Prostate cancer cell proliferation is influenced by leptin

BACKGROUND: Obesity is considered a risk for many cancers. Serum leptin levels are often elevated in obese people. Leptin acts as a mitogenic agent in many tissues; therefore, it may act to promote cancer cell growth. We previously demonstrated that leptin acts as a growth factor for prostate cancer cells in vitro. The purpose of this study was to characterize leptin receptor isoform mRNA expression in leptin-treated DU145 and PC-3 prostate cancer cell lines. Expression levels of SOCS-3, a known leptin-inducible suppressor of leptin signaling, and known mitogenic signaling pathways of PI3K and ERK were also analyzed METHODS: DU145 and PC-3 cells were treated with 0, 4, 40, or 80 ng/ml leptin for 0, 0.5, 1, 2, 4, 24, or 48 h. Multiplex RT-PCR was performed to determine mRNA levels of the short (huOB-Ra) or the long (huOB-Rb) OB-R isoforms or SOCS-3. p-Akt and p-ERK were determined by Western blot. Cell viability and apoptosis were determined by MTT and nucleosomal fragmentation assay RESULTS: DU145 and PC-3 expressed huOB-Ra, huOB-Rb, and SOCS-3 mRNA. huOB-Ra mRNA levels increased in PC-3 at 48 h (P < 0.01); however, no significant changes were observed in DU145. huOB-Rb mRNA levels decreased at 48 h in DU145; however, a twofold increase at 48 h (P < 0.01) was observed with PC-3 and was dose-dependent (P < 0.05). Leptin increased SOCS-3 mRNA in DU145 at 24 and 48 h (P < 0.05) and in PC-3 at 1 h (2-fold) and 48 h (fivefold; P < 0.01). Leptin up-regulated p-Akt in a time- and dose-dependent manner in the DU145 prostate cancer cells via a suppression of apoptosis. Leptin up-regulated p-ERK in a time-dependent manner in PC-3 cells CONCLUSIONS: In prostate cancer cells, the mitogenic effects of leptin are not a consequence of altered receptor isoform mRNA expression. No defect in SOCS-3 signaling was observed, and proliferation appears to be working through the PI3K and MAPK leptin receptor-activated pathways, depending on cell type. Leptin stimulation may be selective for either pathway to suppress apoptosis, thereby enhancing prostate cancer growth.     

Prostate cancer

Prostate cancer is the second commonest cause of death from malignancy amongst men in the Western world. Whilst screening for prostate cancer could reduce this mortality rate, it is controversial as most screen-detected cancers are low risk and many more men require treatment than lives saved. Current evidence suggests screening in men with little co-morbidity is beneficial if treatment is stratified to the extent and risk of the detected disease. Treatment should be aimed at disease stage and risk of metastases, and be balanced against the patient's co-morbidities. Observational protocols (such as ‘active surveillance’) should be used for men with low-risk locally confined tumours or significant co-morbidity. Radical treatments (such as radical prostatectomy or radiotherapy) should be used in men with intermediate or high-risk disease that is either confined within the prostate or at risk of local invasion/spread within the pelvis (locally advanced). Less morbid approaches are being developed for locally confined tumours. These include radiotherapy through seed implants (brachytherapy) and targeted focal therapy to obliterate regions of the prostate (delivered using high-intensity focussed ultrasound, cryotherapy or photo-thermal (Tookad) energy). These approaches are less radical and so are likely to have lower cure rates and less side effects than radical treatments. In high-volume, poorly differentiated or locally advanced tumours, it is likely that multimodal treatments are needed to obtain the highest rates of disease cure or control. Current combinations include radical surgery followed by adjuvant radiotherapy or neo-adjuvant androgen deprivation treatment (ADT) before radical radiotherapy. Ongoing trials are evaluating the benefit of adding chemotherapy and other agents to these combinational regimens. Metastatic prostate cancer is initially treated with ADT in the form of surgical or medical castration. The latter may be continuous or intermittent. Almost all men with ADT-treated metastatic prostate cancer will develop castrate-resistant disease, if they live long enough. There are now many options for the treatment of castrate-resistant prostate cancer, including first- and second-line chemotherapy, immunotherapy (sipuleucel-T), further anti-androgens (abiraterone acetate and enzalutamide) and specific bone-targeted treatments. It is likely that there will be more treatment options for advanced prostate cancer over the next few years.     

