Review Article
Pages: 1 - 5DOI:
Review Article
Pages: 1 - 9Swapna Kolukula and Robert J. Anderson
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Research Article
Pages: 1 - 8Sergey Shishkin, Marina Kovaleva, Alexei Ivanov, Lidia Eryomina, Ksenia Lisitskaya, Ilia Toropygin, Leonid Kovalev, Valeria Okhritz and Oleg Loran
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Comparative proteomic studies of proteins in DU-145, PC-3, LNCaP and BPH-1 cultivated cells as well as in prostate tissue samples obtained from patients with benign and malignant tumors showed differences in protein profiles, in particular, high content in tissue samples of four isoforms of transgelin and profilin-1. Increased expression of protein Dj-1 was observed in cancer cells and biopsy samples of prostate cancer as opposed to BPH-1 cells and biopsy samples of tissues with benign hyperplasia. Dramatic reduction of serpin H1 was noted in the range of cell lines: BPH-1 → PC-3 → DU-145 → LNCaP. Thus, the obtained data are indicative of protein Dj-1 and serpin H1 participation in formation of the cancer phenotype in prostate cells
Research Article
Pages: 1 - 5Arig Ibrahim-Hashim, Jonathan W. Wojtkowiak, Maria de Lourdes Coelho Ribeiro, Veronica Estrella, Kate M. Bailey, Heather H. Cornnell, Robert A. Gatenby and Robert J Gillies
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Background: Malignant tumor cells typically metabolize glucose anaerobically to lactic acid even under normal oxygen tension, a phenomenon called aerobic glycolysis or the Warburg effect. This results in increased acid production and the acidification of the extracellular microenvironment in solid tumors. H + ions tend to flow along concentration gradients into peritumoral normal tissue causing extracellular matrix degradation and increased tumor cell motility thus promoting invasion and metastasis. We have shown that reducing this acidity with sodium bicarbonate buffer decreases the metastatic fitness of circulating tumor cells in prostate cancer and other cancer models. Mathematical models of the tumor-host dynamics predicted that buffers with a pka around 7 will be more effective in reducing intra- and peri-tumoral acidosis and, thus, and possibly more effective in inhibiting tumor metastasis than sodium bicarbonate which has a pKa around 6. Here we test this prediction the efficacy of free base lysine; a non-bicarbonate / non-volatile buffer with a higher pKa (~10), on prostate tumor metastases model.
Methods: Oxygen consumption and acid production rate of PC3M prostate cancer cells and normal prostate cells were determined using the Seahorse Extracellular Flux (XF-96) analyzer. In vivo effect of 200 mM lysine started four days prior to inoculation on inhibition of metastasis was examined in PC3M-LUC-C6 prostate cancer model using SCID mice. Metastases were followed by bioluminescence imaging.
Results: PC3M prostate cancer cells are highly acidic in comparison to a normal prostate cell line indicating that reduction of intra- and perit-tumoral acidosis should inhibit metastases formation. In vivo administration of 200 mM free base lysine increased survival and reduced metastasis.
Conclusion: PC3M prostate cancer cells are highly glycolytic and produce large amounts of acid when compared to normal prostate cells. Administration of non-volatile buffer decreased growth of metastases and improved survival indicating acidity plays a significant role in growth and invasion in-vivo.
Research Article
Pages: 1 - 6Panagiotis J. Vlachostergios, Foteini Karasavvidou, Grigorios Kakkas, George Moutzouris, Anna Patrikidou, Ioannis A. Voutsadakis, Kassiani Kapatou, Danai D. Daliani, Michael D. Melekos and Christos N. Papandreou
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Background: Loss of the membrane endopeptidase CD10 plays an important role in the development of neuropeptide-mediated androgen-independent prostate cancer cell growth. The aim of this study was to investigate the potential prognostic value of the CD10/neuropeptide axis with regard to prostate-specific antigen (PSA) failure after radical prostatectomy in early prostate cancer patients.
