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Sample records for human prostate carcinoma

  1. Preferential radiosensitization of human prostatic carcinoma cells by mild hyperthermia

    International Nuclear Information System (INIS)

    Ryu, Samuel; Brown, Stephen L.; Kim, Sang-Hie; Khil, Mark S.; Kim, Jae Ho

    1996-01-01

    Purpose: Recent cell culture studies by us and others suggest that some human carcinoma cells are more sensitive to heat than are rodent cells following mild hyperthermia. In studying the cellular mechanism of enhanced thermosensitivity of human tumor cells to hyperthermia, prostatic carcinoma cells of human origin were found to be more sensitive to mild hyperthermia than other human cancer cells. The present study was designed to determine the magnitude of radiosensitization of human prostatic carcinoma cells by mild hyperthermia and to examine whether the thermal radiosensitization is related to the intrinsic thermosensitivity of cancer cells. Methods and Materials: Two human prostatic carcinoma cell lines (DU-145 and PC-3) and other carcinoma cells of human origin, in particular, colon (HT-29), breast (MCF-7), lung (A-549), and brain (U-251) were exposed to temperatures of 40-41 deg. C. Single acute dose rate radiation and fractionated radiation were combined with mild hyperthermia to determine thermal radiosensitization. The end point of the study was the colony-forming ability of single-plated cells. Results: DU-145 and PC-3 cells were found to be exceedingly thermosensitive to 41 deg. C for 24 h, relative to other cancer cell lines. Ninety percent of the prostatic cancer cells were killed by a 24 h heat exposure. Prostatic carcinoma cells exposed to a short duration of heating at 41 deg. C for 2 h resulted in a substantial enhancement of radiation-induced cytotoxicity. The thermal enhancement ratios (TERs) of single acute dose radiation following heat treatment 41 deg. C for 2 h were 2.0 in DU-145 cells and 1.4 in PC-3 cells. The TERs of fractionated irradiation combined with continuous heating at 40 deg. C were similarly in the range of 2.1 to 1.4 in prostate carcinoma cells. No significant radiosensitization was observed in MCF-7 and HT-29 cells under the same conditions. Conclusion: The present data suggest that a significant radiosensitization of

  2. Prostate carcinomas

    International Nuclear Information System (INIS)

    Toledano, A.; Chauveinc, L.; Flam, T.; Thiounn, N.; Solignac, S.; Timbert, M.; Rosenwald, J.C.; Cosset, J.M.; Ammor, A.; Bonnetain, F.; Brenier, J.P.; Maingon, P.; Peignaux, K.; Truc, G.; Bosset, M.; Crevoisier, R. de; Tucker, S.; Dong, L.; Cheung, R.; Kuban, D.; Azria, D.; Llacer Moscardo, C.; Ailleres, N.; Allaw, A.; Serre, A.; Fenoglietto, P.; Hay, M.H.; Thezenas, S.; Dubois, J.B.; Pommier, P.; Perol, D.; Lagrange, J.L.; Richaud, P.; Brune, D.; Le Prise, E.; Azria, D.; Beckendorf, V.; Chabaud, S.; Carrie, C.; Bosset, M.; Bosset, J.F.; Maingon, P.; Ammor, A.; Crehangen, G.; Truc, G.; Peignaux, K.; Bonnetain, F.; Keros, L.; Bernier, V.; Aletti, P.; Wolf, D.; Marchesia, V.; Noel, A.; Artignan, X.; Fourneret, P.; Bacconier, M.; Shestaeva, O.; Pasquier, D.; Descotes, J.L.; Balosso, J.; Bolla, M.; Burette, R.; Corbusier, A.; Germeau, F.; Crevoisier, R. de; Dong, L.; Bonnen, M.; Cheung, R.; Tucker, S.; Kuban, D.; Crevoisier, R. de; Melancon, A.; Kuban, D.; Cheung, R.; Dong, L.; Peignaux, K.; Brenier, J.P.; Truc, G.; Bosset, M.; Ammor, A.; Barillot, I.; Maingon, P.; Molines, J.C.; Berland, E.; Cornulier, J. de; Coulet-Parpillon, A.; Cohard, C.; Picone, M.; Fourneret, P.; Artignan, X.; Daanen, V.; Gastaldo, J.; Bolla, M.; Collomb, D.; Dusserre, A.; Descotes, J.L.; Troccaz, J.; Giraud, J.Y.; Quero, L.; Hennequin, C.; Ravery, V.; Desgrandschamps, F.; Maylin, C.; Boccon-Gibod, L.; Salem, N.; Bladou, F.; Gravis, G.; Tallet, A.; Simonian, M.; Serment, G.; Salem, N.; Bladou, F.; Gravis, G.; Simonian, M.; Rosello, R.; Serment, G.

    2005-01-01

    Some short communications on the prostate carcinoma are given here. The impact of pelvic irradiation, conformation with intensity modulation, association of radiotherapy and chemotherapy reduction of side effects, imaging, doses escalation are such subjects studied and reported. (N.C.)

  3. Superoxide dismutase in radioresistant PC-3 human prostate carcinoma cells

    International Nuclear Information System (INIS)

    Prokopovic, J.; Adzic M; Niciforovic, A.; Vucic, V.; Zaric, B.; Radojcic, M. B.

    2006-01-01

    The molecular mechanism of gamma-ionizing radiation (IR) resistance of human prostate cancer cells PC-3 is not known. Since low-LET-IR effects are primarily achieved through generation of reactive oxygen species (ROS), IR-induced expression of ROS-metabolizing antioxidant enzymes, Mn- and CuZn-superoxide dismutase (Mn- and CuZnSOD) and catalase (CAT), and their upstream regulator transcription factor NFκB was followed. Significant elevation of both SODs was found in cells irradiated with 10- and 20 Gy, while CAT and NFκB expression was unchanged. Since, such conditions lead to accumulation of H 2 O 2 , it is concluded that radioresistance of PC-3 cells may emerge from positive feed-forward vicious circle established between H 2 O 2 activation of NFκB and elevated MnSOD activity. (author)

  4. Effect of radiation combined with hyperthermia on human prostatic carcinoma cell lines in culture

    International Nuclear Information System (INIS)

    Kaver, I.; Ware, J.L.; Wilson, J.D.; Koontz, W.W. Jr.

    1991-01-01

    The effect of radiation combined with heat on three human prostatic carcinoma cell lines growing in vitro was investigated. Cells were exposed to different radiation doses followed by heat treatment at 43 degrees C for one hour. Heat treatment, given ten minutes after radiation, significantly enhanced the radiation response of all the cell lines studied. The combined effect of radiation and heat produced greater cytotoxicity than predicted from the additive effects of the two individual treatment modalities alone. These results indicate that a combined treatment regimen of radiation plus hyperthermia (43 degrees, 1 hr) might be an important tool in maintaining a better local control of prostatic cancer

  5. Cytokeratin characterization of human prostatic carcinoma and its derived cell lines.

    Science.gov (United States)

    Nagle, R B; Ahmann, F R; McDaniel, K M; Paquin, M L; Clark, V A; Celniker, A

    1987-01-01

    Two murine monoclonal anti-cytokeratin antibodies with defined specificity were shown to distinguish between basal cells and luminal cells in human prostate tissue. Forty-one biopsies or transurethral resection specimens were characterized using these two antibodies. In cases of benign prostatic hyperplasia, focal loss of the basal cell layer was noted in areas of glandular proliferation. Ten cases of adenocarcinoma of the prostate, varying in Gleason's histological grade from 2 to 4, were also studied. In each case the carcinoma was shown to represent the luminal cell phenotype with no evidence of involvement of the basal cell phenotype. An analysis of three established metastatic prostatic carcinoma cell lines (DU-145, PC-3, and LNCaP) using two-dimensional electrophoresis showed that the cytokeratin complement of each cell line was slightly different but retained the phenotype of the luminal cell. It was concluded that during both hyperplasia and neoplastic transformation of the prostate, the luminal cell phenotype is primarily involved and that the basal cell phenotype does not appear to contribute to either intraluminal proliferation or invasive cell populations.

  6. Urtica dioica Induces Cytotoxicity in Human Prostate Carcinoma ...

    African Journals Online (AJOL)

    Purpose: To evaluate the cytotoxic mechanisms of an extract from the leaves of the Urtica dioica (UD) plant in LNCaP prostate cancer cells. Methods: LNCaP cells were exposed to the UD extract for 24hrs and cell viability assessed using the MTT assay. Reactive oxygen species generation was assessed using the NBT ...

  7. A Novel Role of Silibinin as a Putative Epigenetic Modulator in Human Prostate Carcinoma

    Directory of Open Access Journals (Sweden)

    Ioannis Anestopoulos

    2016-12-01

    Full Text Available Silibinin, extracted from milk thistle (Silybum marianum L., has exhibited considerable preclinical activity against prostate carcinoma. Its antitumor and chemopreventive activities have been associated with diverse effects on cell cycle, apoptosis, and receptor-dependent mitogenic signaling pathways. Here we hypothesized that silibinin’s pleiotropic effects may reflect its interference with epigenetic mechanisms in human prostate cancer cells. More specifically, we have demonstrated that silibinin reduces gene expression levels of the Polycomb Repressive Complex 2 (PRC2 members Enhancer of Zeste Homolog 2 (EZH2, Suppressor of Zeste Homolog 12 (SUZ12, and Embryonic Ectoderm Development (EED in DU145 and PC3 human prostate cancer cells, as evidenced by Real Time Polymerase Chain Reaction (RT-PCR. Furthermore immunoblot and immunofluorescence analysis revealed that silibinin-mediated reduction of EZH2 levels was accompanied by an increase in trimethylation of histone H3 on lysine (Κ-27 residue (H3K27me3 levels and that such response was, in part, dependent on decreased expression levels of phosphorylated Akt (ser473 (pAkt and phosphorylated EZH2 (ser21 (pEZH2. Additionally silibinin exerted other epigenetic effects involving an increase in total DNA methyltransferase (DNMT activity while it decreased histone deacetylases 1-2 (HDACs1-2 expression levels. We conclude that silibinin induces epigenetic alterations in human prostate cancer cells, suggesting that subsequent disruptions of central processes in chromatin conformation may account for some of its diverse anticancer effects.

  8. Prostate carcinomas; Cancer de la prostate

    Energy Technology Data Exchange (ETDEWEB)

    Toledano, A.; Chauveinc, L.; Flam, T.; Thiounn, N.; Solignac, S.; Timbert, M.; Rosenwald, J.C.; Cosset, J.M.; Ammor, A.; Bonnetain, F.; Brenier, J.P.; Maingon, P.; Peignaux, K.; Truc, G.; Bosset, M.; Crevoisier, R. de; Tucker, S.; Dong, L.; Cheung, R.; Kuban, D.; Azria, D.; Llacer Moscardo, C.; Ailleres, N.; Allaw, A.; Serre, A.; Fenoglietto, P.; Hay, M.H.; Thezenas, S.; Dubois, J.B.; Pommier, P.; Perol, D.; Lagrange, J.L.; Richaud, P.; Brune, D.; Le Prise, E.; Azria, D.; Beckendorf, V.; Chabaud, S.; Carrie, C.; Bosset, M.; Bosset, J.F.; Maingon, P.; Ammor, A.; Crehangen, G.; Truc, G.; Peignaux, K.; Bonnetain, F.; Keros, L.; Bernier, V.; Aletti, P.; Wolf, D.; Marchesia, V.; Noel, A.; Artignan, X.; Fourneret, P.; Bacconier, M.; Shestaeva, O.; Pasquier, D.; Descotes, J.L.; Balosso, J.; Bolla, M.; Burette, R.; Corbusier, A.; Germeau, F.; Crevoisier, R. de; Dong, L.; Bonnen, M.; Cheung, R.; Tucker, S.; Kuban, D.; Crevoisier, R. de; Melancon, A.; Kuban, D.; Cheung, R.; Dong, L.; Peignaux, K.; Brenier, J.P.; Truc, G.; Bosset, M.; Ammor, A.; Barillot, I.; Maingon, P.; Molines, J.C.; Berland, E.; Cornulier, J. de; Coulet-Parpillon, A.; Cohard, C.; Picone, M.; Fourneret, P.; Artignan, X.; Daanen, V.; Gastaldo, J.; Bolla, M.; Collomb, D.; Dusserre, A.; Descotes, J.L.; Troccaz, J.; Giraud, J.Y.; Quero, L.; Hennequin, C.; Ravery, V.; Desgrandschamps, F.; Maylin, C.; Boccon-Gibod, L.; Salem, N.; Bladou, F.; Gravis, G.; Tallet, A.; Simonian, M.; Serment, G.; Salem, N.; Bladou, F.; Gravis, G.; Simonian, M.; Rosello, R.; Serment, G

    2005-11-15

    Some short communications on the prostate carcinoma are given here. The impact of pelvic irradiation, conformation with intensity modulation, association of radiotherapy and chemotherapy reduction of side effects, imaging, doses escalation are such subjects studied and reported. (N.C.)

  9. Testicular Metastases From Prostate Carcinoma

    Directory of Open Access Journals (Sweden)

    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.

  10. Overexpression of vimentin in canine prostatic carcinoma

    DEFF Research Database (Denmark)

    Rodrigues, M M P; Rema, A; Gärtner, F

    2011-01-01

    Canine prostatic tumours exhibit similarities to those of man and may represent a useful model system to explore the mechanisms of cancer progression. Tumour progression to malignancy requires a change from an epithelial phenotype to a fibroblastic or mesenchymal phenotype. Vimentin expression...... is associated with the invasive phenotype of human prostate cancer cells. The aim of the present study was to characterize immunohistochemically the expression of vimentin by canine prostatic carcinomas. Primary carcinomas and metastatic tumour foci both showed vimentin expression. This finding suggests...... that the acquisition of the epithelial-mesenchymal transition phenotype in canine prostatic carcinoma may be characterized by the presence of mesenchymal intermediate filament (vimentin) that could lead to a higher likelihood of metastasis....

  11. Serial lectin affinity chromatography with concavalin A and wheat germ agglutinin demonstrates altered asparagine-linked sugar-chain structures of prostatic acid phosphatase in human prostate carcinoma.

    Science.gov (United States)

    Yoshida, K I; Honda, M; Arai, K; Hosoya, Y; Moriguchi, H; Sumi, S; Ueda, Y; Kitahara, S

    1997-08-01

    Differences between human prostate carcinoma (PCA, five cases) and benign prostatic hyperplasia (BPH, five cases) in asparagine-linked (Asn) sugar-chain structure of prostatic acid phosphatase (PAP) were investigated using lectin affinity chromatography with concanavalin A (Con A) and wheat germ agglutinin (WGA). PAP activities were significantly decreased in PCA-derived PAP, while no significant differences between the two PAP preparations were observed in the enzymatic properties (Michaelis-Menten value, optimal pH, thermal stability, and inhibition study). In these PAP preparations, all activities were found only in the fractions which bound strongly to the Con A column and were undetectable in the Con A unbound fractions and in the fractions which bound weakly to the Con A column. The relative amounts of PAP which bound strongly to the Con A column but passed through the WGA column, were significantly greater in BPH-derived PAP than in PCA-derived PAP. In contrast, the relative amounts of PAP which bound strongly to the Con A column and bound to the WGA column, were significantly greater in PCA-derived PAP than in BPH-derived PAP. The findings suggest that Asn-linked sugar-chain structures are altered during oncogenesis in human prostate and also suggest that studies of qualitative differences of sugar-chain structures of PAP might lead to a useful diagnostic tool for PCA.

  12. Comparative analysis of metastasis variants derived from human prostate carcinoma cells: roles in intravasation of VEGF-mediated angiogenesis and uPA-mediated invasion

    DEFF Research Database (Denmark)

    Conn, Erin M; Bøtkjær, Kenneth Alrø; Kupriyanova, Tatyana A

    2009-01-01

    To analyze the process of tumor cell intravasation, we used the human tumor-chick embryo spontaneous metastasis model to select in vivo high (PC-hi/diss) and low (PC-lo/diss) disseminating variants from the human PC-3 prostate carcinoma cell line. These variants dramatically differed in their int...

  13. Effects of oridonin nanosuspension on cell proliferation and apoptosis of human prostatic carcinoma PC-3 cell line

    Directory of Open Access Journals (Sweden)

    Zhen Zhang

    2010-10-01

    Full Text Available Zhen Zhang, Xiumei Zhang, Wei Xue, Yuna YangYang, Derong Xu, Yunxue Zhao, Haiyan LouSchool of Medicine, Shandong University, Jinan, Republic of ChinaAbstract: This study aims to investigate the inhibitory effects of oridonin nanosuspension on human prostatic carcinoma PC-3 cell line in vitro. The PC-3 cells were incubated with increasing concentrations of oridonin solution and nanosuspensions for 12 hours, 24 hours, and 36 hours. MTT [3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide] assay was performed to measure cellular viability and investigate the effect of oridonin on cell growth of PC-3. Annexin V-FITC/PI staining method was used to determine the effect of oridonin by fluorescence microscope and flow cytometry, respectively. Nanosuspension on early apoptosis of PC-3 cells was also evaluated. Oridonin significantly inhibited the growth of PC-3 cells after 12 hours, 24 hours, and 36 hours of treatment in a dose-dependent manner (P < 0.05. Compared with the same concentration of oridonin solution, oridonin nanosuspension enhanced the inhibition ratio of proliferation. The observation of propidium iodide fluorescence staining confirmed the MTT assay results. The cell proportion of PC-3 at the G2/M phase in the nanosuspension treatment group was upregulated compared with that of the control and oridonin solution groups. Both oridonin solution and nanosuspension promoted the early apoptosis of PC-3 cells. Furthermore, while improving the ratio of early apoptosis, oridonin nanosuspensions also enhanced growth suppression, and induced apoptosis of PC-3 cells. This shows great potential in the treatment of androgen-independent carcinoma of prostate by oridonin nanosuspensions.Keywords: oridonin, nanosuspension, carcinoma of prostate, PC-3 cells, cell cycle, apoptosis

  14. Prostate carcinoma: current diagnostic strategy

    International Nuclear Information System (INIS)

    Schwarzschild, Monica Maria Agata Stiepcich; Ferraz, Maria Lucia Cardoso Gomes; Oliveira, Jose Marcelo Amatuzzi; Andriolo, Adagmar

    2001-01-01

    Prostate cancer is the second cause of cancer death in men in the Western world. Despite progress in the treatment of advanced disease, it is recognized that the only possibility of reduction in prostate cancer death is nearly diagnosis when the disease is localized. In the present study our aim was to review the current strategy for diagnosis of prostate carcinoma. Prostate-specific antigen (PSA) is a valuable tumor marker and has demonstrated effectiveness in detecting prostate carcinoma, monitoring therapeutic efficacy, and disclosing disease recurrence. However, alternative methods are been proposed just as the free to total PSA ratio, PSA density, PSA velocity, which could improve the diagnostic sensibility and the specificity. Image diagnostic methods include transrectal ultra sound, computerized tomography, magnetic resonance image, and bone cintigraphy. The ultra sound is the best approach to guide the prostate biopsy and, together with the magnetic resonance is still useful for loco regional graduation. Computerized tomography as magnetic resonance image can be used for identification of linfonodal involvement. Bone cintigraphy is the best method for the identification of metastatic disease. (author)

  15. Ghrelin inhibits proliferation and increases T-type Ca2+ channel expression in PC-3 human prostate carcinoma cells

    International Nuclear Information System (INIS)

    Diaz-Lezama, Nundehui; Hernandez-Elvira, Mariana; Sandoval, Alejandro; Monroy, Alma; Felix, Ricardo; Monjaraz, Eduardo

    2010-01-01

    Research highlights: → Ghrelin decreases prostate carcinoma PC-3 cells proliferation. → Ghrelin favors apoptosis in PC-3 cells. → Ghrelin increase in intracellular free Ca 2+ levels in PC-3 cells. → Grelin up-regulates expression of T-type Ca 2+ channels in PC-3 cells. → PC-3 cells express T-channels of the Ca V 3.1 and Ca V 3.2 subtype. -- Abstract: Ghrelin is a multifunctional peptide hormone with roles in growth hormone release, food intake and cell proliferation. With ghrelin now recognized as important in neoplastic processes, the aim of this report is to present findings from a series of in vitro studies evaluating the cellular mechanisms involved in ghrelin regulation of proliferation in the PC-3 human prostate carcinoma cells. The results showed that ghrelin significantly decreased proliferation and induced apoptosis. Consistent with a role in apoptosis, an increase in intracellular free Ca 2+ levels was observed in the ghrelin-treated cells, which was accompanied by up-regulated expression of T-type voltage-gated Ca 2+ channels. Interestingly, T-channel antagonists were able to prevent the effects of ghrelin on cell proliferation. These results suggest that ghrelin inhibits proliferation and may promote apoptosis by regulating T-type Ca 2+ channel expression.

  16. Phenotypic relationships of prostatic intraepithelial neoplasia to invasive prostatic carcinoma.

    Science.gov (United States)

    Nagle, R. B.; Brawer, M. K.; Kittelson, J.; Clark, V.

    1991-01-01

    Thirty-one snap-frozen human prostate specimens containing examples of benign hyperplasia, prostatic intraepithelial neoplasia (PIN), and invasive carcinoma were analyzed using a panel of 24 antibodies and one lectin. Twenty-seven additional routinely processed radical prostatectomy specimens were studied using selected probes known to work on formalin-fixed paraffin-embedded material. Three probes, anticytokeratin KA4, anti-vimentin V9, and the lectin from Ulex europaeus (UEA-1), demonstrated phenotypic similarities between PIN and invasive carcinoma. Whereas the luminal cells of normal or hyperplastic prostatic epithelium are minimally reactive with KA4 (4%) or UEA-1 (0%) and strongly reactive with anti-vimentin (91%), both the PIN and invasive carcinoma are reactive with KA4 (89% and 93%, respectively) and UEA-1 (96% and 93%, respectively) and minimally reactive with anti-vimentin (15% and 0%, respectively). The increased KA4 staining was shown to be in part due to detection of cytokeratin 19, by using cytokeratin-19-specific antibodies, 4.62 and LP2K. The reasons for the increased expression of this cytokeratin and the decreased expression of vimentin are unclear but seem to indicate a phenotypic relationship between the PIN lesions and invasive carcinoma. Images Figure 4 Figure 1 Figure 2 Figure 3 PMID:1987760

  17. Radiation therapy of prostatic carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    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.

  18. Evaluation of anticancer activity of Cordia dichotoma leaves against a human prostate carcinoma cell line, PC3.

    Science.gov (United States)

    Rahman, Md Azizur; Sahabjada; Akhtar, Juber

    2017-07-01

    Mechanisms of antioxidant and apoptosis induction may be involved in the management of cancer by medicinal plants. Aim of the study was designed to evaluate anticancer activity of the methanolic extract of Cordia dichotoma leaves (MECD) against a human prostate carcinoma cell line, PC3. Flavonoid content was determined by colorimetric principle and antioxidant activity by various in vitro assays. MTT, DCFH-DA and DAPI staining assays were performed for the evaluation of cytotoxicity, analysis of induction of apoptosis and intracellular reactive oxygen species (ROS) activity level by MECD against human prostate carcinoma cell line, PC3. Flavonoid content was found to be 160 mg QE/g extract. IC 50 values for MECD treatment in various assays based on scavenging of 2,2-diphenyl-1-picrylhydrazyl, 2,2-azinobis(3-ethylenebenzothiazoline-6-sulfonic acid), nitric oxide, peroxy radical, superoxide anion, hydroxy radical were found to be 315.5, 38, 476, 523, 197, 82 μg/ml respectively. MECD exposure to PC3 cells significantly increased the cell death (p < 0.001, IC 50  = 74.5 μg/ml), nuclear condensation, apoptosis (p < 0.001) and induced production of ROS (p < 0.001) initiating apoptotic cascade in a dose dependent manner. This study confirms that MECD possesses antioxidant property and can prevent carcinogenesis by reducing oxidative stress. MECD possesses anticancer activity and lead to PC3 cell death via induction of apoptosis mediated through excessive ROS generation. Flavonoids in MECD may be responsible for these activities due to dual antioxidant and pro-oxidant properties.

  19. Prostatic pseudohyperplasia carcinoma. Experiences and criteria.

    OpenAIRE

    Ileana Franco Zunda; Alfredo B. Quiñones Ceballos; Antonio L. Moreno Otero

    2005-01-01

    Fundament: Prostatic deseases are a havoc in male population older than 45 years old. Pseudohyperplastic carcinoma is a non frecuent variety and hard to diagnose. Objective: to reevaluate prostatic hyperplasia diagnoses to identify pseudohyperplastic carcinomas. Methods: retrospective study in which the prostatic hyperplasia diagnoses of 2004 were reevaluated in the Uiversitary Hospital ¨Dr. Gustavo Aldereguia Lima¨, considering as a basis the criteria given by Julian Arista -Nasr, evaluated ...

  20. Prostatic carcinoma in two cats

    International Nuclear Information System (INIS)

    Caney, S.M.A.; Holt, P.E.; Day, M.J.; Rudorf, H.; Gruffydd-Jones, T.J.

    1998-01-01

    Clinical, radiological and pathological features of two cats with prostatic carcinoma are reported. In both cats the presenting history included signs of lower urinary tract disease with haematuria and dysuria. Prostatomegaly was visible radiographically in one cat; an irregular intraprostatic urethra was seen on retrograde contrast urethrography in both cats. In one of the cats, neoplasia was suspected on the basis of a transurethral catheter biopsy. Following a poor response to palliative treatment in both cases, euthanasia was performed with histological confirmation of the diagnosis

  1. Granulomatous prostatitis: a pitfall in MR imaging of prostatic carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Gevenois, P.A. [Dept. of Radiology, Cliniques Univ. de Bruxelles, Hopital Erasme (Belgium); Stallenberg, B. [Dept. of Radiology, Cliniques Univ. de Bruxelles, Hopital Erasme (Belgium); Sintzoff, S.A. [Dept. of Radiology, Cliniques Univ. de Bruxelles, Hopital Erasme (Belgium); Salmon, I. [Dept. of Pathology, Cliniques Univ. de Bruxelles, Hopital Erasme (Belgium); Regemorter, G. van [Dept. of Urology, Cliniques Univ. de Bruxelles, Hopital Erasme (Belgium); Struyven, J. [Dept. of Radiology, Cliniques Univ. de Bruxelles, Hopital Erasme (Belgium)

    1992-08-01

    Granulomatous prostatitis is an uncommon disease that can mimic prostatic carcinoma on both digital rectal examination and transrectal ultrasound. Four patients who underwent magnetic resonance imaging of the prostate had a histological diagnosis of granulomatous prostatitis; three of them had recent urinary tract infections. The other patient had an associated midline prostatic cyst and a focus of malignancy. T1- and T2-weighted spin-echo images were obtained in all cases. Peripheral zone lesions of decreased signal intensity, suggestive of carcinoma, were found in all four patients on T2-weighted images. Granulomatous prostatitis should be considered in the differential diagnosis of low signal intensity areas with prostatic magnetic resonance imaging. (orig.)

  2. Cadmium, Zinc, and Selenium Levels in Carcinoma of the Human Prostate

    National Research Council Canada - National Science Library

    Sarafanov, Andrey; Centeno, Jose A

    2008-01-01

    .... The objectives are: 1) to establish reliability of using formalin-fixed paraffin-embedded (FFPE) prostate tissue for analysis of Zn, Se and Cd tissue by comparing their levels in the fresh specimen...

  3. Proteomic analysis of human oral verrucous carcinoma

    African Journals Online (AJOL)

    Jane

    2011-10-05

    Oct 5, 2011 ... This study is about proteomic analysis of oral verrucous carcinoma (OVC). The total proteins ..... receptor protein (recoverin) through autoimmunity ..... chromosome 8q21.1 and overexpressed in human prostate cancer. Cancer ...

  4. 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.

  5. 15,16-Dihydrotanshinone I, a Compound of Salvia miltiorrhiza Bunge, Induces Apoptosis through Inducing Endoplasmic Reticular Stress in Human Prostate Carcinoma Cells

    Directory of Open Access Journals (Sweden)

    Mao-Te Chuang

    2011-01-01

    Full Text Available 5,16-dihydrotanshinone I (DHTS is extracted from Salvia miltiorrhiza Bunge (tanshen root and was found to be the most effective compound of tanshen extracts against breast cancer cells in our previous studies. However, whether DHTS can induce apoptosis through an endoplasmic reticular (ER stress pathway was examined herein. In this study, we found that DHTS significantly inhibited the proliferation of human prostate DU145 carcinoma cells and induced apoptosis. DHTS was able to induce ER stress as evidenced by the upregulation of glucose regulation protein 78 (GRP78/Bip and CAAT/enhancer binding protein homologous protein/growth arrest- and DNA damage-inducible gene 153 (CHOP/GADD153, as well as increases in phosphorylated eukaryotic initiation factor 2α (eIF2α, c-jun N-terminal kinase (JNK, and X-box-binding protein 1 (XBP1 mRNA splicing forms. DHTS treatment also caused significant accumulation of polyubiquitinated proteins and hypoxia-inducible factor (HIF-1α, indicating that DHTS might be a proteasome inhibitor that is known to induce ER stress or enhance apoptosis caused by the classic ER stress-dependent mechanism. Moreover, DHTS-induced apoptosis was reversed by salubrinal, an ER stress inhibitor. Results suggest that DHTS can induce apoptosis of prostate carcinoma cells via induction of ER stress and/or inhibition of proteasome activity, and may have therapeutic potential for prostate cancer patients.

  6. Prostate-specific antigen superior serum marker for prostatic carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Heaney, J A; Allen, M A; Keane, T; Duffy, J J

    1987-05-01

    A new immunoradiometric assay based on dual monoclonal antibody reaction system (Hybritech-TANDEM/sup R/) was used to measure serum levels of prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) in 39 patients with prostatic carcinoma (CaP), in 57 with benign prostatic hyperplasia (BPH) and in 14 without prostatic disease. Serum PSA was elevated in 82% of patients with CaP while PAP was elevated in only 54%. In this and other studies, PSA is superior to conventional serum markers in sensitivity, prediction of CaP stage and in longitudinal monitoring of disease. A 16% false positive rate precludes PSA as a screening test. The assay used was found to be simple and reliable.

  7. Prostate-specific antigen superior serum marker for prostatic carcinoma

    International Nuclear Information System (INIS)

    Heaney, J.A.; Allen, M.A.; Keane, T.; Duffy, J.J.

    1987-01-01

    A new immunoradiometric assay based on dual monoclonal antibody reaction system (Hybritech-TANDEM R ) was used to measure serum levels of prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) in 39 patients with prostatic carcinoma (CaP), in 57 with benign prostatic hyperplasia (BPH) and in 14 without prostatic disease. Serum PSA was elevated in 82% of patients with CaP while PAP was elevated in only 54%. In this and other studies, PSA is superior to conventional serum markers in sensitivity, prediction of CaP stage and in longitudinal monitoring of disease. A 16% false positive rate precludes PSA as a screening test. The assay used was found to be simple and reliable. (author)

  8. TRP Channels in Human Prostate

    Directory of Open Access Journals (Sweden)

    Carl Van Haute

    2010-01-01

    Full Text Available This review gives an overview of morphological and functional characteristics in the human prostate. It will focus on the current knowledge about transient receptor potential (TRP channels expressed in the human prostate, and their putative role in normal physiology and prostate carcinogenesis. Controversial data regarding the expression pattern and the potential impact of TRP channels in prostate function, and their involvement in prostate cancer and other prostate diseases, will be discussed.

  9. Ghrelin inhibits proliferation and increases T-type Ca{sup 2+} channel expression in PC-3 human prostate carcinoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Diaz-Lezama, Nundehui; Hernandez-Elvira, Mariana [Laboratory of Neuroendocrinology, Institute of Physiology, Autonomous University of Puebla (BUAP), Puebla (Mexico); Sandoval, Alejandro [School of Medicine FES Iztacala, National Autonomous University of Mexico (UNAM), Tlalnepantla (Mexico); Monroy, Alma; Felix, Ricardo [Department of Cell Biology, Center for Research and Advanced Studies of the National Polytechnic Institute (Cinvestav-IPN), Mexico City (Mexico); Monjaraz, Eduardo, E-mail: emguzman@siu.buap.mx [Laboratory of Neuroendocrinology, Institute of Physiology, Autonomous University of Puebla (BUAP), Puebla (Mexico)

    2010-12-03

    Research highlights: {yields} Ghrelin decreases prostate carcinoma PC-3 cells proliferation. {yields} Ghrelin favors apoptosis in PC-3 cells. {yields} Ghrelin increase in intracellular free Ca{sup 2+} levels in PC-3 cells. {yields} Grelin up-regulates expression of T-type Ca{sup 2+} channels in PC-3 cells. {yields} PC-3 cells express T-channels of the Ca{sub V}3.1 and Ca{sub V}3.2 subtype. -- Abstract: Ghrelin is a multifunctional peptide hormone with roles in growth hormone release, food intake and cell proliferation. With ghrelin now recognized as important in neoplastic processes, the aim of this report is to present findings from a series of in vitro studies evaluating the cellular mechanisms involved in ghrelin regulation of proliferation in the PC-3 human prostate carcinoma cells. The results showed that ghrelin significantly decreased proliferation and induced apoptosis. Consistent with a role in apoptosis, an increase in intracellular free Ca{sup 2+} levels was observed in the ghrelin-treated cells, which was accompanied by up-regulated expression of T-type voltage-gated Ca{sup 2+} channels. Interestingly, T-channel antagonists were able to prevent the effects of ghrelin on cell proliferation. These results suggest that ghrelin inhibits proliferation and may promote apoptosis by regulating T-type Ca{sup 2+} channel expression.

  10. Metastatic Breast Carcinoma to the Prostate Gland

    Directory of Open Access Journals (Sweden)

    Meghan E. Kapp

    2016-01-01

    Full Text Available Cancer of the male breast is an uncommon event with metastases to the breast occurring even less frequently. Prostate carcinoma has been reported as the most frequent primary to metastasize to the breast; however, the reverse has not been previously reported. Herein, we present, for the first time, a case of breast carcinoma metastasizing to the prostate gland. Prostate needle core biopsy revealed infiltrative nests of neoplastic epithelioid cells, demonstrated by immunohistochemistry (IHC to be positive for GATA3 and ER and negative for PSA and P501S. A prostate cocktail by IHC study demonstrated lack of basal cells (p63 and CK903 and no expression of P501S. The patient’s previous breast needle core biopsy showed strong ER positivity and negative staining for PR and HER2. Similar to the prostate, the breast was negative for CK5/6, p63, and p40. This case demonstrates the importance of considering a broad differential diagnosis and comparing histology and IHC to prior known malignancies in the setting of atypical presentation or rare tumors.

