates identified, disulfiram (DSF), is an FDA-approved drug that has previously yielded disappointing results in clinical trials in patients with recurrent prostate cancer.
Source: James Heilman, MD / Wikimedia Commons
Similarly, in our studies, DSF alone had a minimal effect on the growth of prostate cancer tumors when propagated as xenografts. However, when DSF was coadministered with copper, a very dramatic inhibition of tumor growth in models of hormone-sensitive and of castrate-resistant disease was observed. Furthermore, we determined that prostate cancer cells express high levels of CTR1, the primary copper transporter, and additional chaperones that are required to maintain intracellular copper homeostasis. The expression levels of most of these proteins are increased further upon treatment of androgen receptor (AR)–positive prostate cancer cell lines with androgens. Not surprisingly, robust CTR1-dependent uptake of copper into prostate cancer cells was observed, an activity that was accentuated by activation of AR.
Given these data linking AR to intracellular copper uptake, we believe that dithiocarbamate/copper complexes are likely to be effective for the treatment of patients with prostate cancer whose disease is resistant to classical androgen ablation therapies.
Cancer Res; 74(20); 5819–31. ©2014 AACR. July 19, 2014.
©2014 American Association for Cancer Research.
Traumatic spinal cord injury (SCI) is a devastating condition with few treatment options. Studies show that damage to the barrier separating blood from the spinal cord can contribute to the neurologic deficits that arise secondary to the initial trauma. Through...
As medical personnel and public health officials are responding to the first reported cases of Ebola Virus in the United States, many of the safety and treatment procedures for treating...
Scientists have created a drug for type 2 diabetes that is switched on by blue light, which they hope will improve treatment of the disease.
UK scientists have discovered that lung cancers can lie dormant for over 20 years before suddenly turning into an aggressive form of the disease, according to a study published in...
Even if they don't show signs of infection, college athletes who play football, soccer and other contact sports are more likely to carry the superbug methicillin-resistant Staphylococcus aureus (MRSA), suggests...
Researchers from the University of Melbourne have established how two diseases that present in similar ways are in fact quite different.
Some cancers, like breast and prostate cancer, are driven by hormones such as estrogen and testosterone, but to date, there are none that are driven by the lack of a...
Antimicrobial usage in animals in Denmark continued to increase in 2013 -- mainly due to an increased use in pigs. However, antimicrobial use in pigs is still 12% lower than...
A new, large-scale study has identified six new genetic variants associated with habitual coffee drinking. The genome-wide meta-analysis, led by Harvard School of Public Health and Brigham and Women's Hospital...
Scientists have been laboring to detect cancer and a host of other diseases in people using promising new biomarkers called "exosomes." Indeed, Popular Science magazine named exosome-based cancer diagnostics one...
A researcher who found that testosterone raised the risk of prostate tumors and exacerbated the effects of carcinogenic chemical exposure in rats is urging caution in prescribing testosterone therapy to...
Researchers from the University of Copenhagen have shown for the first time how bacteria can grow directly in the lungs of Cystic fibrosis patients, giving them the opportunity to get tremendous insights into bacteria behavior and growth in chronic infections.
Results of a small clinical trial suggest that a chemical derived from broccoli sprouts -- and best known for claims that it can help prevent certain cancers -- may ease...
A noninvasive method of delivering a promising therapy for persistent Clostridium difficile (C. difficile) infection appears to be as effective as treatment via colonoscopy or through a nasogastric tube. In...
Some people might consider mucus an icky bodily secretion best left wrapped in a tissue, but to a group of researchers from the University of North Carolina at Chapel Hill,...
Adoption of a combination of five key healthy behaviors is associated with a reduction in the risk of developing bowel cancer. Researchers from the German Institute of Human Nutrition Potsdam-Rehbruecke...
Heart attack survivors often experience dangerous heart rhythm disturbances during treatment designed to restore blood flow to the injured heart muscle, a common and confounding complication of an otherwise lifesaving...
Fad diets come and go, but might there be something to the ones that involve consuming grapefruit and grapefruit juice? New research at the University of California, Berkeley, suggests that...
UPMC Presbyterian Hospital's infection prevention teams have improved hand washing and sanitizing compliance at the hospital to nearly 100 percent among clinical staff through accountability and educational measures. In a...
The risk of having another stroke is higher if patients, after dilation of their blood vessels in the brain, not only receive clot-inhibiting drugs, but also have small tubes called...
Studying rats as model subjects, scientists found that adolescents were at an increased risk of suffering negative health effects from sugar-sweetened beverage consumption.
In a ground-breaking research project at the University of Gothenburg, seven Swedish women have had embryos reintroduced after receiving wombs from living donors. Now the first transplanted woman has delivered..
© 2014 (e) Science News
16 September 2014
Urinary incontinence adversely affects quality of life and results in an increased financial burden for the elderly. Accumulating evidence suggests a connection between neurotrophins, such as brain-derived neurotrophic factor (BDNF), and lower urinary tract function, particularly with regard to normal physiological function and the pathophysiological mechanisms of stress urinary incontinence (SUI) and bladder pain syndrome/interstitial cystitis (BPS/IC).
Figure 1: The neuromodulatory effects of BDNF in the dorsal root ganglion, in relation to lower urinary tract function.