Methods: Tumor samples from 70 early prostate cancer patients who underwent radical prostatectomy were immunohistochemically evaluated for expression of CD10 and endothelin-1 (ET-1). The examined parameters were prospectively correlated with time to PSA failure and combined with Gleason grade and pathological TNM stage.
Results: Membranous and apical cytoplasmic expression of CD10 was directly correlated with time to PSA failure ( P < 0.001). Cytoplasmic ET-1 was inversely correlated with time to PSA relapse ( P = 0.002). CD10 and ET-1 were inversely interrelated ( P < 0.001). CD10 expression (P = 0.012) and stage ( P = 0.013) were independent predictors of biochemical recurrence.
Conclusion: CD10 and ET-1 follow inverse patterns of expression in tumors of early prostate cancer patients, in accordance with their biological roles and molecular interrelations. Evaluation of CD10 expression in early prostate cancer might contribute to a better prediction of PSA relapse-free survival after radical prostatectomy.
Research Article
Pages: 1 - 6Eduardo De Stefani, Hugo Deneo-Pellegrini, Alvaro L Ronco, Paolo Boffetta and Giselle Acosta
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Background: Loss of the membrane endopeptidase CD10 plays an important role in the development of neuropeptide-mediated androgen-independent prostate cancer cell growth. The aim of this study was to investigate the potential prognostic value of the CD10/neuropeptide axis with regard to prostate-specific antigen (PSA) failure after radical prostatectomy (RP) in early prostate cancer (PC) patients.
Methods: Tumor samples from 70 early PC patients who underwent RP were immunohistochemically evaluated for expression of CD10 and endothelin-1 (ET-1). The examined parameters were prospectively correlated with time to PSA failure and combined with Gleason grade and pathological TNM stage.
Results: Membranous and apical cytoplasmic expression of CD10 was directly correlated with time to PSA failure ( P < 0.001). Cytoplasmic ET-1 was inversely correlated with time to PSA relapse ( P = 0.002). CD10 and ET-1 were inversely interrelated ( P < 0.001). CD10 expression (P = 0.012) and stage ( P = 0.013) were independent predictors of biochemical recurrence.
Conclusion: CD10 and ET-1 follow inverse patterns of expression in tumors of early PC patients, in accordance with their biological roles and molecular interrelations. Evaluation of CD10 expression in early PC might contribute to a better prediction of PSA relapse-free survival after RP.
Research Article
Pages: 1 - 3Adnan Sımsır, Cag Cal, Rashad Mammadov, Ibrahim Cureklıbatır and Gurhan Gunaydın
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Purpose: It is well-known that indicators such as biopsy and prostatectomy Gleason score , clinical and pathological stage and preoperative PSA level can be utilized in predicting PSA recurrence in cases who underwent radical prostatectomy (RP) with the diagnosis of organ-confined prostate cancer. The purpose of this study was to investigate the predictability of postoperative PSA recurrence by serum total testosterone levels as well as body mass index (BMI).
Materials and methods: Fourty-eight patients in whom RP was planned with the diagnosis of prostate-confined cancer were enrolled in this study. The data recorded included the patient’s preoperative testosterone levels and BMI as well as age, serum PSA level, clinical stage, Gleason score on biopsy, the presence of PIN and surgical margin positivity. After operation, the patients were kept under follow up according to the guidelines. During the follow-up, the analysis of the selected markers was performed using T-test, Mann-Whitney U test, Chi square test, Anova and Roc analysis in cases with documented PSA recurrence.
Results: Serum total testosterone level, BMI, surgical margin positivity and Gleason score and preoperative PSA level are independent variables that affect PSA recurrence. On Roc analysis, a testosterone level of less than 2,81 ng/dL was found to be significant for the prediction of PSA recurrence (p=0.04).
Conclusion: From this study, we concluded that, besides proven risk factors for PSA recurrence (Pre op. PSA level, Gleason score, surgical margin positivity and stage), preoperative low testosterone levels and high BMI can also be predictive.