  11. Microbeam X-ray fluorescence mapping of Cu and Fe in human prostatic carcinoma cell lines using synchrotron radiation

    Energy Technology Data Exchange (ETDEWEB)

    Rocha, K.M.J.; Leitao, R.G.; Oliveira-Barros, E.G.; Oliveira, M.A.; Canellas, C.G.L.; Anjos, M.J.; Nasciutti, L.E.; Lopes, R.T., E-mail: kjose@nuclear.ufrj.br, E-mail: marcelin@lin.ufrj.br, E-mail: ricardo@lin.ufrj.br, E-mail: roberta@lin.ufrj.br, E-mail: eligouveab@gmail.com, E-mail: maria_aparecida_ufrj@yahoo.com.br, E-mail: luiz.nasciutti@histo.ufrj.br, E-mail: roberta.leitao@uerj.br, E-mail: marcelin@uerj.br [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil). Laboratorio de Instrumentacao Nuclear; Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil). Instituto de Ciencias Biomedicas; Universidade do Estado do Rio de Janeiro (UERJ), RJ (Brazil). Instituto de Fisica

    2017-11-01

    Cancer is a worldwide public health problem and prostate cancer continues to be one of the most common fatal cancers in men. Copper plays an important role in the aetiology and growth of tumours however, whether intratumoral copper is actually elevated in prostate cancer patients has not been established. Iron, an important trace element, plays a vital function in oxygen metabolism, oxygen uptake, and electron transport in mitochondria, energy metabolism, muscle function, and hematopoiesis. The X-ray microfluorescence technique (μXRF) is a rapid and non-destructive method of elemental analysis that provides useful elemental information about samples without causing damage or requiring extra sample preparations. This study investigated the behavior of cells in spheroids of human prostate cells, tumour cell line (DU145) and normal cell line (RWPE-1), after supplementation with zinc chloride by 24 hours using synchrotron X-ray microfluorescence (μSRXRF). The measurements were performed with a standard geometry of 45 deg of incidence, excited by a white beam using a pixel of 25 μm and a time of 300 ms/pixel at the XRF beamline at the Synchrotron Light National Laboratory (Campinas, Brazil). The results by SRμXRF showed non-uniform Cu and Fe distributions in all the spheroids analyzed. (author)

  12. Microbeam X-ray fluorescence mapping of Cu and Fe in human prostatic carcinoma cell lines using synchrotron radiation

    International Nuclear Information System (INIS)

    Rocha, K.M.J.; Leitao, R.G.; Oliveira-Barros, E.G.; Oliveira, M.A.; Canellas, C.G.L.; Anjos, M.J.; Nasciutti, L.E.; Lopes, R.T.; Universidade Federal do Rio de Janeiro; Universidade do Estado do Rio de Janeiro

    2017-01-01

    Cancer is a worldwide public health problem and prostate cancer continues to be one of the most common fatal cancers in men. Copper plays an important role in the aetiology and growth of tumours however, whether intratumoral copper is actually elevated in prostate cancer patients has not been established. Iron, an important trace element, plays a vital function in oxygen metabolism, oxygen uptake, and electron transport in mitochondria, energy metabolism, muscle function, and hematopoiesis. The X-ray microfluorescence technique (μXRF) is a rapid and non-destructive method of elemental analysis that provides useful elemental information about samples without causing damage or requiring extra sample preparations. This study investigated the behavior of cells in spheroids of human prostate cells, tumour cell line (DU145) and normal cell line (RWPE-1), after supplementation with zinc chloride by 24 hours using synchrotron X-ray microfluorescence (μSRXRF). The measurements were performed with a standard geometry of 45 deg of incidence, excited by a white beam using a pixel of 25 μm and a time of 300 ms/pixel at the XRF beamline at the Synchrotron Light National Laboratory (Campinas, Brazil). The results by SRμXRF showed non-uniform Cu and Fe distributions in all the spheroids analyzed. (author)

  13. Expression and localization of GLUT1 and GLUT12 in prostate carcinoma.

    Science.gov (United States)

    Chandler, Jenalle D; Williams, Elizabeth D; Slavin, John L; Best, James D; Rogers, Suzanne

    2003-04-15

    Increased glucose consumption is a characteristic of malignant cells and in prostate carcinoma is associated with the proliferation of both androgen-dependent and independent cells. Transport of polar glucose across the nonpolar membrane relies on glucose transporter proteins, known as GLUTs. Increased expression of GLUT1 is a characteristic of many malignant cells. The authors characterized and cloned the cDNA for a novel glucose transporter, GLUT12, which was identified initially in malignant breast epithelial cells. To the authors' knowledge, there have been no reports on the expression of glucose transporters in the human prostate or human prostate carcinoma cells. The authors evaluated GLUT1 and GLUT12 expression in human prostate carcinoma cells. Reverse transcription-polymerase chain reaction was performed on total RNA extracted from cultured prostate carcinoma cells LNCaP, C4, C4-2, and C4-2B using primers to amplify GLUT1, GLUT12, or the housekeeping gene, 36B4. Total protein extracted from prostate carcinoma cell lines was assessed for GLUT12 protein by Western blot analysis. Cultured cell monolayers were incubated with antibodies to GLUT1 or GLUT12 and a peripheral Golgi protein, Golgi 58K, for detection by immunofluorescent confocal microscopy. Sections of benign prostatic hyperplasia and human prostate carcinoma were stained for immunohistochemical detection of GLUT1 and GLUT12. GLUT1 and GLUT12 mRNA and protein were detected in all cell lines evaluated. Immunofluorescence staining demonstrated both GLUT1 and GLUT12 on the plasma membrane and in the cytoplasm in all cultured prostate carcinoma cell lines, with GLUT1 but not GLUT12 appearing to colocalize with the Golgi. Immunohistochemical staining of benign prostatic hyperplasia indicated expression of GLUT1 but not GLUT12. Malignant tissue stained for GLUT12 but was negative for GLUT1. GLUT1 and GLUT12 are expressed in human prostate carcinoma cells. One possible rationale for the GLUT1 Golgi

  14. Evolution of brachytherapy for prostate carcinoma

    International Nuclear Information System (INIS)

    Qin Lan

    2005-01-01

    Brachytherapy is one of the most main management to prostate carcinoma. This method has been rapidly accepted in clinical application since it is a convenient, little-traumatic, and outpatient therapy. With the development of techniques of production of radio-seeds, imaging modality and three-dimensional radiotherapy plan system, brachytherapy has been made a virtually progress in improving curative-effect and reducing damage to surrounding normal tissue. (authors)

  15. Cyclin D1 expression in prostate carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Pereira, R.A.; Ravinal, R.C.; Costa, R.S.; Lima, M.S. [Universidade de São Paulo, Faculdade de Medicina de Ribeirão Preto, Departamento de Patologia, Ribeirão Preto, SP, Brasil, Departamento de Patologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Tucci, S. [Universidade de São Paulo, Faculdade de Medicina de Ribeirão Preto, Departamento de Cirurgia e Anatomia, Divisão de Urologia, Ribeirão Preto, SP, Brasil, Divisão de Urologia, Departamento de Cirurgia e Anatomia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Muglia, V.F. [Universidade de São Paulo, Faculdade de Medicina de Ribeirão Preto, Departamento de Medicina Interna (Centro de Ciência da Imagem), Ribeirão Preto, SP, Brasil, Departamento de Medicina Interna (Centro de Ciência da Imagem), Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Reis, R.B. Dos [Universidade de São Paulo, Faculdade de Medicina de Ribeirão Preto, Departamento de Cirurgia e Anatomia, Divisão de Urologia, Ribeirão Preto, SP, Brasil, Divisão de Urologia, Departamento de Cirurgia e Anatomia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Silva, G.E.B. [Universidade de São Paulo, Faculdade de Medicina de Ribeirão Preto, Departamento de Patologia, Ribeirão Preto, SP, Brasil, Departamento de Patologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil)

    2014-05-09

    The purpose of this study was to investigate the relationship between cyclin D1 expression and clinicopathological parameters in patients with prostate carcinoma. We assessed cyclin D1 expression by conventional immunohistochemistry in 85 patients who underwent radical prostatectomy for prostate carcinoma and 10 normal prostate tissue samples retrieved from autopsies. We measured nuclear immunostaining in the entire tumor area and based the results on the percentage of positive tumor cells. The preoperative prostate-specific antigen (PSA) level was 8.68±5.16 ng/mL (mean±SD). Cyclin D1 staining was positive (cyclin D1 expression in >5% of tumor cells) in 64 cases (75.4%) and negative (cyclin D1 expression in ≤5% of tumor cells) in 21 cases (including 15 cases with no immunostaining). Normal prostate tissues were negative for cyclin D1. Among patients with a high-grade Gleason score (≥7), 86% of patients demonstrated cyclin D1 immunostaining of >5% (P<0.05). In the crude analysis of cyclin D1 expression, the high-grade Gleason score group showed a mean expression of 39.6%, compared to 26.9% in the low-grade Gleason score group (P<0.05). Perineural invasion tended to be associated with cyclin D1 expression (P=0.07), whereas cyclin D1 expression was not associated with PSA levels or other parameters. Our results suggest that high cyclin D1 expression could be a potential marker for tumor aggressiveness.

  16. Cyclin D1 expression in prostate carcinoma

    International Nuclear Information System (INIS)

    Pereira, R.A.; Ravinal, R.C.; Costa, R.S.; Lima, M.S.; Tucci, S.; Muglia, V.F.; Reis, R.B. Dos; Silva, G.E.B.

    2014-01-01

    The purpose of this study was to investigate the relationship between cyclin D1 expression and clinicopathological parameters in patients with prostate carcinoma. We assessed cyclin D1 expression by conventional immunohistochemistry in 85 patients who underwent radical prostatectomy for prostate carcinoma and 10 normal prostate tissue samples retrieved from autopsies. We measured nuclear immunostaining in the entire tumor area and based the results on the percentage of positive tumor cells. The preoperative prostate-specific antigen (PSA) level was 8.68±5.16 ng/mL (mean±SD). Cyclin D1 staining was positive (cyclin D1 expression in >5% of tumor cells) in 64 cases (75.4%) and negative (cyclin D1 expression in ≤5% of tumor cells) in 21 cases (including 15 cases with no immunostaining). Normal prostate tissues were negative for cyclin D1. Among patients with a high-grade Gleason score (≥7), 86% of patients demonstrated cyclin D1 immunostaining of >5% (P<0.05). In the crude analysis of cyclin D1 expression, the high-grade Gleason score group showed a mean expression of 39.6%, compared to 26.9% in the low-grade Gleason score group (P<0.05). Perineural invasion tended to be associated with cyclin D1 expression (P=0.07), whereas cyclin D1 expression was not associated with PSA levels or other parameters. Our results suggest that high cyclin D1 expression could be a potential marker for tumor aggressiveness

  17. Testosterone metabolism of fibroblasts grown from prostatic carcinoma, benign prostatic hyperplasia and skin fibroblasts

    International Nuclear Information System (INIS)

    Schweikert, H.U.; Hein, H.J.; Romijn, J.C.; Schroeder, F.H.

    1982-01-01

    The metabolism of [1,2,6,7-3H]testosterone was assessed in fibroblast monolayers derived from tissue of 5 prostates with benign hyperplasia (BPH), 4 prostates with carcinoma (PC), and 3 biopsy samples of skin, 2 nongenital skin (NG) and 1 genital skin. The following metabolites could be identified: androstanedione androstenedione, dihydrotestosterone, androsterone, epiandrosterone, androstane-3 alpha, 17 beta-diol and androstane-3 beta, 17 beta-diol. Testosterone was metabolized much more rapidly in fibroblasts originating from prostatic tissue than in fibroblasts derived from NG. A significantly higher formation of 5 alpha-androstanes and 3 alpha-hydroxysteroids could be observed in fibroblasts from BPH as compared to PC. 17-ketosteroid formation exceeded 5 alpha-androstane formation in BPH, whereas 5 alpha-reduction was the predominant pathway in fibroblasts grown from PC and NG. Since testosterone metabolism in fibroblasts of prostatic origin therefore resembles in many aspects that in whole prostatic tissue, fibroblasts grown from prostatic tissues might be a valuable tool for further investigation of the pathogenesis of human BPH and PC

  18. Prostatic carcinoma: limited field irradiation

    International Nuclear Information System (INIS)

    Rounsaville, M.C.; Green, J.P.; Vaeth, J.M.; Purdon, R.P.; Heltzel, M.M.

    1987-01-01

    This is a retrospective study of 251 patients with histologically proven adenocarcinoma treated primarily with limited field radiotherapy techniques, under the principle direction of authors JMV and JPG, between 1968 and 1981 in San Francisco, California. All patients are followed for a minimum of 3 years; mean follow-up is 7.3 years. Routine clinical staging procedures included: HandP, digital prostate exam, cystoscopy, biopsy, blood studies including serum acid phosphatase, and imaging studies including chest X ray, IVP, bone survey or radionucleotide bone scan, and in recent years, pelvic CT scans. Twelve patients are Stage A1, 37-Stage A2, 50-Stage B, 140-Stage C1 and 12-Stage C2. Ninety percent of all cases and 85% of Stage C patients were treated with limited fields to the prostate and periprostatic volume only. Total doses were prescribed at midplane or isocenter and were generally 6500-7000 cGy, daily doses of 180-200 cGy, 5 days per week. Actuarial 5- and 10-year survival rates are: entire population-69% and 47%; Stage A1-74% and 50%; Stage A2-81% and 67%; Stage B-84% and 53%; Stage C1-63% and 42%; Stage C2-32% and 11%. The 5- and 10-year disease-free actuarial survivals are: entire population-71% and 50%; Stage A1-89% and 74%; Stage A2-82% and 69%; Stage B-71% and 52%; Stage C1-67% and 44%; Stage C2-0%. Sites of recurrence, alone or as a component of the failure pattern are: 37 (15%) local, 11 (4%) symptomatic regional recurrence (lower extremity edema, pelvic pain/sciatica, hydroureteronephrosis), and 87 (35%) distant metastasis. Seven (3%) had unknown sites of failure. Local-regional failure occurred in 42% of Stage C2 patients

  19. p53 and PTEN/MMAC1/TEP1 gene therapy of human prostate PC-3 carcinoma xenograft, using transferrin-facilitated lipofection gene delivery strategy.

    Science.gov (United States)

    Seki, Masafumi; Iwakawa, Jun; Cheng, Helen; Cheng, Pi-Wan

    2002-04-10

    We previously reported that supplementation of a cationic liposome with transferrin (Tf) greatly enhanced lipofection efficiency (P.-W. Cheng, Hum. Gene Ther. 1996;7:275-282). In this study, we examined the efficacy of p53 and PTEN tumor suppressor gene therapy in a mouse xenograft model of human prostate PC-3 carcinoma cells, using a vector consisting of dimyristoyloxypropyl-3-dimethylhydroxyethyl ammonium bromide (DMRIE)-cholesterol (DC) and Tf. When the volume of the tumors grown subcutaneously in athymic nude mice reached 50-60 mm(3), three intratumoral injections of the following four formulations were performed during week 1 and then during week 3: (1) saline, (2) DC + Tf + pCMVlacZ, (3) DC + Tf + pCMVPTEN, and (4) DC + Tf + pCMVp53 (standard formulation). There was no significant difference in tumor volume and survival between group 1 and group 2 animals. As compared with group 1 controls, group 3 animals had slower tumor growth during the first 3 weeks but thereafter their tumor growth rate was similar to that of the controls. By day 2 posttreatment, group 4 animals had significantly lower tumor volume relative to initial tumor volume as well as controls at the comparable time point. Also, animals treated with p53 survived longer. Treatment with DC, Tf, pCMVp53, DC + pCMVp53, or Tf + pCMVp53 had no effect on tumor volume or survival. Expression of p53 protein and apoptosis were detected in tumors treated with the standard formulation, thus associating p53 protein expression and apoptosis with efficacy. However, p53 protein was expressed in only a fraction of the tumor cells, suggesting a role for bystander effects in the efficacy of p53 gene therapy. We conclude that intratumoral gene delivery by a nonviral vector consisting of a cationic liposome and Tf can achieve efficacious p53 gene therapy of prostate cancer.

  20. Tissue concentrations of prostate-specific antigen in prostatic carcinoma and benign prostatic hyperplasia.

    Science.gov (United States)

    Pretlow, T G; Pretlow, T P; Yang, B; Kaetzel, C S; Delmoro, C M; Kamis, S M; Bodner, D R; Kursh, E; Resnick, M I; Bradley, E L

    1991-11-11

    Prostate-specific antigen (PSA), as measured in peripheral blood, is currently the most widely used marker for the assessment of tumor burden in the longitudinal study of patients with carcinoma of the prostate (PCA). Studies from other laboratories have led to the conclusion that a given volume of PCA causes a much higher level of PSA in the peripheral circulation of patients than a similar volume of prostate without carcinoma. We have evaluated PSA in the resected tissues immunohistochemically and in extracts of PCA and of prostates resected because of benign prostatic hyperplasia (BPH) with an enzyme-linked immunosorbent assay. Immunohistochemical results were less quantitative than but consistent with the results of the ELISA of tissue extracts. Immunohistochemically, there was considerable heterogeneity in the expression of PSA by both PCA and BPH both within and among prostatic tissues from different patients. While the levels of expression of PSA in these tissues overlap broadly, PSA is expressed at a lower level in PCA than in BPH when PSA is expressed as a function of wet weight of tissue (p = 0.0095), wet weight of tissue/% epithelium (p less than 0.0001), protein extracted from the tissue (p = 0.0039), or protein extracted/% epithelium (p less than 0.0001).

  1. Radioimmunoassay for a human prostate specific antigen

    International Nuclear Information System (INIS)

    Machida, T.; Miki, M.; Ohishi, Y.; Kido, A.; Morikawa, J.; Ogawa, Y.

    1983-01-01

    As a marker for prostatic cancer, a prostate-specific antigen was purified from human prostatic tissues. Double antibody radioimmunoassay utilizing immune reaction was developed on the basis of the purified prostatic antigen (PA). Measurement results have revealed that PA radioimmunoassay is much better than prostatic acid phosphatase (PAP) radioimmunoassay in the diagnosis of prostatic cancer

  2. Studies on the pathogenesis and management of prostate carcinoma in dogs

    NARCIS (Netherlands)

    L'Eplattenier, H.F.

    2009-01-01

    The dog is one of the few species to develop spontaneous prostate carcinoma (PCA) and is thus an attractive model for the study of the disease in humans. Many of the features of the disease in the dog are similar to its human counterpart, however a number of aspects of the pathogenesis, diagnosis

  3. 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

  4. Silibinin inhibits fibronectin induced motility, invasiveness and survival in human prostate carcinoma PC3 cells via targeting integrin signaling

    Energy Technology Data Exchange (ETDEWEB)

    Deep, Gagan [Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Denver, Aurora, CO (United States); University of Colorado Cancer Center, University of Colorado Denver, Aurora, CO (United States); Kumar, Rahul; Jain, Anil K. [Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Denver, Aurora, CO (United States); Agarwal, Chapla [Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Denver, Aurora, CO (United States); University of Colorado Cancer Center, University of Colorado Denver, Aurora, CO (United States); Agarwal, Rajesh, E-mail: Rajesh.agarwal@ucdenver.edu [Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Denver, Aurora, CO (United States); University of Colorado Cancer Center, University of Colorado Denver, Aurora, CO (United States)

    2014-10-15

    Highlights: • Silibinin inhibits fibronectin-induce motile morphology in PC3 cells. • Silibinin inhibits fibronectin-induced migration and invasion in PC3 cells. • Silibinin targets fibronectin-induced integrins and downstream signaling molecule. - Abstract: Prostate cancer (PCA) is the 2nd leading cause of cancer-related deaths among men in the United States. Preventing or inhibiting metastasis-related events through non-toxic agents could be a useful approach for lowering high mortality among PCA patients. We have earlier reported that natural flavonoid silibinin possesses strong anti-metastatic efficacy against PCA however, mechanism/s of its action still remains largely unknown. One of the major events during metastasis is the replacement of cell–cell interaction with integrins-based cell–matrix interaction that controls motility, invasiveness and survival of cancer cells. Accordingly, here we examined silibinin effect on advanced human PCA PC3 cells’ interaction with extracellular matrix component fibronectin. Silibinin (50–200 μM) treatment significantly decreased the fibronectin (5 μg/ml)-induced motile morphology via targeting actin cytoskeleton organization in PC3 cells. Silibinin also decreased the fibronectin-induced cell proliferation and motility but significantly increased cell death in PC3 cells. Silibinin also inhibited the PC3 cells invasiveness in Transwell invasion assays with fibronectin or cancer associated fibroblasts (CAFs) serving as chemoattractant. Importantly, PC3-luc cells cultured on fibronectin showed rapid dissemination and localized in lungs following tail vein injection in athymic male nude mice; however, in silibinin-treated PC3-luc cells, dissemination and lung localization was largely compromised. Molecular analyses revealed that silibinin treatment modulated the fibronectin-induced expression of integrins (α5, αV, β1 and β3), actin-remodeling (FAK, Src, GTPases, ARP2 and cortactin), apoptosis (cPARP and

  5. Silibinin inhibits fibronectin induced motility, invasiveness and survival in human prostate carcinoma PC3 cells via targeting integrin signaling

    International Nuclear Information System (INIS)

    Deep, Gagan; Kumar, Rahul; Jain, Anil K.; Agarwal, Chapla; Agarwal, Rajesh

    2014-01-01

    Highlights: • Silibinin inhibits fibronectin-induce motile morphology in PC3 cells. • Silibinin inhibits fibronectin-induced migration and invasion in PC3 cells. • Silibinin targets fibronectin-induced integrins and downstream signaling molecule. - Abstract: Prostate cancer (PCA) is the 2nd leading cause of cancer-related deaths among men in the United States. Preventing or inhibiting metastasis-related events through non-toxic agents could be a useful approach for lowering high mortality among PCA patients. We have earlier reported that natural flavonoid silibinin possesses strong anti-metastatic efficacy against PCA however, mechanism/s of its action still remains largely unknown. One of the major events during metastasis is the replacement of cell–cell interaction with integrins-based cell–matrix interaction that controls motility, invasiveness and survival of cancer cells. Accordingly, here we examined silibinin effect on advanced human PCA PC3 cells’ interaction with extracellular matrix component fibronectin. Silibinin (50–200 μM) treatment significantly decreased the fibronectin (5 μg/ml)-induced motile morphology via targeting actin cytoskeleton organization in PC3 cells. Silibinin also decreased the fibronectin-induced cell proliferation and motility but significantly increased cell death in PC3 cells. Silibinin also inhibited the PC3 cells invasiveness in Transwell invasion assays with fibronectin or cancer associated fibroblasts (CAFs) serving as chemoattractant. Importantly, PC3-luc cells cultured on fibronectin showed rapid dissemination and localized in lungs following tail vein injection in athymic male nude mice; however, in silibinin-treated PC3-luc cells, dissemination and lung localization was largely compromised. Molecular analyses revealed that silibinin treatment modulated the fibronectin-induced expression of integrins (α5, αV, β1 and β3), actin-remodeling (FAK, Src, GTPases, ARP2 and cortactin), apoptosis (cPARP and

  6. Comparison of two peptide radiotracers for prostate carcinoma targeting

    Directory of Open Access Journals (Sweden)

    Bluma Linkowski Faintuch

    2012-01-01

    Full Text Available OBJECTIVES: Scintigraphy is generally not the first choice treatment for prostate cancer, although successful studies using bombesin analog radiopeptides have been performed. Recently, a novel peptide obtained using a phage display library demonstrated an affinity for prostate tumor cells. The aim of this study was to compare the use of a bombesin analog to that of a phage display library peptide (DUP-1 radiolabeled with technetium-99m for the treatment of prostate carcinoma. The peptides were first conjugated to S-acetyl-MAG3 with a 6-carbon spacer, namely aminohexanoic acid. METHODS: The technetium-99m labeling required a sodium tartrate buffer. Radiochemical evaluation was performed using ITLC and was confirmed by high-performance liquid chromatography. The coefficient partition was determined, and in vitro studies were performed using human prostate tumor cells. Biodistribution was evaluated in healthy animals at various time points and also in mice bearing tumors. RESULTS: The radiochemical purity of both radiotracers was greater than 95%. The DUP-1 tracer was more hydrophilic (log P = -2.41 than the bombesin tracer (log P = -0.39. The biodistribution evaluation confirmed this hydrophilicity by revealing the greater kidney uptake of DUP-1. The bombesin concentration in the pancreas was greater than that of DUP-1 due to specific gastrin-releasing peptide receptors. Bombesin internalization occurred for 78.32% of the total binding in tumor cells. The DUP-1 tracer showed very low binding to tumor cells during the in vitro evaluation, although tumor uptake for both tracers was similar. The tumors were primarily blocked by DUP1 and the bombesin radiotracer primarily targeted the pancreas. CONCLUSION: Further studies with the radiolabeled DUP-1 peptide are recommended. With further structural changes, this molecule could become an efficient alternative tracer for prostate tumor diagnosis.

  7. HUMAN PROSTATE CANCER RISK FACTORS

    Science.gov (United States)

    Prostate cancer has the highest prevalence of any non-skin cancer in the human body, with similar likelihood of neoplastic foci found within the prostates of men around the world regardless of diet, occupation, lifestyle, or other factors. Essentially all men with circulating an...

  8. Education concerning carcinoma of prostate and its early detection.

    Science.gov (United States)

    Dutkiewcz, Sławomir; Jędrzejewska, Sylwia

    2011-01-01

    Prostate cancer is the most common male cancer. Insufficient knowledge of PCa among men causes its low detection. Lack of essential actions in health education and widely understood prophylaxis, the need of the latter are maybe responsible for the increasing mortality rate. According to our assumption, educating men increase their awareness on the need of screening tests and results in increasing reporting to physical examinations. This in turn allows for an early detection of the disease. A research was conducted between the years 2003-2009 on the knowledge of PCa among 260 men. They were divided into two groups. Group A - 63 patients treated for carcinoma of prostate and group B - 197 men reporting spontaneously to screening tests. In order to check the adopted hypothesis, we prepared an educational material and test of knowledge - test with a questionnaire. Knowledge was evaluated before (test I) and after the education process (test II). Until 2009, we were monitoring the number of patients from group B reporting to screening tests and their knowledge was once again checked (test III). Two subgroups C and D were created from group B - 117 healthy men and 80 with diagnosed diseases respectively (70 with benign prostatic hyperplasia, 7 with prostatitis, and 3 with carcinoma of prostate). Patients with prostatitis and PCa and 3 patients from group C not reporting to the tests were excluded from further monitoring. Maths statistics with the use of SPSS 12.0 PL program and Statistica 6.0 constituted the base for working out the results. We observed a higher knowledge about carcinoma of prostate in group A than in group B (p 40 from groups C and D were interested in health care (p70 a lower level of motivation was observed. The interest was proportional to the level of education, and this was differentiating in an analogical way the motivation to extend knowledge about prostate cancer (padvanced state, and during 5 years in group C - in 4 men at an early development

  9. Investigation of the expression of the EphB4 receptor tyrosine kinase in prostate carcinoma

    International Nuclear Information System (INIS)

    Lee, Yen-Ching; Perren, Janeanne R; Douglas, Evelyn L; Raynor, Michael P; Bartley, Maria A; Bardy, Peter G; Stephenson, Sally-Anne

    2005-01-01

    The EphB4 receptor tyrosine kinase has been reported as increased in tumours originating from several different tissues and its expression in a prostate cancer xenograft model has been reported. RT-PCR, western blotting and immunohistochemical techniques were used to examine EphB4 expression and protein levels in human prostate cancer cell lines LNCaP, DU145 and PC3. Immunohistochemistry was also used to examine localisation of EphB4 in tissue samples from 15 patients with prostate carcinomas. All three prostate cancer cell lines expressed the EphB4 gene and protein. EphB4 immunoreactivity in vivo was significantly greater in human prostate cancers as compared with matched normal prostate epithelium and there appeared to be a trend towards increased expression with higher grade disease. EphB4 is expressed in prostate cancer cell lines with increased expression in human prostate cancers when compared with matched normal tissue. EphB4 may therefore be a useful anti-prostate cancer target

  10. Feasibility study of CT perfusion imaging for prostate carcinoma

    International Nuclear Information System (INIS)

    Cullu, Nesat; Kantarci, Mecit; Ogul, Hayri; Pirimoglu, Berhan; Karaca, Leyla; Kizrak, Yesim; Adanur, Senol; Koc, Erdem; Polat, Ozkan; Okur, Aylin

    2014-01-01

    The aim of this feasibility study was to obtain initial data with which to assess the efficiency of perfusion CT imaging (CTpI) and to compare this with magnetic resonance imaging (MRI) in the diagnosis of prostate carcinoma. This prospective study involved 25 patients with prostate carcinoma undergoing MRI and CTpI. All analyses were performed on T2-weighted images (T2WI), apparent diffusion coefficient (ADC) maps, diffusion-weighted images (DWI) and CTp images. We compared the performance of T2WI combined with DWI and CTp alone. The study was approved by the local ethics committee, and written informed consent was obtained from all patients. Tumours were present in 87 areas according to the histopathological results. The diagnostic performance of the T2WI+DWI+CTpI combination was significantly better than that of T2WI alone for prostate carcinoma (P < 0.001). The diagnostic value of CTpI was similar to that of T2WI+DWI in combination. There were statistically significant differences in the blood flow and permeability surface values between prostate carcinoma and background prostate on CTp images. CTp may be a valuable tool for detecting prostate carcinoma and may be preferred in cases where MRI is contraindicated. If this technique is combined with T2WI and DWI, its diagnostic value is enhanced. (orig.)

  11. Local high voltage radiotherapy with curative intent for prostatic carcinoma

    International Nuclear Information System (INIS)

    Jacobi, G.H.; Kurth, K.H.; Hohenfellner, R.

    1979-01-01

    In a 10-year interval 179 patients with prostatic carcinoma were treated by cobalt-60 teletherapy (7600 R). A selected group of 47 patients with localized disease and irradiated with curative intent had serial prostatic biopsies and were analized after a minimum follow-up of 1 year. Biopsies of half of the patients rendered definitively negative, on an average 14 months after radiotherapy. 8 patients with initial negative biopsy changed to positive secondarily. In one third of the patients histological conversion was missed, considered as radiation persister. Persistent carcinoma were of predominant low grade. 5 patients developed distant metastases 30 months after irradiation on an average. These patients had persistent positive tissue studies. Over all cumulative 5-years survival was 89%. In patients with prostatic carcinoma and local high voltage radiotherapy with curative intent (stage A through C) serial prostatic biopsies to document therapy effect seen mandatory. (orig.) 891 AJ/orig. 892 BRE [de

  12. Human Prostate Cancer Hallmarks Map

    Science.gov (United States)

    Datta, Dipamoy; Aftabuddin, Md.; Gupta, Dinesh Kumar; Raha, Sanghamitra; Sen, Prosenjit

    2016-01-01

    Human prostate cancer is a complex heterogeneous disease that mainly affects elder male population of the western world with a high rate of mortality. Acquisitions of diverse sets of hallmark capabilities along with an aberrant functioning of androgen receptor signaling are the central driving forces behind prostatic tumorigenesis and its transition into metastatic castration resistant disease. These hallmark capabilities arise due to an intense orchestration of several crucial factors, including deregulation of vital cell physiological processes, inactivation of tumor suppressive activity and disruption of prostate gland specific cellular homeostasis. The molecular complexity and redundancy of oncoproteins signaling in prostate cancer demands for concurrent inhibition of multiple hallmark associated pathways. By an extensive manual curation of the published biomedical literature, we have developed Human Prostate Cancer Hallmarks Map (HPCHM), an onco-functional atlas of human prostate cancer associated signaling and events. It explores molecular architecture of prostate cancer signaling at various levels, namely key protein components, molecular connectivity map, oncogenic signaling pathway map, pathway based functional connectivity map etc. Here, we briefly represent the systems level understanding of the molecular mechanisms associated with prostate tumorigenesis by considering each and individual molecular and cell biological events of this disease process. PMID:27476486

  13. Frequency of carcinoma of prostate in clinically benign prostatic hyperplasia and role of different screening tests

    International Nuclear Information System (INIS)

    Rasool, M.; Saeed, M.; Ali, S.; Saleem, M.S.; Saleem, M.S.

    2012-01-01

    Objectives: To assess the frequency of carcinoma in clinically benign prostatic hyperplasia and role. of digital rectal examination (DRE) and prostatic specific antigen (PSA) in assessment of these patients. Data source: Patients admitted to the Department of Urology and Renal Transplantation with lower urinary tract symptoms (LUTS) due to enlarged prostate. Design of study: Descriptive Study Place and Duration of Study: Department of Urology and Renal Transplantation, Quaid-e-Azam Medical College Bahawal Victoria Hospital, Bahawalpur, from January 2007 to December 2010. Patients and Methods: Patients presenting with lower urinary tract symptoms over the age of 50 years were evaluated on International Prostate Symptoms Score (IPSS), clinically examined and post-voiding residual urine determined on abdominal ultrasonography. The selection criteria were; Refractory retention of urine, Severe IPSS, absence of signs of malignancy on Digital Rectal Examination (DRE) and post-voiding residual urine more than 100 mI. Thus a total 300 patients were selected. Patient's blood sample was sent to laboratory to assess Prostate Specific Antigen (PSA) level pre-operatively. All these patients underwent either transurethral resection of prostate (TURP) or transvesical prostatectomy (TVP) and prostatic tissue was sent for histopathology. Results: In this study, 13.33% patients were found to have carcinoma of prostate in spite of being clinically benign prostates in all patients, irrespective of PSA range. The PSA value was found 4ngjml. In this study, 9.95% patients had carcinoma prostate in spite having normal PSA and benign prostate on DRE while with rising PSA levels and normal DRE, chances of malignancy detection increases (66.67% ). Conclusion: We conclude that although frequency is low the possibility of malignancy in clinically benign enlarged prostate should be borne in mind whenever subjecting the patient for screening, assessment and treatment. DRE alone is insufficient

  14. Apoptosis Induction of Human Prostate Carcinoma DU145 Cells by Diallyl Disulfide via Modulation of JNK and PI3K/AKT Signaling Pathways

    Directory of Open Access Journals (Sweden)

    Young Hyun Yoo

    2012-11-01

    Full Text Available Diallyl disulfide (DADS, a sulfur compound derived from garlic, has various biological properties, such as anticancer, antiangiogenic and anti-inflammatory effects. However, the mechanisms of action underlying the compound's anticancer activity have not been fully elucidated. In this study, the apoptotic effects of DADS were investigated in DU145 human prostate carcinoma cells. Our results showed that DADS markedly inhibited the growth of the DU145 cells by induction of apoptosis. Apoptosis was accompanied by modulation of Bcl-2 and inhibitor of apoptosis protein (IAP family proteins, depolarization of the mitochondrial membrane potential (MMP, ΔΨm and proteolytic activation of caspases. We also found that the expression of death-receptor 4 (DR4 and Fas ligand (FasL proteins was increased and that the level of intact Bid proteins was down-regulated by DADS. Moreover, treatment with DADS induced phosphorylation of mitogen-activated protein kinases (MAPKs, including extracellular-signal regulating kinase (ERK, p38 MAPK and c-Jun N-terminal kinase (JNK. A specific JNK inhibitor, SP600125, significantly blocked DADS-induced-apoptosis, whereas inhibitors of the ERK (PD98059 and p38 MAPK (SB203580 had no effect. The induction of apoptosis was also accompanied by inactivation of phosphatidylinositol 3-kinase (PI3K/Akt and the PI3K inhibitor LY29004 significantly increased DADS-induced cell death. These findings provide evidence demonstrating that the proapoptotic effect of DADS is mediated through the activation of JNK and the inhibition of the PI3K/Akt signaling pathway in DU145 cells.

  15. Radical external radiotherapy for prostatic carcinoma

    International Nuclear Information System (INIS)

    Beiler, D.D.; Wright, D.J.; Reddy, G.N.

    1981-01-01

    From 1965 through 1974, 88 patients with Stage B or C prostatic carcinoma were treated with radical megavoltage therapy. Treatment technique was small field arc alone for Stage B and 4 field box whole pelvis irradiation to 4400 or 5000 rad with small field rotational boost for Stage C. All were at risk for 5 years and 30 for 10 years or more. None of the 14 Stage B patients have died of cancer. In Stage C (74 patients) uncorrected acturial survival was 55% (5 year) and 28% (10 year). Thirty-one percent of local failures appeared after 5 years. Whole pelvis dose of 5000 rad was associated with a higher 5 and 10 year survival than 4400 rad but the difference was not statistically significant. Comparison between groups treated with radiation alone, versus radiation plus a simultaneous hormonal therapy showed no significant differences in survival, local control or complications. Complications were generally mild, but early in the series 2 patients receiving 7500 rad developed ano-rectal necrosis; one of these patients died. More common problems were urethral stricture (12%) and ano-rectal stenosis (10%). Changes in technique in 1971 drastically reduced the subsequent complications. The failure of whole pelvic irradiation to improve on the 10 year results of local treatment is discussed

  16. miR-221 and miR-222 expression affects the proliferation potential of human prostate carcinoma cell lines by targeting p27Kip1.

