Ureteric stricture secondary to unusual extension of prostatic adenocarcinoma.

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Chalasani, Venu; Macek, Petr; O'Neill, Gordon F; Barret, Wade

2010-02-01

This article describes an unusual finding in a patient who presented with an adenocarcinoma of the prostate and right hydronephrosis. A 68-year-old male presented with right hydronephrosis and a PSA of 96. DRE was consistent with cT3 carcinoma. Cystoscopy showed an exophytic superficial transitional cell carcinoma (TCC) of the bladder and a transrectal biopsy of the prostate confirmed adenocarcinoma Gleason score 4+3. Staging investigations (CT pelvis and bone scan) were negative; androgen deprivation therapy was therefore initiated for the prostatic adenocarcinoma. Upper tract imaging showed multiple filling defects in the proximal ureter. Ureteroscopy showed a stricture at the level of the iliac vessels. With a working diagnosis of upper tract TCC, right open nephroureterectomy was performed. Final histology showed prostatic adenocarcinoma infiltrating the adventitia of the entire ureter up to the level of the renal pelvis. A rare cause of ureteric stricture, contiguous spread of prostatic adenocarcinoma, should be considered in the differential diagnosis of patients presenting with upper tract obstruction and a known history of prostatic adenocarcinoma. Androgen deprivation therapy for several months did not seem to cause resolution of the tumor in the periureteric, ureteric and perihilar tissues.

Multiple urinary bladder masses from metastatic prostate adenocarcinoma

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Richard Choo

2010-12-01

Full Text Available We present an unusual case of metastatic prostate adenocarcinoma that manifested with multiple exophytic intravesical masses, mimicking a multifocal primary bladder tumor. Biopsy with immunohistochemical analysis confirmed metastatic prostate adenocarcinoma. The patient was treated palliatively with external beam radiotherapy to prevent possible symptoms from local tumor progression. This case illustrates that when a patient with known prostate cancer presents with multifocal bladder tumors, the possibility of metastatic prostate cancer should be considered.

Metastatic prostate adenocarcinoma penis: Case report

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Pablo Santiago Caicedo

2014-08-01

Full Text Available Objective: Describe a case report of a patient with prostatic adenocarcinoma metastatic to penis due to shortage reports of similar cases to perform a literature review. Methods: We identified a case of a patient with prostatic adenocarcinoma, who during de the course of a cystoscopy at Hospital Universitario San Jose (Third-level Public Hospital in Popayan, Colombia a suspicious nodule of malignancy was observed in the penis. We described the clinical case in order to proceed to a literature search for the discussion. Results: 72-year-old patient diagnosed with prostatic adenocarcinoma Gleason Score 4+5=9, treated with bilateral orchiectomy and a suspicious nodule of malignancy incidentally observed in the penis, currently undergoing palliative care with Karnofsky score of 30 points. Conclusion: cutaneous metastases are rare; indicate longstanding disease and poor prognosis.

Generalized Lymphadenopathy: Unusual Presentation of Prostate Adenocarcinoma

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Bulent Cetin

2011-01-01

Full Text Available Generalized lymphadenopathy is a rare manifestation of metastatic prostate cancer. Here, we report the case of a 59-year-old male patient with supraclavicular, mediastinal, hilar, and retroperitoneal and inguinal lymphadenopathy, which suggested the diagnosis of lymphoma. There were no urinary symptoms. A biopsy of the inguinal lymph node was compatible with adenocarcinoma, whose prostatic origin was shown by immunohistochemical staining with PSA. The origin of the primary tumor was confirmed by directed prostate biopsy. We emphasize that a suspicion of prostate cancer in men with adenocarcinoma of undetermined origin is important for an adequate diagnostic and therapeutic approach.

Treatment of Hormone Resistance with Docetaxel in Metastatic Prostate Cancer Patients: Results of a Clinical Experience at Omid Hospital, Isfahan, Iran

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Mina Tajvidi

2017-01-01

Full Text Available Background: Metastatic prostate cancer is one of the most important cancers among men worldwide. Androgen ablation therapy can be used in treatment of these patients; however, most will progress to metastatic hormone-refractory prostate cancer. In this regard, docetaxel has been approved to treat metastatic hormone-refractory prostate cancer in the United States. In this study, we aimed to investigate the results of this treatment modality in metastatic prostate cancer patients from Iran. Methods:We evaluated PSA response and bone pain relief in 18 metastatic prostate cancer patients who underwent treatment with docetaxel at a dose of 75 mg/m2 intravenously on the first day of treatment. The treatment was repeated every three weeks (6 cycles along with 10 mg of prednisolone. Results: Of 18 patients, 39% had >50% decline in PSA levels.There were 16% of the patients with a PSA decline of approximately 30% to 50% of the pre-treatment levels. In addition, 29% of the patients had progressive PSA levels during chemotherapy. Among them, 55% had significant pain relief. Conclusion: This research showed the effectiveness of docetaxel to decrease PSA levels in metastatic hormone-refractory prostate cancer patients from Iran. Docetaxel was also valuable in alleviation of pain in these patients. However, prospective studies should validate this approach.

Ductal adenocarcinoma of the prostate: immunohistochemical findings and clinical significance

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Sha JJ

2013-10-01

Full Text Available Jianjun Sha,1,2 Juanjie Bo,1 Jiahua Pan,1 Lianhua Zhang,1 Hanqing Xuan,1 Wei Chen,1 Dong Li,1 Zhaoliang Wang,1 Dongming Liu,1 Yiran Huang1,2 1Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 2School of Biomedical Engineering, Shanghai Jiaotong University, Shanghai, People's Republic of China Introduction: To investigate the clinical features, diagnosis, treatment, and prognosis of ductal adenocarcinoma of the prostate. Methods: The clinicopathological and immunohistochemical data of seven patients with ductal adenocarcinoma of the prostate were retrospectively analyzed. All patients underwent physical examination, magnetic resonance imaging (MRI, bone scan, cystoscopy, and computed tomography (CT scan. The level of prostate-specific antigen (PSA before and after surgery was assessed. Different prostate cancer markers were used for immunohistochemical staining. Results: The mean age of the seven patients diagnosed with prostatic ductal adenocarcinoma in this study was 76.2 years (range 57–88. Five patients presented with intermittent and painless gross hematuria, one patient with progressive dysuria, and one patient with elevated serum PSA on routine health examination. The level of PSA before surgery ranged from 1.3 to 45.0 ng/mL. Immunohistochemical staining results of the prostatic ductal adenocarcinoma confirmed positivity for PSA, prostatic acid phosphatase, androgen receptor, and alpha-methyacyl co-enzyme A (CoA-reductase markers. Two of the patients underwent bilateral orchiectomy combined with anti-androgen therapy, three underwent transurethral resection of prostate, one received radical prostatectomy, and one received medical castration therapy. The clinical outcomes of all patients were satisfactory, based on follow-up data. The symptoms of hematuria and dysuria were ameliorated well, and the postoperative PSA level decreased below 4.0 ng/mL. Recurrence or metastasis of disease was

The use of combined radiation therapy and hormonal therapy in the management of lymph node-positive prostate cancer

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Whittington, Richard; Malkowicz, S Bruce; Machtay, Mitchell; Van Arsdalen, Keith; Barnes, Margaret M; Broderick, Gregory A; Wein, Alan J

1997-10-01

Purpose: To determine the rate of tumor response and patterns of relapse following combined hormonal-radiation therapy of adenocarcinoma of the prostate and to measure the survival in a group of men with tumor metastatic to pelvic lymph nodes. Methods and Materials: 66 patients with adenocarcinoma of the prostate with pathologically confirmed pelvic lymph node involvement were treated with combined radiation therapy and hormonal therapy. An additional five patients declined hormonal therapy. The patients treated with combined therapy represented a group with locally advanced disease including 44 patients (67%) with T3 or T4 tumors and 51 patients (80%) had N2 or N3 lymph node metastases. The pelvic lymph nodes were treated to a dose of 45 Gy and the prostate was boosted to a dose of 65 to 71 Gy. Hormonal therapy began up to 2 months before radiation and continued indefinitely. Patients were allowed to select their hormonal therapy and could choose DES (2 patients), orchiectomy (21 patients), LHRH agonist (7 patients) or combined androgen blockade (34 patients). Results: Median follow-up is 49 months (range 12 to 131 months) and 21 patients have been followed for longer than 5 years. There have been 15 recurrences the entire group including three local recurrences in the prostate, seven patients with distant metastases, four patients with biochemical recurrences without clinical evidence of disease, and one patient where the location was unknown. Two of the PSA recurrences occurred in patients who elected to discontinue hormones after less than 3 years of therapy. The overall survival at 5 and 8 years is 94 and 84%, the clinical disease free survival is 85 and 67%, and the biochemical disease-free survival is 78 and 47%. There was no increased toxicity of the combined modality regimen compared to the expected effects of radiation and hormonal therapy. Conclusion: Combined hormonal and radiation therapy represents an effective treatment option for patients with

The use of combined radiation therapy and hormonal therapy in the management of lymph node-positive prostate cancer

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Whittington, Richard; Malkowicz, S. Bruce; Machtay, Mitchell; Van Arsdalen, Keith; Barnes, Margaret M.; Broderick, Gregory A.; Wein, Alan J.

1997-01-01

Purpose: To determine the rate of tumor response and patterns of relapse following combined hormonal-radiation therapy of adenocarcinoma of the prostate and to measure the survival in a group of men with tumor metastatic to pelvic lymph nodes. Methods and Materials: 66 patients with adenocarcinoma of the prostate with pathologically confirmed pelvic lymph node involvement were treated with combined radiation therapy and hormonal therapy. An additional five patients declined hormonal therapy. The patients treated with combined therapy represented a group with locally advanced disease including 44 patients (67%) with T3 or T4 tumors and 51 patients (80%) had N2 or N3 lymph node metastases. The pelvic lymph nodes were treated to a dose of 45 Gy and the prostate was boosted to a dose of 65 to 71 Gy. Hormonal therapy began up to 2 months before radiation and continued indefinitely. Patients were allowed to select their hormonal therapy and could choose DES (2 patients), orchiectomy (21 patients), LHRH agonist (7 patients) or combined androgen blockade (34 patients). Results: Median follow-up is 49 months (range 12 to 131 months) and 21 patients have been followed for longer than 5 years. There have been 15 recurrences the entire group including three local recurrences in the prostate, seven patients with distant metastases, four patients with biochemical recurrences without clinical evidence of disease, and one patient where the location was unknown. Two of the PSA recurrences occurred in patients who elected to discontinue hormones after less than 3 years of therapy. The overall survival at 5 and 8 years is 94 and 84%, the clinical disease free survival is 85 and 67%, and the biochemical disease-free survival is 78 and 47%. There was no increased toxicity of the combined modality regimen compared to the expected effects of radiation and hormonal therapy. Conclusion: Combined hormonal and radiation therapy represents an effective treatment option for patients with

Clinical and MRI features of prostate sarcoma: comparison with prostate adenocarcinoma

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Ding Jianping; Wang Xiaoying; Wang Zhenzhong; Zhou Liangping; Jiang Xuexiang

2004-01-01

Objective: To summarize the clinical and imaging features of prostate sarcoma, and to compare the features with those of prostate adenocarcinoma (PCa). Method: Six cases of prostate sarcoma proved pathologically were enrolled in this study. The clinical material and imaging features were compared with those of the PCa. Results: (1) Pathological result: Among the 6 prostate sarcomas, 3 were rhabdomyosarcoma, 1 was leiomyosarcoma, and 2 were sarcoma originated from interstitial tissue that could not be classified. (2) Clinical result: The 6 patients of sarcoma were younger (median age 36.5, 15-71 years) than the patients of PCa (median age 72, 50-78 years) (P -3 ng/L] was normal and lower than that of the PCa patients [median 27.80, (1.55-352.00) x 10 -3 ng/ L] (P 3 ) was larger than that of PCa (median 41.57, 17.16-179.44 cm 3 ) (P 2 -weighted images, with grossly normal structure of the prostate. Excapsular extension was more common in the sarcomas than in the PCa (83.3% vs 66.7%). Conclusion: The clinical and imaging features of prostate sarcoma are different from those of prostate adenocarcinoma

Yes-Associated Protein Expression Is Correlated to the Differentiation of Prostate Adenocarcinoma

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Myung-Giun Noh

2017-07-01

Full Text Available Background Yes-associated protein (YAP in the Hippo signaling pathway is a growth control pathway that regulates cell proliferation and stem cell functions. Abnormal regulation of YAP was reported in human cancers including liver, lung, breast, skin, colon, and ovarian cancer. However, the function of YAP is not known in prostate adenocarcinoma. The purpose of this study was to investigate the role of YAP in tumorigenesis, differentiation, and prognosis of prostate adenocarcinoma. Methods The nuclear and cytoplasmic expression of YAP was examined in 188 cases of prostate adenocarcinoma using immunohistochemistry. YAP expression levels were evaluated in the nucleus and cytoplasm of the prostate adenocarcinoma and the adjacent normal prostate tissue. The presence of immunopositive tumor cells was evaluated and interpreted in comparison with the patients’ clinicopathologic data. Results YAP expression levels were not significantly different between normal epithelial cells and prostate adenocarcinoma. However, YAP expression level was significantly higher in carcinomas with a high Gleason grades (8–10 than in carcinomas with a low Gleason grades (6–7 (p < .01. There was no statistical correlation between YAP expression and stage, age, prostate-specific antigen level, and tumor volume. Biochemical recurrence (BCR–free survival was significantly lower in patients with high YAP expressing cancers (p = .02. However high YAP expression was not an independent prognostic factor for BCR in the Cox proportional hazards model. Conclusions The results suggested that YAP is not associated with prostate adenocarcinoma development, but it may be associated with the differentiation of the adenocarcinoma. YAP was not associated with BCR.

Clinicopathologic features of incidental prostatic adenocarcinoma in radical cystoprostatectomy specimens

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Vuruskan Hakan

2011-07-01

Full Text Available Abstract Background The aim of this study is to review all features of incidentally discovered prostate adenocarcinoma in patients undergoing radical cystoprostatectomy for bladder cancer. Methods The medical charts of 300 male patients who underwent radical cystoprostatectomy for bladder cancer between 1997 and 2005 were retrospectively reviewed. The mean age of the patients was 62 (range 51-75 years. Results Prostate adenocarcinoma was present in 60 (20% of 300 specimens. All were acinar adenocarcinoma. Of these, 40 (66.7% were located in peripheral zone, 20 (33.3% had pT2a tumor, 12 (20% had pT2b tumor, 22(36.7% had pT2c and, 6 (10% had pT3a tumor. Gleason score was 6 or less in 48 (80% patients. Surgical margins were negative in 54 (90% patients, and tumor volume was less than 0.5 cc in 23 (38.3% patients. Of the 60 incidentally detected cases of prostate adenocarcinoma 40 (66.7% were considered clinically significant. Conclusion Incidentally detected prostate adenocarcinoma is frequently observed in radical cystoprostatectomy specimens. The majority are clinically significant.

SOCS2 mediates the cross talk between androgen and growth hormone signaling in prostate cancer

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Iglesias Gato, Diego; Chuan, Yin Choy; Wikström, Pernilla

2014-01-01

) as mediator of the cross talk between androgens and GH signals in the prostate and its potential role as tumor suppressor in prostate cancer (PCa). We observed that SOCS2 protein levels assayed by immunohistochemistry are elevated in hormone therapy-naive localized prostatic adenocarcinoma in comparison...... of transcription 5 protein (STAT5) and androgen receptor-dependent transcription. Consequentially, SOCS2 inhibits GH activation of Janus kinase 2, Src and STAT5 as well as both cell invasion and cell proliferation in vitro. In vivo, SOCS2 limits proliferation and production of IGF-1 in the prostate in response......Anabolic signals such as androgens and the growth hormone/insulin-like growth factor 1 (GH/IGF-1) axis play an essential role in the normal development of the prostate but also in its malignant transformation. In this study, we investigated the role of suppressor of cytokine signaling 2 (SOCS2...

TMPRSS2-ERG gene fusions are infrequent in prostatic ductal adenocarcinomas.

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Lotan, Tamara L; Toubaji, Antoun; Albadine, Roula; Latour, Mathieu; Herawi, Mehsati; Meeker, Alan K; DeMarzo, Angelo M; Platz, Elizabeth A; Epstein, Jonathan I; Netto, George J

2009-03-01

Ductal adenocarcinoma of the prostate is an unusual subtype that may be associated with a more aggressive clinical course, and is less responsive to conventional therapies than the more common prostatic acinar adenocarcinoma. However, given its frequent association with an acinar component at prostatectomy, some have challenged the concept of prostatic ductal adenocarcinoma as a distinct clinicopathologic entity. We studied the occurrence of the TMPRSS2-ERG gene fusion, in 40 surgically resected ductal adenocarcinoma cases, and in their associated acinar component using fluorescence in situ hybridization. A group of 38 'pure' acinar adenocarcinoma cases matched with the ductal adenocarcinoma group for pathological grade and stage was studied as a control. Compared with the matched acinar adenocarcinoma cases, the TMPRSS2-ERG gene fusion was significantly less frequently observed in ductal adenocarcinoma (45 vs 11% of cases, P=0.002, Fisher's exact test). Here, of the ductal adenocarcinoma cases with the gene fusion, 75% were fused through deletion, and the remaining case was fused through translocation. The TMPRSS2-ERG gene fusion was also rare in the acinar component of mixed ductal-acinar tumors when compared with the pure acinar adenocarcinoma controls (5 vs 45%, P=0.001, Fisher's exact test). In 95% of the ductal adenocarcinoma cases in which a concurrent acinar component was analyzed, there was concordance for presence/absence of the TMPRSS2-ERG gene fusion between the different histologic subtypes. In the control group of pure acinar adenocarcinoma cases, 59% were fused through deletion and 41% were fused through translocation. The presence of the TMPRSS2-ERG gene fusion in some cases of prostatic ductal adenocarcinoma supports the concept that ductal adenocarcinoma and acinar adenocarcinoma may be related genetically. However, the significantly lower rate of the gene fusion in pure ductal adenocarcinoma cases underscores the fact that genetic and biologic

Prospective trial of an herbal formula BYSH and Saw palmetto in patients with hormonal refractory prostate cancer: a pilot study.

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Ng, Anthony C-F; Cheng, K-F; Leung, P-C

2014-01-01

BYSH, a herbal formula, was evaluated for efficacy and safety in a pilot study for patients with advanced hormone refractory prostate cancer (HRPC). The pilot study was designed as a single-center open-label trial. Patients with HRPC were treated with BYSH for 24 weeks. The primary end point was the changes in serum prostate-specific antigen (PSA) level. Safety parameters such as liver and renal functions were monitored during the study period. Ten patients were eligible for the study. Most of them had stable PSA levels while taking BYSH. However, at the end of the BYSH treatment, the level of PSA increased. The median survival from diagnosis of HRPC was 16.4 months. Liver and renal functions remained normal. BYSH was well tolerated and no patient reported adverse events during the study period. Although it is inappropriate to make a conclusion based on the pilot study results, the trend of improvement is obvious. Further investigations should be conducted to demonstrate its clinical benefits. We have also briefly reviewed some plant products which are patented and also available in market.

TMPRSS2-ERG gene fusion status in minute (minimal) prostatic adenocarcinoma.

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Albadine, Roula; Latour, Mathieu; Toubaji, Antoun; Haffner, Michael; Isaacs, William B; A Platz, Elizabeth; Meeker, Alan K; Demarzo, Angelo M; Epstein, Jonathan I; Netto, George J

2009-11-01

Minute prostatic adenocarcinomas are considered to be of insufficient virulence. Given recent suggestions of TMPRSS2-ERG gene fusion association with aggressive prostatic adenocarcinoma, we evaluated the incidence of TMPRSS2-ERG fusion in minute prostatic adenocarcinomas. A total of 45 consecutive prostatectomies with minute adenocarcinoma were used for tissue microarray construction. A total of 63 consecutive non-minimal, Gleason Score 6 tumors, from a separate PSA Era prostatectomy tissue microarray, were used for comparison. FISH was carried out using ERG break-apart probes. Tumors were assessed for fusion by deletion (Edel) or split (Esplit), duplicated fusions and low-level copy number gain in normal ERG gene locus. Minute adenocarcinomas: Fusion was evaluable in 32/45 tumors (71%). Fifteen out of 32 (47%) tumors were positive for fusion. Six (19%) were of the Edel class and 7 (22%) were classified as combined Edel+Esplit. Non-minute adenocarcinomas (pT2): Fusion was identified in 20/30 tumors (67%). Four (13%) were of Edel class and 5 (17%) were combined Edel+Esplit. Duplicated fusions were encountered in 5 (16%) tumors. Non-minute adenocarcinomas (pT3): Fusion was identified in 19/33 (58%). Fusion was due to a deletion in 6 (18%) tumors. Seven tumors (21%) were classified as combined Edel+Esplit. One tumor showed Esplit alone. Duplicated fusions were encountered in 3 (9%) cases. The incidence of duplicated fusions was higher in non-minute adenocarcinomas (13 vs 0%; P=0.03). A trend for higher incidence of low-level copy number gain in normal ERG gene locus without fusion was noted in non-minute adenocarcinomas (10 vs 0%; P=0.07). We found a TMPRSS2-ERG fusion rate of 47% in minute adenocarcinomas. The latter is not significantly different from that of grade matched non-minute adenocarcinomas. The incidence of duplicated fusion was higher in non-minute adenocarcinomas. Our finding of comparable rate of TMPRSS2-ERG fusion in minute adenocarcinomas may argue

A basal stem cell signature identifies aggressive prostate cancer phenotypes

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Smith, Bryan A.; Sokolov, Artem; Uzunangelov, Vladislav; Baertsch, Robert; Newton, Yulia; Graim, Kiley; Mathis, Colleen; Cheng, Donghui; Stuart, Joshua M.; Witte, Owen N.

2015-01-01

Evidence from numerous cancers suggests that increased aggressiveness is accompanied by up-regulation of signaling pathways and acquisition of properties common to stem cells. It is unclear if different subtypes of late-stage cancer vary in stemness properties and whether or not these subtypes are transcriptionally similar to normal tissue stem cells. We report a gene signature specific for human prostate basal cells that is differentially enriched in various phenotypes of late-stage metastatic prostate cancer. We FACS-purified and transcriptionally profiled basal and luminal epithelial populations from the benign and cancerous regions of primary human prostates. High-throughput RNA sequencing showed the basal population to be defined by genes associated with stem cell signaling programs and invasiveness. Application of a 91-gene basal signature to gene expression datasets from patients with organ-confined or hormone-refractory metastatic prostate cancer revealed that metastatic small cell neuroendocrine carcinoma was molecularly more stem-like than either metastatic adenocarcinoma or organ-confined adenocarcinoma. Bioinformatic analysis of the basal cell and two human small cell gene signatures identified a set of E2F target genes common between prostate small cell neuroendocrine carcinoma and primary prostate basal cells. Taken together, our data suggest that aggressive prostate cancer shares a conserved transcriptional program with normal adult prostate basal stem cells. PMID:26460041

A case with primary signet ring cell adenocarcinoma of the prostate and review of the literature

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Orcun Celik

2014-06-01

Full Text Available Primary signet cell carcinoma of the prostate is a rare histological variant of prostate malignancies. It is commonly originated from the stomach, colon, pancreas, and less commonly in the bladder. Prognosis of the classical type is worse than the adenocarcinoma of the prostate. Primary signet cell adenocarcinoma is diagnosed by eliminating the adenocarcinomas of other organs such as gastrointestinal tract organs. In this case report, we present a case with primary signet cell adenocarcinoma of the prostate who received docetaxel chemotherapy because of short prostate specific antigen doubling time.

Proliferative activity of benign human prostate, prostatic adenocarcinoma and seminal vesicle evaluated by thymidine labeling

International Nuclear Information System (INIS)

Meyer, J.S.; Sufrin, G.; Martin, S.A.

1982-01-01

The thymidine labeling index (TLI) was measured in vitro in the epithelium and stroma of benign prostate glands and seminal vesicles and in the epithelium of prostatic adenocarcinomas. The mean epithelial TLI of normal peripheral (posterior) prostatic zone was 0.12 per cent, and that of the normal central (deep) zone was 0.11 per cent. Mean normal stromal TLI's were 0.08 per cent and 0.06 per cent, respectively. The mean TLI of epithelium in nodular hyperplasia was 0.31 per cent, which differs significantly from normal epithelium, and the mean stromal TLI was also increased. The mean TLI of prostatic adenocarcinomas was 0.90 per cent (range 0.14 to 3.90 per cent) which was significantly higher than for either normal epithelium or epithelium of nodular hyperplasia. Trends of increasing TLI with increasing histologic grades and increasing nuclear size and numbers of nucleoli were not significant. The data support participation of both epithelial and stromal proliferation in nodular hyperplasia, and indicate a low basal proliferative rate in normal prostatic glands. The low TLI's of prostatic adenocarcinomas relative to other malignancies are consistent with their frequently slowly progressive course. The very low proliferative rate of seminal vesicular epithelium may account for the rarity of seminal vesicular carcinomas

Adenosine deaminase complexing protein (ADCP) expression and metastatic potential in prostatic adenocarcinomas.

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Dinjens, W N; Ten Kate, J; Kirch, J A; Tanke, H J; Van der Linden, E P; Van den Ingh, H F; Van Steenbrugge, G J; Meera Khan, P; Bosman, F T

1990-03-01

The expression of the adenosine deaminase complexing protein (ADCP) was investigated by immunohistochemistry in the normal and hyperplastic human prostate, in 30 prostatic adenocarcinomas, and in seven human prostatic adenocarcinoma cell lines grown as xenografts in athymic nude mice. In the normal and hyperplastic prostate, ADCP was localized exclusively in the apical membrane and the apical cytoplasm of the glandular epithelial cells. In prostatic adenocarcinomas, four distinct ADCP expression patterns were observed: diffuse cytoplasmic, membranous, both cytoplasmic and membranous, and no ADCP expression. The expression patterns were compared with the presence of metastases. We found an inverse correlation between membranous ADCP immunoreactivity and metastatic propensity. Exclusively membranous ADCP immunoreactivity occurred only in non-metastatic tumours. In contrast, the metastatic tumours showed no or diffuse cytoplasmic ADCP immunoreactivity. This suggests that immunohistochemical detection of ADCP might predict the biological behaviour of prostatic cancer. However, the occurrence of membranous ADCP immunoreactivity in the xenograft of a cell line (PC-EW), derived from a prostatic carcinoma metastasis, indicates that not only the tendency to metastasize modulates ADCP expression.

Proliferative activity of benign human prostate, prostatic adenocarcinoma and seminal vesicle evaluated by thymidine labeling

International Nuclear Information System (INIS)

Meyer, J.S.; Sufrin, G.; Martin, S.A.

1982-01-01

The thymidine labeling index (TLI) was measured in vitro in the epithelium and stroma of benign prostate glands and seminal vesicles and in the epithelium of prostatic adenocarcinomas. The mean epithelial TLI of normal peripheral (posterior) prostatic zone was 0.12 percent, and that of the normal central (deep) zone was 0.11 percent. Mean normal stromal TLI's were 0.08 percent and 0.06 percent, respectively. The mean TLI of epithelium in nodular hyperplasia was 0.31 percent, which differs significantly from normal epithelium (p less than 0.05), and the mean stromal TLI was also increased (0.16 percent, p less than 0.1). The mean TLI of prostatic adenocarcinomas was 0.90 percent (range 0.14 to 3.90 percent) which was significantly higher than for either normal epithelium (p less than 0.001) or epithelium of nodular hyperplasia (p less than 0.05). Trends of increasing TLI with increasing histologic grades and increasing nuclear size and numbers of nucleoli were not significant. The data support participation of both epithelial and stromal proliferation in nodular hyperplasia, and indicate a low basal proliferative rate in normal prostatic glands. The low TLI's of prostatic adenocarcinomas relative to other malignancies are consistent with their frequently slowly progressive course. The very low proliferative rate of seminal vesicular epithelium (mean TLI 0.02 percent) may account for the rarity of seminal vesicular carcinomas

Combination therapy with hormonal, radiation and chemotherapy for stage C prostate cancer

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Iwasawa, Toshihisa; Matsumoto, Hidetsugu

1996-01-01

To improve the effectiveness of treatment for patients with stage C prostate cancer, therapy in combination with hormonal, radiation and chemotherapy was given for the initial period, and there after, hormonal therapy was continuously administered to 18 patients with chemotherapy and three patients without it. At the Social Health Insurance Medical Center, between May 1988 and August 1991, 21 patients were diagnosed to have stage C histologically confirmed adenocarcinoma of the prostate. The average age of the patients was 69.0 years. The tumor was well, moderate and poorly differentiated in 5, 6 and 10 patients, respectively. As hormonal therapy, orchiectomy was performed on 19 of the 21 patients. Furthermore, 11 patients were administered estramustine phosphate, 9 chlormadinone acetate, and one diethylstilbesterol diphosphate. As, radiation therapy, all patients were treated with AP-PA parallel opposing technique to small pelvis with a 12 cm x 12 cm treatment field (44-45 Gy) combined with conformation radiotherapy to prostate (20-26 Gy). Chemotherapy was performed using either one or a combination of the following; cis-diamminedichloroplatinum, adriamycin, cyclophosphamide, 5-fluorouracil, methotrexate and etoposide. The observation period was 54.5 months on the average. Recurrence was observed in 3 patients, for all of which the sites were at bone. The 5-year non-recurrence rate was 90.4% by Kaplan-Meier's method. There were 4 deaths, three were due to prostate cancer and one to gastric cancer. The 5-year cumulative survival rate by Kaplan-Meier's method was 90.5%. In conclusion, this treatment was effective for stage C cases of prostate cancer. (author)

Radiation therapy of newly diagnosed, advanced prostatic cancer and hormonally relapsed prostatic cancer

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Suzuki, Minoru; Fujiwara, Kazuhisa; Hayakawa, Katsumi; Hida, Shuichi

1994-01-01

Ten patients with newly diagnosed, advanced prostatic cancer were treated with radiotherapy and hormone therapy to improve tumor control and survival. Eight patients with hormonally relapsed prostatic cancer were treated with radiotherapy to improve their quality of life. Local control of the tumor was achieved in 9 of 10 patients with newly diagnosed, advanced prostatic cancer. Five of eight patients with hormonally relapsed prostatic cancer obtained improved quality of life. Combined radiotherapy and hormone therapy were effective in the treatment of newly diagnosed, advanced prostatic cancer, and radiotherapy was useful for improving the quality of life of patients with hormonally relapsed prostatic cancer. (author)

Carcinoid tumor of the verumontanum (colliculus seminalis of the prostatic urethra with a coexisting prostatic adenocarcinoma: a case report

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Werahera Priya N

2010-01-01

Full Text Available Abstract Introduction Urethral carcinoid tumors are very rare tumors with only four cases described in the literature. Case presentation We present the case of a 61-year-old man with a primary carcinoid tumor of the verumontanum (colliculis seminalis portion of the prostatic urethra with a coexisting prostatic adenocarcinoma. In addition to whole mount hematoxylin and eosin staining, special immunoperoxidase staining specific for chromogranin A, neuron specific enolase, synaptophysin, pan-cytokeratin and PSA, and a special combined staining for racemase (α-methyl CoA antigen and p63 antigen were performed. A review of the literature is included. A single focus of invasive prostatic adenocarcinoma was identified in the periphery of the mid-left, posterior quadrant of the prostate. Approximately 17 mm from this adenocarcinoma, within the verumontanum of the prostatic urethra, there was a 3 mm maximal dimension carcinoid tumor. Conclusion Based on different histological features and antigenic profiles, we concluded that the two tumors were distinct.

Transmembrane prostatic acid phosphatase (TMPAP interacts with snapin and deficient mice develop prostate adenocarcinoma.

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Ileana B Quintero

Full Text Available The molecular mechanisms underlying prostate carcinogenesis are poorly understood. Prostatic acid phosphatase (PAP, a prostatic epithelial secretion marker, has been linked to prostate cancer since the 1930's. However, the contribution of PAP to the disease remains controversial. We have previously cloned and described two isoforms of this protein, a secretory (sPAP and a transmembrane type-I (TMPAP. The goal in this work was to understand the physiological function of TMPAP in the prostate. We conducted histological, ultra-structural and genome-wide analyses of the prostate of our PAP-deficient mouse model (PAP(-/- with C57BL/6J background. The PAP(-/- mouse prostate showed the development of slow-growing non-metastatic prostate adenocarcinoma. In order to find out the mechanism behind, we identified PAP-interacting proteins byyeast two-hybrid assays and a clear result was obtained for the interaction of PAP with snapin, a SNARE-associated protein which binds Snap25 facilitating the vesicular membrane fusion process. We confirmed this interaction by co-localization studies in TMPAP-transfected LNCaP cells (TMPAP/LNCaP cells and in vivo FRET analyses in transient transfected LNCaP cells. The differential gene expression analyses revealed the dysregulation of the same genes known to be related to synaptic vesicular traffic. Both TMPAP and snapin were detected in isolated exosomes. Our results suggest that TMPAP is involved in endo-/exocytosis and disturbed vesicular traffic is a hallmark of prostate adenocarcinoma.

Transmembrane Prostatic Acid Phosphatase (TMPAP) Interacts with Snapin and Deficient Mice Develop Prostate Adenocarcinoma

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Quintero, Ileana B.; Herrala, Annakaisa M.; Araujo, César L.; Pulkka, Anitta E.; Hautaniemi, Sampsa; Ovaska, Kristian; Pryazhnikov, Evgeny; Kulesskiy, Evgeny; Ruuth, Maija K.; Soini, Ylermi; Sormunen, Raija T.; Khirug, Leonard; Vihko, Pirkko T.

2013-01-01

The molecular mechanisms underlying prostate carcinogenesis are poorly understood. Prostatic acid phosphatase (PAP), a prostatic epithelial secretion marker, has been linked to prostate cancer since the 1930's. However, the contribution of PAP to the disease remains controversial. We have previously cloned and described two isoforms of this protein, a secretory (sPAP) and a transmembrane type-I (TMPAP). The goal in this work was to understand the physiological function of TMPAP in the prostate. We conducted histological, ultra-structural and genome-wide analyses of the prostate of our PAP-deficient mouse model (PAP−/−) with C57BL/6J background. The PAP−/− mouse prostate showed the development of slow-growing non-metastatic prostate adenocarcinoma. In order to find out the mechanism behind, we identified PAP-interacting proteins byyeast two-hybrid assays and a clear result was obtained for the interaction of PAP with snapin, a SNARE-associated protein which binds Snap25 facilitating the vesicular membrane fusion process. We confirmed this interaction by co-localization studies in TMPAP-transfected LNCaP cells (TMPAP/LNCaP cells) and in vivo FRET analyses in transient transfected LNCaP cells. The differential gene expression analyses revealed the dysregulation of the same genes known to be related to synaptic vesicular traffic. Both TMPAP and snapin were detected in isolated exosomes. Our results suggest that TMPAP is involved in endo-/exocytosis and disturbed vesicular traffic is a hallmark of prostate adenocarcinoma. PMID:24039861

Immunohistochemical profiles of claudin-3 in primary and metastatic prostatic adenocarcinoma

Directory of Open Access Journals (Sweden)

Becich Michael J

2011-01-01

Full Text Available Abstract Background Claudins are integral membrane proteins that are involved in forming cellular tight junctions. One member of the claudin family, claudin-3, has been shown to be overexpressed in breast, ovarian, and pancreatic cancer. Here we use immunohistochemistry to evaluate its expression in benign prostatic hyperplasia (BPH, prostatic intraepithelial neoplasia (PIN, normal tissue adjacent to prostatic adenocarcinoma (NAC, primary prostatic adenocarcinoma (PCa, and metastatic prostatic adenocarcinoma (Mets. Methods Tissue microarrays were immunohistochemically stained for claudin-3, with the staining intensities subsequently quantified and statistically analyzed using a one-way ANOVA with subsequent Tukey tests for multiple comparisons or a nonparametric equivalent. Fifty-three cases of NAC, 17 cases of BPH, 35 cases of PIN, 107 cases of PCa, and 55 cases of Mets were analyzed in the microarrays. Results PCa and Mets had the highest absolute staining for claudin-3. Both had significantly higher staining than BPH (p Conclusions To our knowledge, this represents one of the first studies comparing the immunohistochemical profiles of claudin-3 in PCa and NAC to specimens of PIN, BPH, and Mets. These findings provide further evidence that claudin-3 may serve as an important biomarker for prostate cancer, both primary and metastatic, but does not provide evidence that claudin-3 can be used to predict risk of metastasis.

Nanodiamonds enhance therapeutic efficacy of doxorubicin in treating metastatic hormone-refractory prostate cancer.

Science.gov (United States)

Salaam, Amanee D; Hwang, Patrick T J; Poonawalla, Aliza; Green, Hadiyah N; Jun, Ho-wook; Dean, Derrick

2014-10-24

Enhancing therapeutic efficacy is essential for successful treatment of chemoresistant cancers such as metastatic hormone-refractory prostate cancer (HRPC). To improve the efficacy of doxorubicin (DOX) for treating chemoresistant disease, the feasibility of using nanodiamond (ND) particles was investigated. Utilizing the pH responsive properties of ND, a novel protocol for complexing NDs and DOX was developed using a pH 8.5 coupling buffer. The DOX loading efficiency, loading on the NDs, and pH responsive release characteristics were determined utilizing UV-Visible spectroscopy. The effects of the ND-DOX on HRPC cell line PC3 were evaluated with MTS and live/dead cell viability assays. ND-DOX displayed exceptional loading efficiency (95.7%) and drug loading on NDs (23.9 wt%) with optimal release at pH 4 (80%). In comparison to treatment with DOX alone, cell death significantly increased when cells were treated with ND-DOX complexes demonstrating a 50% improvement in DOX efficacy. Of the tested treatments, ND-DOX with 2.4 μg mL(-1) DOX exhibited superior efficacy (60% cell death). ND-DOX with 1.2 μg mL(-1) DOX achieved 42% cell death, which was comparable to cell death in response to 2.4 μg mL(-1) of free DOX, suggesting that NDs aid in decreasing the DOX dose necessary to achieve a chemotherapeutic efficacy. Due to its enhanced efficacy, ND-DOX can be used to successfully treat HRPC and potentially decrease the clinical side effects of DOX.

MALT lymphoma and concurrent adenocarcinoma of the prostate: a rare case report and review of the literature.

Directory of Open Access Journals (Sweden)

Jung Julie Kang

2010-07-01

Full Text Available Primary MALT lymphoma of the prostate is a rare disease which characteristically follows an indolent course. It is believed that infection or chronic inflammation may be triggers for malignant transformation in the prostate, but it is of unknown etiology. Reports of MALT lymphomas of the prostate with other concurrent primary prostate cancers are even more limited. We present the unique case of a 67 year old male with concurrent adenocarcinoma of the prostate and primary MALT lymphoma of the prostate. The patient was treated with standard therapy for prostate adenocarcinoma, which also sufficiently would treat a primary MALT lymphoma. He has been disease-free for over one year for both his primary malignancies. This case confirms that MALT lymphoma can arise concurrently with adenocarcinoma of the prostate.

Synchronous prostate and rectal adenocarcinomas irradiation utilising volumetric modulated arc therapy

OpenAIRE

Ng, Sweet Ping; Tran, Thu; Moloney, Philip; Sale, Charlotte; Mathlum, Maitham; Ong, Grace; Lynch, Rod

2015-01-01

Abstract Cases of synchronous prostate and colorectal adenocarcinomas have been sporadically reported. There are case reports on patients with synchronous prostate and rectal cancers treated with external beam radiotherapy alone or combined with high?dose rate brachytherapy boost to the prostate. Here, we illustrate a patient with synchronous prostate and rectal cancers treated using the volumetric arc therapy (VMAT) technique. The patient was treated with radical radiotherapy to 50.4 Gy in 2...

Prostatic Adenocarcinoma with Concurrent Sertoli Cell Tumor in a Dog

Science.gov (United States)

Gill, C. W.

1981-01-01

A case of metastatic prostatic adenocarcinoma with concurrent Sertoli cell tumor is presented in an old, miniature Schnauzer dog. The prostatic neoplasm was highly anaplastic and had metastasized widely. Clinical signs were compatible with increased estrogen production. It is interesting to note that the prostatic carcinoma, usually considered to be androgen dependent, developed and metastasized, despite the presence of apparently increased estrogen levels. ImagesFigure 1.Figure 2.Figure 3.Figure 4.Figure 5.Figure 6. PMID:7340923

Co-existence of mucin-producing urothelial-type adenocarcinoma of the prostate and inverted papilloma of the bladder

Directory of Open Access Journals (Sweden)

Xiao-Nan Mu

2017-06-01

Full Text Available Adenocarcinoma of prostate with mucinous differentiation arising in the male urethra is extremely rare, with only 21 cases reported in the previous literature. A diagnosis of mucin-producing urothelial carcinoma of the prostate is based on the pathology, immunohistochemistry, and clinical examination by excluding the secondary adenocarcinoma of the prostate. We present a case of unexpected mucinous urothelial carcinoma of prostate with co-existing inverted papilloma of bladder in a 57-year-old man. The patient underwent transurethral resection of the prostate (TURP and transurethral resection of a bladder tumour (TUR-Bt, and the pathologic result showed mucinous prostate carcinoma and bladder inverted papilloma. Immunohistological stain was negative for prostate-specific antigen (PSA, prostate-specific acid phosphatase (PSAP, and P63, but positive for cytokeratin 7 (CK 7, CK 20, clone 34E12 and P504S. A complete endoscopic examination was performed to exclude the secondary adenocarcinoma of prostate. This case illustrates the clinical and pathological features of a rare and unexpected mucin-producing urothelial carcinoma of prostate in a bladder neoplasm patient.

Metastatic prostatic adenocarcinoma diagnosed in a bronchoalveolar lavage specimen: An unusual presentation of a common tumor

Directory of Open Access Journals (Sweden)

Adrienne E Moul

2016-01-01

Full Text Available Metastatic prostatic adenocarcinoma presenting as a primary lung disease is rare. We present a 52-year-old male with a 3-month history of cough, shortness of breath, and weight loss with clinical and radiological findings suggestive of a primary lung disease: Bilateral interstitial and alveolar opacities with blunting of the costophrenic angles, multiple diffuse foci of consolidations and nodules, predominantly subpleural and located in the lower lobes, and diffuse interlobular septal thickening and peribronchial thickening. The patient underwent bronchoscopy and bronchoalveolar lavage (BAL was obtained. Cytospin smears were diagnostic for a low-grade adenocarcinoma. Clinically, the patient had elevated serum prostate-specific antigen (PSA levels greater than 5,000 ng/mL. Because of this, immunocytochemistry for PSA was performed which was positive, confirming the diagnosis of metastatic prostatic adenocarcinoma. This unusual case of metastatic adenocarcinoma of the prostate first diagnosed by BAL highlights the significance of available clinical information and the use of immunocytochemistry for proper diagnosis.

Androgen suppression plus radiation vs. radiation alone for patients with D1 (pN+) adenocarcinoma of the prostate (results based on a national prospective randomized trial RTOG 85-31)

International Nuclear Information System (INIS)

Lawton, Colleen A.; Pajak, Thomas F.; Byhardt, Roger; Sause, William T.; Hanks, Gerald E.; Russell, Anthony H.; Rotman, Marvin; Porter, Arthur; McGowan, David G.; DelRowe, John D.; Pilepich, Miljenko V.

1996-01-01

Purpose/Objective: To evaluate the effect of immediate androgen suppression in conjunction with standard external beam irradiation versus radiation alone on a group of pathologically staged lymph node positive patients with adenocarcinoma of the prostate. Methods and Materials: A national prospective randomized trial of standard external beam irradiation plus immediate androgen suppression vs. external beam irradiation alone was initiated in 1985 for patients with locally advanced adenocarcinoma of the prostate. One hundred seventy two of the patients in this trial had biopsy proven pathologically involved lymph nodes. Ninety Eight of these patients received radiation plus the immediate androgen suppression (LHRH agonist) while 74 received radiation alone with hormonal manipulation instituted at the time of relapse. Results: With a median followup of 3.9 years actuarial progression free survival at five years was 56% for the patients who received radiation plus immediate LHRH agonist versus 33% patients who received radiation alone with hormonal manipulation at relapse (p = .0009). Since all of these patients had locally advanced disease (i.e. pathologically positive lymph nodes) stage does not explain this difference in outcome and gleason grade was not statistically different between the two groups. Although not statistically different at this point both overall survival and cause specific survival favor radiation and immediate LHRH agonist. Actuarial overall survival at five years for the radiation and LHRH group was 69% versus 59% for the radiation alone group who received androgen suppression at relapse. Actuarial cause specific survival at five years was 84% for the radiation and immediate LHRH agonist group and 73% for the radiation alone group. Conclusion: Patients with adenocarcinoma of the prostate and pathologically involved pelvic lymph nodes (pN+ or clinical stage D 1 ) should be seriously considered for external beam irradiation plus immediate

Intermittent hormonal therapy in the treatment of post-irradiation residual/recurrent prostate cancer

International Nuclear Information System (INIS)

Williams, Aaron O; Kocherill, Paul G; Wallace, Michelle; Forman, Jeffrey D

1996-01-01

Purpose: To evaluate the efficacy and toxicity of intermittent hormonal therapy in the treatment of residual/recurrent prostate cancer. Materials and Methods: Seventeen patients with biochemical evidence of residual/recurrent prostate cancer were initially treated with radiation therapy (RT)(13), neo-adjuvant hormonal therapy and RT (3), or RT following prostatectomy (1). The mean follow-up time was 19.4 months from the initiation of hormonal therapy. Hormonal therapy consisted of an LH-RH agonist alone (7), an anti-androgen alone (1) or a combination of both (9). Hormonal therapy was continued until the prostatic specific antigen (PSA) level became undetectable. IHT was reinstituted when the PSA reached a pre-determined level, usually greater than or equal to 10ng/ml. Results: The mean time from completion of primary treatment to the initiation of hormonal therapy was 32.5 months. The mean PSA at the start of the first cycle of hormonal therapy was 43.9ng/ml, the second cycle, 11.9ng/ml and the third cycle, 24ng/ml. The mean PSA levels at the end of the first and second cycle of hormonal therapy were .48 and .42ng/ml, respectively. No patient has yet completed the third cycle of hormonal therapy. The average duration of hormonal therapy was 10 months for the first cycle and 4 months for the second cycle. The mean intermittent time off hormones were 9.3 months between cycles 1 and 2, and 10 months between cycles 2 and 3. No patient has yet become refractory to hormonal therapy. Currently all patients are alive. All patients experienced hot flashes and decreased libido at varying degrees during treatment. Thirty-five percent experienced gynecomastia. During the intervals between hormonal therapy, most patients reported a decrease in hot flashes. Conclusion: This analysis supplies preliminary evidence that intermittent hormonal therapy is a viable option in patients with biochemical evidence of disease following initial therapy. It is associated with less treatment

[Plastic surgery for the treatment of gynaecomastia following hormone therapy in prostate carcinoma].

Science.gov (United States)

Ryssel, H; Germann, G; Köllensperger, E; Riedel, K

2008-04-01

Gynecomastia is a potential side effect of hormone therapy for prostate cancer. In large, randomized, placebo controlled studies approximately 50% or more of patients with prostate cancer experienced gynecomastia attributable to various mechanisms. Although it is mostly reported as mild to moderate, gynecomastia is one of the reasons most frequently cited for premature discontinuation of such treatment. Prophylactic radiotherapy and prophylactic tamoxifen have been shown to decrease the incidence of hormone-induced gynecomastia; nevertheless, there are still cases of refractory gynecomastia, and in these plastic surgery is needed for correction. Gynecomastia is a benign enlargement of the male breast, requiring no treatment unless it is a source of embarrassment and/or distress for the adolescent or man affected. The indications for surgical treatment of gynecomastia are founded on two main objectives: restoration of the male chest shape and diagnostic evaluation of suspected breast lesions. The authors believe that the complete circumareolar technique with no further scarring creates the best aesthetic results with fewer complications. When this is used in combination with liposuction very pleasing aesthetic results can be achieved.

[Phytotherapy in urology. Current scientific evidence of its application in benign prostatic hyperplasia and prostate adenocarcinoma].

Science.gov (United States)

Morán, E; Budía, A; Broseta, E; Boronat, F

2013-02-01

To evaluate the usefulness of phytotherapy in the treatment of the benign prostatic hyperplasia (BPH) and prostatic adenocarcinoma (ADCP). Systematic review of the evidence published until January 2011 using the following scientific terms: phytotherapy, benign prostate hyperplasia, prostatic adenocarcinoma, prostate cancer and the scientific names of compounds following the rules of the International Code of Botanical Nomenclature. The databases used were Medline and The Cochrane Library. We included articles published until January 2011 written in English and Spanish. We included studies in vitro/in vivo on animal models or human beings. Exclusion criteria were literature not in English and Spanish or articles with serious methodological flaws. We included 65 articles of which 40 met the inclusion criteria. BPH: the most studied products are serenoa repens and pygeum africanum. There are many studies in favour of the use of phytotherapy but its conclusions are inconsistent due to the small number of patients, the lack of control with placebo or short follow-up. However the use of these products is common in our environment. ADCP: there is no evidence to recommend phytotherapy in the treatment of the ADCP. There are works on prevention but only at experimental level so there is no evidence for its recommendation. The scientific evidence on the use of phytotherapy in prostatic pathology is conclusive not recommend ing the use of it for BPH or the ADCP. Copyright © 2012 AEU. Published by Elsevier España. All rights reserved.

Targeting Survivin by 3, 3'-Diindolylmethane (DIM) for Prostate Cancer Therapy

National Research Council Canada - National Science Library

Rahman, K. M

2008-01-01

...) family, is associated with both progression of prostate carcinoma and drug resistance. Therefore, we hypothesized that survivin plays a role in the development of hormone-refractory prostate cancer (HRPC...

Synchronous prostate and rectal adenocarcinomas irradiation utilising volumetric modulated arc therapy.

Science.gov (United States)

Ng, Sweet Ping; Tran, Thu; Moloney, Philip; Sale, Charlotte; Mathlum, Maitham; Ong, Grace; Lynch, Rod

2015-12-01

Cases of synchronous prostate and colorectal adenocarcinomas have been sporadically reported. There are case reports on patients with synchronous prostate and rectal cancers treated with external beam radiotherapy alone or combined with high-dose rate brachytherapy boost to the prostate. Here, we illustrate a patient with synchronous prostate and rectal cancers treated using the volumetric arc therapy (VMAT) technique. The patient was treated with radical radiotherapy to 50.4 Gy in 28 fractions to the pelvis, incorporating the involved internal iliac node and the prostate. A boost of 24 Gy in 12 fractions was delivered to the prostate only, using VMAT. Treatment-related toxicities and follow-up prostate-specific antigen and carcinoembryonic antigen were collected for data analysis. At 12 months, the patient achieved complete response for both rectal and prostate cancers without significant treatment-related toxicities.

Molecular Determinants of Hormone-Refractory Prostate Cancer

Science.gov (United States)

2015-07-01

Suzuki Y, Honda G, et al. Large-scale identification and characterization of human genes that activate NF- kappaB and MAPK signaling pathways. Oncogene...2003 May 22;22(21):3307-18. Mendiratta P, et al. Genomic strategy for targeting therapy in castration-resistant prostate cancer. J Clin Oncol. 2009 Apr

Selective Androgen Receptor Down-Regulators (SARDs): A New Prostate Cancer Therapy

National Research Council Canada - National Science Library

Bhattacharyya, Rumi S

2007-01-01

The androgen receptor (AR) plays a key role in the development and progression of prostate cancer Targeting the AR for down-regulation would be a useful strategy for treating prostate cancer, especially hormone-refractory...

Association of Remitting Seronegative Symmetrical Synovitis with Pitting Edema, Polymyalgia Rheumatica, and Adenocarcinoma of the Prostate

DEFF Research Database (Denmark)

Emamifar, Amir; Hess, Soeren; Gildberg-Mortensen, Rannveig

2016-01-01

BACKGROUND Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) is a rare condition that occurs in elderly individuals. It can present alone or in association with various rheumatic or malignant diseases. CASE REPORT An 83-year-old man presented with anemia, hyper......-sedimentation, and pitting edema of the back of the hands. The patient complained of pain and stiffness of the shoulder and hip girdles, especially in the morning. He was previously diagnosed with adenocarcinoma of the prostate. After 3 years of watchful waiting, treatment with goserelin, a gonadotropin releasing hormone...... of our knowledge, this is the first report of a case of RS3PE that presented twice with 2 different diagnoses in the same patient....

Durable remission of leptomeningeal metastases from hormone-responsive prostate cancer.

Science.gov (United States)

Zhang, Meng; Mahta, Ali; Kim, Ryan Y; Akar, Serra; Kesari, Santosh

2012-06-01

Prostate cancer is rarely associated with leptomeningeal metastasis. An 87-year-old man with a history of prostate cancer presented with leptomeningeal metastasis. He received hormonal therapy with leuprolide. Subsequently, he achieved an impressive response, indicated by a constant fall in his PSA levels and by the stabilization of leptomeningeal disease and clinical improvement. Hormonal therapy may be effective in inducing remission in hormone-sensitive prostate cancer with leptomeningeal metastasis.

Long-Term Treatment Sequelae After External Beam Irradiation With or Without Hormonal Manipulation for Adenocarcinoma of the Prostate: Analysis of Radiation Therapy Oncology Group Studies 85-31, 86-10, and 92-02

International Nuclear Information System (INIS)

Lawton, Colleen A.; Bae, Kyoungwha; Pilepich, Miljenko; Hanks, Gerald; Shipley, William

2008-01-01

Purpose: Late gastrointestinal (GI) and genitourinary (GU) morbidity from external beam irradiation used to treat adenocarcinoma of the prostate continue to be a concern of physicians and patients alike. In addition, for locally advanced/high-risk cancer, the appropriate use of hormonal manipulation in addition to radiation therapy (RT) may increase toxicity. We analyzed three large Radiation Therapy Oncology Group (RTOG) studies (85-31, 86-10, and 92-02) to try to address these issues. Methods and Materials: A total of 2,922 patients were accrued with a median follow-up of 10.3 years for surviving patients. The RTOG scoring scheme was used to assess GI, GU, and other toxicities. Toxicity reported was Grade 3 or higher late toxicity. Patient toxicity level was assessed by study and by treatment type combining RT only vs. RT + short-course hormone therapy (STH) vs. RT + long-term hormone therapy (LTH). Results: Multivariate analysis reveals that age >70 was statistically significantly associated with a decrease in late any Grade 3+ toxicity (hazard ratio [HR] = 0.78, p = 0.0476) adjusted for treatment type. Comparing treatment type, patients treated with RT+STH had a statistically significant lower probability of Grade 3+ GI, GU, and other toxicity compared with RT alone (p = .00006; p = 0.0037; p = 0.0127, respectively). Patients treated with RT+LTH had a statistically significant lower probability of Grade 3+ GU toxicity compared with RT alone (p = 0.023). Conclusions: These data show that external beam radiation therapy remains a safe option for locally advanced/high-risk prostate cancer, and the use of hormonal manipulation does appear to be protective for GU and GI toxicity depending upon length of treatment

Expression of extracellular matrix proteins: tenascin-C, fibronectin and galectin-3 in prostatic adenocarcinoma

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Monika Ulamec

2015-12-01

Full Text Available Introduction: The interchanged stromal-epithelial relations and altered expression profiles of various extracellular matrix (ECM proteins creates a suitable microenvironment for cancer development and growth. We support the opinion that remodeling of the extracellular matrix (ECM plays an important role in the cancer progression. The aim of this study was to examine the expression of ECM proteins tenascin-C, fibronectin and galectin-3 in prostatic adenocarcinoma. Methods: Glands and surrounding stroma were analyzed in randomly selected specimens from 52 patients with prostate cancer and 28 patients with benign prostatic hyperplasia (BHP. To evaluate the intensity of tenascin-C, fibronectin and galectin-3 expression the percentage of positively immunostained stromal cells was examined.Results: Compared to BPH, stroma of prostatic adenocarcinoma showed statistically significant increase in tenascin-C expression (p<0.001, predominantly around neoplastic glands, while fibronectin (p=0.001 and galectin-3 (p<0.001 expression in the same area was decreased.Conclusions: Our study confirms changes in the expression of ECM proteins of prostate cancer which may have important role in the cancer development.

Predictive implications of bone turnover markers after palliative treatment with 186Re-HEDP in hormone-refractory prostate cancer patients with painful osseous metastases

International Nuclear Information System (INIS)

Zafeirakis, Athanasios; Papatheodorou, Georgios; Arhontakis, Athanasios; Gouliamos, Athanasios; Vlahos, Lambros; Limouris, Georgios S.

2010-01-01

To prospectively evaluate the predictive value of various bone formation and resorption markers in patients with bone metastases from prostate cancer after palliative treatment with 186 Re-1,1-hydroxyethylidene diphosphonate ( 186 Re-HEDP). Included in the study were 36 men with prostate cancer, suffering from painful osseous metastases and treated with 186 Re-HEDP. None had received any treatment that would have interfered with bone metabolism before 186 Re-HEDP treatment or throughout the follow-up period. For each patient, pretreatment and posttreatment serum levels of osteocalcin (OC), bone alkaline phosphatase (BALP), aminoterminal (PINP) and carboxyterminal (PICP) propeptides of type I collagen, amino-terminal (NTx) and carboxyterminal (CTx) telopeptides of type I collagen and their combinations were compared with the level and duration of pain response to radionuclide treatment. Pain response was correlated only with pretreatment ΝΤx/PINP, PICP/PINP and NTx/CTx ratios and posttreatment decrease in baseline NTx and PICP values (p=0.0025-0.035). According to multivariate and ROC analyses, the best marker-derived predictors of better and longer duration of response to 186 Re-HEDP treatment were a posttreatment decrease in NTx of ≥20% (RR=3.44, p=0.0005) and a pretreatment NTx/PINP ratio of ≥1.2 (RR=3.04, p=0.036) NTx, a potent collagenous marker of bone resorption, along with the novel NTx/PINP ratio provide useful cut-off values for identifying a group of patients suffering from painful osseous metastases from hormone-refractory prostatic carcinoma who do not respond to palliative treatment with 186 Re-HEDP. This information could help avoid an inefficient and expensive radionuclide treatment. Also, in the cohort of patients who will eventually undergo such treatment, the medium-term posttreatment changes in NTx offer valuable predictive information regarding long-term palliative response. (orig.)

Estramustine phosphate in the treatment of hormone escape prostatic carcinoma - a 3 year follow-up

Directory of Open Access Journals (Sweden)

Altaf H Syed

2003-01-01

Full Text Available Objective: A recent literature review has shown rekin-dled interest in the use of estramustine phosphate (EMP inpatients with advanced prostatic cancer. This led us to assess prostate specific antigen (PSA response and drug tolerability following EMP therapy inpatients with hor-mone refractory prostate cancer Patients and Methods: Twenty-five patients with a mean age of 73.5 years (range 49 to 85 years received EMP for hormone insensitive prostate cancer from January 1996 onwards. They were received at 6 weeks initially followed by 3 monthly intervals to monitor further progression of disease. At each visit clinical examination and blood chem-istry (PSA, etc was done and further investigations, i.e., bone scan, CT scan, etc. were requested if thought neces-sary. Results: According to the WHO score of pain 71 %found immediate symptomatic relief following EMP treatment but only 29% were pain free after one year PSA level showed a persistent decline of> 50% of pre-treatment value in 16 patients (64% at 6 weeks. However, at 1 year 22% had either a still declining PSA or had reached a stable nadir PSA level while the rest showed rising PSA suggesting in-sensitivity to EMP. Three out of 5 patients (excluding I patient with intolerance at 2 months with> 80% decrease in PSA at 6 weeks had longer period of progression free interval (1 year in 2 and 2 years in 1 patient. The treat-ment was generally well tolerated (72% as only 7 patients had to discontinue EMP because of severe side ef-fects. Conclusions: EMP treatment in patients with hormone escaped prostatic cancer does produce immediate PSA response which is reflected simultaneously in pain improve-ment in the majority of cases but overall the benefit is shortlived. Patients who have> 80% reduction in pre-treat-ment PSA value at 6 weeks may have longer period of pro-gressionfree intervals. However EMP was generally well tolerated.

Androgen receptor levels during progression of prostate cancer in the transgenic adenocarcinoma of mouse prostate model

Directory of Open Access Journals (Sweden)

Krisna Murti

2010-02-01

Full Text Available Aim To construct tissue microarrays (TMAs that consisted of prostate tumours from the transgenic adenocarcinoma of mouse prostate (TRAMP mice and non-transgenic murine prostates and to assess androgen receptor (AR levels during progression of prostate cancer in TRAMP mice by immunohistochemistry.Methods Haematoxylin and eosin (H&E sections from the ventral and dorso-lateral prostate lobes of non-transgenic, intact TRAMP and castrated TRAMP were used to demarcate regions of interest for TMAs construction. The samples on TMAs were used to evaluate AR expression using video image analysis (VIA.Results AR was expressed during cancer progression, but AR levels were reduced or absent in late stage disease. Furthermore, when AR levels were compared in tumours from intact and castrate animals, a significant increase in AR levels was observed following androgen ablation.Conclusion Similar to clinical prostate cancer, in the TRAMP model, prostate tumours evolve mechanisms to maintain AR expression and AR responsive gene pathways following castration to facilitate continued tumour growth. (Med J Indones 2010; 19:5-13Keywords : androgen ablation therapy, tissue microarrays, haematoxylin and eosin, video image analysis

Predictive implications of bone turnover markers after palliative treatment with {sup 186}Re-HEDP in hormone-refractory prostate cancer patients with painful osseous metastases

Energy Technology Data Exchange (ETDEWEB)

Zafeirakis, Athanasios [401 Army Hospital of Athens, Department of Nuclear Medicine, Athens (Greece); Papatheodorou, Georgios [401 Army Hospital of Athens, Clinical Research Unit, Athens (Greece); Arhontakis, Athanasios [401 Army Hospital of Athens, Department of Urology, Athens (Greece); Gouliamos, Athanasios; Vlahos, Lambros [Aretaieion University Hospital, Athens Medical School, Department of Radiology, Athens (Greece); Limouris, Georgios S. [Aretaieion University Hospital, Athens Medical School, Department of Nuclear Medicine, Athens (Greece)

2010-01-15

To prospectively evaluate the predictive value of various bone formation and resorption markers in patients with bone metastases from prostate cancer after palliative treatment with {sup 186}Re-1,1-hydroxyethylidene diphosphonate ({sup 186}Re-HEDP). Included in the study were 36 men with prostate cancer, suffering from painful osseous metastases and treated with {sup 186}Re-HEDP. None had received any treatment that would have interfered with bone metabolism before {sup 186}Re-HEDP treatment or throughout the follow-up period. For each patient, pretreatment and posttreatment serum levels of osteocalcin (OC), bone alkaline phosphatase (BALP), aminoterminal (PINP) and carboxyterminal (PICP) propeptides of type I collagen, amino-terminal (NTx) and carboxyterminal (CTx) telopeptides of type I collagen and their combinations were compared with the level and duration of pain response to radionuclide treatment. Pain response was correlated only with pretreatment {nu}{tau}x/PINP, PICP/PINP and NTx/CTx ratios and posttreatment decrease in baseline NTx and PICP values (p=0.0025-0.035). According to multivariate and ROC analyses, the best marker-derived predictors of better and longer duration of response to {sup 186}Re-HEDP treatment were a posttreatment decrease in NTx of {>=}20% (RR=3.44, p=0.0005) and a pretreatment NTx/PINP ratio of {>=}1.2 (RR=3.04, p=0.036) NTx, a potent collagenous marker of bone resorption, along with the novel NTx/PINP ratio provide useful cut-off values for identifying a group of patients suffering from painful osseous metastases from hormone-refractory prostatic carcinoma who do not respond to palliative treatment with {sup 186}Re-HEDP. This information could help avoid an inefficient and expensive radionuclide treatment. Also, in the cohort of patients who will eventually undergo such treatment, the medium-term posttreatment changes in NTx offer valuable predictive information regarding long-term palliative response. (orig.)

Benzimidazole as Novel Therapy for Hormone-Refractory Metastatic Prostate Cancer

Science.gov (United States)

2011-05-01

8 4 INTRODUCTION The focus of this project is to evaluate the anti-tumor effects of benzimidazoles as a...potential anti-metastatic prostate cancer therapy. We identified benzimidazoles , a class of anti-parasitic drug, in a drug screening process for...preferential anti-tumor activity on metastatic prostate cancer cells. We have data indicate that benzimidazoles have potent anti-tumor activities

Prostate specific antigen in the diagnosis and treatment of adenocarcinoma of the prostate. III. Radiation treated patients

International Nuclear Information System (INIS)

Stamey, T.A.; Kabalin, J.N.; Ferrari, M.

