فوق دکترا درجراحی کلیه ومجاری ادرار ازدانشکده پزشکی دانشگاه تهران و عضو انجمن ارولوژی ایران
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كاربر میهمان خوش آمدید
Sat 16 Jul 2011

In The Name Of God

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The Books  That Authored And Translated by

Mohammad Hezarkhani

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ارسال شده توسط دکتر محمد هزارخانی در ساعت 3:32 بعد از ظهر
Thu 20 Nov 2014

Urology news  Des,2014

Jorge Luiz Alves-Pereira,Eliete Dalla Corte Frantz,Cristiane da Fonte Ramos

Laboratory of Morphometry, Metabolism and Cardiovascular Disease, Biomedical Center, Institute of Biology, State University of Rio de Janeiro, Brazil

Accepted: May 19, 2014; Published Online: May 28, 2014

DOI: http://dx.doi.org/10.1016/j.juro.2014.05.093

Purpose

We evaluated whether antihypertensive drugs that act through the renin-angiotensin system would affect testis function.

Materials and Methods

Ten mice were fed standard chow and 40 received a high energy density diet. At 8 weeks the high energy density diet mice were divided into 4 groups of 10 each. The untreated group received the high energy density diet alone. The 3 treated groups received that diet plus aliskiren (50 mg/kg daily), enalapril (30 mg/kg daily) and losartan (10 mg/kg daily), respectively, for the next 6 weeks. Blood pressure was measured twice monthly. At the end of the treatment period all mice were sacrificed. One-way ANOVA and the Holm-Sidak post hoc test were used to analyze results.

Results

The high energy density diet led to a significant increase in blood pressure (p <0.05). All treatments resulted in normalized blood pressure. In regard to reproductive function, and serum testosterone and estradiol the gene and protein expression of StAR, aromatase and luteinizing hormone receptor, and the protein expression of angiotensin-converting enzyme, renin and angiotensin type 1 receptor blocker were significantly decreased by the high energy density diet. Of the treatments only enalapril reverted the changes. Also, angiotensin-converting enzyme, angiotensin type 1 receptor blocker and renin protein expression were lower in all high energy density diet groups except the group that received enalapril.

Conclusions

Only angiotensin-converting enzyme inhibitor reverted the hormonal and testis alterations caused by the high energy density diet. This suggests that enalapril should be the drug of choice for a patient who presents with previous reproductive dysfunction.

ارسال شده توسط دکتر محمد هزارخانی در ساعت 12:47 بعد از ظهر |
Fri 31 Oct 2014

 

 

 

1 Acupuncture and immune function in chronic prostatitis/chronic pelvic pain syndrome: a randomized, controlled study Complementary Therapies in Medicine, October 31, 2014  

 

2 Increasing use of observation among men at low risk for prostate cancer mortality The Journal of Urology, October 31, 2014    

 

3 Do environmental factors modify the genetic risk of prostate cancer? Cancer Epidemiology, Biomarkers & Prevention, October 31, 2014    

 

4 Sexual partners, sexually transmitted infections, and prostate cancer risk Cancer Epidemiology, October 31, 2014    

 

5 Diffusion-weighted MRI in early assessment of tumour response to radiotherapy in high-risk prostate cancer The British Journal of Radiology, October 31, 2014    

 

6 Sequential use of the androgen synthesis inhibitors ketoconazole and abiraterone acetate in castration-resistant prostate cancer and the predictive value of circulating androgens Clinical Cancer Research, October 31, 2014  

 

7 Thromboembolic complications in 3,544 patients undergoing radical prostatectomy with or without lymph node dissection The Journal of Urology, October 31, 2014    

 

8 Intraoperative registered transrectal ultrasound guidance for robot-assisted laparoscopic radical prostatectomy The Journal of Urology, October 31, 2014    

 

9 Practice patterns and individual variability of surgeons performing radical prostatectomies at a high volume academic center The Journal of Urology, October 31, 2014   

 

10 The human agonistic CD40 antibody ADC-1013 eradicates bladder tumors and generates T cell dependent tumor immunity Clinical Cancer Research, October 31, 2014    

 

11 Radical nephroureterectomy versus endoscopic procedures for the treatment of localised upper tract urothelial carcinoma: A meta-analysis and a systematic review of current evidence from comparative studies European Journal of Surgical Oncology, October 31, 2014

 

12 Obstructed hemivagina with ipsilateral renal anomaly (OHVIRA) Journal of Pediatric and Adolescent Gynecology , October 31, 2014

 