    Science.gov (United States)

    Galardi, Silvia; Mercatelli, Neri; Giorda, Ezio; Massalini, Simone; Frajese, Giovanni Vanni; Ciafrè, Silvia Anna; Farace, Maria Giulia

    2007-08-10

    MicroRNAs are short regulatory RNAs that negatively modulate protein expression at a post-transcriptional level and are deeply involved in the pathogenesis of several types of cancers. Here we show that miR-221 and miR-222, encoded in tandem on chromosome X, are overexpressed in the PC3 cellular model of aggressive prostate carcinoma, as compared with LNCaP and 22Rv1 cell line models of slowly growing carcinomas. In all cell lines tested, we show an inverse relationship between the expression of miR-221 and miR-222 and the cell cycle inhibitor p27(Kip1). We recognize two target sites for the microRNAs in the 3' untranslated region of p27 mRNA, and we show that miR-221/222 ectopic overexpression directly results in p27 down-regulation in LNCaP cells. In those cells, we demonstrate that the ectopic overexpression of miR-221/222 strongly affects their growth potential by inducing a G(1) to S shift in the cell cycle and is sufficient to induce a powerful enhancement of their colony-forming potential in soft agar. Consistently, miR-221 and miR-222 knock-down through antisense LNA oligonucleotides increases p27(Kip1) in PC3 cells and strongly reduces their clonogenicity in vitro. Our results suggest that miR-221/222 can be regarded as a new family of oncogenes, directly targeting the tumor suppressor p27(Kip1), and that their overexpression might be one of the factors contributing to the oncogenesis and progression of prostate carcinoma through p27(Kip1) down-regulation.

  17. Prostatic carcinoma. Diagnostic and stating: MR imaging. Cancer de la prostate Diagnostic et bilan: role de l'imagerie

    Energy Technology Data Exchange (ETDEWEB)

    Roy, C; Spittler, G; Jacqmin, D [Centre Hospitalier Universitaire, 67 - Strasbourg (FR); Morel, M [Clinique Saint-Francois, 67 Haguenau (FR)

    1991-01-01

    Prostatic carcinoma is the second most commun cause of cancer death over 60 years. It is suspected by digital examination and prostatic specific antigen dosage. Transrectal ultrasound shows the tumor as an hypoechoic lesion. Sensitivity is good but specificity is low. Transrectal biopsy of prostate guided by transrectal ultrasound made the diagnosis. At present, MR Imaging is the most accurate diagnostic modality for loco-regional staging of prostatic carcinoma.

  18. Endocrine Disruption and Human Prostate Cancer

    National Research Council Canada - National Science Library

    Risbridger, Gail

    2008-01-01

    .... In order to test the concept that Vinclozolin alters human prostate development and induces disease, we used our model system to study human prostate development and maturation over 8-12 weeks...

  19. Androgen regulated genes in human prostate xenografts in mice: relation to BPH and prostate cancer.

    Directory of Open Access Journals (Sweden)

    Harold D Love

    2009-12-01

    Full Text Available Benign prostatic hyperplasia (BPH and prostate carcinoma (CaP are linked to aging and the presence of androgens, suggesting that androgen regulated genes play a major role in these common diseases. Androgen regulation of prostate growth and development depends on the presence of intact epithelial-stromal interactions. Further, the prostatic stroma is implicated in BPH. This suggests that epithelial cell lines are inadequate to identify androgen regulated genes that could contribute to BPH and CaP and which could serve as potential clinical biomarkers. In this study, we used a human prostate xenograft model to define a profile of genes regulated in vivo by androgens, with an emphasis on identifying candidate biomarkers. Benign transition zone (TZ human prostate tissue from radical prostatectomies was grafted to the sub-renal capsule site of intact or castrated male immunodeficient mice, followed by the removal or addition of androgens, respectively. Microarray analysis of RNA from these tissues was used to identify genes that were; 1 highly expressed in prostate, 2 had significant expression changes in response to androgens, and, 3 encode extracellular proteins. A total of 95 genes meeting these criteria were selected for analysis and validation of expression in patient prostate tissues using quantitative real-time PCR. Expression levels of these genes were measured in pooled RNAs from human prostate tissues with varying severity of BPH pathologic changes and CaP of varying Gleason score. A number of androgen regulated genes were identified. Additionally, a subset of these genes were over-expressed in RNA from clinical BPH tissues, and the levels of many were found to correlate with disease status. Our results demonstrate the feasibility, and some of the problems, of using a mouse xenograft model to characterize the androgen regulated expression profiles of intact human prostate tissues.

  20. Intrahepatic portal hypertension secondary to metastatic carcinoma of the prostate.

    Science.gov (United States)

    Attila, Tan; Datta, Milton W; Sudakoff, Gary; Abu-Hajir, Majed; Massey, Benson T

    2007-02-01

    While the liver is a common site of metastasis, tumor metastases are not a common cause of portal hypertension. We report a case of a patient with symptomatic portal hypertension due to diffuse metastatic prostate carcinoma infiltration of liver parenchyma that was not appreciated with routine imaging.

  1. Radical irradiation for carcinoma of the prostate | Abratt | South ...

    African Journals Online (AJOL)

    Ninety-three patients treated by radical irradiation for stage A2, Band C1 carcinoma of the prostate between 1979 and 1988 at a joint radiotherapy service were reviewed. The average age was 63 years, 84% of the patients were white and on histological examination the tumours were well or moderately differentiated in ...

  2. Brain metastasis from prostate small cell carcinoma: not to be neglected.

    NARCIS (Netherlands)

    Erasmus, C.E.; Verhagen, W.I.M.; Wauters, C.A.P.; Lindert, E.J. van

    2002-01-01

    BACKGROUND: Symptomatic brain metastases from prostatic carcinoma are rare (0.05% to 0.5%). CASE REPORT: A 70-year-old man presented with a homonymous hemianopsia due to brain metastatic prostatic carcinoma shortly before becoming symptomatic of prostatic disease. CT and MRI of the brain showed a

  3. Prostate specific antigen, digital rectal examination, transrectal ultrasound: how accurate are they in determining prostate carcinoma?

    International Nuclear Information System (INIS)

    Gomez, John Anthony M.; Pagdanganan, Ernest Jerome A.; Caedo, Florencio Gerardo O.; Magsino, Benjamin C.; Rivera, Eduardo Ll.; Songco, Jaime S.D.

    1998-01-01

    Prostate cancer is an increasing problem. It is the most frequent malignancy in men past the age of 65 years. In the Philippines, 10-20% of males operated for prostatic obstruction had prostate cancer. The potential for cure is optimized by early detection and treatment of organ confined disease. Digital rectal examination, serum prostatic specific antigen and transrectal ultrasound of the prostate have been advocated individually and collectively to determine prostatic cancer. Our study involved forty-nine males who underwent all three screening modalities. Results of the study showed a statistically significant association between the presence of a nodule and occurrence of prostate cancer, a statistically significant association between hardness in consistency and cancer, a statistically significant difference in mean weight between those with Ca and BPH; a statistically significant difference in mean PSA levels between those with Ca and with BPH; statistically significant association between abnormal PSA levels and Ca; and a statistically significant association between a composite positive result and cancer. On the other hand, there was no statistically significant difference in mean age between those with cancer and those with BPH; there is no statistically significant association between the presence of prostatism and whether the patient has Ca or BPH; and there is no statistically significant difference in the mean duration between those with cancer and those with BPH. The study advocates the use of DRE, serum PSA in determining prostatic Ca as well as TRUS for determining occult carcinoma. (Author)

  4. High-voltage therapy of carcinoma of the prostate

    International Nuclear Information System (INIS)

    Schnorr, D.; Kelly, L.U.; Guddat, H.M.; Schubert, J.; Gorski, J.; Schorcht, J.; Mau, S.; Wehnert, J.; Medizinische Akademie, Dresden

    1983-01-01

    High-voltage therapy is becoming increasingly important as a form of individual differential therapy of carcinoma of the prostate. Around 40% of all patients with a diagnosis of carcinoma of the prostate can be treated with high-voltage therapy. The precondition is the absence of bone and soft tissue metastases and of juxtaregional lymph node metastases. Individual carcinoma therapy is based on pre therapeutic tumor classification according to the TNM system. The 5-year survival rates are presented from a retrospective study carried out using primary radiation monotherapy and a combined hormone and radiation therapy; these figures were calculated by the life-table method. The study revealed no significant differences between the two forms of therapy as regards 5-year survival rates. The 5-year survival rates of all patients of the classifications T 0 -T 3 N/sub x/-N 2 M 0 irradiated (n: 198) (72% +- 11% for hormone plus radiation therapy and 74% +- 11% for radiation monotherapy) did not differ greatly from those of a normal male population of the same age (77%). High-voltage therapy of carcinoma of the prostate can thus be classified as a curative method of treatment. (author)

  5. 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

  6. Vitronectin in human breast carcinomas

    DEFF Research Database (Denmark)

    Aaboe, Mads; Offersen, Birgitte Vrou; Christensen, Anni

    2003-01-01

    We have analysed the occurrence of the extracellular glycoprotein vitronectin in carcinomas and normal tissue of human breast. Immunohistochemical analysis of carcinomas revealed a strong vitronectin accumulation in extracellular matrix (ECM) around some cancer cell clusters and in the subendothe......We have analysed the occurrence of the extracellular glycoprotein vitronectin in carcinomas and normal tissue of human breast. Immunohistochemical analysis of carcinomas revealed a strong vitronectin accumulation in extracellular matrix (ECM) around some cancer cell clusters...... and in the subendothelial area of some blood vessels. In normal tissue, vitronectin had a homogeneous periductal occurrence, with local accumulation much lower than that in the carcinomas. Using a new solid phase radioligand assay, the vitronectin concentrations of extracts of carcinomas and normal breast tissue were...... is not synthesised locally in breast tissue but derived by leakage from vessels, followed by extracellular accumulation in patterns distinctly different in carcinomas and normal tissue. The observation of a high vitronectin content in the carcinomas and its localisation in the tissue contributes to the clarification...

  7. Prostate specific antigen levels after definitive irradiation for carcinoma of the prostate

    International Nuclear Information System (INIS)

    Schellhammer, P.F.; Schlossberg, S.M.; El-Mahdi, A.M.; Wright, G.L.; Brassil, D.N.

    1991-01-01

    Prostate specific antigen (PSA) levels were determined in 78 patients judged clinically to be free of disease at intervals of 36 or more months (range 38 to 186 months, median 87 months) after completion of irradiation therapy by 125-iodine implantation or external beam radiation. Of this select group of patients 38% had undetectable serum PSA levels (0.5 ng./ml. or less) and 38% had PSA levels that were within normal limits (4.0 ng./ml. or less). All stages and grades were represented. Undetectable PSA levels were only rarely found (3%) in patients with carcinoma of the prostate before treatment. In 24 of these 78 patients a negative biopsy of the irradiated prostate had been obtained 18 to 42 months after treatment. When the PSA level was drawn, which ranged from 7 to 16 years after treatment, an equal percentage of these biopsied patients had either an undetectable, normal or elevated level. Irradiation is able to decrease PSA to undetectable levels in some patients with prostatic carcinoma. Whether this reflects suppression of marker production alone or, more importantly, ablation of prostate cancer producing that marker remains to be determined

  8. β-catenin is required for prostate development and cooperates with Pten loss to drive invasive carcinoma.

    Directory of Open Access Journals (Sweden)

    Jeffrey C Francis

    Full Text Available Prostate cancer is a major cause of male death in the Western world, but few frequent genetic alterations that drive prostate cancer initiation and progression have been identified. β-Catenin is essential for many developmental processes and has been implicated in tumorigenesis in many tissues, including prostate cancer. However, expression studies on human prostate cancer samples are unclear on the role this protein plays in this disease. We have used in vivo genetic studies in the embryo and adult to extend our understanding of the role of β-Catenin in the normal and neoplastic prostate. Our gene deletion analysis revealed that prostate epithelial β-Catenin is required for embryonic prostate growth and branching but is dispensable in the normal adult organ. During development, β-Catenin controls the number of progenitors in the epithelial buds and regulates a discrete network of genes, including c-Myc and Nkx3.1. Deletion of β-Catenin in a Pten deleted model of castration-resistant prostate cancer demonstrated it is dispensable for disease progression in this setting. Complementary overexpression experiments, through in vivo protein stabilization, showed that β-Catenin promotes the formation of squamous epithelia during prostate development, even in the absence of androgens. β-Catenin overexpression in combination with Pten loss was able to drive progression to invasive carcinoma together with squamous metaplasia. These studies demonstrate that β-Catenin is essential for prostate development and that an inherent property of high levels of this protein in prostate epithelia is to drive squamous fate differentiation. In addition, they show that β-Catenin overexpression can promote invasive prostate cancer in a clinically relevant model of this disease. These data provide novel information on cancer progression pathways that give rise to lethal prostate disease in humans.

  9. Ureteral Metastasis from Prostatic Carcinoma with an Associated Ureteral Stone: A Case Report

    Directory of Open Access Journals (Sweden)

    Chia-Chu Liu

    2004-07-01

    Full Text Available Ureteral metastasis is rare, and only a few cases of ureteral metastasis from prostatic carcinoma have been reported. We present a case of ureteral metastasis from prostatic carcinoma that was also associated with a ureteral stone. To our knowledge, this is the second case with a ureteral stone at the site of the metastatic lesion.

  10. Role of Stromal Paracrine Signals in Proliferative Diseases of the Aging Human Prostate

    Directory of Open Access Journals (Sweden)

    Kenichiro Ishii

    2018-04-01

    Full Text Available Androgens are essential for the development, differentiation, growth, and function of the prostate through epithelial–stromal interactions. However, androgen concentrations in the hypertrophic human prostate decrease significantly with age, suggesting an inverse correlation between androgen levels and proliferative diseases of the aging prostate. In elderly males, age- and/or androgen-related stromal remodeling is spontaneously induced, i.e., increased fibroblast and myofibroblast numbers, but decreased smooth muscle cell numbers in the prostatic stroma. These fibroblasts produce not only growth factors, cytokines, and extracellular matrix proteins, but also microRNAs as stromal paracrine signals that stimulate prostate epithelial cell proliferation. Surgical or chemical castration is the standard systemic therapy for patients with advanced prostate cancer. Androgen deprivation therapy induces temporary remission, but the majority of patients eventually progress to castration-resistant prostate cancer, which is associated with a high mortality rate. Androgen deprivation therapy-induced stromal remodeling may be involved in the development and progression of castration-resistant prostate cancer. In the tumor microenvironment, activated fibroblasts stimulating prostate cancer cell proliferation are called carcinoma-associated fibroblasts. In this review, we summarize the role of stromal paracrine signals in proliferative diseases of the aging human prostate and discuss the potential clinical applications of carcinoma-associated fibroblast-derived exosomal microRNAs as promising biomarkers.

  11. DJ-1 and androgen receptor immunohistochemical expression in prostatic carcinoma: A possible role in carcinogenesis

    International Nuclear Information System (INIS)

    Osman, W.M.; Abd El Atti, R.M.; Abou Gabal, H.H.

    2013-01-01

    Background and Aim: Androgen plays a fundamental role in the growth and differentiation of prostate. Androgen receptor (AR) expression may represent a potential marker of prognosis in prostate cancer. However, there have been variable results regarding its ability to predict clinical progression. Despite the oncogenic properties of DJ-1, its significance in prostate cancer development and progression is not well understood. This research shed some light on the possible role of immunohistochemical expression of DJ-1 in clinically localized prostatic carcinoma in relation to the established role of AR and other clinico pathologic parameters. Materials and Methods: The immunohistochemical expression of AR and DJ-1 was evaluated in 129 samples including benign hyperplasia (n = 60) and prostatic carcinoma (n = 69). Results: The mean value of AR immunostaining was significantly higher in prostatic carcinomas than in benign hyperplasia (P = 0.001). A significant inverse correlation was found between AR immunostaining and the grade of prostatic carcinomas. A significantly higher median DJ-1 score was found in prostatic carcinoma than in benign hyperplasia (P = 0.0001). There was a significant direct correlation between AR and DJ-1 score (P = 0.0001). AR is more sensitive in predicting prostatic carcinoma than DJ-1 but DJ-1 is more specific than AR. Conclusion: AR nuclear expression was consistently present in benign and adenocarcinoma epithelium. But, there may be limited clinical use for AR expression in localized carcinoma due to its constant heterogeneity. DJ-1 with its oncogenic properties, specificity for prostatic carcinoma and homogenous expression gives an ideal complementary role to AR in the detection and treatment of prostatic carcinomas.

  12. Prognostic role of serum prostatic acid phosphatase for 103Pd-based radiation for prostatic carcinoma

    International Nuclear Information System (INIS)

    Dattoli, Michael; Wallner, Kent; True, Lawrence; Sorace, Richard; Koval, John; Cash, Jennifer; Acosta, Rudolph; Biswas, Mohendra; Binder, Michael; Sullivan, Brent; Lastarria, Emilio; Kirwan, Novelle; Stein, Douglas

    1999-01-01

    Purpose: To establish the prognostic role of serum enzymatic prostatic acid phosphatase (PAP) in patients treated with palladium ( 103 Pd) and supplemental external beam irradiation (EBRT) for clinically localized, high-risk prostate carcinoma. Methods and Materials: One hundred twenty-four consecutive patients with Stage T2a-T3 prostatic carcinoma were treated from 1992 through 1995. Each patient had at least one of the following risk factors for extracapsular disease extension: Stage T2b or greater (100 patients), Gleason score 7-10 (40 patients), pretreatment prostate specific antigen (PSA) > 15 ng/ml (32 patients), or elevated serum PAP (25 patients). Patients received 41 Gy conformal EBRT to a limited pelvic field, followed 4 weeks later by a 103 Pd boost (prescription dose 80 Gy). Biochemical failure was defined as a PSA greater than 1 ng/ml (normal < 4 ng/ml). Results: The overall, actuarial freedom from biochemical failure at 4 years after treatment was 79%. In Cox-proportional hazard multivariate analysis, the strongest predictor of failure was elevated pretreatment acid phosphatase (p = 0.02), followed by Gleason score (p = 0.1), and PSA (p = 0.14). Conclusion: PAP was the strongest predictor of long-term biochemical failure. It may be a more accurate indicator of micrometastatic disease than PSA, and as such, we suggest that it be reconsidered for general use in radiation-treated patients

  13. A receptor tyrosine kinase, UFO/Axl, and other genes isolated by a modified differential display PCR are overexpressed in metastatic prostatic carcinoma cell line DU145.

    Science.gov (United States)

    Jacob, A N; Kalapurakal, J; Davidson, W R; Kandpal, G; Dunson, N; Prashar, Y; Kandpal, R P

    1999-01-01

    We have used a modified differential display PCR protocol for isolating 3' restriction fragments of cDNAs specifically expressed or overexpressed in metastatic prostate carcinoma cell line DU145. Several cDNA fragments were identified that matched to milk fat globule protein, UFO/Axl, a receptor tyrosine kinase, human homologue of a Xenopus maternal transcript, laminin and laminin receptor, human carcinoma-associated antigen, and some expressed sequence tags. The transcript for milk fat globule protein, a marker protein shown to be overexpressed in breast tumors, was elevated in DU145 cells. The expression of UFO/Axl, a receptor tyrosine kinase, was considerably higher in DU145 cells as compared to normal prostate cells and prostatic carcinoma cell line PC-3. The overexpression of UFO oncogene in DU145 cells is discussed in the context of prostate cancer metastasis.

  14. Prostate carcinoma mimicking a sphenoid wing meningioma.

    Science.gov (United States)

    Bradley, Lucas H; Burton, Matthew; Gokden, Murat; Serletis, Demitre

    2015-01-01

    We report here on a rare case of a large, lateral sphenoid wing tumor with radiographic and intraoperative findings highly suggestive of meningioma, yet pathology was in fact consistent with metastatic prostate adenocarcinoma. An 81 year-old male presented with expressive dysphasia, right-sided weakness and headaches. Imaging revealed a heterogeneously-enhancing lesion based on the left lateral sphenoid wing. The presumed diagnosis was strongly in favor of meningioma, and the patient underwent complete resection of the dural-based lesion. Final pathology confirmed the unexpected finding of a metastatic prostate adenocarcinoma. Although he tolerated surgery well, the patient was subsequently referred for palliative therapy given findings of widespread systemic disease. Intracranial metastases may involve the dura, at times presenting with rare radiographic features highly suggestive for meningioma, as in our case here. This makes differentiation, at least based on imaging, a challenge. Elderly patients presenting with neurological deficits secondary to a newly-diagnosed, dural-based lesion should thus be considered for metastasis, prompting additional imaging studies (including body CT, MRI or PET) to rule out a primary lesion elsewhere. In some cases, this may affect the overall decision to proceed with surgical resection, or alternatively, to proceed directly to palliative therapy (the latter decision made in the context of widespread metastatic disease). We conclude that dural-based metastatic lesions may mimic meningiomas, warranting thorough pre-operative work-up to exclude the possibility of metastasis. In certain cases, identification of widespread disease might preclude surgery and favor palliation, instead. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  15. Iodine-125 implants for carcinoma of the prostate

    International Nuclear Information System (INIS)

    Peschel, R.E.; Fogel, T.D.; Kacinski, B.M.; Kelly, K.; Mate, T.P.

    1985-01-01

    One hundred-thirteen patients underwent Iodine-125 prostate implant and lymphadenectomy at Yale-New Haven Hospital from 1974 through 1980. The distribution by clinical stage was: 7 Stage A2, 86 Stage B, and 20 Stage C patients. Ninety-four patients had a negative lymphadenectomy and 19 patients (17%) had metastatic disease in the pelvic lymph nodes (N+). The actuarial 5-year survival for all 113 patients was 87%. Local tumor control was 85% for all Stage B patients and 75% for all Stage C patients. Only 10 patients (9%) have developed long-term gastrointestinal or genitourinary complications following their implant. Iodine-125 implant appears to be a reasonable alternate form of therapy in highly selected groups of patients with carcinoma of the prostate

  16. Androgen Receptor Expression in Epithelial and Stromal Cells of Prostatic Carcinoma and Benign Prostatic Hyperplasia.

    Science.gov (United States)

    Filipovski, Vanja; Kubelka-Sabit, Katerina; Jasar, Dzengis; Janevska, Vesna

    2017-08-15

    Prostatic carcinoma (PCa) derives from prostatic epithelial cells. However stromal microenvironment, associated with malignant epithelium, also plays a role in prostatic carcinogenesis. Alterations in prostatic stromal cells contribute to the loss of growth control in epithelial cells that lead to progression of PCa. To analyse the differences between Androgen Receptor (AR) expression in both epithelial and stromal cells in PCa and the surrounding benign prostatic hyperplasia (BPH) and to compare the results with tumour grade. Samples from 70 cases of radical prostatectomy specimens were used. The expression and intensity of the signal for AR was analysed in the epithelial and stromal cells of PCa and BPH, and the data was quantified using histological score (H-score). AR showed significantly lower expression in both epithelial and stromal cells of PCa compared to BPH. In PCa a significant positive correlation of AR expression was found between stromal and epithelial cells of PCa. AR expression showed a correlation between the stromal cells of PCa and tumour grade. AR expression is reduced in epithelial and stromal cells of PCa. Expression of AR in stromal cells of PCa significantly correlates with tumour grade.

  17. Postoperative irradiation in carcinoma of the prostate

    International Nuclear Information System (INIS)

    Pilepich, M.V.; Walz, B.J.; Baglan, R.J.

    1984-01-01

    Twenty-eight patients received postoperative radiotherapy with curative intent following either radical prostatectomy (18 patients) or enucleative prostatectomy (10 patients). In patients undergoing radical prostatectomy, the indications for postoperative radiotherapy included positive margins in 13, close margins in 2, and seminal vesicle involvement in 3 patients. The majority of patients (82%) received total dose to the prostatic bed in excess of 6500 rad. In over 80% of the patients, the pelvic lymphatics are also treated (to a total dose of 4000-5000 rad). All of the patients irradiated after radical prostatectomy clinically remained disease-free locally. Approximately one-half of the patients in both the enucleation and radial prostatectomy groups developed evidence of distant metastases. The complications of treatment have been comparable to those in patients treated with radiotherapy only. The continence status has not been affected significantly. All patients with incontinence following completion of radiotherapy had documented impairment of continence prior to radiotherapy. Postoperative radiotherapy administered following either radical or enucleative prostatectomy was tolerated well and resulted in excellent local control

  18. AR Signaling in Human Malignancies: Prostate Cancer and Beyond.

    Science.gov (United States)

    Antonarakis, Emmanuel S

    2018-01-18

    The notion that androgens and androgen receptor (AR) signaling are the hallmarks of prostate cancer oncogenesis and disease progression is generally well accepted. What is more poorly understood is the role of AR signaling in other human malignancies. This special issue of Cancers initially reviews the role of AR in advanced prostate cancer, and then explores the potential importance of AR signaling in other epithelial malignancies. The first few articles focus on the use of novel AR-targeting therapies in castration-resistant prostate cancer and the mechanisms of resistance to novel antiandrogens, and they also outline the interaction between AR and other cellular pathways, including PI3 kinase signaling, transcriptional regulation, angiogenesis, stromal factors, Wnt signaling, and epigenetic regulation in prostate cancer. The next several articles review the possible role of androgens and AR signaling in breast cancer, bladder cancer, salivary gland cancer, and hepatocellular carcinoma, as well as the potential treatment implications of using antiandrogen therapies in these non-prostatic malignancies.

  19. MicroRNA-125a-5p regulates cancer cell proliferation and migration through NAIF1 in prostate carcinoma.

    Science.gov (United States)

    Fu, Yi; Cao, Fuhua

    2015-01-01

    We investigated the functional roles of microRNA-125a-5p in regulating human prostate carcinoma. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was conducted to evaluate the gene expression levels of miR-125a-5p in eight prostate cancer cell lines and nine biopsy specimens from patients with prostate cancer. miR-125a-5p was genetically knocked down in prostate cancer cell lines, DU145 and VCaP cells by lentiviral transduction. The effects of miR-125a-5p downregulation on prostate cancer cell proliferation and migration were evaluated by MTT assay and transwell assay, respectively. Direct regulation of miR-125a-5p on its downstream targets, NAIF1, and apoptotic gene caspase-3 were evaluated through dual-luciferase reporter assay, qRT-PCR, and Western blot, respectively. NAIF1 was then ectopically overexpressed in DU145 and VCaP cells to modulate prostate cancer cell proliferation and migration. Finally, the effects of miR-125a-5p downregulation or NAIF1 overexpression on the growth of in vivo prostate cancer xenograft were evaluated. miR-125a-5p was upregulated in prostate cancer cell lines and human prostate carcinomas. Lentivirus induced miR-125a-5p downregulation in DU145 and VCaP cells inhibited prostate cancer cell proliferation or migration. NAIF1 was the direct target of miR-125a-5p, as both gene and protein expression levels of NAIF1, as well as caspase-3 were upregulated by miR-125a-5p. Forced overexpression of NAIF1 had similar antitumor effects as miR-125a-5p downregulation on prostate cancer cell proliferation and migration. In vivo prostate xenograft assay confirmed the tumor-suppressive effect of miR-125a-5p downregulation or NAIF1 overexpression. miR-125a-5p regulates prostate cancer cell proliferation and migration through NAIF1.

  20. Dynamic contrast-enhanced MRI of benign prostatic hyperplasia and prostatic carcinoma: correlation with angiogenesis

    International Nuclear Information System (INIS)

    Ren, J.; Huan, Y.; Wang, H.; Chang, Y.-J.; Zhao, H.-T.; Ge, Y.-L.; Liu, Y.; Yang, Y.

    2008-01-01

    Aim: To investigate the diagnostic and differential diagnostic values of dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) in prostatic diseases, and to investigate the correlation between the parameters of SI-T curves and angiogenesis. Materials and methods: Twenty-one patients with proven prostatic carcinoma (Pca) and 29 patients with proven benign prostatic hyperplasia (BPH) were examined using DCE MRI. Diagnostic characteristics for differentiation were examined using threshold values for maximum peak time, enhancement degree, and enhancement rate. Then, the signal intensity-time curves (SI-T curves) were analysed, and the correlations between the parameters of SI-T curves and the expression levels of vascular endothelial growth factor (VEGF) and microvascular density (MVD) were investigated. All patients underwent prostatectomy. DCE MRI and histological findings were correlated. Results: Pca showed stronger enhancement with an earlier peak time, higher enhancement, and enhancement rate (p 2 = 13.57, P < 0.005). The VEGF and MVD expression levels of Pca were higher than those of BPH. Peak time was negatively correlated with the expression levels of VEGF and MVD, whereas the enhancement degree and enhancement rate showed positive correlations (Pearson correlation, p < 0.05). Conclusion: Based on T2-weighted imaging, DCE MRI curves can help to differentiate benign from malignant prostate tissue. In the present study the type C curve was rarely seen with malignant disease, but these results need confirmation

  1. Hemodynamic and metabolic characterization of orthotopic rat prostate carcinomas using dynamic MRI and proton magnetic resonance spectroscopy

    International Nuclear Information System (INIS)

    Kiessling, F.; Lichy, M.; Kauczor, H.U.; Schlemmer, H.P.; Grobholz, R.; Heilmann, M.; Meding, J.; Huber, P.E.; Peschke, P.

    2003-01-01

    The aim of this study was the noninvasive characterization of prostate carcinoma orthotopically implanted in rats using Gd-DTPA-assisted dynamic MRI (dMRI) and proton magnetic resonance spectroscopy ( 1 H-MRS). After surgical exposure of the prostate, Dunning R3327 orthotopic prostate carcinoma was induced by injecting cells of the MAT-LyLu subline. Six rats were examined 5 and 14 days after tumor induction with dMRI and 1 H-MRS at 1.5 T. Six tumor-free rats served as controls. Using an open two-compartment model, the parameters A (amplitude) and k ep (exchange rate constants) were calculated from the signal time curves of the dMRI. The relative signal intensities (Cho/Cr) of the resonances of choline (Cho) and the creatine-phosphocreatine complex (Cr) were computed from the MR spectra. Already after 5 days, the tumors in the prostate could be clearly identified based on the decrease in signal intensity to T2w and increase of A and k ep . High Cho/Cr levels and resonances of two lipid fractions (Lip 1 at 0.8-1.5 ppm and Lip 2 at 2.0-2.2 ppm) were observed by MRS in the highly necrotic tumors. The orthotopic rat prostate carcinoma model resembles human prostate carcinoma in regard to MR morphology, dMRI, and 1 H-MRS. The noninvasive characterization of perfusion and metabolism makes a comparative examination of different treatment modalities possible. (orig.) [de

  2. Expression of androgen receptor and prostate-specific antigen in male breast carcinoma

    International Nuclear Information System (INIS)

    Kidwai, Noman; Gong, Yun; Sun, Xiaoping; Deshpande, Charuhas G; Yeldandi, Anjana V; Rao, M Sambasiva; Badve, Sunil

    2004-01-01

    The androgen-regulated proteins prostate-specific antigen (PSA) and prostate-specific acid phosphatase (PSAP) are present in high concentrations in normal prostate and prostatic cancer and are considered to be tissue-specific to prostate. These markers are commonly used to diagnose metastatic prostate carcinoma at various sites including the male breast. However, expression of these two proteins in tumors arising in tissues regulated by androgens such as male breast carcinoma has not been thoroughly evaluated. In this study we analyzed the expression of PSA, PSAP and androgen receptor (AR) by immunohistochemistry in 26 cases of male breast carcinomas and correlated these with the expression of other prognostic markers. AR, PSA and PSAP expression was observed in 81%, 23% and 0% of carcinomas, respectively. Combined expression of AR and PSA was observed in only four tumors. Although the biological significance of PSA expression in male breast carcinomas is not clear, caution should be exercised when it is used as a diagnostic marker of metastatic prostate carcinoma

  3. Prostate Carcinoma Screening, yes or no?

    Czech Academy of Sciences Publication Activity Database

    Topolčan, O.; Pecen, Ladislav; Toufarová, P.; Klečka, J.; Nekulová, M.; Šimíčková, M.; Roušarová, M.; Pikner, R.; Holubec, L.

    2000-01-01

    Roč. 15, č. 1 (2000), s. 57 ISSN 0886-3849. [International Conference on Human Tumor Markers /17./. 23.03.2000-24.03.2000, Hong Kong] Grant - others:IGA MZ ČR(CZ) NC4780 Institutional research plan: AV0Z1030915

  4. Prostate carcinoma (PC) - an organ-related specific pathological neoplasm

    International Nuclear Information System (INIS)

    Massmann, J.; Funk, A.; Altwein, J.; Praetorius, M.

    2003-01-01

    The organ- and tumour-related specific characteristics of prostate carcinoma (PC) are presented in an overview under various aspects. It is the key for understanding pathological changes, including PC, to consider the subdivision of the prostate into anatomically and functionally distinguishable zones, especially the transitional zone (TZ) and the peripheral zone (PZ). The pseudoneoplastic hyperplasia of the TZ, combined with inflammatory consequences and age-related changes, forms a differential diagnostic challenge to both clinico-radiological diagnosis and macroscopic and microscopic examination. High-degree prostatic intra-epithelial neoplasia (PIN III) and atypical adenomatous hyperplasia (AAH) are presented as precursor lesions of PC with varying significance and assessment. Moreover, there are discussed the following characteristic features of PC: localisation types, focality, volume, progression, double-graduation according to Gleason, tumour stage, and prognosis. The most important prognosis factors of PC (category I) include the categories of the TNM system, such as stage, surgical marginal situation, degree and also the preoperative PSA level as a (poor) substitute for the tumour volume. Potential prognosis parameters (category II) show the tumour volume and the DNS ploidy, while there continues to exist a large number of non-established parameters (category III). The prognostic validity of the pathological examinations depends, on the one hand, on the tissue extent (needle biopsy, transurethral resection (TURP), so-called simple prostatectomy, radical prostatectomy (RPE)) and the prostate zones covered. On the other hand, the prognostic certainty also depends on the tumour-adequate macroscopic and microscopic assessment of an RPE that can only be a partial or complete handling in transversal large-area sections. (orig.) [de

  5. Genotoxic polycyclic aromatic hydrocarbons fail to induce the p53-dependent DNA damage response, apoptosis or cell-cycle arrest in human prostate carcinoma LNCaP cells

    Czech Academy of Sciences Publication Activity Database

    Hrubá, E.; Trilecová, L.; Marvanová, S.; Krčmář, P.; Vykopalová, L.; Milcová, Alena; Líbalová, Helena; Topinka, Jan; Staršíchová, Andrea; Souček, Karel; Vondráček, Jan; Machala, M.

    2010-01-01

    Roč. 198, č. 3 (2010), s. 227-235 ISSN 0378-4274 Grant - others:GA ČR(CZ) GA310/07/0961 Program:GA Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702; CEZ:AV0Z50390512; CEZ:AV0Z50390703 Keywords : prostate epithelial cells * DNA adducts * carcinogenesis Subject RIV: BO - Biophysics Impact factor: 3.581, year: 2010

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

    Directory of Open Access Journals (Sweden)

    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.

  7. Serum testosterone as a prognostic factor in patients with advanced prostatic carcinoma

    DEFF Research Database (Denmark)

    Iversen, P; Rasmussen, F; Christensen, I J

    1994-01-01

    In 245 patients with previously untreated advanced carcinoma of the prostate, serum concentrations of testosterone have been measured before androgen deprivation therapy, and patients were divided in quartiles according to their serum concentration. Pretreatment level of serum testosterone...... parameters suggest that low serum testosterone merely is a consequence of the advanced malignancy rather than a causative factor in the pathogenesis of prostatic cancer....

  8. Canine prostate carcinoma: epidemiological evidence of an increased risk in castrated dogs.

    NARCIS (Netherlands)

    Teske, E.; Naan, E.C.; Dijk, E.M. van; Garderen, E. van; Schalken, J.A.

    2002-01-01

    The present retrospective study investigated the frequency of prostate carcinoma (PCA) among prostate abnormalities in dogs and determined whether castration influences the incidence of PCA in dogs. During the years 1993-1998, 15363 male dogs were admitted to the Utrecht University Clinic of

  9. The detection of prostatic carcinoma. 4- or 7-MHz transrectal ultrasonography?

    NARCIS (Netherlands)

    Vleeming, R.; Noordzij, J. W.; de Reijke, T. M.; Kurth, K. H.

    1993-01-01

    In this prospective study a comparison of 4-versus 7-MHz transrectal ultrasonography for the detection of prostatic carcinoma is reported. A total of 150 prostates were biopsied due to suspicion of malignancy arising at either digital rectal examination, 4- and/or 7-MHz transrectal ultrasonography,

  10. Multi cranial nerve palsies as the presenting features of prostate carcinoma

    International Nuclear Information System (INIS)

    Mitchell, D.M.; Wynne, C.J.; Cowan, I.

    2008-01-01

    Full text: Cranial nerve palsies have previously been reported in metastatic prostate carcinoma, usually occurring late in the course of the disease. We describe the case of a 55-year-old man whose diagnosis of prostate cancer was made following investigation of multiple cranial nerve palsies.