1989-01-01

Serum prostate specific antigen was determined (Yang polyclonal radioimmunoassay) in 183 men after radiation therapy for adenocarcinoma of the prostate. A total of 163 men had received 7,000 rad external beam radiotherapy and 20 had been implanted with iodine-125 seeds. Only 11 per cent of these 183 patients had undetectable prostate specific antigen levels at a mean interval of 5 years since completion of radiotherapy. Prostate specific antigen levels after radiotherapy were directly related to initial clinical stage and Gleason score before treatment. Multiple prostate specific antigen determinations were performed with time in 124 of 183 patients. During year 1 after radiotherapy prostate specific antigen levels were decreasing in 82 per cent of the patients but only 8 per cent continued to decrease beyond year 1. Of 80 patients observed greater than 1 year after completion of radiotherapy 51 per cent had increasing values and 41 per cent had stable values. Increasing prostate specific antigen values after radiotherapy were correlated with progression to metastastic disease and residual cancer on prostate biopsy. Total serum acid phosphatase levels were poorly related to prostate specific antigen levels, were less effective in discriminating patients with metastatic disease and provided no additional information beyond that provided by prostate specific antigen

Origin of Androgen-Insensitive Poorly Differentiated Tumors in the Transgenic Adenocarcinoma of Mouse Prostate Model

Directory of Open Access Journals (Sweden)

Wendy J. Huss

2007-11-01

Full Text Available Following castration, the transgenic adenocarcinoma of mouse prostate (TRAMP model demonstrates rapid development of SV40-Tag-driven poorly differentiated tumors that express neuroendocrine cell markers. The cell population dynamics within the prostates of castrated TRAMP mice were characterized by analyzing the incorporation of 5-bromodeoxyuridine (BrdUrd and the expression of SV40-Tag, synaptophysin, and androgen receptor (AR. Fourteen days postcastration, the remaining epithelial cells and adenocarcinoma cells were nonproliferative and lacked detectable SV40-Tag or synaptophysin expression. In contrast, morphologically distinct intraglandular foci were identified which expressed SV40-Tag, synaptophysin, and Ki67, but that lacked AR expression. These proliferative SV40-Tag and synaptophysin-expressing intraglandular foci were associated with the rare BrdUrd-retaining cells. These foci expanded rapidly in the postcastration prostate environment, in contrast to the AR- and SV40-Tag-expressing adenocarcinoma cells that lost SV40-Tag expression and underwent apoptosis after castration. Intraglandular foci of synaptophysin-expressing cells were also observed in the prostates of intact TRAMP mice at a comparable frequency; however, they did not progress to rapidly expanding tumors until much later in the life of the mice. This suggests that the foci of neuroendocrine-like cells that express SV40-Tag and synaptophysin, but lack AR, arise independent of androgen-deprivation and represent the source of the poorly differentiated tumors that are the lethal phenotype in the TRAMP model.

Expression of immunosuppresive B7-H3 ligand by hormone-treated prostate cancer tumors and metastases.

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Chavin, Grant; Sheinin, Yuri; Crispen, Paul L; Boorjian, Stephen A; Roth, Timothy J; Rangel, Laureano; Blute, Michael L; Sebo, Thomas J; Tindall, Don J; Kwon, Eugene D; Karnes, R Jeffrey

2009-03-15

Prostate cancer cells uniformly express the immune cell inhibitory B7-H3 ligand. Enhanced B7-H3 expression correlates with increased disease progression and cancer-specific death after radical prostatectomy (RP). To further assess whether B7-H3 expression is hormone regulated and persists as a viable target during (or after) androgen-ablative therapy, we examined B7-H3 ligand expression within primary and metastatic cancer lesions in response to neoadjuvant hormone therapy (NHT) or palliative hormone deprivation. Tumor B7-H3 in RP specimens from men treated with >/=3 months of NHT was compared with B7-H3 in tumors from matched patients who received no therapy before RP. Hormone-treated and untreated metastatic lesions involving bone were also compared for levels of B7-H3 expression. Of 165 consecutive RP specimens in each cohort studied, sufficient tissues were available for 148 patients (89.7%) treated with NHT versus 127 patients (77.0%) treated with surgery alone. B7-H3 was expressed in 142 (95.9%) tumors from NHT patients compared with 122 (96.0%) tumors from patients treated with surgery alone (P = 0.91). B7-H3 expression intensity in RP specimens was not affected by NHT (P = 0.12). Bone metastases from 11 (32.4%) untreated and 23 (67.6%) androgen-ablated patients revealed that B7-H3 expression increased in response to hormone therapy (P = 0.04) relative to untreated lesions. Taken together, B7-H3 expression seems to remain stable (or may even increase) in response to hormone therapy. As such, B7-H3 may represent an attractive target to improve treatment of men with high-risk hormone-treated or refractory prostate cancer.

Synchronous Bone Metastasis From Multiple Myeloma and Prostate Adenocarcinoma as Initial Presentation of Coexistent Malignancies

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Diego Andres Adrianzen Herrera

2018-04-01

Full Text Available The radiographic appearance of bone metastases is usually determined by tumor histology and can be osteolytic, osteoblastic, or mixed. We present a patient with coexistent bone metastasis from multiple myeloma and prostate adenocarcinoma who exhibited synchronous bone involvement of both histologies within the same bone lesion, a rare phenomenon that has not been previously reported and led to atypical radiographic findings. The radiograph of a 71-year-old man with thigh swelling and pain demonstrated a lytic femoral lesion. Magnetic resonance imaging (MRI confirmed a destructive process, but showed coexistent metaphyseal sclerosis. Multiple myeloma was suspected by demonstration of monoclonal gammopathy and confirmed by computed tomography (CT-guided biopsy. Incidentally, CT demonstrated areas of sclerosis corresponding to T2 hypointensity on MRI. Further studies revealed osteoblastic spinal metastasis, prostate enhancement on CT and prostate-specific antigen (PSA level of 90 ng/mL, concerning for concomitant prostate neoplasm. After endoprosthetic reconstruction, pathology of the femur identified both plasma cell neoplasm and metastatic prostate adenocarcinoma. An association between prostate cancer and multiple myeloma is hypothesized due to tumor microenvironment similarities and possible common genetic variations, however, coexisting bone metastases have never been reported. This unusual finding explains the discrepant imaging features in our patient and is evidenced that certain clinical situations merit contemplation of atypical presentations of common malignancies even if this leads to additional testing.

Histopathologic Review of Previously Negative Prostatic Core Needle Biopsies following a New Diagnosis of Adenocarcinoma of the Prostate by Core Needle Biopsies: Implications for Quality Assurance Programs

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Jay Patel

2008-01-01

Full Text Available Programs for quality assurance are increasingly important in surgical pathology. Many quality assurance (QA techniques for surgical pathology were adopted from procedures introduced in cytopathology. Surgical pathology specimens have diminished in size such that the majority of diagnostic biopsies of prostatic lesions are now core needle biopsies. These specimens raise issues similar to those of cytology specimens, including concerns regarding adequacy and the representative nature of the biopsy. Due to sample size, some neoplasms may not be diagnosed on initial biopsy, raising concerns regarding false negative results. Cytopathologists have instituted QA procedures including review of all previously negative slides received within five years prior to the new diagnosis of high grade squamous intraepithelial lesion or gynecologic malignancy. No such requirement exists in surgical pathology for review of core biopsies. The Department of Pathology at the University of Utah instituted a QA policy requiring review of prior negative prostatic needle biopsies following a new diagnosis of prostatic adenocarcinoma. We reviewed five years of QA records of prostate needle biopsy review. During this time, nine hundred and fifty-eight core biopsy sets were performed. Two hundred and ninety-five of these contained at least one biopsy with a diagnosis of adenocarcinoma. Two hundred and eight patients had a prior set of prostatic needle biopsies with a diagnosis of adenocarcinoma. The remaining 87 had prior biopsies with either a diagnosis of prostatic intraepithelial neoplasia (23, small atypical acinar proliferation (21 or no evidence of malignancy (43. QA review of these 87 cases revealed two biopsies which revealed foci of adenocarcinoma. Both had been initially diagnosed as no evidence of malignancy. The false negative rate for core biopsy was 0.68%. In an additional twenty-one cases, microscopic foci of atypical small acinar proliferations were found in

Neuroendocrine-type prostatic adenocarcinoma with microsatellite instability in a patient with lynch syndrome.

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Wagner, David G; Gatalica, Zoran; Lynch, Henry T; Kohl, Shane; Johansson, Sonny L; Lele, Subodh M

2010-12-01

Lynch syndrome is an autosomal-dominant cancer syndrome that can be identified with microsatellite instability molecular tests or immunohistochemical stains on pathologic material from patients who meet the Amsterdam Criteria II. The development of prostatic carcinoma in situ or invasive small cell carcinoma (SCC) of the prostate has not been previously reported in a patient with this syndrome. In this report, an 87-year-old White man with the Lynch syndrome had a prostate biopsy that revealed a mixed high-grade conventional adenocarcinoma and SCC of the prostate with high-grade prostatic intraepithelial neoplasia of the small cell neuroendocrine-type (HGPIN-NE), all showing MSH2 microsatellite instability and loss of MSH2 expression, a finding not previously published. These findings suggest that HGPIN-NE is a precursor of invasive SCC and also that prostatic SCC can develop in a patient with the Lynch syndrome.

Androgen-deprivation therapy-induced aggressive prostate cancer with neuroendocrine differentiation

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Julia Lipianskaya

2014-08-01

Full Text Available Most prostate cancers (PCas are classified as acinar type (conventional adenocarcinoma which are composed of tumor cells with luminal differentiation including the expression of androgen receptor (AR and prostate-specific antigen (PSA. There are also scattered neuroendocrine (NE cells in every case of adenocarcinoma. The NE cells are quiesecent, do not express AR or PSA, and their function remains unclear. We have demonstrated that IL8-CXCR2-P53 pathway provides a growth-inhibitory signal and keeps the NE cells in benign prostate and adenocarcinoma quiescent. Interestingly, some patients with a history of adenocarcinoma recur with small cell neuroendocrine carcinoma (SCNC after hormonal therapy, and such tumors are composed of pure NE cells that are highly proliferative and aggressive, due to P53 mutation and inactivation of the IL8-CXCR2-P53 pathway. The incidence of SCNC will likely increase due to the widespread use of novel drugs that further inhibit AR function or intratumoral androgen synthesis. A phase II trial has demonstrated that platinum-based chemotherapy may be useful for such therapy-induced tumors.

Hormonal manipulation of lower urinary tract symptoms secondary to benign prostatic obstruction

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Adita Raja

2014-01-01

Full Text Available Although the etiology of lower urinary tract symptoms (LUTS is often multifactorial, a significant proportion of men over the age of 50 suffer from benign prostatic obstruction (BPO secondary to benign prostatic hyperplasia. Prostate, being an androgen responsive organ is dependent on the male sex hormone, testosterone, for growth. Thus, treatment strategies that manipulate the levels of circulating hormones that influence the level of testosterone and/or prostatic growth represent an important potential option for patients suffering with troublesome LUTS due to BPO. Despite this, the only hormonal treatment that is currently used in daily clinical practice is the 5-alpha reductase inhibitor. In this article, we review the current evidence on the use of the 5-alpha reductase inhibitors finasteride and dutasteride. We also discuss new emerging hormonal manipulation strategies for patients with LUTS secondary to BPO.

Prostatic paracoccidioidomycosis: differential diagnosis of prostate cancer

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Daniel Lima Lopes

2009-02-01

Full Text Available Symptomatic prostatic paracoccidioidomycosis (PCM is a very rare condition; however, it may express as a typical benign prostatic hyperplasia or a simulating prostatic adenocarcinoma. This case report presents PCM mimicking prostatic adenocarcinoma. The purpose of this paper is to call the general physician's attention to this important differential diagnosis.

Xanthogranulomatous Prostatitis, a Rare Prostatic Entity

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Alejandro Noyola

2017-01-01

Full Text Available There are several benign prostatic pathologies that can clinically mimic a prostate adenocarcinoma. Xanthogranulomatous prostatitis is a benign inflammatory condition of the prostate and a rare entity. A 47-year old male, with 3 years of lower urinary tract symptoms, with a palpable hypogastric tumor, digital rectal examination: solid prostate, of approximately 60 g. Initial PSA was 0.90 ng/mL. He underwent surgical excision of the lower abdominal nodule and prostatectomy. Histopathology showed xanthogranulomatous prostatitis, without malignancy. Xanthogranulomatous prostatitis is an extremely rare entity that can simulate prostate adenocarcinoma, therefore having a correct histopathological diagnosis is essential.

Treatment of prostate adenocarcinoma permanent implants with I 125: first experience in Uruguay

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Quarneti, A.; Clark, O.; Glaussius, A.; Kaitasoff, P.; Cosia, G.

2010-01-01

Full text: Objective: To report on the treatment done, toxicity and development of a group of adenocarcinoma patients with localized prostate brachytherapy implants permanent I125. Material and Methods. 37 patients were treated in the period 2001 to 2004 at the Military Hospital Central by this treatment modality. All of them were performed before implantation planning, which consisted of the volumetric calculation and calculation prostate dosimetry that included transrectal prostate ultrasound 3-5 weeks before the procedure. all patients had pathological confirmation of the lesion showed PSA values less than 11 ng / ml and Gleason score less than 7. 70% of patients received neo-adjuvant hormone therapy. In 5 patients an interactive planning system was performed computerized dosimetry, using sequential ultrasound imaging planes, allowed the dosimetric analysis before terminate the procedure and make necessary adjustments if the dose distribution did not conform. This additional dosimetric study we have not been described by other authors. Prescribed in the first 10 patients was dose 144 Gy and 160 Gy in subsequent. All patients underwent post implant CT waffle grid after 15 days of the procedure. analyzed the dose volume histogram (HDV) and D90 values??. Clinical follow-up was performed and PSA biochemical .. Preliminary Results: 33 patients were in local control without biochemical failure. Currently 4 patients presented biochemical recurrence with PSA values ??between 4 and 6 ng / ml. In neither disease was found at a distance and then raises confirmation tumor biopsy active presence will undergo surgical treatment protocols localized prostate cancer. HDV values ??D90 and are consistent with the informed by the international literature will be presented. No patient required hospitalization prolonged (greater than 24 hours) or use of higher analgesics. 2 patients had acute urinary retention (G II complication) between the tenth and twentieth day, the rest of the

Prevalence of pesticide exposure in young males (adenocarcinoma of the prostate

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Panwalkar Amit

2003-01-01

Full Text Available Abstract Evidence implicating pesticides as causative agents of prostate cancer is controversial, and specifically, data in young adults is lacking. Hence, we performed a preliminary study evaluating the relationship between pesticide exposure and prostate cancer in young males. After approval from the University of North Dakota Institutional Review Board and Human Subjects Committee, a retrospective study was performed on all young males (prostate. The records of all patients aged less than/equal to 50 years, with a diagnosis of adenocarcinoma of the prostate, from January 1991 through December 2001 were reviewed. Pesticide risk assessment interviews were performed by a single member of the team, for consistency, via telephone on the basis of a pre-determined questionnaire investigating occupations and hobbies with special emphasis on: Duration of exposure. An exposure index was calculated for each interviewed subject according to the following formula: hours/day × days/year × years. Patients with an exposure index >2400 hours were considered as 'exposed.' The 2400 hour cut-off value was chosen on the basis of previous reports indicating that this figure represents heavy exposure to genotoxic agents. Statistical analysis was obtained using SPSS-10®. Between 1991 and 2001, 61 young males with adenocarcinoma of the prostate were identified, of whom 56 patients with a mean age of 47 years (range: 40–49 had complete records of treatment and could be contacted for completion of the questionnaire. The most common stage at presentation was Stage III and the mean Gleason's score was 7.5 (range 5–9. Interestingly, almost a third (16/56, 28.6% of patients had stage IV disease at presentation. 37/56 (66.1% patients had 'significant' exposure in our study. In addition, interestingly, the mean survival in the subgroup of patients with pesticide exposure was 11.3 months (SD: +/- 2

Intensity Modulated Neutron Radiotherapy for the Treatment of Adenocarcinoma of the Prostate

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Santanam, Lakshmi; He, Tony; Yudelev, Mark; Forman, Jeffrey D.; Orton, Colin G.; Heuvel, Frank van den; Maughan, Richard L.; Burmeister, Jay

2007-01-01

Purpose: This study investigates the enhanced conformality of neutron dose distributions obtainable through the application of intensity modulated neutron radiotherapy (IMNRT) to the treatment of prostate adenocarcinoma. Methods and Materials: An in-house algorithm was used to optimize individual segments for IMNRT generated using an organ-at-risk (OAR) avoidance approach. A number of beam orientation schemes were investigated in an attempt to approach an optimum solution. The IMNRT plans were created retrospectively for 5 patients previously treated for prostate adenocarcinoma using fast neutron therapy (FNT), and a comparison of these plans is presented. Dose distributions and dose-volume histograms (DVHs) were analyzed and plans were evaluated based on percentage volumes of rectum and bladder receiving 95%, 80%, and 50% (V 95 , V 80 , V 50 ) of the prescription dose, and on V 60 for both the femoral heads and GM muscle group. Results: Plans were normalized such that the IMNRT DVHs for prostate and seminal vesicles were nearly identical to those for conventional FNT plans. Use of IMNRT provided reductions in rectum V 95 and V 80 of 10% (2-27%) and 13% (5-28%), respectively, and reductions in bladder V 95 and V 80 of 12% (3-26%) and 4% (7-10%), respectively. The average decrease in V 60 for the femoral heads was 4.5% (1-18%), with no significant change in V 60 for the GM muscle group. Conclusions: This study provides the first analysis of the application of intensity modulation to neutron radiotherapy. The IMNRT technique provides a substantial reduction in normal tissue dose in the treatment of prostate cancer. This reduction should result in a significant clinical advantage for this and other treatment sites

Adenocarcinoma of the prostrate

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Bruce, A.W.; Trachtenberg, J.

1987-01-01

This books contains 13 chapters. Some of the chapter titles are: Imaging Techniques in the Diagnosis and Pelvic Staging of Prostatic Cancer; Interstitial Radiotherapy; The Case for External Beam Radiotherapy of Certain Adenocarcinomas of the Prostate; and Chemotherapy of Prostatic Cancer.

Infiltration of tumour-associated macrophages in prostate biopsy specimens is predictive of disease progression after hormonal therapy for prostate cancer.

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Nonomura, Norio; Takayama, Hitoshi; Nakayama, Masashi; Nakai, Yasutomo; Kawashima, Atsunari; Mukai, Masatoshi; Nagahara, Akira; Aozasa, Katsuyuki; Tsujimura, Akira

2011-06-01

• To evaluate tumour-associated macrophage (TAM) infiltration in prostate biopsy specimens as a possible prognostic factor for prostate cancer (PCa) after hormonal therapy. • Immunostaining of TAMs in prostate biopsy specimens was performed using a monoclonal antibody CD68 for 71 patients having PCa treated with hormonal therapy. • Six microscopic (×400) fields around the cancer foci were selected for TAM counting. • The median value of serum prostate-specific antigen (PSA) was 50.1 ng/mL, and the median TAM count was 22. • Recurrence-free survival was significantly better in patients with fewer TAMs (<22) than in those with higher numbers of TAMs (≥22) (P < 0.001). • TAM count was higher in those with higher serum PSA (PSA), higher Gleason score, clinical T stage or those with PSA failure. Cox multivariate analysis showed that TAM count is one of the prognostic factors for PCa treated by hormonal therapy (P < 0.0001). • TAM infiltration in prostate needle biopsy specimens is a useful predictive factor for PSA failure or progression of PCa after hormonal therapy. © 2010 THE AUTHORS. BJU INTERNATIONAL © 2010 BJU INTERNATIONAL.

Depression related to (neo)adjuvant hormonal therapy for prostate cancer

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Tol-Geerdink, Julia J. van; Leer, Jan Willem; Lin, Emile N.J.T. van; Schimmel, Erik C.; Stalmeier, Peep F.M.

2011-01-01

Background: We studied whether hormonal therapy, (neo)adjuvant to radiotherapy for localized prostate cancer, is related to an increase in depression and whether this is caused by the hormonal therapy itself or by the relatively poor prognosis of patients who get (neo)adjuvant hormonal therapy. Methods: Between 2002 and 2005, 288 patients, irradiated for prostate cancer (T1-3N0M0), were studied prospectively in two clinics. In one clinic almost all patients received (neo)adjuvant androgen deprivation (Bicalutamide + Gosereline). In a second clinic hormonal therapy was prescribed mainly for high risk patients. This allowed us to separate the effects of hormonal therapy and the patient's prognosis. Results: During the course of hormonal therapy, depression was significantly heightened by both hormone use (p < 0.001) and poor prognosis (p < 0.01). After completion of hormonal therapy, poor prognosis continued to affect the depression score (p < 0.01). The increase was, however, small. Conclusions: Depression was mildly increased in patients receiving hormonal therapy. The increase appeared to be related to both the hormone therapy itself and the high risk status of patients. High risk status, with the associated poor prognosis, had a more sustained effect on depression. The rise was statistically significant, but was too small, however, to bear clinical significance.

Mandibular metastasis of adenocarcinoma from prostate cancer: case report according to epidemiology and current therapeutical trends of the advanced prostate cancer

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Juliana Dreyer da Silva de Menezes

2013-09-01

Full Text Available Prostate cancer represents the most frequent non-cutaneous neoplasia in males. This type of neoplasia can develop peculiar patterns of evolution, presenting, in many cases, precocious relapses and metastasis. Bone metastasis in the mouth is extremely rare, and represents 1% of all malignant mouth neoplasias. The aim of the present study is to report a clinical case of bone metastasis in the mandibular region associated with a tumoral prostate adenocarcinoma, as well as to discuss connected aspects about diagnosis, prognosis and integrated treatment of this condition.

The 5th Conference on Asian Trends in Prostate Cancer Hormone Therapy.

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Akaza, Hideyuki; Moore, Malcolm A; Chang, Shu-Jen; Cheng, Christopher; Choi, Han Yong; Esuvaranathan, Kesavan; Hinotsu, Shiro; Hong, Sung-Joon; Kim, Choung-Soo; Kim, Wun-Jae; Murai, Masaru; Naito, Seiji; Soebadi, Doddy; Song, Jae-Mann; Umbas, Rainy; Usami, Michiyuki; Xia, Shujie; Yang, Chi-Rei

2007-01-01

The Conference on Asian Trends in Prostate Cancer Hormone Therapy is an annual forum for Asian urologists now in its 5th year. The 2006 conference, held in Bali, Indonesia, was attended by 27 leading urologic oncologists from China, Indonesia, Japan, Korea, Singapore, and Taiwan and featured a packed program of presentations and discussions on a wide range of topics such as relationships among clinicians and the newly opened Asia Regional Office for Cancer Control of the International Union Against Cancer (UICC), detection rates of prostate cancer by biopsy in each of the 6 Asian countries, and favored treatment modalities for hormone-refractory prostate cancer (HRPC) in each country. The first session of the conference kicked off with a keynote lecture entitled "Activities of the UICC ARO". UICC's new office will be the nerve center for its activities in the Asia region. Along with the Asian Pacific Organization for Cancer Prevention (APOCP), UICC aims to shift the focus of attention to cancer control. As such APOCP's long-running publication the APJCP is to be re-launched as the Asian Pacific Journal of Cancer Control. Although UICC is primarily concerned with cancer, several risk factors for cancer are common also to other non-communicable diseases such as diabetes and heart disease, and an important strategy is to implement measures to control these various pathologic conditions as a whole. Apart from contributing to an Asian prostate cancer registry the UICC-ARO will provide training courses, working groups, and assistance in collecting and processing data. The keynote lecture was followed by a roundtable discussion on possible ways in which clinicians from each Asian country can work with UICC. A number of suggestions were put forth including better registration, epidemiology research, possible implementation of UICC prostate cancer guidelines, early detection and screening, and roles of diet and phytotherapy. The underlying reasons for the large but

Prostate Cancer—Health Professional Version

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Prostate cancers are often adenocarcinomas. Prostatic intraepithelial neoplasia is often present in association with prostatic adenocarcinoma. Find evidence-based information on prostate cancer including treatment, causes and prevention, screening, research, genetics, and statistics.

Vascular pericyte density and angiogenesis associated with adenocarcinoma of the prostate.

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Killingsworth, Murray C; Wu, Xiaojuan

2011-01-01

Angiogenesis facilitates metabolism, proliferation and metastasis of adenocarcinoma cells in the prostate, as without the development of new vasculature tumor growth cannot be sustained. However, angiogenesis is variable with the well-known phenomenon of vascular 'hotspots' seen associated with viable tumor cell mass. With the recent recognition of pericytes as molecular regulators of angiogenesis, we have examined the interaction of these cells in actively growing new vessels. Pericyte interactions with developing new vessels were examined using transmission electron microscopy. Pericyte distribution was mapped from α-SMA+ immunostained histological sections and quantified using image analysis. Data was obtained from peripheral and more central regions of 27 cases with Gleason scores of 4-9. Pericyte numbers were increased around developing new vessel sprouts at sites of luminal maturation. Numbers were reduced around the actively growing tips of migrating endothelial cells and functional new vessels. Tumor regions internal to a 500-μm peripheral band showed higher microvessel pericyte density than the peripheral region. Pericytes were found to be key cellular components of developing new vessels in adenocarcinoma of the prostate. Their numbers increased at sites of luminal maturation with these cells displaying an activated phenotype different to quiescent pericytes. Increased pericyte density was found internal to the peripheral region, suggesting more mature vessels lie more centrally. Copyright © 2011 S. Karger AG, Basel.

Dural metastasis from prostatic adenocarcinoma mimicking meningioma: Report of a case with unilateral loss of vision

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Tokgoz, Ozlem; Voyvoda, Nuray; Tokgoz, Husnu

2011-01-01

We report a case of PCa (prostatic adenocarcinoma) with transdural metastasis which radiologically simulated a meningioma. During the course of the disease, the patient complained of progressive unilateral loss of vision as the first presentation of intracranial, extra-axial metastasis

External beam radiotherapy of localized prostatic adenocarcinoma. Evaluation of conformal therapy, field number and target margins

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Lennernaes, B.; Rikner, G.; Letocha, H.; Nilsson, S.

1995-01-01

The purpose of the present study was to identify factors of importance in the planning of external beam radiotherapy of prostatic adenocarcinoma. Seven patients with urogenital cancers were planned for external radiotherapy of the prostate. Four different techniques were used, viz. a 4-field box technique and four-, five- or six-field conformal therapy set-ups combined with three different margins (1-3 cm). The evaluations were based on the doses delivered to the rectum and the urinary bladder. A normal tissue complication probability (NTCP) was calculated for each plan using Lyman's dose volume reduction method. The most important factors that resulted in a decrease of the dose delivered to the rectum and the bladder were the use of conformal therapy and smaller margins. Conformal therapy seemed more important for the dose distribution in the urinary bladder. Five- and six-field set-ups were not significantly better than those with four fields. NTCP calculations were in accordance with the evaluation of the dose volume histograms. To conclude, four-field conformal therapy utilizing reduced margins improves the dose distribution to the rectum and the urinary bladder in the radiotherapy of prostatic adenocarcinoma. (orig.)

Effects of dietary saw palmetto on the prostate of transgenic adenocarcinoma of the mouse prostate model (TRAMP).

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Wadsworth, Teri L; Worstell, Teresa R; Greenberg, Norman M; Roselli, Charles E

2007-05-01

Several of the proposed mechanisms for the actions of the liposterolic extract of saw palmetto (SPE) are exerted on known risk factors for prostate cancer (CaP). This study investigated whether SPE could prevent the progression of CaP in a transgenic adenocarcinoma of the mouse prostate (TRAMP) model. Two different doses of SPE designed to deliver 50 mg/kg/day SPE and 300 mg/kg/day SPE were administered in a custom diet to TRAMP mice for 12 or 24 weeks. Body and organ weights were used to evaluate toxicity, and radioimmunoassay was used to measure plasma and tissue androgen levels to monitor effects of SPE on 5alpha reductase activity. Prostate tissues were evaluated histologically to determine the effect of treatment on tumor grade, cell proliferation, and apoptosis. Treatment with 300 mg/kg/day SPE from 4 to 24 weeks of age significantly reduced the concentration of 5alpha-dihydrotestosterone (DHT) in the prostate and resulted in a significant increase in apoptosis and significant decrease in pathological tumor grade and frank tumor incidence. Dietary supplementation with SPE may be effective in controlling CaP tumorigenesis. SPE suppression of prostatic DHT levels lends support to the hypothesis that inhibition of the enzyme 5alpha-reductase is a mechanism of action of this substance. (c) 2007 Wiley-Liss, Inc.

Impact of short course hormonal therapy on overall and cancer specific survival after permanent prostate brachytherapy

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Beyer, David C.; McKeough, Timothy; Thomas, Theresa

2005-01-01

Purpose: To review the impact of prior hormonal therapy on 10-year overall and prostate cancer specific survival after primary brachytherapy. Methods and Materials: A retrospective review was performed on the Arizona Oncology Services tumor registry for 2,378 consecutive permanent prostate brachytherapy cases from 1988 through 2001. Hormonal therapy was administered before the implant in 464 patients for downsizing of the prostate or at the discretion of the referring physician. All deceased patients with known clinical recurrence were considered to have died of prostate cancer, irrespective of the immediate cause of death. Risk groups were defined, with 1,135 favorable (prostate-specific antigen [PSA] 70 years (p = 0.0013), Gleason score ≥ 7 (p = 0.0005), and prior hormone use (p = 0.0065) on overall survival. Conclusions: At 10 years, in prostate cancer patients receiving brachytherapy, overall survival is worse in men receiving neoadjuvant hormonal therapy, compared with hormone naive patients. This does not appear to be due to other known risk factors for survival (i.e., stage, grade, PSA, age) on multivariate analysis. The leading causes of death were cardiovascular, prostate cancer, and other cancers with no obvious discrepancy between the two groups. This finding is unexpected and requires confirmation from other centers

Echinophora platyloba DC (Apiaceae crude extract induces apoptosis in human prostate adenocarcinoma cells (PC 3

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Fatemeh Zare Shahneh

2014-10-01

Full Text Available Background: Prostate cancer is the second leading malignancy worldwide and the second prominent cause of cancer-related deaths among men. Therefore, there is a serious necessity for finding advanced alternative therapeutic measures against this lethal malignancy. In this article, we report the cytotoxicity and the mechanism of cell death of the methanolic extract prepared from Echinophora platyloba DC plant against human prostate adenocarcinoma PC 3 cell line and Human Umbilical Vein Endothelial Cells HUVEC cell line. Methods: Cytotoxicity and viability of the methanolic extract were assessed by 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay and dye exclusion assay. Cell death enzyme-linked immunosorbent assay (ELISA was employed to quantify the nucleosome production resulting from nuclear DNA fragmentation during apoptosis and determine whether the mechanism involves induction of apoptosis or necrosis. The cell death was identified as apoptosis using terminal deoxynucleotidyl transferase (TdT-mediated dUTP nick end labeling (TUNEL assay and DNA fragmentation gel electrophoresis. Results: E. platyloba could decrease cell viability in malignant cells in a dose- and time-dependent manner. The IC50 values against PC 3 were determined as 236.136 ± 12.4, 143.400 ± 7.2, and 69.383 ± 1.29 μg/ml after 24, 36, and 48 h, respectively, but there was no significant activity in HUVEC normal cell (IC50 > 800 μg/ml. Morphological characterizations and DNA laddering assay showed that the methanolic extract treated cells displayed marked apoptotic characteristics such as nuclear fragmentation, appearance of apoptotic bodies, and DNA laddering fragment. Increase in an early apoptotic population was observed in a dose-dependent manner. PC 3 cell death elicited by the extract was found to be apoptotic in nature based a clear indication of TUNEL assay and gel electrophoresis DNA fragmentation, which is a hallmark of apoptosis

Local control and survival after external irradiation for adenocarcinoma of the prostate

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Rangala, N.; Cox, J.D.; Byhardt, R.W.; Wilson, J.F.; Greenberg, M.; Conceicao, A.L.D.

1982-01-01

From 1966 through 1978, 128 patients with biopsy-proven adenocarcinoma of the prostate underwent external irradiation to the entire pelvis followed by additional irradiation with a field that encompassed the entire prostate with generous margins. Local recurrence was diagnosed when palpable regrowth occurred and was confirmed by biopsy. Eighteen patients (14%) had local recurrence. Actuarial (life table) local recurrence rates, however, were 24% for both for Stage B and C patients. Actuarial five year survival was 100% for the 10 Stage A patients, 91% for the 25 Stage B, and 78% for the 93 Stage C patients. Actuarial five year disease-free survival was 59% for Stage B and 69% for Stage C patients. Local recurrence was affected by the total dose to the whole pelvis and the dose at the center of the prostate. Disease-free survival was influenced by differentiation. High dose external irradiation to the prostate and regional lymph nodes offers the greatest probability of long-term disease-free survival for patients with localized disease. Late bowel complications were seen in 14 patients (11%), two of whom required colostomies. Late urinary tract complications were observed in five patients (4%)

αVβ6 integrin expression is induced in the POET and Ptenpc-/- mouse models of prostatic inflammation and prostatic adenocarcinoma

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Garlick, David S; Li, Jing; Sansoucy, Brian; Wang, Tao; Griffith, Leeanne; FitzGerald, TJ; Butterfield, Julie; Charbonneau, Bridget; Violette, Shelia M; Weinreb, Paul H; Ratliff, Timothy L; Liao, Chun-Peng; Roy-Burman, Pradip; Vietri, Michele; Lian, Jane B; Stein, Gary S; Altieri, Dario C; Languino, Lucia R

2012-01-01

Chronic inflammation is proposed to prime the development of prostate cancer. However, the mechanisms of prostate cancer initiation and development are not completely understood. The αvβ6 integrin has been shown to play a role in epithelial development, wound healing and some epithelial cancers [1, 2]. Here, we investigate the expression of αvβ6 in mouse models of prostatic inflammation and prostate cancer to establish a possible relationship between inflammation of the prostate, αvβ6 expression and the progression of prostate cancer. Using immunohistochemical techniques, we show expression of αvβ6 in two in vivo mouse models; the Ptenpc-/- model containing a prostate- specific Pten tumor suppressor deletion that causes cancer, and the prostate ovalbumin-expressing transgenic (POET) inflammation mouse model. We show that the αvβ6 integrin is induced in prostate cancer and inflammation in vivo in these two mouse models. αvβ6 is expressed in all the mice with cancer in the Ptenpc-/- model but not in age-matched wild-type mice. In the POET inflammation model, αvβ6 is expressed in mice injected with activated T-cells, but in none of the control mice. In the POET model, we also used real time PCR to assess the expression of Transforming Growth Factor Beta 1 (TGFβ1), a factor in inflammation that is activated by αvβ6. In conclusion, through in vivo evidence, we conclude that αvβ6 integrin may be a crucial link between prostatic inflammation and prostatic adenocarcinoma. PMID:22611469

Gleason grading challenges in the diagnosis of prostate adenocarcinoma: experience of a single institution.

Science.gov (United States)

Chen, Sonja D; Fava, Joseph L; Amin, Ali

2016-02-01

Gleason score (GS) is an important factor in determining management and outcome of prostate adenocarcinoma. A standard GS scheme was introduced by ISUP 2005 consensus conference, but there is still significant discordance in grading prostate adenocarcinomas among pathologists, especially between genitourinary-trained (GU) and non-GU pathologists. All biopsies from outside institutions referred for definitive treatment in our hospital are reviewed by a GU pathologist for confirmation and quality assurance. From 2011 to 2013, 117 consecutive prostate consults were retrieved and compared with the initial outside reports as well as final radical prostatectomy (RP) results. Follow-up prostate specific antigen (PSA) was assessed pre- and post-RP, and the results were analyzed. The overall initial GS was higher for all specimens (p = 0.007) especially for the RP cases (p = 0.002). Overall, the modal GS on initial diagnosis was GS7(4 + 3) that was downgraded to the modal GS6(3 + 3) upon review. Despite an overall substantial agreement between the non-GU and GU pathologists [ICC = 0.66], GS by GU pathologist had higher correlation with the final GS in the RP specimen [ICC = 0.62] than non-GU pathologist [ICC = 0.48]. GS on all reviewed cases were found to correlate significantly with the pre-operative PSA (p = 0.002) but the same was not true for the initial report. A non-GU pathologist is more likely to assign a higher GS than a GU pathologist, with a trend to overcall Gleason pattern 4. Considering the implications on treatment, close attention must be paid to the ISUP 2005 consensus conference recommendations.

Castration resistant prostate cancer in the year 2013

International Nuclear Information System (INIS)

Marencak, J.

2013-01-01

Prostate cancer (PC) is the most frequent solid neoplasm in Europe and therefore is regarded as one of the major medical problems of the male population. PC is extremely complicated and interindividual different tumor. The method of treatment depends on several factors, but mainly on the stage of prostate cancer. The term Hormone resistant (refractory) prostate cancer (HRPC) was used in older terminology. HRPC is cancer that progresses despite castrate levels of testosterone achieved androgen deprivation therapy (ADT), which is resistant to any hormonal therapy. Currently is increasingly used (instead of name HRPC) name CRPC – so called PC resistant for castration (CRPC – castration resistant prostate cancer), which is still able to respond to certain hormonal manipulation, although it meets the the criteria for HRPC. Objectives of article: provide information to the general medical community (and especially urologists and oncologists) mainly about a treatment of complicated issues of CRPC. The basic data on the current and future. The article presented basic data on the current and future possibilities of such therapy and increasing basic knowledge about treating CRPC should improve the care of patients with advanced PC. (author)

Prostate-specific antigen and hormone receptor expression in male and female breast carcinoma

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Cohen Cynthia

2010-09-01

Full Text Available Abstract Background Prostate carcinoma is among the most common solid tumors to secondarily involve the male breast. Prostate specific antigen (PSA and prostate-specific acid phosphatase (PSAP are expressed in benign and malignant prostatic tissue, and immunohistochemical staining for these markers is often used to confirm the prostatic origin of metastatic carcinoma. PSA expression has been reported in male and female breast carcinoma and in gynecomastia, raising concerns about the utility of PSA for differentiating prostate carcinoma metastasis to the male breast from primary breast carcinoma. This study examined the frequency of PSA, PSAP, and hormone receptor expression in male breast carcinoma (MBC, female breast carcinoma (FBC, and gynecomastia. Methods Immunohistochemical staining for PSA, PSAP, AR, ER, and PR was performed on tissue microarrays representing six cases of gynecomastia, thirty MBC, and fifty-six FBC. Results PSA was positive in two of fifty-six FBC (3.7%, focally positive in one of thirty MBC (3.3%, and negative in the five examined cases of gynecomastia. PSAP expression was absent in MBC, FBC, and gynecomastia. Hormone receptor expression was similar in males and females (AR 74.1% in MBC vs. 67.9% in FBC, p = 0.62; ER 85.2% vs. 68.5%, p = 0.18; and PR 51.9% vs. 48.2%, p = 0.82. Conclusions PSA and PSAP are useful markers to distinguish primary breast carcinoma from prostate carcinoma metastatic to the male breast. Although PSA expression appeared to correlate with hormone receptor expression, the incidence of PSA expression in our population was too low to draw significant conclusions about an association between PSA expression and hormone receptor status in breast lesions.

Five-year biochemical outcome following permanent interstitial brachytherapy for clinical T1-T3 prostate cancer

International Nuclear Information System (INIS)

Merrick, Gregory S.; Butler, Wayne M.; Galbreath, Robert W.; Lief, Jonathan H.

2001-01-01

Purpose: To evaluate 5-year biochemical disease-free outcome for men with clinical T1b-T3a NxM0 1977 American Joint Committee on Cancer (1997 AJCC) adenocarcinoma of the prostate gland who underwent transperineal ultrasound-guided permanent prostate brachytherapy. Methods and Materials: Four hundred twenty-five patients underwent transperineal ultrasound-guided prostate brachytherapy using either 103 Pd or 125 I, for clinical T1b-T3a NxM0 (1997 AJCC) adenocarcinoma of the prostate gland, from April 1995 to October 1999. No patient underwent pathologic lymph-node staging. One hundred ninety patients were implanted with either 103 Pd or 125 I monotherapy; 235 patients received moderate-dose external beam radiation therapy (EBRT), followed by a prostate brachytherapy boost; 163 patients received neoadjuvant hormonal manipulation, in conjunction with either 103 Pd or 125 I monotherapy (77 patients) or in conjunction with moderate-dose EBRT and a prostate brachytherapy boost (86 patients). The median patient age was 68.0 years (range, 48.2-81.3 years). The median follow-up was 31 months (range, 11-69 months). Follow-up was calculated from the day of implantation. No patient was lost to follow-up. Biochemical disease-free survival was defined by the American Society of Therapeutic Radiation and Oncology (ASTRO) consensus definition. Results: For the entire cohort, the 5-year actuarial biochemical no evidence of disease (bNED) survival rate was 94%. For patients with low-, intermediate-, and high-risk disease, the 5-year biochemical disease-free rates were 97.1%, 97.5%, and 84.4%, respectively. For hormone-naive patients, 95.7%, 96.4%, and 79.9% of patients with low-, intermediate-, and high-risk disease were free of biochemical failure. Clinical and treatment parameters predictive of biochemical outcome included: clinical stage, pretreatment prostate-specific antigen (PSA), Gleason score, risk group, age > 65 years, and neoadjuvant hormonal therapy. Isotope choice was

Effects of Hormone Deprivation, 2-Methoxyestradiol Combination Therapy on Hormone-Dependent Prostate Cancer In Vivo

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Fuminori Sato

2005-09-01

Full Text Available 2-Methoxyestradiol (2-ME has potent anti proliferative effects on cancer cells. Its utility alone or in combination with other therapies for treating prostate cancer, however, has not been fully explored. Androgendependent, independent human prostate cancer cells were examined in vivo for their response to combination therapy. Efficacy was assessed by terminal deoxynucleotide transferase-mediated dUTP nick-end labeling assay, measuring microvessel density (MVD in excised tumors. Animals harboring hormonedependent tumors treated with 2-ME alone, androgen deprivation therapy alone, or the combination of the two had a 3.1-fold, 5.3-fold, 10.1-fold increase in apoptosis, respectively. For hormone-independent tumors, treatment with 2-ME resulted in a 2.43-fold increase in apoptosis, a 73% decrease in MVD. 2-ME was most effective against hormone-dependent tumors in vivo, combination therapy resulted in a significant increase in efficacy compared to no treatment controls, trended toward greater efficacy than either 2-ME or androgen deprivation alone. Combination therapy should be investigated further as an additional therapeutic option for early prostate cancer.

Accumulation of D- vs. L-isomers of alanine and leucine in rat prostatic adenocarcinoma

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Conti, P.S.; Schmall, B.; Bigler, R.E.; Zanzonico, P.B.; Kleinert, E.; Whitmore, W.F. Jr.

1985-01-01

It has been reported that tumor tissue may accumulate some D-amino acids preferentially over the L-isomers. In order to investigate the potential use of carbon-11 labeled amino acid isomers for in vivo tumor studies with positron emission tomography in patients, the tissue distributions of alanine and leucine, substrates for the A-type and L-type amino acid transport systems, respectively, were studied in Copenhagen rates bearing the Dunning R3327G prostatic adenocarcinoma. The authors have previously reported differences in the accumulation of A-type vs. L-type amino acids in rat prostatic adenocarcinoma and normal tissues. All compounds were labeled with C-14 in the carboxyl position with specific activities of 30.0-56.6 mCi/mmol. Higher levels of C-14 activity (Relative Concentration (RC)=dpm found per gm tissue + dpm inject per gm animal mass) were observed in tumor tissue using D-alanine (0.71) compared to L- (0.21) or DL-alanine (0.27) at 45 min post-injection. While tumor/prostate and tumor/liver ratios were above 2 for all three substrates, tumor/blood and tumor/muscle were above one for only the D-isomer. Comparisons made with D-, L-, and DL-leucine also demonstrated a higher level of RC in tumor tissue with the D-isomer (0.84) vs. the L-(0.66) and DL-leucine (0.63). In this case, however, tumor/blood, tumor/prostate, and tumor/muscle ratios were above one for all three substrates, while tumor/liver ratios were below one. These results support the observation of a preferential accumulation of D-amino acids in tumor tissue over the natural L-isomers. Observed differences in the accumulation of the isomers in normal tissues are discussed

Malignant priapism: Penile metastasis originating on a primary prostate adenocarcinoma

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Sandro Roberto da Silva Gaspar

2015-01-01

Full Text Available Malignant priapism is a definition invented in 1938 by Peacock, defined as a persistent erection, not related with sexual activity, caused by cavernous sinus and associated venous systems invasion with malignant cells. Penile secondary lesions are rare entities. Primary locations are usually the pelvic cavity organs, namely the prostate and the bladder as the most common ones. Priapism as a first manifestation of these kinds of lesions is even rarer. The aim was to present a 52-year-old patient harboring a penile metastasis that originated in the primary prostate adenocarcinoma, manifesting itself as a "common" priapism. The patient referred to the emergency room presenting with a priapism and nodules at the coronal sulcus, without previous similar episodes. His evolution until properly diagnosed was catastrophic with multiple lymph nodes, bone and organ involvement, and with his demise soon after from serious bleeding and congestive heart failure, almost 2 months after he first came to the emergency room. We review the literature concerning malignant priapism, diagnosis, and current treatment and survival perspectives.

Exaggerated venous mural hypertrophy in association with metastatic adenocarcinoma of the prostate

International Nuclear Information System (INIS)

Gerber, W.L.; Dellers, E.A.; Putong, P.B.

1991-01-01

A 61-year-old black man presented with metastases to the right groin 5 years after 125iodine treatment for a well differentiated primary prostatic adenocarcinoma. Medium sized veins within and immediately adjacent to the neoplasm showed marked mural thickening due to hypertrophy and hyperplasia of the inner circular and outer longitudinal muscles. There was no histological evidence of radiation effect in the stroma or in the tumor cells. We could find no report in the literature of such changes associated with metastatic carcinoma

External beam radiation therapy for prostate cancer

International Nuclear Information System (INIS)

Forman, Jeffrey D.

1996-01-01

Purpose/Objectives: The intent of this course is to review the issues involved in the management of non-metastatic adenocarcinoma of the prostate. -- The value of pre-treatment prognostic factors including stage, grade and PSA value will be presented, and their value in determining therapeutic strategies will be discussed. -- Controversies involving the simulation process and treatment design will be presented. The value of CT scanning, Beams-Eye View, 3-D planning, intravesicle, intraurethral and rectal contrast will be presented. The significance of prostate and patient movement and strategies for dealing with them will be presented. -- The management of low stage, low to intermediate grade prostate cancer will be discussed. The dose, volume and timing of irradiation will be discussed as will the role of neo-adjuvant hormonal therapy, neutron irradiation and brachytherapy. The current status of radical prostatectomy and cryotherapy will be summarized. Treatment of locally advanced, poorly differentiated prostate cancer will be presented including a discussion of neo-adjuvant and adjuvant hormones, dose-escalation and neutron irradiation. -- Strategies for post-radiation failures will be presented including data on cryotherapy, salvage prostatectomy and hormonal therapy (immediate, delayed and/or intermittent). New areas for investigation will be reviewed. -- The management of patients post prostatectomy will be reviewed. Data on adjuvant radiation and therapeutic radiation for biochemical or clinically relapsed patients will be presented. This course hopes to present a realistic and pragmatic overview for treating patients with non-metastatic prostatic cancer

Concurrent AURKA and MYCN Gene Amplifications Are Harbingers of Lethal TreatmentRelated Neuroendocrine Prostate Cancer

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Juan Miguel Mosquera

2013-01-01

Full Text Available Neuroendocrine prostate cancer (NEPC, also referred to as anaplastic prostate cancer, is a lethal tumor that most commonly arises in late stages of prostate adenocarcinoma (PCA with predilection to metastasize to visceral organs. In the current study, we explore for evidence that Aurora kinase A (AURKA and N-myc (MYCN gene abnormalities are harbingers of treatment-related NEPC (t-NEPC. We studied primary prostate tissue from 15 hormone naïve PCAs, 51 castration-resistant prostate cancers, and 15 metastatic tumors from 72 patients at different stages of disease progression to t-NEPC, some with multiple specimens. Histologic evaluation, immunohistochemistry, and fluorescence in situ hybridization were performed and correlated with clinical variables. AURKA amplification was identified in overall 65% of PCAs (hormone naïve and treated from patients that developed t-NEPC and in 86% of metastases. Concurrent amplification of MYCN was present in 70% of primary PCAs, 69% of treated PCAs, and 83% of metastases. In contrast, in an unselected PCA cohort, AURKA and MYCN amplifications were identified in only 5% of 169 cases. When metastatic t-NEPC was compared to primary PCA from the same patients, there was 100% concordance of ERG rearrangement, 100% concordance of AURKA amplification, and 60% concordance of MYCN amplification. In tumors with mixed features, there was also 100% concordance of ERG rearrangement and 94% concordance of AURKA and MYCN co-amplification between areas of NEPC and adenocarcinoma. AURKA and MYCN amplifications may be prognostic and predictive biomarkers, as they are harbingers of tumors at risk of progressing to t-NEPC after hormonal therapy.

Oligoadenylate synthetase 1 (OAS1 expression in human breast and prostate cancer cases, and its regulation by sex steroid hormones

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Cláudio Jorge Maia

2016-06-01

Full Text Available Oligoadenylate synthetase 1 (OAS1 is an interferon-induced protein characterised by its capacity to catalyse the synthesis of 2ʹ-5ʹ-linked oligomers of adenosine from adenosine triphosphate (2-5A. The 2-5A binds to a latent Ribonuclease L (RNase L, which subsequently dimerises into its active form and may play an important role in the control of cell growth, differentiation and apoptosis. Previously, our research group identified OAS1 as a differentially-expressed gene in breast and prostate cancer cell lines when compared to normal cells. This study evaluates: i the expression of OAS1 in human breast and prostate cancer specimens; and ii the effect of sex steroid hormones in regulating the expression of OAS1 in breast (MCF-7 and prostate (LNCaP cancer cell lines. The obtained results showed that OAS1 expression was down-regulated in human infiltrative ductal carcinoma of breast, adenocarcinoma of prostate, and benign prostate hyperplasia, both at mRNA and protein level. In addition, OAS1 expression was negatively correlated with the progression of breast and prostate cancer. With regards to the regulation of OAS1 gene, it was demonstrated that 17β-estradiol (E2 down-regulates OAS1 gene in MCF-7 cell lines, an effect that seems to be dependent on the activation of oestrogen receptor (ER. On the other hand, 5α-dihydrotestosterone (DHT treatment showed no effect on the expression of OAS1 in LNCaP cell lines. The lower levels of OAS1 in breast and prostate cancer cases indicated that the OAS1/RNaseL apoptotic pathway may be compromised in breast and prostate tumours. Moreover, the present findings suggested that this effect may be enhanced by oestrogen in ER-positive breast cancers.

α(V)β(6) integrin expression is induced in the POET and Pten(pc-/-) mouse models of prostatic inflammation and prostatic adenocarcinoma.

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Garlick, David S; Li, Jing; Sansoucy, Brian; Wang, Tao; Griffith, Leeanne; Fitzgerald, Tj; Butterfield, Julie; Charbonneau, Bridget; Violette, Shelia M; Weinreb, Paul H; Ratliff, Timothy L; Liao, Chun-Peng; Roy-Burman, Pradip; Vietri, Michele; Lian, Jane B; Stein, Gary S; Altieri, Dario C; Languino, Lucia R

2012-01-01

Chronic inflammation is proposed to prime the development of prostate cancer. However, the mechanisms of prostate cancer initiation and development are not completely understood. The α(v)β(6) integrin has been shown to play a role in epithelial development, wound healing and some epithelial cancers [1, 2]. Here, we investigate the expression of α(v)β(6) in mouse models of prostatic inflammation and prostate cancer to establish a possible relationship between inflammation of the prostate, α(v)β(6) expression and the progression of prostate cancer. Using immunohistochemical techniques, we show expression of α(v)β(6) in two in vivo mouse models; the Pten(pc)-/- model containing a prostate- specific Pten tumor suppressor deletion that causes cancer, and the prostate ovalbumin-expressing transgenic (POET) inflammation mouse model. We show that the α(v)β(6) integrin is induced in prostate cancer and inflammation in vivo in these two mouse models. α(v)β(6) is expressed in all the mice with cancer in the Pten(pc-/-) model but not in age-matched wild-type mice. In the POET inflammation model, α(v)β(6) is expressed in mice injected with activated T-cells, but in none of the control mice. In the POET model, we also used real time PCR to assess the expression of Transforming Growth Factor Beta 1 (TGFβ1), a factor in inflammation that is activated by α(v)β(6). In conclusion, through in vivo evidence, we conclude that α(v)β(6) integrin may be a crucial link between prostatic inflammation and prostatic adenocarcinoma.

Adenocarcinoma of urinary bladder: A report of two patients

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Nitu Kumari

2015-01-01

Full Text Available Adenocarcinoma of the bladder is a rare tumor. Primary and metastatic adenocarcinomas of urinary bladder are morphologically similar, but histogenetically different. We present two cases, a signet ring cell adenocarcinoma with follow-up and another of glandular adenocarcinoma of urinary bladder. Pathological evaluation and immunohistochemical panel of eight markers (E-cadherin, CK20, CK7, CDX2, estrogen receptor (ER, gross cystic disease fluid protein 15 (GCDFP15, 34bE12, and prostate specific antigen (PSA provides a diagnostic confirmation of primary adenocarcinoma with the positive expression of E-cadherin and CK20 in case 1 and metastatic adenocarcinoma of prostate with profile of E-cadherin+, CK20-, GCDFP15+, 34bE12+, and PSA+ in case 2.

Adenocarcinoma of urinary bladder: A report of two patients.

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Kumari, Nitu; Vasudeva, Pawan; Kumar, Anup; Agrawal, Usha

2015-01-01

Adenocarcinoma of the bladder is a rare tumor. Primary and metastatic adenocarcinomas of urinary bladder are morphologically similar, but histogenetically different. We present two cases, a signet ring cell adenocarcinoma with follow-up and another of glandular adenocarcinoma of urinary bladder. Pathological evaluation and immunohistochemical panel of eight markers (E-cadherin, CK20, CK7, CDX2, estrogen receptor (ER), gross cystic disease fluid protein 15 (GCDFP15), 34bE12, and prostate specific antigen (PSA) provides a diagnostic confirmation of primary adenocarcinoma with the positive expression of E-cadherin and CK20 in case 1 and metastatic adenocarcinoma of prostate with profile of E-cadherin+, CK20-, GCDFP15+, 34bE12+, and PSA+ in case 2.

Advanced research on separating prostate cancer stem cells

International Nuclear Information System (INIS)

Hao Yumei; He Xin; Song Naling

2013-01-01

Prostate cancer is a common malignant tumor in male urinary system,and may easily develop into the hormone refractory prostate cancer which can hardly be cured. Recent studies had found that the prostate cancer stem cells may be the source of the prostate cancer's occurrence,development, metastasis and recurrence. The therapy targeting the prostate cancer stem cells may be the effective way to cure prostate cancer. But these cells is too low to be detected. The difficulty lies in the low separation efficiency of prostate cancer stem cell, so the effectively separating prostate cancer stem cells occupied the main position for the more in-depth research of prostate cancer stem cells. This paper reviews the research progress and existing problems on the several main separating methods of prostate cancer stem cells, includes the fluorescence activated cells sorting and magnetic activated cells sorting based on prostate cancer stem cell surface markers, the side-population sorting and serum-free medium sphere forming sorting based on prostate cancer stem cell's biology. (authors)

Increased aPKC Expression Correlates with Prostatic Adenocarcinoma Gleason Score and Tumor Stage in the Japanese Population

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Anthony S. Perry

2014-01-01

Full Text Available Background. Levels of the protein kinase aPKC have been previously correlated with prostate cancer prognosis in a British cohort. However, prostate cancer incidence and progression rates, as well as genetic changes in this disease, show strong ethnic variance, particularly in Asian populations. Objective. The aim of this study was to validate association of aPKC expression with prostatic adenocarcinoma stages in a Japanese cohort. Methods. Tissue microarrays consisting of 142 malignant prostate cancer cases and 21 benign prostate tissues were subject to immunohistological staining for aPKC. aPKC staining intensity was scored by three independent pathologists and categorized as absent (0, dim (1+, intermediate (2+, and bright (3+. aPKC staining intensities were correlated with Gleason score and tumor stage. Results. Increased aPKC staining was observed in malignant prostate cancer, in comparison to benign tissue. Additionally, aPKC staining levels correlated with Gleason score and tumor stage. Our results extend the association of aPKC with prostate cancer to a Japanese population and establish the suitability of aPKC as a universal prostate cancer biomarker that performs consistently across ethnicities.

Metastatic adenocarcinoma of prostate in a 28-year-old male: The outcome is poor in young patients?

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Renu Madan

2015-01-01

Full Text Available Prostate cancer is common in older patients. Rarity in younger population limits the study of natural history and prognosis in this population. Most of the published data has reported poor outcome in younger patients with metastatic prostate cancer. Here, we report a case of prostate cancer in 28-year-old male who presented with bone metastasis. After bilateral inguinal orchidectomy, he was started on anti-androgen therapy and received palliative radiotherapy for bone metastasis. There was only a slight decrease in prostate-specific antigen (PSA level and pelvic disease post treatment. Subsequently, he was started on opioid analgesics (by World Health Organization, WHO, step ladder in view of persistent pain. The index case is being presented for its rarity and probable poor outcome in young patients and to stress on the fact that the possibility of primary prostatic adenocarcinoma should be investigated in a male presenting with bone metastasis irrespective of the age.

Adjuvant radiotherapy for pathologic stage T3/4 adenocarcinoma of the prostate: Ten-year update

International Nuclear Information System (INIS)

Anscher, Mitchell S.; Robertson, Cary N.; Prosnitz, Leonard R.

1995-01-01

Purpose: To determine the role of adjuvant postoperative radiotherapy (RT) following radical prostatectomy (RP) in a group of patients with pathologic Stage T3/4 adenocarcinoma of the prostate followed for a median of 10 years after treatment. Methods and Materials: Between 1970 and 1983, 159 patients underwent RP for newly diagnosed adenocarcinoma of the prostate and were found to have pathologic Stage T3/4 tumors. Forty-six received adjuvant RT and 113 did not. Radiotherapy usually consisted of 45-50 Gy to the whole pelvis followed by a boost to the prostate bed of 10-15 Gy, to a total dose of 55-65 Gy. Patients were analyzed with respect to survival, disease-free survival, local control, and freedom from distant metastases. A rising prostate-specific antigen in the absence of other evidence of relapse was scored as a separate category of recurrence. Results: Both groups of patients have been followed for a median of 10 years. The actuarial survival at 10 and 15 years was 62% and 62% for the RT group compared to 52% and 37%, respectively, for the RP group (p = 0.18). The disease-free survival for the RT group was 55% and 48% at 10 and 15 years, respectively, compared to 37% and 33% for the RP group (p = 0.16). Similarly, there was no difference in the rate of distant metastases between the two groups. In contrast, the local relapse rate was significantly reduced by the addition of postoperative radiotherapy. The actuarial local control rate at 10 and 15 years was 92% and 82%, respectively, for the RT group vs. 60% and 53% for the RP group (p 0.002). Conclusions: While postoperative pelvic RT significantly improves local control compared to RP alone for pathologic Stage T3/4 prostate cancer, it has no impact on distant metastases and consequently does not improve survival. These data are consistent with the conclusion that many patients with pathologic Stage T3/4 prostate cancer have occult metastases at presentation and will not be cured by local therapies alone

CURRENT POSSIBILITIES OF TREATMENT FOR VISCERAL METASTASES IN PATIENTS WITH METASTATIC CASTRATION-REFRACTORY PROSTATE CANCER

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A. V. Govorov

2014-07-01

Full Text Available Medications increasing the survival of patients with metastatic castration-refractory prostate cancer (CRPC are lacking today. In the past 3 years, in the pharmaceutical market there have been a few novel drugs to treat progressive prostate cancer. Abiraterone acetate is an androgen synthesis inhibitor, which is also used to increase the survival of patients with metastatic CRPC that progresses after chemotherapy. The results of treatment for metastatic CRPC depend on a number of factors. Visceral metastases are poor predictors of the course of the disease. The results of abiraterone acetate treatment were analyzed in CRPC patients with visceral metastases.

Hormonal treatment of obstructed kidneys in patients with prostatic cancer

DEFF Research Database (Denmark)

Honnens de Lichtenberg, M; Miskowiak, J; Rolff, H

1993-01-01

A review of 1288 patients with previously untreated prostatic cancer revealed 209 patients (16%) with ureteric obstruction; the obstruction was bilateral in 36%. The effect of hormonal treatment was assessed in 88 patients with 120 obstructed kidneys: 77 patients had androgen deprivation...... or hormonal medication alone and 11 patients needed percutaneous nephrostomy or ureteric catheters in addition. Drainage improved in 58% of the kidneys. The diverting catheter was withdrawn in 9 of the 11 patients after a median of 4 weeks. In all, 95% of patients were discharged. The patients with hormonal...

Long-Term Results of a Phase II Trial of Ultrasound-Guided Radioactive Implantation of the Prostate for Definitive Management of Localized Adenocarcinoma of the Prostate (RTOG 98-05)

International Nuclear Information System (INIS)

Lawton, Colleen A.; Hunt, Daniel; Lee, W. Robert; Gomella, Leonard; Grignon, David; Gillin, Michael; Morton, Gerard; Pisansky, Thomas M.; Sandler, Howard

2011-01-01

Purpose: To evaluate the long-term effectiveness of transrectal ultrasound-guided permanent radioactive I 125 implantation of the prostate for organ confined adenocarcinoma of the prostate compared with historical data of prostatectomy and external beam radiotherapy within a cooperative group setting. Methods and Materials: Patients accrued to this study had histologically confirmed, locally confined adenocarcinoma of the prostate clinical stage T1b, T1c, or T2a; no nodal or metastatic disease; prostate-specific antigen level of ≤10 ng/ml; and a Gleason score of ≤6. All patients underwent transrectal ultrasound-guided radioactive I 125 seed implantation into the prostate. The prescribed dose was 145 Gy to the prostate planning target volume. Results: A total of 101 patients from 27 institutions were accrued to this protocol; by design, no single institution accrued more than 8 patients. There were 94 eligible patients. The median follow up was 8.1 years (range, 0.1-9.2 years). After 8 years, 8 patients had protocol-defined biochemical (prostate-specific antigen) failure (cumulative incidence, 8.0%); 5 patients had local failure (cumulative incidence, 5.5%); and 1 patient had distant failure (cumulative incidence, 1.1%; this patient also had biochemical failure and died of causes not related to prostate cancer). The 8-year overall survival rate was 88%. At last follow-up, no patient had died of prostate cancer or related toxicities. Three patients had maximum late toxicities of Grade 3, all of which were genitourinary. No Grade 4 or 5 toxicities were observed. Conclusions: The long-term results of this clinical trial have demonstrated that this kind of trial can be successfully completed through the RTOG and that results in terms of biochemical failure and toxicity compare very favorably with other brachytherapy published series as well as surgical and external beam radiotherapy series. In addition, the prospective, multicenter design highlights the probable

Radioimmunological determination of plasma testosterone, luteinizing hormone, folliculostimulating hormone and prolactin levels in patients with prostate cancer

International Nuclear Information System (INIS)

Milkov, V.; Maleeva, A.; Tsvetkov, M.; Visheva, N.

1986-01-01

The hormone levels were measured before and after hormonal therapy. Statistically significant changes in the levels of the hormones in this study were recognized (p<0,001) as a result of treatment with estrogen preparations. Plasma prolactin was raised before estrogen therapy (statistically significant rise, p<0,001), as compared to the levels in a control group of normal subjects. A mild tendency was observed toward its increase, depending on the duration of treatment. The results of this study show that control of the hormonal status of patients with prostate cancer may serve as reliable criterion in evaluating the effectiveness of hormonal therapy. The changes in prolactin levels are evidence of hormonal disbalance, which may be observed in these patients

The role of serum osteoprotegerine in metastatic prostate cancer - a case control study.

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Siampanopoulou, M; El, Mantani; Moustakas, G; Haritanti, A; Gotzamani-Psarrakou, A

2016-01-01

Prostate cancer is one of the most common malignant neoplastic diseases in men. Early control of the disease progression contributes significantly to survival rates and patients' quality of life. Osteoprotegerin is a dimeric glycoprotein, which affects bone metabolism and inhibits osteoclastogenesis. In the present study, we evaluated the expression of osteoprotegerin in the serum of prostate cancer patients with or without skeletal metastases. The expression of serum osteoprotegerin, as measured by enzyme-linked immunosorbent assay, has been studied in 82 patients with locally controlled prostate cancer, in 49 patients with metastatic bone disease and in a control group of 41 healthy males. At sampling time 65/131 of included patients were newly diagnosed, while 66/131 patients were already under hormonal therapy. All eligible prostate cancer patients had histologically confirmed malignancy. Serum total prostate-specific antigen (PSA) was determined by an immunoradiometric assay. We investigated the expression of osteoprotegerin in hormone-dependent and hormone-refractory prostate cancer and its relation to disease progression. Among the 131 patients with prostate cancer, higher osteoprotegerin and PSA concentrations have been observed in metastatic bone patients' sera (p cancer patients has shown a statistically significant area curve (p cancer patients (p cancer reflect the bone metastatic extent and may potentially be used in metastatic patients' follow-ups. Hippokratia 2016, 20(2): 133-138.

Early versus delayed hormonal treatment in locally advanced or asymptomatic metastatic prostatic cancer patient dilemma.