Prostate cancer

Prostate cancer is the most commonly diagnosed cancer in adult males. It has a multifactorial aetiology and its presentation varies from an indolent disease managed with surveillance to an aggressive malignancy requiring multidisciplinary treatment. Early diagnosis relies on prostate-specific antigen testing, imaging and prostate biopsy. Curative options for localized disease are guided by adequate image-guided disease stratification. New advances in treatment for advanced stages have prolonged patient survival and quality of life. This article summarises current knowledge of this complex and ever-changing disease.     

Prostate cancer antigen-1 as a potential novel marker for prostate cancer

Aim： To examine the expression of prostate cancer antigen-1 （PCA-1） in prostate cancer （PCa） and to validate it as a potential marker for diagnosis of PCa. Methods： In situ hybridization analysis of PCA-1 mRNA expression was performed on 40 benign prostate hyperplasia （BPH）, 16 high-grade prostatic intraepithelial neoplasm （HG-PIN）, 74 PCa and 34 other malignant carcinoma specimens. The level of PCA- 1 expression was semiquanfitatively scored by assessing both the percentage and intensity of PCA- 1 positive staining cells in the specimens. We then compared the PCA-1 expression between BPH, HG-PIN and PCa and evaluated the correlation of PCA-1 expression level with clinical parameters of PCa. Results： PCA-1 mRNA was expressed in the majority of both PCa and HG-PIN specimens but not in BPH and other malignant carcinoma. The expression level of PCA-1 increased along with a high Gleason score （P 〈 0.05）, and was unrelated to other clinical parameters of PCa （all P 〉 0.05）. Conclusion： The data suggest that PCA-1 might be a novel diagnostic marker for PCa, and that increased PCA-1 expression might denote more aggressive variants of PCa.     

Prostate cancer marker panel with single cell sensitivity in urine

Background

Over one million men undergo prostate biopsies annually in the United States, a majority of whom due to elevated serum PSA. More than half of the biopsies turn out to be negative for prostate cancer (CaP). The limitations of both the PSA test and the biopsy procedure have led to the development for more precise CaP detection assays in urine (e.g., PCA3, TMPRSS2‐ERG) or blood (e.g., PHI, 4K). Here, we describe the development and evaluation of the Urine CaP Marker Panel (UCMP) assay for sensitive and reproducible detection of CaP cells in post‐digital rectal examination (post‐DRE) urine.

Methods

The cellular content of the post‐DRE urine was captured on a translucent filter membrane, which is placed on Cytoclear slides for direct evaluation by microscopy and immuno‐cytochemistry (ICC). Cells captured on the membrane were assayed for PSA and Prostein expression to identify prostate epithelial cells, and for ERG and AMACR to identify prostate tumor cells. Immunostained cells were analyzed for quantitative and qualitative features and correlated with biopsy positive and negative status for malignancy.

Results

The assay was optimized for single cell capture sensitivity and downstream evaluations by spiking a known number of cells from established CaP cell lines, LNCaP and VCaP, into pre‐cleared control urine. The cells captured from the post‐DRE urine of subjects, obtained prior to biopsy procedure, were co‐stained for ERG, AMACR (CaP specific), and Prostein or PSA (prostate epithelium specific) rendering a whole cell based analysis and characterization. A feasibility cohort of 63 post‐DRE urine specimens was assessed. Comparison of the UCMP results with blinded biopsy results showed an assay sensitivity of 64% (16 of 25) and a specificity of 68.8% (22 of 32) for CaP detection by biopsy.

Conclusions

This pilot study assessing a minimally invasive CaP detection assay with single cell sensitivity cell‐capture and characterization from the post‐DRE urine holds promise for further development of this novel assay platform. Prostate 75: 969–975, 2015. © 2015 The Authors. The Prostate, published by Wiley Periodicals, Inc.     

Prostate cancer

Prostate cancer is the most common male cancer in the UK. The disease and treatment options are wide ranging, from indolent disease requiring surveillance only to an aggressive malignancy requiring active treatment. This can prove to be challenging for both the doctor and patient deciding on the best management option. Ongoing research is revolutionizing the diagnostics, risk stratification and treatment of the disease. This article aims to summarize the current knowledge of prostate cancer and treatment options available.     