  11. Interstitial radiotherapy in the treatment of carcinoma of the prostate

    International Nuclear Information System (INIS)

    Knuefermann, H.; Bruggmoser, G.; Wannenmacher, M.

    1981-01-01

    The practical and organisatory sides of interstitial radiation therapy of prostate carcinoma with iodine 125 capsules are reported on. Special stress is laid upon measures and measurements concerning radiation protection. First evaluations of these measurements show that this form of therapy is to be carried out in exact correspondence with the radiation protection law. The computer-supported isodose calculation and in-vivo-measurements in rectum, method and urinary bladder confirm the rapid drop in the dosage outside of the irradiated focus volume. Therefore, the inflammatory accompanying reactions are despite higher tumour dose, significantly milder then with the percutaneous radiation therapy. The indication criteria should be closely adhered to because the operation is a very extensive one. (orig.) [de

  12. Radioimmunoassay of human prostate-specific acid phosphatase in the diagnosis and follow-up of therapy of prostatic cancer

    International Nuclear Information System (INIS)

    Vihko, P.

    1981-01-01

    The author describes the development of a radioimmunoassay for the determination of serum prostate-specific acid phosphatase and studies its application to the diagnosis and follow-up of therapy of prostatic carcinoma. (Auth./C.F.)

  13. Biochemical characterization of prostate-specific membrane antigen from canine prostate carcinoma cells.

    Science.gov (United States)

    Wu, Lisa Y; Johnson, Jacqueline M; Simmons, Jessica K; Mendes, Desiree E; Geruntho, Jonathan J; Liu, Tiancheng; Dirksen, Wessel P; Rosol, Thomas J; Davis, William C; Berkman, Clifford E

    2014-05-01

    Prostate-specific membrane antigen (PSMA) remains an important target for diagnostic and therapeutic application for human prostate cancer. Model cell lines have been recently developed to study canine prostate cancer but their PSMA expression and enzymatic activity have not been elucidated. The present study was focused on determining PSMA expression in these model canine cell lines and the use of fluorescent small-molecule enzyme inhibitors to detect canine PSMA expression by flow cytometry. Western blot and RT-PCR were used to determine the transcriptional and translational expression of PSMA on the canine cell lines Leo and Ace-1. An endpoint HPLC-based assay was used to monitor the enzymatic activity of canine PSMA and the potency of enzyme inhibitors. Flow cytometry was used to detect the PSMA expressed on Leo and Ace-1 cells using a fluorescently tagged PSMA enzyme inhibitor. Canine PSMA expression on the Leo cell line was confirmed by Western blot and RT-PCR, the enzyme activity, and flow cytometry. Kinetic parameters Km and Vmax of PSMA enzymatic activity for the synthetic substrate (PABGγG) were determined to be 393 nM and 220 pmol min(-1)  mg protein(-1) , respectively. The inhibitor core 1 and fluorescent inhibitor 2 were found to be potent reversible inhibitors (IC50  = 13.2 and 1.6 nM, respectively) of PSMA expressed on the Leo cell line. Fluorescent labeling of Leo cells demonstrated that the fluorescent PSMA inhibitor 2 can be used for the detection of PSMA-positive canine prostate tumor cells. Expression of PSMA on Ace-1 was low and not detectable by flow cytometry. The results described herein have demonstrated that PSMA is expressed on canine prostate tumor cells and exhibits similar enzymatic characteristics as human PSMA. The findings show that the small molecule enzyme inhibitors currently being studied for use in diagnosis and therapy of human prostate cancer can also be extended to include canine prostate cancer. Importantly

  14. Three dimensional conformal radiation therapy (3d-crt) in prostate carcinoma: for whom and how?; La radiotherapie conformationnelle dans le cancer de la prostate: pour qui et comment?

    Energy Technology Data Exchange (ETDEWEB)

    Bey, P.; Beckendorf, V.; Aletti, P.; Marchesi, V. [Centre Alexis-Vautrin, Dept. de Radiotherapie, 54 - Vandoeuvre-les-Nancy (France)

    2002-05-01

    External radiotherapy is one of the modalities use o cure localized prostate carcinoma. Most of localized prostate carcinomas, specially those of the intermediate prognostic group, may benefit from escalated dose above 70 Gy at least as regard biochemical and clinical relapse free survival. 3D-CRT allows a reduction of the dose received by organs at risk and an increase of prostate dose over 70 Gy. It is on the way to become a standard. Intensity modulated radiation therapy increases dose homogeneity and reduces rectal dose. These methods necessitate rigorous procedures in reproducibility, delineation of volumes, dosimetry, daily treatment. They need also technological and human means. It is clear that localized prostate cancer is a good example for evaluation of these new radiotherapy modalities. (author)

  15. 103PD brachytherapy and external beam irradiation for clinically localized, high-risk prostatic carcinoma

    International Nuclear Information System (INIS)

    Dattoli, Michael; Wallner, Kent; Sorace, Richard; Koval, John; Cash, Jennifer; Acosta, Rudolph; Brown, Charles; Etheridge, James; Binder, Michael; Brunelle, Richard; Kirwan, Novelle; Sanchez, Servando; Stein, Douglas; Wasserman, Stuart

    1996-01-01

    Purpose: To summarize biochemical failure rates and morbidity of external beam irradiation (EBRT) combined with palladium ( 103 Pd) boost for clinically localized high-risk prostate carcinoma. Methods and Materials: Seventy-three consecutive patients with stage T2a-T3 prostatic carcinoma were treated from 1991 through 1994. Each patient had at least one of the following risk factors for extracapsular disease extension: Stage T2b or greater (71 patients), Gleason score 7-10 (40 patients), prostate specific antigen (PSA) >15 (32 patients), or elevated prostatic acid phosphatase (PAP) (17 patients). Patients received 41 Gy EBRT to a limited pelvic field, followed 4 weeks later by a 103 Pd boost (prescription dose: 80 Gy). Biochemical failure was defined as a PSA greater than 1.0 ng/ml (normal 103 Pd brachytherapy for clinically localized, high-risk prostate cancer compare favorably with that reported after conventional dose EBRT alone. Morbidity has been acceptable

  16. The Role of XMRV, a Novel Xenotropic Murine Retrovirus, in Human Prostate Cancers

    Science.gov (United States)

    2011-05-01

    ultimately determine the true prevalence of these viruses in humans and then to determine whether there is a link to any pathology. BODY...characterization of the novel XMRV virus , documenting its tissue tropism and interferon-sensitivity. We also documented the prevalence of the virus in human ...correlation of XMRV with prostate cancer prognosis. The recog- nition that human papilloma viruses most often initiate cervical carcinomas has focused

  17. Epidermal growth factor increases LRF/Pokemon expression in human prostate cancer cells.

    Science.gov (United States)

    Aggarwal, Himanshu; Aggarwal, Anshu; Agrawal, Devendra K

    2011-10-01

    Leukemia/lymphoma related factor/POK erythroid myeloid ontogenic factor (LRF/Pokemon) is a member of the POK family of proteins that promotes oncogenesis in several forms of cancer. Recently, we found higher LRF expression in human breast and prostate carcinomas compared to the corresponding normal tissues. The aim of this study was to examine the regulation of LRF expression in human prostate cells. Epidermal growth factor (EGF) and its receptors mediate several tumorigenic cascades that regulate cell differentiation, proliferation, migration and survival of prostate cancer cells. There was significantly higher level of LRF expression in the nucleus of LNCaP and PC-3 cells than RWPE-1 cells. A significant increase in LRF expression was observed with increasing doses of EGF in more aggressive and androgen-sensitive prostate cancer cells suggesting that EGF signaling pathway is critical in upregulating the expression of LRF/Pokemon to promote oncogenesis. Copyright © 2011 Elsevier Inc. All rights reserved.

  18. Intraductal Carcinoma of the Prostate on Diagnostic Needle Biopsy Predicts Prostate Cancer Mortality: A Population-Based Study.

    Science.gov (United States)

    Saeter, Thorstein; Vlatkovic, Ljiljana; Waaler, Gudmund; Servoll, Einar; Nesland, Jahn M; Axcrona, Karol; Axcrona, Ulrika

    2017-06-01

    Intraductal carcinoma of the prostate (IDC-P) is a distinct histopathologic feature associated with high-grade, advanced prostate cancer. Although studies have shown that IDC-P is a predictor of progression following surgical or radiation treatment for prostate cancer, there are sparse data regarding IDC-P on diagnostic needle biopsy as a prognosticator of prostate cancer mortality. This was a population-based study of all prostate cancer patients diagnosed using needle biopsy and without evidence of systemic disease between 1991 and 1999 within a defined geographic region of Norway. Patients were identified by cross-referencing the Norwegian Cancer Registry. Of 318 eligible patients, 283 had biopsy specimens available for central pathology review. Clinical data were obtained from medical charts. We examined whether IDC-P on diagnostic needle biopsy was associated with adverse clinicopathological features and prostate cancer mortality. Patients with IDC-P on diagnostic needle biopsy had a more advanced stage and a higher Gleason score compared to patients without IDC-P. IDC-P was also associated with an intensively reactive stroma. The 10-year prostate cancer-specific survival was 69% for patients with IDC-P on diagnostic needle biopsy and 89% for patients without IDC-P (Log rank P-value prostate cancer mortality after adjustments for clinical prognostic factors and treatment. After adjustment for the newly implemented Grade Group system of prostate cancer, IDC-P showed a strong tendency toward statistical significance. However, IDC-P did not remain a statistically significant predictor in the multivariable analysis. IDC-P on diagnostic needle biopsy is an indicator of prostate cancer with a high risk of mortality. Accordingly, a diagnosis of IDC-P on needle biopsy should be reported and considered a feature of high-risk prostate cancer. Moreover, the association between IDC-P and reactive stroma provides evidence in support of the idea that stromal factors

  19. Advanced prostatic carcinomas with low serum levels of prostate-specific antigen

    Directory of Open Access Journals (Sweden)

    Cerović Snežana J.

    2002-01-01

    Full Text Available The serum levels of prostate-specific antigen (PSA represent a significant diagnostic and monitoring parameter of prostatic carcinoma (PC. The aim of the study was to establish correlation of serum PSA level in addition to grade, histological type, and clinical stage of PC in patients with normal or intermediary PSA serum level. In 37 untreated PC patients with preoperative serum PSA levels ranging between 0.1 and 9.6 ng/ml, paraffin-embedded tissue and serum samples were immunohistological studied and immunoassay for PSA was done. The most representative was poorly differentiated PC with D stage In serum samples from PC patients 27 (73.7% normal (≤ 4.0 ng/ml, and 10 (27.3% intermediate (4.1-10 ng/ml PSA levels were found Immunohistochemistry, in 36 PC (97.3% had demonstrated the expression of PSA. Our study results had shown low serum PSA levels in some patients with advanced poorly differentiated PC.

  20. A role of aryl hydrocarbon receptor in the antiandrogenic effects of polycyclic aromatic hydrocarbons in LNCaP human prostate carcinoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Kizu, Ryoichi; Okamura, Kazumasa; Toriba, Akira; Hayakawa, Kazuichi [Graduate School of Natural Science and Technology, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-0934 (Japan); Kakishima, Hiroshi [Research Planning Department, Eiken Chemical Co. Ltd., 5-26-20 Oji, Kita-ku, Tokyo 114-0002 (Japan); Mizokami, Atsushi [School of Medicine, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-8641 (Japan); Burnstein, Kerry L. [Department of Molecular and Cellular Pharmacology, University of Miami School of Medicine, FL 33101, Miami (United States)

    2003-06-01

    The role of aryl hydrocarbon receptor (AhR) on the antiandrogenic effects of polycyclic aromatic hydrocarbons (PAHs) was studied in LNCaP cells. The PAHs used in this study were chrysene (Chr), benzo[k]fluoranthene (BkF), benzo[a]pyrene (BaP), anthracene (Ant) and pyrene (Pyr). Chr, BkF and BaP acted as AhR agonists in LNCaP cells, while Ant and Pyr did not. The antiandrogenic effects of the PAHs were evaluated on the basis of regulation of prostate-specific antigen (PSA) mRNA and protein levels by 5{alpha}-dihydrotestosterone (DHT). Chr, BkF and BaP exhibited an antiandrogenic effect, but Ant and Pyr did not. {alpha}-Naphthoflavone ({alpha}-NF), an AhR antagonist, reversed the antiandrogen action of Chr, BkF and BaP, suggesting a requirement for activated AhR. The antiandrogenic PAHs did not significantly decrease androgen receptor (AR) levels or cellular DHT concentrations. Gel mobility shift assays revealed that Chr, BkF and BaP inhibited the binding of AR in nuclear extracts to oligonucleotide probes containing the AR-responsive element (ARE), whereas Ant and Pyr had no effect. The antiandrogenic PAHs elevated mRNA levels of c-fos and c-jun. Since activator protein-1 (AP-1), a heterodimer of c-jun and c-fos proteins, is known to inhibit binding of AR to ARE by protein-protein interaction with AR, the findings in the present study suggest a possible involvement of AP-1 in the antiandrogenic effects of PAHs acting as AhR agonists. These results suggest that AhR can stimulate AP-1 expression resulting in inhibition of the binding of AR to ARE in the transcription regulatory region of target genes such as PSA. (orig.)

  1. Low grade urothelial carcinoma mimicking basal cell hyperplasia and transitional metaplasia in needle prostate biopsy

    Directory of Open Access Journals (Sweden)

    Julian Arista-Nasr

    2016-04-01

    Full Text Available ABSTRACT Purpose The vast majority of urothelial carcinomas infiltrating the bladder are consistent with high-grade tumors that can be easily recognized as malignant in needle prostatic biopsies. In contrast, the histological changes of low-grade urothelial carcinomas in this kind of biopsy have not been studied. Materials and Methods We describe the clinicopathologic features of two patients with low-grade bladder carcinomas infiltrating the prostate. They reported dysuria and hematuria. Both had a slight elevation of the prostate specific antigen and induration of the prostatic lobes. Needle biopsies were performed. At endoscopy bladder tumors were found in both cases. Results Both biopsies showed nests of basophilic cells and cells with perinuclear clearing and slight atypia infiltrating acini and small prostatic ducts. The stroma exhibited extensive desmoplasia and chronic inflammation. The original diagnosis was basal cell hyperplasia and transitional metaplasia. The bladder tumors also showed low-grade urothelial carcinoma. In one case, the neoplasm infiltrated the lamina propria, and in another, the muscle layer. In both, a transurethral resection was performed for obstructive urinary symptoms. The neoplasms were positive for high molecular weight keratin (34BetaE12 and thrombomodulin. No metastases were found in either of the patients, and one of them has survived for five years. Conclusions The diagnosis of low-grade urothelial carcinoma in prostate needle biopsies is difficult and may simulate benign prostate lesions including basal cell hyperplasia and urothelial metaplasia. It is crucial to recognize low-grade urothelial carcinoma in needle biopsies because only an early diagnosis and aggressive treatment can improve the prognosis for these patients.

  2. Establishing an in vivo model of canine prostate carcinoma using the new cell line CT1258

    International Nuclear Information System (INIS)

    Fork, Melani AM; Bullerdiek, Jörn; Nolte, Ingo; Escobar, Hugo Murua; Soller, Jan T; Sterenczak, Katharina A; Willenbrock, Saskia; Winkler, Susanne; Dorsch, Martina; Reimann-Berg, Nicola; Hedrich, Hans J

    2008-01-01

    Prostate cancer is a frequent finding in man. In dogs, malignant disease of the prostate is also of clinical relevance, although it is a less common diagnosis. Even though there are numerous differences in origin and development of the disease, man and dog share many similarities in the pathological presentation. For this reason, the dog might be a useful animal model for prostate malignancies in man. Although prostate cancer is of great importance in veterinary medicine as well as in comparative medicine, there are only few cell lines available. Thus, it was the aim of the present study to determine whether the formerly established prostate carcinoma cell line CT1258 is a suitable tool for in vivo testing, and to distinguish the growth pattern of the induced tumours. For characterisation of the in vivo behaviour of the in vitro established canine prostate carcinoma cell line CT1258, cells were inoculated in 19 NOD.CB17-Prkdc Scid /J (in the following: NOD-Scid) mice, either subcutaneously or intraperitoneally. After sacrifice, the obtained specimens were examined histologically and compared to the pattern of the original tumour in the donor. Cytogenetic investigation was performed. The cell line CT 1258 not only showed to be highly tumourigenic after subcutaneous as well as intraperitoneal inoculation, but also mimicked the behaviour of the original tumour. Tumours induced by inoculation of the cell line CT1258 resemble the situation in naturally occurring prostate carcinoma in the dog, and thus could be used as in vivo model for future studies

  3. 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.

  4. Quantitative bone scintigraphy. A study in patients with prostatic carcinoma

    International Nuclear Information System (INIS)

    Sundkvist, G.

    1991-01-01

    Quantitative bone scintigraphy was performed in patients with prostatic carcinoma before orchiectomy as well as two weeks, two and six months after operation. The count rate was recorded as serial gamma camera images over the lower thoracic and all lumbar vertebrae from 1 to 240 min and at 24 h after injection of 99T c m -MDP. In almost all abnormal vertebrae an increased count rate was observed within one hour after injection. Most of the vertebrae which were considered normal at 4 h after injection, but had an increased 24h/4h ratio developed into abnormal vertebrae later in the study. The patients with normal bone scintigrams showed no change in 99 Tc m -MDP uptake during the study. The reproducibility of quantitative bone scintigraphy was found to be ± 7% (1 SD). In response to therapy, most of the patients with abnormal bone scintigrams showed an increase in count rate two weeks after operation followed by a decrease to the pre-operative level after two months and a further decrease after six months. This so called 'flare phenomenon' was found to indicate 99 Tc m -MDP in the vascular phase as well as an active bone uptake. In some of the patients the whole-body retention of 99 Tc m -MDP after 24 h and the bone mineral density in the vertebrae were determined and found to be valuable in the interpretation of skeletal metastases and the assessment of response to therapy. (71 refs.)

  5. Metastasis of a Prostatic Carcinoma along an Omental Graft in a Dog

    Directory of Open Access Journals (Sweden)

    Terry M. Jacobs

    2013-01-01

    Full Text Available An 11-year-old male American Bulldog was presented for hematuria and tenesmus. It had been treated for chronic bacterial prostatitis with abscessation two years earlier and underwent castration and a prostatic omentalization procedure. There was no histologic evidence of prostatic neoplasia at that time. On physical examination, an enlarged prostate was found by rectal palpation, and it was characterized with ultrasonography and computed tomography. Surgical biopsies were obtained, and histopathology identified prostatic adenocarcinoma. It received carprofen and mitoxantrone chemotherapy in addition to palliative radiation therapy; it was euthanized six weeks later due to a progression of clinical signs. Necropsy findings included marked localized expansion of the prostatic tumor and dissemination of prostatic carcinoma cells throughout the peritoneal cavity along the omental graft with infiltration onto the serosal surfaces of most abdominal viscera and fat. This case represents a previously unreported potential complication of the omentalization procedure wherein carcinoma cells from a prostatic tumor that independently arose after omentalization may have metastasized along the surgically created omental graft.

  6. Challenges in Optimizing a Prostate Carcinoma Binding Peptide, Identified through the Phage Display Technology

    Directory of Open Access Journals (Sweden)

    Jürgen Debus

    2011-02-01

    Full Text Available The transfer of peptides identified through the phage display technology to clinical applications is difficult. Major drawbacks are the metabolic degradation and label instability. The aim of our work is the optimization of DUP-1, a peptide which was identified by phage display to specifically target human prostate carcinoma. To investigate the influence of chelate conjugation, DOTA was coupled to DUP-1 and labeling was performed with 111In. To improve serum stability cyclization of DUP-1 and targeted D-amino acid substitution were carried out. Alanine scanning was performed for identification of the binding site and based on the results peptide fragments were chemically synthesized. The properties of modified ligands were investigated in in vitro binding and competition assays. In vivo biodistribution studies were carried out in mice, carrying human prostate tumors subcutaneously. DOTA conjugation resulted in different cellular binding kinetics, rapid in vivo renal clearance and increased tumor-to-organ ratios. Cyclization and D-amino acid substitution increased the metabolic stability but led to binding affinity decrease. Fragment investigation indicated that the sequence NRAQDY might be significant for target-binding. Our results demonstrate challenges in optimizing peptides, identified through phage display libraries, and show that careful investigation of modified derivatives is necessary in order to improve their characteristics.

  7. Human papillomavirus DNA in aerodigestive squamous carcinomas ...

    African Journals Online (AJOL)

    A series of 10 oesophageal and 10 laryngeal squamous carcinomas was examined by means of immuno cytochemistry and in situ DNA hybridisation to demonstrate human papillomavirus (HPV) infection. Changes in the epithelium adjacent to the carcinoma were found in 5 of 10 oesophageal and 7 of 10 laryngeal ...

  8. Prognostic significance of epithelial/stromal caveolin‐1 expression in prostatic hyperplasia, high grade prostatic intraepithelial hyperplasia and prostatic carcinoma and its correlation with microvessel density

    Directory of Open Access Journals (Sweden)

    Dareen A. Mohammed

    2017-03-01

    Full Text Available Caveolin-1 may play a role in cancer development and progression. The aim was to record the expression and localization of caveolin-1 in benign prostatic hyperplasia (BPH, high grade prostatic intraepithelial neoplasia (HGPIN and prostatic carcinoma (PCa. Microvessel density was evaluated with CD34 immunostain. Correlations with known prognostic factors of PCa were recorded. Immunohistochemical expression of caveolin-1 and the MVD was evaluated in 65 cases; BPH (25, HGPIN (20 and PCa (20. Stromal caveolin-1expression was significantly higher in BPH than HGPIN and PCca. There was significant inverse relation between stromal caveolin-1 expression and extension to lymph node and seminal vesicle in carcinoma cases. Epithelial caveolin-1 was significantly higher in carcinomas than in BPH and HGPIN. Epithelial expression in carcinoma was significantly associated with preoperative PSA, Gleason score and lymph node extension. MVD was significantly higher in PCa than in BPH and HGPIN. There were significant relations between MVD and preoperative PSA, Gleason score, lymph node and seminal vesicle extension. Stromal caveolin-1 was associated with low MVD while epithelial caveolin-1 with high MVD. Conclusions: Caveolin-1 plays an important role in prostatic carcinogenesis and metastasis. Stromal expression of caveolin-1 in PCa is lowered in relation to BPH and HGPIN. In PCa; stromal caveolin-1 was associated with good prognostic parameters. Epithelial caveolin-1 is significantly increased in PCa than BPH and HGPIN. It is associated with clinically aggressive disease. Caveolin-1 may play a role in angiogenesis.

  9. Analysis of the testicular dose in patients undergoing radiotherapy for carcinoma of the prostate

    International Nuclear Information System (INIS)

    Bejar Navarro, M. J.; Ordonez Marquez, J.; Hervas Moron, A.; Alvarez Rodriguez, S.; Garcia-Galloway, E.; Sanchez Casanueva, R.; Polo Rubio, A.; Rodriguez-Patron, R.; Yanowsky, K.; Gomez Dos Santos, V.

    2013-01-01

    The objectives of this work are: -Studying comparatively the doses received in testes in patients undergoing radiotherapy of prostate carcinoma with external beam radiation and brachytherapy of low rate using I-125 seeds. -Compare doses due to images of verification using Cone Beam CT (CBCT), with doses of radiotherapy treatment itself. -Determine the seminal alterations and cytogenetic after treatment with ionizing radiation (RTE or BQT) in patients diagnosed with prostate cancer and its relation with testicular dose. (Author)

  10. An Aggressive Signet Ring Cell Carcinoma of the Prostate in a Japanese Man

    Directory of Open Access Journals (Sweden)

    Yasuhiro Hashimoto

    2011-10-01

    Full Text Available Signet ring cell carcinoma (SRCC of the prostate is rare, with approximately 100 case reports to date. Here we report a very aggressive case of SRCC of the prostate in a Japanese man. The patient received estramustine, docetaxel, and carboplatin combination chemotherapy, followed by TS-1 and CPT-11 combination therapy. Unfortunately, the disease progressed, and he died of general metastatic disease treated over 16 month with systemic chemotherapy.

  11. Intraductal carcinoma of the prostate: a distinct histopathological entity with important prognostic implications.

    Science.gov (United States)

    Henry, P C; Evans, A J

    2009-07-01

    Intraductal carcinoma of the prostate (IDCP) has been described as a lesion associated with poor prognostic features in prostate cancer. Its recognition and reporting in prostate specimens, particularly in needle biopsies, is critical as it carries significant implications for patient management. Recent histological definitions have been proposed to assist in the recognition of IDCP and to help distinguish it from lesions with similar appearance, but different clinical behaviour. In this review, a historical overview of the description of IDCP will be presented followed by a summary of the current histological diagnostic criteria and the recommendations for management and reporting of IDCP.

  12. Ultrasonically guided 125iodine seed implantation with external radiation in management of localized prostatic carcinoma

    DEFF Research Database (Denmark)

    Iversen, P; Bak, M; Juul, N

    1989-01-01

    Thirty-three patients with localized prostatic carcinoma (16 poorly differentiated) were treated with transperineal 125Iodine seed implantation (160 Gy) guided by transrectal ultrasonography and subsequent external beam irradiation (47.4 Gy). The observation time was six to sixty-eight months...... with a median follow-up of thirty-five months. Median change in prostatic volume was a reduction of 35 percent. Re-biopsy or transurethral resection of the prostate was performed in 25 patients after one to two years, revealing still malignant histology in 12 (48%). Development of distant metastases occurred...

  13. A comparative study of recombinant and native frutalin binding to human prostate tissues

    Directory of Open Access Journals (Sweden)

    Domingues Lucília

    2009-09-01

    Full Text Available Abstract Background Numerous studies indicate that cancer cells present an aberrant glycosylation pattern that can be detected by lectin histochemistry. Lectins have shown the ability to recognise these modifications in several carcinomas, namely in the prostate carcinoma, one of the most lethal diseases in man. Thus, the aim of this work was to investigate if the α-D-galactose-binding plant lectin frutalin is able to detect such changes in the referred carcinoma. Frutalin was obtained from different sources namely, its natural source (plant origin and a recombinant source (Pichia expression system. Finally, the results obtained with the two lectins were compared and their potential use as prostate tumour biomarkers was discussed. Results The binding of recombinant and native frutalin to specific glycoconjugates expressed in human prostate tissues was assessed by using an immuhistochemical technique. A total of 20 cases of prostate carcinoma and 25 cases of benign prostate hyperplasia were studied. Lectins bound directly to the tissues and anti-frutalin polyclonal antibody was used as the bridge to react with the complex biotinilated anti-rabbit IgG plus streptavidin-conjugated peroxidase. DAB was used as visual indicator to specifically localise the binding of the lectins to the tissues. Both lectins bound to the cells cytoplasm of the prostate carcinoma glands. The binding intensity of native frutalin was stronger in the neoplasic cells than in hyperplasic cells; however no significant statistical correlation could be found (P = 0.051. On the other hand, recombinant frutalin bound exclusively to the neoplasic cells and a significant positive statistical correlation was obtained (P Conclusion Native and recombinant frutalin yielded different binding responses in the prostate tissues due to their differences in carbohydrate-binding affinities. Also, this study shows that both lectins may be used as histochemical biomarkers for the prostate

  14. Withanolides from Aeroponically Grown Physalis peruviana and Their Selective Cytotoxicity to Prostate Cancer and Renal Carcinoma Cells.

    Science.gov (United States)

    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.

  15. Percutaneous transperineal placement of gold 198 seeds for treatment of carcinoma of the prostate

    Energy Technology Data Exchange (ETDEWEB)

    Crusinberry, R.A.; Kramolowsky, E.V.; Loening, S.A.

    1987-01-01

    Thirty-one patients have been treated for carcinoma of the prostate with /sup 198/Au seeds placed transperineally using transrectal ultrasonic guidance. Twenty patients have been followed postoperatively for periods ranging from 3 to 31 months, with an average follow-up time of 12 months. Cumulative dose of radiation to the prostate calculated by dosimetry was either 9000 rads or 15,000 rads. Serial transrectal ultrasound examinations performed on these patients showed a decrease in prostate size in all patients within 6 months of treatment, with a statistically significant decrease observed between the third and sixth months. No significant difference in amount or rate of tumor regression was noted when tumor stage and grade were correlated to volume decrease after treatment. Patients who received the larger doses of radiation (15,000 rads) showed a significantly greater rate of decline in prostatic volume than those who received 9000 rads. Seven patients underwent prostate biopsy between 12 and 18 months after treatment; six biopsies showed residual tumor. Complications after treatment included urinary retention because of prostatic edema (three), radiation urethritis (three), and rectal ulceration (one). Transperineal placement of /sup 198/Au is well tolerated and offers an alternative to external beam radiation for treatment of carcinoma of the prostate.

  16. CARCINOMA PROSTATE HISTOPATHOLOGY IN NEEDLE BIOPSIES INCLUDING REVISED GLEASON’S GRADING AND ROLE OF IMMUNOHISTOCHEMICAL MARKERS

    Directory of Open Access Journals (Sweden)

    Rema Priyadarsini

    2017-05-01

    Full Text Available BACKGROUND Adenocarcinoma of prostate is the most common form of cancer in men accounting for 29% of cancers in developed nations and the incidence of prostatic cancer is 6.4% in males of Trivandrum District. MATERIALS AND METHODS All prostatic biopsies taken per rectally and stained by haematoxylin and eosin. In suspected cases of malignancy immunohistochemical markers, the AMACR P504S and high molecular weight cytokeratin 34E12 were done. RESULTS The total number of cases studied were 142. The final diagnosis with histomorphological features show that maximum cases were prostatic carcinoma constituting 45.5% of the samples received. CONCLUSION All prostatic carcinomas were graded by revised Gleason’s grade (ISUP 2005 and the use of immunohistochemical markers in arriving at a definite diagnosis in carcinoma prostate was confirmed.

  17. Radioimmunoassay for prostatic acid phosphatase in human serum. Methodologic aspects

    Energy Technology Data Exchange (ETDEWEB)

    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.

  18. Estramustine: A novel radiation enhancer in human carcinoma cells

    International Nuclear Information System (INIS)

    Ryu, S.; Gabel, M.; Khil, M.S.

    1994-01-01

    Estramustine (EM), an antimicrotubule agent, binds microtubule-associated proteins, causes spindle disassembly, and arrests cells at the late G 2 /M phase of the cell cycle. Since cells in the G 2 /M phase are the most radiosensitive and some human cancer cells contain high level of EM-binding protein, experiments were carried out to determine whether radiation sensitization could be obtained in human carcinoma cells. Cells containing a high level of EM-binding protein such as prostate carcinoma (DU-145), breast carcinoma (MCF-7), and malignant glioma (U-251) were used to demonstrate radiosensitization. Cervical carcinoma (HeLa-S 3 ) and colon carcinoma (HT-29) cells which are not known to contain EM-binding protein were also employed. Cell survival was assayed by the colony forming ability of single plated cells in culture to obtain dose-survival curves. Pretreatment of DU-145, MCF-7, and U-251 cells to a nontoxic concentration (5 μM) of EM for more than one cell cycle time, substantially enhanced the radiation-induced cytotoxicity. The sensitizer enhancement ratio of these cells ranged from 1.35-1.52. The magnitude of the enhancement was dependent on the drug concentration and exposure time. The rate of cell accumulation in G 2 /M phase, as determined by flow cytometry, increased with longer treatment time in the cell lines which showed radiosensitization. Other antimicrotubule agents such as taxol and vinblastine caused minimal or no radiosensitization at nontoxic concentrations. The data provide a radiobiological basis for using EM as a novel radiation enhancer, with the property of tissue selectivity. 29 refs., 4 figs., 1 tab

  19. Multi-parametric MR imaging for prostate carcinoma; Multiparametrische MR-Bildgebung beim Prostatakarzinom

    Energy Technology Data Exchange (ETDEWEB)

    Schlemmer, Heinz-Peter [Deutsches Krebsforschungszentrum, Heidelberg (Germany). Abt. Radiologie

    2017-03-15

    Multi-parametric NMR imaging in case of prostate carcinoma can improve diagnostics, allows reliable prognostic estimations and helps to find the optimum individual therapy. The contribution is focused to deliver the needed methodological tools and background knowledge for the daily routine.

  20. [Cost analysis of ultrasound-guided transrectal needle biopsy in prostatic carcinoma].

    Science.gov (United States)

    Bissoli, E; Fandella, A; La Torre, E; Faggiano, L; Anselmo, G; Frasson, F

    1998-04-01

    The literature mortality and morbidity rates from prostatic carcinoma prompt to the better use of some routine diagnostic tools such as transrectal ultrasound-guided biopsy. We evaluated the overall cost of transrectal ultrasound biopsy (TRUSB) of the prostate and investigated the economic impact of the procedures currently used to diagnose prostatic carcinoma. The total cost of TRUSB was calculated with reference to 247 procedures performed in 1996. The following cost factors were evaluated: personnel, materials, maintenance-equipment depreciation, energy consumption and hospital overheads. A literature review was also carried out to check if our extrapolated costs corresponded to those of other authors worldwide and to consider them in the wider framework of the cost effectiveness of the strategies for the early diagnosis of prostatic cancer. The overall cost of TRUSB was Itl. 249,000, obtained by adding together the costs of: personnel (Itl. 160,000); materials (Itl. 59,000); equipment maintenance and depreciation (Itl. 12,400); energy consumption (Itl. 100); hospital overheads (Itl. 17,500). The literature review points out TRUSB as a clinically invasive tool for diagnosing prostatic carcinoma whose cost-effectiveness is debated. Cadaver studies report the presence of cancer cells in the prostate of 50% of 70-year-old men, while extrapolations calculate a morbidity from prostatic carcinoma in 9.5% of 50-year-old men. It is therefore obvious that randomized prostatic biopsies, methods apart, are very likely to be positive. This probability varies with the patient's age, the level of prostate specific antigen (PSA), the density of PSA/cm3 of prostate volume (PSAD), and the positivity of exploration and/or transrectal ultrasound findings. Despite the strict application of all these criteria and the critical assessment of the patient's general conditions, TRUSB is indicated for 16% of the male population over 50, with obvious implications. It has been recently

  1. Establishing an in vivo model of canine prostate carcinoma using the new cell line CT1258

    Directory of Open Access Journals (Sweden)

    Winkler Susanne

    2008-08-01

    Full Text Available Abstract Background Prostate cancer is a frequent finding in man. In dogs, malignant disease of the prostate is also of clinical relevance, although it is a less common diagnosis. Even though there are numerous differences in origin and development of the disease, man and dog share many similarities in the pathological presentation. For this reason, the dog might be a useful animal model for prostate malignancies in man. Although prostate cancer is of great importance in veterinary medicine as well as in comparative medicine, there are only few cell lines available. Thus, it was the aim of the present study to determine whether the formerly established prostate carcinoma cell line CT1258 is a suitable tool for in vivo testing, and to distinguish the growth pattern of the induced tumours. Methods For characterisation of the in vivo behaviour of the in vitro established canine prostate carcinoma cell line CT1258, cells were inoculated in 19 NOD.CB17-PrkdcScid/J (in the following: NOD-Scid mice, either subcutaneously or intraperitoneally. After sacrifice, the obtained specimens were examined histologically and compared to the pattern of the original tumour in the donor. Cytogenetic investigation was performed. Results The cell line CT 1258 not only showed to be highly tumourigenic after subcutaneous as well as intraperitoneal inoculation, but also mimicked the behaviour of the original tumour. Conclusion Tumours induced by inoculation of the cell line CT1258 resemble the situation in naturally occurring prostate carcinoma in the dog, and thus could be used as in vivo model for future studies.