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Prezioso, Domenico; Iacono, Fabrizio; Romeo, Giuseppe; Ruffo, Antonio; Russo, Nicola; Illiano, Ester

2014-06-01

The objective of this work is to compare the effectiveness of hormonal treatment (luteinizing hormone-releasing hormone agonists and/or antiandrogens) as an early or as a deferred intervention for patients with locally advanced prostate cancer (LAPC) and/or asymptomatic metastasis. Systematic review of trials published in 1950-2007. Sources included MEDLINE and bibliographies of retrieved articles. Eligible trials included adults with a history of LAPC who are not suitable for curative local treatment of prostate cancer. We retrieved 22 articles for detailed review, of which 8 met inclusion criteria. The Veterans Administration Cooperative Urological Research Group suggested that delaying hormonal therapy did not compromise overall survival and that many of the patients died of causes other than prostate cancer. In European Organisation for Research and Treatment of Cancer (EORTC) 30846 trial, the median survival for delayed endocrine treatment was 6.1 year, and for immediate treatment 7.6 year, the HR for survival on delayed versus immediate treatment was 1.23 (95 % CI 0.88-1.71), indicating a 23 % nonsignificant trend in favour of early treatment. In EORTC 30891, the immediate androgen deprivation resulted in a modest but statistically significant increase in overall survival. The protocol SAKK 08/88 showed the lack of any major advantage of immediate compared with deferred hormonal treatment regarding quality of life or overall survival. The early intervention with hormonal treatment for patients with LAPC provides important reductions in all-cause mortality, prostate cancer-specific mortality, overall progression, and distant progression compared with deferring their use until standard care has failed to halt the disease.

Androgenic suppression combined with radiotherapy for the treatment of prostate adenocarcinoma: a systematic review

International Nuclear Information System (INIS)

Sasse, André D; Sasse, Elisa; Carvalho, Albertina M; Macedo, Ligia T

2012-01-01

Locally advanced prostate cancer is often associated with elevated recurrence rates. Despite the modest response observed, external-beam radiotherapy has been the preferred treatment for this condition. More recent evidence from randomised trials has demonstrated clinical benefit with the combined use of androgen suppression in such cases. The aim of this meta-analysis is to compare the combination of distinct hormone therapy modalities versus radiotherapy alone for overall survival, disease-free survival and toxicity. Databases (MEDLINE, EMBASE, LILACS, Cochrane databases and ClinicalTrials.gov) were scanned for randomised clinical trials involving radiotherapy with or without androgen suppression in local prostate cancer. The search strategy included articles published until October 2011. The studies were examined and the data of interest were plotted for meta-analysis. Survival outcomes were reported as a hazard ratio with corresponding 95% confidence intervals. Data from ten trials published from 1988 to 2011 were included, comprising 6555 patients. There was a statistically significant advantage to the use of androgen suppression, in terms of both overall survival and disease free survival, when compared to radiotherapy alone. The use of long-term goserelin (up to three years) was the strategy providing the higher magnitude of clinical benefit. In contrast to goserelin, there were no trials evaluating the use of other luteinizing hormone-releasing hormone (LHRH) analogues as monotherapy. Complete hormonal blockade was not shown to be superior to goserelin monotherapy. Based on the findings of this systematic review, the evidence supports the use of androgen suppression with goserelin monotherapy as the standard treatment for patients with prostate cancer treated with radiotherapy, which are at high risk of recurrence or metastases

Hormone therapy in metastatic prostate cancer

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Jebelameli P

1997-09-01

Full Text Available Only orchiectomy is still commonly used today either as a single therapy or in combination regimens. Hypophysectomy & adrenalectomy showed such devastating effects on the endocrine equilibrium as to be inconsistent with an acceptable quality of life or even with survival. Chemical adrenalectomy was also tried with drugs (eg. aminoglutethmide, spironolactone leading to consequences superimposable to those of surgical adrenalectomy. Along with orchiectomy, three groups of substances are commonly used today for the hormonal therapy of prostate cancer: estrogens, LHRH agonists & anti androgens. Bilateral orchiectomy removes 90-95% of circulating testosterone. Clinical studies document 60-80% of positive responders to castration, on continued evaluation, relapse occurs usually within 6-24 months in responders, with a death rate of 50% within 6 months. The androgenic activity still remaining after castration may explain the partial & progressively decreasing effectiveness of this & other testosterone reducing therapies. Antiandrogens define substances that act directly at the target site, where interacting with steroid hormone receptors, they impede the binding of androgens. A trend towards the combination of testosterone-reducing & androgen-blocking treatment is developing in modern therapy of prostate cancer. This is due to the complementary characteristics of the two different pharmacological mechanisms that are involved. In this study castration+antiandrogen is compared to castration alone. The results demonstrate a significantly greater percentage of positive objective & subjective responses with antiandrogen than with placebo. In addition survival time was increased in patients treated with castration+antiandrogen than castration+placebo.

Treatment of prostate adenocarcinoma permanent implants with I 125: first experience in Uruguay; Tratamiento del adenocarcinoma de prostata con implantes permanentes de I125: primera experiencia en el Uruguay

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Quarneti, A.; Clark, O.; Glaussius, A.; Kaitasoff, P.; Cosia, G.

2010-12-15

Full text: Objective: To report on the treatment done, toxicity and development of a group of adenocarcinoma patients with localized prostate brachytherapy implants permanent I125. Material and Methods. 37 patients were treated in the period 2001 to 2004 at the Military Hospital Central by this treatment modality. All of them were performed before implantation planning, which consisted of the volumetric calculation and calculation prostate dosimetry that included transrectal prostate ultrasound 3-5 weeks before the procedure. all patients had pathological confirmation of the lesion showed PSA values less than 11 ng / ml and Gleason score less than 7. 70% of patients received neo-adjuvant hormone therapy. In 5 patients an interactive planning system was performed computerized dosimetry, using sequential ultrasound imaging planes, allowed the dosimetric analysis before terminate the procedure and make necessary adjustments if the dose distribution did not conform. This additional dosimetric study we have not been described by other authors. Prescribed in the first 10 patients was dose 144 Gy and 160 Gy in subsequent. All patients underwent post implant CT waffle grid after 15 days of the procedure. analyzed the dose volume histogram (HDV) and D90 values??. Clinical follow-up was performed and PSA biochemical .. Preliminary Results: 33 patients were in local control without biochemical failure. Currently 4 patients presented biochemical recurrence with PSA values ??between 4 and 6 ng / ml. In neither disease was found at a distance and then raises confirmation tumor biopsy active presence will undergo surgical treatment protocols localized prostate cancer. HDV values ??D90 and are consistent with the informed by the international literature will be presented. No patient required hospitalization prolonged (greater than 24 hours) or use of higher analgesics. 2 patients had acute urinary retention (G II complication) between the tenth and twentieth day, the rest of the

Sipuleucel-T: Autologous Cellular Immunotherapy for Men with Asymptomatic or Minimally Symptomatic Metastatic Castrate Resistant Prostate Cancer

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Robert B. Sims

2011-01-01

Full Text Available Sipuleucel T is an autologous cellular immunotherapy designed to stimulate an immune response in men diagnosed with asymptomatic or minimally symptomatic metastatic castrate resistant (hormone refractory prostate cancer. Sipuleucel T improves overall survival and provides an additional treatment option for this patient population.

Phase I/II study on docetaxel, gemcitabine and prednisone in castrate refractory metastatic prostate cancer

DEFF Research Database (Denmark)

Buch-Hansen, Trine Zeeberg; Bentzen, Lise Nørgaard; Hansen, Steinbjoern

2010-01-01

DGP, maximum of eight courses, until progression or unacceptable toxicity. Docetaxel 75 mg/m(2) was administered intravenously day 1, gemcitabine was given day 1 and 8 in doses increasing from 600 to 1,000 mg/m(2) every third week. Patients had castrate refractory metastatic prostate cancer (CRMPC......), adequate function of liver, kidney and bone marrow; ECOG performance status...

The effect of androgen deprivation on the early changes in prostate volume following transperineal ultrasound guided interstitial therapy for localized carcinoma of the prostate

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Whittington, Richard; Broderick, Gregory A; Arger, Peter; Malkowicz, S Bruce; Epperson, Robert D; Arjomandy, Bijan; Kassaee, Alireza

1999-07-15

Purpose: To determine the change in volume of the prostate as a result of neoadjuvant androgen deprivation prior to prostate implant and in the early postimplant period following transperineal ultrasound guided palladium-103 brachytherapy for early-stage prostate cancer. Methods and Materials: Sixty-nine men received 3 to 6 months of androgen deprivation therapy followed by treatment planning ultrasound followed 4 to 8 weeks later by palladium-103 implant of the prostate. All patients had clinical and radiographic stage T1c-T2b adenocarcinoma of the prostate. A second ultrasound study was carried out 11 to 13 days following the implant to determine the change in volume of the prostate as a result of the implant. The prehormonal and preimplant volumes were compared to the postimplant volume to determine the effect of hormones and brachytherapy on prostate volume. Results: The median decrease in prostate volume as a result of androgen deprivation was 33% among the 54 patients with prostate volume determinations prior to hormonal therapy. The reduction in volume was greatest in the quartile of men with the largest initial gland volume (59%) and least in the quartile of men with smallest glands (10%). The median reduction in prostate volume between the treatment planning ultrasound and the follow-up study after implant was 3%, but 23 (33%) patients had an increase in prostate volume, including 16 (23%) who had an increase in volume >20%; 11 of these patients (16%) had an increase in volume >30%. The time course of development and resolution of this edema is not known. The severity of the edema was not related to initial or preimplant prostate volume or duration of hormonal therapy. Conclusions: Prostate edema may significantly affect the dose delivered to the prostate following transperineal ultrasound guided brachytherapy. The effect on the actual delivered dose will be greater when shorter lived isotopes are used. It remains to be observed whether this edema will

The management of localized and locally advanced prostate cancer - 1995

International Nuclear Information System (INIS)

Forman, Jeffrey D.

1995-01-01

Purpose/Objectives: The intent of this course is to review the issues involved in the management of non-metastatic adenocarcinoma of the prostate. - The value of pre-treatment prognostic factors including stage, grade and PSA value will be presented, and their value in determining therapeutic strategies will be discussed. - Controversies involving the simulation process and treatment design will be presented. The value of CT scanning, Beams-Eye View, 3-D planning, intravesicle, intraurethral and rectal contrast will be presented. The significance of prostate and patient movement and strategies for dealing with them will be presented. - The management of low stage, low to intermediate grade prostate cancer will be discussed. The dose, volume and timing of irradiation will be discussed as will the role of neo-adjuvant hormonal therapy, neutron irradiation and brachy therapy. The current status of radical prostatectomy and cryotherapy will be summarized. - Treatment of locally advanced, poorly differentiated prostate cancer will be presented including a discussion of neo-adjuvant and adjuvant hormones, dose-escalation and neutron irradiation. - Strategies for post-radiation failures will be presented including data on cryotherapy, salvage prostatectomy and hormonal therapy (immediate, delayed and/or intermittent). New areas for investigation will be reviewed. - The management of patients post prostatectomy will be reviewed. Data on adjuvant radiation and therapeutic radiation for biochemical or clinically relapsed patients will be presented. This course hopes to present a realistic and pragmatic overview for treating patients with non-metastatic prostatic cancer

Inter-observer reproducibility before and after web-based education in the Gleason grading of the prostate adenocarcinoma among the Iranian pathologists.

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Alireza Abdollahi

2014-05-01

Full Text Available This study was aimed at determining intra and inter-observer concordance rates in the Gleason scoring of prostatic adenocarcinoma, before and after a web-based educational course. In this self-controlled study, 150 tissue samples of prostatic adenocarcinoma are re-examined to be scored according to the Gleason scoring system. Then all pathologists attend a free web-based course. Afterwards, the same 150 samples [with different codes compared to the previous ones] are distributed differently among the pathologists to be assigned Gleason scores. After gathering the data, the concordance rate in the first and second reports of pathologists is determined. In the pre web-education, the mean kappa value of Interobserver agreement was 0.25 [fair agreement]. Post web-education significantly improved with the mean kappa value of 0.52 [moderate agreement]. Using weighted kappa values, significant improvement was observed in inter-observer agreement in higher scores of Gleason grade; Score 10 was achieved for the mean kappa value in post web-education was 0.68 [substantial agreement] compared to 0.25 (fair agreement in pre web-education. Web-based training courses are attractive to pathologists as they do not need to spend much time and money. Therefore, such training courses are strongly recommended for significant pathological issues including the grading of the prostate adenocarcinoma. Through web-based education, pathologists can exchange views and contribute to the rise in the level of reproducibility. Such programs need to be included in post-graduation programs.

Absorbed dose distributions in patients with bone metastases from hormone refractory prostate cancer treated with Re-186 HEDP

International Nuclear Information System (INIS)

Denis Bacelar, A.M.; Dearnaley, D.P.; Divoli, A.; Chittenden, S.; Du, Y.; Flux, G.D.; O'Sullivan, J.M.

2015-01-01

Full text of publication follows. Aim: intravenous administration of Re-186 hydroxyethylidene-diphosphonate (HEDP) is used for metastatic bone pain palliation in hormone refractory prostate cancer patients. Dosimetry for bone seeking radionuclides is challenging due to the complex structure with osteoblastic, osteolytic and mixed lesions. The aim of this study was to perform image-based patient-specific 3D convolution dosimetry to obtain a distribution of the absorbed doses to each lesion and estimate inter- and intra-patient variations. Materials and methods: 28 patients received a fixed 5 GBq activity of Re-186 HEDP followed by peripheral blood stem cell rescue at 14 days in a phase II trial. A FORTE dual-headed gamma camera was used to acquire sequential Single-Photon-Emission Computed Tomography (SPECT) data of the thorax and pelvis area at 1, 4, 24, 48 and 72 hours following administration. The projection data were reconstructed using filtered-back projection and were corrected for attenuation and scatter. Voxelised cumulated activity distributions were obtained with two different methods. First, the scans were co-registered and the time-activity curves were obtained on a voxel-by-voxel basis. Second, the clearance curve was obtained from the mean number of counts in each individual lesion and used to scale the uptake distribution taken at 24 hours. The calibration factors required for image quantification were obtained from a phantom experiment. An in-house developed EGSnrc Monte Carlo code was used for the calculation of dose voxel kernels for soft-tissue and cortical/trabecular bone used to perform convolution dosimetry. Cumulative dose-volume histograms were produced and mean absorbed doses calculated for each spinal and pelvic lesion. Results: preliminary results show that the lesion mean absorbed doses ranged from 25 to 55 Gy when the medium was soft tissue and decreased by 40% if bone was considered. The use of the cumulated activity distribution

Hormonal changes after localized prostate cancer treatment. Comparison between external beam radiation therapy and radical prostatectomy.

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Planas, J; Celma, A; Placer, J; Maldonado, X; Trilla, E; Salvador, C; Lorente, D; Regis, L; Cuadras, M; Carles, J; Morote, J

2016-11-01

To determine the influence of radical prostatectomy (RP) and external beam radiation therapy (EBRT) on the hypothalamic pituitary axis of 120 men with clinically localized prostate cancer treated with RP or EBRT exclusively. 120 patients with localized prostate cancer were enrolled. Ninety two patients underwent RP and 28 patients EBRT exclusively. We measured serum levels of luteinizing hormone, follicle stimulating hormone (FSH), total testosterone (T), free testosterone, and estradiol at baseline and at 3 and 12 months after treatment completion. Patients undergoing RP were younger and presented a higher prostate volume (64.3 vs. 71.1 years, p<0.0001 and 55.1 vs. 36.5 g, p<0.0001; respectively). No differences regarding serum hormonal levels were found at baseline. Luteinizing hormone and FSH levels were significantly higher in those patients treated with EBRT at three months (luteinizing hormone 8,54 vs. 4,76 U/l, FSH 22,96 vs. 8,18 U/l, p<0,0001) while T and free testosterone levels were significantly lower (T 360,3 vs. 414,83ng/dl, p 0,039; free testosterone 5,94 vs. 7,5pg/ml, p 0,018). At 12 months FSH levels remained significantly higher in patients treated with EBRT compared to patients treated with RP (21,01 vs. 8,51 U/l, p<0,001) while T levels remained significantly lower (339,89 vs. 402,39ng/dl, p 0,03). Prostate cancer treatment influences the hypothalamic pituitary axis. This influence seems to be more important when patients with prostate cancer are treated with EBRT rather than RP. More studies are needed to elucidate the role that prostate may play as an endocrine organ. Copyright © 2016 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

Síndrome de Fournier secundária a adenocarcinoma de próstata avançado: relato de caso Fournier's syndrome secondary to advanced prostatic adenocarcinoma: case report

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Rodrigo Rocha Batista

2010-06-01

Full Text Available A Síndrome de Fournier é uma fasciite necrotizante rapidamente progressiva que acomete a genitália e região perineal. Mesmo com os avanços na terapêutica, a morbidade e a mortalidade desta afecção permanecem elevadas. É relatado caso de paciente masculino, 70 anos, com diagnóstico de adenocarcinoma de próstata avançado. Há um dia com dor e aumento de volume escrotal associado a febre. Ao exame físico, paciente séptico com gangrena gasosa do pênis e escroto; ao toque retal, lesão ulcero-vegetante em parede anterior do reto estendendo-se de 3 a 7 cm da borda anal. Realizado desbridamento cirúrgico, com identificação de fístula reto-escrotal transtumoral. Estudo histo-patológico da lesão retal confirmou infiltração por adenocarcinoma de próstata. Recebeu alta hospitalar no vigésimo dia de internação, atualmente em acompanhamento oncológico ambulatorial.Fournier's syndrome is a rapidly progressive necrotizing fasciitis affecting the genitalia and perineal region. Even with the advances in therapy, morbidity and mortality of this disease remain high. We report the case of male patient, 70 years old, diagnosed with advanced adenocarcinoma of the prostate. A day with pain and swelling near scrotum associated with fever. The physical examination revealed septic patient with gas gangrene of the penis and scrotum; on digital rectal examination, a vegetative and ulcerated lesion on the anterior wall of the rectum extending from 3 to 7 cm from the anal edge. Performed surgical debridement, with identification of scrotal-rectal fistula transtumoral. Histo-pathological study of the lesion confirmed rectal infiltration by adenocarcinoma of prostate. Was discharged from the hospital on the twentieth day of hospitalization, outpatient cancer currently monitoring.

Computed tomography in the evaluation of the suspected carcinomatous prostate

International Nuclear Information System (INIS)

Price, J.M.; Davidson, A.J.

1979-01-01

Twenty-six patients with physical findings suspicious for prostatic cancer were examined by contrast-enhanced computed tomography (CT) of the prostate region prior to prostatic biopsy or resection. Twelve had benign hypertrophy and/or prostatitis and fourteen had adenocarcinoma. Prostatic contour, density, seminal vesicle 'angle,' extraprostatic soft tissue 'mass,' and the pelvic fat planes were evaluated. A nodular prostatic contour was found only in patients with adenocarcinoma of the prostate, indicating a role for CT in the diagnosis of this disease. Two patients with benign prostatic disease had extraprostatic soft tissue 'masses' identical to those seen in six patients with adenocarcinoma of the prostate, suggesting limited usefulness of CT in staging patients with known tumor. (orig.) [de

Prostate specific membrane antigen- a target for imaging and therapy with radionuclides

DEFF Research Database (Denmark)

Bouchelouche, Kirsten; Choyke, Peter L; Capala, Jacek

2010-01-01

Prostate cancer continues to represent a major health problem, and yet there is no effective treatment available for advanced metastatic disease. Thus, there is an urgent need for the development of more effective treatment modalities that could improve the outcome. Because prostate specific...... membrane antigen (PSMA), a transmembrane protein, is expressed by virtually all prostate cancers, and its expression is further increased in poorly differentiated, metastatic, and hormone-refractory carcinomas, it is a very attractive target. Molecules targeting PSMA can be labelled with radionuclides...... to become both diagnostic and/or therapeutic agents. The use of PSMA binding agents, labelled with diagnostic and therapeutic radio-isotopes, opens up the potential for a new era of personalized management of metastatic prostate cancer....

Lineage plasticity-mediated therapy resistance in prostate cancer.

Science.gov (United States)

Blee, Alexandra M; Huang, Haojie

2018-06-12

Therapy resistance is a significant challenge for prostate cancer treatment in clinic. Although targeted therapies such as androgen deprivation and androgen receptor (AR) inhibition are effective initially, tumor cells eventually evade these strategies through multiple mechanisms. Lineage reprogramming in response to hormone therapy represents a key mechanism that is increasingly observed. The studies in this area have revealed specific combinations of alterations present in adenocarcinomas that provide cells with the ability to transdifferentiate and perpetuate AR-independent tumor growth after androgen-based therapies. Interestingly, several master regulators have been identified that drive plasticity, some of which also play key roles during development and differentiation of the cell lineages in the normal prostate. Thus, further study of each AR-independent tumor type and understanding underlying mechanisms are warranted to develop combinational therapies that combat lineage plasticity in prostate cancer.

Prostate-Specific Antigen (PSA) Bounce After Dose-Escalated External Beam Radiation Therapy Is an Independent Predictor of PSA Recurrence, Metastasis, and Survival in Prostate Adenocarcinoma Patients.

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Romesser, Paul B; Pei, Xin; Shi, Weiji; Zhang, Zhigang; Kollmeier, Marisa; McBride, Sean M; Zelefsky, Michael J

2018-01-01

To evaluate the difference in prostate-specific antigen (PSA) recurrence-free, distant metastasis-free, overall, and cancer-specific survival between PSA bounce (PSA-B) and non-bounce patients treated with dose-escalated external beam radiation therapy (DE-EBRT). During 1990-2010, 1898 prostate adenocarcinoma patients were treated with DE-EBRT to ≥75 Gy with ≥5 years follow-up. Patients receiving neoadjuvant/concurrent androgen-deprivation therapy (n=1035) or with fewer than 4 PSA values obtained 6 months or more after post-EBRT completion (n=87) were excluded. The evaluable 776 patients were treated (median, 81.0 Gy). Prostate-specific antigen bounce was defined as a ≥0.2-ng/mL increase above the interval PSA nadir, followed by a decrease to nadir or below. Prostate-specific antigen relapse was defined as post-radiation therapy PSA nadir + 2 ng/mL. Median follow-up was 9.2 years (interquartile range, 6.9-11.3 years). One hundred twenty-three patients (15.9%) experienced PSA-B after DE-EBRT at a median of 24.6 months (interquartile range, 16.1-38.5 months). On multivariate analysis, younger age (P=.001), lower Gleason score (P=.0003), and higher radiation therapy dose (P=.0002) independently predicted PSA-B. Prostate-specific antigen bounce was independently associated with decreased risk for PSA relapse (hazard ratio [HR] 0.53; 95% confidence interval [CI] 0.33-0.85; P=.008), distant metastatic disease (HR 0.34; 95% CI 0.12-0.94; P=.04), and all-cause mortality (HR 0.53; 95% CI 0.29-0.96; P=.04) on multivariate Cox analysis. Because all 50 prostate cancer-specific deaths in patients without PSA-B were in the non-bounce cohort, competing-risks analysis was not applicable. A nonparametric competing-risks test demonstrated that patients with PSA-B had superior cancer-specific survival compared with patients without PSA-B (P=.004). Patients treated with dose-escalated radiation therapy for prostate adenocarcinoma who experience posttreatment PSA-B have

Combined radio- and hormone therapy of the prostate carcinoma

International Nuclear Information System (INIS)

Papic, R.

1979-08-01

Intention of this study is to detect in 49 patients suffering from prostate carcinomas, effects and side effects of radiotherapy. According to the present results, there is not any doubt that prostate carcinomas are radiosensitive. In all patients radiotherapy induced a prostate shrinkage and an increasing of consistency. It resulted that a prostate biopsy must be carried out in order to control the success of therapy. The success of the treatment depends upon tumour spreading and on its degree of differentiation. Within the observation period only in four cases metastasation of the prostate carcinoma occurred after radiotherapy. According to literature, the 5-year survival rate with an organ-defined prostate carcinoma ranges between 70 and 80% when radiotherapeutic methods are applied. The same authors indicate a 5-year survival rate between 42 and 48% for scattered carcinomas. Only minor side effects are provoked by radiotherapy. In 75% of the patients pollakisuria and dysuria resulted. After irradiation was finished, the symptoms disappeared and did not cause in any case any late complications. In 12% of the cases proctitic pain occurred during irradiation, which in 6% remained even after the treatment was terminated. We could prove unequivocally on our patients that passage impairments caused by a prostate carcinoma are improved by radiotherapy. Finally it can be said that this treatment is applicable for curing carcinoma which is localised on the prostate. In the case of an undefined, scattered carcinoma radiotherapy combined with hormone therapy is the treatment of choice. With regards to undesired side effects radiotherapy is superior to other therapeutic measures. (orig./MG) [de

Evolving perspectives of the role of novel agents in androgen-independent prostate cancer

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Sujith Kalmadi

2008-01-01

Full Text Available Metastatic androgen-independent prostate cancer presents an intriguing clinical challenge, with a subtle interaction between hormone-responsive and refractory tumor cell elements. The treatment of advanced prostate carcinoma, which had remained stagnant for several decades following the understanding of the link between androgenic stimulation and carcinogenesis, has now started to make steady headway with chemotherapy and targeted approaches. Metastatic prostate cancer is almost always treated with initial androgen deprivation, in various forms. However, despite such treatment androgen-independent prostate cancer cells eventually emerge and progress to threaten life. The therapeutic objectives for treatment of metastatic prostate cancer are to maintain the quality of life and prolong survival. The out-dated nihilistic dogma of deferring chemotherapy until the most advanced stages in advanced prostate cancer is now falling by the wayside with the development of newer effective, tolerable agents.

Seminal epithelium in prostate biopsy can mimic malignant and premalignant prostatic lesions.

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Arista-Nasr, J; Trolle-Silva, A; Aguilar-Ayala, E; Martínez-Benítez, B

2016-01-01

In most prostate biopsies, the seminal epithelium is easily recognised because it meets characteristic histological criteria. However, some biopsies can mimic malignant or premalignant prostatic lesions. The aims of this study were to analyse the histological appearance of the biopsies that mimic adenocarcinomas or preneoplastic prostatic lesions, discuss the differential diagnosis and determine the frequency of seminal epithelia in prostate biopsies. We consecutively reviewed 500 prostate puncture biopsies obtained using the sextant method and selected those cases in which we observed seminal vesicle or ejaculatory duct epithelium. In the biopsies in which the seminal epithelium resembled malignant or premalignant lesions, immunohistochemical studies were conducted that included prostate-specific antigen and MUC6. The most important clinical data were recorded. Thirty-six (7.2%) biopsies showed seminal epithelium, and 7 of them (1.4%) resembled various prostate lesions, including high-grade prostatic intraepithelial neoplasia, atypical acinar proliferations, adenocarcinomas with papillary patterns and poorly differentiated carcinoma. The seminal epithelium resembled prostate lesions when the lipofuscin deposit, the perinuclear vacuoles or the nuclear pseudoinclusions were inconspicuous or missing. Five of the 7 biopsies showed mild to moderate cellular atypia with small and hyperchromatic nuclei, and only 2 showed cellular pleomorphism. The patients were alive and asymptomatic after an average of 6 years of progression. The seminal epithelium resembles prostatic intraepithelial neoplasia, atypical acinar proliferations and various types of prostatic adenocarcinomas in approximately 1.4% of prostate biopsies. Copyright © 2015 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

Feasibility of robotic radical prostatectomy for medication refractory chronic prostatitis/chronic pelvic pain syndrome: Initial results

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Sameer Chopra

2016-01-01

Full Text Available Four patients diagnosed with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS, met criteria for National Institute of Health (NIH Category III prostatitis, failed multiple medicinal treatments and underwent robotic radical prostatectomy (RRP. Median operative time (range: 157 (127–259 min. Validated functional questionnaires responses and NIH CP symptom index (NIH-CPSI score were collected for each patient's status at different time points pre- and post-operatively. Median decreases (range were: International Prostate Symptom Score - 14 (1–19; Sexual Health Inventory for Men - 6 (−14–22; and NIH-CPSI total - 23.5 (13–33. Median length of follow-up (range was 34 (24–43 months. RRP appears to be an option for carefully selected patients with medication-refractory CP/CPPS who understand that baseline sexual function may not be restored postoperatively.

External radiation therapy of prostatic carcinoma and its relationship to hormonal therapy

International Nuclear Information System (INIS)

Takada, Chitose; Ito, Koushiro; Nishi, Junko; Yamamoto, Toshihiro; Hatanaka, Yoshimi; Baba, Yuji; Takahashi, Mutsumasa.

1995-01-01

From 1980 to 1990, a total of 54 patients with prostatic carcinoma were treated with external radiation therapy at the Kumamoto National Hospital. Ten patients were classified as Stage B, 22 as Stage C, and another 22 as Stage D according to the American Urological Association Clinical Staging System. The 5-year survival for all 54 patients was 30%. The 5-year disease-specific survival was 67% for Stage B, 47% for Stage C, and 26% for Stage D. The 5-year survival was 43% for patients in whom radiation therapy was initiated immediately after the first diagnosis or with less than one year of hormonal therapy, while it was 0% for patients in whom radiation therapy was initiated after more than one year of hormonal therapy (p=0.01). The cause of intercurrent death was acute myocardial infarction in four patients and acute cardiac failure in one. Four of these patients received hormonal therapy for more than one year. The incidence of radiation-induced proctitis was not severe. This study suggests that long-term hormonal therapy prior to radiation therapy worsens the prognosis of patients with prostatic carcinoma. (author)

N-Myc Drives Neuroendocrine Prostate Cancer Initiated from Human Prostate Epithelial Cells

Science.gov (United States)

Lee, John K.; Phillips, John W.; Smith, Bryan A.; Park, Jung Wook; Stoyanova, Tanya; McCaffrey, Erin F.; Baertsch, Robert; Sokolov, Artem; Meyerowitz, Justin G.; Mathis, Colleen; Cheng, Donghui; Stuart, Joshua M.; Shokat, Kevan M.; Gustafson, W. Clay; Huang, Jiaoti; Witte, Owen N.

2016-01-01

SUMMARY MYCN amplification and overexpression are common in neuroendocrine prostate cancer (NEPC). However, the impact of aberrant N-Myc expression in prostate tumorigenesis and the cellular origin of NEPC have not been established. We define N-Myc and activated AKT1 as oncogenic components sufficient to transform human prostate epithelial cells to prostate adenocarcinoma and NEPC with phenotypic and molecular features of aggressive, late-stage human disease. We directly show that prostate adenocarcinoma and NEPC can arise from a common epithelial clone. Further, N-Myc is required for tumor maintenance and destabilization of N-Myc through Aurora A kinase inhibition reduces tumor burden. Our findings establish N-Myc as a driver of NEPC and a target for therapeutic intervention. PMID:27050099

The relationship between serum PSA, six sex hormones and the benign or malignant prostate diseases

International Nuclear Information System (INIS)

Xu Yancun

2008-01-01

In order to study clinical significance of serum prostate-specific antigen (PSA), free prostate specific antigen (PSA), f/tPSA and six sex hormones in prostate diseases, the serum levels of PSA, fPSA, f/tPSA, T, P, E 2 , PRL, LH and FSH in 72 cases of hyperplasia of prostate patients and 40 patients with prostate cancer were determined by RIA. The results showed that the serum levels of T, E 2 , PRL, LH, FSH in the BPH Group were significantly lower than those of in Pca group, the serum level of P in Pca group were significantly lower than those in BPH group; the levels of fPSA and f/tPSA ratio in BPH Group were significantly higher than those in Pca group. The results suggest that benign and malignant prostate disease (BPH and Pca) was related with the hormone imbalance. The serum total PSA and fPSA can be regarded as important indicators in the diagnosis of BPH and Pea. The combined determination of PSA, fPSA and f/tPSA may improve the diagnostic accuracy of Pca. (authors)

Cholesterol biosynthesis inhibitor RO 48-8071 suppresses growth of hormone-dependent and castration-resistant prostate cancer cells

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Liang Y

2016-05-01

Full Text Available Yayun Liang,1 Benford Mafuvadze,1 Johannes D Aebi,2 Salman M Hyder1 1Dalton Cardiovascular Research Center and Department of Biomedical Sciences, University of Missouri-Columbia, Columbia, MO, USA; 2Medicinal Chemistry, Roche Pharma Research and Early Development (pRED, Roche Innovation Center Basel, F Hoffmann-La Roche Ltd., Basel, Switzerland Abstract: Standard treatment for primary prostate cancer includes systemic exposure to chemotherapeutic drugs that target androgen receptor or antihormone therapy (chemical castration; however, drug-resistant cancer cells generally emerge during treatment, limiting the continued use of systemic chemotherapy. Patients are then treated with more toxic standard therapies. Therefore, there is an urgent need for novel and more effective treatments for prostate cancer. The cholesterol biosynthetic pathway is an attractive therapeutic target for treating endocrine-dependent cancers because cholesterol is an essential structural and functional component of cell membranes as well as the metabolic precursor of endogenous steroid hormones. In this study, we have examined the effects of RO 48-8071 (4'-[6-(allylmethylaminohexyloxy]-4-bromo-2'-fluorobenzophenone fumarate; Roche Pharmaceuticals internal reference: RO0488071 (RO, which is an inhibitor of 2, 3-oxidosqualene cyclase (a key enzyme in the cholesterol biosynthetic pathway, on prostate cancer cells. Exposure of both hormone-dependent and castration-resistant human prostate cancer cells to RO reduced prostate cancer cell viability and induced apoptosis in vitro. RO treatment reduced androgen receptor protein expression in hormone-dependent prostate cancer cells and increased estrogen receptor β (ERβ protein expression in both hormone-dependent and castration-resistant prostate cancer cell lines. Combining RO with an ERβ agonist increased its ability to reduce castration-resistant prostate cancer cell viability. In addition, RO effectively suppressed the

Normal tissue complication probability: Does simultaneous integrated boost intensity-modulated radiotherapy score over other techniques in treatment of prostate adenocarcinoma

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Jothy Basu K

2009-01-01

Full Text Available Aim: The main objective of this study was to analyze the radiobiological effect of different treatment strategies on high-risk prostate adenocarcinoma. Materials and Methods: Ten cases of high-risk prostate adenocarcinoma were selected for this dosimetric study. Four different treatment strategies used for treating prostate cancer were compared. Conventional four-field box technique covering prostate and nodal volumes followed by three-field conformal boost (3D + 3DCRT, four-field box technique followed by intensity-modulated radiotherapy (IMRT boost (3D + IMRT, IMRT followed by IMRT boost (IMRT + IMRT, and simultaneous integrated boost IMRT (SIBIMRT were compared in terms of tumor control probability (TCP and normal tissue complication probability (NTCP. The dose prescription except for SIBIMRT was 45 Gy in 25 fractions for the prostate and nodal volumes in the initial phase and 27 Gy in 15 fractions for the prostate in the boost phase. For SIBIMRT, equivalent doses were calculated using biologically equivalent dose assuming the α/β ratio of 1.5 Gy with a dose prescription of 60.75 Gy for the gross tumor volume (GTV and 45 Gy for the clinical target volume in 25 fractions. IMRT plans were made with 15-MV equispaced seven coplanar fields. NTCP was calculated using the Lyman-Kutcher-Burman (LKB model. Results: An NTCP of 10.7 ± 0.99%, 8.36 ± 0.66%, 6.72 ± 0.85%, and 1.45 ± 0.11% for the bladder and 14.9 ± 0.99%, 14.04 ± 0.66%, 11.38 ± 0.85%, 5.12 ± 0.11% for the rectum was seen with 3D + 3DCRT, 3D + IMRT, IMRT + IMRT, and SIBIMRT respectively. Conclusions: SIBIMRT had the least NTCP over all other strategies with a reduced treatment time (3 weeks less. It should be the technique of choice for dose escalation in prostate carcinoma.

ANX7 as a Bio-Marker in Prostate and Breast Cancer Progression

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Meera Srivastava

2001-01-01

Full Text Available The ANX7 gene codes for a Ca2+-activated GTPase, which has been implicated in both exocytotic secretion in cells and control of growth. In this review, we summarize information regarding increased tumor frequency in the Anx7 knockout mice, ANX7 growth suppression of human cancer cell lines, and ANX7 expression in human tumor tissue micro-arrays. The loss of ANX7 is significant in metastatic and hormone refractory prostate cancer compared to benign prostatic hyperplasia. In addition, ANX7 expression has prognostic value for predicting survival of breast cancer patients.

Long-term disease stabilization by strontium 89 (89Sr) for castration and docetaxel-resistant prostate cancer. A case report

International Nuclear Information System (INIS)

Kamiyama, Yuki; Iguchi, Ryo; Makino, Yuki; Kanamaru, Sojun; Ito, Noriyuki; Imanaka, Kazufumi

2012-01-01

A 67-year old man was diagnosed with advanced prostate cancer with multiple pelvic lymph nodes and multiple bone metastases (cT2N1M1b), with an initial prostate specific antigen of 1,300 ng/ml. Prostate biopsy specimens revealed poorly differentiated adenocarcinoma, Gleason's score 5+3. He was treated with maximal androgen blockade (MAB) from 2001, but showed resistance to hormone therapy and docetaxel in 2007. External radiation therapy for bone pain was difficult due to multiple lesions. 89 Sr therapy was started in 2009. The therapy could be performed 5 times without any side effects. Good pain control and decreasing prostate specific antigen (PSA) was obtained at each dose. (author)

A phase 2 study of high-activity {sup 186}Re-HEDP with autologous peripheral blood stem cell transplant in progressive hormone-refractory prostate cancer metastatic to bone

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O' Sullivan, J.M. [Queen' s University Belfast/Belfast City Hospital, Department of Oncology, Belfast (United Kingdom); Norman, A.R. [Royal Marsden Foundation NHS Trust, Department of Computing, Sutton, Surrey (United Kingdom); McCready, V.R.; Flux, G.; Buffa, F.M. [Royal Marsden Foundation NHS Trust, Department of Physics, Sutton, Surrey (United Kingdom); Johnson, B. [Royal Marsden Foundation NHS Trust, Bob Champion Unit, Sutton, Surrey (United Kingdom); Coffey, J.; Horwich, A.; Huddart, R.A.; Parker, C.C.; Dearnaley, D.P. [Royal Marsden Foundation NHS Trust, Academic Unit of Urology, Sutton, Surrey (United Kingdom); Cook, G. [Royal Marsden Foundation NHS Trust, Department of Nuclear Medicine, Sutton, Surrey (United Kingdom); Treleaven, J. [Royal Marsden Foundation NHS Trust, Department of Haematology, Sutton, Surrey (United Kingdom)

2006-09-15

We investigated the potential for improvement in disease control by use of autologous peripheral blood stem cell transplant (PBSCT) to permit administration of high activities of {sup 186}Re-hydroxyethylidene diphosphonate (HEDP) in patients with progressive hormone-refractory prostate cancer (HRPC). Eligible patients had progressive HRPC metastatic to bone, good performance status and minimal soft tissue disease. Patients received 5,000 MBq of {sup 186}Re-HEDP i.v., followed 14 days later by PBSCT. Response was assessed using PSA, survival, pain scores and quality of life. Thirty-eight patients with a median age of 67 years (range 50-77) and a median PSA of 57 ng/ml (range 4-3,628) received a median activity of 4,978 MBq {sup 186}Re-HEDP (range 4,770-5,100 MBq). The most serious toxicity was short-lived grade 3 thrombocytopenia in 8 (21%) patients. The median survival of the group is 21 months (95%CI 18-24 months) with Kaplan-Meier estimated 1- and 2-year survival rates of 83% and 40% respectively. Thirty-one patients (81%, 95% CI 66-90%) had stable or reduced PSA levels 3 months post therapy while 11 (29%, 95% CI 15-49%) had PSA reductions of >50% lasting >4 weeks. Quality of life measures were stable or improved in 27 (66%) at 3 months. We have shown that it is feasible and safe to deliver high-activity radioisotope therapy with PBSCT to men with metastatic HRPC. Response rates and survival data are encouraging; however, further research is needed to define optimal role of this treatment approach. (orig.)

Multiple primary cancers: Simultaneously occurring prostate cancer ...

African Journals Online (AJOL)

We also reviewed the existing literatures for possible biologic links between prostatic carcinoma and other primary tumors. ... The primary tumors co-existing with prostate cancer were colonic adenocarcinoma, rectal adenocarcinoma, urinary bladder transitional cell carcinoma, primary liver cell carcinoma, and thyroid ...

Benzyl Isothiocyanate Inhibits Prostate Cancer Development in the Transgenic Adenocarcinoma Mouse Prostate (TRAMP Model, Which Is Associated with the Induction of Cell Cycle G1 Arrest

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Han Jin Cho

2016-02-01

Full Text Available Benzyl isothiocyanate (BITC is a hydrolysis product of glucotropaeolin, a compound found in cruciferous vegetables, and has been shown to have anti-tumor properties. In the present study, we investigated whether BITC inhibits the development of prostate cancer in the transgenic adenocarcinoma mouse prostate (TRAMP mice. Five-week old, male TRAMP mice and their nontransgenic littermates were gavage-fed with 0, 5, or 10 mg/kg of BITC every day for 19 weeks. The weight of the genitourinary tract increased markedly in TRAMP mice and this increase was suppressed significantly by BITC feeding. H and E staining of the dorsolateral lobes of the prostate demonstrated that well-differentiated carcinoma (WDC was a predominant feature in the TRAMP mice. The number of lobes with WDC was reduced by BITC feeding while that of lobes with prostatic intraepithelial neoplasia was increased. BITC feeding reduced the number of cells expressing Ki67 (a proliferation marker, cyclin A, cyclin D1, and cyclin-dependent kinase (CDK2 in the prostatic tissue. In vitro cell culture results revealed that BITC decreased DNA synthesis, as well as CDK2 and CDK4 activity in TRAMP-C2 mouse prostate cancer cells. These results indicate that inhibition of cell cycle progression contributes to the inhibition of prostate cancer development in TRAMP mice treated with BITC.

Significance and outcome of nuclear anaplasia and mitotic index in prostatic adenocarcinomas.

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Kır, Gozde; Sarbay, Billur Cosan; Gumus, Eyup

2016-10-01

The Gleason grading system measures architectural differentiation and disregards nuclear atypia and the cell proliferation index. Several studies have reported that nuclear grade and mitotic index (MI) are prognostically useful. This study included 232 radical prostatectomy specimens. Nuclear anaplasia (NA) was determined on the basis of nucleomegali (at least 20µm); vesicular chromatin; eosinophilic macronucleoli, nuclear lobulation, and irregular thickened nuclear membranei. The proportion of area of NA was recorded in each tumor in 10% increments. The MI was defined as the number of mitotic figures in 10 consecutive high-power fields (HPF). In univariate analysis, significant differences included associations between biochemical prostate-specific antigen recurrence (BCR) and Gleason score, extraprostatic extension, positive surgical margin, the presence of high-pathologic stage, NA≥10% of tumor area, MI≥3/10 HPF, and preoperative prostate-specific antigen. In a stepwise Cox regression model, a positive surgical margin, the presence of a NA≥10% of tumor area, and a MI of≥3/10 HPF were independent predictors of BCR after radical prostatectomy. NA≥10% of tumor area appeared to have a stronger association with outcome than MI≥3/10 HPF, as still associated with BCR when Gleason score was in the model. The results of our study showed that, in addition to the conventional Gleason grading system, NA, and MI are useful prognostic parameters while evaluating long-term prognosis in prostatic adenocarcinoma. Copyright © 2016 Elsevier Inc. All rights reserved.

PROSTATE-SPECIFIC ANTIGEN A Clue for the Prostatic Origin of Metastasis

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MANABE, Toshiaki; TSUKAYAMA, Chotatsu; YAMAGUCHI, Masae; YAMASHITA, Koshi

1983-01-01

The prostate-specific antigen is a recently purified glycoprotein which is present only in the prostatic gland. In order to confirm the usefulness of this protein in isolating prostatic carcinomas from socalled metastatic carcinomas of unknown primary site, we immunohistochemically studied 19 non-neoplastic prostatic tissue, 18 primary carcinomas of the prostate, and 32 non-prostatic adenocarcinomas. From our study, we concluded that PSA is highly specific for the prostatic carcinomas. The ab...

Nutrition, hormones and prostate cancer risk: results from the European prospective investigation into cancer and nutrition.

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Key, Timothy J

2014-01-01

Nutritional factors may influence the risk of developing prostate cancer, but understanding of this topic is poor. This chapter discusses research on this subject, mostly from the European Prospective Investigation into Cancer and Nutrition (EPIC), a cohort which includes 150,000 men recruited in the 1990s in eight European countries. So far the EPIC collaborators have published analyses of the relationship of prostate cancer risk with the intake of a range of foods and nutrients, and with blood-based markers of nutritional factors, on up to nearly 3,000 incident cases of prostate cancer. Most of the results of these analyses have been null, with no clear indication that the risk for prostate cancer is related to intakes of meat, fish, fruit, vegetables, fibre, fat or alcohol or with blood levels of fatty acids, carotenoids, tocopherols, B vitamins, vitamin D, or selenium. There is some evidence from EPIC that risk may be increased in men with a high intake of protein from dairy products, and analyses of hormone levels have shown that risk is higher in men with relatively high blood levels of insulin-like growth factor-I (IGF-I). More research is needed to better describe the relationships of prostate cancer risk with IGF-I and related hormones, and to better understand whether nutritional factors may influence risk through hormones or perhaps by other mechanisms.

Total Androgen Blockade Versus a Luteinizing Hormone-Releasing Hormone Agonist Alone in Men With High-Risk Prostate Cancer Treated With Radiotherapy

International Nuclear Information System (INIS)

Nanda, Akash; Chen, M.-H.; Moran, Brian J.; Braccioforte, Michelle H.; Dosoretz, Daniel; Salenius, Sharon; Katin, Michael; Ross, Rudi; D'Amico, Anthony V.

2010-01-01

Purpose: To assess whether short-course total androgen blockade vs. a luteinizing hormone-releasing hormone (LHRH) agonist alone affects the risk of prostate cancer-specific mortality (PCSM) in men with localized but high-risk disease treated with radiotherapy. Methods and Materials: The study cohort comprised 628 men with T1-T4, N0, M0 prostate cancer with high-risk disease (prostate-specific antigen level >20 ng/mL, Gleason score ≥8, or clinical category ≥T3) treated with 45 Gy of external beam radiotherapy followed by a brachytherapy boost in addition to receiving a median of 4.3 (interquartile range [IQR], 3.6-6.4) months of hormonal blockade with an LHRH agonist plus an antiandrogen or monotherapy with an LHRH agonist. Fine and Gray's multivariable regression analysis was used to determine whether combination androgen suppression therapy (AST) vs. monotherapy affected the risk of PCSM, adjusting for treatment year, duration of AST, age, and known prognostic factors. Results: After a median follow-up of 4.9 (IQR, 3.5-6.5) years, men receiving combination AST had a lower risk of PCSM than those treated with monotherapy (adjusted hazard ratio [AHR], 0.18; 95% confidence interval [CI], 0.04-0.90; p = 0.04). An increasing prostate-specific antigen level (AHR, 2.70; 95% CI, 1.64-4.45; p < 0.001) and clinical category T3/4 disease (AHR, 29.6; 95% CI, 2.88-303.5; p = 0.004) were also associated with an increased risk of PCSM. Conclusions: In men with localized but high-risk prostate cancer treated with external beam radiotherapy and brachytherapy, short-course AST with an LHRH agonist plus an antiandrogen is associated with a decreased risk of PCSM when compared with monotherapy with an LHRH agonist.

Talimogene Laherparepvec and Nivolumab in Treating Patients With Refractory Lymphomas or Advanced or Refractory Non-melanoma Skin Cancers

Science.gov (United States)

2018-05-21

Adenoid Cystic Carcinoma; Adnexal Carcinoma; Apocrine Carcinoma; Eccrine Porocarcinoma; Extraocular Cutaneous Sebaceous Carcinoma; Hidradenocarcinoma; Keratoacanthoma; Malignant Sweat Gland Neoplasm; Merkel Cell Carcinoma; Microcystic Adnexal Carcinoma; NK-Cell Lymphoma, Unclassifiable; Non-Melanomatous Lesion; Paget Disease; Papillary Adenocarcinoma; Primary Cutaneous Mucinous Carcinoma; Refractory Anaplastic Large Cell Lymphoma; Refractory Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Refractory Mycosis Fungoides; Refractory Primary Cutaneous T-Cell Non-Hodgkin Lymphoma; Refractory T-Cell Non-Hodgkin Lymphoma; Sezary Syndrome; Signet Ring Cell Carcinoma; Skin Basal Cell Carcinoma; Skin Basosquamous Cell Carcinoma; Skin Squamous Cell Carcinoma; Spiradenocarcinoma; Squamous Cell Carcinoma of Unknown Primary Origin; Stage III Skin Cancer; Stage IV Skin Cancer; Sweat Gland Carcinoma; Trichilemmocarcinoma; Vulvar Squamous Cell Carcinoma

Preclinical Studies of Signaling Pathways in a Mutant Mouse Model of Hormone-Refractory Prostate Cancer

Science.gov (United States)

2011-02-01

intraepithelial neoplasia in the mouse prostate. Cancer Res 63: 8784–8790. Joshua AM, Vukovic B, Braude I, Hussein S, Zielenska M, Srigley J , Evans A, Squire JA...prostate tumors 4. Reportable Outcomes Kinkade, C.W., Castillo-Martin, M., Puzio-Kuter, A., Yan, J ., Foster, T.H., Gao, H., Sun,, Y., Ouyang, X...2) Uzgare, A. R. and Isaacs, J . T. (2004). Enhanced redundancy in Akt and mitogen-activated protein kinase-induced survival of malignant versus

Radiation therapy of prostatic carcinoma

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Jacobsen, A B; Fossaa, S D; Oedegaard, A [Norske Radiumhospital, Oslo

1980-07-10

Between 1971 and 1976, 33 patients with adenocarcinoma of the prostate T2-T4 and without evidence of distant metastases have been treated with high energy radiotherapy 50-70Gy given to the primary tumour. 72% showed local response to the treatment. Actuarial 5 years survival (uncorrected) for patients primarily treated with radiotherapy was 52%, but for patients who had earlier received oestrogens, only 16%. The results in terms of local control as well as survival were best for category T2 and T3 patients who had not previously received hormone treatment. The response rate was better for moderately differentiated carcinomas than for poorly differentiated carcinomas.

Chemoprevention of hormone-dependent prostate cancer in the Wistar-Unilever rat.

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McCormick, D L; Rao, K V

1999-01-01

The high incidence and long latent period of prostate cancer make it an ideal target for chemoprevention. We have evaluated a series of agents for chemopreventive efficacy using a model in which hormone-dependent prostate cancers are induced in the Wistar-Unilever (WU) rat by sequential treatment with antiandrogen (cyproterone acetate), androgen (testosterone propionate), and direct-acting chemical carcinogen (N-methyl-N-nitrosourea), followed by chronic androgen stimulation (testosterone). This regimen reproducibly induces prostate cancers in high incidence, with no gross toxicity and a low incidence of neoplasia in the seminal vesicle and other non-target tissues. Dehydroepiandrosterone (DHEA) and 9-cis-retinoic acid (9-cis-RA) are the most active agents identified to date. DHEA inhibits prostate cancer induction both when chronic administration is begun prior to carcinogen exposure, and when administration is delayed until preneoplastic prostate lesions are present. 9-cis-RA is the most potent inhibitor of prostate carcinogenesis identified; a study to determine the efficacy of delayed administration of 9-cis-RA is in progress. Liarozole fumarate confers modest protection against prostate carcinogenesis, while N-(4-hydroxyphenyl)retinamide (fenretinide), alpha-difluoromethylornithine, oltipraz, DL-alpha-tocopherol acetate (vitamin E), and L-selenomethionine are inactive. Chemoprevention efficacy evaluations in the WU rat will support the identification of agents that merit study for prostate cancer chemoprevention in humans.

Testicular Metastasis of Prostate Cancer: A Case Report

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Ayumu Kusaka

2014-09-01

Full Text Available The incidence of secondary neoplasms of the testis during autopsies is approximately 2.5%. Although most secondary testicular metastases are due to prostate cancer, only a few patients with prostate cancer have clinically manifested testicular metastasis. We report the case of a prostate cancer patient with testicular metastasis who was diagnosed after the presence of a palpable mass in the right testis. A 56-year-old Japanese male presented to our hospital with an elevated serum prostate-specific antigen (PSA level of 137 ng/ml. He was diagnosed with stage IV (T3N1M1b prostate cancer and received androgen deprivation therapy, followed by various hormonal manipulations. His serum PSA level was undetectable for 1 year. No distant metastases were detected during imaging examinations. He received radiation therapy; however, his serum PSA level increased gradually. Four months later, he presented with right testicular swelling. Computed tomography revealed a heterogenous mass in the right testis and a right high inguinal orchiectomy was performed. Histopathological analysis showed that the right testis was infiltrated with metastatic adenocarcinoma with a Gleason score of 8. This is a rare case of right testicular metastasis in a patient with prostate cancer. Testicular metastasis of prostate cancer can be aggressive and metastasize.

Adenocarcinoma Prostate With Neuroendocrine Differentiation: Potential Utility of 18F-FDG PET/CT and 68Ga-DOTANOC PET/CT Over 68Ga-PSMA PET/CT.

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Parida, Girish Kumar; Tripathy, Sarthak; Datta Gupta, Shreya; Singhal, Abhinav; Kumar, Rakesh; Bal, Chandrasekhar; Shamim, Shamim Ahmed

2018-04-01

Ga-PSMA PET/CT is the upcoming imaging modality for staging, restaging and response assessment of prostate cancer. However, due to neuroendocrine differentiation in some of patients with prostate cancer, they express somatostatin receptors instead of prostate specific membrane antigen. This can be exploited and other modalities like Ga-DOTANOC PET/CT and F-FDG PET/CT should be used in such cases for guiding management. We hereby discuss a similar case of 67-year-old man of adenocarcinoma prostate with neuroendocrine differentiation, which shows the potential pitfall of Ga-PSMA PET/CT imaging and benefit of Ga-DOTANOC PET/CT and F-FDG PET/CT in such cases.

Complete androgen blockade safely allows for delay of cytotoxic chemotherapy in castration refractory prostate cancer

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Rafael A. Kaliks

2010-06-01

Full Text Available PURPOSE: Complete androgen blockade (CAB does not prolong overall survival (OS in patients with castration refractory prostate cancer (CRPC. Although there is variable clinical benefit with second-line hormone manipulation, we do not know which patients might benefit the most. OBJECTIVES: To identify clinical predictors of benefit of complete androgen blockade. MATERIALS AND METHODS: We reviewed the records for 54 patients who received treatment with CAB in the setting of disease progression despite castration. We evaluated progression-free survival (PFS and OS according to PSA at diagnosis, Gleason scores, age, testosterone level, and duration of prior disease control during castration in first line treatment. RESULTS: Among 54 patients who received CAB, the median PFS was 9 months (CI 4.3-13.7 and OS was 36 months (CI 24-48. We did not find an effect of PSA at diagnosis (p = 0.32, Gleason score (p = 0.91, age (p = 0.69 or disease control during castration (p = 0.87 on PFS or OS. Thirty-four patients subsequently received chemotherapy, with a mean OS of 21 months (CI 16.4-25.5, median not reached. CONCLUSION: Age, Gleason score, PSA at diagnosis and length of disease control with castration did not affect PFS or OS. In the absence of predictors of benefit, CAB should still be considered in CRPC.

Hormone therapy and radiotherapy for early prostate cancer: A utility-adjusted number needed to treat (NNT) analysis

International Nuclear Information System (INIS)

Jani, Ashesh B.; Kao, Johnny; Heimann, Ruth; Hellman, Samuel

2005-01-01

Purpose: To quantify, using the number needed to treat (NNT) methodology, the benefit of short-term (≤6 months) hormone therapy adjuvant to radiotherapy in the group of patients with early (clinical stage T1-T2c) prostate cancer. Methods and materials: The absolute biochemical control benefit for the use of hormones adjuvant to radiotherapy in early-stage disease was determined by literature review. A model was developed to estimate the utility-adjusted survival detriment due to the side effects of hormone therapy. The NNTs before and after the incorporation of hormone sequelae were computed; the sign and magnitude of the NNTs were used to gauge the effect of the hormones. Results: The absolute NNT analysis, based on summarizing the results of 8 reports including a total of 3652 patients, demonstrated an advantage to the addition of hormones for the general early-stage prostate cancer population as well as for all prognostic groups. After adjustment for hormone-induced functional loss, the advantage of hormones remained considerable in the high- and intermediate-risk groups, with the utility-adjusted NNT becoming weakened in the low-risk group when the utility compromise from complications of hormones was assumed to be considerable. Conclusions: Short-term hormone therapy seems to be beneficial for selected early-stage prostate cancer patients. The advantage seems to be greatest in the intermediate- and high-risk groups; with current follow-up, the side effects of hormones may outweigh their benefit in certain clinical situations in the favorable group. The present investigation demonstrates the significant role of the NNT technique for oncologic and radiotherapeutic management decisions when treatment complications need to be considered and balanced with the beneficial effects of the treatment

Significance of periacinar cleftings as supporting criteria in diagnosis of prostatic adenocarcinoma Gleason score-a 7 (3+4 and Gleason score-a 7 (4+3 and their relationship with parameters of predictive value

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Mijović Milica

2014-01-01

Full Text Available Diagnosis of different pathohystological diseases of prostate in the most cases is based on common benignant and malignant characteristics. The presence of periacinar cleftings (PC is an additional criterion favouring prostatic adenocarcinoma. According to the presence and extent of PC, analysed on high power field (400x, glands were classified into 3 groups: group 1-glands without PC or with PC affecting ≤50% of gland circumference; group 2-glands with PC affecting >50% gland circumference in 50% gland circumference in ≥50% examined glands. The aim of our study was to determine the importance of presence of PC in prostatic adenocarcinoma (ADCP of Gleason score 7(3+4 and 7(4+3 and establish the existence of differences in their appearance at ADCP with first and second dominant histological grade 3 and 4 in each different relationship based on correlation analysis of PC and parameters of the predictive value (preoperative value of serum prostate specific antigen, tumor volume, clinical stage and degree of focal neuroendocrine differentiation. The study included 33 ADCP of Gleason score 7, 26 (78.79% ADCP 7(3+4 and 7 (21.21% ADCP 7(4+3. In ADCP Gleason 7(3+4 periacinar cleftings are more common in tumors that are smaller, better differentiated (produce more PSA, which is diagnosed in less advanced clinical stages and showing a less degree of focal neuroendocrine differentiation. In ADCP Gleason 7(4+3 periacinar cleftings are more common in tumors which produce less value of serum PSA (poorly differentiated and in tumors that are diagnosed in advanced clinical stages. Periacinar cleftings are common findings in prostatic adenocarcinoma Gleason score 7(4+3 which are considerd as tumors with worse prognosis. Because of all we can rank PC among the important additional criteria for the diagnosis of adenocarcinoma of the prostate.

Development of an immunotherapeutic adenovirus targeting hormone-independent prostate cancer

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Kim JS

2013-11-01

Full Text Available Jae Sik Kim,1 Sang Don Lee,2 Sang Jin Lee,3 Moon Kee Chung21Department of Urology, The Catholic University of Korea Incheon St Mary's Hospital, Incheon, 2Pusan National University Yangsan Hospital and Research Institute for Convergence of Biomedical Science and Technology, Yangsan, 3Genitourinary Cancer Branch, National Cancer Center, Goyang, KoreaBackground: To develop a targeting therapy for hormone-independent prostate cancer, we constructed and characterized conditionally replicating oncolytic adenovirus (Ad equipped with mRFP(monomeric red fluorescence protein/ttk (modified herpes simplex virus thymidine kinase This construct was then further modified to express both mRFP/ttk and a soluble form of cytokine FLT3L (fms-related tyrosine kinase 3 ligand simultaneously.Methods: To construct the recombinant oncolytic adenovirus, E1a and E4 genes, which are necessary for adenovirus replication, were controlled by the prostate-specific enhancer sequence (PSES targeting prostate cancer cells expressing prostate-specific antigen (PSA and prostate-specific membrane antigen (PSMA. Simultaneously, it expressed the mRFP/ttk fusion protein in order to be able to elicit the cytotoxic effect.Results: The Ad5/35PSES.mRFP/ttk chimeric recombinant adenovirus was generated successfully. When replication of Ad5/35PSES.mRFP/ttk was evaluated in prostate cancer cell lines under fluorescence microscopy, red fluorescence intensity increased more in LNCaP cells, suggesting that the mRFP/ttk fusion protein was folded functionally. In addition, the replication assay including wild-type adenovirus as a positive control showed that PSES-positive cells (LNCaP and CWR22rv permitted virus replication but not PSES-negative cells (DU145 and PC3. Next, we evaluated the killing activity of this recombinant adenovirus. The Ad5/35PSES.mRFP/ttk killed LNCaP and CWR22rv more effectively. Unlike PSES-positive cells, DU145 and PC3 were resistant to killing by this recombinant

Imaging evaluation of prostate cancer with {sup 18}F-fluorodeoxyglucose PET/CT: utility and limitations

Energy Technology Data Exchange (ETDEWEB)

Jadvar, Hossein [University of Southern California, Division of Nuclear Medicine, Department of Radiology, Keck School of Medicine, Los Angeles, CA (United States)

2013-07-15

Prostate cancer is a major public health problem in developed countries. The remarkable biological and clinical heterogeneity of prostate cancer provides unique opportunities as well as challenges for the diagnostic imaging evaluation of this prevalent disease. The disease is characterized by a natural history that ranges from localized slowly growing hormone-dependent tumor progressing to metastatic hormone-refractory disease. PET is an ideal imaging tool for noninvasive interrogation of the underlying tumor biology. {sup 18}F-FDG is the most common PET radiotracer used for oncological applications based upon elevated glucose metabolism in malignant tissue in comparison to normal tissue. FDG uptake in prostate cancer depends on tumor differentiation with low accumulation in well-differentiated tumors and high uptake in aggressive poorly differentiated tumors. Cumulative current evidence suggests that FDG PET may be useful in detection of disease in a small fraction of patients with biochemical recurrence, in the imaging evaluation of extent and treatment response in metastatic disease and in prediction of patient outcome. (orig.)

Clinical significance of suboptimal hormonal levels in men with prostate cancer treated with LHRH agonists.

Science.gov (United States)

Kawakami, Jun; Morales, Alvaro

2013-01-01

We examined the serum levels of testosterone (T) (total and bioavailable) dehydroepiandrosterone (DHEA), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prostate-specific antigen (PSA) in men receiving treatment with luteinizing hormone releasing-hormone (LHRH) agonists for metastatic prostate cancer. In doing this, we want to determine the efficacy of these agents in lowering T levels and whether a possible relationship exists between PSA values, as a surrogate measure of tumour activity, and hormone levels. This was a single centre prospective study of patients on LHRH agonists. Of all the 100 eligible patients, 31 did not qualify (10 were receiving their first injection, 13 were on intermittent hormonal therapy, 7 refused to enter the trial and 1 patient's blood sample was lost). Therefore in total, 69 patients were included in the final analysis. Each patient had their blood sample drawn immediately before the administration of a LHRH agonist. The new proposed criteria of values are more commonly found in patients with suboptimal levels of testosterone receiving LHRH analogs, but the clinical importance of this finding has not been established. There is no significant difference with respect to hormonal levels reached among patients on a variety of LHRH agonists. Total testosterone determinations should be considered in patients on LHRH agonist therapy, particularly when the PSA values begin to rise since it may lead to further beneficial hormonal manipulation.

Plasma and tissue insulin-like growth factor-I receptor (IGF-IR) as a prognostic marker for prostate cancer and anti-IGF-IR agents as novel therapeutic strategy for refractory cases: a review.

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Ozkan, Emine Elif

2011-09-15

Cancer database analysis indicates that prostate cancer is one of the most seen cancers in men meanwhile composing the leading cause of morbidity and mortality among developed countries. Current available therapies are surgery, radiotherapy and androgene ablation for prostate carcinoma. The response rate is as high nearly 90% however, most of these recur or become refractory and androgene independent (AI). Therefore recent studies intensified on molecular factors playing role on development of prostate carcinoma and novel treatment strategies targetting these factors and their receptors. Insulin-like growth factor-I (IGF-I) and its primary receptor insulin-like growth factor receptor-I (IGF-IR) are among these factors. Biologic functions and role in malign progression are primarily achieved via IGF-IR which is a type 2 tyrosine kinase receptor. IGF-IR plays an important role in mitogenesis, angiogenesis, transformation, apoptosis and cell motility. It also generates intensive proliferative signals leading to carcinogenesis in prostate tissue. So IGF-IR and its associated signalling system have provoked considerable interest over recent years as a novel therapeutic target in cancer. In this paper it is aimed to sum up the lately published literature searching the relation of IGF-IR and prostate cancer in terms of incidence, pathologic features, and prognosis. This is followed by a discussion of the different possible targets within the IGF-1R system, and drugs developed to interact at each target. A systems-based approach is then used to review the in vitro and in vivo data in the published literature of the following compounds targeting IGF-1R components using specific examples: growth hormone releasing hormone antagonists (e.g. JV-1-38), growth hormone receptor antagonists (e.g. pegvisomant), IGF-1R antibodies (e.g. CP-751,871, AVE1642/EM164, IMC-A12, SCH-717454, BIIB022, AMG 479, MK-0646/h7C10), and IGF-1R tyrosine kinase inhibitors (e.g. BMS-536942, BMS-554417

Comparison of gamma radiation - induced effects in two human prostate cancer cells

International Nuclear Information System (INIS)

Vucic, V.; Adzic, M.; Ruzdijic, S.; Radojcic, M.B. . E-mail address of corresponding author: vesnav@vin.bg.ac.yu; Vucic, V.)