BDNF expression is mediated by the NGF-dependent PI3K–Akt pathway. Expression of NMDA and AMPA receptors is regulated by the Ras–MAPK pathway, and modulated by BDNF–Trk-B signalling. Abbreviations: Akt, protein kinase B; AMPA, α-amino-…
Figure 2: Schematic diagram of the interaction between BDNF and glutamate receptors.
BDNF binds to the extracellular domain of Trk-B receptor, activating an intracellular signalling cascade that includes PI3K–Akt, Ras–MAPK and the PLCγ–Ca2+ pathways. a | BDNF can facilitate NMDA receptor and AMPA receptor signalling th…
The interaction between BDNF and glutamate receptors affects both bladder and external urethral sphincter function during micturition. Clinical findings indicate reduced BDNF levels in antepartum and postpartum women, potentially correlating with postpartum SUI. Experiments with animal models demonstrate that BDNF is decreased after simulated childbirth injury, thereby impeding the recovery of injured nerves and the restoration of continence.
Figure 3: BDNF regulation of lower urinary tract function.
BDNF facilitates PN function and could increase EUS muscle tone (1). Retrograde transport of BDNF from the bladder to the DRG has a role in DOA (2). BDNF-mediated glutamate signalling participates in bladder and EUS contractility (3).…
Treatment with exogenous BDNF facilitates neural recovery and the restoration of continence. Serotonin and noradrenaline reuptake inhibitors, used to treat both depression and SUI, result in enhanced BDNF levels. Understanding the neurophysiological roles of BDNF in maintaining normal urinary function and in the pathogenesis of SUI and BPS/IC could lead to future therapies based on these mechanisms.
Is chronic inhibition of phosphodiesterase type 5 cardioprotective and safe? A meta-analysis of randomized controlled trials
Elisa Giannetta1, Tiziana Feola1, Daniele Gianfrilli1, Riccardo Pofi1, Valentina Dall’Armi2, Roberto Badagliacca3, Federica Barbagallo1, Andrea Lenzi1 and Andrea M Isidori1* 1 Department of Experimental Medicine, Sapienza University of Rome, Viale del Policlinico 155, Rome 00161, Italy 2 Unit of Clinical and Molecular Epidemiology, IRCCS San Raffaele Pisana of Rome, Via della Pisana 235, Rome 00163, Italy 3 Department of Cardiovascular and Respiratory Science, Sapienza University of Rome, Piazzale Aldo Moro 5, Rome 00185, Italy
BMC Medicine 2014, 12:185 doi:10.1186/s12916-014-0185-3
20 October 2014
Background----The myocardial effects of phosphodiesterase type 5 inhibitors (PDE5i) have recently received consideration in several preclinical studies. The risk/benefit ratio in humans remains unclear.
Methods----We performed a meta-analysis of randomized, placebo-controlled trials (RCTs) to evaluate the efficacy and safety of PDE5i on cardiac morphology and function. From March 2012 to December 2013 (update: May 2014), we searched English-language studies from MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and SCOPUS-selecting RCTs of continuous PDE5i administration that reported cardiovascular outcomes: cardiac geometry and performance, afterload, endothelial function and safety. The pooled estimate of a weighted mean difference between treatment and placebo was obtained for all outcomes using a random effects model. A test for heterogeneity was performed and the I2 statistic calculated.
Results----Overall, 1,622 subjects were treated, with 954 randomized to PDE5i and 772 to placebo in 24 RCTs. According to our analysis, sustained PDE5 inhibition produced: (1) an anti-remodeling effect by reducing cardiac mass (−12.21 g/m2, 95% confidence interval (CI): −18.85; −5.57) in subjects with left ventricular hypertrophy (LVH) and by increasing end-diastolic volume (5.00 mL/m2; 95% CI: 3.29; 6.71) in non-LVH patients; (2) an improvement in cardiac performance by increasing cardiac index (0.30 L/min/m2, 95% CI: 0.202; 0.406) and ejection fraction (3.56%, 95% CI: 1.79; 5.33). These effects are parallel to a decline of N-terminal-pro brain natriuretic peptide (NT-proBNP) in subjects with severe LVH (−486.7 pg/ml, 95% CI: −712; -261). PDE5i administration also produced: (3) no changes in afterload parameters and (4) an improvement in flow-mediated vasodilation (3.31%, 95% CI: 0.53; 6.08). Flushing, headache, epistaxis and gastric symptoms were the commonest side effects.
Conclusions----This meta-analysis suggests for the first time that PDE5i have anti-remodeling properties and improve cardiac inotropism, independently of afterload changes, with a good safety profile. Given the reproducibility of the findings and tolerability across different populations, PDE5i could be reasonably offered to men with cardiac hypertrophy and early stage heart failure. Given the limited gender data, a larger trial on the sex-specific response to long-term PDE5i treatment is required.
4 Updated interim efficacy analysis and long-term safety of abiraterone acetate in metastatic castration-resistant prostate cancer patients without prior chemotherapy (COU-AA-302) Full Text European Urology, October 14, 2014
7 Whole-body 18F-fluorocholine (FCH) PET/CT and MRI of the spine for monitoring patients with castration-resistant prostate cancer metastatic to bone: A pilot study Clinical Nuclear Medicine , October 14, 2014
10 A combined prognostic serum interleukin-8 and interleukin-6 classifier for stage 1 lung cancer in the prostate, lung, colorectal, and ovarian cancer screening trial Journal of Thoracic Oncology, October 14, 2014