  2. Comparison of serum prostate specific antigen levels and bone scintigraphy in patients with prostate carcinoma

    International Nuclear Information System (INIS)

    Bielickaite, J.; Zadeikaite, R.; Jurkiene, N. and others

    2003-01-01

    The aim of this study was to analyze the levels of serum prostate specific antigen in patients with and without bone metastases detected by means of bone scintigraphy and to determine the highest prostate specific antigen level in patients without bone metastases. The 50 patients consecutively diagnosed of prostate cancer between 1999 and 2001 in our institution made up the study population. Prostate specific antigen plasmatic levels were determined and bone scintigraphy was performed (whole body study after 99mTc-methyl-diphosphonate administration) in all the patients. In patients with positive bone scans (n=23), the mean prostate specific antigen level was 71.4±35.2 ng/ml and was significantly (p<0.00005) higher than in 14 patients with negative bone scans (mean prostate specific antigen level was 10.1±10.5 ng/ml). Suspicious lesions were found in 13 patients and their mean prostate specific antigen level was 8.5±7.7 ng/ml. Regarding prostate specific antigen levels, no statistically significant differences were found between patients with suspicious lessons and normal bone scans. The highest determined prostate specific antigen level in patients without bone metastases was 18 ng/ml. The bone scintigraphy should be performed in all patients with prostate specific antigen level above 18 ng/ml, but it is of limited value in patients with prostate specific antigen level below 18 ng/ml. (author)

  3. Expression of leukemia/lymphoma related factor (LRF/Pokemon) in human benign prostate hyperplasia and prostate cancer.

    Science.gov (United States)

    Aggarwal, Himanshu; Aggarwal, Anshu; Hunter, William J; Yohannes, Paulos; Khan, Ansar U; Agrawal, Devendra K

    2011-04-01

    Leukemia/lymphoma related factor (LRF), also known as Pokemon, is a protein that belongs to the POK family of transcriptional repressors. It has an oncogenic role in many different solid tumors. In this study, the expression of LRF was evaluated in benign prostate hyperplastic (BPH) and prostate cancer (PC) tissues. The functional expression of LRF was studied using multiple cellular and molecular methods including RT-PCR, western blotting, immunohistochemistry, and immunofluorescence. Paraffin-embedded human tissues of BPH and PC were used to examine LRF expression. Histological staining of the BPH and PC tissue sections revealed nuclear expression of LRF with minimal expression in the surrounding stroma. The semi-quantitative RT-PCR and western immunoblot analyses demonstrated significantly higher mRNA transcripts and protein expression in PC than BPH. High expression of LRF suggests that it may have a potential role in the pathogenesis of both BPH and prostate cancer. Further studies will help elucidate the mechanisms and signaling pathways that LRF may follow in the pathogenesis of prostate carcinoma. Copyright © 2011 Elsevier Inc. All rights reserved.

  4. Role of IAPs in prostate cancer progression: immunohistochemical study in normal and pathological (benign hyperplastic, prostatic intraepithelial neoplasia and cancer) human prostate

    International Nuclear Information System (INIS)

    Rodríguez-Berriguete, Gonzalo; Paniagua, Ricardo; Royuela, Mar; Fraile, Benito; Bethencourt, Fermín R de; Prieto-Folgado, Angela; Bartolome, Nahikari; Nuñez, Claudia; Prati, Bruna; Martínez-Onsurbe, Pilar; Olmedilla, Gabriel

    2010-01-01

    In this study was investigate IAPs in normal human prostate (NP), benign prostatic hyperplasia (BPH), prostatic intraepithelial neoplasia (PIN) and prostatic carcinoma (PC), and their involvement in apoptosis/proliferation via NF-kB (TNF-α, IL-1) stimulation. Immunohistochemical and Western blot analyses were performed in 10 samples of normal prostates, 35 samples of BPH, 27 samples diagnosis of PIN (with low-grade PIN or high-grade PIN) and 95 samples of PC (with low, medium or high Gleason grades). In NP, cytoplasm of epithelial cells were positive to c-IAP1/2 (80% of samples), c-IAP-2 (60%), ILP (20%), XIAP (20%); negative to NAIP and survivin. In BPH, epithelial cells were immunostained to c-IAP1/2 (57.57%), c-IAP-2 (57.57%), ILP (66.6%), NAIP (60.6%), XIAP (27.27%), survivin (9.1%). Whereas low-grade PIN showed intermediate results between NP and BPH; results in high-grade PIN were similar to those found in PC. In PC, epithelial cells were immunostained to c-IAP1/2, c-IAP-2, ILP, NAIP, XIAP (no Gleason variation) and survivin (increasing with Gleason). IAPs could be involved in prostate disorder (BPH, PIN and PC) development since might be provoke inhibition of apoptosis and subsequently cell proliferation. At the same time, different transduction pathway such as IL-1/NIK/NF-kB or TNF/NF-kB (NIK or p38) also promotes proliferation. Inhibitions of IAPs, IL-1α and TNFα might be a possible target for PC treatment since IAPs are the proteins that inhibited apoptosis (favour proliferation) and IL-1α and TNFα would affect all the transduction pathway involucrate in the activation of transcription factors related to survival or proliferation (NF-kB, Elk-1 or ATF-2)

  5. Fractionation and protraction for radiotherapy of prostate carcinoma

    International Nuclear Information System (INIS)

    Brenner, David J.; Hall, Eric J.

    1999-01-01

    Purpose: To investigate whether current fractionation and brachytherapy protraction schemes for the treatment of prostatic cancer with radiation are optimal, or could be improved. Methods and Materials: We analyzed two mature data sets on radiotherapeutic tumor control for prostate cancer, one using EBRT and the other permanent seed implants, to extract the sensitivity to changes in fractionation of prostatic tumors. The standard linear-quadratic model was used for the analysis. Results: Prostatic cancers appear significantly more sensitive to changes in fractionation than most other cancers. The estimated α/β value is 1.5 Gy [0.8, 2.2]. This result is not too surprising as there is a documented relationship between cellular proliferative status and sensitivity to changes in fractionation, and prostatic tumors contain exceptionally low proportions of proliferating cells. Conclusions: High dose rate (HDR) brachytherapy would be a highly appropriate modality for treating prostate cancer. Appropriately designed HDR brachytherapy regimens would be expected to be as efficacious as low dose rate, but with added advantages of logistic convenience and more reliable dose distributions. Similarly, external beam treatments for prostate cancer can be designed using larger doses per fraction; appropriately designed hypofractionation schemes would be expected to maintain current levels of tumor control and late sequelae, but with reduced acute morbidity, together with the logistic and financial advantages of fewer numbers of fractions

  6. Anatomy and Histology of the Human and Murine Prostate.

    Science.gov (United States)

    Ittmann, Michael

    2018-05-01

    The human and murine prostate glands have similar functional roles in the generation of seminal fluid to assist in reproduction. There are significant differences in the anatomy and histology of murine and human prostate and knowledge of the normal anatomy and histology of the murine prostate is essential to interpreting changes in genetically engineered mouse models. In this review, the normal anatomy and histology of both human and mouse prostate will be described. Copyright © 2018 Cold Spring Harbor Laboratory Press; all rights reserved.

  7. Prognostic significance of epithelial/stromal caveolin-1 expression in prostatic hyperplasia, high grade prostatic intraepithelial hyperplasia and prostatic carcinoma and its correlation with microvessel density.

    Science.gov (United States)

    Mohammed, Dareen A; Helal, Duaa S

    2017-03-01

    Caveolin-1 may play a role in cancer development and progression. The aim was to record the expression and localization of caveolin-1 in benign prostatic hyperplasia (BPH), high grade prostatic intraepithelial neoplasia (HGPIN) and prostatic carcinoma (PCa). Microvessel density was evaluated with CD34 immunostain. Correlations with known prognostic factors of PCa were recorded. Immunohistochemical expression of caveolin-1 and the MVD was evaluated in 65 cases; BPH (25), HGPIN (20) and PCa (20). Stromal caveolin-1expression was significantly higher in BPH than HGPIN and PCca. There was significant inverse relation between stromal caveolin-1 expression and extension to lymph node and seminal vesicle in carcinoma cases. Epithelial caveolin-1 was significantly higher in carcinomas than in BPH and HGPIN. Epithelial expression in carcinoma was significantly associated with preoperative PSA, Gleason score and lymph node extension. MVD was significantly higher in PCa than in BPH and HGPIN. There were significant relations between MVD and preoperative PSA, Gleason score, lymph node and seminal vesicle extension. Stromal caveolin-1 was associated with low MVD while epithelial caveolin-1 with high MVD. Caveolin-1 plays an important role in prostatic carcinogenesis and metastasis. Stromal expression of caveolin-1 in PCa is lowered in relation to BPH and HGPIN. In PCa; stromal caveolin-1 was associated with good prognostic parameters. Epithelial caveolin-1 is significantly increased in PCa than BPH and HGPIN. It is associated with clinically aggressive disease. Caveolin-1 may play a role in angiogenesis. Copyright © 2017 National Cancer Institute, Cairo University. Production and hosting by Elsevier B.V. All rights reserved.

  8. Diagnosis and Follow Up of Prostate Carcinoma by an in House Prostate Specific Antigen ELISA Kit at Pramongkutklao Hospital

    International Nuclear Information System (INIS)

    Dumrongpisutikut, S.; Raungdilokrut, S.

    1998-01-01

    PSA ELISA kit was developed and compared to a commercial PSA ELISA kit (Cobas Registered trade mark Core PSA EIA, Roche Switzerland) with a correlation of 98.9% (r 0.989, p < 0.05). The precision of the assay kit evaluated by intermal quality control studies shown that the coefficient of variation of high, medium and low control were 4.4, 3.6 and 4.7% respectively. The sentuvity of detection was 0.25 ng/ml. This PSA ELISA kit has been used for detection of PSA in serum of 571 patients ages between 25-93 years old with satisfactory results. The normal range of PSA is 0 - 3.46 ng/ml (X-bar = 2SD, n = 384). The mean value of PSA in Prostate carcinoma before treatment and after successful treatment are 77.30 ng/ml (n = 53) and 1.64 ng/ml (n = 25) and increase to 53.71 ng/ml (n = 8) in metastasis. In Benign Prostate Hyperplasia (BPH) the range of PSA is 0 - 27.52 ng/ml (n = 74). Phi (φ) coefficient analysis shown that the correlation of PSA and Prostate carcinoma is 63.8% with a sensitivity and specificity of 100% and 86.9% respectively

  9. Human seminal proteinase and prostate-specific antigen are the ...

    Indian Academy of Sciences (India)

    https://www.ias.ac.in/article/fulltext/jbsc/033/02/0195-0207. Keywords. Kallikrein; prostate cancer biomarker; proteinase activity; seminal plasma; tumour proliferation and metastasis; therapeutic target. Abstract. Human seminal proteinase and prostate-specific antigen (PSA) were each isolated from human seminal fluid and ...

  10. Role of computed tomography in the evaluation and management of carcinoma of the prostate

    International Nuclear Information System (INIS)

    Giri, P.G.S.; Walsh, J.W.; Hazra, T.A.; Texter, J.H.; Koontz, W.W.

    1982-01-01

    Between January 1978 to March 1980, 25 patients with biopsy-proven prostate carcinoma were evaluated by computerized tomography (CT). CT differed from clinical stage in 7 of 25 patients (28%). In 6 of the 7 patients, change in stage resulted because of demonstration of extracapsular extension and/or pelvic lymph node involvement. Twelve of the 25 patients (48%) underwent surgery with histological confirmation of CT findings. CT identified nodal involvement accurately in 10 of 12 patients (83%). We recommend use of CT for initial staging, treatment planning and assessment of response in the management of prostate cancer

  11. PrognosticValue of PINP,BoneAlkaline Phosphatase, CTX-I, andYKL-40 in Patients With Metastatic Prostate Carcinoma

    DEFF Research Database (Denmark)

    Brasso, Klaus; Christensen, Ib Jarle; Johansen, Julia S

    2006-01-01

    Prognostic value of PINP, bone alkaline phosphatase, CTX-I, and YKL-40 in patients with metastatic prostate carcinoma. Prostate. 2006 Apr 1;66(5):503-13. PMID: 16372331 [PubMed - indexed for MEDLINE]......Prognostic value of PINP, bone alkaline phosphatase, CTX-I, and YKL-40 in patients with metastatic prostate carcinoma. Prostate. 2006 Apr 1;66(5):503-13. PMID: 16372331 [PubMed - indexed for MEDLINE]...

  12. Estrogen receptors in the human male bladder, prostatic urethra, and prostate. An immunohistochemical and biochemical study

    DEFF Research Database (Denmark)

    Bødker, A; Balslev, E; Juul, B R

    1995-01-01

    The distribution and quantity of estrogen receptors (ERs) in the human male bladder, prostatic urethra and the prostate were studied in eight males with recurrent papillomas of the bladder or monosymptomatic hematuria (median age 61 years), 14 men undergoing transurethral resection due to benign...

  13. Radiolabeling of anti-human prostatic specific membrane antigen antibody with 99Tcm and its biodistribution in nude mice bearing human prostate cancer

    International Nuclear Information System (INIS)

    Tu Shaohua; Shen Jiangfan; Tao Rong; Ji Xiaowen; Wang Yancheng

    2012-01-01

    Objective: To study the binding affinity of 99 Tc m labeled anti-human prostatic specific membrane antigen (PSMA) monoclonal antibody (McAb) J591 to prostate cancer cells and the biodistribution of 99 Tc m -J591 in nude mice bearing human prostate cancer. Methods: The McAb J591 was labeled with vTcm by improved Schwarz method and the labeled McAb was purified by Sephadex G-50. The binding affinity of J591 with prostate cancer cells was measured by Flow Cytometry. The nude mice bearing PSMA-positive C4-2 prostate carcinoma xenografts were served as experiment groups, mice with PSMA-negative pc3 tumors served as controls. The biodistribution of 99 Tc m -J591 were carried out in both model nude mice. Results: The radiolabeling efficiency of 99 Tc m -J591 was 78.9±6.2%, and radiochemical purity was more than 90% after purification. The 99 Tc m -J591 showed a good combination with PSMA-positive C4-2 cells and no combination with PSMA-negative PC3 cells in vitro. The biodistribution results showed that 99 Tcm-J591 was accumulated in tumor tissue during the 2-24 hours after injection in experiment groups, and no significant uptake in control group. The uptake of 99 Tcm-J591 in tumor tissue reached a maximum 15.91±5.16 % ID/g in experimental group at 12h post-injection. There was a significant difference compared with controls (P 0.05). Conclusion: The monoclonal antibody J591 exhibits an excellent immuno-reactivity and tumor targeting property, and it may be used in diagnosis and target therapy of prostate cancer. (authors)

  14. Estrogen receptors in the human male prostatic urethra and prostate in prostatic cancer and benign prostatic hyperplasia

    DEFF Research Database (Denmark)

    Bødker, A; Bruun, J; Balslev, E

    1999-01-01

    Estrogen receptors (ERs) in the prostate and prostatic urethra were examined in 33 men with benign prostatic hyperplasia (BPH) and in 11 with prostate cancer (PC). The Abbot monoclonal ER-ICA assay was used for immunohistochemical investigation. In the BPH group, ERs were revealed in the prostatic...... demonstrated in the prostatic stroma and/or prostatic urethra in 6 out of 11 cases. In both BPH and PC patients, immunoreactivity was weak and confined to few cells, indicating low ER content in the prostate as well as in the prostatic urethra. Dextran-coated charcoal (DCC) analysis was used for detection...... and quanticization of cytosolic and nuclear ERs. In the BPH group, ERs were detected once in the prostate and prostatic urethra in the nuclear and cytosol, and additionally in the prostatic urethra in the cytosol fraction in three cases. In all cases, ER content was low, ranging from 10-15 fmol/mg protein. In the PC...

  15. Metastasis in urothelial carcinoma mimicking prostate cancer metastasis in Ga-68 prostate-specific membrane antigen positron emission tomography-computed tomography in a case of synchronous malignancy

    International Nuclear Information System (INIS)

    Gupta, Manoj; Choudhury, Partha Sarathi; Gupta, Gurudutt; Gandhi, Jatin

    2016-01-01

    Prostate cancer is the second most common cancer in man. It commonly presents with urinary symptoms, bone pain, or diagnosed with elevated prostate-specific antigen.(PSA) levels. Correct staging and early diagnosis of recurrence by a precise imaging tool are the keys for optimum management. Molecular imaging of prostate cancer with Ga-68 prostate-specific membrane antigen.(PSMA), positron emission tomography-computed tomography.(PET-CT) has recently received significant attention and frequently used with a signature to prostate cancer-specific remark. However, this case will highlight the more cautious use of it. A-72-year-old male treated earlier for synchronous double malignancy.(invasive papillary urothelial carcinoma right ureter and carcinoma prostate) presented with rising PSA.(0.51.ng/ml) and referred for Ga-68 PSMA PET-CT, which showed a positive enlarged left supraclavicular lymph node. Lymph node biopsy microscopic and immunohistochemistry examination revealed metastatic carcinoma favoring urothelial origin. Specificity of PSMA scan to prostate cancer has been seen to be compromised in a certain situation mostly due to neoangiogenesis, and false positives emerged in renal cell cancer, differentiated thyroid cancer, glioblastoma, breast cancer brain metastasis, and paravertebral schwannomas. Understanding the causes of false positive will further enhance the confidence of interpretating PSMA scans

  16. Collagen derived serum markers in carcinoma of the prostate

    DEFF Research Database (Denmark)

    Rudnicki, M; Jensen, L T; Iversen, P

    1995-01-01

    of prostatic bone metastases. Blood samples were obtained prior to biopsy or TURP. Serum PICP, PIIINP and ICTP were measured with commercial available RIAs and PSA by IRMA. Serum PSA was increased in patients with local prostatic cancer compared with patients with hyperplasia (p ..., ICTP, and PICP did not differ between these two groups. In patients with metastatic prostatic cancer all five markers were increased compared to the level measured in patients with localized cancer (p .... The sensitivity ranged from 0.53 to 0.62 and specificity from 0.91 to 0.95. The sensitivity for alkaline phosphatase and PSA was 0.69 and 0.66 and specificity 0.91 and 0.68, respectively....

  17. Collagen derived serum markers in carcinoma of the prostate

    DEFF Research Database (Denmark)

    Rudnicki, M; Jensen, L T; Iversen, P

    1995-01-01

    Three new collagen markers deriving from the collagenous matrix, e.g. carboxyterminal propeptide of type I procollagen (PICP), carboxy-terminal pyridinoline cross-linked telopeptide of type I collagen (ICTP), and aminoterminal propeptide of type III procollagen (PIIINP) were used for the diagnose...... of prostatic bone metastases. Blood samples were obtained prior to biopsy or TURP. Serum PICP, PIIINP and ICTP were measured with commercial available RIAs and PSA by IRMA. Serum PSA was increased in patients with local prostatic cancer compared with patients with hyperplasia (p

  18. Rectal necrosis following external radiation therapy for carcinoma of the prostate: report of a case

    International Nuclear Information System (INIS)

    Quan, S.H.Q.; O'Kelly, P.J.

    1975-01-01

    Increasing attention is being paid to the use of radiation therapy in the management of primary carcinoma of the prostate. Since 1965, radical radiation therapy has been used at Memorial Hospital to treat primary carcinoma of the prostate. Small primary tumors are treated by implantation with radioactive iodine ( 125 I) seeds and larger tumors considered unsuitable for implantation are treated by external supervoltage beam therapy. Fifty patients had been treated by implantation and 30 by external beam therapy at the time of this report. None of the patients treated by implantation developed rectal symptoms. Proctitis developed in all patients treated by external radiation therapy and in half the patients chronic proctitis ensued, accompanied by the passage of mucus. The constant leaking of mucus through the anal sphincter produces irritation of the skin and intermittent attacks of pruritus ani, a discomfiting sequel. Apart from the proctitis, most patients tolerated treatment well, with one notable exception, in whom rectal necrosis developed. This case is described

  19. Half-body irradiation in the treatment of metastatic prostatic carcinoma

    International Nuclear Information System (INIS)

    Rowland, C.G.; Bullimore, J.A.; Smith, P.J.B.; Roberts, J.B.M.

    1981-01-01

    High dose radiation therapy given as a single fraction to the upper and lower halves of the body gives effective palliation for metastatic solid tumours. This treatment modality appears to be particularly effective in tumours which may have a slow doubling time such as carcinoma of the prostate. Fifty-two patients with metastatic carcinoma of the prostate involving the skeletal system have received half-body irradiation (8 MeV X-rays at a dose rate of about 100 cGy/min). All had prior treatment with additive hormones or orchiectomy and the majority had received localised irradiation and/or chemotherapy. Significant immediate pain relief was achieved in 42 out of 52 patients (80%). This pain relief was maintained until death in 29 out of 43 patients (67%). Pain relief in responders appears to occur within 24 to 48 h of treatment. (author)

  20. 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

  1. Estrogen receptors in the human male prostatic urethra and prostate in prostatic cancer and benign prostatic hyperplasia

    DEFF Research Database (Denmark)

    Bødker, A; Bruun, J; Balslev, E

    1999-01-01

    Estrogen receptors (ERs) in the prostate and prostatic urethra were examined in 33 men with benign prostatic hyperplasia (BPH) and in 11 with prostate cancer (PC). The Abbot monoclonal ER-ICA assay was used for immunohistochemical investigation. In the BPH group, ERs were revealed in the prostatic...... stroma in eight cases and in the glandular epithelium in one. In four cases ERs were seen in the prostatic stroma and in the glandular epithelium. In the prostatic urethra, ERs were found in 19 cases located in the urothelium, lamina propria and/or periurethral glands. In the PC group, ERs were...... demonstrated in the prostatic stroma and/or prostatic urethra in 6 out of 11 cases. In both BPH and PC patients, immunoreactivity was weak and confined to few cells, indicating low ER content in the prostate as well as in the prostatic urethra. Dextran-coated charcoal (DCC) analysis was used for detection...

  2. Detection of prostate carcinomas with T1-weighted dynamic contrast-enhanced MRI. Value of two-compartment model

    International Nuclear Information System (INIS)

    Kiessling, F.; Lichy, M.; Farhan, N.; Delorme, S.; Kauczor, H.U.; Grobholz, R.; Heilmann, M.; Michel, M.S.; Trojan, L.; Werner, A.; Rabe, J.; Schlemmer, H.P.

    2003-01-01

    Aim The suitability of dynamic parameters of the two-compartment model for detecting prostate carcinomas and its correlation with tumor microvascular density were evaluated. The study included 43 patients with biopsy-proven prostate carcinoma: 28 were examined by 1.0-T MRI (Turbo-FLASH) and 15 by 1.5-T MRI (FLASH) with infusion of 0.1 mmol/kg Gd-DTPA. Signal time curves were parametrized with an open two-compartment model in amplitude and exchange rate constants (k ep ).The microvascular density of resected prostate carcinomas was determined. The microvascular density in the tumors was significantly higher than in the adjacent healthy prostate tissue and correlated in both sequences with k ep . Prostate carcinomas of the peripheral zone were demarcated by amplitude and k ep . In the Turbo-FLASH sequence there was a significant difference between the tumor tissue and healthy peripheral zone in terms of k ep and in the FLASH sequence in terms of amplitude. Prostate carcinomas can be visualized with dynamic T1-weighted MR sequences using a two-compartment model. Moreover, the parameter k ep reveals the microvascular density in the tumor and can thus provide valuable clinical information for characterizing the tumors. (orig.) [de

  3. Phosphorus 32 in the treatment of the bony metastasis for carcinoma prostatic

    International Nuclear Information System (INIS)

    Portilla Fabregat, Ivette; Alsina Sarmiento, Sofia de la C.; Oliva Gonzalez, Juan P.; Barroso Alvarez, Maria del C.; Chi Ramirez, Daysi

    2000-01-01

    The results of the treatment with phosphorus 32 of 50 patients affected by metastatic prostatic carcinoma with intense bone pains were reported. Age groups, objective and subjective responses and their duration were examined. 50 % patients showed full responses and 46 % partial responses to treatment, 42 patients (84 %) declared that their pains had disappeared whereas 6 (12 %) reported some palliation of pain. The advantages of this method were presented

  4. Novel Topical Photodynamic Therapy of Prostate Carcinoma Using Hydroxy-aluminum Phthalocyanine Entrapped in Liposomes

    Czech Academy of Sciences Publication Activity Database

    Sutoris, K.; Rakušan, J.; Karásková, M.; Mattová, J.; Beneš, J.; Nekvasil, Miloš; Ježek, Petr; Zadinová, M.; Poučková, P.; Větvička, D.

    2013-01-01

    Roč. 33, č. 4 (2013), s. 1563-1568 ISSN 0250-7005 R&D Projects: GA MPO(CZ) 2A-1TP1/026; GA MŠk(CZ) OE09026; GA TA ČR(CZ) TA01010781 Institutional support: RVO:67985823 Keywords : PC prostate carcinomas * LNCaP * liposomes * hydroxy-aluminum phthalocyanine * photodynamic therapy Subject RIV: FR - Pharmacology ; Medidal Chemistry Impact factor: 1.872, year: 2013

  5. Urethrography and ischial intertuberosity line in radiation therapy planning for prostate carcinoma

    International Nuclear Information System (INIS)

    Sadeghi, Ahmad; Kuisk, Hans; Tran, Luu; St Royal, Leslie

    1996-01-01

    We analyzed our urethrography procedure regarding the validity of using the ischial tuberosity line (ITL) as the caudal margin of treatment portals for prostate carcinoma. The distances of the external urethral sphincter and the lowest margin of the opacified urinary bladder were analyzed in one hundred fifteen consecutive urethrograms. None showed the urethral sphincter to be caudal to the ITL. Ten percent of the sphincters were located less than 1.0 cm cephalad to the ITL, yielding inadequate treatment coverage if the ITL was relied on. Arbitrarily considering 2.0 cm or more of the urethral irradiation to be excessive, the use of the ITL would then have resulted in unnecessary normal tissue irradiation of 42.5%. The ITL should not be used as the caudal margin for prostate treatment portals. Variation in sphincter position, as also seen on lateral projections, reveal a need for urethrography as a necessary supplement to computed tomography to plan radiation portals for prostate cancer

  6. 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

  7. 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

  8. Interlink between cholesterol & cell cycle in prostate carcinoma

    Directory of Open Access Journals (Sweden)

    Govind Singh

    2017-01-01

    Interpretation & conclusions: The present findings along with increased expression of cell cycle protein cyclin E in the cell nucleus of the tumour tissue suggested the possibility of an intriguing role of cholesterol in the mechanism of cell cycle process of prostate cell proliferation.

  9. The specific role of radiotherapy in the management of prostate carcinoma at different stages of tumor development

    International Nuclear Information System (INIS)

    Huber, J.

    1987-01-01

    The study described here was based on the case reports of 135 patients of the Radiological Department at Kiel's University Hospital, who were treated for carcinomas of the prostate at any time during the period between 1965 and 1980. It was the aim of these evaluations to define the particular role of radiotherapy in the management of carcinomas of the prostate and to compare it to that of other methods of treatment (hormones, surgery). Percutaneous local irradiation of the carcinoma or irradiation of metastases were the criteria of inclusion into this retrospective study. The stage of the tumour was a decisive factor in the final analysis of the results. (orig.) [de

  10. Ethacrynic acid: a novel radiation enhancer in human carcinoma cells

    International Nuclear Information System (INIS)

    Khil, Mark S.; Sang, Hie Kim; Pinto, John T.; Jae, Ho Kim

    1996-01-01

    Purpose: Because agents that interfere with thiol metabolism and glutathione S-transferase (GST) functions have been shown to enhance antitumor effects of alkylating agents in vitro and in vivo, the present study was conceived on the basis that an inhibitor of GST would enhance the radiation response of some selected human carcinoma cells. Ethacrynic acid (EA) was chosen for the study because it is an effective inhibitor of GST and is a well known diuretic in humans. Methods and Materials: Experiments were carried out with well-established human tumor cells in culture growing in Eagle's minimum essential medium (MEM) supplemented with 10% fetal calf serum (FCS). Cell lines used were MCF-7, MCF-7 adriamycin resistant (AR) cells (breast carcinoma), HT-29 cells (colon carcinoma), DU-145 cells (prostate carcinoma), and U-373 cells (malignant glioma). Cell survival following the exposure of cells to drug alone, radiation alone, and a combined treatment was assayed by determining the colony-forming ability of single plated cells in culture to obtain dose-survival curves. The drug enhancement ratio was correlated with levels of GST. Results: The cytotoxicity of EA was most pronounced in MCF-7, U-373, and DU-145 cells compared to MCF-7 AR and HT-29 cells. The levels of GST activity were found to be lower in those EA-sensitive cells. A significant radiation enhancement was obtained with EA-sensitive cells exposed to nontoxic concentrations of the drug immediately before or after irradiation. The sensitizer enhancement ratio (SER) of MCF-7 cells was 1.55 with EA (20 μg/ml), while the SER of MCF-7 AR was less than 1.1. Based on five different human tumor cells, a clear inverse relationship was demonstrated between the magnitude of SER and GST levels of tumor cells prior to the combined treatment. Conclusion: The present results suggest that EA, which acts as both a reversible and irreversible inhibitor of GST activity, could significantly enhance the radiation response of

  11. The prostate specific antigen: a new marker for diagnosis of prostate-carcinomas

    International Nuclear Information System (INIS)

    Spitz, J.; Clemenz, N.; Koellermann, M.W.

    1986-01-01

    Determination of serum PSA levels in the primary diagnosis and follow-up of patients with prostatic cancer has all the advantages of a prostate-specific marker that are known from PAP assays. But PSA levels have higher amplitudes that those of PAP so that the signalling effect is improved. In addition, information is available earlier than from PAP levels. Elevation of PSA levels in patients with BPH is suggestive of increased risk, but further studies are required for confirmation. As PSA molecules are less sensitive than PAP molecules, handling of serum samples is less problematic so that systematic follow-ups of patients with prostatic cancer can be done on a wider basis. Experience available sofar suggest that PSA and PAP levels should be determined simultaneously in the primary diagnosis and follow-up of patients with prostatic cancer. (Author)

  12. Prostate specific antigen levels during and after external beam radiotherapy for localized carcinoma of the prostate: Predictor of therapeutic efficancy

    International Nuclear Information System (INIS)

    Rodrigus, P.; Landeghem, A.A.J. van

    1992-01-01

    For 105 patients with locoregional carcinoma of the prostate, prostate specific antigen (PSA) levels were evaluated before, during and after external beam radiotherapy. The median follow-up is 17 months. In 51 patients (48.5%) initial PSA levels exceeded the maximum normal value of 20 ng/ml. Nine patients kept non-declining high levels just after radiotherapy. Only one of these is free of disease. Assuming PSA levels decrease exponentially during radiotherapy, a mean half-life of 62 days (median 54, SD 26 days) was calculated. Three out of five patients with a PSA half-life of more than 88 days relapsed as compared to a 8% (3/37) relapse rate in patients with a 'normal' half-life. Prolonged PSA half-life suggests residual disease. PSA levels are expected to further decrease after radiation. Six months after irradiation persistent high PSA levels were found in 14/51 (27.5%) patients. Only four of them had no evidence of manifest disease. Important negative prognostic factors for disease control in our series were non-declining high levels of PSA, a PSA serum half-life exceeding 88 days and persistence of elevated PSA values longer than six months after treatment. In our opinion, PSA is a valuable marker in the follow-up of prostate cancer patients during and after radiotherapy. (orig.) [de

  13. Collagen derived serum markers in carcinoma of the prostate

    DEFF Research Database (Denmark)

    Rudnicki, M; Jensen, L T; Iversen, P

    1995-01-01

    Three new collagen markers deriving from the collagenous matrix, e.g. carboxyterminal propeptide of type I procollagen (PICP), carboxy-terminal pyridinoline cross-linked telopeptide of type I collagen (ICTP), and aminoterminal propeptide of type III procollagen (PIIINP) were used for the diagnose......, ICTP, and PICP did not differ between these two groups. In patients with metastatic prostatic cancer all five markers were increased compared to the level measured in patients with localized cancer (p

  14. ERG oncoprotein expression in prostate carcinoma patients of different ethnicities

    OpenAIRE

    KELLY, GREGORY M.; KONG, YINK HEAY; DOBI, ALBERT; SRIVASTAVA, SHIV; SESTERHENN, ISABELL A.; PATHMANATHAN, RAJADURAI; TAN, HUI MENG; TAN, SHYH-HAN; CHEONG, SOK CHING

    2014-01-01

    Overexpression of the erythroblast transformation-specific-related gene (ERG) oncoprotein due to transmembrane protease, serine 2 (TMPRSS2)-ERG fusion, the most prevalent genomic alteration in prostate cancer (CaP), is more frequently observed among Caucasian patients compared to patients of African or Asian descent. To the best of our knowledge, this is the first study to investigate the prevalence of ERG alterations in a multiethnic cohort of CaP patients. A total of 191 formalin-fixed para...

  15. Molecular Profiling of Intraductal Carcinoma of the Prostate

    Science.gov (United States)

    2016-12-01

    months or 10% Supporting Agency: Department of the Army Name of Procuring Contracting/Grants Officer: Lymor Barnhard Address of Funding Agency: 820...Name of Procuring Contracting/Grants Officer: Romy Reis Address of Funding Agency: NIH 616 Executive Boulevard, Suite 7013, MSC 8347, Rockville, MD...T.L.L.), the NIH/NCI Prostate SPORE P50CA58236, and a generous gift from Mr David H. Koch (A.M.D.M.). The authors have disclosed that they have no sig

  16. Local control after brachytherapy for localized prostatic carcinomas

    International Nuclear Information System (INIS)

    Wachter, T.; Peneau, M.; Sabattier, R.; Breteau, N.

    1996-01-01

    From 1991 to 1995; 31 patients (mid-age: 70 years) underwent prostatic brachytherapy for localized prostate cancers using Iridium 192 transperineal percutaneous interstitial implantation guided by transrectal ultrasonography. Initial staging included among other evaluations a bilateral staging, iliac and obturator lymph nodes dissection. Classification according to stage was : T1b=16%, T1c=36%, T2a=19%, T2b=13%, T2c=13%, T3a=3%. All patients were N (-). Gleason score was 5 for 55%. 77% of the initial PSA was < 25μg/l. Follow-up included one clinical control and psa determination at 1-3-6-12 and 18 months, bone scanning at 12 months and prostate biopsy guided by transrectal ultrasonography at 18, 24, 30 months. Up to now, mean follow-up is 32 months. At one month, psa was normal (< 2,5μg/l) in 21% of the patients, at 12 months 60% and 67% two years after brachytherapy. Biopsies at 18 months were negative for 60% of the patients and 63% at 24 months. 3 patients were metastased after 3 years. 4 patients had severe complications with colostomy and/or urinary derivation. This technic seems to be interesting for localized prostate cancers T1 and T2 with initial psa < 25μg/l. Two third of the patients had normal psa and negative biopsies after 2 years. The rate of ano-rectal and urinary morbidity is high but is explained by the technic used at the beginning of this study

  17. 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

  18. Efficient CT simulation of the four-field technique for conformal radiotherapy of prostate carcinoma

    International Nuclear Information System (INIS)

    Valicenti, Richard K.; Waterman, Frank M.; Croce, Raymond J.; Corn, Benjamin; Suntharalingam, Nagalingam; Curran, Walter J.

    1997-01-01

    Purpose: Conformal radiotherapy of prostate carcinoma relies on contouring of individual CT slices for target and normal tissue localization. This process can be very time consuming. In the present report, we describe a method to more efficiently localize pelvic anatomy directly from digital reconstructed radiographs (DRRs). Materials and Methods: Ten patients with prostate carcinoma underwent CT simulation (the spiral mode at 3 mm separation) for conformal four-field 'box' radiotherapy. The bulbous urethra and bladder were opacified with iodinated contrast media. On lateral and anteroposterior DRRs, the volume of interest (VOI) was restricted to 1.0-1.5 cm tissue thickness to optimize digital radiograph reconstruction of the prostate and seminal vesicles. By removing unessential voxel elements, this method provided direct visualization of those structures. For comparison, the targets of each patient were also obtained by contouring CT axial slices. Results: The method was successfully performed if the target structures were readily visualized and geometrically corresponded to those generated by contouring axial images. The targets in 9 of 10 patients were reliable representations of the CT-contoured volumes. One patient had 18 mm variation due to the lack of bladder opacification. Using VOIs to generate thin tissue DRRs, the time required for target and normal tissue localization was on the average less than 5 min. Conclusion: In CT simulation of the four-field irradiation technique for prostate carcinoma, thin-tissue DRRs allowed for efficient and accurate target localization without requiring individual axial image contouring. This method may facilitate positioning of the beam isocenter and provide reliable conformal radiotherapy

  19. 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

  20. Positron tomographic assessment of androgen receptors in prostatic carcinoma

    International Nuclear Information System (INIS)

    Dehdashti, Farrokh; Siegel, Barry A.; Welch, Michael J.; Picus, Joel; Michalski, Jeff M.; Dence, Carmen S.; Katzenellenbogen, John A.