2005-01-01

In this study, the effects of gamma radiation on two hormone refractory human prostate cancer cell lines, DU 145 and PC-3, were followed. It was shown that gamma radiation induced significant inhibition of cell proliferation and viability in dose dependent manner. Antiproliferative effects of radiation were similar in both cell lines, and more pronounced than cytotoxic effects. In addition to that, PC-3 cell line was more resistant to radiation -induced cytotoxicity. (author)

Long-term Efficacy and Safety of Enzalutamide Monotherapy in Hormone-naïve Prostate Cancer

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Tombal, Bertrand; Borre, Michael; Rathenborg, Per

2015-01-01

BACKGROUND: Enzalutamide is an androgen receptor inhibitor with a demonstrated overall survival benefit in metastatic castration-resistant prostate cancer. A phase 2 study of enzalutamide monotherapy in patients with hormone-naïve prostate cancer (HNPC) showed a high response rate...... cancer, enzalutamide maintained long-term reductions in prostate-specific antigen, with a minimal impact on total-body bone mineral density. TRIAL REGISTRATION: NCT01302041....... for the prespecified primary endpoint (ie, prostate-specific antigen [PSA] response at week 25), regardless of metastases at baseline, and favorable tolerability. OBJECTIVE: To determine the long-term efficacy and safety of enzalutamide monotherapy at 1 and 2 yr. DESIGN, SETTING, AND PARTICIPANTS: Open-label, single...

Granulomatous prostatitis - an infrequent diagnosis

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RPS Punia

2002-01-01

Full Text Available Granulomatous prostatitis is a rare disorder of pros-tate. We encountered 10 cases of′grmudomatous prosta-titis consisting of 5 cases of non-specific granulomatous prostatitis, 2 cases of xanthogranulomatous prostatitis, I case of tuberculous prostatitis, I case of malakoplakia prostate and I case of granulomatous prostatitis associ-ated with adenocarcinoma prostate. The diagnosis was made by histopathologic examination of trucut biopsy, TURP chips or retropubic prostatectomy specimen. In all the cases, granulomatous prostatitis was an incidental find-ing.

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

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Siegfried Wagner

2014-01-01

Full Text Available Prostate cancer is worldwide the sixth leading cause of cancer related death in men thus early detection and successful treatment are still of major interest. The commonly performed screening of the prostate-specific antigen (PSA is controversially discussed, as in many patients the prostate-specific antigen levels are chronically elevated in the absence of cancer. Due to the unsatisfying efficiency of available prostate cancer screening markers and the current treatment outcome of the aggressive hormone refractory prostate cancer, the evaluation of novel molecular markers and targets is considered an issue of high importance. MicroRNAs are relatively stable in body fluids orchestrating simultaneously the expression of many genes. These molecules are currently discussed to bear a greater diagnostic potential than protein-coding genes, being additionally promising therapeutic drugs and/or targets. Herein we review the potential impact of the microRNA let-7 family on prostate cancer and show how deregulation of several of its target genes could influence the cellular equilibrium in the prostate gland, promoting cancer development as they do in a variety of other human malignant neoplasias.

[Hormonal and metabolic effects of drinking mineral water and phytoaeronisation in experimental prostatitis].

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Polushina, N D; Agaev, A A; Shchelkunov, A V; Eseneev, S M

2004-01-01

Prostatitis modelled in 53 Wistar male rats (300-350 body mass) 7 days after its induction was treated with mineral water "Essentuki N 17" (MW) which was taken in a dose 1.5-2 ml per 100 g body mass for 23-24 days. In addition, some animals received phytoaeroionisation (PAI) with solution of essential oils of mint, sage and lavender. Prostatitis is associated with disorders in prostatic tissue, levels of sex hormones (testosterone, prolactin, FSH, LH), a rise in total cholesterol, glucose. Watering of animals with MW and PAI raised blood insulin, hydrocortisone and testosterone, normalized blood glucose and cholesterol. There was a correlation between blood levels of hydrocortisone and testosterone.

Neoadjuvant hormonal therapy and external-beam radiotherapy versus external-beam irradiation alone for prostate cancer. A quality-of-life analysis

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Pinkawa, Michael; Piroth, Marc D.; Asadpour, Branka; Gagel, Bernd; Fischedick, Karin; Siluschek, Jaroslav; Kehl, Mareike; Krenkel, Barbara; Eble, Michael J. [RWTH Aachen (Germany). Dept. of Radiotherapy

2009-02-15

To evaluate the impact of neoadjuvant hormonal therapy (NHT) on quality of life after external-beam radiotherapy (EBRT) for prostate cancer. A group of 170 patients (85 with and 85 without NHT) has been surveyed prospectively before EBRT (70.2-72 Gy), at the last day of EBRT, a median time of 2 months and 15 months after EBRT using a validated questionnaire (Expanded Prostate Cancer Index Composite). Pairs with and without NHT (median treatment time of 3.5 months before EBRT) were matched according to the respective planning target volume and prostate volume. Before EBRT, significantly lower urinary function/bother, sexual function and hormonal function/bother scores were found for patients with NHT. More than 1 year after EBRT, only sexual function scores remained lower. In a multivariate analysis, NHT and adjuvant hormonal therapy (HT) versus NHT only (hazard ratio 14; 95% confidence interval 2.7-183; p = 0.02) and luteinizing hormone-releasing hormone (LHRH) agonists versus antiandrogens (hazard ratio 3.6; 95% confidence interval 1.1-12; p = 0.04) proved to be independent risk factors for long-term erectile dysfunction (no or very poor ability to have an erection). With the exception of sexual function (additional adjuvant HT and application of LHRH analog independently adverse), short-term NHT was not found to decrease quality of life after EBRT for prostate cancer. (orig.)

Adenocarcinoma of the prostate and metastatic medullary compression. A retrospective study of 22 patients

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Honnens de Lichtenberg, M; Kvist, E; Hjortberg, P

1992-01-01

A retrospective study of 709 patients with prostatic cancer was carried out. Twenty-two developed medullary cord compression (an incidence of 3%). All but two of the 22 patients were treated by radiation and 10 had additional hormonal treatment. Ten had some benefit from the treatment, but only 2...... of 19 regained their ability to walk. The need for immediate diagnosis and treatment is stressed....

Palliative prostate radiotherapy for symptomatic advanced prostate cancer

International Nuclear Information System (INIS)

Din, Omar S.; Thanvi, Narottam; Ferguson, Catherine J.; Kirkbride, Peter

2009-01-01

Background and purpose: To report the results for the use of short-course palliative radiotherapy to the prostate for localised symptoms. Materials and methods: Fifty-eight patients were identified from radiotherapy records between 2003 and 2007. Data were collected retrospectively on patients' demographics, radiotherapy details and response. Symptoms and toxicity were scored, retrospectively, according to the following scale: 0 = no symptoms, 1 = mild symptoms, 2 = moderate symptoms, and 3 = severe symptoms. Results: All the 58 patients had advanced prostate carcinoma. The median age at radiotherapy was 76.6 years (range 54-91). Fifty-six patients (97%) had hormone refractory disease. Twenty-seven patients (47%) had evidence of metastatic disease. 20Gy in 5 fractions was the most commonly used fractionation. The most frequent baseline symptom was haematuria (54%). Eighty-nine percent (31/35) of the patients had a complete or partial resolution of symptoms at 4 months. Response rates for individual symptoms (including unknown responses) were: rectal symptoms (75%), pelvic pain (69%), urinary obstruction (54%) and haematuria (42%). A >50% reduction in PSA occurred in five patients. Toxicity was mild to moderate only and was self-limiting. Conclusion: Palliative radiotherapy to the prostate gland for local symptoms appears to be an effective means of palliation with minimal toxic side effects. Prospective studies are now required to assess its benefits in more detail.

Do differences in age specific androgenic steroid hormone levels account for differing prostate cancer rates between Arabs and Caucasians?

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Kehinde, Elijah O; Akanji, Abayomi O; Al-Hunayan, Adel; Memon, Anjum; Luqmani, Yunus; Al-Awadi, Khaleel A; Varghese, Ramani; Bashir, Abdul Aziz; Daar, Abdallah S

2006-04-01

Factors responsible for the low incidence of clinical prostate cancer in the Arab population remain unclear, but may be related to differences in androgenic steroid hormone metabolism between Arabs and other populations, especially as prostate cancer is believed to be androgen dependent. We therefore measured the levels of serum androgenic steroids and their binding proteins in Arab men and compared results obtained with values reported for Caucasian populations to determine if any differences could at least partially account for differences in incidence of prostate cancer rates between the two populations. Venous blood samples were obtained from 327 unselected apparently healthy indigenous Arab men (Kuwaitis and Omanis) aged 15-79 years. Samples were also obtained from 30 Arab men with newly diagnosed prostate cancer. Serum levels of total testosterone (TT), sex hormone binding globulin (SHBG), derived free androgen index (FAI); adrenal C19 -steroids, dehydroepiandrosterone sulfate (DHEAS) and androstenedione (ADT) were determined by chemiluminescent immunoassay. Age specific reference intervals, mean and median for each analyte were determined. Frequency distribution pattern for each hormone was plotted. The reference range for hormones with normal distribution was mean +/- 2SD and 2.5-97.5% for those with non-normal distribution. The mean serum levels of the hormones in Arab men with prostate cancer were compared with values in healthy age-matched Arab men. There was a significant decrease between the 21-29 years age group and the 70-79 years age group for TT (-38.77%), DHEAS (-70%), ADT (-36%) and FAI (-63.25%), and an increase for SHBG (+64%). The calculated reference ranges are TT (2.73-30.45 nmol/L), SHBG (6.45-65.67 nmol/L), FAI (14.51-180.34), DHEAS (0.9-11.0 micromol/L) and ADT (0.54-4.26 ng/mL). The mean TT, SHBG, DHEAS and ADT in Arab men were significantly lower than those reported for Caucasians especially in the 21-29 years age group. Arab men with

Rare Presentation of Prostate Cancer Mimicking Malignant Lymphoma with Generalized Lymphadenopathy

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Yu-Fen Tsai

2014-06-01

Full Text Available Prostate cancer typically metastasizes to bones and regional lymph nodes. Generalized lymphadenopathy is a rare manifestation of metastatic prostate cancer. We report a case of prostate cancer in a 65-year-old male with initial presentation of generalized lymphadenopathy and no urinary symptoms. Lymph node biopsy revealed metastatic adenocarcinoma, and immunohistochemical staining was positive for prostate-specific antigen (PSA compatible with a prostatic origin. Directed biopsy confirmed that the tumor originated in the prostate. Therefore, the prostate should be considered a possible origin of metastatic adenocarcinoma in men, and presentations consistent with generalized lymphadenopathy cannot exclude a diagnosis of prostate cancer.

Radiotherapy and local hyperthermia plus androgen suppression in locally advanced prostate cancer

International Nuclear Information System (INIS)

Maluta, S.; Marciai, N.; Gabbani, M.; Palazzi, M.; Dall'Oglio, S.; Grandinetti, A.

2005-01-01

Full text: In advanced prostatic cancer, hyperthermia may be useful in order to enhance irradiation efficacy so to avoid delivering of too high dose of radiotherapy which increases acute and late sequelae. A multi-centric phase II study is warranted to give hyperthermia a level 3 evidence in prostate cancer treatment. A randomized phase III study to demonstrate efficacy of hyperthermia is not available because of the optimal results obtained by using radiotherapy combined with androgen suppression. To evaluate hyperthermia gain, LHT should be combined with radiotherapy alone in patients refusing androgen suppression or affected by hormone refractory prostate carcinoma (HRPC). Patients with HRPC have multiple possibilities of treatment improving performance status and median survival, as chemotherapy regimens, and new agents. All these treatments modalities need to be confirmed by phase III trials. Also hyperthermia may be considered among these promising approaches. (author)

If you 'watch and wait,' prostate cancer may progress dramatically

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Allison, Ron R.; Schulsinger, Alan; Vongtama, Vitune; Grant, Pat; Shin, Kyu H.; Huben, Robert

1997-01-01

Purpose: Observation has been proposed as an option for localized prostate cancer. However, most series reporting on 'watch and wait' include patients treated by TUR or hormones that may affect results. We retrospectively reviewed the natural history of truly untreated prostate cancer and report the outcome for these patients. Methods and Materials: From 1976 to 1992, 34 patients of median age 70 years (range 56-88) with biopsy proven localized adenocarcinoma of the prostate refused therapy. All had negative bone scan and none underwent TUR or hormone treatment. No patient was lost to follow-up (median 76 months). Failure patterns and survival were analyzed. Results: At diagnosis 27 patients had palpable nodules (T2), of which 13 were well differentiated and 14 moderately differentiated. Seven had moderately differentiated T3 lesions. Mild prostatitis including nocturia, hesistancy, and urgency were reported in 16 T2 and 6 T3 patients. Within 36 months, local progression requiring therapy occurred in all T3, all T2 moderate and 5 of 13 T2 well-differentiated patients. Systemic progression occurred in 6 of 7 T3, 9 of 14 T2 (mod), and 2 of 13 T2 (well) patients. Overall 59% are alive, 26% succumbed to prostate carcinoma and 15% to other causes. Conclusion: Observation results in a high rate of local progression requiring intervention (77%) and excessive systemic disease development (50%) for patients with clinically palpable disease. Perhaps this strategy is viable for earlier stage lesions detected by PSA but it must be tested in a rigorous fashion before accepted

If you 'watch and wait', prostate cancer may progress dramatically

International Nuclear Information System (INIS)

Allison, R. R.; Schulsinger, A.; Vongtama, V.; Grant, P.; Shin, K. H.; Huben, R.

1996-01-01

Objective: Observation has been proposed as an option for localized prostate cancer. However, most series reporting on 'watch and wait include patients treated by TUR or hormones which may affect results. We retrospectively reviewed the natural history of truly untreated prostate cancer and report the outcome for these patients. Materials and Methods: From 1976 to 1992, 34 patients of median age 70 yrs (range 56-88) with biopsy proven localized adenocarcinoma of the prostate refused therapy. All had negative bone scan and none underwent TUR or hormone treatment. No patient was lost to follow-up (median 76 months). Failure patterns and survival were analyzed. Results: At diagnosis 27 patients had palpable nodules (T 2 ) of which 13 were well differentiated and 14 moderately differentiated. Seven had moderately differentiated T 3 lesions. Mild prostatitis was reported in 16 T 2 and 6 T 3 patients. Within 36 months, local progression requiring therapy occurred in all T 3 , all T 2 moderate and (5(13)) T 2 well differentiated patients. Systemic progression occurred in (6(7)) T 3 , (9(14)) T 2 (mod) and (3(13)) T 2 (well) patients. Overall 59% are alive, 26% succumbed to prostate carcinoma and 15% to other causes. Conclusion: Observation results in a high rate of local progression requiring intervention (77%) and excessive systemic disease development (52%) for patients with clinically palpable disease. Perhaps this strategy is viable for earlier stage lesions detected by PSA but it must be tested in a rigorous fashion before accepted

Circulating and intraprostatic sex steroid hormonal profiles in relation to male pattern baldness and chest hair density among men diagnosed with localized prostate cancers.

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Zhou, Cindy Ke; Stanczyk, Frank Z; Hafi, Muhannad; Veneroso, Carmela C; Lynch, Barlow; Falk, Roni T; Niwa, Shelley; Emanuel, Eric; Gao, Yu-Tang; Hemstreet, George P; Zolfghari, Ladan; Carroll, Peter R; Manyak, Michael J; Sesterhenn, Isabell A; Levine, Paul H; Hsing, Ann W; Cook, Michael B

2017-12-01

Prospective cohort studies of circulating sex steroid hormones and prostate cancer risk have not provided a consistent association, despite evidence from animal and clinical studies. However, studies using male pattern baldness as a proxy of early-life or cumulative androgen exposure have reported significant associations with aggressive and fatal prostate cancer risk. Given that androgens underlie the development of patterned hair loss and chest hair, we assessed whether these two dermatological characteristics were associated with circulating and intraprostatic concentrations of sex steroid hormones among men diagnosed with localized prostate cancer. We included 248 prostate cancer patients from the NCI Prostate Tissue Study, who answered surveys and provided a pre-treatment blood sample as well as fresh frozen adjacent normal prostate tissue. Male pattern baldness and chest hair density were assessed by trained nurses before surgery. General linear models estimated geometric means and 95% confidence intervals (95%CIs) of each hormone variable by dermatological phenotype with adjustment for potential confounding variables. Subgroup analyses were performed by Gleason score (balding status with serum testosterone, dihydrotestosterone (DHT), estradiol, and sex hormone-binding globulin (SHBG), and a weak association with elevated intraprostatic testosterone. Conversely, neither circulating nor intraprostatic sex hormones were statistically significantly associated with chest hair density. Age-adjusted correlation between binary balding status and three-level chest hair density was weak (r = 0.05). There was little evidence to suggest that Gleason score or race modified these associations. This study provides evidence that balding status assessed at a mean age of 60 years may serve as a clinical marker for circulating sex hormone concentrations. The weak-to-null associations between balding status and intraprostatic sex hormones reaffirm differences in organ

Estrogen receptor signaling in prostate cancer: Implications for carcinogenesis and tumor progression.

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Bonkhoff, Helmut

2018-01-01

The androgen receptor (AR) is the classical target for prostate cancer prevention and treatment, but more recently estrogens and their receptors have also been implicated in prostate cancer development and tumor progression. Recent experimental and clinical data were reviewed to elucidate pathogenetic mechanisms how estrogens and their receptors may affect prostate carcinogenesis and tumor progression. The estrogen receptor beta (ERβ) is the most prevalent ER in the human prostate, while the estrogen receptor alpha (ERα) is restricted to basal cells of the prostatic epithelium and stromal cells. In high grade prostatic intraepithelial neoplasia (HGPIN), the ERα is up-regulated and most likely mediates carcinogenic effects of estradiol as demonstrated in animal models. The partial loss of the ERβ in HGPIN indicates that the ERβ acts as a tumor suppressor. The tumor promoting function of the TMPRSS2-ERG fusion, a major driver of prostate carcinogenesis, is triggered by the ERα and repressed by the ERβ. The ERβ is generally retained in hormone naïve and metastatic prostate cancer, but is partially lost in castration resistant disease. The progressive emergence of the ERα and ERα-regulated genes (eg, progesterone receptor (PR), PS2, TMPRSS2-ERG fusion, and NEAT1) during prostate cancer progression and hormone refractory disease suggests that these tumors can bypass the AR by using estrogens and progestins for their growth. In addition, nongenomic estrogen signaling pathways mediated by orphan receptors (eg, GPR30 and ERRα) has also been implicated in prostate cancer progression. Increasing evidences demonstrate that local estrogen signaling mechanisms are required for prostate carcinogenesis and tumor progression. Despite the recent progress in this research topic, the translation of the current information into potential therapeutic applications remains highly challenging and clearly warrants further investigation. © 2017 Wiley Periodicals, Inc.

Prognostic Factors for Hormone Sensitive Metastatic Prostate Cancer: Impact of Disease Volume

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Alhanafy, Alshimaa Mahmoud; Zanaty, Fouad; Ibrahem, Reda; Omar, Suzan

2018-04-27

Background and Aim: The optimal management of metastatic hormone-sensitive prostate cancer has been controversial in recent years with introduction of upfront chemohormonal treatment based on results of several Western studies. This changing landscape has renewed interest in the concept “disease volume”, the focus of the present study is the Egyptian patients. Methods: Patients with hormone sensitive metastatic prostate cancer presenting at Menoufia University Hospital, Egypt, during the period from June 2013 to May 2016, were enrolled. All received hormonal treatment. Radiologic images were evaluated and patients were stratified according to their disease volume into high or low, other clinical and pathological data that could affect survival also being collected and analyzed. Results: A total of 128 patients were included, with a median age of 70 years (53.9% ≥70). About 46% had co-morbidities, 62% having high volume disease. During the median follow up period of 28 months about half of the patients progressed and one third received chemotherapy. On univariate analysis, disease volume, performance status (PS), prostate specific antigen level (PSA) and presence of pain at presentation were identified as factors influencing overall survival. Multivariate analysis revealed the independent predictor factors for survival to be PS, PSA and disease volume. The median overall survival with 27 months was high volume versus 49 with low volume disease (hazard ratio 2.1; 95% CI 1.2 - 4.4; P=0.02). Median progression free survival was 19 months in the high volume, as compared with 48 months in the low volume disease patients (hazard ratio, 2.44; 95% CI, 1.42 – 7.4; P=0.009). Conclusions: Disease volume is a reliable predictor of survival which should be incorporated with other important factors as; patient performance status and comorbidities in treatment decision-making. Creative Commons Attribution License

Prostate Artery Embolization (PAE) in the Management of Refractory Hematuria of Prostatic Origin Secondary to Iatrogenic Urological Trauma: A Safe and Effective Technique.

Science.gov (United States)

Kably, Isaam; Pereira, Keith; Chong, William; Bhatia, Shivank

2016-02-01

Incidence of refractory hematuria of prostatic origin (RHPO) is extremely rare, with an iatrogenic etiology even rarer. When conservative methods fail to control bleeding, more invasive surgical methods are needed. In this article we describe our experience with prostatic artery embolization (PAE) as a minimally invasive alternative treatment option in patients with RHPO secondary to iatrogenic urologic trauma. Three patients presented with RHPO. The etiologies were transurethral resection of prostate surgery, Foley catheter removal with a supratherapeutic international normalized ratio and self-traumatic Foley catheter removal respectively. Stepwise management with conservative and medical methods failed to control bleeding. Under local anesthesia and moderate sedation, bilateral PAE was performed via a right common femoral artery access and using cone beam computed tomography. An embolic mixture containing 300-500 um Embosphere® Microspheres (Biosphere Medical, Rockland, MA) was injected under fluoroscopic guidance until stasis was achieved. PAE using the described technique was a technical and clinical success in all three patients. Hematuria resolved within a period of 24 hours. There were no intra- or periprocedural complications. PAE offers a reasonable option in treatment of RHPO, regardless of the cause and may be attempted prior to surgical techniques or sometimes in conjunction. Being minimally invasive and performed under local anesthesia, PAE is especially useful when excessive bleeding prevents adequate visualization of a bleeding source during cystoscopy and in the elderly age group with several comorbidities. An added advantage is the prostatic parenchymal ischemia leading to significant prostate volume reduction and alleviation of the obstructive symptoms. Copyright © 2016 Elsevier Inc. All rights reserved.

Adjuvant hormone therapy in patients undergoing high-intensity focused ultrasound therapy for locally advanced prostate cancer

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A. I. Neimark

2014-01-01

Full Text Available Objective: to evaluate the efficiency and safety of using the luteinizing hormone releasing hormone leuprorelin with the Atrigel delivery system in doses of 7.5, 22.5, and 45 mg as an adjuvant regimen in high- and moderate-risk cancer patients who have received high-intensity focused ultrasound (HIFU therapy.Subjects and methods. Moderate- and high-risk locally advanced prostate cancer (PC patients treated with HIFU (n = 28 and HIFU in combination with hormone therapy during 6 months (n = 31 were examined.Results. The investigation has shown that leuprorelin acetate monotherapy used within 6 months after HIFU therapy can achieve the highest reduction in prostate-specific antigen levels and positively affect the symptoms of the disease. HIFU in combination with androgen deprivation substantially diminishes the clinical manifestations of the disease and improves quality of life in HIFU-treated patients with PC, by reducing the degree of infravesical obstruction (according to uroflowmetric findings and IPSS scores, and causes a decrease in prostate volume as compared to those who have undergone HIFU only. Treatment with leuprorelin having the Atrigel delivery system has demonstrated the low incidence of adverse reactions and good tolerability.

Hormonal therapy with external radiation therapy for metastatic spinal cord compression from newly diagnosed prostate cancer

International Nuclear Information System (INIS)

Kato, So; Hozumi, Takahiro; Yamakawa, Kiyofumi; Higashikawa, Akiro; Goto, Takahiro; Shinohara, Mitsuru; Kondo, Taiji

2013-01-01

Although hormonal therapy is effective for treatment of prostate cancer, its effect in the treatment of metastatic spinal cord compression (MSCC) has not been established. The objective of this study was to clarify the efficacy of conservative treatment of MSCC-induced paralysis resulting from prostate cancer for patients without a previous treatment history. We reviewed data from 38 patients with MSCC-induced paralysis from newly diagnosed prostate cancer who presented to our service between 1984 and 2010. Conservative treatment consisted of hormonal therapy with external radiation therapy (ERT). Patient demographic data, treatment details, involved spine MRI images, complications, and the course of neurologic recovery were investigated. Twenty-five patients were treated conservatively. Mean follow-up period was 36.8 months. Sixteen patients (two with Frankel B, 14 with Frankel C) were unable to walk at initial presentation. After initiating conservative treatment, 75% (12 of 16) of these patients regained the ability to walk within 1 month, 88% (14 in 16) did so within 3 months, and all non-ambulatory patients did so within 6 months. No one had morbid complications. Four patients who did not regain the ability to walk at 1 month were found to have progressed to paraplegia rapidly, and tended to have severe compression as visualized on MRI, with a delay in the start of treatment in comparison with those who did so within 1 month (21.0 vs. 7.8 days). Hormonal therapy associated with ERT is an important option for treatment of MSCC resulting from newly diagnosed prostate cancer. (author)

Enzalutamide monotherapy: Phase II study results in patients with hormone-naive prostate cancer

DEFF Research Database (Denmark)

Tombal, Bertrand; Borre, Michael; Rathenborg, Per

2013-01-01

1 or 2). Most frequent treatment-emergent AEs included gynaecomastia (36%), fatigue (34%), and hot flush (18%). 7% of men experienced SAEs; none were drug-related. Conclusions: ENZA monotherapy (160 mg) was associated with significant PSA response in nearly all men with hormone-naïve prostate cancer...

Liarozole (R75251) in hormone-resistant prostate cancer patients.

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Dijkman, G A; Fernandez del Moral, P; Bruynseels, J; de Porre, P; Denis, L; Debruyne, F M

1997-09-15

Liarozole is an imidazole derivative that has been identified as an inhibitor of the cytochrome P450-dependent all-trans retinoid acid (RA) breakdown. RA is one of the principal endogenous compounds that controls growth and differentiation of epithelial tissues in mammals. Fifty-five patients with hormone-resistant prostate cancer in progression, following at least first-line androgen ablation therapy, were evaluated. Thirty-one patients were treated with liarozole 300 mg b.i.d., while 24 patients started with 150 mg b.i.d., which was increased to 300 mg b.i.d. after 4 or 8 weeks. Two patients were not evaluable because they withdrew after initial consent. The WHO performance status was 0 (n = 18), 1 (n = 22), 2 (n = 17), and 3 (n = 6). Most patients (80%) used analgesics. For 11 out of the 53 patients, treatment lasted less than 1 month (they were therefore not evaluable for response) due to: poor compliance (n = 1); early death (n = 3); side-effects (n = 2); and decline of physical condition and continuous progression (n = 4). One patient refused to report for follow-up. In all responders, except one, the dose was increased to 300 mg b.i.d. In 23 of the 42 patients evaluable for response, the pain score improved. In 5 patients the pain score had reduced from 2 or 3 to 0. In 11 out of the 42 patients there was a 1-point improvement of WHO performance status. The prostatic-specific antigen (PSA) response rate was 41%; 15 out of 42 evaluable patients presented a decrease of > or = 50%, whereas PSA normalized in 2 further patients. Most of the side effects mimicked retinoid acid toxicity: cutaneous manifestations (such as dry skin, dry lips, sticky skin, brittle nails, erythema, or itch). All patients experienced one or more of these side effects. Other side effects include nausea, fatigue, and slight alopecia. Liarozole can be an enrichment of the therapeutic armamentarium for treatment of hormone-resistant prostate cancer patients after first-line androgen ablation

Clinical benefit of bone-targeted radiometabolic therapy with 153Sm-EDTMP combined with chemotherapy in patients with metastatic hormone-refractory prostate cancer

International Nuclear Information System (INIS)

Ricci, Sergio; Pastina, Ilaria; Cianci, Claudia; Orlandini, Cinzia; Chioni, Aldo; Di Donato, Samantha; Boni, Giuseppe; Genovesi, Dario; Grosso, Mariano; AlSharif, Abedallatif; Mariani, Giuliano; Francesca, Francesco

2007-01-01

Bone metastases are responsible for most of the morbidity associated with hormone-refractory prostate cancer (HRPC). 153 Sm-ethylenediaminetetramethylene phosphonate ( 153 Sm-EDTMP) has been approved for palliation of painful skeletal metastases. We retrospectively investigated the possible synergistic effect on survival of 153 Sm-EDTMP (given to HRPC patients for bone pain palliation) and chemotherapy. Forty-five HRPC patients were evaluated, with a median age of 71 years. The number of metastatic bone sites was ≤10 in 25 patients and >10 in 20 patients. Median serum PSA was 224 ng/ml. Bone pain was mild in 6 patients, moderate in 16, severe in 22 and intolerable in 1. Fifteen patients were only treated with 153 Sm-EDTMP (group A), while 30 patients also received chemotherapy (estramustine phosphate or mitoxantrone plus prednisone) at variable times: between 3 and 5 months after 153 Sm-EDTMP (14 patients, group B) or within 1 month after 153 Sm-EDTMP (16 patients, group C). Haematological toxicities observed after either regimen were in general mild, consistent with common observations after either 153 Sm-EDTMP or chemotherapy, and without any additive adverse effects in the patients receiving both 153 Sm-EDTMP and chemotherapy. Bone pain palliation to some degree was induced by 153 Sm-EDTMP in 32/45 patients (71.1%), the proportion of patients with a favourable clinical response being significantly higher in group C than in group A (87.5% vs 53.3%, p = 0.0388). Also in terms of biochemical response (serum PSA levels), patients of group C performed significantly better than patients of group A (p = 0.0235). Overall median survival from the time of administration of 153 Sm-EDTMP was 15 months in the total cohort of 45 patients, and was significantly longer in group C than in either group B (30 months vs 11 months, p = 0.023) or group A (30 months vs 10 months, p = 0.008). The results of this study confirm that 153 Sm-EDTMP is effective in terms of pain relief and

Quality of life in locally advanced prostate cancer patients who underwent hormonal treatment combined with radiotherapy

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Koga, Hirofumi; Naito, Seiji; Fukui, Iwao; Tsukamoto, Taiji; Matsuoka, Naoki; Fujimoto, Hiroyuki

2004-01-01

The aim of this study is to estimate the feasibility of quality of life (QOL) research and to evaluate the QOL prospectively in locally advanced prostate cancer patients treated with hormonal treatment combined with radiotherapy. The treatment schedule was that patients with decreasing prostatic specific antigen (PSA) levels below 10 ng/ml after receiving 6 months of neoadjuvant hormonal treatment were randomly divided into two groups; one group was the continuous hormonal treatment group and the other was the intermittent hormonal treatment group. Both groups received a total dose of 72 Gy external beam radiotherapy with concomitant hormonal treatment followed by 6 months of adjuvant hormonal treatment following radiotherapy. At 14 months, patients either underwent continuous or intermittent hormonal treatment according to the random allocation. QOL was assessed at baseline, and at 6, 8, 14, and 20 months after treatment using functional assessment of cancer treatment-general (FACT-G), P with the other 3 items comprising bother of urination, bother of bowel movement, and bother of sexual activity. Between January 2000 and June 2003, a total of 188 patients were enrolled in this study. The rate of collection of baseline QOL sheets was 98.0%. The rate of answer to questions of QOL sheets was 99.0%. At baseline, the average score of FACT-G, P was 120.7 and the maximum score was more than twice the minimum score. Dysfunction of urination and bowel movement was correlated with the bother of urination and bowel movement, respectively. On the other hand, dysfunction of sexual activity was not correlated with the bother of sexual activity. In June 2003, all of the QOL sheets at baseline, and at 6, 8, and 14 months were completely collected from a total of 72 patients. Although QOL at 8 months was significantly affected compared with QOL at baseline and at 6 months, QOL at 14 months was significantly improved compared with that at 8 months and there was no significant

Novel expressed sequences identified in a model of androgen independent prostate cancer

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Jones Steven JM

2007-01-01

Full Text Available Abstract Background Prostate cancer is the most frequently diagnosed cancer in American men, and few effective treatment options are available to patients who develop hormone-refractory prostate cancer. The molecular changes that occur to allow prostate cells to proliferate in the absence of androgens are not fully understood. Results Subtractive hybridization experiments performed with samples from an in vivo model of hormonal progression identified 25 expressed sequences representing novel human transcripts. Intriguingly, these 25 sequences have small open-reading frames and are not highly conserved through evolution, suggesting many of these novel expressed sequences may be derived from untranslated regions of novel transcripts or from non-coding transcripts. Examination of a large metalibrary of human Serial Analysis of Gene Expression (SAGE tags demonstrated that only three of these novel sequences had been previously detected. RT-PCR experiments confirmed that the 6 sequences tested were expressed in specific human tissues, as well as in clinical samples of prostate cancer. Further RT-PCR experiments for five of these fragments indicated they originated from large untranslated regions of unannotated transcripts. Conclusion This study underlines the value of using complementary techniques in the annotation of the human genome. The tissue-specific expression of 4 of the 6 clones tested indicates the expression of these novel transcripts is tightly regulated, and future work will determine the possible role(s these novel transcripts may play in the progression of prostate cancer.

Radioimmunoassay for prostatic acid phosphatase in human serum. Methodologic aspects

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Pradalier, N; Canal, P; Pujol, A; Fregevu, Y [Groupe de Recherches du Centre Claudius-Regaud, Toulouse (France); Soula, G [Faculte des Sciences Pharmaceutiques, Toulouse (France)

1982-01-01

We propose a double antibody radioimmunoassay for human prostatic acid phosphatase (PAP) in serum for diagnosis and management of prostatic adenocarcinoma under treatment. The antigen is purified from human prostatic fluid by a gel-filtration on Sephadex G 100 followed by affinity chromatography on Con A Sepharose. A specific antibody is raised in rabbits and purified by immunoadsorption with a female serum. The described technique offers both radioisotopic sensibility and immunologic specificity. Physiological values determined in the serum of 125 healthy males are below 2 ng/ml. No significative differences are observed with age. The proposed technique also shows significant differences between values evaluated for benign prostatic hyperplasia and prostatic adenocarcinoma.

EGFR Mutation Status in Uighur Lung Adenocarcinoma Patients

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Li SHAN

2013-02-01

Full Text Available Background and objective Epidermal growth factor receptor (EGFR, a transmembrane protein, is a member of the tyrosine kinase family. Gefitinib, an EGFR tyrosine-kinase inhibitors, has shown a high response rate in the treatment of lung cancer in patients with EGFR mutation. However, significant differences in EGFR mutations exist among different ethnic groups. The aim of this study is to investigate the prevalence of EGFR mutations in Uighur lung adenocarcinoma patients by using a rapid and sensitive detection method and to analyze EGFR mutation differences compared with Han lung adenocarcinoma patients. Methods We examined lung adenocarcinoma tissues from 138 patients, including 68 Uighur lung adenocarcinoma patients and 70 Han lung adenocarcinoma patients, for EGFR mutations in exons 18, 19, 20, and 21 by using the amplification refractory mutation system (ARMS PCR method. The mutation differences between Uighur and Han lung adenocarcinoma were compared by using the chi-square test method. Results EGFR mutations were detected in 43 (31.2% of the 138 lung adenocarcinoma patients. EGFR mutations were detected in 11 (16.2% of the 68 Uighur lung adenocarcinoma patients and in 32 (45.7% of the 70 Han lung adenocarcinoma patients. Significant differences were observed in the EGFR mutations between Uighur lung adenocarcinoma patients and Han lung adenocarcinoma patients (P<0.001. Conclusion Our results indicate that the EGFR mutation in Uighur lung adenocarcinoma patients (16.2% is significantly lower than that in Han lung adenocarcinoma patients (45.7%.

Metronomic Treatment with Low-Dose Trofosfamide Leads to a Long-Term Remission in a Patient with Docetaxel-Refractory Advanced Metastatic Prostate Cancer

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Jochen Greiner

2010-01-01

Full Text Available The treatment of metastatic prostate cancer patients refractory to androgen withdrawal and docetaxel therapy is currently discouraging and new therapeutic approaches are vastly needed. Here, we report a long-term remission over one year in a 68-year-old patient with metastatic docetaxel-refractory prostate cancer employing low-dose trofosfamide. The patient suffered from distant failure with several bone lesions and lymph node metastases depicted by a (11 C-Choline positron emission tomography/computerized tomography (PET/CT. After initiation of trofosfamide 100 mg taken orally once a day we observed a steadily decreasing PSA value from initial 46.6 down to 2.1 g/l. The Choline-PET/CT was repeated after 10 months of continuous therapy and demonstrated a partial remission of the bone lesions and a regression of all involved lymph nodes but one. Taken together we found an astonishing and durable activity of the alkylating agent trofosfamide given in a metronomic fashion. We rate the side effects as low and state an excellent therapeutic ratio of this drug in our patient.

The prospect of gene therapy for prostate cancer: update on theory and status.

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Koeneman, K S; Hsieh, J T

2001-09-01

Molecularly based novel therapeutic agents are needed to address the problem of locally recurrent, or metastatic, advanced hormone-refractory prostate cancer. Recent basic science advances in mechanisms of gene expression, vector delivery, and targeting have rendered clinically relevant gene therapy to the prostatic fossa and distant sites feasible in the near future. Current research and clinical investigative efforts involving methods for more effective vector delivery and targeting, with enhanced gene expression to selected (specific) sites, are reviewed. These areas of research involve tissue-specific promoters, transgene exploration, vector design and delivery, and selective vector targeting. The 'vectorology' involved mainly addresses selective tissue homing with ligands, mechanisms of innate immune system evasion for durable transgene expression, and the possibility of repeat administration.

Increased expression of Golgi phosphoprotein-3 is associated with tumor aggressiveness and poor prognosis of prostate cancer

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Hua Xing

2012-09-01

Full Text Available Abstract Background To investigate the expression of Golgi phosphoprotein-3 (GOLPH3 in prostate cancer and determine its prognostic value. Methods Immunohistochemical staining for GOLPH3 was performed on tissue microarrays of 342 prostate patients. The correlation between GOLPH3 expression with its clinicopathologic factors was also analyzed in order to determine its prognostic significance. Results GOLPH3 expression of normal prostate tissues, benign prostate hyperplasia, high-grade prostatic intraepithelial neoplasia, and hormone-dependent prostate cancer (HDPC did not show any statistically significant difference. In contrast, statistically significant difference was reported in moderate/intense GOLPH3 expression in cases diagnosed with HDPC and castration resistant prostate cancer (CRPC (P P = 0.012, higher Gleason score (P = 0.017, bone metastasis (P = 0.024, higher baseline prostate-specific antigen (PSA (P = 0.038, and higher PSA nadir (P = 0.032. A significantly negative correlation was found between moderate/intense GOLPH3 expression and disease-free survival (DFS (HR = 0.28, P = 0.012 and overall survival (OS (HR = 0.42, P = 0.027. Univariated analysis indicated that moderate/intense GOLPH3 expression created a significantly prognostic impact in patients with CRPC. On the other hand, multivariate analysis indicated that GOLPH3 was a significantly independent prognostic factor of DFS (P = 0.027 in all prostate cancer patients. Conclusions In this study, it was discovered that the overexpression of GOLPH3 is associated with the transition of prostate cancer from hormone sensitive phase to hormone refractory phase. GOLPH3 might be an important prognostic factor of DFS and OS in patients with prostate cancer. In totality, GOLPH3 could be used as a novel candidate in devising a more effective therapeutic strategy to tackle CRPC. Virtual slides The virtual slide(s for this article can be found here

Inhibition of growth of experimental prostate cancer with sustained delivery systems (microcapsules and microgranules) of the luteinizing hormone-releasing hormone antagonist SB-75.

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Korkut, E; Bokser, L; Comaru-Schally, A M; Groot, K; Schally, A V

1991-02-01

Inhibitory effects of the sustained delivery systems (microcapsules and microgranules) of a potent antagonist of luteinizing hormone-releasing hormone N-Ac-[3-(2-naphthyl)-D-alanine1, 4-chloro-D-phenylalanine2, 3-(3-pyridyl)-D-alanine3, D-citrulline6, D-alanine10]LH-RH (SB-75) on the growth of experimental prostate cancers were investigated. In the first experiment, three doses of a microcapsule preparation releasing 23.8, 47.6, and 71.4 micrograms of antagonist SB-75 per day were compared with microcapsules of agonist [D-Trp6]LH-RH liberating 25 micrograms/day in rats bearing Dunning R3327H transplantable prostate carcinoma. During 8 weeks of treatment, tumor growth was decreased by [D-Trp6]LH-RH and all three doses of SB-75 as compared to untreated controls. The highest dose of SB-75 (71.4 micrograms/day) caused a greater inhibition of prostate cancer growth than [D-Trp6]LH-RH as based on measurement of tumor volume and percentage change in tumor volume. Doses of 23.8 and 47.6 micrograms of SB-75 per day induced a partial and submaximal decrease, respectively, in tumor weight and volume. Tumor doubling time was the longest (50 days) with the high dose of SB-75 vs. 15 days for controls. The body weights were unchanged. The weights of testes, seminal vesicles, and ventral prostate were greatly reduced in all three groups that received SB-75, and testosterone levels were decreased to nondetectable values in the case of the two higher doses of SB-75. LH levels were also diminished. Similar results were obtained in the second experiment, in which the animals were treated for a period of 8 weeks with microgranules of SB-75. Therapy with microgranules of SB-75 significantly decreased tumor growth as measured by the final tumor volume, the percentage change from the initial tumor volume, and the reduction in tumor weight. The results indicate that antagonist SB-75, released from sustained delivery systems, can produce a state of chemical castration and effectively

Positive resection margin and/or pathologic T3 adenocarcinoma of prostate with undetectable postoperative prostate-specific antigen after radical prostatectomy: to irradiate or not?

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Choo, Richard; Hruby, George; Hong, Julie; Hong, Eugene; DeBoer, Gerrit; Danjoux, Cyril; Morton, Gerard; Klotz, Laurence; Bhak, Edward; Flavin, Aileen

2002-01-01

Purpose: To evaluate the efficacy of postoperative adjuvant radiotherapy (RT) for positive resection margin and/or pathologic T3 (pT3) adenocarcinoma of the prostate with undetectable postoperative prostate-specific antigen (PSA) levels. Methods and materials: We retrospectively analyzed 125 patients with a positive resection margin and/or pT3 adenocarcinoma of the prostate who had undetectable postoperative serum PSA levels after radical prostatectomy. Seventy-three patients received postoperative adjuvant RT and 52 did not. Follow-up ranged from 1.5 to 12.0 years (median 4.2 for the irradiated group and 4.9 for the nonirradiated group). PSA outcome was available for all patients. Freedom from failure was defined as the maintenance of a serum PSA level of ≤0.2 ng/mL, as well as the absence of clinical local recurrence and distant metastasis. Results: No difference was found in the 5-year actuarial overall survival between the irradiated and nonirradiated group (94% vs. 95%). However, patients receiving adjuvant RT had a statistically superior 5-year actuarial relapse-free rate, including freedom from PSA failure, compared with those treated with surgery alone (88% vs. 65%, p=0.0013). In the irradiated group, 8 patients had relapse with PSA failure alone. None had local or distant recurrence. In the nonirradiated group, 15, 1, and 2 had PSA failure, local recurrence, and distant metastasis, respectively. On Cox regression analysis, pre-radical prostatectomy PSA level and adjuvant RT were statistically significant predictive factors for relapse, and Gleason score, extracapsular invasion, and resection margin status were not. There was a suggestion that seminal vesicle invasion was associated with an increased risk of relapse. The morbidity of postoperative adjuvant RT was acceptable, with only 2 patients developing Radiation Therapy Oncology Group Grade 3 genitourinary complications. Adjuvant RT had a minimal adverse effect on urinary continence and did not cause

EFFICACY OF IMMUNOHISTOCHEMISTRY IN PROSTATE NEEDLE BIOPSIES

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Tameem Afroz

2016-10-01

Full Text Available BACKGROUND Prostate needle biopsies can pose a major diagnostic challenge when it comes to differentiating adenocarcinoma and its variants from its benign mimics. In needle biopsies, when the suspicious focus is small, morphological features may not suffice to differentiate it from its morphologic mimics like atrophy, basal cell hyperplasia, reactive inflammatory changes, seminal vesicles and adenosis. Immunohistochemical marker for basal cells, p63 and prostate cancer specific marker, Alpha-Methylacyl-CoA Racemase (AMACR help in overcoming such diagnostic dilemmas. MATERIALS AND METHODS We analysed 157 prostate core needle biopsies over a period of 2 years. Routine Hematoxylin and Eosin (H and E sections and immunohistochemical markers for basal cells (p63 and prostate cancer specific marker (AMACR were used. Prospective study was done on prostate needle core biopsies. Biopsy was done under ultrasound guidance with an 18-gauge needle. Biopsy was done in patients with raised serum PSA levels for exclusion of prostate carcinoma. RESULTS Over a period of two years, 157 prostate core needle biopsies were studied. 83 were benign lesions comprising 69 benign prostatic hyperplasias, five basal cell hyperplasias, four granulomatous lesions and three showed atrophic changes. Two biopsies morphologically resembled seminal vesicles. Prostate cancer specific marker, AMACR was negative in all, but two lesions. In these two lesions, it showed weak nonspecific staining. Basal cell marker p63 showed a continuous staining pattern highlighting the basal cells in all the 69 cases of benign prostatic hyperplasia, 5 cases of basal hyperplasia showed positivity in all the hyperplastic basal cells. In the two cases of seminal vesicles, it showed intense basal cell positivity. It showed a discontinuous pattern in two of the four granulomatous lesions and showed a weak, but a continuous staining pattern in the atrophic lesions. 74 were adenocarcinomas; the predominant

A large, benign prostatic cyst presented with an extremely high serum prostate-specific antigen level.

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Chen, Han-Kuang; Pemberton, Richard

2016-01-08

We report a case of a patient who presented with an extremely high serum prostate specific antigen (PSA) level and underwent radical prostatectomy for presumed prostate cancer. Surprisingly, the whole mount prostatectomy specimen showed only small volume, organ-confined prostate adenocarcinoma and a large, benign intraprostatic cyst, which was thought to be responsible for the PSA elevation. 2016 BMJ Publishing Group Ltd.

The curative role of radiotherapy in adenocarcinoma of the prostate in patients under 55 years of age: A rare cancer network retrospective study

International Nuclear Information System (INIS)

Nguyen, Tan Dat; Poortmans, Philip M.P.; Hulst, Marleen van der; Studer, Gabriela; Pigois, Eva; Collen, Timothy D.; Belkacemi, Yazid; Beckendorf, Veronique; Miralbell, Raymond; Scandolaro, Luciano; Soete, Guy; Villa, Salvador; Gez, Eliahu; Thomas, Olivier; Krengli, Marco; Jovenin, Nicolas

2005-01-01

To determine whether radiation therapy could be an acceptable alternative to surgery in young patients with adenocarcinoma of the prostate, we analysed the outcome of 39 patients aged under 55 with organ confined tumours who received external radiation therapy in a curative intent. Our results suggest that similar local control in younger and older patients can be expected from either external beam radiotherapy or radical prostatectomy

Radioimmunoassay for prostatic acid phosphatase in human serum. Methodologic aspects

International Nuclear Information System (INIS)

Pradalier, N.; Canal, P.; Pujol, A.; Fregevu, Y.; Soula, G.

1982-01-01

We propose a double antibody radioimmunoassay for human prostatic acid phosphatase (PAP) in serum for diagnosis and management of prostatic adenocarcinoma under treatment. The antigen is purified from human prostatic fluid by a gel-filtration on Sephadex G 100 followed by affinity chromatography on Con A Sepharose. A specific antibody is raised in rabbits and purified by immunoadsorption with a female serum. The described technique offers both radioisotopic sensibility and immunologic specificity. Physiological values determined in the serum of 125 healthy males are below 2 ng/ml. No significative differences are observed with age. The proposed technique also shows significant differences between values evaluated for benign prostatic hyperplasia and prostatic adenocarcinoma [fr

Vinclozolin Exposure in Utero Induces Postpubertal Prostatitis and Reduces Sperm Production via a Reversible Hormone-Regulated Mechanism

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Cowin, Prue A.; Gold, Elspeth; Aleksova, Jasna; O'Bryan, Moira K.; Foster, Paul M. D.; Scott, Hamish S.; Risbridger, Gail P.

2010-01-01

Vinclozolin is an endocrine-disrupting chemical (EDC) that binds with high affinity to the androgen receptor (AR) and blocks the action of gonadal hormones on male reproductive organs. An alternative mechanism of action of Vinclozolin involves transgenerational effects on the male reproductive tract. We previously reported in utero Vinclozolin exposure-induced prostatitis (prostate inflammation) in postpubertal rats concurrent with down-regulation of AR and increased nuclear factor-κB activat...

Coexistence of prostate neoplasia in patients undergoing radical cystoprostatectomy due to vesical neoplasia

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Frederico R. Romero

2004-08-01

Full Text Available OBJECTIVE: To assess the incidence of bladder carcinoma infiltrating the prostate and prostate adenocarcinoma in patients undergoing radical cystoprostatectomy due to bladder cancer, as well as to assess if the characteristics of the bladder neoplasia influence the prostatic involvement by this neoplasia. MATERIALS AND METHODS: We retrospectively assessed 60 male patients, who underwent radical cystoprostatectomy between July 1997 and December 2003. Mean age was 66.7 years (40 and 93 years. The product of radical cystoprostatectomies was checked for involvement of urethra and prostate parenchyma by the primary neoplasia, and for the presence of associated prostate adenocarcinoma. Bladder neoplasia characteristics, such as localization, size, multifocality, association with in situ carcinoma and histological grade, were studied in order to assess the possibility of using such characteristics as predictive factors of prostate infiltration by bladder urothelial carcinoma. RESULTS: We observed the presence of 20% of patients with bladder carcinoma infiltrating the prostatic urethra, 23.3% of patients with infiltration of the prostate parenchyma and 28.3% of patients with associate prostate adenocarcinoma, resulting in a total of 55% of patients with prostatic involvement (infiltrative bladder carcinoma and/or adenocarcinoma. We also observed a statistically significant correlation between tumor location in the trigone, the presence of in situ carcinoma and the histological grade of the bladder tumor with prostatic infiltration by the vesical neoplasia. CONCLUSION: The coexistence of prostatic neoplasia in patients operated for bladder neoplasia was frequent in our sample (55%. We observed that the prostatic infiltration by bladder tumors occurs more frequently with tumors located in the trigone, with associated in situ carcinoma and with high histological grade. There was no correlation between neoplastic infiltration of prostate and multifocality

Castration resistant prostate cancer - something new in the year 2014?

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Marencak, J.

2014-01-01

Prostate cancer (PC) is the most frequent solid neoplasm in Europe and therefore is regarded as one of the major medical problem of the male population. PC is extremely complicated and interindividual different tumor. The method of treatment depends on several factors, but mainly on the stage of prostate cancer. The term Hormone resistant (refractory) prostate cancer (HRPC) was used in older terminology. HRPC is cancer that progresses despite castrate levels of testosterone achieved androgen deprivation therapy (ADT), which is resistant to any hormonal therapy. Currently is increasingly used (instead of name HRPC) name CRPC – so called PC resistant for castration (CRPC – castration resistant prostate cancer), which is still able to respond to certain hormonal manipulation, although it meets the the criteria for HRPC. This state probably arises from either clonal selection of androgen – independent cell lines or increased ligand – independent activation of androgen receptors. Men with CRPC are quite a heterogeneous group; they include men with increasing prostate specific antigen (PSA) only and no demonstrable metastases, and men who have many bone and/ or visceral metastases, pain and poor functional status. Survival can range from only a few months to 4 years or more. Historically, therapy had little effect beyond modest palliation. More recently, significantly more options have become available and there are now several treatments that not only improve quality of life and pain palliation, but also increase overall survival. Some of the trials with important results for the treatment of CRPC are summarized in this paper. Objectives of article: provide information to the general medical community (and especially urologists and oncologists) about the possible pathogenesis of CRPC, complicated issues of treatment and evaluation of its effectiveness in patients with CRPC. The article presented basic data on the current and future possibilities of such therapy

Non-Coding RNAs in Castration-Resistant Prostate Cancer: Regulation of Androgen Receptor Signaling and Cancer Metabolism.

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Shih, Jing-Wen; Wang, Ling-Yu; Hung, Chiu-Lien; Kung, Hsing-Jien; Hsieh, Chia-Ling

2015-12-04

Hormone-refractory prostate cancer frequently relapses from therapy and inevitably progresses to a bone-metastatic status with no cure. Understanding of the molecular mechanisms conferring resistance to androgen deprivation therapy has the potential to lead to the discovery of novel therapeutic targets for type of prostate cancer with poor prognosis. Progression to castration-resistant prostate cancer (CRPC) is characterized by aberrant androgen receptor (AR) expression and persistent AR signaling activity. Alterations in metabolic activity regulated by oncogenic pathways, such as c-Myc, were found to promote prostate cancer growth during the development of CRPC. Non-coding RNAs represent a diverse family of regulatory transcripts that drive tumorigenesis of prostate cancer and various other cancers by their hyperactivity or diminished function. A number of studies have examined differentially expressed non-coding RNAs in each stage of prostate cancer. Herein, we highlight the emerging impacts of microRNAs and long non-coding RNAs linked to reactivation of the AR signaling axis and reprogramming of the cellular metabolism in prostate cancer. The translational implications of non-coding RNA research for developing new biomarkers and therapeutic strategies for CRPC are also discussed.

Proton MRS detects metabolic changes in hormone sensitive and resistant human prostate cancer models CWR22 and CWR22r.

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Le, H Carl; Lupu, Mihaela; Kotedia, Khushali; Rosen, Neal; Solit, David; Koutcher, Jason A

2009-11-01

17-Allylamino, 17-demethoxygeldanamycin (17-AAG), an effective inhibitor of the heat shock protein hsp90, preferentially inhibiting tumor hsp90 compared to hsp90 from normal cells, has shown promising results against several cancers, including hormone-resistant prostate cancer. Levels of several oncogenic proteins critical to tumor growth and progression, such as androgen receptor and HER2/neu, were reduced 4 h post 17-allylamino, 17-demethoxygeldanamycin treatment. Posttreatment metabolic changes have also been observed in several tumor cell lines. In this study, total choline distributions in hormone sensitive CWR22 and hormone resistant CWR22r prostate cancer xenograft tumors in mice were measured before and at 4 h and 48 h after a single-bolus 17-allylamino, 17-demethoxygeldanamycin treatment at 100 mg/kg, using proton MR spectroscopy. Our results show that tumor total choline levels declined 4 h after the treatment for CWR22 (P = 0.001) and 48 h post treatment for CWR22r (P = 0.003). Metabolic changes, in particular of total choline intensity detected by proton magnetic resonance spectroscopic imaging (MRSI), are consistent with the observed immunohistochemistry changes, tumor growth inhibition for CWR22r (P = 0.01 at 14 days post treatment), and a constant prostate specific antigen level versus increasing prostate specific antigen for control CWR22 (P = 0.01). Metabolic changes in total choline by proton MRSI can be used as an early biomarker of response for advanced-stage prostate cancer in targeted therapy such as 17-allylamino, 17-demethoxygeldanamycin. (c) 2009 Wiley-Liss, Inc.

Sex Steroid Hormone Gene Variants, Pesticide Use and the Risk of Prostate Cancer: A Nested Case-Control Study within the Agricultural Health Study

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Carol H Christensen

2016-11-01

Full Text Available Experimental and epidemiologic investigations suggest that certain pesticides may alter sex steroid hormone synthesis, metabolism or regulation and the risk of hormone-related cancers. Here we evaluated whether single nucleotide polymorphisms (SNPs involved in hormone homeostasis alter the effect of pesticide exposure on prostate cancer risk. We evaluated pesticide–SNP interactions between 39 pesticides and SNPs with respect to prostate cancer among 776 cases and 1444 controls nested in the Agricultural Health Study cohort. In these interactions, we included candidate SNPs involved in hormone synthesis, metabolism and regulation (N=1100, as well as SNPs associated with circulating sex steroid concentrations as identified by genome-wide association studies (N=17. Unconditional logistic regression was used to estimate odds ratios (ORs and 95% confidence intervals (CIs. Multiplicative SNP–pesticide interactions were calculated using a likelihood ratio test. We translated p-values for interaction into q-values, which reflected the false discovery rate, to account for multiple comparisons. We observed a significant interaction, which was robust to multiple comparison testing, between the herbicide dicamba and rs8192166 in the testosterone metabolizing gene SRD5A1 (p-interaction=4.0x10-5; q-value=0.03, such that men with two copies of the wild-type genotype CC had a reduced risk of prostate cancer associated with low use of dicamba (OR=0.62 95% CI: 0.41, 0.93, and high use of dicamba (OR=0.44, 95% CI: 0.29, 0.68, compared to those who reported no use of dicamba; in contrast, there was no significant association between dicamba and prostate cancer among those carrying one or two copies of the variant T allele at rs8192166. In addition, interactions between two organophosphate insecticides and SNPs related to estradiol metabolism were observed to result in an increased risk of prostate cancer. While replication is needed, these data suggest both

HOXB13 promotes androgen independent growth of LNCaP prostate cancer cells by the activation of E2F signaling

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Choi Chan

2010-05-01

Full Text Available Abstract Background Androgen signaling plays a critical role in the development of prostate cancer and its progression. However, androgen-independent prostate cancer cells emerge after hormone ablation therapy, resulting in significant clinical problems. We have previously demonstrated that the HOXB13 homeodomain protein functions as a prostate cancer cell growth suppressor by inhibiting androgen-mediated signals. However, the role of the HOXB13 in androgen-independent growth of prostate cancer cells remains unexplained. Results In this report, we first demonstrated that HOXB13 was highly overexpressed in hormone-refractory tumors compared to tumors without prostate-specific antigen after initial treatment. Functionally, in an androgen-free environment minimal induction of HOXB13 in LNCaP prostate cancer cells, to the level of the normal prostate, markedly promoted cell proliferation while suppression inhibited cell proliferation. The HOXB13-mediated cell growth promotion in the absence of androgen, appears to be mainly accomplished through the activation of RB-E2F signaling by inhibiting the expression of the p21waf tumor suppressor. Indeed, forced expression of HOXB13 dramatically decreased expression of p21waf; this inhibition largely affected HOXB13-mediated promotion of E2F signaling. Conclusions Taken together, the results of this study demonstrated the presence of a novel pathway that helps understand androgen-independent survival of prostate cancer cells. These findings suggest that upregulation of HOXB13 is associated with an additive growth advantage of prostate cancer cells in the absence of or low androgen concentrations, by the regulation of p21-mediated E2F signaling.

Human Papilloma Virus Detection by INNOLiPA HPV in Prostate Tissue from Men of Northeast Mexico

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Dávila-Rodríguez, Martha I; Ignacio Morales, Cesar V; Aragón Tovar, Anel R; Olache Jimenez, Delia; Castelán Maldonado, Edmundo; Lara Miranda, Sandra; Cortés Gutiérrez, Elva I

2016-11-01

Background: Prostatic adenocarcinoma by Prosate cancer (PCa) is the most prevalent cancer and the second cause of cancer-related death among men in the Western world. Human papilloma virus (HPV) may be considered as a preventable risk factor. In this study, we assessed the frequencies of HPV infection in prostatic adenocarcinoma and benign prostatic hyperplasia (BPH) cases in Northeast Mexico. Materials and Methods: A total of 87 paraffin-embedded blocks (from 25 and 62 patients with definite diagnoses of BPH and adenocarcinoma, respectively) were selected and subjected to INNOLiPA HPV Genotyping to detect 28 high- and low-risk HPV types. The rates of infection were compared in the two studied groups. Results: INNOLiPA HPV demonstrated great sensitivity for HPV detection on paraffin-embedded tissue. Global prevalence was 14.9% (13/87). HPV infection was positive in 19.4% (12/62) of patients with adenocarcinoma and 4.0% (1/25) of patients with BPH. HPV-11, which is considered to be low risk, was more prevalent. Interestingly, one patient with BPH and six with prostate cancer showed examples considered to be high risk (HPV-18, -51, -52, and -66). Conclusion: A higher rate of HPV infection among Mexican patients with prostatic carcinoma than among those with BPH was observed. HPV infections may thus contribute to the risk of prostate cancer. Further studies are required to elucidate any roles of HPV infection in prostate disease in Mexico and the effect of prevention and treatment of HPV infection on prostatic adenocarcinoma. Creative Commons Attribution License

Copper as a target for prostate cancer therapeutics: copper-ionophore pharmacology and altering systemic copper distribution

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Denoyer, Delphine; Pearson, Helen B.; Clatworthy, Sharnel A.S.; Smith, Zoe M.; Francis, Paul S.; Llanos, Roxana M.; Volitakis, Irene; Phillips, Wayne A.; Meggyesy, Peter M.; Masaldan, Shashank; Cater, Michael A.

2016-01-01

Copper-ionophores that elevate intracellular bioavailable copper display significant therapeutic utility against prostate cancer cells in vitro and in TRAMP (Transgenic Adenocarcinoma of Mouse Prostate) mice. However, the pharmacological basis for their anticancer activity remains unclear, despite impending clinical trails. Herein we show that intracellular copper levels in prostate cancer, evaluated in vitro and across disease progression in TRAMP mice, were not correlative with copper-ionophore activity and mirrored the normal levels observed in patient prostatectomy tissues (Gleason Score 7 & 9). TRAMP adenocarcinoma cells harbored markedly elevated oxidative stress and diminished glutathione (GSH)-mediated antioxidant capacity, which together conferred selective sensitivity to prooxidant ionophoric copper. Copper-ionophore treatments [CuII(gtsm), disulfiram & clioquinol] generated toxic levels of reactive oxygen species (ROS) in TRAMP adenocarcinoma cells, but not in normal mouse prostate epithelial cells (PrECs). Our results provide a basis for the pharmacological activity of copper-ionophores and suggest they are amendable for treatment of patients with prostate cancer. Additionally, recent in vitro and mouse xenograft studies have suggested an increased copper requirement by prostate cancer cells. We demonstrated that prostate adenocarcinoma development in TRAMP mice requires a functional supply of copper and is significantly impeded by altered systemic copper distribution. The presence of a mutant copper-transporting Atp7b protein (tx mutation: A4066G/Met1356Val) in TRAMP mice changed copper-integration into serum and caused a remarkable reduction in prostate cancer burden (64% reduction) and disease severity (grade), abrogating adenocarcinoma development. Implications for current clinical trials are discussed. PMID:27175597

Human Papilloma Virus Detection by INNOLiPA HPV in Prostate Tissue from Men of Northeast Mexico

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Rodriguez, Martha I Dávila; Morales, Cesar V Ignacio; Tovar, Anel R Aragón; Jimenez, Delia Olache; Maldonado, Edmundo Castelán; Miranda, Sandra Lara; Gutiérrez, Elva I Cortés

2016-01-01

Background: Prostatic adenocarcinoma by Prosate cancer (PCa) is the most prevalent cancer and the second cause of cancer-related death among men in the Western world. Human papilloma virus (HPV) may be considered as a preventable risk factor. In this study, we assessed the frequencies of HPV infection in prostatic adenocarcinoma and benign prostatic hyperplasia (BPH) cases in Northeast Mexico. Materials and Methods: A total of 87 paraffin-embedded blocks (from 25 and 62 patients with definite diagnoses of BPH and adenocarcinoma, respectively) were selected and subjected to INNOLiPA HPV Genotyping to detect 28 high- and low-risk HPV types. The rates of infection were compared in the two studied groups. Results: INNOLiPA HPV demonstrated great sensitivity for HPV detection on paraffin-embedded tissue. Global prevalence was 14.9% (13/87). HPV infection was positive in 19.4% (12/62) of patients with adenocarcinoma and 4.0% (1/25) of patients with BPH. HPV-11, which is considered to be low risk, was more prevalent. Interestingly, one patient with BPH and six with prostate cancer showed examples considered to be high risk (HPV-18, -51, -52, and -66). Conclusion: A higher rate of HPV infection among Mexican patients with prostatic carcinoma than among those with BPH was observed. HPV infections may thus contribute to the risk of prostate cancer. Further studies are required to elucidate any roles of HPV infection in prostate disease in Mexico and the effect of prevention and treatment of HPV infection on prostatic adenocarcinoma. PMID:28030912

Testicular dose in prostate cancer radiotherapy. Impact on impairment of fertility and hormonal function

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Boehmer, D.; Badakhshi, H.; Budach, V. [Dept. of Radiation Oncology, Charite - Univ. Clinic - Campus Mitte, Berlin (Germany); Kuschke, W.; Bohsung, J. [Dept. of Medical Physics, Charite - Univ. Clinic - Campus Mitte, Berlin (Germany)

2005-03-01

Purpose: to determine the dose received by the unshielded testicles during a course of 20-MV conventional external-beam radiotherapy for patients with localized prostate cancer. Critical evaluation of the potential impact on fertility and hormonal impairment in these patients according to the literature. Patients and methods: the absolute dose received by the testicles of 20 randomly selected patients undergoing radiotherapy of prostate cancer was measured by on-line thermoluminescence dosimetry. Patients were treated in supine position with an immobilization cushion under their knees. A flexible tube, containing three calibrated thermoluminescence dosimeters (TLDs) was placed on top or underneath the testicle closest to the perineal region with a day-to-day alternation. The single dose to the planning target volume was 1.8 Gy. Ten subsequent testicle measurements were performed on each patient. The individual TLDs were then read out and the total absorbed dose was calculated. Results: the mean total dose ({+-} standard deviation) measured in a series of 10 subsequent treatment days in all patients was 49 cGy ({+-} 36 cGy). The calculated projected doses made on a standard series of 40 fractions of external-beam radiotherapy were 196 cGy ({+-} 145 cGy). The results of this study are appraised with the available data in the literature. Conclusion: the dose received by the unshielded testes can be assessed as a risk for permanent infertility and impairment of hormonal function in prostate cancer patients treated with external-beam radiotherapy. (orig.)

Dissecting the expression of EEF1A1/2 genes in human prostate cancer cells: the potential of EEF1A2 as a hallmark for prostate transformation and progression.