13 The artificial somato-autonomic reflex arch does not improve lower urinary tract function in patients with spinal cord lesions The Journal of Urology, October 31, 2014

 

14 Human papillomavirus prevalence in invasive penile cancer and association with clinical outcome The Journal of Urology, October 31, 2014    

 

15 5-year longitudinal followup after retropubic and transobturator mid urethral slings The Journal of Urology, October 31, 2014   

 

16 Novel bladder preservation therapy, omc-regimen: combined therapy using balloon-occluded arterial infusion of anticancer agent and hemodialysis with concurrent radiation The Journal of Urology, October 31, 2014    

 

17 Association of moderate to severe lower urinary tract symptoms with incident type 2 diabetes and heart disease The Journal of Urology, October 31, 2014

 

18 Outcomes of endoscopic incision for the treatment of ureterocele in children at a single institution The Journal of Urology, October 31, 2014    

 

19 Characteristics and survival of end stage renal disease (ESRD) patients with spina bifida in the United States Renal Data System (USRDS) The Journal of Urology, October 31, 2014

 

20 Rates of teratoma and viable cancer at post-chemotherapy retroperitoneal lymph node dissection after induction chemotherapy for good risk non-seminomatous germ cell tumors The Journal of Urology, October 31, 2014    

ارسال شده توسط دکتر محمد هزارخانی در ساعت 8:47 بعد از ظهر |
Wed 29 Oct 2014

 

Edited by:Mohammad  Hezarkhani  MD,Urologist

Board-Certified of Urology,Tehran  University ,The Member  of  Iranian  Urological  Association

Madaen Hospital  Tehran Iran

Tehranclinic  Hospital Tehran Iran

Mohammad.hezarkhani@yahoo.com

www.Hezarkhani.blogfa.com  hosted in Washington DC, United States

October,29. 2014

 

In the genome, the GDF15 gene is localized on chromosome 19 in the region p13.1-13.2. The macrophage inhibitory cytokine (MIC-1) DNA sequence is 2,746 bp long and consists of two exons separated by an intron. A conserved TATA-like motif (TATAAA) is present nearer to the start codon.

 

The expression of GDF15/MIC-1 is upregulated by IL1β, TNFa, IL2, MCSF, TGFβ and p53. Androgen also regulates the expression of GDF15/MIC-1 in vitro and in vivo. In prostate cancer cells, calcitriol induces GDF15/MIC-1 expression. Furthermore, it has been shown that the basal transcription of MIC-1 gene is regulated by Sp1 and Sp3.

 

 

Description

The premature GDF/PDF/MIC-1 protein consists of 308 amino acids that contain a 29 amino acid signal peptide, a 167 amino acid propeptide, and a 112 amino acid mature protein. The mature protein is secreted as a homodimer linked by disulfide bonds and is released from the propeptide following intracellular cleavage at RXXR furine-like cleavage site. The mature peptide of GDF-1/MIC-1 contains two additional cysteine residues in addition to the seven conserved cysteines necessary for the cysteine knot, a structural hallmark of this TGF-β superfamily. The exact function of these two additional cysteine residues is still unknown. The propeptide has a consensus N-linked glycosylation site in it. Unlike all other TGF-β superfamily members, MIC-1 mature peptide can be correctly folded and secreted without a propeptide. The propeptide plays a novel role in proteosomal targeting of the monomeric precursor and ensures that only dimeric precursor exists in the endoplasmic reticulum.

Expression

GDF15/PDF/MIC-1 is expressed at high levels in placenta, adult prostate, skin and at a low level in several other tissues including colon, kidney and fetal brain.

Localisation

MIC-1 is an extracelluarly localized secretory protein.

Function

GDF15/MIC-1 plays diverse biological functions in varied cellular context. It has been proposed that GDF15/MIC-1 can regulate the late phase macrophage activation by inhibiting TNF-a as an autocrine/paracrine regulatory molecule. Its role in the early stages of endochondrial bone formation, hematopoietic development, embryonic implantation and placental function has been reported. Animal studies have shown the role of GDF15/MIC-1 as a central regulator of appetite and body weight. For midbrain dopaminergic neurons, GDF15/MIC-1 acts as a both neurotrophic and neuroprotective factor, in vitro and in vivo. A role of GDF15/MIC-1 in cancer progression has also been reported by impacting on cell signaling.

Homology

It shares a significant homology with the GDF15 gene of Pan troglodytes, Bos Taurus and Canis lupus familiaris. In addition, it is also similar to Gdf15 gene of Mus musculus and Rattus norvegicus.