    2005-01-01

    The purpose of this study was to evaluate the feasibility of androgen receptor (AR) imaging with 16β-[ 18 F]fluoro-5α-dihydrotestosterone (FDHT) by positron emission tomography (PET) and to assess the binding selectivity of FDHT to AR in patients with prostate cancer. Twenty men (age range 56-87 years) with advanced prostate cancer were studied. All except one had metastatic disease confirmed by biopsy and/or radiological studies. One patient who had radiological findings suggesting a single hepatic metastasis was found to have focal fatty infiltration on biopsy obtained after FDHT-PET and was excluded from further data analysis. FDHT uptake was assessed semiquantitatively by determination of the standardized uptake value (SUV) and tumor-to-muscle ratio (T/M). Additionally, to assess the AR binding selectivity of FDHT, patients with one or more foci of abnormally increased FDHT accumulation were studied after administration of an AR antagonist (flutamide). Conventional imaging demonstrated innumerable lesions in two patients and 43 lesions in the remaining 17 patients with advanced prostate cancer. FDHT-PET was positive in 12 of 19 patients (sensitivity of 63%), including the two patients with innumerable lesions. FDHT-PET detected 24 of 28 known lesions (86%) in the remaining ten patients. In addition, FDHT-PET detected 17 unsuspected lesions in five of these ten patients. All 12 patients with positive FDHT-PET underwent a repeat PET study after receiving flutamide for 1 day (250 mg t.i.d.). In all of these patients, there was a decrease in tumor FDHT uptake after flutamide; the mean (± standard deviation) SUV and T/M decreased from 7.0±4.7 and 6.9±3.9, respectively, to 3.0±1.5 and 3.0±1.6, respectively (p=0.002). The mean PSA in patients with positive FDHT-PET was significantly higher than that in patients with negative FDHT-PET (p=0.006). Our results document the feasibility of PET imaging of prostate cancer with FDHT and suggest that tumor uptake of FDHT

  1. Semiquantitative morphology of human prostatic development and regional distribution of prostatic neuroendocrine cells.

    Science.gov (United States)

    Aumüller, G; Leonhardt, M; Renneberg, H; von Rahden, B; Bjartell, A; Abrahamsson, P A

    2001-02-01

    The neuroendocrine cells of the human prostate have been related to proliferative disorders such as prostatic cancer. Their origin, distribution, and development have therefore been studied and discussed in terms of current stem cell concepts in the prostate. Prostatic tissue specimens (n = 20) from human fetuses (n = 8), prepubertal and pubertal children (n = 8) and mature men (n = 4) were studied immunohistochemically using antibodies directed against neuroendocrine, epithelial as well as secretory markers. Semiquantitative computer-assisted evaluation of different epithelial and stromal components based on stereological principles was performed on azan-stained sections representative of all developmental stages. By the end of gestational Week 9, neuroendocrine (NE) cells appear in the epithelium of the urogenital sinus and are subsequently closely associated with the formation of urethral prostatic buds. The fetal and postnatal distribution pattern of NE cells within the gland is characterized by a relatively constant number of cells per gland similar to prostatic smooth muscle cells. Likewise, a density gradient exists with the highest density in the large collicular ducts and almost no NE cells in subcapsular peripheral acini. In peripheral ducts, the distribution is random. Maturation of the NE cells precedes that of the secretory cells by about 10-16 years. A second prostatic stem cell lineage, different from the urogenital sinus (UGS)-lineage is hypothesized originating from immature neuroendocrine cells. Being morphologically indistinguishable from the UGS-derived prostatic secretory cell lineage, it gives rise to neuroendocrine cells. Their presence is apparently important for proliferation regulation of the UGS-derived lineage of the prostate. Copyright 2001 Wiley-Liss, Inc.

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

    Science.gov (United States)

    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.

  3. PPARγ-independent induction of growth arrest and apoptosis in prostate and bladder carcinoma

    International Nuclear Information System (INIS)

    Chaffer, Christine L; Thomas, David M; Thompson, Erik W; Williams, Elizabeth D

    2006-01-01

    Although PPARγ antagonists have shown considerable pre-clinical efficacy, recent studies suggest PPARγ ligands induce PPARγ-independent effects. There is a need to better define such effects to permit rational utilization of these agents. We have studied the effects of a range of endogenous and synthetic PPARγ ligands on proliferation, growth arrest (FACS analysis) and apoptosis (caspase-3/7 activation and DNA fragmentation) in multiple prostate carcinoma cell lines (DU145, PC-3 and LNCaP) and in a series of cell lines modelling metastatic transitional cell carcinoma of the bladder (TSU-Pr1, TSU-Pr1-B1 and TSU-Pr1-B2). 15-deoxy-prostaglandin J 2 (15dPGJ2), troglitazone (TGZ) and to a lesser extent ciglitazone exhibited inhibitory effects on cell number; the selective PPARγ antagonist GW9662 did not reverse these effects. Rosiglitazone and pioglitazone had no effect on proliferation. In addition, TGZ induced G0/G1 growth arrest whilst 15dPGJ2 induced apoptosis. Troglitazone and 15dPGJ2 inhibit growth of prostate and bladder carcinoma cell lines through different mechanisms and the effects of both agents are PPARγ-independent

  4. External beam radiotherapy for carcinoma of the prostate

    International Nuclear Information System (INIS)

    Sagerman, R.H.; Chun, H.C.; King, G.A.; Chung, C.T.; Dalal, P.S.

    1989-01-01

    Five hundred nineteen patients with prostate cancer were seen in the Radiation Oncology Division of the State University of New York (SUNY) Health Science Center, Syracuse, New York, between 1969 and 1981. The results for the 239 patients treated with radical intent are reported here. All patients received 60 to 70 Gy to the prostate with megavoltage beam irradiation; 142 with a small field (10 X 10 cm) 360 degrees rotational technique for Stage A, B, or C disease and 69 with a four-field pelvic brick technique (followed by a boost to the prostate) for Stage A through C and D1 disease. Twenty-eight patients were treated postoperatively for residual disease after radical prostatectomy or for recurrent tumor. The minimum follow-up time was 5 years. Actuarial 5-year and 7-year survival rates for Stage A (n = 34), B (n = 100), C (n = 63), and D1 (n = 14) were 91% and 76%, 86% and 75%, 67% and 40%, and 46% and 36%, respectively. The corresponding 5-year and 7-year relapse-free survival rates were 72% and 65%, 77% and 60%, 46% and 28%, and 38% and 25%. The local tumor control rates at 5 years were 91%, 85%, 77%, and 62% for Stage A, B, C, and D1, respectively. In our experience, there was no significant difference in relapse-free survival rates for patients who underwent transurethral resection (TURP) versus those who did not (67% versus 78% for Stage B [P greater than 0.25] and 38% versus 47% for Stage C [P greater than 0.25], respectively). Also there was no significant difference in relapse-free survival rates between large and small field techniques (64% versus 77% for Stage B [P greater than 0.25] and 56% versus 41% for Stage C [P greater than 0.25], respectively). The 5-year and 7-year actuarial survival rates were 90% and 71%, respectively, for the 15 patients with residual tumor and 58% and 33%, respectively, for the 13 patients treated for postprostatectomy recurrence

  5. Radiation protection in brachytherapic treatment of prostatic carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Mannino, G.; Bona, R.; Occhipinti, A. [Catania Univ. Hospital, ' Vittorio Emanuele, Ferrarotto e Santo Bambino' (Italy); Testagrossa, B.; Vermiglio, G.; Tripepi, M.G. [Messina Univ., Dept. of Protezionistica Ambientale, Sanitaria, Sociale ed Industriale (Italy)

    2006-07-01

    Purpose: To evaluate absorbed doses for medical staff and general public deriving from prostate brachytherapy with I-125 seeds. Methods And Materials: Radiation exposure measurements were made for staff and on a subset of 64 patients of the 100 trans perineal I-125 implanted seeds implants at the Vittorio Emanuele, Ferrarotto e Santo Bambino Universitary Hospital. Results: Absorbed doses for operators are very low when using radiation safety devices. The exposure rate at the anterior skin surface due to I-125 implanted seeds ranged from 32 to 120 {mu}Sv/hour. Conclusions: The evaluation of dose measurements shows that radiation risk associated to this practice is very low, both for staff that for critical group of population, if they follow the specific radioprotection statements supplied by health physicists. (authors)

  6. Radiation protection in brachytherapic treatment of prostatic carcinoma

    International Nuclear Information System (INIS)

    Mannino, G.; Bona, R.; Occhipinti, A.; Testagrossa, B.; Vermiglio, G.; Tripepi, M.G.

    2006-01-01

    Purpose: To evaluate absorbed doses for medical staff and general public deriving from prostate brachytherapy with I-125 seeds. Methods And Materials: Radiation exposure measurements were made for staff and on a subset of 64 patients of the 100 trans perineal I-125 implanted seeds implants at the Vittorio Emanuele, Ferrarotto e Santo Bambino Universitary Hospital. Results: Absorbed doses for operators are very low when using radiation safety devices. The exposure rate at the anterior skin surface due to I-125 implanted seeds ranged from 32 to 120 μSv/hour. Conclusions: The evaluation of dose measurements shows that radiation risk associated to this practice is very low, both for staff that for critical group of population, if they follow the specific radioprotection statements supplied by health physicists. (authors)

  7. ERG oncoprotein expression in prostate carcinoma patients of different ethnicities.

    Science.gov (United States)

    Kelly, Gregory M; Kong, Yink Heay; Dobi, Albert; Srivastava, Shiv; Sesterhenn, Isabell A; Pathmanathan, Rajadurai; Tan, Hui Meng; Tan, Shyh-Han; Cheong, Sok Ching

    2015-01-01

    Overexpression of the erythroblast transformation-specific-related gene (ERG) oncoprotein due to transmembrane protease, serine 2 ( TMPRSS2 ) -ERG fusion, the most prevalent genomic alteration in prostate cancer (CaP), is more frequently observed among Caucasian patients compared to patients of African or Asian descent. To the best of our knowledge, this is the first study to investigate the prevalence of ERG alterations in a multiethnic cohort of CaP patients. A total of 191 formalin-fixed paraffin-embedded sections of transrectal ultrasound-guided prostate biopsy specimens, collected from 120 patients treated at the Sime Darby Medical Centre, Subang Jaya, Malaysia, were analyzed for ERG protein expression by immunohistochemistry using the anti-ERG monoclonal antibody 9FY as a surrogate for the detection of ERG fusion events. The overall frequency of ERG protein expression in the population evaluated in this study was 39.2%. Although seemingly similar to rates reported in other Asian communities, the expression of ERG was distinct amongst different ethnic groups (P=0.004). Malaysian Indian (MI) patients exhibited exceedingly high expression of ERG in their tumors, almost doubling that of Malaysian Chinese (MC) patients, whereas ERG expression was very low amongst Malay patients (12.5%). When collectively analyzing data, we observed a significant correlation between younger patients and higher ERG expression (P=0.04). The prevalence of ERG expression was significantly different amongst CaP patients of different ethnicities. The higher number of ERG-expressing tumors among MI patients suggested that the TMPRSS2-ERG fusion may be particularly important in the pathogenesis of CaP amongst this group of patients. Furthermore, the more frequent expression of ERG among the younger patients analyzed suggested an involvement of ERG in the early onset of CaP. The results of this study underline the value of using ERG status to better understand the differences in the

  8. Sexual function disorders after local radiotherapy for carcinoma of the prostate

    International Nuclear Information System (INIS)

    Van Heeringen, C.; Verbeek, E.; De Schryver, A.

    1988-01-01

    In order to contribute some insight into the extent to which local radiotherapy for carcinoma of the prostate is followed by disorders in sexual functioning, 18 patients whose age ranged from 60 to 82, were interviewed 4 to 45 months after their Radiotherapy (RT). Our results confirmed the fact that RT was followed by impotence as such in only a minority of cases (3 out of 12 or 0.25). However, when other aspects of sexuality were taken into account, a higher proportion appeared to have problems. In a substantial number of patients, psychogenic factors seemed to be (at least partly) responsible. More attention to these facts and, when necessary, psychiatric assistance, may help reduce the incidence of sexual disorders following RT to the prostate

  9. Dural metastases from prostate carcinoma: A systematic review of the literature apropos of six patients

    International Nuclear Information System (INIS)

    Vasconcelos Sobreira Guedes, Bruno de; Rocha, Antonio Jose da; Pereira Pinto Gama, Hugo; Silva, Carlos Jorge da

    2011-01-01

    Intracranial metastases are a rare manifestation of prostate carcinoma and the dura mater is the most affected site. We report a series of six patients with dural prostate metastases (DPM) and perform a systematic review of the current literature in order to depict imaging trademarks of this condition. This review points to a magnetic resonance imaging (MRI) pattern of meningeal involvement characterized by a diffuse smooth thickening, nodular appearance or dural-based masses. We also demonstrate an osteoblastic pattern of lesions, particularly in sphenoid wing, by computed tomography (CT) scans. We suggest that these imaging findings may support an elevated index of suspicion of DPM in elderly men, including those patients without urologic symptoms.

  10. The association between human papillomavirus and oropharyngeal squamous cell Carcinoma

    DEFF Research Database (Denmark)

    Walvik, Lena; Svensson, Amanda Björk; Friborg, Jeppe

    2016-01-01

    carcinoma using the Bradford Hill criteria. The strength of the association is supported by, detection of human papillomavirus infection and antibodies prior to oropharyngeal squamous cell carcinoma. This is furthermore reinforced by the absence of human papillomavirus DNA in healthy tonsils...... incidence in human papillomavirus positive oropharyngeal squamous cell carcinoma is associated with sexual behaviour. These associations have been repeatedly observed and are in accordance with our current knowledge. The time relation between cause and effect remains the main challenge, due to the lack...... of well-defined premalignant lesions. However, a causal relationship between human papillomavirus infection and oropharyngeal squamous cell carcinoma seems evident....

  11. Serum prostate-specific antigen in monitoring the response of carcinoma of the prostate to radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Fijuth, J; Chauvet, B; Vincent, P; Felix-Faure, C; Reboul, F [Clinique Saint-Catherine, Avignon (France)

    1992-04-01

    In order to assess value of serum prostate-specific antigen (PSA) levels in the monitoring of patients with localized prostatic carcinoma undergoing radical radiation therapy, 146 previously untreated patients were studied. To the prostate 60-70 Gy were administered over 8-9 weeks. Median follow-up was 28 every 3 months during 1st year and every 6 months after. Pre-treatment PSA values exceeded 10 ng/ml in 62%. Initial PSA values were correlated with tumor size and Gleason score. PSA levels decreased 6 months after completion of radiation therapy, compared to initial value in 88.3%. It had fallen to 10 ng/ml or less in 59% with initial abnormal PSA levels. Patients whose initial PSA exceeded 50 ng/ml attained levels of 10 ng/ml or less in only 19%. Only 3/55 with both initial and 6-month PSA values of about 10 ng/ml developed metastases. Of 91 patients with initial PSA values over 10 ng/ml 54 had a 6-month PSA level of 10 ng/ml or less, and only 4/54 relapsed. By contrast, 13/37 patients with a 6-month PSA level persistently above 10 ng/ml relapsed. The 3-year relapse-free survival is 85.1% for 6-month PSA level of about 10 ng/ml, and 50.2% for patients with persistently elevated PSA values. The pattern of decline of PSA level was also analyzed: 11/22 patients with initial PSA>10 ng/ml and relative difference between an initial and a 6-month PSA value of less than 50%, developed metastases. By contrast, when relative difference was greater than 50%, only 6/69 belonging to this group had local recurrence or developed metastases. The 3-year relapse-free survival rate was significantly superior in latter group.

  12. Studies of rhodamine-123: effect on rat prostate cancer and human prostate cancer cells in vitro.

    Science.gov (United States)

    Arcadi, J A; Narayan, K S; Techy, G; Ng, C P; Saroufeem, R M; Jones, L W

    1995-06-01

    The effect of the lipophilic, cationic dye, Rhodamine-123 (Rh-123), on prostate cancer in rats, and on three tumor cell lines in vitro is reported here. The general toxicity of Rh-123 in mice has been found to be minimal. Lobund-Wistar (L-W) rats with the autochthonous prostate cancer of Pollard were treated for six doses with Rh-123 at a dose of 15 mg/kg subcutaneously every other day. Microscopic examination of the tumors revealed cellular and acinar destruction. The effectiveness of Rh-123 as a cytotoxic agent was tested by clonogenic and viability assays in vitro with three human prostate cancer cell lines. Severe (60-95%) growth inhibition was observed following Rh-123 exposure for 2-5 days at doses as low as 1.6 micrograms/ml in all three prostate cancer cell lines.

  13. 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.

  14. Androgen deprivation therapy and fracture risk in Chinese patients with prostate carcinoma.

    Directory of Open Access Journals (Sweden)

    Chi-Ho Lee

    Full Text Available Androgen deprivation therapy (ADT increases fracture risk in men with carcinoma of the prostate, but little is known about the fracture risk for different types of ADT. We studied the fracture risk amongst Chinese patients with carcinoma of the prostate prescribed different ADT regimens.This was a single-centered observational study that involved 741 patients with carcinoma of the prostate from January 2001 to December 2011.After a median follow-up of 5 years, 71.7% of the study cohort received ADT and the incidence rate of fracture was 8.1%. Multivariable Cox regression analysis revealed that use of ADT was significantly associated with risk of incident fracture (Hazard Ratio [HR] 3.60; 95% Confidence Interval [95% CI] 1.41-9.23; p = 0.008, together with aged >75 years and type 2 diabetes. Compared with no ADT, all three types of ADT were independently associated with the risk of incident fracture: anti-androgen monotherapy (HR 4.47; 95% CI 1.47-13.7; p = 0.009, bilateral orchiectomy ± anti-androgens (HR 4.01; 95% CI 1.46-11.1; p = 0.007 and luteinizing hormone-releasing hormone agonists ± anti-androgens (HR 3.16; 95% CI 1.18-8.43; p = 0.022. However, there was no significant difference in the relative risks among the three types of ADT.Fracture risk increases among all types of ADT. Clinicians should take into account the risk-benefit ratio when prescribing ADT, especially in elderly patients with type 2 diabetes.

  15. Pathophysiology and Natural History of Anorectal Sequelae Following Radiation Therapy for Carcinoma of the Prostate

    International Nuclear Information System (INIS)

    Yeoh, Eric K.; Holloway, Richard H.; Fraser, Robert J.; Botten, Rochelle J.; Di Matteo, Addolorata C.; Butters, Julie

    2012-01-01

    Purpose: To characterize the prevalence, pathophysiology, and natural history of chronic radiation proctitis 5 years following radiation therapy (RT) for localized carcinoma of the prostate. Methods and Materials: Studies were performed in 34 patients (median age 68 years; range 54-79) previously randomly assigned to either 64 Gy in 32 fractions over 6.4 weeks or 55 Gy in 20 fractions over 4 weeks RT schedule using 2- and later 3-dimensional treatment technique for localized prostate carcinoma. Each patient underwent evaluations of (1) gastrointestinal (GI) symptoms (Modified Late Effects in Normal Tissues Subjective, Objective, Management and Analytic scales including effect on activities of daily living [ADLs]); (2) anorectal motor and sensory function (manometry and graded balloon distension); and (3) anal sphincteric morphology (endoanal ultrasound) before RT, at 1 month, and annually for 5 years after its completion. Results: Total GI symptom scores increased after RT and remained above baseline levels at 5 years and were associated with reductions in (1) basal anal pressures, (2) responses to squeeze and increased intra-abdominal pressure, (3) rectal compliance and (4) rectal volumes of sensory perception. Anal sphincter morphology was unchanged. At 5 years, 44% and 21% of patients reported urgency of defecation and rectal bleeding, respectively, and 48% impairment of ADLs. GI symptom scores and parameters of anorectal function and anal sphincter morphology did not differ between the 2 RT schedules or treatment techniques. Conclusions: Five years after RT for prostate carcinoma, anorectal symptoms continue to have a significant impact on ADLs of almost 50% of patients. These symptoms are associated with anorectal dysfunction independent of the RT schedules or treatment techniques reported here.

  16. Pathophysiology and Natural History of Anorectal Sequelae Following Radiation Therapy for Carcinoma of the Prostate

    Energy Technology Data Exchange (ETDEWEB)

    Yeoh, Eric K., E-mail: eric.yeoh@health.sa.gov.au [Department of Radiation Oncology, Royal Adelaide Hospital, Adelaide (Australia); Discipline of Medicine, University of Adelaide, Adelaide (Australia); Holloway, Richard H. [Discipline of Medicine, University of Adelaide, Adelaide (Australia); Department of Gastroenterology, Royal Adelaide Hospital, Adelaide (Australia); Fraser, Robert J. [Discipline of Medicine, University of Adelaide, Adelaide (Australia); Gastrointestinal Investigation Unit, Repatriation General Hospital, Adelaide (Australia); Botten, Rochelle J.; Di Matteo, Addolorata C.; Butters, Julie [Department of Radiation Oncology, Royal Adelaide Hospital, Adelaide (Australia)

    2012-12-01

    Purpose: To characterize the prevalence, pathophysiology, and natural history of chronic radiation proctitis 5 years following radiation therapy (RT) for localized carcinoma of the prostate. Methods and Materials: Studies were performed in 34 patients (median age 68 years; range 54-79) previously randomly assigned to either 64 Gy in 32 fractions over 6.4 weeks or 55 Gy in 20 fractions over 4 weeks RT schedule using 2- and later 3-dimensional treatment technique for localized prostate carcinoma. Each patient underwent evaluations of (1) gastrointestinal (GI) symptoms (Modified Late Effects in Normal Tissues Subjective, Objective, Management and Analytic scales including effect on activities of daily living [ADLs]); (2) anorectal motor and sensory function (manometry and graded balloon distension); and (3) anal sphincteric morphology (endoanal ultrasound) before RT, at 1 month, and annually for 5 years after its completion. Results: Total GI symptom scores increased after RT and remained above baseline levels at 5 years and were associated with reductions in (1) basal anal pressures, (2) responses to squeeze and increased intra-abdominal pressure, (3) rectal compliance and (4) rectal volumes of sensory perception. Anal sphincter morphology was unchanged. At 5 years, 44% and 21% of patients reported urgency of defecation and rectal bleeding, respectively, and 48% impairment of ADLs. GI symptom scores and parameters of anorectal function and anal sphincter morphology did not differ between the 2 RT schedules or treatment techniques. Conclusions: Five years after RT for prostate carcinoma, anorectal symptoms continue to have a significant impact on ADLs of almost 50% of patients. These symptoms are associated with anorectal dysfunction independent of the RT schedules or treatment techniques reported here.

  17. Evaluation of Tumor Heterogeneity of Prostate Carcinoma by Flow- and Image DNA Cytometry and Histopathological Grading

    Directory of Open Access Journals (Sweden)

    Naining Wang

    2000-01-01

    Full Text Available Background. Heterogeneity of prostate carcinoma is one of the reasons for pretreatment underestimation of tumor aggressiveness. We studied tumor heterogeneity and the probability of finding the highest tumor grade and DNA aneuploidy with relation to the number of biopsies. Material and methods. Specimens simulating core biopsies from five randomly selected tumor areas from each of 16 Böcking’s grade II and 23 grade III prostate carcinomas were analyzed for tumor grade and DNA ploidy by flow‐ and fluorescence image cytometry (FCM, FICM. Cell cycle composition was measured by FCM. Results. By determination of ploidy and cell cycle composition, morphologically defined tumors can further be subdivided. Heterogeneity of tumor grade and DNA ploidy (FCM was 54% and 50%. Coexistence of diploid tumor cells in aneuploid specimens represents another form of tumor heterogeneity. The proportion of diploid tumor cells decreased significantly with tumor grade and with increase in the fraction of proliferating cell of the aneuploid tumor part. The probability of estimating the highest tumor grade or aneuploidy increased from 40% for one biopsy to 95% for 5 biopsies studied. By combining the tumor grade with DNA ploidy, the probability of detecting a highly aggressive tumor increased from 40% to 70% and 90% for one and two biopsies, respectively. Conclusion. Specimens of the size of core biopsies can be used for evaluation of DNA ploidy and cell cycle composition. Underestimation of aggressiveness of prostate carcinoma due to tumor heterogeneity is minimized by simultaneous study of the tumor grade and DNA ploidy more than by increasing the number of biopsies. The biological significance of coexistent diploid tumor cell in aneuploid lesions remains to be evaluated.

  18. Prostatitis

    Science.gov (United States)

    Prostatitis Overview Prostatitis is swelling and inflammation of the prostate gland, a walnut-sized gland situated directly below the bladder in ... produces fluid (semen) that nourishes and transports sperm. Prostatitis often causes painful or difficult urination. Other symptoms ...

  19. Serum testosterone as a prognostic factor in patients with advanced prostatic carcinoma

    DEFF Research Database (Denmark)

    Iversen, P; Rasmussen, F; Christensen, I J

    1994-01-01

    In 245 patients with previously untreated advanced carcinoma of the prostate, serum concentrations of testosterone have been measured before androgen deprivation therapy, and patients were divided in quartiles according to their serum concentration. Pretreatment level of serum testosterone...... was confirmed as having significant prognostic value on progression-free, overall, and cancer-specific survival, and the hazard ratios of lower quartiles compared to the upper quartile for these endpoints were 2.3, 2.1, and 2.0, respectively. However, correlations with symptomatology and other pretreatment...

  20. Identification of prognostic molecular features in the reactive stroma of human breast and prostate cancer.

    Directory of Open Access Journals (Sweden)

    Anne Planche

    Full Text Available Primary tumor growth induces host tissue responses that are believed to support and promote tumor progression. Identification of the molecular characteristics of the tumor microenvironment and elucidation of its crosstalk with tumor cells may therefore be crucial for improving our understanding of the processes implicated in cancer progression, identifying potential therapeutic targets, and uncovering stromal gene expression signatures that may predict clinical outcome. A key issue to resolve, therefore, is whether the stromal response to tumor growth is largely a generic phenomenon, irrespective of the tumor type or whether the response reflects tumor-specific properties. To address similarity or distinction of stromal gene expression changes during cancer progression, oligonucleotide-based Affymetrix microarray technology was used to compare the transcriptomes of laser-microdissected stromal cells derived from invasive human breast and prostate carcinoma. Invasive breast and prostate cancer-associated stroma was observed to display distinct transcriptomes, with a limited number of shared genes. Interestingly, both breast and prostate tumor-specific dysregulated stromal genes were observed to cluster breast and prostate cancer patients, respectively, into two distinct groups with statistically different clinical outcomes. By contrast, a gene signature that was common to the reactive stroma of both tumor types did not have survival predictive value. Univariate Cox analysis identified genes whose expression level was most strongly associated with patient survival. Taken together, these observations suggest that the tumor microenvironment displays distinct features according to the tumor type that provides survival-predictive value.

  1. induced acute cytotoxicity in human cervical epithelial carcinoma cells

    African Journals Online (AJOL)

    Molecular basis of arsenite (As +3 )-induced acute cytotoxicity in human cervical epithelial carcinoma cells. ... Libyan Journal of Medicine ... Methods: After performing cytotoxic assays on a human epithelial carcinoma cell line, expression analysis was done by quantitative polymerase chain reaction, western blotting, and ...

  2. A preliminary investigation of the enzymatic inhibition of 5alpha-reduction and growth of prostatic carcinoma cell line LNCap-FGC by natural astaxanthin and Saw Palmetto lipid extract in vitro.

    Science.gov (United States)

    Anderson, Mark L

    2005-01-01

    Inhibition of 5alpha-reductase has been reported to decrease the symptoms of benign prostate hyperplasia (BPH) and possibly inhibit or help treat prostate cancer. Saw Palmetto berry lipid extract (SPLE) is reported to inhibit 5alpha-reductase and decrease the clinical symptoms of BPH. Epidemiologic studies report that carotenoids such as lycopene may inhibit prostate cancer. In this investigation the effect of the carotenoid astaxanthin, and SPLE were examined for their effect on 5alpha-reductase inhibition as well as the growth of prostatic carcinoma cells in vitro. These studies support patent #6,277,417 B1. The results show astaxanthin demonstrated 98% inhibition of 5alpha-reductase at 300 microg/mL in vitro. Alphastat, the combination of astaxanthin and SPLE, showed a 20% greater inhibition of 5alpha-reductase than SPLE alone n vitro. A nine day treatment of prostatic carcinoma cells with astaxanthin in vitro produced a 24% decrease in growth at 0.1 mcg/mL and a 38% decrease at 0.01 mcg/mL. SPLE showed a 34% decrease at 0.1 mcg/mL. Low levels of carotenoid astaxanthin inhibit 5alpha-reductase and decrease the growth of human prostatic cancer cells in vitro. Astaxanthin added to SPLE shows greater inhibition of 5alpha-reductase than SPLE alone in vitro.

  3. Treatment decision-making strategies and influences in patients with localized prostate carcinoma.

    Science.gov (United States)

    Gwede, Clement K; Pow-Sang, Julio; Seigne, John; Heysek, Randy; Helal, Mohamed; Shade, Kristin; Cantor, Alan; Jacobsen, Paul B

    2005-10-01

    Patients diagnosed with localized prostate carcinoma need to interpret complicated medical information to make an informed treatment selection from among treatments that have comparable efficacy but differing side effects. The authors reported initial results for treatment decision-making strategies among men receiving definitive treatment for localized prostate carcinoma. One hundred nineteen men treated with radical prostatectomy (44%) or brachytherapy (56%) consented to participate. Guided by a cognitive-affective theoretic framework, the authors assessed differences in decision-making strategies, and treatment and disease-relevant beliefs and affects, in addition to demographic and clinical variables. Approximately half of patients reported difficulty (49%) and distress (45%) while making treatment decisions, but no regrets (74%) regarding the treatment choice they made. Patients who underwent prostatectomy were younger, were more likely to be employed, had worse tumor grade, and had a shorter time since diagnosis (P Decision-making aids or other interventions to reduce decisional difficulty and emotional distress during decision making were indicated.

  4. 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)

  5. Clinical eveluation of metastasis from carcinoma of the prostate by bone scintiscanning

    International Nuclear Information System (INIS)

    Okada, Kiyoki; Igarashi, Jotaro; Nogaki, Joji; Kinoshita, Masayuki; Kishimoto, Takashi

    1981-01-01

    Eighty radioisotopic bone scintiscans in conjunction with radiographic skeletal survey were carried out in 47 patients with prostatic carcinoma encountered over the past 6 years. Five patients were excluded because of false positive bone scan. None of the patients was found with false negative bone scan irrespective of the presence of osteolytic lesions. In 21 of the remaining 42 cases (40.0%), increased information on bone metastasis was obtained by the bone scan. A positive bone scan was interpreted at 156 sites, of which 67 (42.9%) were negative on bone survey. Bone scan was superior to bone survey for detecting metastatic sites of the sternum, cervical and thoracic spine, ribs, scapula and skull. Serial bone scans in some cases demonstrated an objective response of the metastasis following hormonal treatment. At the time of bone scan, 22 of 47 cases (46.8%) showed an abnormal renal image, which represented the degree of bone metastasis as well as that of renal function. Thus, bone scan represents a useful tool for detecting metastatic lesions from prostatic carcinoma and for assessing the response to treatment. (author)

  6. Skeletal metastases of carcinomas of prostate in dependence on tumor size and tumor differentiation

    International Nuclear Information System (INIS)

    Krause, U.

    1981-01-01

    153 patients with carcinoma of the prostate underwent holebody skeletal scintiscanning. It resulted that the tendency to the development of skeletal metastases increases with increasing dedifferentiation of the tumor. Also the tumor size correlated with the metastase identification. The tumor dedifferentiation also increased with the tumor size. The findings proved that the early diagnosis of a carcinoma of the prostate is a necessary prerequisite, because a radical total removal can only be curative when any metastases are absent. The comparative evaluation of the diagnostic methods proved the superiority of the nuclear medical examination. In 68% of the cases the roentgenologic examination led to correctly positive results. This investigation showed with 98% a high diagnostic specificity and therefore it should be applied in addition to scintiscanning in order to obtain supplementary information. The alkaline and the acid phosphatase offering an almost identical informative value resulted to be not useful for establishing an early diagnosis of skeletal metastases. It was found that the determination of the blood sedimentation rate and of the lactate dehydrogenase do also not render possible the early diagnosis of skeletal metastases. (orig./MG) [de

  7. A novel combination of multiple primary carcinomas: Urinary bladder transitional cell carcinoma, prostate adenocarcinoma and small cell lung carcinoma- report of a case and review of the literature

    Directory of Open Access Journals (Sweden)

    Giannikaki Elpida

    2005-07-01

    Full Text Available Abstract Background The incidence of multiple primary malignant neoplasms increases with age and they are encountered more frequently nowadays than before, the phenomenon is still considered to be rare. Case presentation We report a case of a man in whom urinary bladder transitional cell carcinoma, metachronous prostate adenocarcinoma and small cell lung carcinoma were diagnosed within an eighteen-month period. The only known predisposing factor was that he was heavy smoker (90–100 packets per year. The literature on the phenomenon of multiple primary malignancies in a single patient is reviewed and the data is summarized. Conclusion It is important for the clinicians to keep in mind the possibility of a metachronous (successive or a synchronous (simultaneous malignancy in a cancer patient. It is worthy mentioning this case because clustering of three primary malignancies (synchronous and metachronous is of rare occurrence in a single patient, and, to our knowledge, this is the first report this combination of three carcinomas appearing in the same patient.

  8. Papillary urothelial carcinoma with squamous differentiation in association with human papilloma virus: case report and literature review.

    Science.gov (United States)

    Guma, Sergei; Maglantay, Remegio; Lau, Ryan; Wieczorek, Rosemary; Melamed, Jonathan; Deng, Fang-Ming; Zhou, Ming; Makarov, Danil; Lee, Peng; Pincus, Matthew R; Pei, Zhi-Heng

    2016-01-01

    The human papilloma virus (HPV) is a carcinogen known for its strong association with cervical cancers and cervical lesions. It is also known to be associated with a variety of squamous cell carcinomas in other areas, such as the penis, vulva, anus and head and neck. However, the association with urothelial carcinoma remains controversial. Here, we report a case of urothelial carcinoma with squamous differentiation associated with HPV-6/HPV-11. This is a case of a 70 year old man who presented with nocturia and pressure during urination. During the TURP procedure for what was clinically thought to be benign prostate hyperplasia with pathologic diagnosis as prostate carcinoma, a 2 cm papillary mass was found in the distal penile urethra. The papillary mass was found to be a high grade urothelial carcinoma positive for GATA 3 expression, with focal areas of squamous differentiation. The areas with squamous differentiation demonstrated koilocytic differentiation, which were positive for strong p16 expression. The tumor was found to harbor low risk HPV 6/11 by in situ hybridization. This study case demonstrates HPV infection with a low risk subtype (HPV 6/11) associated with an urothelial carcinoma with squamous differentiation and condylomatous features.

  9. Tissue polypeptide-specific antigen (TPS) determinations before and during intermittent maximal androgen blockade in patients with metastatic prostatic carcinoma

    NARCIS (Netherlands)

    Kil, P. J. M.; Goldschmidt, H. M. J.; Wieggers, B. J. A.; Kariakine, O. B.; Studer, U. E.; Whelan, P.; Hetherington, J.; de Reijke, Th M.; Hoekstra, J. W.; Collette, L.