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Scaggiante, B; Dapas, B; Bonin, S; Grassi, M; Zennaro, C; Farra, R; Cristiano, L; Siracusano, S; Zanconati, F; Giansante, C; Grassi, G

2012-01-03

In prostate adenocarcinoma, the dissection of the expression behaviour of the eukaryotic elongation factors (eEF1A1/2) has not yet fully elucidated. The EEF1A1/A2 expressions were investigated by real-time PCR, western blotting (cytoplasmic and cytoskeletal/nuclear-enriched fractions) and immunofluorescence in the androgen-responsive LNCaP and the non-responsive DU-145 and PC-3 cells, displaying a low, moderate and high aggressive phenotype, respectively. Targeted experiments were also conducted in the androgen-responsive 22Rv1, a cell line marking the progression towards androgen-refractory tumour. The non-tumourigenic prostate PZHPV-7 cell line was the control. Compared with PZHPV-7, cancer cells showed no major variations in EEF1A1 mRNA; eEF1A1 protein increased only in cytoskeletal/nuclear fraction. On the contrary, a significant rise of EEF1A2 mRNA and protein were found, with the highest levels detected in LNCaP. Eukaryotic elongation factor 1A2 immunostaining confirmed the western blotting results. Pilot evaluation in archive prostate tissues showed the presence of EEF1A2 mRNA in near all neoplastic and perineoplastic but not in normal samples or in benign adenoma; in contrast, EEF1A1 mRNA was everywhere detectable. Eukaryotic elongation factor 1A2 switch-on, observed in cultured tumour prostate cells and in human prostate tumour samples, may represent a feature of prostate cancer; in contrast, a minor involvement is assigned to EEF1A1. These observations suggest to consider EEF1A2 as a marker for prostate cell transformation and/or possibly as a hallmark of cancer progression.

Correlation between bone scan findings and serum PSA level in prostate cancer patients in Bangladesh: both newly diagnosed and hormonally treated cases

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Yasmeen, S.; Nasreen, F.; Kabir, M.F.

2007-01-01

Full text: The objective of the current study was to determine whether pre- treatment serum prostate specific antigen (PSA) levels can identify a group with low probability of osseous metastases and safely eliminate the need for bone scan as a routine part of the staging evaluation in Bangladeshi patients with newly diagnosed prostate carcinoma. Also, to find out a cut off value for serum PSA level for predicting positive bone scan in newly diagnosed Bangladeshi prostate cancer patients and to assess the role of PSA level in hormonally treated cases. Prostate cancer most commonly metastasizes to the bone. Bone scintigraphy is one of the best methods in detecting bone metastases, assessing the progression of the disease and response to therapy. For more than 30 yrs it has been known that bone scintigraphy is more sensitive than radiographic, clinical evaluation or chemical markers such as alkaline phosphatase or acid phosphatase in detection of early osseous metastatic prostate cancer. The introduction of PSA has dramatically changed the management of prostate cancer. Serum PSA level has proven to be a useful serum marker for detection of metastatic prostate cancer and it provides the best overall correlation. It also has considerable impact on bone scanning. Of special significance is the fact that patients who have a low PSA level in previously untreated carcinoma of prostate are extremely unlikely to have positive findings on a bone scan for metastases. The picture is different in patients who has received and responded to hormonal therapy. Bone scintigraphy appears to be extremely useful in patients whose PSA level begins to rise after surgical procedure. Patients, who were on anti- androgen therapy, even though they had visible metastatic disease on bone scans, had normal level of PSA Patients and methods: A total of 390 cases were studied. Some (n=242) were newly diagnosed without having any specific treatment other than surgery. Others (n=148) were old cases

Prostate cancer in young adults-Seventeen-year clinical experience of a single center.

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Huang, Tzu-Hao; Kuo, Junne-Yih; Huang, Yi-Hsiu; Chung, Hsiao-Jen; Huang, William J S; Wu, Howard H H; Chang, Yen-Hwa; Lin, Alex T L; Chen, Kuang-Kuo

2017-01-01

In the general population, prostate adenocarcinoma affects predominately older men. If fact, most current guidelines suggest that males over the age of 50 years should undergo prostate cancer screening. However, the clinical behavior and prognosis of prostate cancer in young adults is not well defined. The aim of this study was to evaluate the clinical behavior, pathological characteristics, and prognosis of prostate cancer in young adults. We retrospectively reviewed the records of young patients (age, ≤50 years) in our hospital with prostate adenocarcinoma between 1997 and 2013. We compared data including initial presentation, cancer cell type, Gleason score, disease stage, prostate-specific antigen (PSA) level, prostate volume, treatment, and survival between patients both younger and older than 50 years. Data were analyzed using the Kaplan-Meier method to assess survival. Twenty-six patients were enrolled in our study, accounting for 0.55% of all patients with a diagnosis of prostate cancer at our facility. All 26 patients had a pathology diagnosis of adenocarcinoma, with a mean age on diagnosis of 46.8±2.8 years (range, 39-50 years). On initial presentation, patients older than 50 years more frequently displayed lower urinary tract symptoms (LUTS) than younger patients (62.3% vs. 30.4%, p=0.008). There was no statistical difference in histological grade, disease stage, PSA level, overall survival, and biochemical-free survival between the two groups. The result of our investigation indicated that prostate adenocarcinoma patients younger than 50 years had similar histological grade, disease stage, PSA level, overall survival, and biochemical-free survival as the older population. However, patients younger than 50 years with prostate cancer less frequently showed initial symptoms of LUTS. Copyright © 2016. Published by Elsevier Taiwan LLC.

Characterisation of prostate cancer lesions in heterozygous Men1 mutant mice

International Nuclear Information System (INIS)

Seigne, Christelle; Fontanière, Sandra; Carreira, Christine; Lu, Jieli; Tong, Wei-Ming; Fontanière, Bernard; Wang, Zhao-Qi; Zhang, Chang Xian; Frappart, Lucien

2010-01-01

Mutations of the MEN1 gene predispose to multiple endocrine neoplasia type 1 (MEN1) syndrome. Our group and others have shown that Men1 disruption in mice recapitulates MEN1 pathology. Intriguingly, rare lesions in hormone-dependent tissues, such as prostate and mammary glands, were also observed in the Men1 mutant mice. To study the occurrence of prostate lesions, we followed a male mouse cohort of 47 Men1 +/- mice and 23 age-matched control littermates, starting at 18 months of age, and analysed the prostate glands from the cohort. Six Men1 +/- mice (12.8%) developed prostate cancer, including two adenocarcinomas and four in situ carcinomas, while none of the control mice developed cancerous lesions. The expression of menin encoded by the Men1 gene was found to be drastically reduced in all carcinomas, and partial LOH of the wild-type Men1 allele was detected in three of the five analysed lesions. Using immunostaining for the androgen receptor and p63, a basal epithelial cell marker, we demonstrated that the menin-negative prostate cancer cells did not display p63 expression and that the androgen receptor was expressed but more heterogeneous in these lesions. Furthermore, our data showed that the expression of the cyclin-dependent kinase inhibitor CDKN1B (p27), a Men1 target gene known to be inactivated during prostate cell tumorigenesis, was notably decreased in the prostate cancers that developed in the mutant mice. Our work suggests the possible involvement of Men1 inactivation in the tumorigenesis of the prostate gland

Lung papillary adenocarcinoma complicated with paraneoplastic autoimmune hemolytic anemia: A case report

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Xing, Limin; Wang, Huaquan; Qu, Wen; Fang, Fang; Dong, Qi-e; Shao, Zonghong

2014-01-01

A middle-aged woman presented at our facility and was diagnosed after surgery with lung papillary adenocarcinoma. Seven years earlier, she had suffered from autoimmune hemolytic anemia (AIHA), which was refractory. Following lung surgery, the AIHA was cured.

Co-Targeting Prostate Cancer Epithelium and Bone Stroma by Human Osteonectin-Promoter-Mediated Suicide Gene Therapy Effectively Inhibits Androgen-Independent Prostate Cancer Growth.

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Shian-Ying Sung

Full Text Available Stromal-epithelial interaction has been shown to promote local tumor growth and distant metastasis. We sought to create a promising gene therapy approach that co-targets cancer and its supporting stromal cells for combating castration-resistant prostate tumors. Herein, we demonstrated that human osteonectin is overexpressed in the prostate cancer epithelium and tumor stroma in comparison with their normal counterpart. We designed a novel human osteonectin promoter (hON-522E containing positive transcriptional regulatory elements identified in both the promoter and exon 1 region of the human osteonectin gene. In vitro reporter assays revealed that the hON-522E promoter is highly active in androgen receptor negative and metastatic prostate cancer and bone stromal cells compared to androgen receptor-positive prostate cancer cells. Moreover, in vivo prostate-tumor-promoting activity of the hON-522E promoter was confirmed by intravenous administration of an adenoviral vector containing the hON-522E promoter-driven luciferase gene (Ad-522E-Luc into mice bearing orthotopic human prostate tumor xenografts. In addition, an adenoviral vector with the hON-522E-promoter-driven herpes simplex virus thymidine kinase gene (Ad-522E-TK was highly effective against the growth of androgen-independent human prostate cancer PC3M and bone stromal cell line in vitro and in pre-established PC3M tumors in vivo upon addition of the prodrug ganciclovir. Because of the heterogeneity of human prostate tumors, hON-522E promoter-mediated gene therapy has the potential for the treatment of hormone refractory and bone metastatic prostate cancers.

[Concomitant oncopathological changes in the prostate of urinary bladder cancer patients undergoing radical cystoprostateectomy].

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Komyakov, B K; Sergeev, A V; Fadeev, V A; Ismailov, K I; Ulyanov, A Yu; Shmelev, A Yu; Onoshko, M V

2017-09-01

To determine the incidence of spreading bladder transitional cell carcinoma and primary adenocarcinoma to the prostate in patients with bladder cancer undergoing radical cystectomy. From 1995 to 2016, 283 men underwent radical cystectomy with removal of the bladder, perivesical tissue, prostate, seminal vesicles and pelvic lymph nodes. Prostate sparing cystectomy was performed in 45 (13.7%) patients. The whole prostate and the apex of the prostate were preserved in 21 (6.4%) and 24 (7.3%) patients, respectively. The spread of transitional cell cancer of the bladder to the prostate occurred in 50 (15.2%) patients. Twelve (3.6%) patients were found to have primary prostate adenocarcinoma. Clinically significant prostate cancer was diagnosed in 4 (33.3%) patients. We believe that the high oncological risk of prostate sparing cystectomy, despite some functional advantages, dictates the need for complete removal of the prostate in the surgical treatment of bladder cancer.

Stromal Activation Associated with Development of Prostate Cancer in Prostate-Targeted Fibroblast Growth Factor 8b Transgenic Mice

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Teresa D. Elo

2010-11-01

Full Text Available Expression of fibroblast growth factor 8 (FGF-8 is commonly increased in prostate cancer. Experimental studies have provided evidence that it plays a role in prostate tumorigenesis and tumor progression. To study how increased FGF-8 affects the prostate, we generated and analyzed transgenic (TG mice expressing FGF-8b under the probasin promoter that targets expression to prostate epithelium. Prostates of the TG mice showed an increased size and changes in stromal and epithelialmorphology progressing fromatypia and prostatic intraepithelial neoplasia (mouse PIN, mPIN lesions to tumors with highly variable phenotype bearing features of adenocarcinoma, carcinosarcoma, and sarcoma. The development of mPIN lesions was preceded by formation of activated stroma containing increased proportion of fibroblastic cells, rich vasculature, and inflammation. The association between advancing stromal and epithelial alterations was statistically significant. Microarray analysis and validation with quantitative polymerase chain reaction revealed that expression of osteopontin and connective tissue growth factor was markedly upregulated in TG mouse prostates compared with wild type prostates. Androgen receptor staining was decreased in transformed epithelium and in hypercellular stroma but strongly increased in the sarcoma-like lesions. In conclusion, our data demonstrate that disruption of FGF signaling pathways by increased epithelial production of FGF-8b leads to strongly activated and atypical stroma, which precedes development of mPIN lesions and prostate cancer with mixed features of adenocarcinoma and sarcoma in the prostates of TG mice. The results suggest that increased FGF-8 in human prostate may also contribute to prostate tumorigenesis by stromal activation.

Prostate Brachytherapy in Men ≥75 Years of Age

International Nuclear Information System (INIS)

Merrick, Gregory S.; Wallner, Kent E.; Galbreath, Robert W.; Butler, Wayne M.; Brammer, Sarah G.; Allen, Zachariah A.; Adamovich, Edward

2008-01-01

Purpose: To evaluate cause-specific survival (CSS), biochemical progression-free survival (bPFS), and overall survival (OS) in prostate cancer patients aged ≥75 years undergoing brachytherapy with or without supplemental therapies. Methods and Materials: Between April 1995 and August 2004, 145 consecutive patients aged ≥75 years underwent permanent prostate brachytherapy. Median follow-up was 5.8 years. Biochemical progression-free survival was defined by a prostate-specific antigen level ≤0.40 ng/mL after nadir. Patients with metastatic prostate cancer or hormone-refractory disease without obvious metastases who died of any cause were classified as dead of prostate cancer. All other deaths were attributed to the immediate cause of death. Multiple clinical, treatment, and dosimetric parameters were evaluated for impact on survival. Results: Nine-year CSS, bPFS, and OS rates for the entire cohort were 99.3%, 97.1%, and 64.5%, respectively. None of the evaluated parameters predicted for CSS, whereas bPFS was most closely predicted by percentage positive biopsies. Overall survival and non-cancer deaths were best predicted by tobacco status. Thirty-seven patients have died, with 83.8% of the deaths due to cardiovascular disease (22 patients) or second malignancies (9 patients). To date, only 1 patient (0.7%) has died of metastatic prostate cancer. Conclusions: After brachytherapy, high rates of CSS and bPFS are noted in elderly prostate cancer patients. Overall, approximately 65% of patients are alive at 9 years, with survival most closely related to tobacco status. We believe our results support an aggressive locoregional approach in appropriately selected elderly patients

Small cell carcinoma of the prostate presenting with Cushing Syndrome. A narrative review of an uncommon condition.

Science.gov (United States)

Rueda-Camino, José Antonio; Losada-Vila, Beatriz; De Ancos-Aracil, Cristina Lucía; Rodríguez-Lajusticia, Laura; Tardío, Juan Carlos; Zapatero-Gaviria, Antonio

2016-01-01

Small cell carcinoma (SCC) of the prostate is an uncommon condition; there are very few cases in which presenting symptoms are consistent with Cushing Syndrome (CS). We report a new case in which CS triggers the suspicion of an SCC of the prostate and a review of the published cases of SCC of the prostate presenting with CS. The origin of these neoplasms is still unclear. It may be suspected when laboratory features appear in patients diagnosed with prostatic adenocarcinoma which becomes resistant to specific therapy. SCC usually occurs after the 6th decade. Patients suffering SCC of the prostate presenting with CS usually present symptoms such as hypertension, hyperglycemia, alkalosis or hypokalemia; cushingoid phenotype is less frequent. Cortisol and ACTH levels are often high. Prostatic-specific antigen levels are usually normal. CT scan is the preferred imaging test to localize the lesion, but its performance may be improved by adding other tests, such as FDG-PET scan. All patients have metastatic disease at the time of diagnosis. Lymph nodes, liver and bone are the most frequent metastases sites. Surgery and Ketokonazole are the preferred treatments for CS. The prognosis is very poor: 2- and 5-year survival rates are 27.5 and 14.3%, respectively. Key messages When a patient presents with ectopic Cushing Syndrome but lungs are normal, an atypical localization should be suspected. We should suspect a prostatic origin if Cushing Syndrome is accompanied by obstructive inferior urinary tract symptoms or in the setting of a prostatic adenocarcinoma with rapid clinical and radiological progression with relatively low PSA levels. Although no imaging test is preferred to localize these tumors, FDG-PET-TC can be very useful. Hormone marker scintigraphy (e.g. somatostatin) could be used too. As Cushing Syndrome is a paraneoplastic phenomenon, treatment of the underlying disease may help control hypercortisolism manifestations. These tumors are usually metastatic by the

Testicular Metastases From Prostate Carcinoma

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Harrina Erlianti Rahardjo

2010-07-01

Full Text Available Metastasis of prostate carcinoma to the testis is seldom reported. The tumour may spread from the prostatic urethra by retrograde venous extension, arterial embolism or through direct invasion into the lymphatics and lumen of the vas deferens. Clinical manifestations of secondary testicular tumours from the prostate are most often unsuspected clinically and are instead detected incidentally during orchidectomy. Less frequently, a palpable mass is detected, which may be confused with a primary testicular neoplasm. We report a case of a 66-year-old patient with adenocarcinoma of the prostate, and a left testicular tumour that was diagnosed as metastases from prostate carcinoma after radical orchidectomy.

Efficacy and tolerability of tamsulosin 0.4 mg in Asian patients with lower urinary tract symptoms secondary to benign prostatic hyperplasia refractory to tamsulosin 0.2 mg: a randomized placebo controlled trial.

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Kim, Jung Jun; Han, Deok Hyun; Sung, Hyun Hwan; Choo, Seol Ho; Lee, Sung Won

2014-07-01

To evaluate the efficacy and safety of tamsulosin dose increase to 0.4 mg daily in Asian patients with lower urinary tract symptoms secondary to benign prostatic hyperplasia refractory to tamsulosin 0.2 mg treatment. We carried out a 12-week, single-center, randomized, placebo-controlled trial in 220 patients. Patients treated with 0.2 mg tamsulosin daily without other lower urinary tract symptoms secondary to benign prostatic hyperplasia medication for more than 3 months and refractory to this treatment were enrolled. We defined "refractory" as an International Prostate Symptom Score of 13 or greater and a maximum flow rate of 15 or under despite medication. Patients with a surgical history related to lower urinary tract symptoms secondary to benign prostatic hyperplasia or a postvoid residual of 150 mL or greater were excluded. Eligible patients were randomly assigned to the 0.4 mg group (two tablets of 0.2 mg tamsulosin once daily) or the 0.2 mg group (one tablet of 0.2 mg tamsulosin and one tablet of placebo once daily). International Prostate Symptom Score, maximum flow rate, blood pressure, heart rate, and adverse events were compared between the two groups at 4 weeks and 12 weeks. A total of 220 patients were enrolled and analyzed. There were no differences in baseline characteristics between the two groups. After 12 weeks of medication, the International Prostate Symptom Score was not different between the two groups. However, the improvement in maximum flow rate was greater in the 0.4 mg group than the 0.2 mg group (3.0 ± 0.48 mL/s vs -0.25 ± 0.30 mL/s, P Tamsulosin 0.4 mg appears to be a safe treatment regimen for treating lower urinary tract symptoms secondary to benign prostatic hyperplasia in Asian patients who do not respond to 0.2 mg treatment. Increasing the dose of tamsulosin results in a significant improvement in maximum flow rate without any increase in cardiovascular complications. © 2014 The

Hormonal response recovery after long-term androgen deprivation therapy in patients with prostate cancer.

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Planas, Jacques; Celma, Ana; Placer, José; Cuadras, Mercè; Regis, Lucas; Gasanz, Carlos; Trilla, Enrique; Salvador, Carlos; Lorente, David; Morote, Juan

2016-12-01

The aim of this study was to evaluate hormonal recovery after cessation of androgen deprivation therapy (ADT) in a group of elderly prostate cancer patients. Forty patients with locally advanced or metastatic prostate cancer, with a mean age of 71.5 years [95% confidence interval (CI) 69.1-73.9], were treated with ADT for a mean duration of 74.6 months (95% CI 59.7-89.5 months). Mean follow-up time after ADT cessation was 36.5 months (95% CI 30.6-42.3 months). Serum testosterone and luteinizing hormone (LH) were determined at 6 month intervals after ADT cessation. After 18 months of follow-up, all patients had recovered normal LH levels, while 38% of patients still presented castration levels of testosterone (50 ng/dl). Neither age at start of ADT nor clinical stage reached statistical significance. Only time under ADT was correlated with testosterone recovery (p = .031). Kaplan-Meier curves were obtained. Mean time for testosterone recovery was 14.5 months (95% CI 6.5-22.6 months) in patients treated with ADT for less than 60 months compared to 29.3 months (95% CI 19.6-39.1 months) in patients treated with ADT for more than 60 months (log-rank p = .029). Age did not correlate with testosterone recovery in a group of elderly prostate cancer patients in whom ADT was stopped. Testosterone recovery after ADT cessation was significantly correlated with time under ADT treatment. Significant implications related to economic aspects of the dosage schedule may be considered.

Novel Fatty Acid Lipoxygenases in the Development of Human and Murine Prostate Cancer

Science.gov (United States)

1999-10-01

with Dr. Matthew Breyer on a study utilizing bladder biopsy and cystectomy specimens and in situ hybridization and immunohistochemistry which...Reduced in Prostate Adenocarcinoma Scott B. Shappell,* William E. Boeglin,t prostate adenocarcinomas. (Am J Patbol 1999, Sandy J. Olson,* Susan Kasper...this novel enzyme in secretory function. 33157-33160 5. Samuelsson B. Dahlen SE, Lindgren JA, Rouzer CA, Serhan CN: Reduced expression in atrophic

ホルモン療法が奏効した前立腺粘液癌の1例

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石津, 和彦; 吉弘, 悟; 城甲, 啓治; 瀧原, 博史; 酒徳, 治三郎; 田中, 一成

1991-01-01

A 79-year-old man complained of pollakisuria and sense of retention. The prostate was stony hard and heterogeneously enhanced on computed tomographic (CT) scan. The serum levels of prostatic specific antigen, prostatic acid phosphatase and gamma-Seminoprotein were abnormally high. Prostatic biopsy showed mucinous adenocarcinoma which was stained by prostatic specific antigen. Bone scintigraphy revealed multiple metastases. Hormonal therapy was performed. Each prostatic tumor marker decreased ...

Primary mucinous adenocarcinoma of the bladder with signet-ring cells: case report

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Marcelo Lorenzi Marques

Full Text Available CONTEXT: Primary adenocarcinomas of the bladder are uncommon and usually occur by contiguity with or hematogenic dissemination of other adenocarcinomas such as colorectal, prostate and gynecological tract carcinomas. Mucinous and signet-ring cell histological patterns are even rarer and it is often difficult to morphologically distinguish them from metastatic colorectal adenocarcinoma. CASE REPORT: We present and discuss a rare case of primary mucinous adenocarcinoma of the bladder with signet-ring cells in a 57-year-old male patient. Other primary sites for the tumor had been excluded and, in the absence of digestive tract tumor and for confirmation that it was a primary bladder tumor, an immunohistochemistry study was performed.

Validation of the D'amico risk groups classification, valuation of high-risk patients with or without hormonal therapy and complications of patients with adenocarcinoma of the prostate, after treatment with external radiotherapy, Hospital Calderon Guardia, 2003-2004

International Nuclear Information System (INIS)

Lopez Arias, Ever Roy

2008-01-01

D'amico risk groups have been classified to estimate the probability of biochemical recurrence after treatment for localized prostate cancer. The evolution of patients that have received external radiotherapy were analyzed according to the risk group. The medical records of 50 patients between 2003 and 2004 have been assessed and has observed the evolution of Prostatic Specific Antigen after treatment ends, at Hospital Calderon Guardia. Adverse reactions resulting from radiotherapy treatment and the organs most affected by the same have been documented nith the possibility to compare the results of similar studies in the literature. The best performance is given by receiving concomitant hormonal therapy that high risk patients of D'amico without receiving. (author) [es

Bispecific small molecule-antibody conjugate targeting prostate cancer.

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Kim, Chan Hyuk; Axup, Jun Y; Lawson, Brian R; Yun, Hwayoung; Tardif, Virginie; Choi, Sei Hyun; Zhou, Quan; Dubrovska, Anna; Biroc, Sandra L; Marsden, Robin; Pinstaff, Jason; Smider, Vaughn V; Schultz, Peter G

2013-10-29

Bispecific antibodies, which simultaneously target CD3 on T cells and tumor-associated antigens to recruit cytotoxic T cells to cancer cells, are a promising new approach to the treatment of hormone-refractory prostate cancer. Here we report a site-specific, semisynthetic method for the production of bispecific antibody-like therapeutics in which a derivative of the prostate-specific membrane antigen-binding small molecule DUPA was selectively conjugated to a mutant αCD3 Fab containing the unnatural amino acid, p-acetylphenylalanine, at a defined site. Homogeneous conjugates were generated in excellent yields and had good solubility. The efficacy of the conjugate was optimized by modifying the linker structure, relative binding orientation, and stoichiometry of the ligand. The optimized conjugate showed potent and selective in vitro activity (EC50 ~ 100 pM), good serum half-life, and potent in vivo activity in prophylactic and treatment xenograft mouse models. This semisynthetic approach is likely to be applicable to the generation of additional bispecific agents using drug-like ligands selective for other cell-surface receptors.

Bispecific small molecule–antibody conjugate targeting prostate cancer

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Kim, Chan Hyuk; Axup, Jun Y.; Lawson, Brian R.; Yun, Hwayoung; Tardif, Virginie; Choi, Sei Hyun; Zhou, Quan; Dubrovska, Anna; Biroc, Sandra L.; Marsden, Robin; Pinstaff, Jason; Smider, Vaughn V.; Schultz, Peter G.

2013-01-01

Bispecific antibodies, which simultaneously target CD3 on T cells and tumor-associated antigens to recruit cytotoxic T cells to cancer cells, are a promising new approach to the treatment of hormone-refractory prostate cancer. Here we report a site-specific, semisynthetic method for the production of bispecific antibody-like therapeutics in which a derivative of the prostate-specific membrane antigen-binding small molecule DUPA was selectively conjugated to a mutant αCD3 Fab containing the unnatural amino acid, p-acetylphenylalanine, at a defined site. Homogeneous conjugates were generated in excellent yields and had good solubility. The efficacy of the conjugate was optimized by modifying the linker structure, relative binding orientation, and stoichiometry of the ligand. The optimized conjugate showed potent and selective in vitro activity (EC50 ∼100 pM), good serum half-life, and potent in vivo activity in prophylactic and treatment xenograft mouse models. This semisynthetic approach is likely to be applicable to the generation of additional bispecific agents using drug-like ligands selective for other cell-surface receptors. PMID:24127589

Establishment of prostate cancer spheres from a prostate cancer cell line after phenethyl isothiocyanate treatment and discovery of androgen-dependent reversible differentiation between sphere and neuroendocrine cells.

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Chen, Yamei; Cang, Shundong; Han, Liying; Liu, Christina; Yang, Patrick; Solangi, Zeeshan; Lu, Quanyi; Liu, Delong; Chiao, J W

2016-05-03

Prostate cancer can transform from androgen-responsive to an androgen-independent phenotype. The mechanism responsible for the transformation remains unclear. We studied the effects of an epigenetic modulator, phenethyl isothiocyanate (PEITC), on the androgen-responsive LNCaP cells. After treatment with PEITC, floating spheres were formed with characteristics of prostate cancer stem cells (PCSC). These spheres were capable of self-renewal in media with and without androgen. They have been maintained in both types of media as long term cultures. Upon androgen deprivation, the adherent spheres differentiated to neuroendocrine cells (NEC) with decreased proliferation, expression of androgen receptor, and PSA. NEC reverse differentiated to spheres when androgen was replenished. The sphere cells expressed surface marker CD44 and had enhanced histone H3K4 acetylation, DNMT1 down-regulation and GSTP1 activation. We hypothesize that PEITC-mediated alteration in epigenomics of LNCaP cells may give rise to sphere cells, whereas reversible androgenomic alterations govern the shuttling between sphere PCSC and progeny NEC. Our findings identify unrecognized properties of prostate cancer sphere cells with multi-potential plasticity. This system will facilitate development of novel therapeutic agents and allow further exploration into epigenomics and androgenomics governing the transformation to hormone refractory prostate cancer.

Patient-derived Hormone-naive Prostate Cancer Xenograft Models Reveal Growth Factor Receptor Bound Protein 10 as an Androgen Receptor-repressed Gene Driving the Development of Castration-resistant Prostate Cancer.

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Hao, Jun; Ci, Xinpei; Xue, Hui; Wu, Rebecca; Dong, Xin; Choi, Stephen Yiu Chuen; He, Haiqing; Wang, Yu; Zhang, Fang; Qu, Sifeng; Zhang, Fan; Haegert, Anne M; Gout, Peter W; Zoubeidi, Amina; Collins, Colin; Gleave, Martin E; Lin, Dong; Wang, Yuzhuo

2018-06-01

Although androgen deprivation therapy is initially effective in controlling growth of hormone-naive prostate cancers (HNPCs) in patients, currently incurable castration-resistant prostate cancer (CRPC) inevitably develops. To identify CRPC driver genes that may provide new targets to enhance CRPC therapy. Patient-derived xenografts (PDXs) of HNPCs that develop CRPC following host castration were examined for changes in expression of genes at various time points after castration using transcriptome profiling analysis; particular attention was given to pre-CRPC changes in expression indicative of genes acting as potential CRPC drivers. The functionality of a potential CRPC driver was validated via its knockdown in cultured prostate cancer cells; its clinical relevance was established using data from prostate cancer patient databases. Eighty genes were found to be significantly upregulated at the CRPC stage, while seven of them also showed elevated expression prior to CRPC development. Among the latter, growth factor receptor bound protein 10 (GRB10) was the most significantly and consistently upregulated gene. Moreover, elevated GRB10 expression in clinical prostate cancer samples correlated with more aggressive tumor types and poorer patient treatment outcome. GRB10 knockdown markedly reduced prostate cancer cell proliferation and activity of AKT, a well-established CRPC mediator. A positive correlation between AKT activity and GRB10 expression was also found in clinical cohorts. GRB10 acts as a driver of CRPC and sensitizes androgen receptor pathway inhibitors, and hence GRB10 targeting provides a novel therapeutic strategy for the disease. Development of castration-resistant prostate cancer (CRPC) is a major problem in the management of the disease. Using state-of-the-art patient-derived hormone-naive prostate cancer xenograft models, we found and validated the growth factor receptor bound protein 10 gene as a driver of CRPC, indicating that it may be used as a

Prostate-specific antigen-positive extramammary Paget's disease--association with prostate cancer

DEFF Research Database (Denmark)

Hammer, Anne; Hager, Henrik; Steiniche, Torben

2008-01-01

Extramammary Paget's disease (EMPD) is a rare intraepidermal adenocarcinoma that primarily affects the anogenital region. Cases of EMPD reacting with PSA (prostate-specific antigen) have previously been associated with underlying prostate cancer. However, a recent case of EMPD in our department has...... led us to question the value of PSA as an indicator of underlying prostate cancer. Clinical and pathological data were obtained for 16 cases of EMPD. Formalin-fixed, paraffin-embedded tissue blocks from the primary skin lesions were investigated using PSA and other immunohistochemical markers. 5...... of the 16 cases of EMPD stained positive for PSA (2 women and 3 men). However, no reactivity was seen for the prostatic marker P501S. Three of the five patients had been diagnosed with internal malignant disease-two with prostate cancer, stage 1. Immunohistochemical investigations of the tumour specimens...

Inhibition of RM-1 prostate carcinoma and eliciting robust immune responses in the mouse model by using VEGF-M2-GnRH3-hinge-MVP vaccine.

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Wang, Yiqin; Alahdal, Murad; Ye, Jia; Jing, Liangliang; Liu, Xiaoxin; Chen, Huan; Jin, Liang; Cao, Rongyue

2018-01-23

GnRH and VEGF have been investigated as prostate carcinoma enhancers that support tumor spread and progression. Although both have documented roles in prostate carcinoma and many cancer types, the weak immunogenicity of these peptides has remained a major challenge for use in immunotherapy. Here, we describe a novel strategy to inhibit GnRH and VEGF production and assess the effect on the immune responses against these hormones using the RM-1 prostate cancer model. We designed a novel recombinant fusion protein which combined GnRH and VEGF as a vaccine against this tumor. The newly constructed fusion protein hVEGF121-M2-GnRH3-hinge-MVP contains the human vascular endothelial growth factor (hVEGF121) and three copies of GnRH in sequential linear alignment and T helper epitope MVP as an immunogenic vaccine. The effectiveness of the vaccine in eliciting an immune response and attenuating the prostate tumor growth was evaluated. Results showed that administration of a new vaccine effectively elicited humoral and cellular immune responses. We found that, a novel fusion protein, hVEGF121-M2-GnRH3-hinge-MVP, effectively inhibited growth of RM-1 prostate model and effectively promoted immune response. In conclusion, hVEGF121-M2-GnRH3-hinge-MVP is an effective dual mechanism tumor vaccine that limits RM-1 prostate growth. This vaccine may be a promising strategy for the treatment of hormone refractory prostate malignancies.

Tumor Volume Changes on 1.5 Tesla Endorectal MRI During Neoadjuvant Androgen Suppression Therapy for Higher-Risk Prostate Cancer and Recurrence in Men Treated Using Radiation Therapy Results of the Phase II CALGB 9682 Study

International Nuclear Information System (INIS)

D'Amico, Anthony V.; Halabi, Susan; Tempany, Clare; Titelbaum, David; Philips, George K.; Loffredo, Marian; McMahon, Elizabeth; Sanford, Ben; Vogelzang, Nicholas J.; Small, Eric J.

2008-01-01

Purpose: We prospectively determined whether the change in tumor volume (TV) during 2 months of neoadjuvant androgen suppression therapy (nAST) measured using conventional 1.5 Tesla endorectal magnetic resonance imaging (eMRI) was associated with the risk of recurrence after radiation (RT) and 6 months of AST. Patients and Methods: Between 1997 and 2001, 180 men with clinical stage T1c-T3cN0M0 adenocarcinoma of the prostate were registered. Fifteen were found to be ineligible and the institutional MR radiologist could not assess the TV in 32, leaving 133 for analysis. Multivariable Cox regression analysis was used to assess whether a significant association existed between eMRI-defined TV progression during nAST and time to recurrence adjusting for prostate-specific antigen (PSA) level, Gleason score (8 to 10 or 7 vs. 6 or less) and stage (T3 vs. T1-2). Results: After a median follow up of 6.7 years and adjusting for known prognostic factors, there was a significant increase in the risk of PSA failure (HR, 2.3 [95% CI, 1.1-4.5; p = 0.025) in men with eMRI-defined TV progression during nAST. Specifically, adjusted estimates of PSA failure were significantly higher (p = 0.032) in men with, compared with men without, eMRI-defined TV progression reaching 38% vs. 19%, respectively, by 5 years. Conclusion: Eradicating intraprostatic hormone refractory prostate cancer (HRPC) by maximizing local control and randomized trials assessing whether survival is improved when agents active against HRPC are combined with maximal local therapy are needed in men who progress based on eMRI during nAST

Variations of serum testosterone levels in prostate cancer patients under LH-releasing hormone therapy: an open question.

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Reis, Leonardo Oliveira

2012-06-01

The hypothesis 'the lower the better when achieving castration levels of testosterone' is based on the data from second-line hormonal manipulation and its molecular basis, and on better oncological results reported for lower castration levels in prostate cancer (PCa) patients, including those achieved with maximal androgen blockade. In this regard, the equivalence of surgical and different pharmacological castrations has been controversial. The modified amino acid structure that makes LH-releasing hormone (LHRH) analogs more potent than LHRH, and the method of delivering the analogs impacts on bioavailibility and potentially causes differences in androgen levels and in its final oncological efficacy. In addition to this, there is a myriad of circumstances, such as those related to ethnic variations and co-morbidities, which uniquely impact on the pharmacological approach in a highly heterogeneous population of castration-resistant prostate cancer (CRPC) patients. Ineffective testosterone suppression through hormonal escape is currently poorly recognized and may result in increased PCa mortality. Until now, the optimal serum testosterone level in patients under castration, and the impact of its variations in patients under LHRH therapy, remain open questions and have been merged to a broad spectra of patients who are highly heterogeneous. This heterogeneity relates to a number of mechanisms regarding response to treatment, which influences the biology of the relapsing tumor and the sensitivity to subsequent therapies in the individual patient. The rationale to achieve testosterone levels below 20-50 ng/dl warrant further investigation as these levels have recently rescued CRPC patients. In the last few years and months, important advancements in prostate cancer treatment have been achieved. Nevertheless, these advances are measured in a few months of additional survival and under high costs, not available to most of the world population, compared with the benefits

TRPV6 alleles do not influence prostate cancer progression

International Nuclear Information System (INIS)

Kessler, Thorsten; Wissenbach, Ulrich; Grobholz, Rainer; Flockerzi, Veit

2009-01-01

The transient receptor potential, subfamily V, member 6 (TRPV6) is a Ca 2+ selective cation channel. Several studies have shown that TRPV6 transcripts are expressed in locally advanced prostatic adenocarcinoma, metastatic and androgen-insensitive prostatic lesions but are undetectable in healthy prostate tissue and benign prostatic hyperplasia. Two allelic variants of the human trpv6 gene have been identified which are transcribed into two independent mRNAs, TRPV6a and TRPV6b. We now asked, whether the trpv6a allele is correlated with the onset of prostate cancer, with the Gleason score and the tumour stage. Genomic DNA of prostate cancer patients and control individuals was isolated from resections of prostatic adenocarcinomas and salivary fluid respectively. Genotyping of SNPs of the TRPV6 gene was performed by restriction length polymorphism or by sequencing analysis. RNA used for RT-PCR was isolated from prostate tissue. Data sets were analyzed by Chi-Square test. We first characterized in detail the five polymorphisms present in the protein coding exons of the trpv6 gene and show that these polymorphisms are coupled and are underlying the TRPV6a and the TRPV6b variants. Next we analysed the frequencies of the two TRPV6 alleles using genomic DNA from saliva samples of 169 healthy individuals. The homozygous TRPV6b genotype predominated with 86%, whereas no homozygous TRPV6a carriers could be identified. The International HapMap Project identified a similar frequency for an Utah based population whereas in an African population the a-genotype prevailed. The incidence of prostate cancer is several times higher in African populations than in non-African and we then investigated the TRPV6a/b frequencies in 141 samples of prostatic adenocarcinoma. The TRPV6b allele was found in 87% of the samples without correlation with Gleason score and tumour stage. Our results show that the frequencies of trpv6 alleles in healthy control individuals and prostate cancer patients

TRPV6 alleles do not influence prostate cancer progression.

Science.gov (United States)

Kessler, Thorsten; Wissenbach, Ulrich; Grobholz, Rainer; Flockerzi, Veit

2009-10-26

The transient receptor potential, subfamily V, member 6 (TRPV6) is a Ca(2+) selective cation channel. Several studies have shown that TRPV6 transcripts are expressed in locally advanced prostatic adenocarcinoma, metastatic and androgen-insensitive prostatic lesions but are undetectable in healthy prostate tissue and benign prostatic hyperplasia. Two allelic variants of the human trpv6 gene have been identified which are transcribed into two independent mRNAs, TRPV6a and TRPV6b. We now asked, whether the trpv6a allele is correlated with the onset of prostate cancer, with the Gleason score and the tumour stage. Genomic DNA of prostate cancer patients and control individuals was isolated from resections of prostatic adenocarcinomas and salivary fluid respectively. Genotyping of SNPs of the TRPV6 gene was performed by restriction length polymorphism or by sequencing analysis. RNA used for RT-PCR was isolated from prostate tissue. Data sets were analyzed by Chi-Square test. We first characterized in detail the five polymorphisms present in the protein coding exons of the trpv6 gene and show that these polymorphisms are coupled and are underlying the TRPV6a and the TRPV6b variants. Next we analysed the frequencies of the two TRPV6 alleles using genomic DNA from saliva samples of 169 healthy individuals. The homozygous TRPV6b genotype predominated with 86%, whereas no homozygous TRPV6a carriers could be identified. The International HapMap Project identified a similar frequency for an Utah based population whereas in an African population the a-genotype prevailed. The incidence of prostate cancer is several times higher in African populations than in non-African and we then investigated the TRPV6a/b frequencies in 141 samples of prostatic adenocarcinoma. The TRPV6b allele was found in 87% of the samples without correlation with Gleason score and tumour stage. Our results show that the frequencies of trpv6 alleles in healthy control individuals and prostate cancer patients

TRPV6 alleles do not influence prostate cancer progression

Directory of Open Access Journals (Sweden)

Flockerzi Veit

2009-10-01

Full Text Available Abstract Background The transient receptor potential, subfamily V, member 6 (TRPV6 is a Ca2+ selective cation channel. Several studies have shown that TRPV6 transcripts are expressed in locally advanced prostatic adenocarcinoma, metastatic and androgen-insensitive prostatic lesions but are undetectable in healthy prostate tissue and benign prostatic hyperplasia. Two allelic variants of the human trpv6 gene have been identified which are transcribed into two independent mRNAs, TRPV6a and TRPV6b. We now asked, whether the trpv6a allele is correlated with the onset of prostate cancer, with the Gleason score and the tumour stage. Methods Genomic DNA of prostate cancer patients and control individuals was isolated from resections of prostatic adenocarcinomas and salivary fluid respectively. Genotyping of SNPs of the TRPV6 gene was performed by restriction length polymorphism or by sequencing analysis. RNA used for RT-PCR was isolated from prostate tissue. Data sets were analyzed by Chi-Square test. Results We first characterized in detail the five polymorphisms present in the protein coding exons of the trpv6 gene and show that these polymorphisms are coupled and are underlying the TRPV6a and the TRPV6b variants. Next we analysed the frequencies of the two TRPV6 alleles using genomic DNA from saliva samples of 169 healthy individuals. The homozygous TRPV6b genotype predominated with 86%, whereas no homozygous TRPV6a carriers could be identified. The International HapMap Project identified a similar frequency for an Utah based population whereas in an African population the a-genotype prevailed. The incidence of prostate cancer is several times higher in African populations than in non-African and we then investigated the TRPV6a/b frequencies in 141 samples of prostatic adenocarcinoma. The TRPV6b allele was found in 87% of the samples without correlation with Gleason score and tumour stage. Conclusion Our results show that the frequencies of trpv6

Is There a Role for Pelvic Irradiation in Localized Prostate Adenocarcinoma? Update of the Long-Term Survival Results of the GETUG-01 Randomized Study

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Pommier, Pascal, E-mail: Pascal.pommier@lyon.unicancer.fr [Department of Radiation Oncology, Centre Léon Bérard, Lyon (France); Chabaud, Sylvie [Department of Clinical Research and Innovation, Centre Léon Bérard, Lyon (France); Lagrange, Jean-Leon [Department of Radiation Oncology, Centre Hospitalo-Universitaire H. Mondor, Créteil (France); Richaud, Pierre [Department of Radiation Oncology, Institut Bergognié, Bordeaux (France); Le Prise, Elisabeth [Department of Radiation Oncology, Centre Eugène Marquis, Rennes (France); Wagner, Jean-Philippe [Department of Radiation Oncology, Institut Andrée Dutreix, Dunkerque (France); Azria, David [Department of Radiation Oncology, Institut de Cancérologie de Montpellier, Montpellier (France); Beckendorf, Veronique [Department of Radiation Oncology, Institut de Cancérologie de Lorraine, Nancy (France); Suchaud, Jean-Philippe [Department of Radiation Oncology, Centre Hospitalier de Roanne, Roanne (France); Bernier, Valerie [Department of Radiation Oncology, Centre Oscar Lambret, Lille (France); Perol, David [Department of Clinical Research and Innovation, Centre Léon Bérard, Lyon (France); Carrie, Christian [Department of Radiation Oncology, Centre Léon Bérard, Lyon (France)

2016-11-15

Purpose: To report the long-term results of the French Genitourinary Study Group (GETUG)-01 study in terms of event-free survival (EFS) and overall survival (OS) and assess the potential interaction between hormonotherapy and pelvic nodes irradiation. Patients and Methods: Between December 1998 and June 2004, 446 patients with T1b-T3, N0pNx, M0 prostate carcinoma were randomly assigned to either pelvic nodes and prostate or prostate-only radiation therapy. Patients were stratified into 2 groups: “low risk” (T1-T2 and Gleason score 6 and prostate-specific antigen <3× the upper normal limit of the laboratory) (92 patients) versus “high risk” (T3 or Gleason score >6 or prostate-specific antigen >3× the upper normal limit of the laboratory). Short-term 6-month neoadjuvant and concomitant hormonal therapy was allowed only for high-risk patients. Radiation therapy was delivered with a 3-dimensional conformal technique, using a 4-field technique for the pelvic volume (46 Gy). The total dose recommended to the prostate moved from 66 Gy to 70 Gy during the course of the study. Criteria for EFS included biologic prostate-specific antigen recurrences and/or a local or metastatic progression. Results: With a median follow-up of 11.4 years, the 10-year OS and EFS were similar in the 2 treatment arms. A higher but nonsignificant EFS was observed in the low-risk subgroup in favor of pelvic nodes radiation therapy (77.2% vs 62.5%; P=.18). A post hoc subgroup analysis showed a significant benefit of pelvic irradiation when the risk of lymph node involvement was <15% (Roach formula). This benefit seemed to be limited to patients who did not receive hormonal therapy. Conclusion: Pelvic nodes irradiation did not statistically improve EFS or OS in the whole population but may be beneficial in selected low- and intermediate-risk prostate cancer patients treated with exclusive radiation therapy.

Tomotherapy for prostate adenocarcinoma: A report on acute toxicity

International Nuclear Information System (INIS)

Keiler, Louis; Dobbins, Donald; Kulasekere, Ravi; Einstein, Douglas

2007-01-01

Background and purpose: To analyze the impact of Tomotherapy (TOMO) intensity modulated radiotherapy (IMRT) on acute gastrointestinal (GI) and genitourinary (GU) toxicity in prostate cancer. Materials and methods: The records of 55 consecutively treated TOMO patients were reviewed. Additionally a well-matched group of 43 patients treated with LINAC-based step and shoot IMRT (LINAC) was identified. Acute toxicity was scored according to Radiation Therapy Oncology Group acute toxicity criterion. Results: The grade 2-3 acute GU toxicity rates for the TOMO vs. LINAC groups were 51% vs. 28% (p = 0.001). Acute grade 2 GI toxicity was 25% vs. 40% (p = 0.024), with no grade 3 GI toxicity in either group. In univariate analysis, androgen deprivation, prostate volume, pre-treatment urinary toxicity, and prostate dose homogeneity correlated with acute GI and GU toxicity. With multivariate analysis use of Tomotherapy, median bladder dose and bladder dose homogeneity remained significantly correlated with GU toxicity. Conclusions: Acute GI toxicity for prostate cancer is improved with Tomotherapy at a cost of increased acute GU toxicity possibly due to differences in bladder and prostate dose distribution

Loss of PDEF, a prostate-derived Ets factor is associated with aggressive phenotype of prostate cancer: Regulation of MMP 9 by PDEF

Directory of Open Access Journals (Sweden)

Meacham Randall B

2010-06-01

Full Text Available Abstract Background Prostate-derived Ets factor (PDEF is expressed in tissues of high epithelial content including prostate, although its precise function has not been fully established. Conventional therapies produce a high rate of cure for patients with localized prostate cancer, but there is, at present, no effective treatment for intervention in metastatic prostate cancer. These facts underline the need to develop new approaches for early diagnosis of aggressive prostate cancer patients, and mechanism based anti-metastasis therapies that will improve the outlook for hormone-refractory prostate cancer. In this study we evaluated role of prostate-derived Ets factor (PDEF in prostate cancer. Results We observed decreased PDEF expression in prostate cancer cell lines correlated with increased aggressive phenotype, and complete loss of PDEF protein in metastatic prostate cancer cell lines. Loss of PDEF expression was confirmed in high Gleason Grade prostate cancer samples by immuno-histochemical methods. Reintroduction of PDEF profoundly affected cell behavior leading to less invasive phenotypes in three dimensional cultures. In addition, PDEF expressing cells had altered cell morphology, decreased FAK phosphorylation and decreased colony formation, cell migration, and cellular invasiveness. In contrast PDEF knockdown resulted in increased migration and invasion as well as clonogenic activity. Our results also demonstrated that PDEF downregulated MMP9 promoter activity, suppressed MMP9 mRNA expression, and resulted in loss of MMP9 activity in prostate cancer cells. These results suggested that loss of PDEF might be associated with increased MMP9 expression and activity in aggressive prostate cancer. To confirm results we investigated MMP9 expression in clinical samples of prostate cancer. Results of these studies show increased MMP9 expression correlated with advanced Gleason grade. Taken together our results demonstrate decreased PDEF expression

DNA aptamer evolved by cell-SELEX for recognition of prostate cancer.

Directory of Open Access Journals (Sweden)

Yuanyuan Wang

Full Text Available Morbidity and mortality of prostate cancer (PCa have increased in recent years worldwide. Currently existing methods for diagnosis and treatment do not make the situation improve, especially for hormone refractory prostate cancer (HRPC. The lack of molecular probes for PCa hindered the early diagnosis of metastasis and accurate staging for PCa. In this work, we have developed a new aptamer probe Wy-5a against PCa cell line PC-3 by cell-SELEX technique. Wy-5a shows high specificity to the target cells with dissociation constants in the nanomolar range, and does not recognize other tested PCa cell lines and other tested tumor cell lines. The staining of clinical tissue sections with fluorescent dye labeled Wy-5a shows that sections from high risk group with metastasis exhibited stronger fluorescence and sections from Benign Prostatic Hyperplasia (BPH did not exhibit notable fluorescence, which suggests that aptamer Wy-5a may bind to protein related to the progression of PCa. The high affinity and specificity of Wy-5a makes this aptamer hold potential for application in diagnosis and target therapy of PCa.

Association of serum prostate-specific antigen levels with the results of the prostate needle biopsy.

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Janbaziroudsari, Hamid; Mirzaei, Arezoo; Maleki, Nasrollah

2016-09-01

To investigate the relationship of serum prostate-specific antigen (PSA) levels with outcomes of prostate needle biopsy in men 50 or more years old. We measured serum PSA levels in 1472 healthy men 50 or more years old. Men who had serum PSA values 4.0ng/mL or higher underwent digital rectal examination. If there were either an elevated PSA level (≥4ng/mL) or abnormal digital rectal examination, a transrectal ultrasound-guided prostate biopsy was performed. The mean serum total PSA level was 13.73±11.44ng/mL, and the mean serum free PSA level was 4.99±0.97ng/mL. Of the 260 men who had serum total PSA levels of≥4ng/mL, 139 underwent biopsy. Of these 139 men, 45 (32.4%) had prostate cancer. Benign prostatic hyperplasia with or without prostatitis was diagnosed in 94 patients (67.6%). There was no significant correlation between age and histologic results of prostate needle biopsy (P-value=0.469). The serum free PSA showed no significant correlation with histologic results of prostate needle biopsy, whereas the serum total PSA level had a significant correlation in patients with adenocarcinoma compared with other diagnosis. The overall frequency of detection of prostate adenocarcinoma was 32.4%. This study revealed that no level of PSA was associated with a 100% positive predictive value and negative biopsy can occur virtually at any PSA level. There is a need to create awareness among the general population and health professionals for an early diagnosis of this common form of cancer. Copyright © 2016 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

Urinary prostate-specific antigen: predictor of benign prostatic hyperplasia progression?

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Pejcic, Tomislav P; Tulic, Cane Dz; Lalic, Natasa V; Glisic, Biljana D; Ignjatovic, Svetlana D; Markovic, Biljana B; Hadzi-Djokic, Jovan B

2013-04-01

Urinary prostate-specific antigen (uPSA) can be used as additional parameter of benign prostatic hyperplasia (BPH) progression. From January 2001 to December 2011, uPSA was determined in 265 patients with benign prostate. Based on total prostate volume (TPV), the patients with benign prostate were divided in two groups: TPV specificity of 0.83 and sensitivity of 0.67. The level of uPSA reflects prostatic hormonal activity and correlates with TPV, PSA and age. UPSA level ≥ 150 ng/mL can be used as additional predictive parameter of BPH progression.

In vivo targeting of ADAM9 gene expression using lentivirus-delivered shRNA suppresses prostate cancer growth by regulating REG4 dependent cell cycle progression.

Directory of Open Access Journals (Sweden)

Che-Ming Liu

Full Text Available Cancer cells respond to stress by activating a variety of survival signaling pathways. A disintegrin and metalloproteinase (ADAM 9 is upregulated during cancer progression and hormone therapy, functioning in part through an increase in reactive oxygen species. Here, we present in vitro and in vivo evidence that therapeutic targeting of ADAM9 gene expression by lentivirus-delivered small hairpin RNA (shRNA significantly inhibited proliferation of human prostate cancer cell lines and blocked tumor growth in a murine model of prostate cancer bone metastasis. Cell cycle studies confirmed an increase in the G1-phase and decrease in the S-phase population of cancer cells under starvation stress conditions, which correlated with elevated intracellular superoxide levels. Microarray data showed significantly decreased levels of regenerating islet-derived family member 4 (REG4 expression in prostate cancer cells with knockdown of ADAM9 gene expression. This REG4 downregulation also resulted in induction of expression of p21(Cip1/WAF1, which negatively regulates cyclin D1 and blocks the G1/S transition. Our data reveal a novel molecular mechanism of ADAM9 in the regulation of prostate cancer cell proliferation, and suggests a combined modality of ADAM9 shRNA gene therapy and cytotoxic agents for hormone refractory and bone metastatic prostate cancer.

A phase II randomized trial of Observation versus stereotactic ablative RadiatIon for OLigometastatic prostate CancEr (ORIOLE).

Science.gov (United States)

Radwan, Noura; Phillips, Ryan; Ross, Ashley; Rowe, Steven P; Gorin, Michael A; Antonarakis, Emmanuel S; Deville, Curtiland; Greco, Stephen; Denmeade, Samuel; Paller, Channing; Song, Daniel Y; Diehn, Maximilian; Wang, Hao; Carducci, Michael; Pienta, Kenneth J; Pomper, Martin G; DeWeese, Theodore L; Dicker, Adam; Eisenberger, Mario; Tran, Phuoc T

2017-06-29

We describe a randomized, non-blinded Phase II interventional study to assess the safety and efficacy of stereotactic ablative radiotherapy (SABR) for hormone-sensitive oligometastatic prostate adenocarcinoma, and to describe the biology of the oligometastatic state using immunologic, cellular, molecular, and functional imaging correlates. 54 men with oligometastatic prostate adenocarcinoma will be accrued. The primary clinical endpoint will be progression at 6 months from randomization with the hypothesis that SABR to all metastases will forestall progression by disrupting the metastatic process. Secondary clinical endpoints will include local control at 6 months post-SABR, toxicity and quality of life, and androgen deprivation therapy (ADT)-free survival (ADT-FS). Further fundamental analysis of the oligometastatic state with be achieved through correlation with investigational 18 F-DCFPyL PET/CT imaging and measurement of circulating tumor cells, circulating tumor DNA, and circulating T-cell receptor repertoires, facilitating an unprecedented opportunity to characterize, in isolation, the effects of SABR on the dynamics of and immunologic response to oligometastatic disease. Patients will be randomized 2:1 to SABR or observation with minimization to balance assignment by primary intervention, prior hormonal therapy, and PSA doubling time. Progression after 6 months will be compared using Fisher's exact test. Hazard ratios and Kaplan-Meier estimates of progression free survival (PFS), ADT free survival (ADT-FS), time to locoregional progression (TTLP) and time to distant progression (TTDP) will be calculated based on an intention-to-treat. Local control will be assessed using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. Withdrawal from the study prior to 6 months will be counted as progression. Adverse events will be summarized by type and grade. Quality of life pre- and post- SABR will be measured by Brief Pain Inventory. The ORIOLE

Hypofractionated Intensity-Modulated Radiotherapy for Carcinoma of the Prostate: Analysis of Toxicity

International Nuclear Information System (INIS)

Coote, Joanna H.; Wylie, James P.; Cowan, Richard A.; Logue, John P.; Swindell, Ric; Livsey, Jacqueline E.

2009-01-01

Purpose: Dose escalation for prostate cancer improves biological control but with a significant increase in late toxicity. Recent estimates of low α/β ratio for prostate cancer suggest that hypofractionation may result in biological advantage. Intensity-modulated radiotherapy (IMRT) should enable dose escalation to the prostate while reducing toxicity to local organs. We report late toxicity data of a hypofractionated IMRT regime. Methods and Materials: Eligible men had T2-3N0M0 adenocarcinoma prostate, and either Gleason score ≥ 7 or prostate-specific antigen 20-50 ng/L. Patients received 57-60 Gy to prostate in 19-20 fractions using five-field IMRT. All received hormonal therapy for 3 months before radiotherapy to a maximum of 6 months. Toxicity was assessed 2 years postradiotherapy using the RTOG criteria, LENT/SOMA, and UCLA prostate index assessment tools. Results: Acute toxicity was favorable with no RTOG Grade 3 or 4 toxicity. At 2 years, there was 4% Grade 2 bowel and 4.25% Grade 2 bladder toxicity. There was no Grade 3 or 4 bowel toxicity; one patient developed Grade 3 bladder toxicity. UCLA data showed a slight improvement in urinary function at 2 years compared with pretreatment. LENT/SOMA assessments demonstrated general worsening of bowel function at 2 years. Patients receiving 60 Gy were more likely to develop problems with bowel function than those receiving 57 Gy. Conclusions: These data demonstrate that hypofractionated radiotherapy using IMRT for prostate cancer is well tolerated with minimal late toxicity at 2 years posttreatment. Ongoing studies are looking at the efficacy of hypofractionated regimes with respect to biological control.

Combinatorial strategy of epigenetic and hormonal therapies: A novel promising approach for treating advanced prostate cancer.

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Motawi, Tarek K; Darwish, Hebatallah A; Diab, Iman; Helmy, Maged W; Noureldin, Mohamed H

2018-04-01

Estrogens act as key factors in prostate biology, cellular proliferation and differentiation as well as cancer development and progression. The expression of estrogen receptor (ER)-β appears to be lost during prostate cancer progression through hypermethylation mechanism. Epigenetic drugs such as 5-aza-2'-deoxycytidine (5-AZAC) and Trichostatin A (TSA) showed efficacy in restoring ERβ expression in prostate cancer cells. This study was designed to explore the potential anti-carcinogenic effects resulting from re-expressing ERβ1 using 5-AZAC and/or TSA, followed by its stimulation with Diarylpropionitrile (DPN), a selective ERβ1 agonist, in prostate cancer cell line PC-3. Cells were treated with 5-AZAC, TSA, DPN and their combination. Subsequently, they were subjected to proliferation assays, determinations of ERβ1 expression, protein levels of active caspase-3, cyclin D1, β-catenin and VEGF. Treatment with these drugs exhibited an increase in ERβ1 expression to different extents as well as active caspase-3 levels. Meanwhile, a significant reduction in cyclin D1, VEGF and β-catenin levels was achieved as compared to the vehicle control group (p epigenetic and hormonal therapies may be beneficial in treating advanced prostate cancer. Copyright © 2018. Published by Elsevier Inc.

Prostate-Specific G-Protein Coupled Receptor, an Emerging Biomarker Regulating Inflammation and Prostate Cancer Invasion.

Science.gov (United States)

Rodriguez, M; Siwko, S; Liu, M

2016-01-01

Prostate cancer is highly prevalent among men in developed countries, but a significant proportion of detected cancers remain indolent, never progressing into aggressive carcinomas. This highlights the need to develop refined biomarkers that can distinguish between indolent and potentially dangerous cases. The prostate-specific G-protein coupled receptor (PSGR, or OR51E2) is an olfactory receptor family member with highly specific expression in human prostate epithelium that is highly overexpressed in PIN and prostate cancer. PSGR has been functionally implicated in prostate cancer cell invasiveness, suggesting a potential role in the transition to metastatic PCa. Recently, transgenic mice overexpressing PSGR in the prostate were reported to develop an acute inflammatory response followed by emergence of low grade PIN, whereas mice with compound PSGR overexpression and loss of PTEN exhibited accelerated formation of invasive prostate adenocarcinoma. This article will review recent PSGR findings with a focus on its role as a potential prostate cancer biomarker and regulator of prostate cancer invasion and inflammation.

TRPV6 alleles do not influence prostate cancer progression

OpenAIRE

Kessler, Thorsten; Wissenbach, Ulrich; Grobholz, Rainer; Flockerzi, Veit

2009-01-01

Abstract Background The transient receptor potential, subfamily V, member 6 (TRPV6) is a Ca2+ selective cation channel. Several studies have shown that TRPV6 transcripts are expressed in locally advanced prostatic adenocarcinoma, metastatic and androgen-insensitive prostatic lesions but are undetectable in healthy prostate tissue and benign prostatic hyperplasia. Two allelic variants of the human trpv6 gene have been identified which are transcribed into two independent mRNAs, TRPV6a and TRPV...

Current State of ERG as Biomarker in Prostatic Adenocarcinoma.

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Acs, Balazs; Szarvas, Tibor; Szekely, Nora; Nyirady, Peter; Szasz, A Marcell

2015-01-01

In this review we briefly discuss the possible biomarkers of prostate cancer among them we focus and analyze the relevance of TMPRSS2-ERG fusion gene in line with ERG expression in the diagnosis of prostate cancer. Starting at diagnosis and genetic alterations in prostate carcinomas, we examine the incidence and detection of the most common genetic aberration in this tumor and its protein product as well. We also examined the correlation of clinicopathological factors and prognosis with ERG and the TMPRSS2-ERG fusion oncogene and ERG expression as predictive markers.

PSA-alpha-2-macroglobulin complex is enzymatically active in the serum of patients with advanced prostate cancer and can degrade circulating peptide hormones.

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Kostova, Maya B; Brennen, William Nathaniel; Lopez, David; Anthony, Lizamma; Wang, Hao; Platz, Elizabeth; Denmeade, Samuel R

2018-08-01

Prostate cancer cells produce high levels of the serine protease Prostate-Specific Antigen (PSA). PSA is enzymatically active in the tumor microenvironment but is presumed to be enzymatically inactive in the blood due to complex formation with serum protease inhibitors α-1-antichymotrypsin and α-2-macroglobulin (A2M). PSA-A2M complexes cannot be measured by standard ELISA assays and are also rapidly cleared from the circulation. Thus the exact magnitude of PSA production by prostate cancer cells is not easily measured. The PSA complexed to A2M is unable to cleave proteins but maintains the ability to cleave small peptide substrates. Thus, in advanced prostate cancer, sufficient PSA-A2M may be in circulation to effect total A2M levels, levels of cytokines bound to A2M and hydrolyze small circulating peptide hormones. Total A2M levels in men with advanced prostate cancer and PSA levels above 1000 ng/mL were measured by ELISA and compared to controls. Additional ELISA assays were used to measure levels of IL-6 and TGF-beta which can bind to A2M. The ability of PSA-A2M complexes to hydrolyze protein and peptide substrates was analyzed ± PSA inhibitor. Enzymatic activity of PSA-A2M in serum of men with high PSA levels was also assayed. Serum A2M levels are inversely correlated with PSA levels in men with advanced prostate cancer. Il-6 Levels are significantly elevated in men with PSA >1000 ng/mL compared to controls with PSA PSA-A2M complex in serum of men with PSA levels >1000 ng/mL can hydrolyze small fluorescently labeled peptide substrates but not large proteins that are PSA substrates. PSA can hydrolyze small peptide hormones like PTHrP and osteocalcin. PSA complexed to A2M retains the ability to degrade PTHrP. In advanced prostate cancer with PSA levels >1000 ng/mL, sufficient PSA-A2M is present in circulation to produce enzymatic activity against circulating small peptide hormones. Sufficient PSA is produced in advanced prostate cancer to alter

Cytosolic Phospholipase A2-α: A Potential Therapeutic Target for Prostate Cancer

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Patel, Manish I.; Singh, Jaskirat; Niknami, Marzieh; Kurek, Caroline; Yao, Mu; Lu, Sasa; Maclean, Fiona; King, Nicholas J.C.; Gelb, Michael H.; Scott, Kieran F.; Russell, Pamela J.; Boulas, John; Dong., Qihan

2008-01-01

Purpose Cytosolic Phospholipase A2-α (cPLA2-α) provides intracellular arachidonic acid to supply both cyclooxygenase and lipoxygenase pathways. We aim to determine the expression and activation of cPLA2-α in prostate cancer (PC) cell line and tissue and the effect of targeting cPLA2-α in-vitro and in-vivo. Experimental Design The expression of cPLA2-α was determined in PC cells by RT-PCR, Western blot and immunocytochemistry. Growth inhibition, apoptosis and cPLA2-α activity were determined after inhibition with cPLA2-α siRNA or inhibitor (Wyeth-1). cPLA2-α inhibitor or vehicle was also administered to PC xenograft mouse models. Finally the expression of phospho-cPLA2-α was determined by immunohistochemistry in human normal, androgen sensitive and insensitive PC specimens. Results cPLA2-α is present in all PC cells lines, but increased in androgen insensitive cells. Inhibition with siRNA or Wyeth-1 results in significant reductions in PC cell numbers, as a result of reduced proliferation as well as increased apoptosis and this was also associated with a reduction in cPLA2-α activity. Expression of cyclin D1 and phosphorylation of Akt were also observed to decrease. Wyeth-1 inhibited PC3 xenograft growth by approximately 33% and again, also reduced cyclin D1. Immunohistochemistry of human prostate tissue revealed that phospho-cPLA2-α is increased when hormone refractory is reached. Conclusions cPLA2-α expression and activation is increased in the androgen insensitive cancer cell line and tissue. Inhibition of cPLA2-α results in cells and xenograft tumor growth inhibition and serves as a potentially effective therapy for hormone refractory PC. PMID:19088022

Cost-efficacy analysis of hormonal treatments for advanced prostate cancer

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Sergio Iannazzo

2008-09-01

Full Text Available Introduction: prostatic cancer is the second more frequent cancer in Italy (after lung cancer and is the third cancer-related death cause. Age is the principal risk factor and, given the ageing process undergoing in the Italian population, it seems clear that the public sanitary expenditure to treat the disease is bound to increase, arising the need to perform pharmacoeconomic evaluations of the therapeutic strategies available. Methods: we performed a cost/utility analysis, through a Markov model, of several hormonal therapies in patients with advanced prostate cancer who underwent radical prostatectomy, from the biochemical recurrence to death. Nine androgen suppression therapies were considered: orchiectomy, two nonsteroidal antiandrogens (NSAA, four luteinizing hormone-releasing hormone (LHRH agonists, cyproterone acetate and the association of a NSAA and a LHRH (BAT. In the simulation the androgen suppression therapies were started at the PSA recurrence and never stopped until death. The model used the Italian NHS prospective and a time horizon corresponding to patient’s lifetime. Drug costs were calculated for each therapy, considering the less costly brand. Results: all the considered therapies produced a life expectancy (LE of about 12 life years (LYs with a small variability ranging from 12.3 LYs for BAT (the most effective to 11.37 LYs for NSAA-flutamide (the least effective. Quality adjusted life expectancy ranged from 9.98 QALYs for BAT to 9.28 QALYs for NSAA-flutamide. The average cost per patient presented a more enhanced variability, from 12,538 Euro for orchiectomy to 59,496 Euro for NSAA-bicalutamide. Among all the alternatives orchiectomy resulted the most cost/effective alternative with a cost/utility ratio of about 1,300 Euro/QALY. In the LHRH-agonists class leuprorelin was the most cost/effective with about 2,200 Euro/QALY. A one-way sensitivity analysis showed a substantial stability of the results. Conclusions: BAT

Radiotherapy combined with hormonal therapy in prostate cancer: the state of the art

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Piotr Milecki

2010-10-01

Full Text Available Piotr Milecki1,2, Piotr Martenka1, Andrzej Antczak3, Zbigniew Kwias31Department of Radiotherapy, Greater Poland Cancer Center, Poznan, Poland; 2Department of Electroradiology, Medical University, Poznan, Poland; 3Chair of Urology, Medical University, Poznan, PolandAbstract: Androgen-deprivation therapy (ADT is used routinely in combination with definitive external beam radiation therapy (EBRT in patients with high-risk clinically localized or locally advanced disease. The combined treatment (ADT–EBRT also seems to play a significant role in improving treatment results in the intermediate-risk group of prostate cancer patients. On the other hand, there is a growing body of evidence that treatment with ADT can be associated with serious and lifelong adverse events including osteoporosis, cardiovascular disease, diabetes, and many others. Almost all ADT adverse events are time dependant and tend to increase in severity with prolongation of hormonal manipulation. Therefore, it is crucial to clearly state the optimal schedule for ADT in combination with EBRT, that maintaining the positive effect on treatment efficacy would keep the adverse events risk at reasonable level. To achieve this goal, treatment schedule may have to be highly individualized on the basis of the patient-specific potential vulnerability to adverse events. In this study, the concise and evidence-based review of current literature concerning the general rationales for combining radiotherapy and hormonal therapy, its mechanism, treatment results, and toxicity profile is presented.Keywords: prostate cancer, radiotherapy, androgen deprivation, combined treatment

Proton MRS detects Metabolic Changes in Hormone Sensitive and Resistant Human Prostate Cancer Model CWR22 and CWR22r

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Le, H. Carl; Lupu, Mihaela; Kotedia, Khushali; Rosen, Neal; Solit, David; Koutcher, Jason A.