 

 

Entity

Various Cancers

Disease

GDF15/MIC-1 over expression is associated with different cancers, including gastric, pancreatic, prostate and colorectal cancer. It has been shown that measurement of serum GDF15/MIC-1 level aids in the diagnosis of prostrate and pancreatic cancer.

Prognosis

Recently, a direct association of elevated serum GDF15/MIC-1 and metastatic prostrate, colorectal, and breast cancer has been reported. Additionally, higher serum GDF15/MIC-1 level was correlated with higher incidence of lymph node metastasis and shorter relapse and shorter overall survival period.

Oncogenesis

The oncogenic property of GDF15/MIC-1 in different cancer has been reported. In prostrate cancer, it promotes AR-positive prostrate cancer cell proliferation trough the activation of ERK1 / ERK2 signal pathway. Additionally, GDF15 promotes the drug resistance property of prostrate cancer cells. The role of GDF15/MIC-1 in promoting the invasive property of gastric cancer cells has been reported. This may be due to GDF15/MIC-1 mediated up-regulation of Urokinase-type plasminogen activator system. In contrast, some studies have reported an antitumorigenic role of GDF15/MIC-1 in colon, breast and glioblastoma cell lines. Most of these reports suggest a role of GDF15/MIC-1 in the induction of apoptosis via both p53-dependent and independent mechanisms.

 

 

Entity

Thalassemia

Disease

Expanded erythroid compartment secrete high level of GDF15, which leads to iron overload in thalassemia syndromes by inhibiting hepcidin expression.

 

 

A new study by Lambert et al. in the journal Prostate proposes that some forms of chronic prostatic inflammation, driven by low levels of a molecule known as growth differentiation factor-15 (GDF-15), may lead to prostate cancer development. Why? Because GDF-15 is normally highly expressed in the prostate and low levels of GDF-15 can lead to chronic prostatic inflammation and tumorigenesis.

In an associated post on the blog site of the University of Colorado Cancer Center, the authors also explain that the gene for GDF-15 is known to be upregulated by vitamin D, and that this gene is “notably absent” in samples of human prostate cancer driven by inflammation. Thus, if men have low levels of vitamin D, they may be at high risk for prostatic inflammation, which may drive certain subtypes of prostate cancer. (Not all prostate cancers are necessarily caused by inflammation, but some certainly are.)

It would be premature to conclude, on the basis of this one study, that the majority of prostate cancers are being caused by low levels of vitamin D and an associated risk for chronic prostatic inflammation. However, Lambert and his colleagues have developed an interesting hypothesis that does lead to ideas about new ways to prevent development of at least some types of prostate cancer. This is just an hypothesis at the present time, but we look forward to seeing whether the hypothesis can be validated.

References:

1-GDF15 (growth differentiation factor 15)

Atlas of Genetics and Cytogenetics in Oncology and Haematology   Oct,14,2014

2-GDF-15, vitamin D, and risk for prostate cancer

October 23, 2014 by Sitemaster /THE "NEW" PROSTATE CANCER INFOLINK

ارسال شده توسط دکتر محمد هزارخانی در ساعت 10:43 قبل از ظهر |
Thu 23 Oct 2014

 

Urology News

Oct.23,2014

 

1 Particle radiotherapy for prostate cancer International Journal of Urology, October 23, 2014

 

2 Meta-analysis of nonsteroidal anti-inflammatory drug intake and prostate cancer risk World Journal of Surgical Oncology, October 23, 2014  

 

3 Androgen receptor splice variants contribute to prostate cancer aggressiveness through induction of EMT and expression of stem cell marker genes The Prostate, October 23, 2014

 

4 Quality of life improvement for patients treated with degarelix versus leuprorelin in advanced prostate cancer The Journal of Urology, October 23, 2014   

 

5 Predictive value of magnetic resonance imaging determined tumor contact length for extra-capsular extension of prostate cancer The Journal of Urology, October 23, 2014   

 

6 A systematic review of experience of 180w xps greenlight laser vaporization of the prostate in 1640 men BJU International, October 23, 2014    

 

7 Clinical utility of 18F-fluorocholine PET-CT in biochemical relapse of prostate cancer after radical treatment: Results of a multicentre study BJU International, October 23, 2014

 

8 Efficacy and safety of radium-223 dichloride in patients with castration-resistant prostate cancer and symptomatic bone metastases, with or without previous docetaxel use: A prespecified subgroup analysis from the randomised, double-blind, phase 3 ALSYMPCA trial The Lancet Oncology, October 23, 2014    