    2003-01-01

    To evaluate the prognostic significance of serially measured tissue polypeptide-specific antigen (TPS) levels in patients with metastatic prostatic carcinoma treated with intermittent maximal androgen blockade (MAB). To determine its value with respect to predicting response to treatment and time to

  10. Differential Modulation of Transcription Factors and Cytoskeletal Proteins in Prostate Carcinoma Cells by a Bacterial Lactone

    Directory of Open Access Journals (Sweden)

    Senthil R. Kumar

    2018-01-01

    Full Text Available The present study tested the effect of a bacterial lactone N-(3-oxododecanoyl-homoserine lactone (C12-HSL on the cytoskeletal and transcriptional genes and proteins in prostate adenocarcinoma (PA cells (DU145 and LNCaP and prostate small cell neuroendocrine carcinoma (SCNC PC3 cells including their cellular viability and apoptosis. Our data indicate that cell migration and colony formation were affected in the presence of C12-HSL. C12-HSL induced apoptosis and altered viability of both PA and SCNC cells in a concentration dependent manner as measured by fluorescence and chemiluminescence assays. Compared to PCa cells, noncancerous prostate epithelial cells (RWPE1 were resistant to modification by C12-HSL. Further, the viability of PC3 cells in 3D matrix was suppressed by C12-HSL treatment as detected using calcein AM fluorescence in situ. C12-HSL treatment induced cytoskeletal associated protein expression of vinculin and RhoC, which may have implications in cancer cell motility, adhesion, and metastasis. IQGAP protein expression was reduced in DU145 and RWPE1 cells in the presence of C12-HSL. C12-HSL decreased STAT3 phosphorylation in DU145 cells but increased STAT1 protein phosphorylation in PC3 and LNCaP cells. Overall, these studies indicate that C12-HSL can trigger changes in transcription factors and cytoskeletal proteins and thereby modulate growth and migration properties of PCa cells.

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

    Directory of Open Access Journals (Sweden)

    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.

  12. A Network Biology Approach Identifies Molecular Cross-Talk between Normal Prostate Epithelial and Prostate Carcinoma Cells.

    Directory of Open Access Journals (Sweden)

    Victor Trevino

    2016-04-01

    Full Text Available The advent of functional genomics has enabled the genome-wide characterization of the molecular state of cells and tissues, virtually at every level of biological organization. The difficulty in organizing and mining this unprecedented amount of information has stimulated the development of computational methods designed to infer the underlying structure of regulatory networks from observational data. These important developments had a profound impact in biological sciences since they triggered the development of a novel data-driven investigative approach. In cancer research, this strategy has been particularly successful. It has contributed to the identification of novel biomarkers, to a better characterization of disease heterogeneity and to a more in depth understanding of cancer pathophysiology. However, so far these approaches have not explicitly addressed the challenge of identifying networks representing the interaction of different cell types in a complex tissue. Since these interactions represent an essential part of the biology of both diseased and healthy tissues, it is of paramount importance that this challenge is addressed. Here we report the definition of a network reverse engineering strategy designed to infer directional signals linking adjacent cell types within a complex tissue. The application of this inference strategy to prostate cancer genome-wide expression profiling data validated the approach and revealed that normal epithelial cells exert an anti-tumour activity on prostate carcinoma cells. Moreover, by using a Bayesian hierarchical model integrating genetics and gene expression data and combining this with survival analysis, we show that the expression of putative cell communication genes related to focal adhesion and secretion is affected by epistatic gene copy number variation and it is predictive of patient survival. Ultimately, this study represents a generalizable approach to the challenge of deciphering cell

  13. A Network Biology Approach Identifies Molecular Cross-Talk between Normal Prostate Epithelial and Prostate Carcinoma Cells.

    Science.gov (United States)

    Trevino, Victor; Cassese, Alberto; Nagy, Zsuzsanna; Zhuang, Xiaodong; Herbert, John; Antczak, Philipp; Clarke, Kim; Davies, Nicholas; Rahman, Ayesha; Campbell, Moray J; Guindani, Michele; Bicknell, Roy; Vannucci, Marina; Falciani, Francesco

    2016-04-01

    The advent of functional genomics has enabled the genome-wide characterization of the molecular state of cells and tissues, virtually at every level of biological organization. The difficulty in organizing and mining this unprecedented amount of information has stimulated the development of computational methods designed to infer the underlying structure of regulatory networks from observational data. These important developments had a profound impact in biological sciences since they triggered the development of a novel data-driven investigative approach. In cancer research, this strategy has been particularly successful. It has contributed to the identification of novel biomarkers, to a better characterization of disease heterogeneity and to a more in depth understanding of cancer pathophysiology. However, so far these approaches have not explicitly addressed the challenge of identifying networks representing the interaction of different cell types in a complex tissue. Since these interactions represent an essential part of the biology of both diseased and healthy tissues, it is of paramount importance that this challenge is addressed. Here we report the definition of a network reverse engineering strategy designed to infer directional signals linking adjacent cell types within a complex tissue. The application of this inference strategy to prostate cancer genome-wide expression profiling data validated the approach and revealed that normal epithelial cells exert an anti-tumour activity on prostate carcinoma cells. Moreover, by using a Bayesian hierarchical model integrating genetics and gene expression data and combining this with survival analysis, we show that the expression of putative cell communication genes related to focal adhesion and secretion is affected by epistatic gene copy number variation and it is predictive of patient survival. Ultimately, this study represents a generalizable approach to the challenge of deciphering cell communication networks

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

    Directory of Open Access Journals (Sweden)

    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.

  15. Zinc in human prostate gland. Normal, hyperplastic and cancerous

    International Nuclear Information System (INIS)

    Zaichick, V.Ye.; Sviridova, T.V.; Zaichick, S.V.

    1997-01-01

    Zinc concentration in a prostate gland is much higher than that in other human tissues. Data about zinc changes for different prostate diseases are limited and greatly contradictory. Zinc content was determined for biopsy and resected materials of transrectal puncture tissues from benign prostate hyperplasia (BPH) and prostate cancer. There were 109 patients (50 BPH and 59 cancer) available for the present study. Control group consisted of 37 intact glands of men died an unexpected death (accident, murder, acute cardiac insufficiency, etc.). All materials studied were divided into two parts. One of them was morphologically examined, while another one was subjected to zinc analysis by INAA. Zinc contents (M ± SE) of normal, benign hyperplastic and cancerous prostate glands were found to be 1018 ± 124, 1142 ± 77, and 146 ± 10 μg/g dry tissue, respectively. It was shown that zinc assessments in the materials of transrectal puncture biopsy of indurated prostate sites can be used as an additional test for differential diagnostics of BPH and cancer. Accuracy, sensitivity and specificity of the test are 98 ± 2%. (author)

  16. PSA doubling time of prostate carcinoma managed with watchful observation alone

    International Nuclear Information System (INIS)

    Choo, Richard; DeBoer, Gerrit; Klotz, Lawrence; Danjoux, Cyril; Morton, Gerard C.; Rakovitch, Eileen; Fleshner, Neil; Bunting, Peter; Kapusta, Linda; Hruby, George

    2001-01-01

    Purpose: To study prostate-specific antigen (PSA) doubling time of untreated, favorable grade, prostate carcinoma. Methods and Materials: A prospective single-arm cohort study has been in progress to assess the feasibility of a watchful observation protocol with selective delayed intervention using clinical, histologic, or PSA progression as treatment indication in untreated, localized, favorable grade prostate adenocarcinoma (T1b-T2bN0 M0, Gleason Score ≤7, and PSA ≤15 ng/mL). Patients are conservatively managed with watchful observation alone, as long as they do not meet the arbitrarily defined disease progression criteria. Patients are followed regularly and undergo blood tests including PSA at each visit. PSA doubling time (Td) is estimated from a linear regression of ln(PSA) on time, assuming a simple exponential growth model. Results: As of March 2000, 134 patients have been on the study for a minimum of 12 months (median, 24; range, 12-52) and have a median frequency of PSA measurement of 7 times (range, 3-15). Median age is 70 years. Median PSA at enrollment is 6.3 (range, 0.5-14.6). The distribution of Td is as follows: 50 years, 27. The median Td is 5.1 years. In 44 patients (33%), Td is greater than 10 years. There was no correlation between Td and patient age, clinical T stage, Gleason score, or initial PSA level. Conclusion: Td of untreated prostate cancer varies widely. In our cohort, 33% have Td >10 years. Td may be a useful tool to guide treatment intervention for patients managed conservatively with watchful observation alone

  17. Radioimmunoassay for tumor antigen of human cervical squamous cell carcinoma

    International Nuclear Information System (INIS)

    Kato, H.; Torigoe, T.

    1977-01-01

    A heterologous antiserum for human cervical squamous cell carcinoma was prepared and specificity determined by Ouchterlony immunodiffusion and immunofluorescence studies. With this antiserum, a tumor antigen was purified from human cervical squamous cell carcinoma tissue. The specificities of the antigen and the antiserum were then re-examined by a radioimmunoassay method using 125 I-labeled purified antigen. Although normal cervical tissue extract showed a moderate cross-reactivity in the radioimmunoassay, the circulating antigen activity could not be detected in normal women or in several patients with other carcinomas, whereas 27 of 35 patients with cervical squamous cell carcinoma showed detectable serum antigen activity. All patients with advanced stages of cervical squamous cell carcinoma showed detectable antigen levels. These results indicate that there is a quantitative abnormality, at least, of this tumor antigen in patients with cervical squamous cell carcinoma and that the radioimmunoassay for the antigen is a potentially useful tool in clinical care

  18. Rad9 Has a Functional Role in Human Prostate Carcinogenesis

    Science.gov (United States)

    Zhu, Aiping; Zhang, Charles Xia; Lieberman, Howard B.

    2013-01-01

    Prostate cancer is currently the most common type of neoplasm found in American men, other than skin cancer, and is the second leading cause of cancer death in males. Because cell cycle checkpoint proteins stabilize the genome, the relationship of one such protein, Rad9, to prostate cancer was investigated. We found that four prostate cancer cell lines (CWR22, DU145, LNCaP, and PC-3), relative to PrEC normal prostate cells, have aberrantly high levels of Rad9 protein. The 3′-end region of intron 2 of Rad9 in DU145 cells is hypermethylated at CpG islands, and treatment with 5′-aza-2′-deoxycytidine restores near-normal levels of methylation and reduces Rad9 protein abundance. Southern blot analyses indicate that PC-3 cells contain an amplified Rad9 copy number. Therefore, we provide evidence that Rad9 levels are high in prostate cancer cells due at least in part to aberrant methylation or gene amplification. The effectiveness of small interfering RNA to lower Rad9 protein levels in CWR22, DU145, and PC-3 cells correlated with reduction of tumorigenicity in nude mice, indicating that Rad9 actively contributes to the disease. Rad9 protein levels were high in 153 of 339 human prostate tumor biopsy samples examined and detectable in only 2 of 52 noncancerous prostate tissues. There was a strong correlation between Rad9 protein abundance and cancer stage. Rad9 protein level can thus provide a biomarker for advanced prostate cancer and is causally related to the disease, suggesting the potential for developing novel diagnostic, prognostic, and therapeutic tools based on detection or manipulation of Rad9 protein abundance. PMID:18316588

  19. Serum prostate-specific antigen in monitoring the response of carcinoma of the prostate to radiation therapy

    International Nuclear Information System (INIS)

    Fijuth, J.; Chauvet, B.; Vincent, P.; Felix-Faure, C.; Reboul, F.

    1992-01-01

    In order to assess value of serum prostate-specific antigen (PSA) levels in the monitoring of patients with localized prostatic carcinoma undergoing radical radiation therapy, 146 previously untreated patients were studied. To the prostate 60-70 Gy were administered over 8-9 weeks. Median follow-up was 28 every 3 months during 1st year and every 6 months after. Serum PSA levels were measured prior to radiotherapy. Pre-treatment PSA values exceeded 10 ng/ml in 62%. Initial PSA values were correlated with tumor size and Gleason score. PSA levels decreased 6 months after completion of radiation therapy, compared to initial value in 88.3%. It had fallen to 10 ng/ml or less in 59% with initial abnormal PSA levels. Patients whose initial PSA exceeded 50 ng/ml attained levels of 10 ng/ml or less in only 19%. Only 3/55 with both initial and 6-month PSA values ≤ 10 ng/ml developed metastases. Of 91 patients with initial PSA values over 10 ng/ml 54 had a 6-month PSA level of 10 ng/ml or less, and only 4/54 relapsed. By contrast, 13/37 patients with a 6-month PSA level persistently above 10 ng/ml relapsed. The 3-year relapse-free survival is 85.1% for 6-month PSA level ≤ 10 ng/ml, and 50.2% for patients with persistently elevated PSA values. This difference is highly significant (p 10 ng/ml and relative difference between an initial and a 6-month PSA value of less than 50%, developed metastases. By contrast, when relative difference was ≥50%, only 6/69 belonging to this group had local recurrence or developed metastases. The 3-year relapse-free survival rate was significantly superior in latter group (76.9 versus 30.2%, p<0.0001). It is concluded that a PSA value in excess of 10 mg/nl 6 months after radiation therapy or a relative difference between an initial and a 6- month PSA value of less than 50% have a poor prognostic significance and are discriminant criteria to identify a subset of patients with a high risk of relapse who may benefit from early hormonal therapy

  20. Radical prostatectomy and postoperative irradiation in patients with pathological stage C (T3) carcinoma of the prostate

    International Nuclear Information System (INIS)

    Petrovich, Zbigniew; Lieskovsky, Gary; Langholz, Bryan; Formenti, Silvia; Baert, Luc; Streeter, Oscar; Skinner, Donald G.

    1998-01-01

    Purpose: Adenocarcinoma of the prostate is the most common human cancer of internal organs. Radical surgery is regarded by many to be the treatment of choice for capsule confined disease. Since accurate preoperative assessment of tumor stage is difficult to define, many patients are subsequently found to have pathological stage C (T3) disease. These patients should be considered for adjuvant radiotherapy. Methods and Materials: A group of 201 PS C (T3) unselected patients, treated with radical prostatectomy and limited pelvic lymphadenectomy, received postoperative irradiation to the prostate bed. This radiotherapy was given between 42-90 days after surgery and consisted of a median dose of 48 Gy. Patient survival, disease free survival, time to clinical and chemical relapse and the incidence of local and systemic relapse were analyzed. The influence of multiple parameters on the treatment outcome including patient age, treatment period, clinical stage, pathological stage, Gleason's score, prostate specific antigen (PSA), radiotherapy techniques and radiation dose were examined using univariate and multivariate analysis. Follow-up ranged from 3 to 15 years, with a median of 5 years. Results: The overall 5- and 10-year actuarial survival was 92% and 83% (median > 10 years), respectively and the 5- and 10-year disease-free survival (clinical and PSA) was 67% and 53% (median > 10 years), respectively. A total of 61 (30%) patients had a recurrence, including 23 (11%) patients who had clinical and 38 (19%) who had PSA recurrence. Of the 23 patients with clinical recurrence, 10 (5%) had local recurrence, including two patients who had local and systemic recurrence. Pathological stage and Gleason's score were independently predictive of recurrence (each with p 25 ng/ml) was also an important independent factor predicting tumor recurrence, p = 0.05. All other investigated parameters were not significant in predicting tumor recurrence. This treatment program was very well

  1. Constitutive Activation of NF-kappaB in Prostate Carcinoma Cells Through a Positive Feedback Loop: Implication of Inducible IKK-Related Kinase (IKKi)

    National Research Council Canada - National Science Library

    Budunova, Irina V

    2004-01-01

    The overall goal of this project is to understand the role of inducible IKK-related kinase IKKi in constitutive activation of anti-apoptotic transcription factor NF-kB prostate carcinoma (PC) cells...

  2. Constitutive Activation of NF-KB in Prostate Carcinoma Cells Through a Positive Feedback Loop: Implication of Inducible IKK-Related Kinase (IKKi)

    National Research Council Canada - National Science Library

    Budunova, Irina V

    2005-01-01

    The overall goal of this project is to understand the role of inducible IKK-related kinase IKKi in constitutive activation of anti-apoptotic transcription factor NF-KB prostate carcinoma (PC) cells...

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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

  5. The inhibition of the highly expressed miR-221 and miR-222 impairs the growth of prostate carcinoma xenografts in mice.

    Directory of Open Access Journals (Sweden)

    Neri Mercatelli

    Full Text Available BACKGROUND: MiR-221 and miR-222 are two highly homologous microRNAs whose upregulation has been recently described in several types of human tumors, for some of which their oncogenic role was explained by the discovery of their target p27, a key cell cycle regulator. We previously showed this regulatory relationship in prostate carcinoma cell lines in vitro, underlying the role of miR-221/222 as inducers of proliferation and tumorigenicity. METHODOLOGY/PRINCIPAL FINDINGS: Here we describe a number of in vivo approaches confirming our previous data. The ectopic overexpression of miR-221 is able, per se, to confer a high growth advantage to LNCaP-derived tumors in SCID mice. Consistently, the anti-miR-221/222 antagomir treatment of established subcutaneous tumors derived from the highly aggressive PC3 cell line, naturally expressing high levels of miR-221/222, reduces tumor growth by increasing intratumoral p27 amount; this effect is long lasting, as it is detectable as long as 25 days after the treatment. Furthermore, we provide evidence in favour of a clinical relevance of the role of miR-221/222 in prostate carcinoma, by showing their general upregulation in patient-derived primary cell lines, where we find a significant inverse correlation with p27 expression. CONCLUSIONS/SIGNIFICANCE: These findings suggest that modulating miR-221/222 levels may have a therapeutic potential in prostate carcinoma.

  6. Chromosomal instability detected by interphase fluorescence in situ hybridization and its relation to p3 alteration in prostate carcinoma in Saudi patients

    International Nuclear Information System (INIS)

    Al-Maghrabi, Jaudah A.

    2005-01-01

    Chromosomal instability (CIN) is a feature of human neoplasm. The p53 mutation has been shown to be associated with CIN in many human dysplastic and neoplastic lesions. The objective of this study was to examine CIN and p53 mutations in prostate carcinoma (Pca) resected from Saudi patients. Testing of p53 alterations using immunohistochemistry was performed on 28 archived prostatic carcinoma specimens containing Pca foci from Saudi patients seen at King Abdul-Aziz University Hospital, Jeddah, Kingdom of Saudi Arabia. Chrosomal instability was evaluated in the same tissues by interphase in situ hybridization (IFISH) using centromere probes for chromosomes 7 and 8. Immunochemistry and IFISH were performed at Princess Margaret Hospital, University Health Network, Toronto, Ontario, Canada in 2001. The p53 immunoreactivity was found in 29% in Pca and 0% in benign epithelium. Interphase in situ hybridization revealed numerical chromosomal alterations in keeping with CIN in 63% of p53 positive and 20% p53 negative Pca. No evidence of CIN was seen in non-neoplastic epithelium. We concluded that CIN as determined by IFISH is present in Pca from Saudi patients similarly to those reported in western countries. The p53 mutation occurs relatively infrequently in Pca and associated with the presence of CIN at least in a subset of Pca. (author)

  7. Biomarkers of Prostatic Cancer: An Attempt to Categorize Patients into Prostatic Carcinoma, Benign Prostatic Hyperplasia, or Prostatitis Based on Serum Prostate Specific Antigen, Prostatic Acid Phosphatase, Calcium, and Phosphorus

    Directory of Open Access Journals (Sweden)

    Shahana Sarwar

    2017-01-01

    Full Text Available Prostatitis, BPH, and P.Ca are the most frequent pathologies of the prostate gland that are responsible for morbidity in men. Raised levels of PSA are seen in different pathological conditions involving the prostate. PAP levels are altered in inflammatory or infectious or abnormal growth of the prostate tissue. Serum calcium and phosphorus levels were also found to be altered in prostate cancer and BPH. The present study was carried out to study the levels of PSA, PAP, calcium, and phosphorus in serum of patients with Prostatitis, BPH, or P.Ca and also to evaluate the relationship between them. Males in the age group of 50–85 years with LUTS disease symptoms and with PSA levels more than 4 ng/mL were included. A total of 114 patients were analyzed including 30 controls. Prostatitis in 35.7% of cases, BPH in 35.7% of the cases, and P.Ca in 28.57% of the cases were observed. Thus, the nonmalignant cases constitute a majority. PSA, a marker specific for prostatic conditions, was significantly high in all the diseases compared to controls. A rise in serum PSA and PAP indicates prostatitis or, in combination with these two tests, decreased serum calcium shows advanced disease.

  8. SEM and X-ray microanalysis of human prostatic calculi

    International Nuclear Information System (INIS)

    Vilches, J.; Lopez, A.; De Palacio, L.; Munoz, C.; Gomez, J.

    1982-01-01

    Calculi removed from human prostates affected with nodular hyperplasia were analyzed with scanning electron microscopy and EDAX system. The general spectrum was made up of Na, Al, Mg, S, P, Ca and Zn. Two types of stone were identified morphostructurally and microanalytically: calculi type I of nodular surface with high peaks of S, and calculi type II polyfaceted with high peaks of P and Ca. Their formation from corpora amylacea and/or exogenous constituents is discussed. The superficial deposit of Zn suggests its incorporation from the prostatic liquid and does not seem to play an important role in the genesis

  9. Different Phenotypes in Human Prostate Cancer: α6 or α3 Integrin in Cell-extracellular Adhesion Sites

    Directory of Open Access Journals (Sweden)

    Monika Schmelz

    2002-01-01

    Full Text Available The distribution of α6/α3 integrin in adhesion complexes at the basal membrane in human normal and cancer prostate glands was analyzed in 135 biopsies from 61 patients. The levels of the polarized α6/α3 integrin expression at the basal membrane of prostate tumor glands were determined by quantitative immunohistochemistry. The α6/α3 integrin expression was compared with Gleason sum score, pathological stage, and preoperative serum prostate-specific antigen (PSA. The associations were assessed by statistical methods. Eighty percent of the tumors expressed the α6 or α3 integrin and 20% was integrin-negative. Gleason sum score, but not serum PSA, was associated with the integrin expression. Low Gleason sum score correlated with increased integrin expression, high Gleason sum score with low and negative integrin expression. Three prostate tumor phenotypes were distinguished based on differential integrin expression. Type I coexpressed both α6 and α3 subunits, type II exclusively expressed a6 integrin, and type III expressed α3 integrin only. Fifteen cases were further examined for the codistribution of vinculin, paxillin, and CD 151 on frozen serial sections using confocal laser scanning microscopy. The α6/α3 integrins, CD151, paxillin, and vinculin were present within normal glands. In prostate carcinoma, α6 integrin was colocalized with CD 151, but not with vinculin or paxillin. In tumor phenotype I, the α6 subunit did not colocalize with the α3 subunit indicating the existence of two different adhesion complexes. Human prostate tumors display on their cell surface the α6β1 and/or α3β1 integrins. Three tumor phenotypes associated with two different adhesion complexes were identified, suggesting a reorganization of cell adhesion structures in prostate cancer.

  10. The expression of prostate-specific antigen in invasive breast carcinoma and its relationship with routine clinicopathologic parameters

    Directory of Open Access Journals (Sweden)

    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.

  11. Some aspects of the relation between the volume of prostate carcinoma and its interstitial BT volume

    International Nuclear Information System (INIS)

    Zivanovic, A; Babic, J; Erak, M.; Dabic, K.; Donat, D.; Kuzmanovic, Z.; Savic, D.

    1996-01-01

    It is a fact that the volume achieved by the interstitial procedure during the brachy treatment of prostate carcinoma is several times smaller than the one we get in, so called, external beam therapy. Furthermore, interstitial brachytherapy offers the possibility to apply large dose into the small volume. However, both dose and volume are at the same time the factors that limit the therapy and the main technical offenders in case of therapy failure. We tried, through a strong individual approach, to compare the volume obtained mathematically and the volume obtained by planning (TPS). By means of clinical examinations and CT scans we conceived a prostate as half of the volume of ellipsoid under one condition only: the magnification of the prostate has to be a symmetrical one. Finally, we applied the following formula: V prostate=(1(2)) ellipsoid=2.09·a/2·e/2·b where a=(1(2)) of sagittal diameter b=prostate height (from apex to base) c=(1(2)) of transversal diameter Each volume obtained in the this way has been taken into account during the application of interstitial needles which in their own way and in accordance to a routine planning, form an active therapeutic interstitial volume. The obtained data showed differences between these two types of volumes. From the statistical point of view, mathematically obtained volume of CV was 16.6% while interstitial volume was 14.9%. T-test was 3.9. On average, mathematical volume is lower and this balance is a desirable one because it means a smaller possibility for potential positive biopsy as a result of a 'rest' tumour. If on the other hand, positive biopsy is a result of the 'rest' tumour and our interpretation has been a contradictory one, precious time with disappointing results will be lost. At the end we achieved: a) double checked control of the embraced volumes, b) stronger fulcrum for the next step: dose-fraction balance

  12. Pulmonary embolization of permanently implanted radioactive palladium-103 seeds for carcinoma of the prostate

    International Nuclear Information System (INIS)

    Nag, Subir; Vivekanandam, Singhavajhala; Martinez-Monge, Rafael

    1997-01-01

    Purpose: It has been reported that permanently implanted iodine-125 seeds can embolize to the lungs. There is little data on the embolization of palladium-103 seeds. The purpose of this study is to collect and evaluate data on the embolization of Pd-103 seeds. Methods and Materials: The records of 112 patients implanted with Pd-103 for carcinoma of the prostate were reviewed to systemically study the incidence and dynamics of pulmonary embolism of Pd-103 seeds. Five patients had no postoperative chest radiograph and were thus excluded, leaving 107 patients for review. Results: Chest radiographs of 19 of the 107 patients showed embolized seeds in the lungs (18%). Two patients had three seeds each, nine patients had two seeds each; and in the remaining eight patients, a single seed migrated to the lungs. The seeds migrated mainly (84%) to the lower lobes. None of the eight patients who had their first postoperative chest radiograph on the day of the implant showed any embolized seeds. The embolized seed appeared only on subsequent chest radiographs taken 27 to 40 days later. Ten of the other 11 patients who had their first radiograph 1 to 97 days after brachytherapy had embolized seeds on their first chest radiograph. In the other patient, the embolized seed appeared only on a subsequent chest radiograph taken after 127 days. There were no clinical pulmonary or cardiac effects evident on routine follow-up of these patients with pulmonary embolized seeds. Conclusion: Embolization of Pd-103 seeds to the lungs after implantation for carcinoma of the prostate is an unusual event. In this study only 0.3% of the seeds implanted migrated to the lungs. Although it was previously thought that pulmonary seed migration mainly occurred on the day of brachytherapy, our experience shows that seeds usually migrated to the lungs after the day of the implant. There were no clinical pulmonary or cardiac effects attributable to embolized seeds in the lungs on routine follow-up

  13. Honokiol, a constituent of Magnolia species, inhibits adrenergic contraction of human prostate strips and induces stromal cell death

    Directory of Open Access Journals (Sweden)

    Daniel Herrmann

    2014-09-01

    Conclusions: Honokiol inhibits smooth muscle contraction in the human prostate, and induces cell death in cultured stromal cells. Because prostate smooth muscle tone and prostate growth may cause LUTS, it appears possible that honokiol improves voiding symptoms.

  14. Meta-analysis of rates of erectile function after treatment of localized prostate carcinoma

    International Nuclear Information System (INIS)

    Robinson, John W.; Moritz, Sabine; Fung, Tak

    2002-01-01

    Purpose: The results of a 1997 meta-analysis of the rates of erectile function after external beam radiotherapy (EBRT) and radical prostatectomy have been widely used in patient and professional education materials and as a reference against which new findings are compared. With a number of recent publications, it is now possible to update this analysis and compare brachytherapy with or without EBRT with EBRT alone, standard and nerve-sparing radical prostatectomy, and cryotherapy. Methods: A comprehensive literature review and subsequent meta-analysis of the rates of erectile dysfunction associated with the treatments of localized prostate carcinoma was conducted. A simple logistic regression analysis was used to combine the data from the 54 articles that met the selection criteria. Results: The predicted probability of maintaining erectile function after brachytherapy was 0.76, after brachytherapy plus EBRT 0.60, after EBRT 0.55, after nerve-sparing radical prostatectomy 0.34, after standard radical prostatectomy 0.25, and after cryotherapy 0.13. When only studies reporting ≥2 years follow-up were considered, the only significant change was a decline in the probability for nerve-sparing radical prostatectomy. No brachytherapy studies had a follow-up of ≥2 years. When the probabilities were adjusted for age, the spread between the RT methods and surgical approaches was greater. Conclusion: The differences in the probability of maintaining erectile function after different treatments of localized prostate cancer are significant

  15. External beam radiotherapy for carcinoma of the prostate: a retrospective study

    International Nuclear Information System (INIS)

    Mithal, N.P.; Hoskin, P.J.

    1993-01-01

    Two hundred and thirty-seven consecutive patients receiving radiotherapy for primary prostatic carcinoma have been reviewed. The presenting symptoms included acute retention, chronic outflow obstruction and haematuria. The diagnosis was confirmed at trans-urethral resection of the prostate (TURP) in 95%; all but seven patients had adenocarcinoma. The clinical stage at presentation was T 0 (3%), T 1 (9%), T 2 (49%), T 3 (21%) and T 4 (17%). Two hundred and six patients received primary radiotherapy, 38 had concurrent endocrine therapy. Local relapse alone occurred in 38 patients (16%), distant relapse alone occurred in 30 (13%), and both local and distant relapse occurred in 30 (13%). Median time to local relapse alone was 25 months, distant relapse alone 14 months, and local and distant relapse 22 months. Overall survival was related to stage and grade at presentation. No influence of endocrine therapy, dose or planning technique was seen, but a significant advantage for those patients treated using a planned volume compared with parallel opposed fields was observed. Acute radiation toxicity affecting the bladder occurred in 42% and the bowel in 45%. Late toxicity affecting the bladder occurred in 7% and the bowel in 2%. (author)

  16. Preoperative irradiation, lymphadenectomy, and 125iodine implantation for patients with localized carcinoma of the prostate

    International Nuclear Information System (INIS)

    DeLaney, T.F.; Shipley, W.U.; O'Leary, M.P.; Biggs, P.J.; Prout, G.R. Jr.

    1986-01-01

    Fifty-four patients with clinically and surgically localized prostatic carcinoma were treated with low-dose preoperative irradiation (1050 cGy), pelvic lymphadenectomy, and interstitial 125 Iodine implantation. The follow-up range is 2 to 9 years with a median follow-up of 5 years. Overall local tumor control is 92%. Actuarial 5-year survival is 86% and the actuarial disease-free survival at 5 years is 73%. Patients with poorly differentiated tumors have a significantly worse actuarial survival (62%) at 5 years than patients with well (95%) or moderately well differentiated tumors (93%), p = 0.04. Disease-free survival at 5 years was influenced by grade: well (100%), moderate (60%), and poor (48%), p = 0.03. Multivariate regression analysis indicates that only the degree of differentiation (p = 0.05) significantly impacts on survival. Both degree of differentiation (p = 0.04) and nodal status (p = 0.03) significantly influence disease-free survival. Potency has been maintained in 71% of patients potent at the time of implantation. Late reactions have been acceptable to date: bladder outlet obstruction (13%), mild proctitis (13%), cystourethritis (6%), incontinence (2%), and prostatic calculi (2%)

  17. Relevance of prostate cancer in patients with synchronous invasive bladder urothelial carcinoma: a monocentric retrospective analysis

    Directory of Open Access Journals (Sweden)

    Lucio Dell’Atti

    2015-03-01

    Full Text Available Objectives: We retrospectively reviewed data of patients with incidental prostate cancer (PCa who underwent radical cystoprostatectomy (RCP for invasive bladder cancer and we analyzed their features with regard to incidence, pathologic characteristics, clinical significance, and implications for management. Material and Methods: Clinical data and pathological features of 64 patients who underwent standard RCP for bladder cancer were included in this study. Besides the urothelial carcinoma of the urinary bladder, the location and tumor volume of the PCa, prostate apex involvement, Gleason score, pathological staging and surgical margins were evaluated. Clinically significant PCa was defined as a tumor with a Gleason 4 or 5 pattern, stage ≥ pT3, lymph node involvement, positive surgical margin or multifocality of three or more lesions. Postoperative follow-up was scheduled every 3 months in the first year, every 6 months in the second and third year, annually thereafter. Results: 11 out of 64 patients (17.2% who underwent RCP had incidentally diagnosed PCa. 3 cases (27.3% were diagnosed as significant PCa, while 8 cases (72.7% were clinically insignificant. The positive surgical margin of PCa was detected in 1 patient with significant disease. The prostate apex involvement was present in 1 patient of the significant PCa group. Median follow-up period was 47.8 ± 29.2 (range 4-79. During the follow-up, biochemical recurrence occurred in 1 patient (9%. Concernig the cancer specific survival there was no statistical significance (P = 0.326 between the clinically significant and clinical insignificant cancer group. Conclusions: In line with published studies, incidental PCa does not impact on the prognosis of bladder cancer of patients undergoing RCP.

  18. Human papillomas virus infection in the case of larynx carcinoma

    International Nuclear Information System (INIS)

    Makowska, W.; Rogozinski, T.; Zawadowski, J.; Waloryszak, B.

    1993-01-01

    The case of 59 year old man treated (with surgery and radiotherapy) for larynx carcinoma was presented. The potentially oncogenic human papillomavirus type 16/18 was detected in the tissue surrounding the tumor. (author)

  19. Parallel routes of human carcinoma development: implications of the age-specific incidence data.

    Directory of Open Access Journals (Sweden)

    James P Brody

    Full Text Available BACKGROUND: The multi-stage hypothesis suggests that cancers develop through a single defined series of genetic alterations. This hypothesis was first suggested over 50 years ago based upon age-specific incidence data. However, recent molecular studies of tumors indicate that multiple routes exist to the formation of cancer, not a single route. This parallel route hypothesis has not been tested with age-specific incidence data. METHODOLOGY/PRINCIPAL FINDINGS: To test the parallel route hypothesis, I formulated it in terms of a mathematical equation and then tested whether this equation was consistent with age-specific incidence data compiled by the Surveillance Epidemiology and End Results (SEER cancer registries since 1973. I used the chi-squared goodness of fit test to measure consistency. The age-specific incidence data from most human carcinomas, including those of the colon, lung, prostate, and breast were consistent with the parallel route hypothesis. However, this hypothesis is only consistent if an immune sub-population exists, one that will never develop carcinoma. Furthermore, breast carcinoma has two distinct forms of the disease, and one of these occurs at significantly different rates in different racial groups. CONCLUSIONS/SIGNIFICANCE: I conclude that the parallel route hypothesis is consistent with the age-specific incidence data only if carcinoma occurs in a distinct sub population, while the multi-stage hypothesis is inconsistent with this data.

  20. Human papilloma virus prevalence in laryngeal squamous cell carcinoma.

    Science.gov (United States)

    Gungor, A; Cincik, H; Baloglu, H; Cekin, E; Dogru, S; Dursun, E

    2007-08-01

    To determine the prevalence and type of human papilloma virus deoxyribonucleic acid (DNA) in cases of laryngeal squamous cell carcinoma. We analysed the prevalence of human papilloma virus infection in archived paraffin block specimens taken from 99 cases of laryngeal squamous cell carcinoma between 1990 and 2005, using polymerase chain reaction techniques. Biopsy specimens from five proven verrucous skin lesions were used as positive controls, and peripheral blood samples from five healthy volunteers were used as negative controls. Four test samples were found to have inadequate deoxyribonucleic acid purity and were therefore excluded from the study. Human papilloma virus deoxyribonucleic acid was detected in seven of 95 cases of laryngeal squamous cell carcinoma (7.36 per cent). Human papilloma virus genotyping revealed double human papilloma virus infection in three cases and single human papilloma virus infection in the remaining four cases. The human papilloma virus genotypes detected were 6, 11 and 16 (the latter detected in only one case). In our series, a very low human papilloma virus prevalence was found among laryngeal squamous cell carcinoma cases. The human papilloma virus genotypes detected were mostly 6 and/or 11, and 16 in only one case. To the best of our knowledge, this is the first report of human papilloma virus prevalence in laryngeal squamous cell carcinoma, based on polymerase chain reaction genotyping in a Turkish population.

  1. Tuft (caveolated) cells in two human colon carcinoma cell lines.

    OpenAIRE

    Barkla, D. H.; Whitehead, R. H.; Foster, H.; Tutton, P. J.

    1988-01-01

    The presence of an unusual cell type in two human colon carcinoma cell lines is reported. The cells show the same morphology as "tuft" (caveolated) cells present in normal gastrointestinal epithelium. Tuft cells were seen in cell line LIM 1863 growing in vitro and in human colon carcinoma cell line LIM 2210 growing as subcutaneous solid tumour xenografts in nude mice. Characteristic morphologic features of tuft cells included a wide base, narrow apex and a tuft of long microvilli projecting f...