Research Article
Pages: 1 - 7Serge Grabtchak, Tyler J. Palmer and William M. Whelan
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Background: We have developed a new approach to map localized inclusions of gold nanoparticles in the Intralipid-1% liquid phantom. Our goal was to show that combined spectroscopic and angular snapshots of liquid phantoms and phantoms with inclusions allow obtaining information relevant for prostate cancer diagnostics and treatment.
Methods: A combination of the point radiance spectroscopy and white light spectroscopy was used to measure angular resolved light distribution in 450-900 nm spectral range in Intralipid-1% liquid phantoms with and without localized inclusions of gold nanoparticles.
Results: Characteristic spectro-angular snapshots of the liquid phantom alone and with the localized inclusion of gold nanoparticles were obtained. For liquid phantoms without inclusions, the snapshots demonstrate wavelength dependent light distribution inside the turbid medium, visualize the transparency window and provide a quantification of angular spread of different wavelengths of light. For liquid phantoms with gold inclusions, the approach allows to isolate the spectroscopic signatures of the inclusions from the background, identify locations of the inclusions in the angular domain and quantify the detection limits in terms of the contrast value attainable for the selected quantity of gold nanoparticles located at the specific depth in tissue. A detection of 3x10 13 particles up to 25 mm deep in Intralipid-1% was demonstrated.
Conclusions: The encouraging results indicate a promising potential of radiance spectroscopy in prostate treatment and diagnostics with gold nanoparticles.
Case Report
Pages: 1 - 4MG Cristofaro, Giudice A, Colangeli W, Giofrè E, Riccelli U and M Giudice
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Prostate cancer is the most frequently diagnosed cancer in men and the second leading cause of cancer death among men in the United States. The most common site of prostate cancer metastasis is the bone, with skeletal metastases identified at autopsy in up to 90% of patients dying from prostate cancer. The route of metastasis to bone is thought the prostatic venous plexus draining with the vertebral veins. In this report jaw bones metastases occur before the patient has been diagnosed a primary tumour; in a smaller rate their diagnoses coincides with the diagnosis of the primary tumour. Data reported in literature a low incidence of jaw bones metastases; they are even less recurrent in mandibular condyles owing to their low red bone marrow (hematopoietic active) content in adulthood. Just in a few exceptional cases, like this case, bone metastases is the first clinical evidence of an occult or initial cancer, a site occurs above all in prostate, bladder and lung cancer. Our case are exceptional because the mandibular condyle metastasis was the first clinical sign of an occult primary prostate carcinoma, whose early diagnosis made the treatment of both (primary tumour and sigle metastasis) more effective.
Research Article
Pages: 1 - 5Syed M Nazim, Farhat Abbas, Nuzhat Faruqui, Muhammad Islam and Zubair Ahmad
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Objectives: To establish the usefulness and validity of 2007 Partin’s table in our population with prostate cancer.
Materials and methods: Between January 1998 to June 2009, all patients with clinically localized carcinoma prostate who were treated with intent of radical retro-pubic prostatectomy (RRP) were included. Clinical, operative and pathological data was gathered. All biopsy and final histopathology Gleason scores were re-assigned in a double blind manner. Pre-operative serum PSA, TNM clinical stage and biopsy Gleason scores were plotted on Partin’s table and its predictive value and pathological findings of specimen were compared and analyzed by using Receiver operating characteristic (ROC) analysis.
Results: A total of 109 of 138 patients were included in final analysis. The median age was 65 ± 5.8 years. The pre-operative serum PSA values and clinical stages were higher in our cohort of patients as compared to Partin’s cohort. At pathological assessment of resected specimen, organ confined disease was present in 58 % of patients, seminal vesicles were involved in 22 % and lymph node metastasis was present in 12 % of patients. The accuracy of Partin’s table derived probability was high with area under curve (AUC) of 0.82 for organ confinement, 0.805 for seminal vesicle involvement and 0.714 for lymph node involvement respectively.
Conclusions: The 2007 Partin’s table has a reasonably high predictive value for the final histo-pathological features. This predictive model can be used in Pakistani patients with carcinoma prostate with comparable accuracy.
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