 

9 Risk of acute myocardial infarction after androgen deprivation therapy for prostate cancer in the Chinese population BJU International, October 23, 2014   

 

10 Nocturnal enuresis is associated with moderate-to-severe obstructive sleep apnea in children with snoring Pediatric Research, October 23, 2014    

 

11 International multicenter psychometric evaluation of patient reported outcome data for the treatment of Peyronie's disease BJU International, October 23, 2014   

 

12 Development of the lymphoedema genito-urinary cancer questionnaire British Journal of Nursing, October 23, 2014

 

13 Mechanistic analysis of nonoxygenated hypothermic machine perfusions protection on warm ischemic kidney uncovers greater enos phosphorylation and vasodilation American Journal of Transplantation, October 23, 2014  

 

14 Diarrhea after kidney transplantation: a new look at a frequent symptom Transplantation, October 23, 2014    

 

15 A systematic review of the use of rituximab for desensitization in renal transplantation Transplantation, October 23, 2014    

 

16 Aluminum content of human semen: Implications for semen quality Reproductive Toxicology, October 23, 2014

 

17 Pheochromocytoma as the first manifestation of MEN2A with RET mutation S891A: report of a case Surgery Today, October 23, 2014    

 

18 Retraction-related acute liver failure after urological laparoscopic surgery Current Urology, October 23, 2014

 

19 Recurrent 2,8-Dihydroxyadenine nephropathy: A rare but preventable cause of renal allograft failure American Journal of Transplantation, October 23, 2014    

 

20 Elective urological surgery following coronary stent implantation: to whom, how to do it? Current Urology, October 23, 2014   

ارسال شده توسط دکتر محمد هزارخانی در ساعت 4:54 بعد از ظهر |
Tue 21 Oct 2014

 

Oct.21.2014

1 Healthy Lifestyle Behaviors of Breast Cancer Survivors Clinical Nursing Research, October 21, 2014  

 

2 Is there a relationship between endometrial polyps and obesity, diabetes mellitus, hypertension? Archives of Gynecology and Obstetrics, October 21, 2014

 

3 Use of medical, surgical and complementary treatments among women with fibroids European Journal of Obstetrics & Gynecology and Reproductive Biology, October 21, 2014

 

4 Identification of women at high risk for severe perineal lacerations European Journal of Obstetrics & Gynecology and Reproductive Biology, October 21, 2014  

 

5 Calcitonin gene- and parathyroid hormone-related peptides in normotensive and preeclamptic pregnancies: A nested case-control study Archives of Gynecology and Obstetrics, October 21, 2014    

 

6 Adherence to healthy lifestyle and risk of gestational diabetes mellitus: prospective cohort study BMJ, October 21, 2014

 

7 The prevention and treatment of postpartum haemorrhage: What do we know, and where do we go to next? BJOG: An International Journal of Obstetrics and Gynaecology, October 21, 2014

 

8 Two follicle-stimulating hormone receptor polymorphisms and polycystic ovary syndrome risk: A meta-analysis European Journal of Obstetrics & Gynecology and Reproductive Biology, October 21, 2014   

 

9 Interaction between TP63 and MDM2 genes and the risk of recurrent pregnancy loss European Journal of Obstetrics & Gynecology and Reproductive Biology, October 21, 2014

 

10 Urine cortisol concentration as a biomarker of stress is unrelated to IVF outcomes in women and men Journal of Assisted Reproduction and Genetics, October 21, 2014

 

11 Effect of implementation of the mass breast cancer screening programme in older women in the Netherlands: population based study BMJ, October 21, 2014  

 

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  

 

14 Predicting breast tumor response to neoadjuvant chemotherapy with Diffuse Optical Spectroscopic Tomography prior to treatment Clinical Cancer Research, October 21, 2014

 

15 Early origins of adult disease: Low birth weight and vascular remodelling Atherosclerosis, October 21, 2014

 

16 Serum anti-Mullerian hormone levels across different ethnic groups: A cross-sectional study BJOG: An International Journal of Obstetrics and Gynaecology, 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    

 

19 Single incision sling (Ajust) for the treatment of female stress urinary incontinence: 2-year follow-up European Journal of Obstetrics & Gynecology and Reproductive Biology, October 21, 2014  

 

20 Borderline ovarian tumor in women aged ≥65 years: Impact on recurrence and survival European Journal of Obstetrics & Gynecology and Reproductive Biology, October 21, 2014