2010-01-01

17-Allylamino, 17-Demethoxygeldanamycin (17-AAG), an effective inhibitor of the heat shock protein hsp90, preferentially inhibiting tumor hsp90 compared to hsp90 from normal cells (1), has shown promising results against several cancers, including hormone resistant prostate cancer. Levels of several oncogenic proteins critical to tumor growth and progression, such as AR (androgen receptor) and HER2/neu, were reduced 4 hours post 17-AAG treatment. Post treatment metabolic changes have also been observed in several tumor cell lines. In this study total choline (t-cho) distributions in hormone sensitive CWR22 and hormone resistant CWR22r prostate cancer xenograft tumors in mice were measured before, 4 hours and 48 hours after a single bolus 17-AAG treatment at 100 mg/kg using proton MRS. Our results show that tumor t-cho levels declined 4 hours after the treatment for CWR22 (P = 0.001) and 48 hours post treatment for CWR22r (P=0.003). Metabolic changes, in particular of t-cho intensity detected by 1H MRSI, are consistent with the observed immunohistochemistry changes, tumor growth inhibition for CWR22r (P=0.01 at 14 days post treatment) and a constant PSA level versus increasing PSA for control CWR22 (P=0.01). Metabolic changes in t-cho by proton MRSI can be used as an early biomarker of response for advanced stage prostate cancer in targeted therapy such as 17-AAG. PMID:19780165

The diet as a cause of human prostate cancer.

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Nelson, William G; Demarzo, Angelo M; Yegnasubramanian, Srinivasan

2014-01-01

Asymptomatic prostate inflammation and prostate cancer have reached epidemic proportions among men in the developed world. Animal model studies implicate dietary carcinogens, such as the heterocyclic amines from over-cooked meats and sex steroid hormones, particularly estrogens, as candidate etiologies for prostate cancer. Each acts by causing epithelial cell damage, triggering an inflammatory response that can evolve into a chronic or recurrent condition. This milieu appears to spawn proliferative inflammatory atrophy (PIA) lesions, a type of focal atrophy that represents the earliest of prostate cancer precursor lesions. Rare PIA lesions contain cells which exhibit high c-Myc expression, shortened telomere segments, and epigenetic silencing of genes such as GSTP1, encoding the π-class glutathione S-transferase, all characteristic of prostatic intraepithelial neoplasia (PIN) and prostate cancer. Subsequent genetic changes, such as the gene translocations/deletions that generate fusion transcripts between androgen-regulated genes (such as TMPRSS2) and genes encoding ETS family transcription factors (such as ERG1), arise in PIN lesions and may promote invasiveness characteristic of prostatic adenocarcinoma cells. Lethal prostate cancers contain markedly corrupted genomes and epigenomes. Epigenetic silencing, which seems to arise in response to the inflamed microenvironment generated by dietary carcinogens and/or estrogens as part of an epigenetic "catastrophe" affecting hundreds of genes, persists to drive clonal evolution through metastatic dissemination. The cause of the initial epigenetic "catastrophe" has not been determined but likely involves defective chromatin structure maintenance by over-exuberant DNA methylation or histone modification. With dietary carcinogens and estrogens driving pro-carcinogenic inflammation in the developed world, it is tempting to speculate that dietary components associated with decreased prostate cancer risk, such as intake of

Sustained long-term immune responses after in situ gene therapy combined with radiotherapy and hormonal therapy in prostate cancer patients

International Nuclear Information System (INIS)

Fujita, Tetsuo; Teh, Bin S.; Timme, Terry L.; Mai, W.-Y.; Satoh, Takefumi; Kusaka, Nobuyuki; Naruishi, Koji; Fattah, Elmoataz Abdel; Aguilar-Cordova, Estuardo; Butler, E. Brian; Thompson, Timothy C.

2006-01-01

Purpose: To explore long-term immune responses after combined radio-gene-hormonal therapy. Methods and Materials: Thirty-three patients with prostate specific antigen 10 or higher or Gleason score of 7 or higher or clinical stage T2b to T3 were treated with gene therapy that consisted of 3 separate intraprostatic injections of AdHSV-tk on Days 0, 56, and 70. Each injection was followed by 2 weeks of valacyclovir. Intensity-modulated radiation therapy was delivered 2 days after the second AdHSV-tk injection for 7 weeks. Hormonal therapy was initiated on Day 0 and continued for 4 months or 2.3 years. Blood samples were taken before, during, and after treatment. Lymphocytes were analyzed by fluorescent antibody cell sorting (FACS). Results: Median follow-up was 26 months (range, 4-48 months). The mean percentages of DR + CD8 + T cells were increased at all timepoints up to 8 months. The mean percentages of DR + CD4 + T cells were increased later and sustained longer until 12 months. Long-term (2.3 years) use of hormonal therapy did not affect the percentage of any lymphocyte population. Conclusions: Sustained long-term (up to 8 to 12 months) systemic T-cell responses were noted after combined radio-gene-hormonal therapy for prostate cancer. Prolonged use of hormonal therapy does not suppress this response. These results suggest the potential for sustained activation of cell-mediated immune responses against cancer

The link between benign prostatic hyperplasia and prostate cancer

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Ørsted, David Dynnes; Bojesen, Stig E

2013-01-01

Benign prostatic hyperplasia (BPH) and prostate cancer are among the most common diseases of the prostate gland and represent significant burdens for patients and health-care systems in many countries. The two diseases share traits such as hormone-dependent growth and response to antiandrogen...... therapy. Furthermore, risk factors such as prostate inflammation and metabolic disruption have key roles in the development of both diseases. Despite these commonalities, BPH and prostate cancer exhibit important differences in terms of histology and localization. Although large-scale epidemiological...... studies have shown that men with BPH have an increased risk of prostate cancer and prostate-cancer-related mortality, it remains unclear whether this association reflects a causal link, shared risk factors or pathophysiological mechanisms, or detection bias upon statistical analysis. Establishing BPH...

Potential use of carbon-11 labeled thymidine (TdR) for studying the effect of therapy on prostatic adenocarcinoma in vivo

International Nuclear Information System (INIS)

Conti, P.S.; Kleinert, E.L.; Schma, B.; Herr, H.W.; Whitmore, W.F. Jr.

1984-01-01

Alterations in tumor growth, such as those which occur during therapeutic manipulation, may be followed by measuring variations in radiolabeled TdR uptake. In order to study such parameters in vivo using external imaging techniques, the authors have synthesized TdR labeled with cyclotron produced carbon-11, a short-lived (T1/2=20.4 min) positron-emitting radionuclide. The Copenhagen rat bearing the transplantable Dunning R3327G prostatic adenocarcinoma can be used as a model for poorly differentiated carcinoma of the prostate in humans. The tissue distribution of C-14 TdR was studied in untreated tumor rats and in tumor rats receiving a combination of difluoromethyl ornithine and methylglyoxal-bis-guanylhydrazone, effective inhibitors of polyamine biosynthesis. The tissue distribution at 45 min post-injection (5 rats/group) was determined by calculating the relative concentration (RC) of radioactivity in blood and tissue samples (RC=dpm found per gm tissue/dpm injected per gm animal mass). The mean RC in untreated tumor was 2.55 +- 0.46, compared to 0.85 +- 0.12 in treated tumor. Tumor/blood, tumor/muscle and tumor/prostate ratios were 3.07, 7.08, and 6.89 in untreated tumor, and 1.23, 3.04, and 2,93 in treated tumor. The differences in RC for the untreated and treated tumors suggest that external imaging with C-11 TdR may be useful for monitoring the effects of therapy on tumors in vivo

Sleep Deprivation Alters Rat Ventral Prostate Morphology, Leading to Glandular Atrophy: A Microscopic Study Contrasted with the Hormonal Assays

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Daniel P. Venâncio

2012-01-01

Full Text Available We investigated the effect of 96 h paradoxical sleep deprivation (PSD and 21-day sleep restriction (SR on prostate morphology using stereological assays in male rats. After euthanasia, the rat ventral prostate was removed, weighed, and prepared for conventional light microscopy. Microscopic analysis of the prostate reveals that morphology of this gland was altered after 96 h of PSD and 21 days of SR, with the most important alterations occurring in the epithelium and stroma in the course of both procedures compared with the control group. Both 96 h PSD and 21-day SR rats showed lower serum testosterone and higher corticosterone levels than control rats. The significance of our result referring to the sleep deprivation was responsible for deep morphological alterations in ventral prostate tissue, like to castration microscopic modifications. This result is due to the marked alterations in hormonal status caused by PSD and SR.

Sleep Deprivation Alters Rat Ventral Prostate Morphology, Leading to Glandular Atrophy: A Microscopic Study Contrasted with the Hormonal Assays

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Venâncio, Daniel P.; Andersen, Monica L.; Vilamaior, Patricia S. L.; Santos, Fernanda C.; Zager, Adriano; Tufik, Sérgio; Taboga, Sebastião R.; De Mello, Marco T.

2012-01-01

We investigated the effect of 96 h paradoxical sleep deprivation (PSD) and 21-day sleep restriction (SR) on prostate morphology using stereological assays in male rats. After euthanasia, the rat ventral prostate was removed, weighed, and prepared for conventional light microscopy. Microscopic analysis of the prostate reveals that morphology of this gland was altered after 96 h of PSD and 21 days of SR, with the most important alterations occurring in the epithelium and stroma in the course of both procedures compared with the control group. Both 96 h PSD and 21-day SR rats showed lower serum testosterone and higher corticosterone levels than control rats. The significance of our result referring to the sleep deprivation was responsible for deep morphological alterations in ventral prostate tissue, like to castration microscopic modifications. This result is due to the marked alterations in hormonal status caused by PSD and SR. PMID:22927719

Addition of docetaxel and/or zoledronic acid to standard of care for hormone-naive prostate cancer: a cost-effectiveness analysis.

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Zhang, Pengfei; Wen, Feng; Fu, Ping; Yang, Yu; Li, Qiu

2017-07-31

The effectiveness of the addition of docetaxel and/or zoledronic acid to the standard of care (SOC) for hormone-naive prostate cancer has been evaluated in the STAMPEDE trial. The object of the present analysis was to evaluate the cost-effectiveness of these treatment options in the treatment of advanced hormone-naive prostate cancer in China. A cost-effectiveness analysis using a Markov model was carried out from the Chinese societal perspective. The efficacy data were obtained from the STAMPEDE trial and health utilities were derived from previous studies. Transition probabilities were calculated based on the survival in each group. The primary endpoint in the analysis was the incremental cost-effectiveness ratio (ICER), and model uncertainties were explored by 1-way sensitivity analysis and probabilistic sensitivity analysis. SOC alone generated an effectiveness of 2.65 quality-adjusted life years (QALYs) at a lifetime cost of $20,969.23. At a cost of $25,001.34, SOC plus zoledronic acid was associated with 2.69 QALYs, resulting in an ICER of $100,802.75/QALY compared with SOC alone. SOC plus docetaxel gained an effectiveness of 2.85 QALYs at a cost of $28,764.66, while the effectiveness and cost data in the SOC plus zoledronic acid/docetaxel group were 2.78 QALYs and $32,640.95. Based on the results of the analysis, SOC plus zoledronic acid, SOC plus docetaxel, and SOC plus zoledronic acid/docetaxel are unlikely to be cost-effective options in patients with advanced hormone-naive prostate cancer compared with SOC alone.

Degarelix: A Novel Gonadotropin-Releasing Hormone (GnRH) Receptor Blocker-Results from a 1-yr, Multicentre, Randomised, Phase 2 Dosage-Finding Study in the Treatment of Prostate Cancer

NARCIS (Netherlands)

van Poppel, Hendrik; Tombal, Bertrand; de la Rosette, Jean J.; Persson, Bo-Eric; Jensen, Jens-Kristian; Kold Olesen, Tine

2008-01-01

Background: Degarelix is a gonadotropin-releasing hormone antagonist (GnRH receptor blocker) with immediate onset of action, suppressing gonadotropins, testosterone, and prostate-specific antigen (PSA) in prostate cancer. Objective: To determine the efficacy and safety of initial doses of 200 mg or

Metastatic prostate cancer with elevated serum levels of CEA and CA19-9

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Guang-Dar Juang

2014-03-01

Full Text Available Prostate-specific antigen (PSA is well known as a specific tumor marker for prostate cancer, but carcinoembryonic antigen (CEA- and carbohydrate antigen 19-9 (CA19-9-elevating adenocarcinomas originating in the prostate gland are rare. We report a case of metastatic adenocarcinoma of the prostate gland with a high serum level of CEA and CA19-9 in a 78-year-old man in whom prostate cancer (T3N1M1 had been diagnosed 2 years ago and who was treated with androgen deprivation therapy. He visited the emergency department because of a loss of appetite and abdominal pain. The serum CEA and CA19-9 levels were increased to 218.9 ng/mL (normal, <5 ng/mL and 212 ng/mL (normal, <27 ng/mL, respectively. The serum PSA level was slightly elevated (4.41 ng/mL. Computed tomography demonstrated multiple liver metastases, para-aortic lymph node enlargement, and lung metastases. A liver biopsy was performed and the specimen showed high-grade adenocarcinoma with focal positive staining for PSA. Despite chemotherapy with docetaxel, the patient died 3 months after treatment. Based on this case and a review of the literature, an aggressive variant of prostatic carcinoma with a high serum level of CEA and CA19-9 and a low PSA level was shown to progress rapidly with a poor prognosis.

Epigenetic repression of regulator of G-protein signaling 2 promotes androgen-independent prostate cancer cell growth.

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Wolff, Dennis W; Xie, Yan; Deng, Caishu; Gatalica, Zoran; Yang, Mingjie; Wang, Bo; Wang, Jincheng; Lin, Ming-Fong; Abel, Peter W; Tu, Yaping

2012-04-01

G-protein-coupled receptor (GPCR)-stimulated androgen-independent activation of androgen receptor (AR) contributes to acquisition of a hormone-refractory phenotype by prostate cancer. We previously reported that regulator of G-protein signaling (RGS) 2, an inhibitor of GPCRs, inhibits androgen-independent AR activation (Cao et al., Oncogene 2006;25:3719-34). Here, we show reduced RGS2 protein expression in human prostate cancer specimens compared to adjacent normal or hyperplastic tissue. Methylation-specific PCR analysis and bisulfite sequencing indicated that methylation of the CpG island in the RGS2 gene promoter correlated with RGS2 downregulation in prostate cancer. In vitro methylation of this promoter suppressed reporter gene expression in transient transfection studies, whereas reversal of this promoter methylation with 5-aza-2'-deoxycytidine (5-Aza-dC) induced RGS2 reexpression in androgen-independent prostate cancer cells and inhibited their growth under androgen-deficient conditions. Interestingly, the inhibitory effect of 5-Aza-dC was significantly reduced by an RGS2-targeted short hairpin RNA, indicating that reexpressed RGS2 contributed to this growth inhibition. Restoration of RGS2 levels by ectopic expression in androgen-independent prostate cancer cells suppressed growth of xenografts in castrated mice. Thus, RGS2 promoter hypermethylation represses its expression and unmasks a latent pathway for AR transactivation in prostate cancer cells. Targeting this reversible process may provide a new strategy for suppressing prostate cancer progression by reestablishing its androgen sensitivity. Copyright © 2011 UICC.

Osteogenic sarcoma of the prostate

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Nishiyama, Tsutomu; Terunuma, Masahiro [Koseiren Nagaoka Chuo General Hospital, Niigata (Japan); Ikarashi, Toshihiko; Ishizaki, Satoshi

2001-04-01

A 76-year-old man was treated with bilateral orchiectomy, estramustine phosphate and pelvic irradiation for prostate cancer. Osteogenic sarcoma of the prostate developed 18 months after the treatment. Postmortem examination revealed that the tumor was 8 cm in diameter and had infiltrated into the bladder and rectal walls and had resulted in peritoneal dissemination. There was no distant metastasis. Macroscopically, the tumor was ashen, firm and relatively homogenous and diffusely spread. Histologically, it was composed of spindle and pleomorphic cells, which were making osteoid with calcification. There was no ordinary tubular formation as shown in adenocarcinoma of the prostate. No positive immunostaining for prostate-specific antigen, epithelial membrane antigen and cytokeratin (AE-1, AE-3) were confirmed. Positive immunostaining for nonepithelial marker vimentin was confirmed. The ultimate diagnosis was osteogenic sarcoma of the prostate. (author)

Highly potent metallopeptide analogues of luteinizing hormone-releasing hormone

International Nuclear Information System (INIS)

Bajusz, S.; Janaky, T.; Csernus, V.J.; Bokser, L.; Fekete, M.; Srkalovic, G.; Redding, T.W.; Schally, A.V.

1989-01-01

Metal complexes related to the cytotoxic complexes cisplatin [cis-diamminedichloroplatinum(II)] and transbis(salicylaldoximato)copper(II) were incorporated into suitably modified luteinizing hormone-releasing hormone (LH-RH) analogues containing D-lysine at position 6. Some of the metallopeptides thus obtained proved to be highly active LH-RH agonists or antagonists. Most metallopeptide analogues of LH-RH showed high affinities for the membrane receptors of rat pituitary and human breast cancer cells. Some of these metallopeptides had cytotoxic activity against human breast cancer and prostate cancer and prostate cancer cell lines in vitro. Such cytostatic metallopeptides could be envisioned as targeted chemotherapeutic agents in cancers that contain receptors for LH-RH-like peptides

Emerging Therapies in Metastatic Prostate Cancer.

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Sonnenburg, Daniel W; Morgans, Alicia K

2018-04-11

In the last decade, there have been multiple landmark therapeutic advances for the treatment of metastatic prostate cancer, both in the castration-resistant and hormone-sensitive setting. In this review, we highlight recent progress and ongoing trials for metastatic prostate cancer, including advances in chemotherapy, androgen receptor-directed therapy, targeted therapies, and immunotherapy. Several landmark studies for men with metastatic hormone-sensitive prostate cancer demonstrated improvement in overall survival with the addition of docetaxel chemotherapy or abiraterone acetate to standard androgen deprivation therapy. A single-arm phase 2 study of the PARP inhibitor olaparib demonstrated high response rates and more favorable progression-free and overall survival for men with metastatic castration-resistant prostate cancer and DNA repair defects treated with olaparib compared with men without DNA repair defects. Multiple ongoing clinical trials are investigating novel hormonal therapies and combinations of chemotherapy, targeted small molecules, immunotherapy, and radiopharmaceuticals. Progress continues to be made in the treatment of metastatic prostate cancer, and ongoing clinical trials continue to investigate novel agents and approaches to treatment.

Radical radiation therapy for prostate cancer in Japan. A patterns of care study report

International Nuclear Information System (INIS)

Nakamura, Katsumasa; Mitsuhashi, Norio

2003-01-01

The patterns of radical radiation therapy for prostate cancer are unclear in Japan. A Patterns of Care Study was performed throughout Japan to examine the patterns of radiation therapy for prostate cancer. From 1999 to 2000, extramural audits were performed on 50 randomly selected institutions (∼7% of all institutions in Japan). Detailed information was collected on a total of 311 prostate cancer patients without evidence of distant metastases, who were treated by radiation therapy between 1996 and 1998. Of these 311 patients, 162 treated radically using photon beams were analyzed in this study. Eighty percent of the patients had high-risk diseases defined as T3 or T4 tumors, a pretreatment prostate-specific antigen level >20 ng/ml or poorly differentiated adenocarcinoma. Androgen ablation was performed in 85.8% of patients and the median duration of hormonal therapy before and after radiation therapy was 5.3 and 21.4 months, respectively. The median total dose of radiation therapy to the prostate was 65.0 Gy (range: 20-74 Gy). The 3-year overall and biochemical relapse-free survival rates were 86.7 and 86.1%, respectively. Late toxicity was mild, with only nine patients (5.6%) exhibiting grade 2 late morbidity. The majority of the patients who received radical radiation therapy in Japan have high-risk disease. Androgen ablation plus radiation therapy was commonly used to treat these patients and resulted in high rates of initial control with a low risk of complications. (author)

The dosimetry of prostate brachytherapy-induced urethral strictures

International Nuclear Information System (INIS)

Merrick, Gregory S.; Butler, Wayne M.; Tollenaar, Bryan G.; Galbreath, Robert W.; Lief, Jonathan H.

2002-01-01

Purpose: There is a paucity of data regarding the incidence of urethral strictures after prostate brachytherapy. In this study, we evaluate multiple clinical, treatment, and dosimetric parameters to identify factors associated with the development of brachytherapy-induced urethral strictures. Methods and Materials: 425 patients underwent transperineal ultrasound-guided prostate brachytherapy using either 103 Pd or 125 I for clinical T1b/T3a NxM0 (1997, American Joint Committee on Cancer) adenocarcinoma of the prostate gland from April 1995 to October 1999. No patient was lost to follow-up. 221 patients were implanted with 103 Pd and 204 patients with 125 I. The median patient age was 68 years (range 48-81 years). The median follow-up was 35.2 months (range 15-72 months). Follow-up was calculated from the day of implantation. Thirteen patients developed brachytherapy-induced strictures, and all strictures involved the membranous urethra. A control group of 35 patients was rigorously matched to the stricture patients in terms of treatment approach; i.e., choice of isotope, plus or minus radiation therapy, and plus or minus hormonal manipulation. Nine of the 13 stricture patients had detailed Day 0 urethral dosimetry available for review. The apex of the prostate gland and the membranous urethra were defined by CT evaluation. Urethral dosimetry was reported for the prostatic urethra, the apical slice of the prostate gland, and the membranous urethra which was defined as extending 20 mm in length. Results: The 5-year actuarial risk of a urethral stricture was 5.3%, with a median time to development of 26.6 months (range 7.8-44.1 months). Of multiple clinical and treatment parameters evaluated, only the duration of hormonal manipulation (>4 months, p=0.011) was predictive for the development of a urethral stricture. The radiation dose to the membranous urethra was significantly greater in patients with strictures than those without: 97.6%±20.8% vs. 81.0%±19.8% of

Multifaceted role of EZH2 in breast and prostate tumorigenesis: epigenetics and beyond.

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Deb, Gauri; Thakur, Vijay S; Gupta, Sanjay

2013-05-01

Overexpression of EZH2 and other PRC2 subunits, such as SUZ12, is associated with tumor progression and poor prognosis in several human malignancies. Nevertheless, the underlying mechanisms driving aberrant EZH2 expression are poorly understood. This review provides molecular insights into the essential role of EZH2 in breast and prostate tumorigenesis. We addressed the current understanding on the oncogenic role of EZH2, with an emphasis on: (1) the less known PRC2-independent role of EZH2 in gene activation, in addition to its canonical role in transcriptional silencing as a histone methyltransferase catalyzing the trimethylation of histone H3 at lysine 27; (2) causes and consequences of its deregulation in tumor cells and; (3) collaboration of EZH2 with other epigenetic and hormone receptor-mediated oncogenic signaling pathways. We also summarize how EZH2 has emerged as a promising therapeutic target in hormone-refractory cancers and the prospects for integrating EZH2 blockade with available pharmacological inhibitors.

Second-Line Hormonal Therapy for Men With Chemotherapy-Naïve, Castration-Resistant Prostate Cancer: American Society of Clinical Oncology Provisional Clinical Opinion.

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Virgo, Katherine S; Basch, Ethan; Loblaw, D Andrew; Oliver, Thomas K; Rumble, R Bryan; Carducci, Michael A; Nordquist, Luke; Taplin, Mary-Ellen; Winquist, Eric; Singer, Eric A

2017-06-10

Purpose ASCO provisional clinical opinions (PCOs) offer direction to the ASCO membership after publication or presentation of potential practice-changing data. This PCO addresses second-line hormonal therapy for chemotherapy-naïve men with castration-resistant prostate cancer (CRPC) who range from being asymptomatic with only biochemical evidence of CRPC to having documented metastases but minimal symptoms. Clinical Context The treatment goal for CRPC is palliation. Despite resistance to initial androgen deprivation therapy, most men respond to second-line hormonal therapies. However, guidelines have neither addressed second-line hormonal therapy for nonmetastatic CRPC nor provided specific guidance with regard to the chemotherapy-naïve population. Recent Data Six phase III randomized controlled trials and expert consensus opinion inform this PCO. Provisional Clinical Opinion For men with CRPC, a castrate state should be maintained indefinitely. Second-line hormonal therapy (eg, antiandrogens, CYP17 inhibitors) may be considered in patients with nonmetastatic CRPC at high risk for metastatic disease (rapid prostate-specific antigen doubling time or velocity) but otherwise is not suggested. In patients with radiographic evidence of metastases and minimal symptoms, enzalutamide or abiraterone plus prednisone should be offered after discussion with patients about potential harms, benefits, costs, and patient preferences. Radium-223 and sipuleucel-T also are options. No evidence provides guidance about the optimal order of hormonal therapies for CRPC beyond second-line treatment. Prostate-specific antigen testing every 4 to 6 months is reasonable for men without metastases. Routine radiographic restaging generally is not suggested but can be considered for patients at risk for metastases or who exhibit symptoms or other evidence of progression. Additional information is available at www.asco.org/genitourinary-cancer-guidelines and www.asco.org/guidelineswiki .

Evaluation of follow-up bone scintigraphy for assessing the effects of hormone and chemotherapy of bone metastases from prostatic cancer

Energy Technology Data Exchange (ETDEWEB)

Otsuka, Nobuaki; Ito, Yasuhiko; Morita, Rikushi; Yoneda, Masaya; Muranaka, Akira [Kawasaki Medical School, Kurashiki, Okayama (Japan)

1983-08-01

To assess the clinical usefulness of bone scintigraphy for the osseous metastases of prostatic cancer after treatment, we attempted the correlative studies on laboratory data (TAP, PAP, ALP, and LDH) and scintigraphy. In 77 patients with prostatic cancer, bone scintigraphies were performed with sup(99m)Tc-phosphorous compounds to detect bone metastases. In 34 cases (44 %) bone metastases were detected. In 21 patients out of them, we assessed the effects of hormone and chemotherapy for bone metastases using serial bone scintigraphy. In 19 cases (24.7 %) of the bone scintigraphy showed equivocal results. Of 21 patients with bone metastases, 15 patients showed improvement on scintigram after hormone or chemotherapy. In much improved group (5 patients) and moderately improved group (5 patients), TAP and PAP levels were low and stable. On the other hand, in slightly improved group (5 patients) which showed partially effective on scintigram after treatment, serum TAP and PAP level were unstable. Some cases in the group of which the 1st scintigrams showed normal were turned to positive on scintigram, while TAP, PAP, ALP and LDH level were not elevated. Therefore, follow-up bone scintigraphies have value in evaluating the disease extent in patients with prostatic carcinoma.

Prostate cancer risk: the significance of differences in age related changes in serum conjugated and unconjugated steroid hormone concentrations between Arab and Caucasian men.

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Kehinde, E O; Akanji, A O; Memon, A; Bashir, A A; Daar, A S; Al-Awadi, K A; Fatinikun, T

2006-01-01

Factors responsible for the low incidence of clinical prostate cancer (3-8/100,000 men/year) in the Arab population remain unclear, but may be related to changes in steroid hormone metabolism. We compared the levels of serum conjugated and unconjugated steroids between Arab and Caucasian populations, to determine if these can provide a rational explanation for differences in incidence of prostate cancer between the two populations. Venous blood samples were obtained from 329 unselected apparently healthy indigenous Arab men (Kuwaitis and Omanis) aged 15-80 years. Samples were also obtained from similar Arab men with newly diagnosed prostate cancer or benign prostatic hyperplasia (BPH). The samples were taken between 8:00 am and 12:00 noon. Serum levels of total testosterone, (TT), sex hormone binding globulin (SHBG), free androgen index (FAI); adrenal C19-steroids, dehydroepiandrosterone sulphate (DHEAS) and androstenedione (ADT) were determined using Immulite kits (Diagnostic Systems Laboratories Inc, Webster Texas, USA). The results obtained in Arab men were compared with those reported for similarly aged Chinese, German and White USA men. In all four ethnic groups, median TT and FAI declined with age, while SHBG increased with age. However, the mean TT and SHBG was significantly lower (p Arab men (p Arabs (p Arabs. There was no significant difference in mean serum levels of DHEAS between German and USA men. Similarly, there was no significant difference in the level of the hormones between Arab and Chinese men. Arab men with newly diagnosed prostate cancer had high serum TT, SHBG and DHEAS compared to those without the disease. The mean TT and SHBG was significantly lower in Arab men compared to Caucasian men especially in early adulthood. Caucasians have significantly higher serum levels of the precursor androgens DHEAS and ADT especially in early adulthood compared to Arab men. These observations of low circulating androgens and their adrenal precursors in

Prostate Enlargement: Benign Prostatic Hyperplasia (BPH)

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... of substances that promote prostate cell growth. Another theory focuses on dihydrotestosterone (DHT), a male hormone that ... physical exam medical tests Personal and Family Medical History Taking a personal and family medical history is ...

Chromosomal deletion, promoter hypermethylation and downregulation of FYN in prostate cancer

DEFF Research Database (Denmark)

Sørensen, Karina Dalsgaard; Borre, Michael; Ørntoft, Torben Falck

2008-01-01

prostate hyperplasia (BPH), as well as in 6 prostate adenocarcinoma cell lines compared with that in BPH-1 cells. By immunohistochemistry, FYN protein was detected in nonmalignant prostate epithelium, but not in cancerous glands. Moreover, genomic bisulfite sequencing revealed frequent aberrant methylation......, consistent with gene silencing, was detected in 2 of 18 tumors (11%). No methylation was found in BPH-1 cells or nonmalignant prostate tissue samples (0 of 7). These results indicate that FYN is downregulated in prostate cancer by both chromosomal deletion and promoter hypermethylation, and therefore...

Prostatic carcinosarcoma with lung metastases.

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Furlan, Stefanie R; Kang, David J; Armas, Armando

2013-01-01

Carcinosarcoma of the prostate is an uncommon malignancy with poor long-term prognosis. The cancer is typically discovered at an advanced stage, and with less than 100 reported cases, there is limited literature concerning treatment options. Our patient presented with a history of benign prostatic hypertrophy, erectile dysfunction, and nocturia. Biopsy of his prostate indicated that the patient had prostatic adenocarcinoma, but histopathology after prostatectomy revealed carcinosarcoma. It has been over six years since this patient's diagnosis of carcinosarcoma. Over this span of time, he has received a radical prostatectomy, radiotherapy, and androgen ablative therapy. The patient also developed multiple lung metastases that have been treated with video-assisted thoracic surgery and stereotactic body radiosurgery. Overall, he has remained unimpaired and in good condition despite his aggressive form of cancer.

Role of Growth Hormone in Prostate Cancer

National Research Council Canada - National Science Library

Swanson, Steven M

2007-01-01

We have established a GH-deficient prostate cancer model (Tag/Ghdr/dr rat) indicating that a reduction in GH and/or IGF-I can significantly inhibit prostate carcinogenesis in this model in contrast to GH wild-type controls...

Spindle-cell carcinoma of the prostate

Directory of Open Access Journals (Sweden)

Carlos Hirokatsu Watanabe Silva

2012-03-01

Full Text Available Sarcoma of the prostate and sarcomatoid carcinoma of the prostate are rareconditions, both characterized by a poor prognosis. Sarcomatoid carcinoma ofthe prostate typically arises from the evolution of an underlying adenocarcinoma,occasionally featuring heterologous elements, bulky disease being possiblebut rare. In contrast, sarcoma of the prostate derives from non-epithelialmesenchymal components of the prostatic stroma, shows rapid growth, andfrequently presents as massive pelvic tumors obstructing the urinary tractat the time of diagnosis. We report the case of a 55-year-old patient with atwo-month history of symptoms of urinary obstruction. The patient presentedwith an extremely enlarged heterogeneous prostate, although his prostatespecificantigen level was low. The lack of a history of prostatic neoplasia ledus to suspect sarcoma, and a transrectal prostate biopsy was carried out. Animmunohistochemical study of the biopsy specimen did not confirm the clinicalsuspicion. However, in view of the clinical features, we believe that sarcoma ofthe prostate was the most likely diagnosis. The patient received neoadjuvantchemotherapy followed by radiation therapy. At this writing, surgical resectionhad yet to be scheduled.

Radiotherapy and hormone therapy in intermediate risk prostate cancer: a critical review

International Nuclear Information System (INIS)

Franco, Rejane Carolina; Souhami, Luis

2015-01-01

Introduction: The standard treatment for patients with high risk prostate cancer is the combined use of radiation therapy (RT ) and hormone therapy (HT). In regards to patients stratified as intermediate risk, the use of HT associated with RT remains controversial, and its use should be carefully planned and based on available evidence. Objective: To critically assess results of randomized studies published in the literature that associated the use of HT of short duration with an average period of 6 months with RT in the treatment of patients with localized prostate cancer classified as intermediate risk. Method: Only randomized studies comparing these treatments were eligible for this review. A structured search through 'PubMed' was carried out using the terms 'androgen suppression therapy', 'radiotherapy', 'randomized trials', 'phase 3 trials', 'prostate cancer' and 'intermediate risk'. Results: Four randomized studies comparing RT alone to RT plus short course HT were found and selected. The majority of the trials had a mixed population of intermediate and high risk disease and did not include patients with only intermediate risk. Despite that, there appears to be a significant benefit for the combined approach regarding disease-free survival, biochemical free survival and overall survival. Conclusion: The randomized studies published so far suggest improved outcomes for the group of patients receiving RT and short course HT. Data from randomized trials comparing RT alone to RT and short course HT in patients with intermediate risk only are forthcoming. (author)

3,3'-Diindolylmethane downregulates pro-survival pathway in hormone independent prostate cancer

International Nuclear Information System (INIS)

Garikapaty, Venkata P.S.; Ashok, Badithe T.; Tadi, Kiranmayi; Mittelman, Abraham; Tiwari, Raj K.

2006-01-01

Epidemiological evidences suggest that the progression and promotion of prostate cancer (CaP) can be modulated by diet. Since all men die with prostate cancer rather than of the disease, it is of particular interest to prevent or delay the progression of the disease by chemopreventive strategies. We have been studying the anticancer properties of compounds present in cruciferous vegetables such as indole-3-carbinol (I3C). Diindolylmethane (DIM) is a dimer of I3C that is formed under acidic conditions and unlike I3C is more stable with higher anti-cancer effects. In the present report, we demonstrate that DIM is a potent anti-proliferative agent compared to I3C in the hormone independent DU 145 CaP cells. The anti-prostate cancer effect is mediated by the inhibition of the Akt signal transduction pathway as DIM, in sharp contrast to I3C, induces the downregulation of Akt, p-Akt, and PI3 kinase. DIM also induced a G1 arrest in DU 145 cells by flow cytometry and downstream concurrent inhibition of cell cycle parameters such as cyclin D1, cdk4, and cdk6. Our data suggest a need for further development of DIM, as a chemopreventive agent for CaP, which justifies epidemiological evidences and molecular targets that are determinants for CaP dissemination/progression. The ingestion of DIM may benefit CaP patients and reduce disease recurrence by eliminating micro-metastases that may be present in patients who undergo radical prostatectomy

Validation of International Society of Urological Pathology (ISUP) grading for prostatic adenocarcinoma in thin core biopsies using TROG 03.04 'RADAR' trial clinical data.

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Delahunt, B; Egevad, L; Srigley, J R; Steigler, A; Murray, J D; Atkinson, C; Matthews, J; Duchesne, G; Spry, N A; Christie, D; Joseph, D; Attia, J; Denham, J W

2015-10-01

In 2014 a consensus conference convened by the International Society of Urological Pathology (ISUP) adopted amendments to the criteria for Gleason grading and scoring (GS) for prostatic adenocarcinoma. The meeting defined a modified grading system based on 5 grading categories (grade 1, GS 3+3; grade 2, GS 3+4; grade 3, GS 4+3; grade 4, GS 8; grade 5, GS 9-10). In this study we have evaluated the prognostic significance of ISUP grading in 496 patients enrolled in the TROG 03.04 RADAR Trial. There were 19 grade 1, 118 grade 2, 193 grade 3, 88 grade 4 and 79 grade 5 tumours in the series, with follow-up for a minimum of 6.5 years. On follow-up 76 patients experienced distant progression of disease, 171 prostate specific antigen (PSA) progression and 39 prostate cancer deaths. In contrast to the 2005 modified Gleason system (MGS), the hazards of the distant and PSA progression endpoints, relative to grade 2, were significantly greater for grades 3, 4 and 5 of the 2014 ISUP grading scheme. Comparison of predictive ability utilising Harrell's concordance index, showed 2014 ISUP grading to significantly out-perform 2005 MGS grading for each of the three clinical endpoints.

Comparison of biochemical failure definitions for permanent prostate brachytherapy

International Nuclear Information System (INIS)

Kuban, Deborah A.; Levy, Larry B.; Potters, Louis; Beyer, David C.; Blasko, John C.; Moran, Brian J.; Ciezki, Jay P.; Zietman, Anthony L.; Zelefsky, Michael J.; Pisansky, Thomas M.; Elshaikh, Mohamed; Horwitz, Eric M.

2006-01-01

Purpose: To assess prostate-specific antigen (PSA) failure definitions for patients with Stage T1-T2 prostate cancer treated by permanent prostate brachytherapy. Methods and Materials: A total of 2,693 patients treated with radioisotopic implant as solitary treatment for T1-T2 prostatic adenocarcinoma were studied. All patients had a pretreatment PSA, were treated at least 5 years before analysis, 1988 to 1998, and did not receive hormonal therapy before recurrence. Multiple PSA failure definitions were tested for their ability to predict clinical failure. Results: Definitions which determined failure by a certain increment of PSA rise above the lowest PSA level to date (nadir + x ng/mL) were more sensitive and specific than failure definitions based on PSA doubling time or a certain number of PSA rises. The sensitivity and specificity for the nadir + 2 definition were 72% and 83%, vs. 51% and 81% for 3 PSA rises. The surgical type definitions (PSA exceeding an absolute value) could match this sensitivity and specificity but only when failure was defined as exceeding a PSA level in the 1-3 ng/mL range and only when patients were allowed adequate time to nadir. When failure definitions were compared by time varying covariate regression analysis, nadir + 2 ng/mL retained the best fit. Conclusions: For patients treated by permanent radioisotopic implant for prostate cancer, the definition nadir + 2 ng/mL provides the best surrogate for failure throughout the entire follow-up period, similar to patients treated by external beam radiotherapy. Therefore, the same PSA failure definition could be used for both modalities. For brachytherapy patients with long-term follow-up, at least 6 years, defining failure as exceeding an absolute PSA level in the 0.5 ng/mL range may be reasonable

Analysis of the molecular networks in androgen dependent and independent prostate cancer revealed fragile and robust subsystems.

Directory of Open Access Journals (Sweden)

Ryan Tasseff

Full Text Available Androgen ablation therapy is currently the primary treatment for metastatic prostate cancer. Unfortunately, in nearly all cases, androgen ablation fails to permanently arrest cancer progression. As androgens like testosterone are withdrawn, prostate cancer cells lose their androgen sensitivity and begin to proliferate without hormone growth factors. In this study, we constructed and analyzed a mathematical model of the integration between hormone growth factor signaling, androgen receptor activation, and the expression of cyclin D and Prostate-Specific Antigen in human LNCaP prostate adenocarcinoma cells. The objective of the study was to investigate which signaling systems were important in the loss of androgen dependence. The model was formulated as a set of ordinary differential equations which described 212 species and 384 interactions, including both the mRNA and protein levels for key species. An ensemble approach was chosen to constrain model parameters and to estimate the impact of parametric uncertainty on model predictions. Model parameters were identified using 14 steady-state and dynamic LNCaP data sets taken from literature sources. Alterations in the rate of Prostatic Acid Phosphatase expression was sufficient to capture varying levels of androgen dependence. Analysis of the model provided insight into the importance of network components as a function of androgen dependence. The importance of androgen receptor availability and the MAPK/Akt signaling axes was independent of androgen status. Interestingly, androgen receptor availability was important even in androgen-independent LNCaP cells. Translation became progressively more important in androgen-independent LNCaP cells. Further analysis suggested a positive synergy between the MAPK and Akt signaling axes and the translation of key proliferative markers like cyclin D in androgen-independent cells. Taken together, the results support the targeting of both the Akt and MAPK

Results of radiation therapy combined with neoadjuvant hormonal therapy for stage III prostate cancer. Comparison of two different definitions of PSA failure

International Nuclear Information System (INIS)

Mitsumori, Michihide; Sasaki, Yoshihide; Mizowaki, Takashi

2006-01-01

We herein report the clinical outcome of radical radiation therapy combined with neoadjuvant hormonal therapy (NHT) for stage III (International Union Against Cancer [UICC] 1997: UICC 97) prostate cancer. Prostate-specific antigen (PSA) failure-free survival was assessed according to two different definitions, and the appropriateness of each definition is discussed. Between October 1997 and December 2000, 27 patients with stage III prostate cancer were enrolled in this study. The median pretreatment PSA level was 29 ng/ml (range, 7.4-430 ng/ml). The Gleason score (GS) was 7 or more in 22 patients (81%). All patients received 3 months of NHT with a luteinizing hormone-releasing hormone (LH-RH) analogue, in combination with an antiandrogen (flutamide), given during the first 2 weeks, followed by 70-Gy external-beam radiation therapy (EBRT) in 35 fractions. The initial 46 Gy was given with a four-field technique, while the remainder was given with a dynamic conformal technique. No adjuvant hormonal therapy (AHT) was given. The median follow-up time was 63 months. PSA levels decreased to the normal range (<4 ng/ml) after irradiation in all but one patient. The 5-year PSA failure-free survival was 34.8% according to the American Society for Therapeutic Radiology and Oncology (ASTRO) definition and it was 43.0% according to the ''nadir plus 2'' definition. Discordance of the results between the two definitions was seen in two patients. The 5-year overall and cause-specific survivals were 83.0% and 93.3%, respectively. No severe acute or late adverse effects were observed. Seventy Gy of EBRT following 3 months of NHT produced therapeutic results comparable to those reported in other studies which used long-term AHT. The value of long-term AHT for Japanese men should be tested in a clinical trial. (author)

Comparison of clinical and survival characteristics between prostate cancer patients of PSA-based screening and clinical diagnosis in China.

Science.gov (United States)

Xu, Libo; Wang, Jinguo; Guo, Baofeng; Zhang, Haixia; Wang, Kaichen; Wang, Ding; Dai, Chang; Zhang, Ling; Zhao, Xuejian

2018-01-02

Prostate-specific antigen (PSA)-based mass screening remains the most controversial topic in prostate cancer. PSA-based mass screening has not been widely used in China yet. The aim of our study was to evaluate the effect of the PSA-based screening in China. The cohort consisted of 1,012 prostate cancer patients. Data were retrospectively collected and clinical characteristics of the cohorts were investigated. Survival was analyzed for prostatic carcinoma of both PSA screened and clinically diagnosed patients according to clinical characteristics and the National Comprehensive Cancer Network (NCCN) risk classification. Cox Proportional Hazards Model analysis was done for risk predictor identification. The median age was 71 years old. Five-year overall and prostate-cancer-specific survival in prostatic adenocarcinoma patients were 77.52% and 79.65%; 10-year survivals were 62.57% and 68.60%, respectively. Survival was significantly poorer in patients with metastases and non-curative management. T staging and Gleason score by NCCN classification effectively stratified prostatic adenocarcinoma patients into different risk groups. T staging was a significant predictor of survival by COX Proportional Hazard Model. PSA screened patients had a significantly higher percentage diagnosed in early stage. PSA screened prostatic adenocarcinoma patients had a better prognosis in both overall and prostate cancer-specific survivals. This Chinese cohort had a lower overall and prostate cancer survival rate than it is reported in western countries. The incidence of early-stage prostate cancer found in PSA-based mass screening was high and there were significant differences in both overall and prostate cancer-specific survival between the PSA-screened and clinically diagnosed patients.

Ultrasonographic and cytopathologic aspects of prostate disease in 52 dogs

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Antonio Carlos Cunha Lacreta Junior

2012-03-01

Full Text Available This study evaluated 52 dogs, which were male, intact, varied in age, of pure or mixed breed, with clinical signs suggestive of prostatic disease. Each individual underwent an ultrasound examination and fine-needle aspiration biopsy of the prostate gland for cytological evaluation. Benign prostatic hyperplasia (BPH was the most frequent prostatic disease, followed by cystic benign prostatic hyperplasia, bacterial prostatitis, abscesses, cysts, adenocarcinoma, nonbacterial prostatitis and paraprostatic cysts. The highest frequencies of prostate disorder were found in mixed breeds, followed by poodles and German shepherds. Ultrasound examination allowed the determination of prostate size, as well as the visualization of the diseases affecting the gland, and was effective in guiding aspiration biopsy. The cytological evaluation of the gland, especially when associated with changes in ultrasound images, revealed the presumptive diagnosis of the condition.

Endometrial adenocarcinoma arising in a Turner's syndrome patient with spontaneous menstruation: a case report.

Science.gov (United States)

Sasamoto, Naoko; Ueda, Yutaka; Amemiya, Kyoka; Enomoto, Takayuki; Morii, Eiichi; Adachi, Kazushige

2014-01-01

Women with Turner's syndrome exhibit anovulation, and the majority do not spontaneously menstruate. We present an unusual case of endometrial adenocarcinoma developing in a Turner's syndrome patient who was exhibiting spontaneous menstruation while not receiving regular hormone therapy. The patient's karyotype from blood lymphocytes was a mosaic of 45,XO/ 46,XX. Menarche and sexual development were normal. Her menstrual cycle had been regular for one year, but then became noticeably irregular. At age 26 she was referred to our hospital after bleeding for almost 1 year. An endometrial adenocarcinoma was detected during performance of diagnostic endometrial curettage. A total abdominal hysterectomy with bilateral salpingo-oophorectomy and pelvic lymphadenectomy was conducted. The final histological diagnosis was endometrial adenocarcinoma, Grade 1, pT1a N0 M0. Fluorescence in situ hybridization analysis of the right and left ovaries revealed a mosaic karyotype of 45,XO/ CONCLUSION: Previous reports regarding Turner's syndrome detected spontaneous menstruation in only 16% of patients; however, spontaneous menstruation was observed in 8 of 10 (80%) Turner's syndrome cases that developed endometrial carcinoma without receiving regular hormone therapy (p < 0.0001). Hormone therapy may be indicated for an irregular menstrual cycle in Turner's syndrome patients.

[Molecular biology of castration-resistant prostate cancer].

Science.gov (United States)

Doucet, Ludovic; Terrisse, Safae; Gauthier, Hélène; Pouessel, Damien; Le Maignan, Christine; Teixeira, Luis; Culine, Stéphane

2015-06-01

Castration-resistant prostate cancer was subjected to a paradigm switch from hormone resistance to androgen deprivation therapy resistance during the last decade. Indeed, new therapeutics targeting the androgen receptor showed clinical efficacy in patients with progressive disease under castration. Thus, it is a proof that the AR remains a dominant driver of oncogenesis in earlier-called hormone resistant prostate cancer. This review summarizes the molecular mechanisms involved in castration-resistant prostate cancer. Copyright © 2015 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

Serum Testosterone Levels in Prostate Cancer Patients Undergoing Luteinizing Hormone-Releasing Hormone Agonist Therapy.

Science.gov (United States)

Morote, Juan; Comas, Inma; Planas, Jacques; Maldonado, Xavier; Celma, Ana; Placer, José; Ferrer, Roser; Carles, Joan; Regis, Lucas

2018-04-01

Serum testosterone measurement is recommended to assess the efficacy of androgen deprivation therapy (ADT) and to diagnose castration resistance in patients with prostate cancer (PCa). Currently, the accepted castrate level of serum testosterone is 50 ng/dL. Liquid chromatography and tandem mass spectrometry (LC MSMS) is the appropriate method to measure testosterone, especially at low levels. However, worldwide, chemiluminescent assays (CLIAs) are used in clinical laboratories, despite their lack of accuracy and reproducibility, because they are automatable, fast, sensitive, and inexpensive. We compared serum testosterone levels measured using LC MSMS and CLIAs in 126 patients with PCa undergoing luteinizing hormone-releasing hormone (LHRH) agonist therapy. The median serum testosterone level was 14.0 ng/dL (range, 2.0-67.0 ng/dL) with LC MSMS and 31.9 ng/dL (range, 10.0-91.6 ng/dL) with CLIA (P  50 ng/dL in 3 patients (2.4%). These ranges were found in 34 (27%), 72 (57.1%), and 20 (15.9%) patients when testosterone was measured using CLIA (P < .001). The castrate level of serum testosterone using LC MSMS and CLIA was 39.8 ng/dL (95% confidence interval [CI], 37.1-43.4 ng/dL) and 66.5 ng/dL (95% CI, 62.3-71.2 ng/dL), respectively. We found that CLIA overestimated the testosterone levels in PCa patients undergoing LHRH agonist therapy. Thus, the castration level was incorrectly considered inadequate with CLIA in almost 15% of patients. The true castration level of serum testosterone using an appropriate method is < 50 ng/dL. Copyright © 2017 Elsevier Inc. All rights reserved.

A Randomized Trial (Irish Clinical Oncology Research Group 97-01) Comparing Short Versus Protracted Neoadjuvant Hormonal Therapy Before Radiotherapy for Localized Prostate Cancer.

LENUS (Irish Health Repository)

Armstrong, John G

2010-08-24

PURPOSE: To examine the long-term outcomes of a randomized trial comparing short (4 months; Arm 1) and long (8 months; Arm 2) neoadjuvant hormonal therapy before radiotherapy for localized prostate cancer. METHODS AND MATERIALS: Between 1997 and 2001, 276 patients were enrolled and the data from 261 were analyzed. The stratification risk factors were prostate-specific antigen level >20 ng\\/mL, Gleason score >\\/=7, and Stage T3 or more. The intermediate-risk stratum had one factor and the high-risk stratum had two or more. Staging was done from the bone scan and computed tomography findings. The primary endpoint was biochemical failure-free survival. RESULTS: The median follow-up was 102 months. The overall survival, biochemical failure-free survival. and prostate cancer-specific survival did not differ significantly between the two treatment arms, overall or at 5 years. The cumulative probability of overall survival at 5 years was 90% (range, 87-92%) in Arm 1 and 83% (range, 80-86%) in Arm 2. The biochemical failure-free survival rate at 5 years was 66% (range, 62-71%) in Arm 1 and 63% (range, 58-67%) in Arm 2. CONCLUSION: No statistically significant difference was found in biochemical failure-free survival between 4 months and 8 months of neoadjuvant hormonal therapy before radiotherapy for localized prostate cancer.

Severe Cushing’s syndrome due to small cell prostate carcinoma: a case and review of literature

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M S Elston

2017-07-01

Full Text Available Cushing’s syndrome (CS due to ectopic adrenocorticotrophic hormone (ACTH is associated with a variety of tumours most of which arise in the thorax or abdomen. Prostate carcinoma is a rare but important cause of rapidly progressive CS. To report a case of severe CS due to ACTH production from prostate neuroendocrine carcinoma and summarise previous published cases. A 71-year-old male presented with profound hypokalaemia, oedema and new onset hypertension. The patient reported two weeks of weight gain, muscle weakness, labile mood and insomnia. CS due to ectopic ACTH production was confirmed with failure to suppress cortisol levels following low- and high-dose dexamethasone suppression tests in the presence of a markedly elevated ACTH and a normal pituitary MRI. Computed tomography demonstrated an enlarged prostate with features of malignancy, confirmed by MRI. Subsequent prostatic biopsy confirmed neuroendocrine carcinoma of small cell type and conventional adenocarcinoma of the prostate. Adrenal steroidogenesis blockade was commenced using ketoconazole and metyrapone. Complete biochemical control of CS and evidence of disease regression on imaging occurred after four cycles of chemotherapy with carboplatin and etoposide. By the sixth cycle, the patient demonstrated radiological progression followed by recurrence of CS and died nine months after initial presentation. Prostate neuroendocrine carcinoma is a rare cause of CS that can be rapidly fatal, and early aggressive treatment of the CS is important. In CS where the cause of EAS is unable to be identified, a pelvic source should be considered and imaging of the pelvis carefully reviewed.

Investigation of a Putative Estrogen-Imprinting Gene, Phosphodiesterase Type IV Variant (PDE4D4), in Determining Prostate Cancer Risk

National Research Council Canada - National Science Library

Tang, Wan-Yee

2007-01-01

.... Estrogen imprinting of the prostate gland is believed to associate with an increased incidence of prostatic lesions including inflammation epithelial hyperplasia squamous metaplasia dysplasia and adenocarcinoma...

Investigation of a Putative Estrogen-Imprinting Gene, Phosphodiesterase Type IV Variant (Pde4d4), in Determining Prostate Cancer Risk

National Research Council Canada - National Science Library

Tang, Wan-Yee

2008-01-01

.... Estrogen imprinting of the prostate gland is believed to associate with an increased incidence of prostatic lesions including inflammation, epithelial hyperplasia, squamous metaplasia, dysplasia and adenocarcinoma...

Benign or Malignant? Two Case Reports of Gigantic Prostatic Cyst

Directory of Open Access Journals (Sweden)

Jiang Yu

2016-09-01

Full Text Available A 60-year-old male with a huge prostate cyst presented with obstruction symptom of urethra and intestinal tract. Complete excision of the cystic prostate failed as a result of the strong adherence and twice operations history, but we confirmed prostate adenocarcinoma and relieved his obstruction symptom. Case 2 was a 77-year-old male with an 8 cm cyst of which biopsy showed prostate cancer in local hospital. He was admitted 18 months later because of intestinal obstruction. Radical resection had a satisfied result of obstruction symptom and PSA. Here we summarized malignant characteristics of cystic lesions in prostate or surrounding structures and management.

MRI to assess chemoprevention in transgenic adenocarcinoma of mouse prostate (TRAMP)

International Nuclear Information System (INIS)

Arbab, Ali S; Shankar, Adarsh; Varma, Nadimpalli RS; Deeb, Dorrah; Gao, Xiaohua; Iskander, ASM; Janic, Branislava; Ali, Meser M; Gautam, Subhash C

2011-01-01

The current method to determine the efficacy of chemoprevention in TRAMP mouse model of carcinoma of prostate (CaP) is by extracting and weighing the prostate at different time points or by immunohistochemistry analysis. Non-invasive determination of volumes of prostate glands and seminal vesicles before, during and after treatment would be valuable in investigating the efficacy of newer chemopreventive agents in CaP. The purpose of this study was to determine whether in vivo magnetic resonance imaging (MRI) using a 3 tesla clinical MRI system can be used to follow the effect of chemoprevention in TRAMP model of mouse CaP. Mice were randomized into control and treated groups. The animals in treated group received 10 µmol/kg of CDDO, 5 days a week for 20 weeks. Animals underwent in vivo MRI of prostate gland and seminal vesicles by a clinical 3 Tesla MRI system just before (at 5 weeks), during and at the end of treatment, at 25 weeks. T1-weighted and fat saturation (FATSAT) multiecho fast spin echo T2- weighted images (T2WI) were acquired. Volume of the prostate glands and seminal vesicles was determined from MR images. T2 signal intensity changes in the seminal vesicles were determined by subtracting higher echo time (TE) from lower TE T2WI. Following treatments all animals were sacrificed, prostate and seminal vesicles collected, and the tissues prepared for histological staining. All data were expressed as mean ± 1 standard deviation. Two-way or multivariate analysis of variance followed by post-hoc test was applied to determine the significant differences. A p-value of <0.05 was considered significant. Histological analysis indicated tumor in 100% of control mice, whereas 10% of the treated mice showed tumor in prostate gland. Both MRI and measured prostate weights showed higher volume/weight in control mouse group. MRI showed significantly higher volume of seminal vesicles in control animals and T2 signal intensity changes in seminal vesicles of control mice

Immunohistochemical differentiation of high-grade prostate carcinoma from urothelial carcinoma.

Science.gov (United States)

Chuang, Ai-Ying; DeMarzo, Angelo M; Veltri, Robert W; Sharma, Rajni B; Bieberich, Charles J; Epstein, Jonathan I

2007-08-01

The histologic distinction between high-grade prostate cancer and infiltrating high-grade urothelial cancer may be difficult, and has significant implications because each disease may be treated very differently (ie, hormone therapy for prostate cancer and chemotherapy for urothelial cancer). Immunohistochemistry of novel and established prostatic and urothelial markers using tissue microarrays (TMAs) were studied. Prostatic markers studied included: prostate-specific antigen (PSA), prostein (P501s), prostate-specific membrane antigen (PSMA), NKX3.1 (an androgen-related tumor suppressor gene), and proPSA (pPSA) (precursor form of PSA). "Urothelial markers" included high molecular weight cytokeratin (HMWCK), p63, thrombomodulin, and S100P (placental S100). TMAs contained 38 poorly differentiated prostate cancers [Gleason score 8 (n=2), Gleason score 9 (n=18), Gleason score 10 (n=18)] and 35 high-grade invasive urothelial carcinomas from radical prostatectomy and cystectomy specimens, respectively. Each case had 2 to 8 tissue spots (0.6-mm diameter). If all spots for a case showed negative staining, the case was called negative. The sensitivities for labeling prostate cancers were PSA (97.4%), P501S (100%), PSMA (92.1%), NKX3.1 (94.7%), and pPSA (94.7%). Because of PSA's high sensitivity on the TMA, we chose 41 additional poorly differentiated primary (N=36) and metastatic (N=5) prostate carcinomas which showed variable PSA staining at the time of diagnosis and performed immunohistochemistry on routine tissue sections. Compared to PSA, which on average showed 18.8% of cells with moderate to strong positivity, cases stained for P501S, PSMA, and NKX3.1 had on average 42.5%, 53.7%, 52.9% immunoreactivity, respectively. All prostatic markers showed excellent specificity. HMWCK, p63, thrombomodulin, and S100P showed lower sensitivities in labeling high-grade invasive urothelial cancer in the TMAs with 91.4%, 82.9%, 68.6%, and 71.4% staining, respectively. These urothelial

Long term results in radiotherapy of prostatic cancer

International Nuclear Information System (INIS)

Bagshaw, M.A.; Ray, G.R.; Cox, R.S.

1987-01-01

Discounting skin cancer, prostatic cancer remains second only to lung cancer in incidence in the United States. Colon Cancer is a close third. The incidence of lung cancer has started to decline slightly in the male, while prostatic cancer continues to increase, no doubt related to the aging of the population. Radiation therapy was first used in the treatment of prostatic cancer in the United States about 1915, having been introduced as intracavitary radium treatments by the American urologist, Hugh Young. External beam irradiation was used in the 1930's, but mostly for palliation of ureteral and vascular obstruction. Definitive use was first described by other investigators in the 1940's' however, attention changed to hormonal manipulation following Huggin's discovery of the dependency of prostate cancer on male hormone. Improved radiation therapy sources were invented, such as Cobalt 60 units, linear accelerators and betatrons, stimulated a reinvestigation of the definitive use of radiation therapy to prostate cancer in the 1950's. According to the current American College of Surgeon's survey of patterns of care of patients with prostate cancer, the use of external beam irradiation for the treatment of prostatic cancer has doubled in the United States during the past decade; however, apparently in Europe, hormone deprivation remains the therapeutic standard

Vinclozolin exposure in utero induces postpubertal prostatitis and reduces sperm production via a reversible hormone-regulated mechanism.

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Cowin, Prue A; Gold, Elspeth; Aleksova, Jasna; O'Bryan, Moira K; Foster, Paul M D; Scott, Hamish S; Risbridger, Gail P

2010-02-01

Vinclozolin is an endocrine-disrupting chemical (EDC) that binds with high affinity to the androgen receptor (AR) and blocks the action of gonadal hormones on male reproductive organs. An alternative mechanism of action of Vinclozolin involves transgenerational effects on the male reproductive tract. We previously reported in utero Vinclozolin exposure-induced prostatitis (prostate inflammation) in postpubertal rats concurrent with down-regulation of AR and increased nuclear factor-kappaB activation. We postulated the male reproductive abnormalities induced by in utero Vinclozolin exposure could be reversed by testosterone supplementation, in contrast to the permanent modifications involving DNA methyltransferases (Dnmts) described by others. To test this hypothesis, we administered high-dose testosterone at puberty to Vinclozolin-treated rats and determined the effect on anogenital distance (AGD); testicular germ cell apoptosis, concentration of elongated spermatids, and the onset of prostatitis. Concurrently we examined Dnmt1, -3A, -3B, and -3L mRNA expression. Consistent with previous reports, in utero exposure to Vinclozolin significantly reduced AGD, increased testicular germ cell apoptosis 3-fold, reduced elongated spermatid number by 40%, and induced postpubertal prostatitis in 100% of exposed males. Administration of high-dose testosterone (25 mg/kg) at puberty normalized AGD, reduced germ cell apoptosis, and restored elongated spermatid number. Testosterone restored AR and nuclear factor-kappaB expression in the prostate and abolished Vinclozolin-induced prostatitis. Altered Dnmt expression was evident with in utero Vinclozolin exposure and was not normalized after testosterone treatment. These data demonstrate in utero Vinclozolin-induced male reproductive tract abnormalities are AR mediated and reversible and involve a mechanism independent of Dnmt expression.

Dietary Phytoestrogens and Prostate Cancer Prevention

National Research Council Canada - National Science Library

Kurzer, Mindy S; Slaton, Joel

2007-01-01

The main objective of this project is to evaluate the effects of soy phytoestrogens on reproductive hormones and prostate tissue markers of cell proliferation and androgen action in men at high risk of prostate cancer...

Concomitant prostatic schistosomiasis and sdenocarcinoma: case report and review

Directory of Open Access Journals (Sweden)

Carlos Alberto Basílio-de-Oliveira

Full Text Available The term schistosomiasis encompasses a group of infectious disorders caused by five species of the genus Schistosoma, a blood trematode of outstanding importance in tropical areas. Some of these disorders have long been associated with malignant neoplasia, the most striking association being between disease caused by Schistosoma haematobium, the predominant etiological agent of urinary schistosomiasis, and squamous cell carcinoma of the bladder, a relatively uncommon vesical cancer in non-endemic areas. Four cases of simultaneous adenocarcinoma and schistosomiasis of the prostate have been previously reported (S. haematobium in three and S. mansoni in one. We report a fifth case of concomitant adenocarcinoma and schistosomiasis of the prostate in a 68-year-old Brazilian patient infected with S. mansoni. We also review the medical literature on the association between schistosomiasis and cancer.