Prostate cancer survival is dependent on season of diagnosis

BACKGROUND: We have earlier found that the prognosis for several cancers is dependent on season of diagnosis. More recently, both prostate cancer incidence and mortality have been shown to increase with increasing latitude, which probably relates to photosynthesis of vitamin D. METHODS: The 3 year survival of prostate cancer patients has been analyzed with the Cox regression method for two age groups at different latitudes in Norway. RESULTS: Patients diagnosed during the summer and autumn had the best prognosis (Ralative risk (RR) death 0.8; 95% CI 0.75-0.85). Similar results were observed in three regions of the country that differ with respect to annual fluences of solar UV radiation, incidence rates of squamous cell carcinoma (SCC) and intake of fish. Furthermore, similar relationship between the season and survival was seen among patients 65 years old, although the younger group had a slightly larger advantage of summer and autumn diagnosis. CONCLUSIONS: The seasonal effect on prognosis may be related to the seasonal variations of calcidiol (the marker of vitamin D status). The lack of latitude effect and the similarity of prognosis for different age groups may be related to higher consumption of vitamin D in food in the north region and to increase of such consumption with age.     

Prostate cancer

Prostate cancer is the most common male cancer in the UK representing approximately a quarter of all male cancer diagnosis. The disease and treatment options are wide ranging from a relatively benign disease requiring monitoring only, to an aggressive malignancy requiring active treatment. This can prove a challenge to both the doctor and patient deciding on the best management option. Ongoing research is revolutionizing both the diagnostics and treatment of the disease. This article aims to summarize the current knowledge of prostate cancer and treatment options available.     

BPH开放手术发现前列腺偶发癌临床分析(附15例报告)

目的：探讨提高早期前列腺癌诊断率的方法。方法：回顾性分析1999－2001年术前诊断为良性前列腺增生（BPH）患者103例的临床资料，均常规施行PSA、TRUS或DRE检查，对可疑患者施行前列腺穿刺活检，并全部施行耻骨上经膀胱前列腺切除术。结果：从103例患者中检出前列腺偶发癌15例，占手术总数的14.6%。经临床分期均为Jewett A期肿瘤。结论：开放手术治疗BPH可提高前列腺癌的检出率。     

Prostate cancer in patients with Hansen''s disease

Hansen's disease causes testicular failure secondarily, and because of this, it has been considered that prostate cancer would not be found in association. Three of 14 patients with chronic leprosy in Suruga National Sanatorium Hansen's Disease Hospital were found to have prostate cancer. A 72-year-old with lepromatous leprosy was diagnosed with stage T3a prostate cancer and treated with radical prostatectomy after hormonal therapy, plus irradiation. An 80-year-old with lepromatous leprosy was diagnosed with stage T2 prostate cancer and treated with irradiation and follow up only without hormone therapy and surgery because of his low testosterone level and old age. An 82-year-old with borderline leprosy was diagnosed with stage T1c prostate cancer and because of the pathological finding of low Gleason score and his old age, he was treated with hormonal therapy only. Two of the three cases had elevated concentrations of follicle-stimulating hormone and luteinizing hormone, which suggests that their prostatic cancers might have been equivalent to be under the influence of hormone therapy. Therefore, in aged male patients with Hansen's disease, the follicle-stimulating hormone, luteinizing hormone and testosterone concentrations should be measured, as well as that of prostate-specific antigen, and a prostate biopsy should be also considered if the prostate-specific antigen concentration is increased, even with hypogonadism.     

Prostate cancer in a Sprague-Dawley rat

An adenocarcinoma of the prostate gland developed in one rat of the Lobund Sprague-Dawley (S-D) strain, following treatments with testosterone propionate in silastic membranes. The transplanted cells (PA-SD1) developed local tumors, metastasized through lymphatic channels to the lungs, and induced osteolytic lesions when deposited adjacent to the calvarium. In vitro-propagated PA-SD1 cells produced the same tumor type in Lobund strain S-D rats as that from which it was derived.     

Prostate cancer risk prediction based on complete prostate cancer family history

BACKGROUND

Prostate cancer (PC) relative risks (RRs) are typically estimated based on status of close relatives or presence of any affected relatives. This study provides RR estimates using extensive and specific PC family history.

METHODS

A retrospective population‐based study was undertaken to estimate RRs for PC based on complete family history of PC. A total of 635,443 males, all with ancestral genealogy data, were analyzed. RRs for PC were determined based upon PC rates estimated from males with no PC family history (without PC in first, second, or third degree relatives). RRs were determined for a variety of constellations, for example, number of first through third degree relatives; named (grandfather, father, uncle, cousins, brothers); maternal, paternal relationships, and age of onset.