ارسال شده توسط دکتر محمد هزارخانی در ساعت 7:59 بعد از ظهر |
Tue 21 Oct 2014

 

Oct.21.2014

1 Diethylstilboestrol (1 mg) in the management of castration-resistant prostate cancer Urologia Internationalis, October 21, 2014   

 

2 Obesity is associated with risk of progression for low-risk prostate cancers managed expectantly Full Text European Urology, October 21, 2014    

 

3 Patterns of repeat prostate biopsy utilization in contemporary clinical practice The Journal of Urology, 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   

 

5 The cistrome and gene signature of androgen receptor splice variants in castration-resistant prostate cancer cells The Journal of Urology, October 21, 2014    

 

6 Family history in the Finnish Prostate Cancer Screening Trial International Journal of Cancer, 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   

 

8 AZD1152-HQPA induces growth arrest and apoptosis in androgen-dependent prostate cancer cell line (LNCaP) via producing aneugenic micronuclei and polyploidy Tumor Biology, October 21, 2014    

 

9 Avoiding and managing vascular injury during robotic-assisted radical prostatectomy Therapeutic Advances in Urology, October 21, 2014

 

10 Phase 2 trial of neoadjuvant axitinib in patients with locally advanced nonmetastatic clear cell renal cell carcinoma European Urology, October 21, 2014    

 

11 The potential role of stem cells in the treatment of urinary incontinence Therapeutic Advances in Urology, October 21, 2014

 

12 Association between predonation serum uric acid concentration and change in renal function after living kidney donation in women Internal Medicine Journal, October 21, 2014

 

13 Surgical Technique for Laparoscopic Kidney Donation Zentralblatt für Chirurgie - Zeitschrift für Allgemeine, Viszeral-, Thorax- und Gefäßchirurgie, October 21, 2014

 

14 Single incision sling (Ajust) for the treatment of female stress urinary incontinence: 2-year follow-up European Journal of Obstetrics & Gynecology and Reproductive Biology, 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

 

16 Fetal diagnosis of testicular torsion: What shall we tell the parents? Prenatal Diagnosis, 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

 

18 Relationship between absence of annulus and asthenozoospermia in Iranian men Journal of Assisted Reproduction and Genetics, October 21, 2014   

 

19 Surgical management of early and late ureteral complications after renal transplantation: techniques and outcomes Clinical Transplantation, October 21, 2014  

 

20 Does presumed consent save lives? Evidence from Europe Health Economics, October 21, 2014   

Source:MDLINX

ارسال شده توسط دکتر محمد هزارخانی در ساعت 2:40 بعد از ظهر |
Mon 20 Oct 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.

BACKGROUND

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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.

ارسال شده توسط دکتر محمد هزارخانی در ساعت 9:45 بعد از ظهر |
Mon 20 Oct 2014

 

Oct.20.2014

Smoking Raises Prostate Cancer Death Risk

Aspirin May Reduce Risk of Aggressive Prostate Cancer

Neuroendocrine (Small-Cell) Carcinomas: Why They Teach Us Essential Lessons About Prostate Cancer.

Raf kinase inhibitor protein (RKIP) deficiency decreases latency of tumorigenesis and increases metastasis in a murine genetic model of prostate cancer

ADDENDUM: Increased Akt Signaling Resulting from the Loss of Androgen Responsiveness in Prostate Cancer. Dulinska-Litewka J, McCubrey JA, Laidler P. Curr. Med. Chem., 2013, 20(1), 144-157.

Role of miRNA Let-7 and Its Major Targets in Prostate Cancer.

Estrogen receptor, progesterone receptor, interleukin-6 and interleukin-8 are variable in breast cancer and benign stem/progenitor cell populations

A Pilot Study of Estradiol Followed by Exemestane for Reversing Endocrine Resistance in Postmenopausal Women With Hormone Receptor-Positive Metastatic Breast Cancer.

TGF-β1 mediates the radiation response of prostate cancer

Androstenedione is the preferred androgen source in hormone refractory prostate cancer-response.

ارسال شده توسط دکتر محمد هزارخانی در ساعت 9:34 بعد از ظهر |
Mon 20 Oct 2014

Research news

Oct.20.2014

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.

Prostate cancer cells self-destruct when a copper-activated drug is delivered to the infected cells, research finds

Source: James Heilman, MD / Wikimedia Commons

Prostate cancer cell growth reduced when a copper-activated drug is used, research suggests

 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.

ارسال شده توسط دکتر محمد هزارخانی در ساعت 11:45 قبل از ظهر |