Pumpkin seed extract: Cell growth inhibition of hyperplastic and cancer cells, independent of steroid hormone receptors.

Science.gov (United States)

Medjakovic, Svjetlana; Hobiger, Stefanie; Ardjomand-Woelkart, Karin; Bucar, Franz; Jungbauer, Alois

2016-04-01

Pumpkin seeds have been known in folk medicine as remedy for kidney, bladder and prostate disorders since centuries. Nevertheless, pumpkin research provides insufficient data to back up traditional beliefs of ethnomedical practice. The bioactivity of a hydro-ethanolic extract of pumpkin seeds from the Styrian pumpkin, Cucurbita pepo L. subsp. pepo var. styriaca, was investigated. As pumpkin seed extracts are standardized to cucurbitin, this compound was also tested. Transactivational activity was evaluated for human androgen receptor, estrogen receptor and progesterone receptor with in vitro yeast assays. Cell viability tests with prostate cancer cells, breast cancer cells, colorectal adenocarcinoma cells and a hyperplastic cell line from benign prostate hyperplasia tissue were performed. As model for non-hyperplastic cells, effects on cell viability were tested with a human dermal fibroblast cell line (HDF-5). No transactivational activity was found for human androgen receptor, estrogen receptor and progesterone receptor, for both, extract and cucurbitin. A cell growth inhibition of ~40-50% was observed for all cell lines, with the exception of HDF-5, which showed with ~20% much lower cell growth inhibition. Given the receptor status of some cell lines, a steroid-hormone receptor independent growth inhibiting effect can be assumed. The cell growth inhibition for fast growing cells together with the cell growth inhibition of prostate-, breast- and colon cancer cells corroborates the ethnomedical use of pumpkin seeds for a treatment of benign prostate hyperplasia. Moreover, due to the lack of androgenic activity, pumpkin seed applications can be regarded as safe for the prostate. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Novel epigenetic target therapy for prostate cancer: a preclinical study.

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Ilaria Naldi

Full Text Available Epigenetic events are critical contributors to the pathogenesis of cancer, and targeting epigenetic mechanisms represents a novel strategy in anticancer therapy. Classic demethylating agents, such as 5-Aza-2'-deoxycytidine (Decitabine, hold the potential for reprograming somatic cancer cells demonstrating high therapeutic efficacy in haematological malignancies. On the other hand, epigenetic treatment of solid tumours often gives rise to undesired cytotoxic side effects. Appropriate delivery systems able to enrich Decitabine at the site of action and improve its bioavailability would reduce the incidence of toxicity on healthy tissues. In this work we provide preclinical evidences of a safe, versatile and efficient targeted epigenetic therapy to treat hormone sensitive (LNCap and hormone refractory (DU145 prostate cancers. A novel Decitabine formulation, based on the use of engineered erythrocyte (Erythro-Magneto-Hemagglutinin Virosomes, EMHVs drug delivery system (DDS carrying this drug, has been refined. Inside the EMHVs, the drug was shielded from the environment and phosphorylated in its active form. The novel magnetic EMHV DDS, endowed with fusogenic protein, improved the stability of the carried drug and exhibited a high efficiency in confining its delivery at the site of action in vivo by applying an external static magnetic field. Here we show that Decitabine loaded into EMHVs induces a significant tumour mass reduction in prostate cancer xenograft models at a concentration, which is seven hundred times lower than the therapeutic dose, suggesting an improved pharmacokinetics/pharmacodynamics of drug. These results are relevant for and discussed in light of developing personalised autologous therapies and innovative clinical approach for the treatment of solid tumours.

Novel epigenetic target therapy for prostate cancer: a preclinical study.

Science.gov (United States)

Naldi, Ilaria; Taranta, Monia; Gherardini, Lisa; Pelosi, Gualtiero; Viglione, Federica; Grimaldi, Settimio; Pani, Luca; Cinti, Caterina

2014-01-01

Epigenetic events are critical contributors to the pathogenesis of cancer, and targeting epigenetic mechanisms represents a novel strategy in anticancer therapy. Classic demethylating agents, such as 5-Aza-2'-deoxycytidine (Decitabine), hold the potential for reprograming somatic cancer cells demonstrating high therapeutic efficacy in haematological malignancies. On the other hand, epigenetic treatment of solid tumours often gives rise to undesired cytotoxic side effects. Appropriate delivery systems able to enrich Decitabine at the site of action and improve its bioavailability would reduce the incidence of toxicity on healthy tissues. In this work we provide preclinical evidences of a safe, versatile and efficient targeted epigenetic therapy to treat hormone sensitive (LNCap) and hormone refractory (DU145) prostate cancers. A novel Decitabine formulation, based on the use of engineered erythrocyte (Erythro-Magneto-Hemagglutinin Virosomes, EMHVs) drug delivery system (DDS) carrying this drug, has been refined. Inside the EMHVs, the drug was shielded from the environment and phosphorylated in its active form. The novel magnetic EMHV DDS, endowed with fusogenic protein, improved the stability of the carried drug and exhibited a high efficiency in confining its delivery at the site of action in vivo by applying an external static magnetic field. Here we show that Decitabine loaded into EMHVs induces a significant tumour mass reduction in prostate cancer xenograft models at a concentration, which is seven hundred times lower than the therapeutic dose, suggesting an improved pharmacokinetics/pharmacodynamics of drug. These results are relevant for and discussed in light of developing personalised autologous therapies and innovative clinical approach for the treatment of solid tumours.

Risk of hormone escape in a human prostate cancer model depends on therapy modalities and can be reduced by tyrosine kinase inhibitors.

Directory of Open Access Journals (Sweden)

Charlotte Guyader

Full Text Available Almost all prostate cancers respond to androgen deprivation treatment but many recur. We postulated that risk of hormone escape--frequency and delay--are influenced by hormone therapy modalities. More, hormone therapies induce crucial biological changes involving androgen receptors; some might be targets for escape prevention. We investigated the relationship between the androgen deprivation treatment and the risk of recurrence using nude mice bearing the high grade, hormone-dependent human prostate cancer xenograft PAC120. Tumor-bearing mice were treated by Luteinizing-Hormone Releasing Hormone (LHRH antagonist alone, continuous or intermittent regimen, or combined with androgen receptor (AR antagonists (bicalutamide or flutamide. Tumor growth was monitored. Biological changes were studied as for genomic alterations, AR mutations and protein expression in a large series of recurrent tumors according to hormone therapy modalities. Therapies targeting Her-2 or AKT were tested in combination with castration. All statistical tests were two-sided. Tumor growth was inhibited by continuous administration of the LH-RH antagonist degarelix (castration, but 40% of tumors recurred. Intermittent castration or complete blockade induced by degarelix and antiandrogens combination, inhibited tumor growth but increased the risk of recurrence (RR as compared to continuous castration (RR(intermittent: 14.5, RR(complete blockade: 6.5 and 1.35. All recurrent tumors displayed new quantitative genetic alterations and AR mutations, whatever the treatment modalities. AR amplification was found after complete blockade. Increased expression of Her-2/neu with frequent ERK/AKT activation was detected in all variants. Combination of castration with a Her-2/neu inhibitor decreased recurrence risk (0.17 and combination with an mTOR inhibitor prevented it. Anti-hormone treatments influence risk of recurrence although tumor growth inhibition was initially similar. Recurrent

Lactate - A new frontier in the immunology and therapy of prostate cancer.

Science.gov (United States)

Nenu, Iuliana; Gafencu, Grigore-Aristide; Popescu, Tiberiu; Kacso, Gabriel

2017-01-01

Prostate cancer, one of the most common male malignancies with an increasing incidence in the recent years, requires the development of new methods of treatment. One of the most debated subjects is the tumor-associated macrophages (TAM). Although, the pathophysiological mechanisms are still a subject of intense research, TAM acts as procarcinogenic factors. It was also demonstrated that hypoxia-inducible factor 1 (HIF1) induces the expression of TAM genes involved in prostate carcinogenesis. Furthermore, it should be noted that the stromal extracellular lactate, the result of tumoral glycolysis process is one of the HIF1 activators. In addition, lactate inhibits the differentiation of monocytes and dendritic cells and also induces the inactivation of the cytotoxic T-lymphocytes. Through an analysis of recent studies, we conclude that lactate is a vital component of several ways of modulating the immune response at the stromal prostatic adenocarcinoma including TAM activation and cytotoxic T lymphocytes immunosuppression. Our review focuses on the impact of lactate on prostatic adenocarcinoma progression in terms of its immunology, and how this influences the therapy of this condition and the clinical outcome.

Benefits of Using Stereotactic Body Radiotherapy in Patients With Metachronous Oligometastases of Hormone-Sensitive Prostate Cancer Detected by [18F]fluoromethylcholine PET/CT

NARCIS (Netherlands)

Bouman-Wammes, Esther W.; van Dodewaard-de Jong, Joyce M.; Dahele, Max; Cysouw, Matthijs C. F.; Hoekstra, Otto S.; van Moorselaar, R. Jeroen A.; Piet, Maartje A. H.; Verberne, Hein J.; Bins, Adriaan D.; Verheul, Henk M. W.; Slotman, Ben J.; Oprea-Lager, Daniela E.; van den Eertwegh, Alfons J. M.

2017-01-01

Stereotactic body radiation therapy (SBRT) might postpone the start of androgen deprivation therapy (ADT) in patients with oligometastatic recurrence of hormone-sensitive prostate cancer. We included 43 SBRT-treated patients, and a control cohort of 20 noneSBRT-treated patients, in this

Radiation therapy for prostate cancer

International Nuclear Information System (INIS)

Nakamura, Katsumasa

2001-01-01

In Japan, where the mortality rate of prostate cancer is lower than in Western countries, radical prostatectomy or hormonal therapy has been applied more frequently than radiation therapy. However, the number of patients with prostate cancer has been increasing recently and the importance of radiation therapy has rapidly been recognized. Although there have been no randomized trials, results from several institutions in Western countries suggest that similar results of cancer control are achieved with either radiation therapy or radical prostatectomy. For higher-risk cases, conformal high-dose therapy or adjuvant hormonal therapy is more appropriate. In this article, the results of radiation therapy for prostate cancer were reviewed, with a view to the appropriate choice of therapy in Japan. (author)

Docetaxel, Carboplatin, and Rucaparib Camsylate in Treating Patients With Metastatic Castration Resistant Prostate Cancer With Homologous Recombination DNA Repair Deficiency

Science.gov (United States)

2018-02-20

ATM Gene Mutation; BRCA1 Gene Mutation; BRCA2 Gene Mutation; Castration Levels of Testosterone; Castration-Resistant Prostate Carcinoma; Homologous Recombination Deficiency; Prostate Carcinoma Metastatic in the Bone; PSA Level Greater Than or Equal to Two; PSA Progression; Stage IV Prostate Adenocarcinoma AJCC v7

A patient who sufferred pulmonary tuberculosis with syndrome of inappropriate secretion of antidiuretic hormone, after radiotherapy for pulmonary adenocarcinoma

International Nuclear Information System (INIS)

Kobayashi, Kashin; Horiguchi, Takahiko; Hata, Hideharu; Sasaki, Yasushi; Hirose, Masahiro; Shiga, Mamoru; Kondo, Rieko; Tachikawa, Souichi

2007-01-01

A 62-year-old man presented in June 2006 with right thoracic pain, cough, and weight loss, which had persisted for 3 months. Chest X-ray showed a mass-like shadow in the right pulmonary apex, suggesting a stage IIIb adenocarcinoma which was confirmed by biopsy. We gave a total radiation dose of 60 Gy, after this which general malaise and weakness were noted. The results of endocrinological examinations suggested syndrome of inappropriate antidiuretic hormone secretion (SIADH). Thoracic CT showed ground-glass opacity (GGO) in both lungs, and we could not rule out pulmonary tuberculosis. A sputum was positive for acid-fast stain and polymerase polymerase chain reaction-Tuberculosa (PCR-Tb), suggesting that SIADH was associated with pulmonary tuberculosis. Water restriction, i.v. physiological saline, and anti-tuberculosis therapy relieved hyponatremia and the symptoms. (author)

Heat shock protein 90 chaperone complex inhibitor enhanced radiosensitivity through modification of response to hormone and degradation of androgen receptor in hormone sensitive prostate cancer cell line

International Nuclear Information System (INIS)

Mitsuhashi, N.; Harashima, K.; Akimoto, T.

2003-01-01

It is easily speculated that androgen or androgen deprivation affects proliferative activity or radiosensitivity, but there has been enough information how androgen or androgen deprivation influences the response to radiation. In this setting, the effect of dihydrotestosterone (DHT) on cellular growth and radiosensitivity was examined in hormone-responsive human prostate cancer cell line (LnCap). The binding of androgen receptor (AR) with heat shock protein 90 (Hsp90) plays an important role in stability of the function of receptor. It was, therefore, examined how Hsp90 chaperone complex inhibitor modified the effect of DHT on radiosensitivity in addition to the effect of DHT, especially focusing on AR and its downstream signal transduction pathways. Hydroxy-flutamide (OH-flutamide) was also used to confirm the effect of activation of AR on radiosensitivity because AR of LnCap has a point mutation, leading to activation of AR caused by the binding of OH-flutamide. Radicicol was used as a Hsp90 chaperone complex inhibitor, and incubated with cells at a concentration of 500 nM. Radicicol was incubated with cells for 9 h, and cells were irradiated 1 h after the start of incubation. DHT and OH-flutamide were incubated with cells until staining. DHT or OH-flutamide resulted in stimulation of cellular growth in contrast to inhibition of cellular growth caused by higher concentrations, so that we adopted 1 nM as a concentration of DHT and 1μM as a concentration of OH-flutamide. DHT or OH-flutamide in combination with radiation resulted in slight decrease in radiosensitivity compared with radiation alone. Radicicol at a concentration of 500 nM in combination with DHT or OH-flutamide abolished decrease in radiosensitivity caused by DHT or OH-flutamide. In terms of the expression of AR, radicicol in combination with radiation and/or DHT, OH-flutamide induced degradation of AR. In consistent with degradation of AR, the expression of prostate specific antigen (PSA) decreased

Canine ovarian serous papillary adenocarcinoma with neoplastic hypercalcemia.

Science.gov (United States)

Hori, Yasutomo; Uechi, Masami; Kanakubo, Kayo; Sano, Tadashi; Oyamada, Toshifumi

2006-09-01

A female golden retriever was referred to assess a history of a palpable abdominal mass. A serum chemistry analysis revealed elevated concentrations of blood urea nitrogen, creatinine, calcium, and parathyroid hormone-related protein (PTH-rP). Exploratory laparotomy revealed an ovoid mass within the right ovary. This mass was removed surgically by performing an ovariohysterectomy. The right ovarian mass was diagnosed as a serous papillary adenocarcinoma. Following surgery, the dog recovered, and the serum calcium and PTH-rP concentrations decreased. Therefore, concentrations of PTH-rP and calcium might be associated with serous papillary adenocarcinomas. Serial evaluation of the serum PTH-rP and calcium was useful for evaluating the prognosis.

Concentrations of testosterone, luteal hormone and prolactin in the serum as well as comparisons of sensitivity between radioimmunoassays and enzyme assays for the detection of acid prostate phosphatase in the presence of carcinomas of the prostate

International Nuclear Information System (INIS)

Vopelius-Feldt, F. von.

1986-01-01

The relationship between carcinomas of the prostate and the plasma levels of testosterone, luteal hormone and prolactin as well as the possible influence of these neoplasms on the testosterone binding capacity and free testosterone index are investigated for various tumour stages and degrees of histological differentiation, in connection with several forms of local therapy as well as a variety of contrasexual methods. The sensitivity of enzyme assays and radioimmunoassays for the detection of acid prostate phosphatase is evaluated within the framework of this study. (MBL) [de

Internet-Based Education for Prostate Cancer Screening

Science.gov (United States)

2007-12-01

cells. n Hormone therapy: Certain hormones are given or removed. This helps to keep cancer cells from growing. n Cryotherapy : A special probe is placed...are many other diseases that are more deadly than prostate cancer . Talk to your doctor about how to prevent them. n As a result, most men with...prostate cancer ranks 5th, behind heart disease, lung cancer , stroke, and emphysema. Centers for Disease Control and Prevention , National Canter for Health

Prostatic disorders in acromegalic patients experience of a Brazilian center

Directory of Open Access Journals (Sweden)

Livia L. Correa

2013-06-01

Full Text Available Introduction Published data suggest that patients with acromegaly have an increased prevalence of prostate disorders. Objective To evaluate prostatic disorders in acromegalic patients comparing these results after one year of treatment of acromegaly and with a group of healthy men. Materials and Methods This study was composed of two parts: sectional study comparing patients with healthy controls (baseline and prospective, longitudinal study (at baseline and after one year of treatment. Forty acromegalic patients were enrolled and evaluated at baseline and after one year with the application of international prostatic symptoms score (IPSS, digital rectal examination, measurements of growth hormone (GH, insulin-like growth factor-I (IGF-I, insulin-like growth factor-binding protein-3 (IGFBP-3, sex hormone-binding globulin (SHBG, prolactin, luteinizing hormone (LH, follicle-stimulating hormone (FSH, total testosterone, total and free prostate-specific antigen (PSA levels and prostate ultrasonography (US. Thirty healthy men were selected as control group. Results We stratified patients and controls according to age, considering 40 years-old as cut off. Healthy controls under 40 had IPSS values lower than acromegalic patients. When considering only older patients and controls prostate hyperplasia and structural abnormalities were more frequent in acromegalics. After one year of treatment there was significant decrease in GH, IGF-I and prostate volume in acromegalics over 40 years-old. Conclusions Acromegalics under 40 have more urinary symptoms according to IPSS and above 40 years-old higher frequency of structural changes and increased prostate volume than healthy men. Significant reduction of GH and IGF-I levels during treatment of acromegaly leads to decrease in the prostate volume.

[Medical treatment of prostate cancer].

Science.gov (United States)

Lobel, B; Cipolla, B; Labrador, J

1994-03-01

Hormone dependence of prostate cancer is well known. In 80% of cases with metastases, hormone suppression leads to the reduction of tumour volume and related disorders. However the treatment is generally palliative because malignant process recurs after about around 16 months. Mean survival is less than 3 years in these forms. Lack of response come always together with a poor prognosis, and there is 90% mortality at 2 years. Advanced prostatic cancer should not be treated with hormones if the patient has few symptoms and his quality of life is satisfactory. Symptomatic forms require hormone manipulation. Orchidectomy or LH-RH are recommended. Total androgen ablation (combined treatment) leads rapidly to more relief of symptoms, but its drawbacks and especially high cost indicate that its use should be weighed individually. Estramustine is not a first-lune treatment. Presently, there is no criteria to predict response to treatment.

Correlation between Microvascular Density and Matrix Metalloproteinase 11 Expression in Prostate Cancer Tissues: a Preliminary Study in Thailand.

Science.gov (United States)

Kanharat, Nongnuch; Tuamsuk, Panya

2015-01-01

Prostate cancer is a major concern of public health. Microvascular density (MVD) is one of the prognostic markers for various solid cancers. Matrix metalloproteinase 11 (MMP11) plays an important role in angiogenesis and changes in its expression level are known to be associated with tumor progression and clinical outcome. To investigate the relationship between MVD and MMP11 expression in prostatic adenocarcinoma tissues. The expression levels of MMP11 and MVD were analyzed immunohistochemically for 50 specimens of prostatic adenocarcinoma. MMP11 was mainly expressed in stromal cells but rarely seen in epithelial cells. Mean MVD was 36/mm2, and it was correlated significantly only with bone metastases. MVD was also significantly correlated with MMP11 expression (r=0.29, p=0.044). MMP11 may alter the stromal microenvironment of prostate cancer to stimulate tumor angiogenesis.

Prostate cancer involving bilateral seminal vesicles along with bone and testicular metastases: a case report.

Science.gov (United States)

Gao, Qingqiang; Chen, Jianhuai; Dai, Yutian

2018-03-09

In the past 20 years, the incidence of prostate cancer has risen rapidly. It has been ranked as the third most common malignant tumor of the male genitourinary system. Testicular metastasis is uncommon in prostate cancer. Most cases are incidentally found in the treatment of prostate cancer with orchiectomy. Therefore, we believed it was necessary to report the case of our patient with this disease. We present a case of a 69-year-old Han Chinese man with a high total prostate-specific antigen level. A transrectal ultrasound-guided prostate biopsy was performed. A pathology report showed prostate cancer tissue with a Gleason score of 4 + 4 = 8/10. Imaging findings suggested that the prostate cancer tissue involved bilateral seminal vesicles and multiple bones. Next, radioactive seed implantation was carried out, and endocrine therapy was continued after the operation. Then enlargement of the left scrotum was found along with a total prostate-specific antigen level of 19.21 ng/ml. Computed tomography of the middle abdomen and pelvic cavity revealed 2.0 × 1.3-cm lesions of the left testis. The patient underwent a left testicular high resection and right orchiectomy. The postoperative pathology report showed metastatic prostate cancer cells in the left testis. Testicular metastasis of prostate cancer is rare. Therefore, a testicular physical examination is necessary for patients without relapse to avoid a missed diagnosis. Testicular metastasis should be treated according to the principle of treatment for advanced prostate adenocarcinoma if testicular metastasis of prostate adenocarcinoma is detected.

Ultrasound-guided seminal vesicle biopsies in prostate cancer

NARCIS (Netherlands)

Wymenga, LFA; Duisterwinkel, FJ; Groenier, K; Mensink, HJA

2000-01-01

Invasion of prostatic adenocarcinoma into the seminal vesicles (SV) is generally accepted as an index of poor prognosis. The pre-operative identification of SV invasion is an important element in staging since it may alter subsequent treatment decisions. We studied the possibility of diagnosing SV

Fracture risk in Danish men with prostate cancer

DEFF Research Database (Denmark)

Abrahamsen, Bo; Nielsen, Morten F; Eskildsen, Peter Claes

2007-01-01

To assess the risk of fracture attributable to prostate cancer, and the impact of exposure to prescribed gonadotrophin-releasing hormone agonists and antiandrogens on this risk in a nationwide, population-based case-control study.......To assess the risk of fracture attributable to prostate cancer, and the impact of exposure to prescribed gonadotrophin-releasing hormone agonists and antiandrogens on this risk in a nationwide, population-based case-control study....

MOLECULAR MARKERS FOR METASTATIC PROSTATE ADENOCARCINOMA

Directory of Open Access Journals (Sweden)

I. S. Kunin

2012-01-01

Full Text Available The search of molecular markers of metastasing and prognosis in prostate cancer remains an urgent task. In this study, we investigated the relationship of gene expression heparanase-1 (HPSE1 and D-glucuronil C5-epimerase (GLCE with early disease relapse and metastasis of a 2,5−3 years after diagnosis. It was shown that the ratio of the expression levels of genes HPSE1/GLCE > 1 may serve as a prognostic relapse marker and trends of the tumour to metastasis. The data obtained suggest to use this option as a molecular marker for the diagnostics of metastatic process and the disease prognosis.

Changes in Treatment Volume of Hormonally Treated and Untreated Cancerous Prostate and its Impact on Rectal Dose

International Nuclear Information System (INIS)

Lilleby, Wolfgang; Dale, Einar; Olsen, Dag R.; Gude, Unn; Fossaa, Sophie D.

2003-01-01

Late chronic side effects of the rectum constitute one of the principal limiting factors for curative radiation therapy in patients with prostate cancer. The purpose of the study was to determine the impact of immediate androgen deprivation (IAD) prior to conformal radiotherapy on rectal volume exposed to high doses, as compared with a deferred treatment strategy (DAD). Twenty-five patients (13 in the IAD group and 12 in the DAD group) with bulky tumours of the prostate, T3pN1-2M0 from the prospective EORTC trial 30846 were analysed. Three-dimensional conformal radiation treatment plans (3D CRT) using a 4-field box technique were generated based on the digitized computed tomographic or magnetic resonance findings acquired during the first 9 months after inclusion in the EORTC trial. Dose-volume histograms (DVHs) were calculated for the prostate and rectum. In the DAD group, there was no obvious alteration in the mean size of the prostate or other evaluated structures. In the IAD patients, a statistically significant reduction of approximately 40% of the gross tumour volume (GTV) was reached after a 6 months' course of hormonal treatment (p<0.001). High-dose rectal volume was correlated with the volume changes of the GTV (p<0.001). Mean rectal volume receiving 95% or more of the target dose was significantly reduced by 20%. Our study confirms the effect of downsizing of locally advanced prostate tumours following AD treatment and demonstrates the interdependence of the high-dose rectal volume with the volume changes of the GTV. However, the mean beneficial sparing of rectal volume was outweighed in some patients by considerable inter-patient variations

3D conformal radiation therapy and hormonal therapy for localized prostate cancer: Is age a limiting factor?

International Nuclear Information System (INIS)

Faure, A.; Negrea, T.; Lechevallier, E.; Coulange, C.; Murraciole, X.; Jouvea, E.; Sambuca, R.; Cowen, D.

2011-01-01

No study on side effects had showed that conformal radiation therapy for prostate cancer is more harmful in patients older than 70 years to patients younger. The aim of this study was to evaluate acute and late toxicities of conformal radiotherapy, with high dose for localized prostate cancer in patients older than 70 years and compared to patients younger than 70 years. Between 1996 and 2009, 104 patients were treated with radiation therapy and hormonal therapy for localized cancer prostate. Median follow-up was 105 months (9 300). Acute (occurred at ≤ three months) and late side effects of 55 patients older than 70 years (median age: 75 [71 92]) were graded according to the CTCAE 3.0 criteria and compared to the younger population. Median dose to the prostate was 75.6 Gy (67 80) in both groups. There were no significant differences in acute and late side effects between age groups. For patients above 70 years, the incidence of grade II or higher acute and late side effects were respectively 27 and 22% for urologic symptoms and 13 and 16% for rectal symptoms. The frequency of grade III late symptoms was low and ranged between 0 and 6% for the evaluated symptoms, irrespective of age group. Older patients had a better biochemical recurrence-free survival than younger patients (86 versus 77% at four years, P ≡ ns). High dose 3D conformal radiotherapy for localized prostate cancer was well tolerated in patients older than 70 years. Age is not a limiting factor for conformal radiation therapy and hormonotherapy for older patients. (authors)

Antiproliferative Evaluation of Isofuranodiene on Breast and Prostate Cancer Cell Lines

Directory of Open Access Journals (Sweden)

Michela Buccioni

2014-01-01

Full Text Available The anticancer activity of isofuranodiene, extracted from Smyrnium olusatrum, was evaluated in human breast adenocarcinomas MDA-MB 231 and BT 474, and Caucasian prostate adenocarcinoma PC 3 cell lines by MTS assay. MTS assay showed a dose-dependent growth inhibition in the tumor cell lines after isofuranodiene treatment. The best antiproliferative activity of the isofuranodiene was found on PC 3 cells with an IC50 value of 29 μM, which was slightly less than the inhibition against the two breast adenocarcinoma cell lines with IC50 values of 59 and 55 μM on MDA-MB 231 and BT 474, respectively. Hoechst 33258 assay was performed in order to study the growth inhibition mechanism in prostate cancer cell line; the results indicate that isofuranodiene induces apoptosis. Overall, the understudy compound has a good anticancer activity especially towards the PC 3. On the contrary, it is less active on Chinese hamster ovary cells (CHO and human embryonic kidney (HEK 293 appearing as a good candidate as a potential natural anticancer drug with low side effects.

Understanding Prostate Changes: A Health Guide for Men

Science.gov (United States)

... enzyme changes the male hormone testosterone into dihydrotestosterone (DHT), which stimulates prostate growth. When the action of 5-alpha reductase is blocked, DHT production is lowered and prostate growth slows. This ...

Biochemical failure after radical external beam radiotherapy for prostate cancer

International Nuclear Information System (INIS)

Nomoto, Satoshi; Imada, Hajime; Kato, Fumio; Yahara, Katsuya; Morioka, Tomoaki; Ohguri, Takayuki; Nakano, Keita; Korogi, Yukunori

2005-01-01

The purpose of this study was to evaluate biochemical failures after radical external beam radiotherapy for prostate cancer. A total of 143 patients with prostate cancer (5 cases in stage A2, 95 in stage B and 43 in stage C; 18 in low risk group, 37 in intermediate risk group, 67 in high risk group and 21 in unknown group) were included in this study. Patients of stage A2 and B underwent external irradiation of 46 Gy to the prostate gland and seminal vesicle and additional 20 Gy to the prostate gland, while patients of stage C underwent external irradiation of 66 Gy to the prostate gland and seminal vesicle including 46 Gy to the pelvis. Neoadjuvant hormonal therapy was done in 66 cases, and long-term hormonal therapy in 75 cases; two cases were treated with radiation therapy alone. The 3-year relapse free survival rates by stage A2, B and C were 100%, 96.7% and 88.1%, respectively. The 3-year relapse free survival rates by low, intermediate and high risk groups were 100%, 92.3% and 89.7%, respectively. Biochemical failure was noted in nine cases during the average observation term of 32.2 months; in this group the median of prostate specific antigen (PSA) value was 2.6 ng/ml, the doubling time was 8.6 months, and the term of biochemical failure was 33.2 months. Six of eight cases with biochemical failure were the neoadjuvant hormonal therapy group, but biochemical no evidence of disease (bNED) curve showed no significant difference between neoadjuvant and long-term hormonal groups. It is supposed that unnecessary hormonal therapies were performed based on the nonspecific diagnosis of biochemical failure after radical radiotherapy in our group of patients. A precise criterion of biochemical failure after radical radiotherapy for prostate cancer is necessary. (author)

Fibulin-1 functions as a prognostic factor in lung adenocarcinoma.

Science.gov (United States)

Cui, Yuan; Liu, Jian; Yin, Hai-Bing; Liu, Yi-Fei; Liu, Jun-Hua

2015-09-01

Fibulin-1 is a member of the fibulin gene family, characterized by tandem arrays of epidermal growth factor-like domains and a C-terminal fibulin-type module. Fibulin-1 plays important roles in a range of cellular functions including morphology, growth, adhesion and mobility. It acts as a tumor suppressor gene in cutaneous melanoma, prostate cancer and gastric cancer. However, whether fibulin-1 also acts as a tumor suppressor gene in lung adenocarcinoma remains unknown. We also determined the association of fibulin-1 expression with various clinical and pathological parameters, which would show its potential role in clinical prognosis. We investigated and followed up 140 lung adenocarcinoma patients who underwent lung resection without pre- and post-operative systemic chemotherapy at the Affiliated Hospital of Nantong University from 2009 to 2013. Western blot assay and immunohistochemistry were used to evaluate the expression of fibulin-1 in lung adenocarcinoma tissues. We then analyzed the correlations between fibulin-1 expression and clinicopathological variables as well as the patients' overall survival rate. Both western blot assay and immunohistochemistry demonstrated that the level of fibulin-1 was downregulated in human lung adenocarcinoma tissues compared with that of normal lung tissues. Fibulin-1 expression significantly correlated with histological differentiation (P = 0.046), clinical stage (P< 0.01), lymph node status (P = 0.038) and expression of Ki-67 (P = 0.013). More importantly, multivariate analysis revealed that fibulin-1 was an independent prognostic marker for lung adenocarcinoma, and high expression of fibulin-1 was significantly associated with better prognosis of lung adenocarcinoma patients. The results supported our hypothesis that fibulin-1 can act as a prognostic factor in lung adenocarcinoma progression. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Amino acid containing thapsigargin analogues deplete androgen receptor protein via synthesis inhibition and induce the death of prostate cancer cells

DEFF Research Database (Denmark)

Griend, Donald J Vander; Antony, Lizamma; Dalrymple, Susan L

2009-01-01

There are quantitative and/or qualitative mechanisms allowing androgen receptor (AR) growth signaling in androgen ablation refractory prostate cancer cells. Regardless of the mechanism, agents that deplete AR protein expression prevent such AR growth signaling. Thapsigargin (TG) is a highly cell......-penetrant sequiterpene-lactone that once inside cells inhibits (IC(50), approximately 10 nmol/L) critically important housekeeping SERCA 2b calcium pumps in the endoplasmic reticulum. Using a series of five genetically diverse androgen ablation refractory human prostate cancer lines (LNCaP, LAPC-4, VCaP, MDA-PCa-2b......-specific proteases, such as prostate-specific antigen and prostate-specific membrane antigen, or cancer-specific proteases, such as fibroblast activation protein, so that toxicity of these prodrugs is selectively targeted to metastatic sites of prostate cancer. Based on these results, these prodrugs are undergoing...

Bone dissemination of prostate cancer after holmium laser enucleation of the prostate: a case report and a review of the literature.

Science.gov (United States)

Koguchi, Dai; Nishi, Morihiro; Satoh, Takefumi; Shitara, Toshiya; Matsumoto, Kazumasa; Fujita, Tetsuo; Yoshida, Kazunari; Iwamura, Masatsugu

2014-02-01

We report a case of dissemination of prostate cancer after holmium laser enucleation of the prostate in an 80-year-old patient. The patient presented at hospital because of nocturia. Transrectal ultrasound-guided biopsy was carried out because of high serum prostate-specific antigen (3.55 ng/mL), but it showed no malignancies. Benign prostate hyperplasia was diagnosed, and he was started on an α1-blocker. Although the urinary symptom improved with silodosin, acute urinary retention occurred 3 years after therapy began. Holmium laser enucleation of the prostate for relief of bladder outlet obstruction enabled discharge of urine. Pathological examination of the resected tissue found adenocarcinoma with a high Gleason score, 4 + 5. Serum alkaline phosphatase increased rapidly after holmium laser enucleation, and bone scintigraphy confirmed multiple bone metastases. Prostate cancer, T1bN0M1b, was diagnosed. © 2013 The Japanese Urological Association.

Localization of the prostatic apex for radiotherapy treatment planning

International Nuclear Information System (INIS)

Wilder, Richard B.; Fone, Patricia D.; Jones, C. Darryl; White, Ralph DeVere

1996-01-01

Purpose/Objective: There is no consensus on the optimal method for localizing the prostatic apex in patients with early stage adenocarcinoma of the prostate. Some radiation oncologists have recommended that transrectal ultrasound or MRI scans be used to define the inferior border of radiation portals. The purpose of this prospective study is to assess the ability of retrograde urethrograms and CT scans to accurately define the prostatic apex in the craniocaudad dimension, using urethroscopy as a reference. Materials and Methods: Following construction of an Alpha cradle, plain radiographs of the pelvis were obtained in 15 patients with early stage adenocarcinoma of the prostate, with the tip of a urethroscope placed at the superior border of the external sphincter (which most closely approximates the prostatic apex). The scope was then withdrawn, and a retrograde urethrogram was performed. Immediately afterwards, a treatment planning CT scan of the pelvis was obtained. Since differential filling of the bladder and rectum affects the position of the prostatic apex, patients voided prior to rather than in between the 3 consecutive studies. Results: The urethroscopy-defined prostatic apex was located 28 ± 3 mm (mean ± SE) superior to the ischial tuberosities, 12 ± 1 mm (mean ± SE) superior to the urethrogram tip and 8 ± 2 mm (mean ± SE) superior to the CT-defined apex. Placement of the inferior border of the radiation portals at the ischial tuberosities would have resulted in irradiation of > 20 mm membranous and spongy urethra in all of the patients. Conclusion: Retrograde urethrograms provide more helpful information than CT scans with regard to localization of the prostatic apex and are more cost effective than sonograms or MRI scans. The prostatic apex is typically 12 mm superior to the urethrogram tip with little variability. Retrograde urethrograms allow one to spare as much urethra as possible in the radiation portals, which should theoretically reduce

Lower testosterone levels with luteinizing hormone-releasing hormone agonist therapy than with surgical castration: new insights attained by mass spectrometry

NARCIS (Netherlands)

van der Sluis, Tim M.; Bui, Hong N.; Meuleman, Eric J. H.; Heijboer, Annemieke C.; Hartman, Jeroen F.; van Adrichem, Nick; Boevé, Egbert; de Ronde, Willem; van Moorselaar, R. Jeroen A.; Vis, André N.

2012-01-01

Androgen deprivation therapy by bilateral orchiectomy (surgical castration) or luteinizing hormone-releasing hormone agonist therapy (medical castration) is recommended for advanced or metastatic prostate cancer. Both methods aim at reducing serum testosterone concentrations to a castrate level

GC-MS-Based Endometabolome Analysis Differentiates Prostate Cancer from Normal Prostate Cells

Directory of Open Access Journals (Sweden)

Ana Rita Lima

2018-03-01

Full Text Available Prostate cancer (PCa is an important health problem worldwide. Diagnosis and management of PCa is very complex because the detection of serum prostate specific antigen (PSA has several drawbacks. Metabolomics brings promise for cancer biomarker discovery and for better understanding PCa biochemistry. In this study, a gas chromatography–mass spectrometry (GC-MS based metabolomic profiling of PCa cell lines was performed. The cell lines include 22RV1 and LNCaP from PCa with androgen receptor (AR expression, DU145 and PC3 (which lack AR expression, and one normal prostate cell line (PNT2. Regarding the metastatic potential, PC3 is from an adenocarcinoma grade IV with high metastatic potential, DU145 has a moderate metastatic potential, and LNCaP has a low metastatic potential. Using multivariate analysis, alterations in levels of several intracellular metabolites were detected, disclosing the capability of the endometabolome to discriminate all PCa cell lines from the normal prostate cell line. Discriminant metabolites included amino acids, fatty acids, steroids, and sugars. Six stood out for the separation of all the studied PCa cell lines from the normal prostate cell line: ethanolamine, lactic acid, β-Alanine, L-valine, L-leucine, and L-tyrosine.

A novel histone deacetylase inhibitor, CG200745, potentiates anticancer effect of docetaxel in prostate cancer via decreasing Mcl-1 and Bcl-XL.

Science.gov (United States)

Hwang, Jung Jin; Kim, Yong Sook; Kim, Taelim; Kim, Mi Joung; Jeong, In Gab; Lee, Je-Hwan; Choi, Jene; Jang, Sejin; Ro, Seonggu; Kim, Choung-Soo

2012-08-01

We synthesized a novel hydroxamate-based pan-histone deacetylase inhibitor (HDACI), CG200745 {(E)-2-(Naphthalen-1-yloxymethyl)-oct-2-enedioic acid 1-[(3-dimethylamino-propyl)-amide] 8-hydroxyamide]}. Like other inhibitors, for example vorinostat and belinostat, CG200745 has the hydroxamic acid moiety to bind zinc at the bottom of catalytic pocket. Firstly, we analyzed its inhibitory activity against histone deacetylase (HDAC) in hormone-dependent LNCaP cells and hormone-independent DU145 and PC3 cells. CG200745 inhibited deacetylation of histone H3 and tubulin as much as vorinostat and belinostat did. CG200745 also inhibited growth of prostate cancer cells, increased sub-G1 population, and activated caspase-9, -3 and -8 in LNCaP, DU145 and PC3 cells. These results indicate that CG200745 induces apoptosis. Next, we examined the effect of CG200745 on cell death induced by docetaxel in DU145 cells in vitro and in vivo. Compared to mono-treatment with each drug, pre-treatment of DU145 cells with docetaxel followed by CG200745 showed synergistic cytotoxicity, and increased the apoptotic sub-G1 population, caspase activation, and tubulin acetylation. Moreover, the combination treatment decreased Mcl-1 and Bcl-(XL). Docetaxel and CG200745 combination reduced tumor size in the DU145 xenograft model. These preclinical results show that combination treatment with docetaxel and new HDACI, CG200745, potentiated anti-tumor effect in hormone-refractory prostate cancer (HRPC) cells via activation of apoptosis.

Baldness, benign prostate hyperplasia, prostate cancer and androgen levels.

Science.gov (United States)

Faydaci, Gökhan; Bilal, Eryildirim; Necmettin, Penpegül; Fatih, Tarhan; Asuman, Orçun; Uğur, Kuyumcuoğlu

2008-12-01

We evaluated the pattern of baldness and serum androgen levels in patients with benign prostate hyperplasia (BPH) and prostate cancer. BPH, prostate cancer and androgenic alopecia (AA) were somehow androgen dependent and affect large population of elderly men. A total of 152 patients, 108 patients with BPH and 44 patients with prostate cancer were included in the study. We measured serum total, free and bioavailable testosterone, FSH, LH, prolactin, estradiol, albumin and SHBG levels. Baldness classification was based on Norwood's classification and we categorised baldness as vertex and frontal baldness. The frequency of AA in BPH and prostate cancer groups were not different. We looked for some correlation between the two groups with respect to AA and hormone levels. We did not find any correlation between AA and total testosterone, free testosterone, bioavailable testosterone or SHBG levels in both groups. This prospective study with selected small group of patients showed that there is no difference of male pattern baldness in BPH and prostate cancer patients and also there is no correlation between pattern of baldness and serum androgen levels.

FOXA1 promotes tumor progression in prostate cancer and represents a novel hallmark of castration-resistant prostate cancer.

Science.gov (United States)

Gerhardt, Josefine; Montani, Matteo; Wild, Peter; Beer, Marc; Huber, Fabian; Hermanns, Thomas; Müntener, Michael; Kristiansen, Glen

2012-02-01

Forkhead box protein A1 (FOXA1) modulates the transactivation of steroid hormone receptors and thus may influence tumor growth and hormone responsiveness in prostate cancer. We therefore investigated the correlation of FOXA1 expression with clinical parameters, prostate-specific antigen (PSA) relapse-free survival, and hormone receptor expression in a large cohort of prostate cancer patients at different disease stages. FOXA1 expression did not differ significantly between benign glands from the peripheral zone and primary peripheral zone prostate carcinomas. However, FOXA1 was overexpressed in metastases and particularly in castration-resistant cases, but was expressed at lower levels in both normal and neoplastic transitional zone tissues. FOXA1 levels correlated with higher pT stages and Gleason scores, as well as with androgen (AR) and estrogen receptor expression. Moreover, FOXA1 overexpression was associated with faster biochemical disease progression, which was pronounced in patients with low AR levels. Finally, siRNA-based knockdown of FOXA1 induced decreased cell proliferation and migration. Moreover, in vitro tumorigenicity was inducible by ARs only in the presence of FOXA1, substantiating a functional cooperation between FOXA1 and AR. In conclusion, FOXA1 expression is associated with tumor progression, dedifferentiation of prostate cancer cells, and poorer prognosis, as well as with cellular proliferation and migration and with AR signaling. These findings suggest FOXA1 overexpression as a novel mechanism inducing castration resistance in prostate cancer. Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Interventional embolization for refractory hyperthyroidism

International Nuclear Information System (INIS)

Jiang Guomin; Zhang Yunping; Chen Yaxian; Zhao Jinwei; Yang Weihuai; Chen Jinluo

2001-01-01

Objective: To evaluate the clinical effects of the thyroid artery embolization for refractory hyperthyroidism. Methods: Super selective catheterization and interventional embolization of thyroid superior and inferior arteries were performed with PVA microspheres and Gelfoam particles. Changes of function and size of thyroid were investigated after embolization. Results: The procedures were succeeded in all 21 patients. Followed up by 3-12 months, serum level of thyroid hormones dropped significantly (median FT 3 from 17.1 pmol/L to 7.44 pmol/L, median FT 4 from 51.1 pmol/L to 23.3 pmol/L, P< 0.01). The size of thyroid glands decreased remarkably. Symptoms of hyperthyroidism were controlled in 4 patients and were effectively controlled through low dose antithyroid medication in 17 patients. No serious complications occurred. Conclusions: Thyroid artery embolization is a new safe and effective method for refractory hyperthyroidism

SoyCaP: Soy and Prostate Cancer Prevention

National Research Council Canada - National Science Library

Hamilton-Reeves, Jill M; Kurzer, Mindy S; Slaton, Joel

2007-01-01

The main objective of this project is to evaluate the effects of soy phytoestrogens on reproductive hormones and prostate tissue markers of cell proliferation and androgen action in men at high risk of prostate cancer...

SoyCaP: Soy and Prostate Cancer Prevention

National Research Council Canada - National Science Library

Hamilton-Reeves, Jim M; Kurzer, Mindy S; Slaton, Joel

2006-01-01

The main objective of this project is to evaluate the effects of soy phytoestrogens on reproductive hormones and prostate tissue markers of cell proliferation and androgen action in men at high risk of prostate cancer...

Wide variation of prostate-specific antigen doubling time of untreated, clinically localized, low-to-intermediate grade, prostate carcinoma.

Science.gov (United States)

Choo, Richard; Klotz, Laurence; Deboer, Gerrit; Danjoux, Cyril; Morton, Gerard C

2004-08-01

To assess the prostate specific antigen (PSA) doubling time of untreated, clinically localized, low-to-intermediate grade prostate carcinoma. A prospective single-arm cohort study has been in progress since November 1995 to assess the feasibility of a watchful-observation protocol with selective delayed intervention for clinically localized, low-to-intermediate grade prostate adenocarcinoma. The PSA doubling time was estimated from a linear regression of ln(PSA) against time, assuming a simple exponential growth model. As of March 2003, 231 patients had at least 6 months of follow-up (median 45) and at least three PSA measurements (median 8, range 3-21). The distribution of the doubling time was: 50 years, 56. The median doubling time was 7.0 years; 42% of men had a doubling time of >10 years. The doubling time of untreated clinically localized, low-to-intermediate grade prostate cancer varies widely.

Sodium Iodide Symporter Gene Transfer for Imaging and Ablation of Prostate Cancer

National Research Council Canada - National Science Library

Jhiang, Sissy M

2005-01-01

.... The specific aims of this project are to: (1) confirm metastatic progression to distant lymph nodes and lungs following subcutaneous inoculation of rats with MATLyLu prostatic adenocarcinoma cells expressing hNIS; (2...

Effect of Her-2/neu Signaling on Sensitivity to TRAIL in Prostate Cancer

National Research Council Canada - National Science Library

Lee, Yong J

2005-01-01

.... In this study, we observed that pretreatment of acetyl salicylic acid (ASA) augmented TRAIL-induced apoptotic death in human prostate adenocarcinoma LNCaP and human colorectal carcinoma CX-1 cells...

Testosterone levels and the genetic variation of sex hormone ...

Indian Academy of Sciences (India)

Lillian

1Physiology and Hormones Department, Animal Health Research Institute, ... hormone-binging globulin (SHBG) that is the major transporter protein of sex ... genotypes, one of which is likely to be associated with low testosterone ..... sex steroid hormones in men from the NCI-Breast and Prostate Cancer Cohort Consortium.

MR diffusion weighted imaging of the prostate adenocarcinoma after endocrinotherapy: preliminary results

International Nuclear Information System (INIS)

Chen Zhiqiang; Wang Xiaoying; Li Feiyu; Guo Xuemei; Jiang Xuexiang; Guo Yulin

2007-01-01

Objective: To assess the changes of the apparent diffusion coefficient (ADC) values of cancerous and noncancerous regions of prostate peripheral zone in prostate cancer patients with and without endocrinotherapy. Methods: Diffusion-weighted echo-planar imaging (EPI) were performed in 32 patients with diagnosed prostate cancer, including 18 patients who were treated with endocrinotherapy over 6 months and 14 untreated matched control patients. According to the pathological results obtained by ultrasound guided biopsy, the locations of the prostate cancerous regions were marked at one or more of the sextants. The ADC values of the bladder and the obturator internus were also measured. Results: The mean ADC values of cancerous and noncancerous regions in 14 untreated controls were (1.22±0.25) x 10 -3 , (1.59 ± 0.19) x 10 -3 mm 2 /s, respectively (t=7.03, P -3 mm 2 /s in noncancerous regions, but increased to (1.46 ± 0.30) x 10 -3 mm 2 /s in cancerous regions. There still had significant difference between the cancerous and the noncancerous regions (t=2.46, P 0.05), in bladder and the obturator internus (t=0.48, 1.64; P>0.05). Conclusion: Measurement of ADCs might be useful to evaluate the efficacy of endocrinotherapy for patients with prostate cancer. (authors)

Integrative Genomic Analysis of Coincident Cancer Foci Implicates CTNNB1 and PTEN Alterations in Ductal Prostate Cancer.

Science.gov (United States)

Gillard, Marc; Lack, Justin; Pontier, Andrea; Gandla, Divya; Hatcher, David; Sowalsky, Adam G; Rodriguez-Nieves, Jose; Vander Griend, Donald; Paner, Gladell; VanderWeele, David

2017-12-08

Ductal adenocarcinoma of the prostate is an aggressive subtype, with high rates of biochemical recurrence and overall poor prognosis. It is frequently found coincident with conventional acinar adenocarcinoma. The genomic features driving evolution to its ductal histology and the biology associated with its poor prognosis remain unknown. To characterize genomic features distinguishing ductal adenocarcinoma from coincident acinar adenocarcinoma foci from the same patient. Ten patients with coincident acinar and ductal prostate cancer underwent prostatectomy. Laser microdissection was used to separately isolate acinar and ductal foci. DNA and RNA were extracted, and used for integrative genomic and transcriptomic analyses. Single nucleotide mutations, small indels, copy number estimates, and expression profiles were identified. Phylogenetic relationships between coincident foci were determined, and characteristics distinguishing ductal from acinar foci were identified. Exome sequencing, copy number estimates, and fusion genes demonstrated coincident ductal and acinar adenocarcinoma diverged from a common progenitor, yet they harbored distinct alterations unique to each focus. AR expression and activity were similar in both histologies. Nine of 10 cases had mutually exclusive CTNNB1 hotspot mutations or phosphatase and tensin homolog (PTEN) alterations in the ductal component, and these were absent in the acinar foci. These alterations were associated with changes in expression in WNT- and PI3K-pathway genes. Coincident ductal and acinar histologies typically are clonally related and thus arise from the same cell of origin. Ductal foci are enriched for cases with either a CTNNB1 hotspot mutation or a PTEN alteration, and are associated with WNT- or PI3K-pathway activation. These alterations are mutually exclusive and may represent distinct subtypes. The aggressive subtype ductal adenocarcinoma is closely related to conventional acinar prostate cancer. Ductal foci

Further evidence for increased macrophage migration inhibitory factor expression in prostate cancer

Directory of Open Access Journals (Sweden)

Iczkowski Kenneth A

2005-07-01

Full Text Available Abstract Background Macrophage migration inhibitory factor (MIF is a cytokine associated with prostate cancer, based on histologic evidence and circulating (serum levels. Recent studies from another laboratory failed to document these results. This study's aims were to extend and confirm our previous data, as well as to define possible mechanisms for the discrepant results. Additional aims were to examine MIF expression, as well as the location of MIF's receptor, CD74, in human prostatic adenocarcinoma compared to matched benign prostate. Methods MIF amounts were determined in random serum samples remaining following routine PSA screening by ELISA. Native, denaturing and reducing polyacrylamide gels and Western blot analyses determined the MIF form in serum. Prostate tissue arrays were processed for MIF in situ hybridization and immunohistochemistry for MIF and CD74. MIF released into culture medium from normal epithelial, LNCaP and PC-3 cells was detected by Western blot analysis. Results Median serum MIF amounts were significantly elevated in prostate cancer patients (5.87 ± 3.91 ng/ml; ± interquartile range; n = 115 compared with patients with no documented diagnosis of prostate cancer (2.19 ± 2.65 ng/ml; n = 158. ELISA diluent reagents that included bovine serum albumin (BSA significantly reduced MIF serum detection (p Conclusion Increased serum MIF was associated with prostate cancer. Diluent reagents that included BSA resulted in MIF serum immunoassay interference. In addition, significant amounts of complexed MIF (180 kDa under denaturing conditions by Western blot found in the serum do not bind to the MIF capture antibody. Increased MIF mRNA expression was observed in prostatic adenocarcinoma compared to benign tissue from matched samples, supporting our earlier finding of increased MIF gene expression in prostate cancer.

Further evidence for increased macrophage migration inhibitory factor expression in prostate cancer

International Nuclear Information System (INIS)

Meyer-Siegler, Katherine L; Iczkowski, Kenneth A; Vera, Pedro L

2005-01-01

Macrophage migration inhibitory factor (MIF) is a cytokine associated with prostate cancer, based on histologic evidence and circulating (serum) levels. Recent studies from another laboratory failed to document these results. This study's aims were to extend and confirm our previous data, as well as to define possible mechanisms for the discrepant results. Additional aims were to examine MIF expression, as well as the location of MIF's receptor, CD74, in human prostatic adenocarcinoma compared to matched benign prostate. MIF amounts were determined in random serum samples remaining following routine PSA screening by ELISA. Native, denaturing and reducing polyacrylamide gels and Western blot analyses determined the MIF form in serum. Prostate tissue arrays were processed for MIF in situ hybridization and immunohistochemistry for MIF and CD74. MIF released into culture medium from normal epithelial, LNCaP and PC-3 cells was detected by Western blot analysis. Median serum MIF amounts were significantly elevated in prostate cancer patients (5.87 ± 3.91 ng/ml; ± interquartile range; n = 115) compared with patients with no documented diagnosis of prostate cancer (2.19 ± 2.65 ng/ml; n = 158). ELISA diluent reagents that included bovine serum albumin (BSA) significantly reduced MIF serum detection (p < 0.01). MIF mRNA was localized to prostatic epithelium in all samples, but cancer showed statistically greater MIF expression. MIF and its receptor (CD74) were localized to prostatic epithelium. Increased secreted MIF was detected in culture medium from prostate cancer cell lines (LNCaP and PC-3). Increased serum MIF was associated with prostate cancer. Diluent reagents that included BSA resulted in MIF serum immunoassay interference. In addition, significant amounts of complexed MIF (180 kDa under denaturing conditions by Western blot) found in the serum do not bind to the MIF capture antibody. Increased MIF mRNA expression was observed in prostatic

Administration of zoledronic acid enhances the effects of docetaxel on growth of prostate cancer in the bone environment

Directory of Open Access Journals (Sweden)

Vessella Robert L

2006-01-01

Full Text Available Abstract Background After development of hormone-refractory metastatic disease, prostate cancer is incurable. The recent history of chemotherapy has shown that with difficult disease targets, combinatorial therapy frequently offers the best chance of a cure. In this study we have examined the effects of a combination of zoledronic acid (ZOL, a new-generation bisphosphonate, and docetaxel on LuCaP 23.1, a prostate cancer xenograft that stimulates the osteoblastic reaction when grown in the bone environment. Methods Intra-tibial injections of LuCaP 23.1 cells were used to generate tumors in the bone environment, and animals were treated with ZOL, docetaxel, or a combination of these. Effects on bone and tumor were evaluated by measurements of bone mineral density and histomorphometrical analysis. Results ZOL decreased proliferation of LuCaP 23.1 in the bone environment, while docetaxel at a dose that effectively inhibited growth of subcutaneous tumors did not show any effects in the bone environment. The combination of the drugs significantly inhibited the growth of LuCaP 23.1 tumors in the bone. Conclusion In conclusion, the use of the osteolysis-inhibitory agent ZOL in combination with docetaxel inhibits growth of prostate tumors in bone and represents a potential treatment option.

Differentially methylated genes and androgen receptor re-expression in small cell prostate carcinomas.

Science.gov (United States)

Kleb, Brittany; Estécio, Marcos R H; Zhang, Jiexin; Tzelepi, Vassiliki; Chung, Woonbok; Jelinek, Jaroslav; Navone, Nora M; Tahir, Salahaldin; Marquez, Victor E; Issa, Jean-Pierre; Maity, Sankar; Aparicio, Ana

2016-03-03

Small cell prostate carcinoma (SCPC) morphology is rare at initial diagnosis but often emerges during prostate cancer progression and portends a dismal prognosis. It does not express androgen receptor (AR) or respond to hormonal therapies. Clinically applicable markers for its early detection and treatment with effective chemotherapy are needed. Our studies in patient tumor-derived xenografts (PDX) revealed that AR-negative SCPC (AR(-)SCPC) expresses neural development genes instead of the prostate luminal epithelial genes characteristic of AR-positive castration-resistant adenocarcinomas (AR(+)ADENO). We hypothesized that the differences in cellular lineage programs are reflected in distinct epigenetic profiles. To address this hypothesis, we compared the DNA methylation profiles of AR(-) and AR(+) PDX using methylated CpG island amplification and microarray (MCAM) analysis and identified a set of differentially methylated promoters, validated in PDX and corresponding donor patient samples. We used the Illumina 450K platform to examine additional regions of the genome and the correlation between the DNA methylation profiles of the PDX and their corresponding patient tumors. Struck by the low frequency of AR promoter methylation in the AR(-)SCPC, we investigated this region's specific histone modification patterns by chromatin immunoprecipitation. We found that the AR promoter was enriched in silencing histone modifications (H3K27me3 and H3K9me2) and that EZH2 inhibition with 3-deazaneplanocin A (DZNep) resulted in AR expression and growth inhibition in AR(-)SCPC cell lines. We conclude that the epigenome of AR(-) is distinct from that of AR(+) castration-resistant prostate carcinomas, and that the AR(-) phenotype can be reversed with epigenetic drugs.

Health-related quality of life and treatment outcomes for men with prostate cancer treated by combined external-beam radiotherapy and hormone therapy

International Nuclear Information System (INIS)

Hashine, Katsuyoshi; Azuma, Kouji; Koizumi, Takahiro; Sumiyoshi, Yoshiteru

2005-01-01

Health-related quality of life (HR-QOL) is important when considering the treatment options for prostate cancer. From 1992 to 1998, 57 patients were treated by radiotherapy plus hormone therapy (median age, 79 years; median prostate-specific antigen concentration, 15.0 ng/ml; median radiotherapy dosage, 60 Gy). General HR-QOL was measured by the European Organization for Research and Treatment of Cancer Prostate Cancer QOL Questionnaire, and a newly developed disease-specific QOL survey was used to assess urinary and bowel functions. QOL was also measured in a control group of patients admitted for prostate biopsy. The general HR-QOL scores in the radiation group ranged from 70.0 to 91.3, with sexual problems showing the lowest (i.e., worst) score (38.5). Compared with the control group, the scores in the radiation group were worse for physical function and sexual problems. For disease-specific QOL, the radiation group had worse urinary function than controls, but were more satisfied with their urinary function. There was no difference between the radiation group and controls in satisfaction with bowel function. When the control group was subdivided at into two groups: age 75 years or less, and age over 75 years, the QOL score in the radiation group was the same as that in the subgroup aged over 75 years. In subgroups of the radiation patients, according to survey period, there was no difference between the first and last surveys in longitudinal HR-QOL evaluations. The 5- and 10-year overall survival rates were 67.6% and 41.6%, respectively, and the 5- and 10-year cause-specific survival rates were 97.9% and 94.7%. The combination of radiotherapy and hormone therapy has a good outcome and patients do not experience poor HR-QOL, except for sexual problems. Moreover, the disease-specific QOL is good, especially for urinary bother. (author)

Endocrine Disruption and Human Prostate Cancer

Science.gov (United States)

2008-03-01

PND 28 and 56) and blood collected by cardiac puncture for hormonal analysis. External genitalia, including scrotum, prepuce and penis were visually...early changes to branching morphogenesis reveals multiple mechanisms of prostate enlargement . Journal of Pathology 206:52-61 (IF 5.8) 25. Gold EJ...malignant prostate enlargement in aromatase knockout (ArKO) mice. The Prostate, 56 (1): 54-64 (IF 3.7) Cited 2 42. Gold EJ, Francis RJB, Zimmermann A

Immunohistochemical staining of precursor forms of prostate-specific antigen (proPSA) in metastatic prostate cancer.

Science.gov (United States)

Parwani, Anil V; Marlow, Cameron; Demarzo, Angelo M; Mikolajczyk, Stephen D; Rittenhouse, Harry G; Veltri, Robert W; Chan, Theresa Y

2006-10-01

Precursors of prostate-specific antigen (proPSA) have been previously shown to be more concentrated in prostate cancer tissue. This study characterizes the immunohistochemical staining (IHS) of proPSA forms in metastatic prostate cancer compared with prostate specific antigen (PSA) and prostatic acid phosphatase (PAP). A tissue microarray, consisting of 74 cases of metastatic prostate carcinoma and control tissues, was used. IHS, using monoclonal antibodies against proPSA with a truncated proleader peptide containing 2 amino acids ([-2]pPSA), native ([-5/-7]pPSA), PSA, and PAP, was analyzed. The monoclonal antibodies were specific for both benign and malignant prostatic glandular tissue. IHS with [-5/-7]pPSA showed the least number of cases with negative staining (3%), and the most number of cases with moderate or strong staining (76%). In the 60 cases where all 4 stains could be evaluated, none of them were negative for proPSA and positive for PSA or PAP, and all 7 cases that were negative for both PSA and PAP showed IHS to proPSA. [-5/-7]pPSA (native proPSA) may be a better marker than PSA and PAP in characterizing metastatic prostate adenocarcinoma, with most of the cases showing positivity for the marker. Even cases that were negative for PSA and PAP, were reactive for proPSA. Such enhanced detection is particularly important in poorly differentiated carcinomas involving metastatic sites where prostate carcinoma is a consideration. A panel of markers, including proPSA, should be performed when metastatic prostate carcinoma is in the differential diagnosis.

Serum-sex steroids, gonadotrophins and sex hormone-binding globulin inprostatic hyperplasia

International Nuclear Information System (INIS)

Ansari, Mohammad A. Jalil; Begum, D.; Islam, F.

2008-01-01

Benign prostatic hyperplasia (BPH) develops in elderly males when serumandrogens are relatively lower than in healthy younger males, but is not wellunderstood whether and how sex steroids are altered in prostatic hyperplasia.It is also uncertain that whether there is any change in sex steroids levelsin males older than 40 years of age. The use of androgens in elderly males isoften discouraged because of the probable worsening effect of androgens onprostatism. This study aimed to determine the relationship between prostatichyperplasia and sex steroid levels and whether there is any significantchange in these hormones after the age of 40 years. We studied healthy malesof >40 years with (n=92) or without (n=93) clinical prostatic hyperplasia.Serum testosterone, estradiol, gonadotrophins and sex hormone-bindingglobulin (SHBG) were compared. The hormones and SHGB were also correlatedwith age. No significant difference was found in any hormone in cases withprostatic hyperplasia as compared with the controls. There was no significantage-related change in any hormone except estradiol where as a negativecorrelation (P<0.003) with age was found. Serum sex steroids and SHGBremained unchanged in symptomatic prostatic hyperplasia and except forestrdoil there was no significant age-related change in serum testosterone,gonadotrophins and SHGB in healthy males after the fourth decade. Morestudies are needed to confirm the age-related decline of estrogens in males.(author)

Clear Cell Adenocarcinoma of the Urethra: Review of the Literature

Directory of Open Access Journals (Sweden)

Anthony Kodzo-Grey Venyo

2015-01-01

Full Text Available Background. Clear cell adenocarcinoma of the urethra (CCAU is extremely rare and a number of clinicians may be unfamiliar with its diagnosis and biological behaviour. Aims. To review the literature on CCAU. Methods. Various internet databases were used. Results/Literature Review. (i CCAU occurs in adults and in women in the great majority of cases. (ii It has a particular association with urethral diverticulum, which has been present in 56% of the patients; is indistinguishable from clear cell adenocarcinoma of the female genital tract but is not associated with endometriosis; and probably does not arise by malignant transformation of nephrogenic adenoma. (iii It is usually, readily distinguished from nephrogenic adenoma because of greater cytological a-typicality and mitotic activity and does not stain for prostate-specific antigen or prostatic acid phosphatase. (iv It has been treated by anterior exenteration in women and cystoprostatectomy in men and at times by radiotherapy; chemotherapy has rarely been given. (v CCAU is aggressive with low 5-year survival rates. (vi There is no consensus opinion of treatment options that would improve the prognosis. Conclusions. Few cases of CCAU have been reported. Urologists, gynaecologists, pathologists, and oncologists should report cases of CCAU they encounter and enter them into a multicentric trial to determine the best treatment options that would improve the prognosis.

Unique Approaches to Androgen Effects on Prostate Cancer

National Research Council Canada - National Science Library

Rosner, W; Kahn, S. M

2007-01-01

Sex hormone-binding globulin (SHBG) is a plasma protein that binds andrngens and it acts as a transducer of androgen signaling at the plasma membrane of prostate cancer cells The human prostate cancer cell line LNCaP in addition...

The adaptive immune system promotes initiation of prostate carcinogenesis in a human c-Myc transgenic mouse model.

Science.gov (United States)

Melis, Monique H M; Nevedomskaya, Ekaterina; van Burgsteden, Johan; Cioni, Bianca; van Zeeburg, Hester J T; Song, Ji-Ying; Zevenhoven, John; Hawinkels, Lukas J A C; de Visser, Karin E; Bergman, Andries M

2017-11-07

Increasing evidence from epidemiological and pathological studies suggests a role of the immune system in the initiation and progression of multiple cancers, including prostate cancer. Reports on the contribution of the adaptive immune system are contradictive, since both suppression and acceleration of disease development have been reported. This study addresses the functional role of lymphocytes in prostate cancer development using a genetically engineered mouse model (GEMM) of human c-Myc driven prostate cancer (Hi-Myc mice) combined with B and T cell deficiency (RAG1 -/- mice). From a pre-cancerous stage on, Hi-Myc mice showed higher accumulation of immune cells in their prostates then wild-type mice, of which macrophages were the most abundant. The onset of invasive adenocarcinoma was delayed in Hi-MycRAG1 -/- compared to Hi-Myc mice and associated with decreased infiltration of leukocytes into the prostate. In addition, lower levels of the cytokines CXCL2, CCL5 and TGF-β1 were detected in Hi-MycRAG1 -/- compared to Hi-Myc mouse prostates. These results from a GEMM of prostate cancer provide new insights into the promoting role of the adaptive immune system in prostate cancer development. Our findings indicate that the endogenous adaptive immune system does not protect against de novo prostate carcinogenesis in Hi-Myc transgenic mice, but rather accelerates the formation of invasive adenocarcinomas. This may have implications for the development of novel treatment strategies.