RESULTS

In the 635,443 males analyzed, 18,105 had PC. First‐degree RRs ranged from 2.46 (=1 first‐degree relative affected, CI = 2.39–2.53) to 7.65 (=4 first‐degree relatives affected, CI = 6.28–9.23). Second‐degree RRs for probands with 0 affected first‐degree relatives ranged from 1.51 (≥1 second‐degree relative affected, CI = 1.47–1.56) to 3.09 (≥5 second‐degree relatives affected, CI = 2.32–4.03). Third‐degree RRs with 0 affected first‐ and 0 affected second‐degree relatives ranged from 1.15 (≥1 affected third‐degree relative, CI = 1.12–1.19) to 1.50 (≥5 affected third‐degree relatives, CI = 1.35–1.66). RRs based on age at diagnosis were higher for earlier age at diagnoses; for example, RR = 5.54 for ≥1 first‐degree relative diagnosed before age 50 years (CI = 1.12–1.19) and RR = 1.78 for > 1 second‐degree relative diagnosed before age 50 years, CI = 1.33, 2.33. RRs for equivalent maternal versus paternal family history were not significantly different.

CONCLUSIONS

A more complete PC family history using close and distant relatives and age at diagnosis results in a wider range of estimates of individual RR that are potentially more accurate than RRs estimated from summary family history. The presence of PC in second‐ and even third‐degree relatives contributes significantly to risk. Maternal family history is just as significant as paternal family history. PC RRs based on a proband's complete constellation of affected relatives will allow patients and care providers to make more informed screening, monitoring, and treatment decisions. Prostate 75:390–398, 2015. © 2014 Wiley Periodicals, Inc.     

Decreased prostate cancer cell migration by inhibition of the insulin-like growth factor II/Mannose-6-Phosphate receptor

The 270-kDa insulin-like growth factor II (IGF-II)/cation-independent mannose-6-phosphate receptor (MPR) is a multifunctional receptor protein. Endocytoses and intracellular transport of soluble enzymes bearing mannose6-phosphate (M-6-P) residues to lysosomes is mediated by the IGF-II/MPR. We examined human prostate cancer cells for IGF-II/MPR expression to determine whether this receptor mediates cell migration. PC3 human prostate cancer cells were studied for intracellular IGF-II/MPR by immunoblotting. PC3 cell surface IGF-II/MPR expression was assessed by flow cytometric analysis. Cell motility was quantitated by a scratch migration assay, and IGF-II/MPR blockade was achieved using M-6-P or affinity-purified rabbit anti-bovine cation-independent IGF-II/MPR immunoglobulin. IGF-II/MPR is expressed in the cytoplasm and on the surface of PC3 prostate cancer cells. The mean number of PC3 cells migrating per high powered field in medium containing polyclonal anti-IGF-II/MPR immunoglobulin or M-6-P decreased significantly (5 ± 4 cells and 34 ± 5 cells, respectively) compared with control medium containing mouse immunoglobulin G (70 ± 12 cells) or mannose-1-phosphate (67 ± 7 cells). This decreased PC3 cell migration following cell surface IGF-II/MPR blockade suggests that the IGF-II/MPR may play an important role in prostate cancer cell motility.     

Prostate cancer

Prostate cancer is the most prevalent type of solid malignant tumour among men in UK. The incidence rate each year amongst age standardized males in the UK was 98.3/100,000. Increasing age is the strongest predeterminant for the development of prostate cancer. Virtually all prostate cancers are adenocarcinomas with their differentiation graded by means of the Gleason score. Since there are often no presenting symptoms, diagnosis is usually reliant on investigations such as digital rectal examination (DRE), the serum prostate-specific antigen (PSA) level, PCA3 m-RNA levels and biopsies guided by a trans-rectal ultrasound probe. Staging consists of magnetic resonance imaging or computed tomography for locally advanced disease and/or a bone scan for detection of bony metastases. Management depends largely on the stage of the disease. For localized prostate cancer, radical prostatectomy can offer a potential cure. Side effects include erectile dysfunction and incontinence. Prostate cancer is also radio-sensitive and can be treated by external-beam radiotherapy or brachytherapy. Hormonal therapy, such as luteinizing-hormone-releasing hormone (LHRH) analogues and anti-androgens are used in locally advanced and metastatic disease. Patients may opt for prostate-specific antigen (PSA) surveillance allowing other therapeutic options to be employed if the PSA starts to rise or the tumour progresses locally. Cytotoxic chemotherapy is increasingly being used for hormone escaped/resistant prostate cancer, and other newer treatment options are in the pipeline. The survival rate for all stages of prostate cancer is now extending.