Insufficiency fracture of the sacrum after hormonal therapy and radiotherapy for prostate cancer. A case in which 99mTc-MDP bone scintigraphy was useful for differential diagnosis

International Nuclear Information System (INIS)

Yokokawa, Tokuzou; Shirai, Tatsuo; Ogata, Hitoshi; Furui, Shigeru

2005-01-01

A case in which radiotherapy was requested for bone metastases from prostate carcinoma after hormonal and radiation therapy and diagnosed as insufficiency fracture of the sacrum on bone scan was reported. A 78-year-old man underwent endocrine therapy with luteinizing hormone releasing hormone agonists and radical radiotherapy toward pelvis for prostate cancer. The onset of buttock pain started from the nine-month after the beginning of radiotherapy, and was diagnosed as sacrum metastasis by MRI, and radiotherapy was requested again for pain control. However, on bone scan, butterfly-like changed accumulation was noted, therefore sacrum insufficiency fracture was suspected. Addition of CT inspection and reconfirmation of MRI were performed, and bone metastases became negative, and serial observation was performed of the painkilling effect after that. No tumor marker rise was seen after five months without sigh of new bone metastases and the final diagnosis became insufficient fracture. In order to avoid unnecessary treatment, we think that the view of bone scintigram for diagnosis of sacrum insufficient fracture should be known. (author)

Duration of Androgen Deprivation in Locally Advanced Prostate Cancer: Long-Term Update of NRG Oncology RTOG 9202

International Nuclear Information System (INIS)

Lawton, Colleen A.F.; Lin, Xiaolei; Hanks, Gerald E.; Lepor, Herbert; Grignon, David J.; Brereton, Harmar D.; Bedi, Meena; Rosenthal, Seth A.; Zeitzer, Kenneth L.; Venkatesan, Varagur M.; Horwitz, Eric M.; Pisansky, Thomas M.; Kim, Harold; Parliament, Matthew B.; Rabinovitch, Rachel; Roach, Mack; Kwok, Young; Dignam, James J.; Sandler, Howard M.

2017-01-01

Purpose: Trial RTOG 9202 was a phase 3 randomized trial designed to determine the optimal duration of androgen deprivation therapy (ADT) when combined with definitive radiation therapy (RT) in the treatment of locally advanced nonmetastatic adenocarcinoma of the prostate. Long-term follow-up results of this study now available are relevant to the management of this disease. Methods and Materials: Men (N=1554) with adenocarcinoma of the prostate (cT2c-T4, N0-Nx) with a prostate-specific antigen (PSA) <150 ng/mL and no evidence of distant metastasis were randomized (June 1992 to April 1995) to short-term ADT (STAD: 4 months of flutamide 250 mg 3 times per day and goserelin 3.6 mg per month) and definitive RT versus long-term ADT (LTAD: STAD with definitive RT plus an additional 24 months of monthly goserelin). Results: Among 1520 protocol-eligible and evaluable patients, the median follow-up time for this analysis was 19.6 years. In analysis adjusted for prognostic covariates, LTAD improved disease-free survival (29% relative reduction in failure rate, P<.0001), local progression (46% relative reduction, P=.02), distant metastases (36% relative reduction, P<.0001), disease-specific survival (30% relative reduction, P=.003), and overall survival (12% relative reduction, P=.03). Other-cause mortality (non–prostate cancer) did not differ (5% relative reduction, P=.48). Conclusions: LTAD and RT is superior to STAD and RT for the treatment of locally advanced nonmetastatic adenocarcinoma of the prostate and should be considered the standard of care.

Duration of Androgen Deprivation in Locally Advanced Prostate Cancer: Long-Term Update of NRG Oncology RTOG 9202

Energy Technology Data Exchange (ETDEWEB)

Lawton, Colleen A.F., E-mail: clawton@mcw.edu [Medical College of Wisconsin, Milwaukee, Wisconsin (United States); Lin, Xiaolei [University of Chicago, Chicago, Illinois (United States); Hanks, Gerald E. [Fox Chase Cancer Center, Philadelphia, Pennsylvania (United States); Lepor, Herbert [New York University, New York, New York (United States); Grignon, David J. [Indiana University, Indianapolis, Indiana (United States); Brereton, Harmar D. [Northeast Radiation Oncology Center, Dunmore, Pennsylvania (United States); Bedi, Meena [Medical College of Wisconsin, Milwaukee, Wisconsin (United States); Rosenthal, Seth A. [Sutter General Hospital, Sacramento, California (United States); Zeitzer, Kenneth L. [Albert Einstein Medical Center, Philadelphia, Pennsylvania (United States); Venkatesan, Varagur M. [London Regional Cancer Program, London, Ontario (Canada); Horwitz, Eric M. [Fox Chase Cancer Center, Philadelphia, Pennsylvania (United States); Pisansky, Thomas M. [Mayo Clinic, Rochester, Minnesota (United States); Kim, Harold [Wayne State University-Karmanos Cancer Institute, Detroit, Michigan (United States); Parliament, Matthew B. [Cross Cancer Institute, Edmonton, Alberta (Canada); Rabinovitch, Rachel [University of Colorado Denver, Denver, Colorado (United States); Roach, Mack [University of California, San Francisco, California (United States); Kwok, Young [University of Maryland Medical System, Baltimore, Maryland (United States); Dignam, James J. [University of Chicago, Chicago, Illinois (United States); NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvania (United States); Sandler, Howard M. [Cedars-Sinai Medical Center, Los Angeles, California (United States)

2017-06-01

Purpose: Trial RTOG 9202 was a phase 3 randomized trial designed to determine the optimal duration of androgen deprivation therapy (ADT) when combined with definitive radiation therapy (RT) in the treatment of locally advanced nonmetastatic adenocarcinoma of the prostate. Long-term follow-up results of this study now available are relevant to the management of this disease. Methods and Materials: Men (N=1554) with adenocarcinoma of the prostate (cT2c-T4, N0-Nx) with a prostate-specific antigen (PSA) <150 ng/mL and no evidence of distant metastasis were randomized (June 1992 to April 1995) to short-term ADT (STAD: 4 months of flutamide 250 mg 3 times per day and goserelin 3.6 mg per month) and definitive RT versus long-term ADT (LTAD: STAD with definitive RT plus an additional 24 months of monthly goserelin). Results: Among 1520 protocol-eligible and evaluable patients, the median follow-up time for this analysis was 19.6 years. In analysis adjusted for prognostic covariates, LTAD improved disease-free survival (29% relative reduction in failure rate, P<.0001), local progression (46% relative reduction, P=.02), distant metastases (36% relative reduction, P<.0001), disease-specific survival (30% relative reduction, P=.003), and overall survival (12% relative reduction, P=.03). Other-cause mortality (non–prostate cancer) did not differ (5% relative reduction, P=.48). Conclusions: LTAD and RT is superior to STAD and RT for the treatment of locally advanced nonmetastatic adenocarcinoma of the prostate and should be considered the standard of care.

The Hypercoagulable state in Hyperthyroidism is mediated via the Thyroid Hormone β Receptor pathway

NARCIS (Netherlands)

Elbers, Laura P. B.; Moran, Carla; Gerdes, Victor E. A.; van Zaane, Bregje; Meijers, Joost C. M.; Endert, Erik; Lyons, Greta; Chatterjee, V. Krishna; Bisschop, Peter H.; Fliers, Eric

2016-01-01

Hyperthyroidism is associated with a hypercoagulable state, but the underlying mechanism is unknown. Patients with resistance to thyroid hormone (RTH) due to defective thyroid hormone receptor β (TRβ) exhibit elevated circulating thyroid hormones (TH) with refractoriness to TH action in

A partial differential equation model and its reduction to an ordinary differential equation model for prostate tumor growth under intermittent hormone therapy.

Science.gov (United States)

Tao, Youshan; Guo, Qian; Aihara, Kazuyuki

2014-10-01

Hormonal therapy with androgen suppression is a common treatment for advanced prostate tumors. The emergence of androgen-independent cells, however, leads to a tumor relapse under a condition of long-term androgen deprivation. Clinical trials suggest that intermittent androgen suppression (IAS) with alternating on- and off-treatment periods can delay the relapse when compared with continuous androgen suppression (CAS). In this paper, we propose a mathematical model for prostate tumor growth under IAS therapy. The model elucidates initial hormone sensitivity, an eventual relapse of a tumor under CAS therapy, and a delay of a relapse under IAS therapy, which are due to the coexistence of androgen-dependent cells, androgen-independent cells resulting from reversible changes by adaptation, and androgen-independent cells resulting from irreversible changes by genetic mutations. The model is formulated as a free boundary problem of partial differential equations that describe the evolution of populations of the abovementioned three types of cells during on-treatment periods and off-treatment periods. Moreover, the model can be transformed into a piecewise linear ordinary differential equation model by introducing three new volume variables, and the study of the resulting model may help to devise optimal IAS schedules.

Incidental detection of prostate-specific antigen-negative metastatic prostate cancer initially presented with solitary pulmonary nodule on fluorodeoxyglucose positron emission tomography/computed tomography

International Nuclear Information System (INIS)

Erdogan, Ezgi Basak; Buyukpinarbasili, Nur; Ziyade, Sedat; Akman, Tolga; Turk, Haci Mehmet; Aydin, Mehmet

2005-01-01

A 71-year-old male patient with solitary pulmonary nodule underwent fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) showing slightly increased FDG uptake in this nodule. In addition, PET/CT detected hypermetabolic sclerotic bone lesions in the right second rib and 7 th thoracic vertebrae, which were interpreted as possible metastases, and mildly increased FDG uptake in the prostate gland highly suspicious of malignancy. The patient's prostate-specific antigen (PSA) level was within normal range (3.8 ng/dL). The histopathological examination of the lung nodule and right second rib lesion proved metastases from prostate cancer, then the prostate biopsy-confirmed prostate adenocarcinoma. The unique feature of this case is to emphasize the importance of performing PET/CT for solitary pulmonary nodule in detecting PSA-negative metastatic prostate cancer. This case indicated that it should be kept in mind that, even if the PSA is negative, a lung metastasis of prostate cancer may be an underlying cause in patients evaluated for solitary pulmonary nodule by FDG PET/CT

Molecular Targets for Radiation Oncology in Prostate Cancer

International Nuclear Information System (INIS)

Wang, Tao; Languino, Lucia R.; Lian, Jane; Stein, Gary; Blute, Michael; FitzGerald, Thomas J.

2011-01-01

Recent selected developments of the molecular science of prostate cancer (PrCa) biology and radiation oncology are reviewed. We present potential targets for molecular integration treatment strategies with radiation therapy (RT), and highlight potential strategies for molecular treatment in combination with RT for patient care. We provide a synopsis of the information to date regarding molecular biology of PrCa, and potential integrated research strategy for improved treatment of PrCa. Many patients with early-stage disease at presentation can be treated effectively with androgen ablation treatment, surgery, or RT. However, a significant portion of men are diagnosed with advanced stage/high-risk disease and these patients progress despite curative therapeutic intervention. Unfortunately, management options for these patients are limited and are not always successful including treatment for hormone refractory disease. In this review, we focus on molecules of extracellular matrix component, apoptosis, androgen receptor, RUNX, and DNA methylation. Expanding our knowledge of the molecular biology of PrCa will permit the development of novel treatment strategies integrated with RT to improve patient outcome

APPLICATION IMMUNOHISTOCHEMICALLY RESEARCH METHODS IN THE DIAGNOSIS OF PROSTATE CANCER

Directory of Open Access Journals (Sweden)

S. A. Pulbere

2017-01-01

Full Text Available Introduction. The actual problem of modern urology remains differential diagnostics of various diseases of the prostate gland. The purpose of the study. Increasing the effectiveness of differential diagnosis of diseases of the prostate. Materials and methods. In the biopsy specimens of patients with benign prostatic hyperplasia (BPH and prostate cancer (PCa, an immunohistochemical study of the production of the Ki-67 proliferation marker, matrix metalloproteinase-9, the matrix metalloproteinase inhibitor TIMP-1, and the distribution of collagen type IV was performed. Results. A moderate positive correlation was found between Gleason gradation and the cell proliferation index for Ki 67 (rs = 0.674 and a moderate negative correlation of Gleason gradation with the level of production of matrix metalloproteinase-9 (rs = -0.660. A weak significant negative correlation was established between the level of proliferative cell activity and the production of  MMP-9 tumor cells (rs = -0.369. A significant decrease in the level of MMP-9 and TIMP-1 in adenocarcinoma of different grades was revealed. The invasive properties of tumor cells, expressed in the destruction of collagen of the IV type of the basal membrane and connective tissue prostatic stroma, are mediated by the imbalance between MMP-9 and the protein blocking this enzyme - TIMP-1, whose production decreases in adenocarcinomas of different grades compared with BPH. Conclusions: 1. BPH is characterized by high production of MMP-9 type, which destroys the collagen of the basal membranes and stroma, the proteolytic action of which is blocked by the high content of TIMP-1.

Management of patients with advanced prostate cancer

DEFF Research Database (Denmark)

Gillessen, S; Omlin, A; Attard, G

2015-01-01

The first St Gallen Advanced Prostate Cancer Consensus Conference (APCCC) Expert Panel identified and reviewed the available evidence for the ten most important areas of controversy in advanced prostate cancer (APC) management. The successful registration of several drugs for castration......-resistant prostate cancer and the recent studies of chemo-hormonal therapy in men with castration-naïve prostate cancer have led to considerable uncertainty as to the best treatment choices, sequence of treatment options and appropriate patient selection. Management recommendations based on expert opinion...

Development of New Treatments for Prostate Cancer

Energy Technology Data Exchange (ETDEWEB)

DiPaola, R. S.; Abate-Shen, C.; Hait, W. N.

2005-02-01

The Dean and Betty Gallo Prostate Cancer Center (GPCC) was established with the goal of eradicating prostate cancer and improving the lives of men at risk for the disease through research, treatment, education and prevention. GPCC was founded in the memory of Dean Gallo, a beloved New Jersey Congressman who died tragically of prostate cancer diagnosed at an advanced stage. GPCC unites a team of outstanding researchers and clinicians who are committed to high-quality basic research, translation of innovative research to the clinic, exceptional patient care, and improving public education and awareness of prostate cancer. GPCC is a center of excellence of The Cancer Institute of New Jersey, which is the only NCI-designated comprehensive cancer center in the state. GPCC efforts are now integrated well as part of our Prostate Program at CINJ, in which Dr. Robert DiPaola and Dr. Cory Abate-Shen are co-leaders. The Prostate Program unites 19 investigators from 10 academic departments who have broad and complementary expertise in prostate cancer research. The overall goal and unifying theme is to elucidate basic mechanisms of prostate growth and oncogenesis, with the ultimate goal of promoting new and effective strategies for the eradication of prostate cancer. Members' wide range of research interests collectively optimize the chances of providing new insights into normal prostate biology and unraveling the molecular pathophysiology of prostate cancer. Cell culture and powerful animal models developed by program members recapitulate the various stages of prostate cancer progression, including prostatic intraepithelial neoplasia, adenocarcinoma, androgen-independence, invasion and metastases. These models promise to further strengthen an already robust program of investigator-initiated therapeutic clinical trials, including studies adopted by national cooperative groups. Efforts to translate laboratory results into clinical studies of early detection and

Calcitonin and parathyroid hormone in blood serum of cancer patients

Energy Technology Data Exchange (ETDEWEB)

Tkacheva, G A; Kirsanov, A G; Burenin, I S [Akademiya Meditsinskikh Nauk SSSR, Moscow. Onkologicheskij Nauchnyj Tsentr

1982-01-01

A comparative radiommunoassay in the ratio of calcitonin and parathyroid hormone secretion was carried out in healthy controls (young and older than 40 years), patients with benign tumors, inflamatory processes and malignancies of the stomach, kidney, breast, prostate and lung. A significant increase in the ''calcitonin index'' (ratio of molar concentrations of calcitonin and parathyroid hormone) was established in patients with cancer of the breast, prostate and skeletal metastases of lung cancer, irrespective of the presence of primary tumor. This index is irrelevant in cases of gastric and renal carcinoma and cannot be used as indication of skeletal dissemination because of the predominant level of parathyroid hormone secretion.

Salvage brachytherapy for local recurrences of prostate cancer treated previously with radiotherapy.

Science.gov (United States)

Gawkowska-Suwinska, Marzena; Fijałkowski, Marek; Białas, Brygida; Szlag, Marta; Kellas-Ślęczka, Sylwia; Nowicka, Elżbieta; Behrendt, Katarzyna; Plewicki, Grzegorz; Smolska-Ciszewska, Beata; Giglok, Monika; Zajusz, Aleksander; Owczarek, Grzegorz

2009-12-01

The aim of the study was to analyze early effects and toxicity of salvage high dose rate brachytherapy for local recurrences of adenocarcinoma of the prostate after external beam radiotherapy (EBRT). In MCS Memorial Institute of Oncology in Gliwice a research programme on salvage HDR brachytherapy for local recurrences of prostate cancer treated previously with EBRT has been ongoing since February 2008. The treatment consisted of 3 fractions of 10 Gy each given every 14 days. Maximal urethral doses were constrained to be ≤ 120% of the prescribed dose. Maximal bladder and rectum doses were constrained to be ≤ 70% of the prescribed dose. Fifteen eligible patients were treated and analyzed from February 2008. All patients completed the treatment without major complications. The most common early complications were: macroscopic haematuria, pain in lower part of the abdomen, and transient dysuria. During the first week after the procedure a transient increase in IPSS score was noticed. The Foley catheter was removed on day 2 to 5. No complications after spinal anaesthesia were observed. Acute toxicity according to EORTC/RTOG was low. For bladder EORTC/RTOG score ranged from 0 to 2. Only in two patients grade 1 toxicity for rectum was observed. The follow-up ranged from 3 to 9 months. In one patient grade 2 rectal toxicity was observed, and one had urethral stricture. Other patients did not have any other significant late toxicity of the treatment. Two patients developed bone metastases. Salvage brachytherapy for localized prostate cancer (3 × 10 Gy every 14 days) seems to be a safe and well tolerated procedure. A significant decline in prostate-specific antigen (PSA) level is seen in patients with hormone-responsive cancer. Long-term efficiency and toxicity of the procedure are yet to be established.

[Epigenetics of prostate cancer].

Science.gov (United States)

Yi, Xiao-Ming; Zhou, Wen-Quan

2010-07-01

Prostate cancer is one of the most common malignant tumors in males, and its etiology and pathogenesis remain unclear. Epigenesis is involved in prostate cancer at all stages of the process, and closely related with its growth and metastasis. DNA methylation and histone modification are the most important manifestations of epigenetics in prostate cancer. The mechanisms of carcinogenesis of DNA methylation include whole-genome hypomethylation, aberrant local hypermethylation of promoters and genomic instability. DNA methylation is closely related to the process of prostate cancer, as in DNA damage repair, hormone response, tumor cell invasion/metastasis, cell cycle regulation, and so on. Histone modification causes corresponding changes in chromosome structure and the level of gene transcription, and it may affect the cycle, differentiation and apoptosis of cells, resulting in prostate cancer. Some therapies have been developed targeting the epigenetic changes in prostate cancer, including DNA methyltransferases and histone deacetylase inhibitors, and have achieved certain desirable results.

Disparities in Prostate Cancer Treatment Modality and Quality of Life

Science.gov (United States)

2010-11-01

producing hormones) 1 0 10 11 B8f. Watchful waiting (no treatment, wait and see if your prostate cancer grows) 1 0 10 11 B8g. Cryotherapy (process...your prostate cancer grows) 7 Cryotherapy (process to freeze and destroy prostate tissue) 8 Chemotherapy (use of anti- cancer drugs) 9 Any other...and attitudes concerning prostate cancer and preventative measures. Prostate Cancer Questionnaire IRB1012# – Version 3 08/01/08 33 Now, I

Prostate-Derived Ets Transcription Factor Overexpression is Associated with Nodal Metastasis, Hormone Receptor Positivity in Invasive Breast Cancer

Directory of Open Access Journals (Sweden)

Simon Turcotte

2007-10-01

Full Text Available Prostate-derived Ets transcription factor (PDEF has recently been associated with invasive breast cancer, but no expression profile has been defined in clinical specimens. We undertook a comprehensive PDEF transcriptional expression study of 86 breast cancer clinical specimens, several cell lines, normal tissues. PDEF expression profile was analyzed according to standard clinicopathologic parameters, compared with hormonal receptor, HER-2/neu status, to the expression of the new tumor biomarker Dikkopf-1 (DKK1. Wide ranging PDEF overexpression was observed in 74% of tested tumors, at higher levels than the average expression found in normal breasts. High PDEF expression was associated with hormone receptor positivity (P < .001, moderate to good differentiation (less than grade III, P = .01, dissemination to axillary lymph nodes (P = .002. PDEF was an independent risk factor for nodal involvement (multivariate analysis, odds ratio 1.250, P = .002. It was expressed in a different subgroup compared to DKK1-expressing tumors (P < .001. Our data imply that PDEF mRNA expression could be useful in breast cancer molecular staging. Further insights into PDEF functions at the protein level, possible links with hormone receptors biology, bear great potential for new therapeutic avenues.

On-line conformal HDR dose escalation trial in prostate cancer

International Nuclear Information System (INIS)

Martinez, Alvaro; Stromberg, Jannifer; Edmundson, Gregory; Gustafson, Gary; Vicini, Frank; Brabbins, Donald

1996-01-01

Purpose: To improve treatment results on prostatic adenocarcinoma, we began the first prospective Phase I/II dose-escalating clinical trial of conformal brachytherapy (CB) and concurrent external beam irradiation. Methods and Materials: Fifty-four patients with T2b-T3c prostatic adenocarcinoma received 172 transperineal conformal high-dose rate (HDR) boost implants. All patients received concomitant external beam pelvic irradiation. Dose escalation of the three HDR fractions were: 5.5 Gy (18 patients), 6 Gy (15 patients), and 6.5 Gy (21 patients). The urethra, anterior rectal wall, and prostate boundaries were identified individually and outlined at 5 mm intervals from the base to the apex of the gland. The CB using real-time ultrasound guidance with interactive online isodose distributions was performed on an outpatient basis. As needles were placed into the prostate, corrections for prostate displacement were recorded and the isodose distributions were recalculated to represent the new relationship between the needles, prostate, and normal structures. Results: Craniocaudal motion of the gland ranged from 0.5-2.0 cm (mean=1.0 cm), whereas lateral displacement was 0.1-0.4 cm. With the interactive online planning system, organ motion was immediately detected, accounted for, and corrected prior to each HDR treatment. The rectal dose has ranged from 45 to 87%, and the urethral dose from 97 to 112% of the prostate dose. Negative prostatic biopsies at 18 months were seen in (30(32)) patients. Biochemical (PSA <1.5 ng/ml) control at 36 months is is 89%. It is significant that operator dependence has been completely removed because the interactive online planning system uniformly guides the physicians. Conclusions: With ultrasound guidance and the interactive online dosimetry system, organ motion is insignificant because it can be corrected during the procedure. Common pitfalls of brachytherapy, including operator dependence and difficulty with reproducibility, have been

Neuroendocrine differentiation in prostate cancer – a review

Directory of Open Access Journals (Sweden)

R. Popescu

2015-12-01

Full Text Available Objectives: This review aims to provide practicing clinicians with the most recent knowledge of the biological nature of prostate cancer especially the information regarding neuroendocrine differentiation. Methods: Review of the literature using PubMed search and scientific journal publications. Results: Much progress has been made towards an understanding of the development and progression of prostate cancer. The prostate is a male accessory sex gland which produces a fraction of seminal fluid. The normal human prostate is composed of a stromal compartment (which contains: nerves, fibroblast, smooth muscle cells, macrophages surrounding glandular acins – epithelial cells. Neuroendocrine cells are one of the epithelial populations in the normal prostate and are believed to provide trophic signals trough the secretion of neuropeptides that diffuse and influence surrounding epithelial cells. Prostate cancer is the most frequently diagnosed malignancy in men. In prostate cancer, neuroendocrine cells can stimulate growth of surrounding prostate adenocarcinoma cells (proliferation of neighboring cancer cells in a paracrine manner by secretion of neuroendocrine products. Neuroendocrine prostate cancer is an aggressive variant of prostate cancer that commonly arises in later stages of castration resistant prostate cancer. The detection of neuroendocrine prostate cancer has clinical implications. These patients are often treated with platinum chemotherapy rather than with androgen receptor targeted therapies. Conclusion: This review shows the need to improve our knowledge regarding diagnostic and treatment methods of the Prostate Cancer, especially cancer cells with neuroendocrine phenotype.

Care of the cancer survivor: metabolic syndrome following hormone-modifying therapy

OpenAIRE

Redig, Amanda J.; Munshi, Hidayatullah G.

2010-01-01

Emerging evidence implicates metabolic syndrome as a long-term cancer risk factor but also suggests that certain cancer therapies may increase patients’ risk of developing metabolic syndrome secondary to cancer therapy. In particular, breast cancer and prostate cancer are driven in part by sex hormones, thus treatment for both diseases is often based on hormone-modifying therapy. Androgen suppression therapy in men with prostate cancer is associated with dyslipidemia, increasing risk of cardi...

Vitamins, metabolomics, and prostate cancer.

Science.gov (United States)

Mondul, Alison M; Weinstein, Stephanie J; Albanes, Demetrius

2017-06-01

How micronutrients might influence risk of developing adenocarcinoma of the prostate has been the focus of a large body of research (especially regarding vitamins E, A, and D). Metabolomic profiling has the potential to discover molecular species relevant to prostate cancer etiology, early detection, and prevention, and may help elucidate the biologic mechanisms through which vitamins influence prostate cancer risk. Prostate cancer risk data related to vitamins E, A, and D and metabolomic profiling from clinical, cohort, and nested case-control studies, along with randomized controlled trials, are examined and summarized, along with recent metabolomic data of the vitamin phenotypes. Higher vitamin E serologic status is associated with lower prostate cancer risk, and vitamin E genetic variant data support this. By contrast, controlled vitamin E supplementation trials have had mixed results based on differing designs and dosages. Beta-carotene supplementation (in smokers) and higher circulating retinol and 25-hydroxy-vitamin D concentrations appear related to elevated prostate cancer risk. Our prospective metabolomic profiling of fasting serum collected 1-20 years prior to clinical diagnoses found reduced lipid and energy/TCA cycle metabolites, including inositol-1-phosphate, lysolipids, alpha-ketoglutarate, and citrate, significantly associated with lower risk of aggressive disease. Several active leads exist regarding the role of micronutrients and metabolites in prostate cancer carcinogenesis and risk. How vitamins D and A may adversely impact risk, and whether low-dose vitamin E supplementation remains a viable preventive approach, require further study.

High-Dose-Rate Brachytherapy of a Single Implant With Two Fractions Combined With External Beam Radiotherapy for Hormone-Naive Prostate Cancer

International Nuclear Information System (INIS)

Sato, Morio; Mori, Takashi; Shirai, Shintaro; Kishi, Kazushi; Inagaki, Takeshi; Hara, Isao

2008-01-01

Purpose: To evaluate the preliminary outcomes of high-dose-rate (HDR) brachytherapy of a single implant with two fractions and external beam radiotherapy (EBRT) for hormone-naive prostate cancer. Methods and Materials: Between March 2000 and Sept 2003, a total of 53 patients with tumor Stage T1c-T3b N0 M0 prostate cancer were treated with HDR brachytherapy boost doses (7.5 Gy/fraction) and 50-Gy EBRT during a 5.5-week period. Median follow-up was 61 months. Patients were divided into groups with localized (T1c-T2b) and advanced disease (T3a-T3b). We used the American Society for Therapeutic Radiology and Oncology (ASTRO) definition for biochemical failure. According to recommendations of the Radiation Therapy Oncology Group-ASTRO Phoenix Consensus Conference, biochemical failure-free control rates (BF-FCRs) at 3 years were investigated as 2 years short of the median follow-up. Results: Between April 2000 and Sept 2007, Common Terminology Criteria for Adverse Events Version 2.0 late Grade 2 genitourinary and gastrointestinal toxicity rates were 0% and 3.8%, respectively. Erectile preservation was 25% at 5 years. Overall survival was 88.1% and cause-specific survival was 100%. At 3 years, ASTRO BF-FCRs of the localized and advanced groups were 100% and 42%, respectively (p = 0.001). Conclusions: The HDR brachytherapy of a single implant with two fractions plus EBRT is effective in treating patients with localized hormone-naive prostate cancer, with the least genitourinary and gastrointestinal toxicities; however, longer median BF-FCR follow-up is required to assess these findings

Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer: Long-Term Survival Analysis of the Randomized Phase III E3805 CHAARTED Trial.

Science.gov (United States)

Kyriakopoulos, Christos E; Chen, Yu-Hui; Carducci, Michael A; Liu, Glenn; Jarrard, David F; Hahn, Noah M; Shevrin, Daniel H; Dreicer, Robert; Hussain, Maha; Eisenberger, Mario; Kohli, Manish; Plimack, Elizabeth R; Vogelzang, Nicholas J; Picus, Joel; Cooney, Matthew M; Garcia, Jorge A; DiPaola, Robert S; Sweeney, Christopher J

2018-04-10

Purpose Docetaxel added to androgen-deprivation therapy (ADT) significantly increases the longevity of some patients with metastatic hormone-sensitive prostate cancer. Herein, we present the outcomes of the CHAARTED (Chemohormonal Therapy Versus Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer) trial with more mature follow-up and focus on tumor volume. Patients and Methods In this phase III study, 790 patients with metastatic hormone-sensitive prostate cancer were equally randomly assigned to receive either ADT in combination with docetaxel 75 mg/m 2 for up to six cycles or ADT alone. The primary end point of the study was overall survival (OS). Additional analyses of the prospectively defined low- and high-volume disease subgroups were performed. High-volume disease was defined as presence of visceral metastases and/or ≥ four bone metastases with at least one outside of the vertebral column and pelvis. Results At a median follow-up of 53.7 months, the median OS was 57.6 months for the chemohormonal therapy arm versus 47.2 months for ADT alone (hazard ratio [HR], 0.72; 95% CI, 0.59 to 0.89; P = .0018). For patients with high-volume disease (n = 513), the median OS was 51.2 months with chemohormonal therapy versus 34.4 months with ADT alone (HR, 0.63; 95% CI, 0.50 to 0.79; P OS benefit was observed (HR, 1.04; 95% CI, 0.70 to 1.55; P = .86). Conclusion The clinical benefit from chemohormonal therapy in prolonging OS was confirmed for patients with high-volume disease; however, for patients with low-volume disease, no OS benefit was discerned.

Role of Hsp90 in Androgen-Refractory Prostate Cancer

Science.gov (United States)

2010-03-01

designed siRNA sequence using Intergrated DNA Technologies RNAi online software tool (IDT, Coralville, IA). The sequence of siRNA specific for...proliferation and production of prostate-specific antigen in androgen-sensitive pros- tatic cancer cells, LNCaP, by dihydrotestosterone. Endocrinology 136

Characterization of Heterogeneous Prostate Tumors in Targeted Pten Knockout Mice.

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Hanneke Korsten

Full Text Available Previously, we generated a preclinical mouse prostate tumor model based on PSA-Cre driven inactivation of Pten. In this model homogeneous hyperplastic prostates (4-5m developed at older age (>10m into tumors. Here, we describe the molecular and histological characterization of the tumors in order to better understand the processes that are associated with prostate tumorigenesis in this targeted mouse Pten knockout model. The morphologies of the tumors that developed were very heterogeneous. Different histopathological growth patterns could be identified, including intraductal carcinoma (IDC, adenocarcinoma and undifferentiated carcinoma, all strongly positive for the epithelial cell marker Cytokeratin (CK, and carcinosarcomas, which were negative for CK. IDC pattern was already detected in prostates of 7-8 month old mice, indicating that it could be a precursor stage. At more than 10 months IDC and carcinosarcoma were most frequently observed. Gene expression profiling discriminated essentially two molecular subtypes, denoted tumor class 1 (TC1 and tumor class 2 (TC2. TC1 tumors were characterized by high expression of epithelial markers like Cytokeratin 8 and E-Cadherin whereas TC2 tumors showed high expression of mesenchyme/stroma markers such as Snail and Fibronectin. These molecular subtypes corresponded with histological growth patterns: where TC1 tumors mainly represented adenocarcinoma/intraductal carcinoma, in TC2 tumors carcinosarcoma was the dominant growth pattern. Further molecular characterization of the prostate tumors revealed an increased expression of genes associated with the inflammatory response. Moreover, functional markers for senescence, proliferation, angiogenesis and apoptosis were higher expressed in tumors compared to hyperplasia. The highest expression of proliferation and angiogenesis markers was detected in TC2 tumors. Our data clearly showed that in the genetically well-defined PSA-Cre;Pten-loxP/loxP prostate tumor

Glucose Metabolism of Human Prostate Cancer Mouse Xenografts

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Hossein Jadvar

2005-04-01

Full Text Available We hypothesized that the glucose metabolism of prostate cancer is modulated by androgen. We performed in vivo biodistribution and imaging studies of [F-18] fluorodeoxyglucose (FDG accumulation in androgen-sensitive (CWR-22 and androgen-independent (PC-3 human prostate cancer xenografts implanted in castrated and noncastrated male athymic mice. The growth pattern of the CWR-22 tumor was best approximated by an exponential function (tumor size in mm3 = 14.913 e0.108 × days, R2 = .96, n = 5. The growth pattern of the PC-3 tumor was best approximated by a quadratic function (tumor size in mm3 = 0.3511 × days2 + 49.418 × day −753.33, R2 = .96, n = 3. The FDG accumulation in the CWR-22 tumor implanted in the castrated mice was significantly lower, by an average of 55%, in comparison to that implanted in the noncastrated host (1.27 vs. 2.83, respectively, p < .05. The 3-week maximal standardized uptake value (SUVmax was 0.99 ± 0.43 (mean ± SD for CWR-22 and 1.21 ± 0.32 for PC-3, respectively. The 5-week SUVmax was 1.22 ± 0.08 for CWR-22 and 1.35 ± 0.17 for PC-3, respectively. The background muscle SUVmax was 0.53 ± 0.11. Glucose metabolism was higher in the PC-3 tumor than in the CWR-22 tumor at both the 3-week (by 18% and the 5-week (by 9.6% micro-PET imaging sessions. Our results support the notions that FDG PET may be useful in the imaging evaluation of response to androgen ablation therapy and in the early prediction of hormone refractoriness in men with metastatic prostate cancer.

Ethnicity and Prostate Cancer in Southern Nigeria: A Preliminary Report.

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Sapira, Monday K; Eke, Ndubuisi; Nwofor, Alexander Me

2015-01-01

The natural history of prostate cancer varies among patients. The aim of this study is to detect any variations in clinical and pathological characteristics of the tumor in patients from different ethnic groups in Southern Nigeria. Consecutive patients who presented with features of prostatic diseases at the Urology Units of University of Port Harcourt Teaching Hospital, Port Harcourt and Nnamdi Azikiwe University Teaching Hospital, Nnewi, were evaluated prospectively with history, physical examination, and relevant investigations using a proforma. Data obtained were collated and analyzed statistically using the Chi-square test and Microsoft Excel. Of 187 patients studied, 169 were analyzed. Eighty-six were Ibos, 31 Ijaws, 25 Ikwerres, and 12 Ogonis. Two were from each Etche, Urhobo, Opobo, and Effik; 4 from Andoni, and 3 Ibibio. Fifty-seven (66.3%) Ibos presented with the disease at higher ages (70-80 years) than 19 (61.3%) Ijaws and 11 (91.7%) Ogonis. These age differences were statistically significant with 95% and 99.9% confidence, respectively. All cases were adenocarcinomas. Clinical features, pattern of serum prostate-specific antigen levels, grades of the tumors, tumor metastases, and complications were similar for all ethnic groups. Although more Ibos had tumors with relatively more aggressive metastatic features, there was no statistical significance. Clinical and pathological features of adenocarcinoma of the prostate in Ibos, Ikwerres, Ijaws, and Ogonis were found to be similar. However, Ibos presented with the disease at older ages than Ijaws and Ogonis.

Prostate cancer outcome in Burkina Faso

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Yameogo Clotaire

2011-09-01

Full Text Available Abstract Introduction African-American black men race is one of non-modifiable risk factors confirmed for prostate cancer. Many studies have been done in USA among African- American population to evaluate prostate cancer disparities. Compared to the USA very few data are available for prostate cancer in Sub-Saharan African countries. The objective of this study was to describe incident prostate cancer (PC diagnosis characteristics in Burkina Faso (West Africa. Methods We performed a prospective non randomized patient’s cohort study of new prostate cancer cases diagnosed by histological analysis of transrectal prostate biopsies in Burkina Faso. Study participants included 166 patients recruited at the urology division of the university hospital of Ouagadougou. Age of the patients, clinical symptoms, digital rectal examination (DRE result, serum prostate-specific antigen (PSA level, histological characteristics and TNM classification were taking in account in this study. Results 166 transrectal prostate biopsies (TRPB were performed based on high PSA level or abnormal DRE. The prostate cancer rate on those TRPB was 63, 8 % (n=106. The mean age of the patients was 71, 5 years (52 to 86. Urinary retention was the first clinical patterns of reference in our institution (55, 7 %, n = 59. Most patients, 56, 6 % (n = 60 had a serum PSA level over than 100 ng/ml. All the patients had adenocarcinoma on histological study of prostate biopsy cores. The majority of cases (54, 7 % n = 58 had Gleason score equal or higher than 7. Conclusion Prostate cancer is diagnosed at later stages in our country. Very high serum PSA level and poorly differentiated tumors are the two major characteristics of PC at the time of diagnosis.

Withanolides from Aeroponically Grown Physalis peruviana and Their Selective Cytotoxicity to Prostate Cancer and Renal Carcinoma Cells.

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Xu, Ya-Ming; Wijeratne, E M Kithsiri; Babyak, Ashley L; Marks, Hanna R; Brooks, Alan D; Tewary, Poonam; Xuan, Li-Jiang; Wang, Wen-Qiong; Sayers, Thomas J; Gunatilaka, A A Leslie

2017-07-28

Investigation of aeroponically grown Physalis peruviana resulted in the isolation of 11 new withanolides, including perulactones I-L (1-4), 17-deoxy-23β-hydroxywithanolide E (5), 23β-hydroxywithanolide E (6), 4-deoxyphyperunolide A (7), 7β-hydroxywithanolide F (8), 7β-hydroxy-17-epi-withanolide K (9), 24,25-dihydro-23β,28-dihydroxywithanolide G (10), and 24,25-dihydrowithanolide E (11), together with 14 known withanolides (12-25). The structures of 1-11 were elucidated by the analysis of their spectroscopic data, and 12-25 were identified by comparison of their spectroscopic data with those reported. All withanolides were evaluated for their cytotoxic activity against a panel of tumor cell lines including LNCaP (androgen-sensitive human prostate adenocarcinoma), 22Rv1 (androgen-resistant human prostate adenocarcinoma), ACHN (human renal adenocarcinoma), M14 (human melanoma), SK-MEL-28 (human melanoma), and normal human foreskin fibroblast cells. Of these, the 17β-hydroxywithanolides (17-BHWs) 6, 8, 9, 11-13, 15, and 19-22 showed selective cytotoxic activity against the two prostate cancer cell lines LNCaP and 22Rv1, whereas 13 and 20 exhibited selective toxicity for the ACHN renal carcinoma cell line. These cytotoxicity data provide additional structure-activity relationship information for the 17-BHWs.

Elucidation of the Molecular Mechanisms Underlying Lymph Node Metastasis in Prostate Cancer

National Research Council Canada - National Science Library

Datta, Kaustubh

2007-01-01

.... Again, the cancer will often progress to an androgen refractory (independent), metastatic stage. Recent reports have suggested that the expression of VEGF-C is directly correlated with lymph node dissemination in prostate cancer...

Differential action of glycoprotein hormones: significance in cancer progression.

Science.gov (United States)

Govindaraj, Vijayakumar; Arya, Swathy V; Rao, A J

2014-02-01

Growth of multicellular organisms depends on maintenance of proper balance between proliferation and differentiation. Any disturbance in this balance in animal cells can lead to cancer. Experimental evidence is provided to conclude with special reference to the action of follicle-stimulating hormone (FSH) on Sertoli cells, and luteinizing hormone (LH) on Leydig cells that these hormones exert a differential action on their target cells, i.e., stimulate proliferation when the cells are in an undifferentiated state which is the situation with cancer cells and promote only functional parameters when the cell are fully differentiated. Hormones and growth factors play a key role in cell proliferation, differentiation, and apoptosis. There is a growing body of evidence that various tumors express some hormones at high levels as well as their cognate receptors indicating the possibility of a role in progression of cancer. Hormones such as LH, FSH, and thyroid-stimulating hormone have been reported to stimulate cell proliferation and act as tumor promoter in a variety of hormone-dependent cancers including gonads, lung, thyroid, uterus, breast, prostate, etc. This review summarizes evidence to conclude that these hormones are produced by some cancer tissues to promote their own growth. Also an attempt is made to explain the significance of the differential action of hormones in progression of cancer with special reference to prostate cancer.

Incidental Prostate Cancer in Patients Undergoing Radical Cystoprostatectomy for Bladder Cancer

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Mustafa Hiroš

2008-05-01

Full Text Available The objective of this work is to verify the incidence of incidental prostate adenocarcinoma in patients who underwent radical cystoprostatectomy for invasive bladder carcinoma. We have retrospectively reviewed patients who underwent radical cystoprostatectomy for infiltrative bladder tumors in period between 2003 and 2007 year, 94 men with bladder cancer underwent radical cystoprostatectomy at Urology Clinic-University of Sarajevo Clinics Centre. Mean age of patients was 67 years, with age limits ranging between 48 and 79 years. Pathohystological evaluation was used for all specimens from RCP. We found that 9,57% of cystoprostatectomy specimens in patients with bladder cancer also contained incidental prostate cancer. This result was much lower than overall mean frequency of incidentally detected prostate cancer in other series of cystoprostatectomy cases (range, 23%-68%. In conclusion we recommended digital rectal examination (DRE and prostate-specific antigen (PSA test as part of the bladder cancer work up and complete removal of the prostate at cystoprostatectomy to prevent residual prostate cancer.

Implant R100 Predicts Rectal Bleeding in Prostate Cancer Patients Treated with IG-IMRT to 45 Gy and Pd-103 Implant

International Nuclear Information System (INIS)

Packard, M.; Fuhrer, R.; Valakh, V.

2014-01-01

Purpose. To define factors associated with rectal bleeding in patients treated with IG-IMRT followed by Pd-103 seed implant. Methods and Materials. We retrospectively reviewed 61 prostate adenocarcinoma patients from 2002 to 2008. The majority (85.2%) were of NCCN intermediate risk category. All received IG-IMRT to the prostate and seminal vesicles followed by Pd-103 implant delivering a mean D90 of 100.7 Gy. Six patients received 45 Gy to the pelvic nodes and 10 received androgen deprivation. Results. Ten patients (16.4%) developed rectal bleeding: 4 were CTCAE v.3 grade 1, 5 were grade 2, and 1 was grade 3. By univariate analysis, age, stage, Gleason sum, PSA, hormonal therapy, pelvic radiation, postoperative prostate volume, D9, V100, individual source activity, total implanted activity per cm 3 , and duration of interval before implant did not impact rectal bleeding. Implant R100 was higher in patients with rectal bleeding: on average, 0.885 versus 0.396 cm 3 ,(Ρ =0.02) , odds ratio of 2.26 per .5 cm 3 (95% CI, 1.16–4.82). A trend for significance was seen for prostate V200 and total implanted activity. Conclusion. Higher implant R100 was associated with development of rectal bleeding in patients receiving IG-IMRT to 45 Gy followed by Pd-103 implant. Minimizing implant R100 may reduce the rate of rectal bleeding in similar patients.

Value of Diffusion Tensor Imaging of Prostate Cancer: Comparison with Systemic Prostate Biopsy

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Yoon, Seong Kuk; Kim, Dong Won; Ha, Dong Ho; Kwon, Hee Jin; Kang, Myong Jin; Choi, Sun Seob; Nam, Kyung Jin; Kim, Jung Il [Dong-A University, Medical Center, Busan (Korea, Republic of)

2011-02-15

This study was performed to evaluate the usefulness of diffusion tensor imaging (DTI) and to correlate systemic twelve biopsy in prostate cancer. Thirty-one patients with suspected prostate cancer underwent MR imaging. DTI was performed prior to a prostate biopsy. We prospectively calculated the apparent diffusion coefficient (ADC) and fractional anisotropy (FA) value in each corresponding biopsy site. Twenty-three of 31 patients had histopathologically proven adenocarcinoma. Among the 276 biopsy cores of 23 patients with prostate cancer, 109 cores showed positive results (39%). The ADC and FA value of positive cores were 1.31 {+-} 0.34x10-3 mm2/s and 0.68 {+-} 0.07, and those of the negative cores were 1.74 {+-} 0.45x10-3 mm2/s and 0.54 {+-} 0.09, respectively. Eight patients without carcinoma showed an ADC value of 1.83 {+-} 0.26x10-3 mm2/s and an FA value of 0.47 {+-} 0.07. The ADC and FA value of positive cores were significantly lower and higher than those of negative cores and cancer-free patients, respectively (p < 0.05). The ADC and FA values using DTI may provide useful diagnostic information in the differentiation of cancerous tissues, although there is overlap in some cases

Toxicity report of once weekly radiation therapy for low-risk prostate adenocarcinoma: preliminary results of a phase I/II trial

International Nuclear Information System (INIS)

Menkarios, Cathy; Fortin, Bernard; Lambert, Carole; Vigneault, Éric; Brochet, Nicolas; Nguyen, David HA; Bahary, Jean-Paul; Jolicoeur, Marjory; Beauchemin, Marie-Claude; Villeneuve, Hugo; Van Nguyen, Thu

2011-01-01

Increasing clinical data supports a low α/β ratio for prostate adenocarcinoma, potentially lower than that of surrounding normal tissues. A hypofractionated, weekly radiation therapy (RT) schedule should result in improved tumour control, reduced acute toxicity, and similar or decreased late effects. We report the toxicity profile of such treatment. We conducted a multi-institution phase I/II trial of three-dimensional conformal radiation therapy (3D-CRT) for favourable-risk prostate cancer (T1a-T2a, Gleason ≤ 6 and PSA < 10 ng/ml). RT consisted of 45 Gy in nine 5 Gy fractions, once weekly. Primary end-points were feasibility and late gastrointestinal (GI) toxicity (RTOG scale), while secondary end-points included acute GI toxicity, acute and late genitourinary (GU) toxicity, biochemical control, and survival. Between 2006 and 2008, 80 patients were treated. No treatment interruptions occurred. The median follow-up is 33 months (range: 20-51). Maximal grade 1, 2, and 3 acute (< 3 months) GU toxicity was 29%, 31% and 5% respectively (no grade 4). Acute GI grade 1 toxicity was reported in 30% while grade 2 occurred in 14% (no grade 3 or 4). Crude late grade ≥ 3 toxicity rates at 31 months were 2% for both GU and GI toxicity. Cumulative late grade ≥ 3 GI toxicity at 3 years was 11%. Two patients had PSA failure according to the Phoenix definition. The three-year actuarial biochemical control rate is 97%. Weekly RT with 45 Gy in 9 fractions is feasible and results in comparable toxicity. Long term tumour control and survival remain to be assessed

Epigenetic Regulation in Prostate Cancer Progression.

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Ruggero, Katia; Farran-Matas, Sonia; Martinez-Tebar, Adrian; Aytes, Alvaro

2018-01-01

An important number of newly identified molecular alterations in prostate cancer affect gene encoding master regulators of chromatin biology epigenetic regulation. This review will provide an updated view of the key epigenetic mechanisms underlying prostate cancer progression, therapy resistance, and potential actionable mechanisms and biomarkers. Key players in chromatin biology and epigenetic master regulators has been recently described to be crucially altered in metastatic CRPC and tumors that progress to AR independency. As such, epigenetic dysregulation represents a driving mechanism in the reprograming of prostate cancer cells as they lose AR-imposed identity. Chromatin integrity and accessibility for transcriptional regulation are key features altered in cancer progression, and particularly relevant in nuclear hormone receptor-driven tumors like prostate cancer. Understanding how chromatin remodeling dictates prostate development and how its deregulation contributes to prostate cancer onset and progression may improve risk stratification and treatment selection for prostate cancer patients.

Cardiovascular risk during hormonal treatment in patients with prostate cancer

International Nuclear Information System (INIS)

Van Poppel, Hein; Tombal, Bertrand

2011-01-01

The objective of this review is to provide information on cardiovascular risk following androgen-deprivation therapy (ADT) in prostate cancer patients and to suggest potential prevention and management strategies. Androgen deprivation therapy can cause peripheral insulin resistance, increase fat mass and low-density lipoprotein cholesterol, and induce type 2 diabetes. While recent studies have reported an association in patients with prostate cancer between ADT and increased risk of cardiovascular events, other studies have not detected the association. However, at this time, it is plausible that ADT could increase cardiovascular risk because of the adverse effect of ADT on risk factors for cardiovascular disease. It is advisable that prostate cancer patients in whom ADT is initiated be referred to their physician, who will carefully monitor them for potential metabolic effects. Therefore, physicians should be informed about these potential side effects. This especially applies to men aged >65 years and those with pre-existing cardiovascular comorbidities. Adopting a healthy lifestyle including a balanced diet and regular physical activity is recommended. Patients with cardiovascular disease should receive appropriate preventive therapies, including lipid-lowering, antihypertensive, glucose-lowering, and antiplatelet therapy. ADT should preferably not be unnecessarily administered to prostate cancer patients with pre-existing cardiovascular disease, certainly not to those in whom the risk of prostate cancer-specific mortality is low. The physician should carefully weigh the potential benefits of ADT against the possible risks in individual patients with prostate cancer

Postdiagnosis statin use and mortality in danish patients with prostate cancer

DEFF Research Database (Denmark)

Larsen, Signe Benzon; Dehlendorff, Christian; Skriver, Charlotte

2017-01-01

Purpose Increasing evidence indicates that statin use may reduce mortality from prostate cancer. In this work, we examined whether postdiagnosis statin use was associated with reduced cancer-specific mortality or all-cause mortality among patients with prostate cancer in Denmark. Material...... and Methods From nationwide Danish registries, we identified all patients with incident prostate adenocarcinoma from 1998 to 2011 and retrieved data on tumor and patient characteristics, drug use, and primary treatment. We defined postdiagnosis use (two or more prescriptions) of statins as a time......-varying covariate with 1-year lag. Cox proportional hazards regression models used to compute hazard ratios (HRs) for prostate cancer-specific mortality and all-cause mortality through 2013 associated with postdiagnosis statin use. In secondary and sensitivity analyses, we assessed statin use within exposure...

Optimization of laser capture microdissection and RNA amplification for gene expression profiling of prostate cancer

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Vasmatzis George

2007-03-01

Full Text Available Abstract Background To discover prostate cancer biomarkers, we profiled gene expression in benign and malignant cells laser capture microdissected (LCM from prostate tissues and metastatic prostatic adenocarcinomas. Here we present methods developed, optimized, and validated to obtain high quality gene expression data. Results RNase inhibitor was included in solutions used to stain frozen tissue sections for LCM, which improved RNA quality significantly. Quantitative PCR assays, requiring minimal amounts of LCM RNA, were developed to determine RNA quality and concentration. SuperScript II™ reverse transcriptase was replaced with SuperScript III™, and SpeedVac concentration was eliminated to optimize linear amplification. The GeneChip® IVT labeling kit was used rather than the Enzo BioArray™ HighYield™ RNA transcript labeling kit since side-by-side comparisons indicated high-end signal saturation with the latter. We obtained 72 μg of labeled complementary RNA on average after linear amplification of about 2 ng of total RNA. Conclusion Unsupervised clustering placed 5/5 normal and 2/2 benign prostatic hyperplasia cases in one group, 5/7 Gleason pattern 3 cases in another group, and the remaining 2/7 pattern 3 cases in a third group with 8/8 Gleason pattern 5 cases and 3/3 metastatic prostatic adenocarcinomas. Differential expression of alpha-methylacyl coenzyme A racemase (AMACR and hepsin was confirmed using quantitative PCR.

Correlation of Serum Androgens and Pituitary Hormone Levels with Serum PSA Less Than 2.5 NG/ML

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Mustafa Sofikerim

2007-01-01

Full Text Available The aim of this clinical study was to determine whether there is a relationship between total serum testosterone, free testosterone, FSH (Follicle-Stimulating Hormone, LH (Luteinizing Hormone and serum prostate specific antigen (PSA levels. We postulated that such a correlation existed then the use of hormone specific reference ranges might enhance the usefullness of PSA concentrations <2.5 ng/mL as a marker for prostate cancer.

A Case of Appendiceal Adenocarcinoma with Clinical Benefit from FOLFOX and Bevacizumab

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Erin D. Powell

2009-07-01

Full Text Available A 44-year-old woman presented with lower abdominal pain and bilateral ovarian masses on ultrasound. Exploratory laparotomy revealed extensive peritoneal and intra-abdominal disease and an abnormal appendix. Bilateral salpingo-oophorectomy, infracolic omentectomy, ileocolic resection and primary anastomosis were performed. Final pathology revealed a primary appendiceal adenocarcinoma, poorly differentiated, of signet ring cell type. CT scan postoperatively revealed gross residual disease. The patient was treated with FOLFOX chemotherapy combined with bevacizumab. Repeat CT scan showed a decrease in residual disease and the patient clinically improved. After her treatment has been continued for 13 months, she remains clinically well and her CT scan shows sustained disease stability. Disseminated appendiceal carcinoma is generally considered to be refractory to 5-FU-based chemotherapy and, to our knowledge, this is the first reported case of a patient with appendiceal adenocarcinoma demonstrating clinical benefit and sustained stability of disease with combination chemotherapy plus bevacizumab.

The expression of prostate-specific antigen in invasive breast carcinoma and its relationship with routine clinicopathologic parameters

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Fereshteh Mohammadizadeh

2012-01-01

Full Text Available Background: Invasive breast carcinoma is one of the most common cancers of women. Parameters such as lymph node status, tumor grade, and the status of hormone receptors are among the main prognostic determinants of this cancer. Immunohistochemical detection of prostate-specific antigen (PSA is widely used to identify metastatic prostatic adenocarcinoma. However, its immunoreactivity has been found in some non-prostatic tissues. This study was conducted to assess PSA expression in invasive breast carcinoma and its relationship with routine clinicopathologic parameters. Materials and Methods: 100 formalin-fixed and paraffin-embedded invasive breast carcinoma tissue specimens from the pathology archive of Alzahra hospital (Isfahan, Iran were studied for the expression of estrogen receptor (ER, progesterone receptor (PR, HER2/neu, and PSA by immunohistochemistry. Stained sections were classified according to the intensity of staining and the percentage of cells showing PSA staining. The relationship between PSA expression and other markers, age, lymph node status, tumor subtype, and tumor grade was then studied. Results: No association was found between PSA expression on one hand and PR, Her2/neu, age, lymph node status, tumor grade, and tumor subtype on the other. PSA score was reversely correlated with ER expression (P = 0.015. Conclusion: Despite the reverse relationship between PSA expression and the immunoreactivity of ER, PSA expression was not correlated with other prognostic factors. Therefore, the detection of PSA by immunohistochemistry does not seem to be a significant prognostic parameter in patients with invasive breast carcinoma.

Urethral dose and increment of international prostate symptom score (IPSS) in transperineal permanent interstitial implant (TPI) of prostate cancer

International Nuclear Information System (INIS)

Murakami, N.; Itami, J.; Okuma, K.; Marino, H.; Ban, T.; Nakazato, M.; Kanai, K.; Naoi, K.; Fuse, M.; Nakagawa, K.

2008-01-01

Purpose: to find the factors which influence the acute increment of international prostate symptom score (IPSS) after transperineal permanent interstitial implant (TPI) using 125 I seeds. Patients and methods: from April 2004 through September 2006, 104 patients with nonmetastatic prostate cancer underwent TPI without external-beam irradiation. Median patient age was 70 years with a median follow-up of 13.0 months. 73 patients (70%) received neoadjuvant hormone therapy. The increment of IPSS was defined as the difference between pre- and postimplant maximal IPSS. Clinical, treatment, and dosimetric parameters evaluated included age, initial prostate-specific antigen, Gleason Score, neoadjuvant hormone therapy, initial IPSS, post-TPI prostatic volume, number of implanted seeds, prostate V 100 , V 150 , D 90 , urethral D max , and urethral D 90 . In order to further evaluate detailed urethral doses, the base and apical urethra were defined and the dosimetric parameters were calculated. Results: the IPSS peaked 3 months after TPI and returned to baseline at 12-15 months. Multivariate analysis demonstrated a statistically significant correlation of post-TPI prostatic volume, number of implanted seeds, and the dosimetric parameters of the base urethra with IPSS increment. Conclusion: the base urethra appears to be susceptible to radiation and the increased dose to this region deteriorates IPSS. It remains unclear whether the base urethral dose relates to the incidence of late urinary morbidities. (orig.)

Life-threatening meningitis resulting from transrectal prostate biopsy

Institute of Scientific and Technical Information of China (English)

Zhou-Jun Shen; Shan-Wen Chen; Hua Wang; Xie-Lai Zhou; Ju-Ping Zhao

2005-01-01

After antibiotic prophylaxis with metronidazole and levofloxacin, a transrectal sextant biopsy was performed under the guide of transrectal ultrasonography (TRUS) for a 75-year-old suspicious patient with prostate adenocarcinoma.Although antibiotics were also given after this procedure, the patient still developed fever, anxious, agrypnia and headache. Blood cultures remained negative. Lumbar puncture was performed and was consistent with Escherichia coli bacterial meningitis.

High dose rate interstitial brachytherapy with external beam irradiation for localized prostate cancer. Preliminary results

Energy Technology Data Exchange (ETDEWEB)

Hiratsuka, Junichi; Jo, Yoshimasa; Yoden, Eisaku; Tanaka, Hiroyoshi; Imajo, Yoshinari [Kawasaki Medical School, Kurashiki, Okayama (Japan); Nagase, Naomi; Narihiro, Naomasa; Kubota, Juichi

2000-12-01

This study was undertaken to assess the biochemical and pathological results of combined external beam radiotherapy and high dose rate Ir-192 brachytherapy (HDR-Ir192) for clinically localized prostate cancer. Between October 1997 and August 1999, 39 evaluable patients with adenocarcinoma of prostate diagnosed by biopsy were treated with interstitial and external beam irradiation. Patients ranged in age from 58-82 years, with a mean of 69.7 years. T1c, T2 and T3 tumors, according to the UICC classification system (1997), were found in 7, 21 and 11 cases respectively. The mean initial pre-treatment PSA was 35.9 ng/ml (median 13.2), with 77% of the patients having had a pre-treatment PSA greater than 10 ng/ml. Of all patients, 17 had received pre-treatment hormonal therapy. Hormonal pretreatment was stopped at the beginning of radiotherapy in all cases. External beam four-field box irradiation was given to the small pelvis to a dose of 45 Gy/25 fractions. Three HDR-Ir192 treatments were given over a 30-h period, with 5.5 Gy per fraction at the circumference of the prostate gland over the course of this study. Biochemical failure was defined as a PSA level >1.5 ng/ml and rising on three consecutive values. If serial post-treatment PSA levels showed a continuous downward trend, failure was not scored. The patient with clinical evidence of progression was classified as a clinical failure. The median follow-up at the time of evaluation was 19.6 months. A post-treatment PSA level {<=}1.0 ng/ml was seen in 26 (67%) patients, and values from >1.0 to {<=}2.0 ng/ml were seen in 10 (26%) patients. Biochemical failure was not seen in 38 patients except for one patient who developed a distant bone metastasis with negative prostatic biopsy 15 months after treatment. Biochemical control rate was 100% (38/38) except for the patient with bone metastasis classified as clinical failure. Negative biopsies 18 months after treatment were found in 93% (14/15) of patients. Only one patient

Prospective Randomized Phase 2 Trial of Intensity Modulated Radiation Therapy With or Without Oncolytic Adenovirus-Mediated Cytotoxic Gene Therapy in Intermediate-Risk Prostate Cancer

Energy Technology Data Exchange (ETDEWEB)

Freytag, Svend O., E-mail: sfreyta1@hfhs.org [Department of Radiation Oncology, Henry Ford Health System, Detroit, Michigan (United States); Stricker, Hans [Vattikuti Urology Institute, Henry Ford Health System, Detroit, Michigan (United States); Lu, Mei [Public Health Sciences, Henry Ford Health System, Detroit, Michigan (United States); Elshaikh, Mohamed; Aref, Ibrahim; Pradhan, Deepak; Levin, Kenneth; Kim, Jae Ho [Department of Radiation Oncology, Henry Ford Health System, Detroit, Michigan (United States); Peabody, James [Vattikuti Urology Institute, Henry Ford Health System, Detroit, Michigan (United States); Siddiqui, Farzan; Barton, Kenneth; Pegg, Jan; Zhang, Yingshu; Cheng, Jingfang [Department of Radiation Oncology, Henry Ford Health System, Detroit, Michigan (United States); Oja-Tebbe, Nancy; Bourgeois, Renee [Public Health Sciences, Henry Ford Health System, Detroit, Michigan (United States); Gupta, Nilesh; Lane, Zhaoli [Pathology, Henry Ford Health System, Detroit, Michigan (United States); Rodriguez, Ron [Urology, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); DeWeese, Theodore [Department of Radiation Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); and others

2014-06-01

Purpose: To assess the safety and efficacy of combining oncolytic adenovirus-mediated cytotoxic gene therapy (OAMCGT) with intensity modulated radiation therapy (IMRT) in intermediate-risk prostate cancer. Methods and Materials: Forty-four men with intermediate-risk prostate cancer were randomly assigned to receive either OAMCGT plus IMRT (arm 1; n=21) or IMRT only (arm 2; n=23). The primary phase 2 endpoint was acute (≤90 days) toxicity. Secondary endpoints included quality of life (QOL), prostate biopsy (12-core) positivity at 2 years, freedom from biochemical/clinical failure (FFF), freedom from metastases, and survival. Results: Men in arm 1 exhibited a greater incidence of low-grade influenza-like symptoms, transaminitis, neutropenia, and thrombocytopenia than men in arm 2. There were no significant differences in gastrointestinal or genitourinary events or QOL between the 2 arms. Two-year prostate biopsies were obtained from 37 men (84%). Thirty-three percent of men in arm 1 were biopsy-positive versus 58% in arm 2, representing a 42% relative reduction in biopsy positivity in the investigational arm (P=.13). There was a 60% relative reduction in biopsy positivity in the investigational arm in men with <50% positive biopsy cores at baseline (P=.07). To date, 1 patient in each arm exhibited biochemical failure (arm 1, 4.8%; arm 2, 4.3%). No patient developed hormone-refractory or metastatic disease, and none has died from prostate cancer. Conclusions: Combining OAMCGT with IMRT does not exacerbate the most common side effects of prostate radiation therapy and suggests a clinically meaningful reduction in positive biopsy results at 2 years in men with intermediate-risk prostate cancer.

Prospective Randomized Phase 2 Trial of Intensity Modulated Radiation Therapy With or Without Oncolytic Adenovirus-Mediated Cytotoxic Gene Therapy in Intermediate-Risk Prostate Cancer

International Nuclear Information System (INIS)

Freytag, Svend O.; Stricker, Hans; Lu, Mei; Elshaikh, Mohamed; Aref, Ibrahim; Pradhan, Deepak; Levin, Kenneth; Kim, Jae Ho; Peabody, James; Siddiqui, Farzan; Barton, Kenneth; Pegg, Jan; Zhang, Yingshu; Cheng, Jingfang; Oja-Tebbe, Nancy; Bourgeois, Renee; Gupta, Nilesh; Lane, Zhaoli; Rodriguez, Ron; DeWeese, Theodore

2014-01-01

Purpose: To assess the safety and efficacy of combining oncolytic adenovirus-mediated cytotoxic gene therapy (OAMCGT) with intensity modulated radiation therapy (IMRT) in intermediate-risk prostate cancer. Methods and Materials: Forty-four men with intermediate-risk prostate cancer were randomly assigned to receive either OAMCGT plus IMRT (arm 1; n=21) or IMRT only (arm 2; n=23). The primary phase 2 endpoint was acute (≤90 days) toxicity. Secondary endpoints included quality of life (QOL), prostate biopsy (12-core) positivity at 2 years, freedom from biochemical/clinical failure (FFF), freedom from metastases, and survival. Results: Men in arm 1 exhibited a greater incidence of low-grade influenza-like symptoms, transaminitis, neutropenia, and thrombocytopenia than men in arm 2. There were no significant differences in gastrointestinal or genitourinary events or QOL between the 2 arms. Two-year prostate biopsies were obtained from 37 men (84%). Thirty-three percent of men in arm 1 were biopsy-positive versus 58% in arm 2, representing a 42% relative reduction in biopsy positivity in the investigational arm (P=.13). There was a 60% relative reduction in biopsy positivity in the investigational arm in men with <50% positive biopsy cores at baseline (P=.07). To date, 1 patient in each arm exhibited biochemical failure (arm 1, 4.8%; arm 2, 4.3%). No patient developed hormone-refractory or metastatic disease, and none has died from prostate cancer. Conclusions: Combining OAMCGT with IMRT does not exacerbate the most common side effects of prostate radiation therapy and suggests a clinically meaningful reduction in positive biopsy results at 2 years in men with intermediate-risk prostate cancer