  2. Nuclear/Nucleolar morphometry and DNA image cytometry as a combined diagnostic tool in pathology of prostatic carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Kavantzas, N.; Agapitos, E.; Lazaris, A. C.; Pavlopulos, P.M.; Sofikitis, N.; Davaris, P. [National University of Athens, Dept. of Pathology, Medical School, Athens (Greece)

    2001-12-01

    Paraffin tissue sections from 50 patients with prostate adenocarcinoma were used to study nuclear and nucleolar morphometric features by image analysis. The results were compared to DNA ploidy and Gleason grade. In the examined histological samples nuclear and nucleolar areas were positively interrelated. It was also noticed that the higher the percentage of nucleolated nuclei, the bigger the nuclear and nucleolar areas. The morphometric characteristics did not differ significantly among the four grades of the examined specimens. In well-differentiated carcinomas the DNA index was lower than in the rest at a statistically significant level. Hypodiploid carcinomas were found to possess significantly bigger nuclear areas than any other DNA index group. Morphonuclear evidence of anaplasia and DNA aneuploidy may be used as diagnostic tools in prostate cancer in addition to Gleason grade.

  3. Nuclear/Nucleolar morphometry and DNA image cytometry as a combined diagnostic tool in pathology of prostatic carcinoma

    International Nuclear Information System (INIS)

    Kavantzas, N.; Agapitos, E.; Lazaris, A. C.; Pavlopulos, P.M.; Sofikitis, N.; Davaris, P.

    2001-01-01

    Paraffin tissue sections from 50 patients with prostate adenocarcinoma were used to study nuclear and nucleolar morphometric features by image analysis. The results were compared to DNA ploidy and Gleason grade. In the examined histological samples nuclear and nucleolar areas were positively interrelated. It was also noticed that the higher the percentage of nucleolated nuclei, the bigger the nuclear and nucleolar areas. The morphometric characteristics did not differ significantly among the four grades of the examined specimens. In well-differentiated carcinomas the DNA index was lower than in the rest at a statistically significant level. Hypodiploid carcinomas were found to possess significantly bigger nuclear areas than any other DNA index group. Morphonuclear evidence of anaplasia and DNA aneuploidy may be used as diagnostic tools in prostate cancer in addition to Gleason grade

  4. Late effects of radiation therapy for prostate carcinoma: The patient`s perspective of bladder, bowel and sexual morbidity

    Energy Technology Data Exchange (ETDEWEB)

    Franklin, C.I.V.; Parker, C.A.; Morton, K.M. [Queensland Radium Institute, Herston, QLD (Australia)

    1998-02-01

    The patients` perceptions of the late effects of radiation therapy for carcinoma of the prostate on bladder, bowel and sexual function were determined by using a self-administered questionnaire (included as an appendix) which was posted in June 1996 to patients who had been treated for carcinoma of the prostate between February 1993 and April 1994 at the Herston centre of the Queensland Radium Institute. The questions were based on the SOMA-LENT subjective scales. Moderate bladder morbidity was reported by 15% of patients, with 2% reporting major morbidity. Moderate bowel morbidity was reported by 19% of patients with 2% reporting major morbidity, the major symptoms being bowel urgency and mucus discharge. Sexual function was a problem, with 72% of patients reporting dissatisfaction with their current level of sexual activity. Copyright (1998) Blackwell Science Pty Ltd 12 refs., 5 tabs., 2 figs.

  5. Late effects of radiation therapy for prostate carcinoma: The patient's perspective of bladder, bowel and sexual morbidity

    International Nuclear Information System (INIS)

    Franklin, C.I.V.; Parker, C.A.; Morton, K.M.

    1998-01-01

    The patients' perceptions of the late effects of radiation therapy for carcinoma of the prostate on bladder, bowel and sexual function were determined by using a self-administered questionnaire (included as an appendix) which was posted in June 1996 to patients who had been treated for carcinoma of the prostate between February 1993 and April 1994 at the Herston centre of the Queensland Radium Institute. The questions were based on the SOMA-LENT subjective scales. Moderate bladder morbidity was reported by 15% of patients, with 2% reporting major morbidity. Moderate bowel morbidity was reported by 19% of patients with 2% reporting major morbidity, the major symptoms being bowel urgency and mucus discharge. Sexual function was a problem, with 72% of patients reporting dissatisfaction with their current level of sexual activity. Copyright (1998) Blackwell Science Pty Ltd

  6. Long-term outcome of radical radiation therapy for prostatic carcinoma: 1967-1987

    International Nuclear Information System (INIS)

    Hahn, Per; Baral, Edward; Cheang, Mary; Math, M.; Kostyra, Jeri; Roelss, Randall

    1996-01-01

    Purpose: This study was done to review long-term results of radical radiotherapy for prostate cancer. Methods and Materials: The records of 674 patients with Stage T1a, T1b, T2a, T2b, T3, and any T,N1,M0 disease, treated with external beam radiotherapy between January 1, 1967 and December 1987, were reviewed. These patients were treated to an average total dose of 66 Gy, with an average fractional dose of 2.05 Gy, using megavoltage. The duration of follow-up for surviving patients ranged from a minimum of 7 years to more than 20 years. Results: The survival for 151 Stage T1a,T1b patients was 98.5% at 5 years, 93.6% at 10 years, and 75.2% at 15 years. Survival for 346 Stage T2a,b patients was 94.4% at 5 years, 67.9% at 10 years, and 41.5% at 15 years. Survival for 92 Stage T3 patients was 87.3% at 5 years, 54% at 10 years, and 26.6% at 15 years. The survival for 85 any T,N1,M0 patients was 73.9% at 5 years, 34.4% at 10 years, and 8.5% at 15 years. At 15 years, 75.2% of Stage T1a,b patients, 41.5% of Stage T2a,b patients, 21.7% of Stage T3 patients, and 8.5% of Stage T,N1,M0 patients remained free of local recurrence and distant metastases. The elevation of prostatic acid phosphatase prior to radiotherapy was an unfavorable prognostic factor, with impact on both loco-regional recurrences and survival. Conclusions: The external beam radiotherapy for localized carcinoma of the prostate produced a good loco-regional control, NED, and overall survival. Patients with smaller tumors and low grade fared better than the ones with more aggressive and/or bulky tumors. The weakness of this study is the absence of serial prostate-specific measurements, which were not available during the period under study. The complication rate requiring surgical intervention was low, i.e. 0.4%

  7. The value of bladder mapping and prostatic urethra biopsies for detection of carcinoma in situ (CIS).

    Science.gov (United States)

    Gudjónsson, Sigurdur; Bläckberg, Mats; Chebil, Gunilla; Jahnson, Staffan; Olsson, Hans; Bendahl, Pär-Ola; Månsson, Wiking; Liedberg, Fredrik

    2012-07-01

    It is well known that CIS is a major risk factor for muscle-invasive bladder cancer and that this entity can be difficult to diagnose. Taking cold-cup mapping biopsies from different areas of the bladder (BMAP) is commonly used in patients at risk of harbouring CIS. The diagnostic accuracy of this approach has not been assessed until now. By using the CIS found in the cystoprostatectomy specimen as an indicator of the true occurrence of CIS and comparing that with the findings of BMAP, it is clear that the sensitivity of BMAP to detect CIS when present is low and that negative findings should be considered unreliable. To assess the value of bladder mapping and prostatic urethra biopsies for detection of urothelial carcinoma in situ (CIS). CIS of the urinary bladder is a flat high-grade lesion of the mucosa associated with a significant risk of progression to muscle-invasive disease. CIS is difficult to identify on cystoscopy, and definite diagnosis requires histopathology. Traditionally, if CIS is suspected, multiple cold-cup biopsies are taken from the bladder mucosa, and resection biopsies are obtained from the prostatic urethra in males. This approach is often called bladder mapping (BMAP). The accuracy of BMAP as a diagnostic tool is not known. Male patients with bladder cancer scheduled for cystectomy underwent cold-cup bladder biopsies (sidewalls, posterior wall, dome, trigone), and resection biopsies were taken from the prostatic urethra. After cystectomy, the surgical specimen was investigated in a standardised manner and subsequently compared with the BMAP biopsies for the presence of CIS. The histopathology reports of 162 patients were analysed. CIS was detected in 46% of the cystoprostatectomy specimens, and multiple (≥2) CIS lesions were found in 30%. BMAP (cold-cup bladder biopsies + resection biopsies from the prostatic urethra) provided sensitivity of 51% for any CIS, and 55% for multiple CIS lesions. The cold-cup biopsies for CIS in the bladder

  8. The integrin α6β4 as a signaling membrane protein for a damage response to ionizing radiation in human prostate cancer cell lines

    International Nuclear Information System (INIS)

    Woo, Charles; Nagle, Ray B.; Stea, Baldassarre; Cress, Anne E.

    1996-01-01

    Purpose/Object: Integrins are cell surface receptors that exist as heterodimers. The integrin α6β4 is a receptor for laminin and is present in normal human prostate tissue. In prostate carcinoma however, there is loss of β4 expression. Prior studies demonstrated that when a low β4 expressing rectal carcinoma cell line was transfected with β4, the cells underwent apoptosis. We investigated the effects that the β4 integrin had on DNA damage responses in a human prostate carcinoma line. Materials and Methods: DU-145 human prostate carcinoma cells previously selected by us for α6β1 expression were transfected with either a full length β4 construct or vector only. Both cell lines were grown simultaneously and maintained in geneticin for selection purposes. Cells were grown on glass coverslips in 60mm tissue culture dishes under optimal growth conditions. Radiation was delivered using a Co-60 machine with a dose rate of 35 Gy/hr. The cells were given 0, 2, 5, and 10 Gy. Three different radiation damage responses were assayed and include micronuclei (MN) formation, cell cycle distribution, and cell survival. 24 hours after irradiation, the cells were fixed and stained with propidium iodide. Micronuclei formation was detected using a Zeiss LSM10 confocal microscope, and the resulting digital images were analyzed using the NIH Image program. The observed MN were detected without the use of cytochalasin B, but were noted to contain nuclear histone and DNA and were morphologically distinct from apoptotic or necrotic bodies. Results: The quantitative analysis of MN formation revealed a radiation dose dependence of MN formation in both the α6β4 and α6β1 expressing cell lines. The presence of MN 24 hours after irradiation was observed at clinically significant doses (2 Gy) with the largest effect occurring at 5 Gy. The α6β4 expressing cells consistently produced approximately two fold more MN as compared to the α6β1 expressing cells at all radiation doses. The

  9. Cellular and molecular effects of the liposomal mTHPC derivative Foslipos in prostate carcinoma cells in-vitro

    OpenAIRE

    Besic Gyenge, E; Hiestand, S; Graefe, S; Walt, H; Maake, C

    2011-01-01

    BACKGROUND: Meso-tetra-hydroxyphenyl-chlorine (mTHPC) is among the most powerful photosensitizers available for photodynamic therapy (PDT). However, the mechanisms leading to cell death are poorly understood. We here focused on changes at DNA and RNA levels after treatment with the liposomal mTHPC derivative Foslipos in vitro. METHODS: After determination of darktoxicity, laser conditions and uptake kinetics, PC-3 prostate carcinoma cells were subjected to PDT with Foslipos, followed by as...

  10. Small cell carcinoma of the prostate in an elderly patient: a case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Dale Alan Whitaker Jr.

    2016-12-01

    Full Text Available Prostate cancer is the most common malignancy of men in the United States. Small-cell carcinoma (SCC, which typically presents as an aggressive lung malignancy, is a rare diagnosis within the setting of prostate cancer pathology. Due to its limited prevalence, little information regarding the treatment and prognosis of this disease in large populations is available. To date our current knowledge base is largely limited to case reports and retrospective case reviews. The mainstay of treatment for this particular histology most often involves a multimodality approach utilizing chemotherapy in conjunction with radiation therapy, androgen deprivation therapy, or prostatectomy. Here we present the case of an elderly 89- year-old Caucasian male who was diagnosed with SCC of the prostate. Despite proceeding with a course of definitive radiotherapy, the patient experienced rapid progression of disease and ultimately elected to discontinue radiation therapy and receive hospice care.

  11. 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

  12. PC-3 prostate carcinoma cells release signal substances that influence the migratory activity of cells in the tumor's microenvironment

    Directory of Open Access Journals (Sweden)

    Zänker Kurt S

    2010-07-01

    Full Text Available Abstract Background Tumor cells interact with the cells of the microenvironment not only by cell-cell-contacts but also by the release of signal substances. These substances are known to induce tumor vascularization, especially under hypoxic conditions, but are also supposed to provoke other processes such as tumor innervation and inflammatory conditions. Inflammation is mediated by two organ systems, the neuroendocrine system and the immune system. Therefore, we investigated the influence of substances released by PC-3 human prostate carcinoma cells on SH-SY5Y neuroblastoma cells as well as neutrophil granulocytes and cytotoxic T lymphocytes, especially with regard to their migratory activity. Results PC-3 cells express several cytokines and growth factors including vascular endothelial growth factors, fibroblast growth factors, interleukins and neurotrophic factors. SH-SY5Y cells are impaired in their migratory activity by PC-3 cell culture supernatant, but orientate chemotactically towards the source. Neutrophil granulocytes increase their locomotory activity only in response to cell culture supernantant of hypoxic but not of normoxic PC-3 cells. In contrast, cytotoxic T lymphocytes do not change their migratory activity in response to either culture supernatant, but increase their cytotoxicity, whereas supernatant of normoxic PC-3 cells leads to a stronger increase than that of hypoxic PC-3 cells. Conclusions PC-3 cells release several signal substances that influence the behavior of the cells in the tumor's microenvironment, whereas no clear pattern towards proinflammatory or immunosuppressive conditions can be seen.

  13. Differential Effects of Leptin on the Invasive Potential of Androgen-Dependent and -Independent Prostate Carcinoma Cells

    Directory of Open Access Journals (Sweden)

    Dayanand D. Deo

    2008-01-01

    Full Text Available Obesity has been linked with an increased risk of prostate cancer. The formation of toxic free oxygen radicals has been implicated in obesity mediated disease processes. Leptin is one of the major cytokines produced by adipocytes and controls body weight homeostasis through food intake and energy expenditure. The rationale of the study was to determine the impact of leptin on the metastatic potential of androgen-sensitive (LNCaP cells as well as androgen-insensitive (PC-3 and DU-145 cells. At a concentration of 200_nm, LNCaP cells showed a significant increase (20% above control; P<.0001 in cellular proliferation without any effect on androgen-insensitive cells. Furthermore, exposure to leptin caused a significant (P<.01 to P<.0001 dose-dependent decrease in migration and invasion of PC3 and Du-145 prostate carcinoma cell lines. At the molecular level, exposure of androgen-independent prostate cancer cells to leptin stimulates the phosphorylation of MAPK at early time point as well as the transcription factor STAT3, suggesting the activation of the intracellular signaling cascade upon leptin binding to its cognate receptor. Taken together, these results suggest that leptin mediates the invasive potential of prostate carcinoma cells, and that this effect is dependent on their androgen sensitivity.

  14. Linking γ-aminobutyric acid A receptor to epidermal growth factor receptor pathways activation in human prostate cancer.

    Science.gov (United States)

    Wu, Weijuan; Yang, Qing; Fung, Kar-Ming; Humphreys, Mitchell R; Brame, Lacy S; Cao, Amy; Fang, Yu-Ting; Shih, Pin-Tsen; Kropp, Bradley P; Lin, Hsueh-Kung

    2014-03-05

    Neuroendocrine (NE) differentiation has been attributed to the progression of castration-resistant prostate cancer (CRPC). Growth factor pathways including the epidermal growth factor receptor (EGFR) signaling have been implicated in the development of NE features and progression to a castration-resistant phenotype. However, upstream molecules that regulate the growth factor pathway remain largely unknown. Using androgen-insensitive bone metastasis PC-3 cells and androgen-sensitive lymph node metastasis LNCaP cells derived from human prostate cancer (PCa) patients, we demonstrated that γ-aminobutyric acid A receptor (GABA(A)R) ligand (GABA) and agonist (isoguvacine) stimulate cell proliferation, enhance EGF family members expression, and activate EGFR and a downstream signaling molecule, Src, in both PC-3 and LNCaP cells. Inclusion of a GABA(A)R antagonist, picrotoxin, or an EGFR tyrosine kinase inhibitor, Gefitinib (ZD1839 or Iressa), blocked isoguvacine and GABA-stimulated cell growth, trans-phospohorylation of EGFR, and tyrosyl phosphorylation of Src in both PCa cell lines. Spatial distributions of GABAAR α₁ and phosphorylated Src (Tyr416) were studied in human prostate tissues by immunohistochemistry. In contrast to extremely low or absence of GABA(A)R α₁-positive immunoreactivity in normal prostate epithelium, elevated GABA(A)R α₁ immunoreactivity was detected in prostate carcinomatous glands. Similarly, immunoreactivity of phospho-Src (Tyr416) was specifically localized and limited to the nucleoli of all invasive prostate carcinoma cells, but negative in normal tissues. Strong GABAAR α₁ immunoreactivity was spatially adjacent to the neoplastic glands where strong phospho-Src (Tyr416)-positive immunoreactivity was demonstrated, but not in adjacent to normal glands. These results suggest that the GABA signaling is linked to the EGFR pathway and may work through autocrine or paracine mechanism to promote CRPC progression. Copyright © 2013 Elsevier

  15. Muscarinic receptor subtype mRNA expression in the human prostate: association with age, pathological diagnosis, prostate size, or potentially interfering medications?

    NARCIS (Netherlands)

    Witte, Lambertus P. W.; Teitsma, Christine A.; de La Rosette, Jean J. M. C. H.; Michel, Martin C.

    2014-01-01

    As the prostate abundantly expresses muscarinic receptors and antagonists for such receptors are increasingly used in the treatment of men with voiding function and large prostates, we have explored an association of the mRNA expression of human M1, M2, M3, M4, and M5 receptors in human prostate

  16. Chronic effects of therapeutic irradiation for localized prostatic carcinoma on anorectal function

    International Nuclear Information System (INIS)

    Yeoh, Eric E.K.; Botten, Rochelle; Russo, Antonietta; McGowan, Roz; Fraser, Robert; Roos, Daniel; Penniment, Michael; Borg, Martin; Sun Weiming

    2000-01-01

    Purpose: To evaluate prospectively the prevalence and pathophysiology of anorectal dysfunction following radiation therapy (RTH) for localized carcinoma of the prostate. Methods and Materials: The following parameters of anorectal function were evaluated in each of 35 patients (aged 55-82 years) with localized prostatic carcinoma treated with RTH either to a dose of 55 Gy/20 fractions/4 weeks (18 patients) or 64 Gy/32 fractions/6.5 weeks (17 patients), before RTH and 4-6 weeks and at a mean (± SD) of 1.4 (± 0.2) years after its completion: (1) anorectal symptoms (questionnaire), (2) anorectal pressures at rest and in response to voluntary squeeze and increases in intra-abdominal pressure (multiport anorectal manometry), (3) rectal sensation (balloon distension) and (4) anal sphincteric morphology (endoanal ultrasound). Results: All but 1 patient completed three series of measurements. RTH had no effect on anal sphincteric morphology. The increase in frequency of defecation and fecal urgency and incontinence scores previously reported in the patients 4-6 weeks after RTH were sustained 1 year later (p < 0.001, p < 0.001, and p < 0.05, cf. baseline, respectively). At this time, 56% (19 of 34), 50% (17 of 34) and 26% (9 of 34) of the patients had increased frequency of defecation, fecal urgency, and incontinence, respectively. Decreases in anal sphincteric pressures at rest and in response to voluntary squeeze recorded in the patients 4-6 weeks after RTH were not sustained 1 year later but the volumes of rectal distension associated with perception of the stimulus and desire to defecate were lower compared with baseline volumes (p < 0.01 and p < 0.05, respectively), reflecting heightened rectal sensitivity in the patients. There was no difference in measurements between the two radiation dose regimens. Univariate logistical regression analysis was performed on patients who had experienced increased symptom scores or decreases in recorded motor and sensory manometric

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

    OpenAIRE

    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...

  18. 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...

  19. Conditional Expression of Human 15-Lipoxygenase-1 in Mouse Prostate Induces Prostatic Intraepithelial Neoplasia: The FLiMP Mouse Model

    Directory of Open Access Journals (Sweden)

    Uddhav P. Kelavkar

    2006-06-01

    Full Text Available The incidence and mortality of prostate cancer (PCa vary greatly in different geographic regions, for which lifestyle factors, such as dietary fat intake, have been implicated. Human 15-lipoxygenase-1 (h15-LO-1, which metabolizes polyunsaturated fatty acids, is a highly regulated, tissue-specific, lipid-peroxidating enzyme that functions in physiological membrane remodeling and in the pathogenesis of atherosclerosis, inflammation, and carcinogenesis. We have shown that aberrant overexpression of 15-LO-1 occurs in human PCa, particularly high-grade PCa, and in high-grade prostatic intraepithelial neoplasia (HGPIN, and that the murine orthologue is increased in SV40-based genetically engineered mouse (GEM models of PCa, such as LADY and TRansgenic Adenocarcinoma of Mouse Prostate. To further define the role of 15-LO-1 in prostate carcinogenesis, we established a novel GEM model with targeted overexpression of h15-LO-1 in the prostate [human fifteen lipoxygenase-1 in mouse prostate (FLiMP]. We used a Cre- mediated and a loxP-mediated recombination strategy to target h15-LO-1 specifically to the prostate of C57BL/6 mice. Wild-type (wt, FLiMP+/-, and FLiMP+/+ mice aged 7 to 21, 24 to 28, and 35 weeks were characterized by histopathology, immunohistochemistry (IHC, and DNA/RNA and enzyme analyses. Compared to wt mice, h15-LO-1 enzyme activity was increased similarly in both homozygous FLiMP+/+ and hemizygous FLiMP+/- prostates. Dorsolateral and ventral prostates of FLiMP mice showed focal and progressive epithelial hyperplasia with nuclear atypia, indicative of the definition of mouse prostatic intraepithelial neoplasia (mPIN according to the National Cancer Institute. These foci showed increased proliferation by Ki-67 IHC. No progression to invasive PCa was noted up to 35 weeks. By IHC, h15-LO-1 expression was limited to luminal epithelial cells, with increased expression in mPIN foci (similar to human HGPIN. In summary, targeted overexpression of h

  20. Hypofractionated stereotactic boost in intermediate risk prostate carcinoma: Preliminary results of a multicenter phase II trial (CKNO-PRO.

    Directory of Open Access Journals (Sweden)

    David Pasquier

    Full Text Available Dose escalation may improve curability in intermediate-risk prostate carcinoma. A multicenter national program was developed to assess toxicity and tumor response with hypofractionated stereotactic boost after conventional radiotherapy in intermediate-risk prostate cancer.Between August 2010 and April 2013, 76 patients with intermediated-risk prostate carcinoma were included in the study. A first course delivered 46 Gy by IMRT (68.4% of patients or 3D conformal radiotherapy (31.6% of patients. The second course delivered a boost of 18 Gy (3x6Gy within 10 days. Gastrointestinal (GI and genitourinary (GU toxicities were evaluated as defined by NCI-CTCAE (v4.0. Secondary outcome measures were local control, overall and metastasis-free survival, PSA kinetics, and patient functional status (urinary and sexual according to the IIEF5 and IPSS questionnaires.The overall treatment time was 45 days (median, range 40-55. Median follow-up was 26.4 months (range, 13.6-29.9 months. Seventy-seven per cent (n = 58 of patients presented a Gleason score of 7. At 24 months, biological-free survival was 98.7% (95% CI, 92.8-99.9% and median PSA 0.46 ng/mL (range, 0.06-6.20 ng/mL. Grade ≥2 acute GI and GU toxicities were 13.2% and 23.7%, respectively. Grade ≥2 late GI and GU toxicities were observed in 6.6% and 2.6% of patients, respectively. No grade 4 toxicity was observed.Hypofractionated stereotactic boost is effective and safely delivered for intermediate-risk prostate carcinoma after conventional radiation. Mild-term relapse-free survival and tolerance results are promising, and further follow-up is warranted to confirm the results at long term.ClinicalTrials.gov NCT01596816.

  1. Sulphur XANES Analysis of Cultured Human Prostate Cancer Cells

    International Nuclear Information System (INIS)

    Kwiatek, W.M.; Podgorczyk, M.; Paluszkiewicz, Cz.; Balerna, A.; Kisiel, A.

    2008-01-01

    Prostate cancer is one of the most commonly diagnosed cancers in men throughout the world. It is believed that changes to the structure of protein binding sites, altering its metabolism, may play an important role in carcinogenesis. Sulphur, often present in binding sites, can influence such changes through its chemical speciation. Hence there is a need for precise investigation of coordination environment of sulphur. X-ray absorption near edge structure spectroscopy offers such possibility. Cell culture samples offer histologically well defined areas of good homogeneity, suitable for successful and reliable X-ray absorption near edge structure analysis. This paper presents sulphur speciation data collected from three different human prostate cancer cell lines (PC-3, LNCaP and DU-145). Sulphur X-ray absorption near edge structure analysis was performed on K-edge structure. The spectra of cells were compared with those of cancerous tissue and with organic substances as well as inorganic compounds. (authors)

  2. Prevention of carcinoma of cervix with human papillomavirus vaccine.

    Science.gov (United States)

    Gavarasana, S; Kalasapudi, R S; Rao, T D; Thirumala, S

    2000-01-01

    Carcinoma of cervix is the most common cancer found among the women of India. Though cervical cytology screening was effective in preventing carcinoma of cervix in developed nations, it is considered unsuitable in developing countries. Recent research has established an etiological link between human papillomavirus infection and carcinoma of cervix. In this review, an attempt is made to answer the question, 'whether carcinoma of cervix can be prevented with human papillomavirus vaccine?' Literature search using Pubmed and Medline was carried out and relevant articles were reviewed. There is ample experimental evidence to show that DNA of human papillomavirus integrates with cervical cell genome. Viral genes E6 and E7 of HPV type 16 and 18 inactivate p53 function and Rb gene, thus immortalize the cervical epithelial cells. Recombinant vaccines blocked the function of E6 and E7 genes preventing development of papillomas in animals. Vaccination with HPV-VLPs encoding for genes of E6 and E7 neutralizes HPV integrated genome of malignant cells of uterine cervix. Based on experimental evidence, it is possible to prevent carcinoma of cervix with human papillomavirus vaccine, Further research is necessary to identify a effective and safe HPV vaccine, routes of administration and characteristics of potential beneficiaries.

  3. Application of biological dose concept in dose optimization for conformal radiotherapy of prostate carcinoma

    International Nuclear Information System (INIS)

    Li Yunhai; Liao Yuan; Zhou Lijun; Pan Ziqiang; Feng Yan

    2003-01-01

    Objective: On basis of physical dose optimization, LQ model was used to investigate the difference between the curves of biological effective dose and physical isodose. The influence of applying the biological dose concept on three dimensional conformal radiotherapy of prostate carcinoma was discussed. Methods: Four treatment plannings were designed for physical dose optimization: three fields, four-box fields, five fields and six fields. Target dose uniformity and protection of the critical tissue-rectum were used as the principal standard for designing the treatment planning. Biological effective dose (BED) was calculated by LQ model. The difference between the BED curve drawn in the central layer and the physical isodose curve was studied. The difference between the adjusted physical dose (APD) and the physical dose was also studied. Results: Five field planning was the best in target dose uniformity and protection of the critical tissue-rectum. The physical dose was uniform in the target, but the biological effective doses revealed great discrepancy in the biological model. Adjusted physical dose distribution also displayed larger discrepancy than the physical dose unadjusted. Conclusions: Intensified Modulated Radiotherapy (IMRT) technique with inversion planning using biological dose concept may be much more advantageous to reach a high tumor control probability and low normal tissue complication probability

  4. Intracavitary irradiation of prostatic carcinoma by a high dose-rate afterloading technique

    Energy Technology Data Exchange (ETDEWEB)

    Odelberg-Johnson, O.; Underskog, I.; Johansson, J.E.; Bernshaw, D.; Sorbe, B.; Persson, J.E. (Oerebro Medical Center Hospital (Sweden). Dept. of Oncology Oerebro Medical Center Hospital (Sweden). Dept. of Urology Oerebro Medical Center Hospital (Sweden). Dept. of Gynecologic Oncology Oerebro Medical Center Hospital (Sweden). Dept. of Radiation Physics)

    1991-01-01

    A high dose-rate ({sup 60}Co) afterloading technique was evaluated in a series of 73 patients with prostatic carcinoma stages I-IV. The intraurethral irradiation was combined with external pelvic radiotherapy. A minimum total dose of 78 Gy was delivered to the target volume. In a subgroup of patients extramustine (Estracyt) was given as adjuvant chemohormonal therapy during irradiation. The median follow-up for the whole group was 63 months. The crude 5-year survival rate was 60% and the corrected survival rate 90%. Survival was related to the tumor grade. Local pelvic recurrences were recorded in 17.8%. 'Viable cells' in posttherapy aspiration biopsy were not associated with tumor recurrences or survival. Four patients (5%) had grade 3 late radiation reactions with urethral structure or bladder fibrosis. Urinary tract infections and prior transurethral resections were not associated with a higher frequency of reactions. Concurrent estramustine therapy seemed to increase the frequency of both acute and chronic radiation reactions. Local control, recurrence, and survival were not affected by chemohormonal therapy. The use of tomography, magnetic resonance, and ultrasound as aids to computerized dosimetry may improve local dose distribution and reduce the irradiated volume. (orig.).

  5. Prophylactic radiotherapy of the breast in patients with prostatic carcinoma before application of contrasexual hormones

    Energy Technology Data Exchange (ETDEWEB)

    Arndt, D.; Heibel, J.H.

    1983-08-01

    Symptoms and objective parameters of gynecomastia are analysed in 113 patients, who received prophylactic irradiation of the breast (12 Gy in 3 fractions) prior to estrogen therapy of prostatic carcinoma. Another 10 patients were treated equally after estrogens had caused severe complaints. Symptoms increased from 10% to 100% in relation to 4 classes of gynecomastia. They were mild in 27.5%, moderate in 23.9% and severe in 8.8%. A correlation between metric classification and graded symptoms became more evident when only 2 groups were distinguished. With a maximum diameter of 3.5 cm only 17% of the patients had mostly slight discomfort in contrast to 70% of the patients with a gland of more than 3.5 cm in diameter; they revealed moderate or serious complaints. These results indicate that prophylactic radiotherapy may reduce severe complications to less than 10% as compared to 70-80% without irradiation. If gynecomastia has developed, regression by subsequent radiotherapy seems to be impossible; but the intensity of complaints could be reduced in our ten patients. Provided that irradiation precedes estrogen application, this sequence may be considered as a reasonable alternative to expensive antiandrogen therapy.

  6. Human endogenous retrovirus HERV-K(HML-2) activity in prostate cancer is dominated by a few loci.

    Science.gov (United States)

    Goering, Wolfgang; Schmitt, Katja; Dostert, Melanie; Schaal, Heiner; Deenen, René; Mayer, Jens; Schulz, Wolfgang A

    2015-12-01

    Increased expression of human endogenous retroviruses, especially HERV-K(HML-2) proviruses, has recently been associated with prostate carcinoma progression. In particular, a HML-2 locus in chromosome 22q11.23 (H22q) is upregulated in many cases. We therefore aimed at delineating the extent and repertoire of HML-2 transcription in prostate cancer tissues and cell lines and to define the transcription pattern and biological effects of H22q. Sanger and high throughput amplicon sequencing was used to define the repertoire of expressed HML-2 in a selected set of samples. qRT-PCR was used to quantify expression of selected proviruses in an extended set of prostate cancer tissues. Transcription factor binding sites (TFBS) were compared bioinformatically using the Transfac database. Expression of H22q was further characterized by siRNA-mediated knockdown, 5' RACE mapping of transcriptional start sites (TSS) and identification of splice sites. Functional effects of H22q knockdown were investigated by viability and apoptosis assays. In addition to H22q, a limited number of other proviruses were found expressed by sequencing. Of these, provirus ERVK-5 and to a lesser degree ERVK-15 were frequently upregulated in prostate cancer. In contrast, expression of ERVK-24, predominant in germ cell tumors, was not detectable in prostatic tissues. While HML-2 LTRs contain binding sites for the androgen receptor and cofactors, no consistent differences in transcription factor binding sites were found between expressed and non-expressed proviruses. The H22q locus contains two 5'-LTRs of which the upstream LTR is predominantly used in prostatic cells, with an imprecise TSS. Splicing of H22q transcripts is complex, generating, among others, a transcript with an Np9-like ORF. Knockdown of H22q did not significantly affect proliferation or apoptosis of prostate cancer cells. Our findings further underline that HML-2 expression is commonly highly tissue-specific. In prostate cancer, a limited

  7. CARCINOMA OF THE LARYNX AND HUMAN PAPILLOMA VIRUS INFECTION

    Directory of Open Access Journals (Sweden)

    Georgi N. Nikolov

    2016-03-01

    Full Text Available Background: Laryngeal carcinoma is one of the most common form of head and neck cancer. During the last two decades, it has been recognized that this cancer is causally related to human papillomavirus (HPV. Objective: We presented a study on prevalence of human papilloma viruses (HPV in patients with laryngeal carcinoma. Methods: This study consists of 43 patients with laryngeal carcinoma who were diagnosed and treated with surgical techniques in Department of Otorhinolaryngology, University Hospital, Pleven, Bulgaria. Immunohistochemistry of p16INK4a and Ki-67 were used to prove the relationship between high-risk-HPV (HR-HPV and carcinogenesis. Results: Papilloma virus infection with high-risk oncogenic types of HPV was determined in more than 39.5% of surgically treated patients with histologically proven laryngeal cancer. HPV-induced carcinogenesis was assumed in 17 (13.9% of all patients whose spouses were operated from cervical cancer. The patients with HPV-positive laryngeal carcinoma were younger than the others in the group (8 years on average. Risk factors for development of HPV-associated laryngeal carcinoma were related to higher number of sexual partners and the practice of oral sex. Frequently, in patients with HPV-associated laryngeal carcinoma we find data for so-called “family’s carcinogenesis”. The possibility of appearance (either preceding or following the treatment of a second carcinoma and/or tumour recurrence is higher in HPV-positive laryngeal carcinomas. Conclusion: It is recommended to extend the diagnostic methods for laryngeal and hypo pharyngeal cancer with a routine search for high-risk oncogenic HPV strains.

  8. Racial influence on the prevalence of prostate carcinoma in Brazilian volunteers

    Directory of Open Access Journals (Sweden)

    Edson L Paschoalin

    2003-08-01

    Full Text Available PURPOSE: To investigate the prevalence of prostate carcinoma in a sample of volunteers known to have a large proportion of Bantu African ancestors, and the performance of total PSA (tPSA, PSA density (PSAD and free-to-total PSA ratio (f/tPSA on the diagnosis. MATERIALS AND METHODS: A total of 473 volunteers (range: 40 - 79 years were screened for prostate carcinoma. Those with tPSA >2 ng/ml and/or abnormal digital rectal examination were submitted to a transrectal ultrasound-directed biopsy (10 cores. The volunteers were classified as White, Mulatto or Black according to physical characteristics and to ancestors race reference. The following variable number of tandem repeats (VNTR were analyzed in the blood of 120 volunteers without cancer and in 27 patients with prostate cancer: D4S43, PAH, F13A1, APOB and vW-1. RESULTS: The biopsies performed in 121 volunteers revealed cancer in 27 (5.7% of 473. The proportions of cancer in White, Mulatto and Black were respectively: 0.6% (1/148, 6.7% (6/90 and 8.5% (20/235 (p = 0.006. The VNTRs analysis revealed heterogeneity in White, Mulatto and Black anthropologic phenotypes with the following admixture of Caucasian, African and Amerindian gene lineages: 67.5 ± 8%, 20.8 ± 8%, 11.7 ± 7%; 54.8 ± 9%, 36.3 ± 5%, 8.9 ± 7%; and, 45.3 ± 3%, 45.9 ± 4%, 8.8 ± 7%. Such a mixture was 50.5 ± 9%, 49 ± 8% and 0.5 ± 4% in volunteers bearing cancer, and 59.1 ± 7%, 31.7 ± 8% and 9.2 ± 5% in those without cancer. The sensitivity and specificity of tPSA at cut-off levels of 2, 2.5 and 4 ng/ml for volunteers with tPSA <= 10 ng/ml were respectively: 100% and 6,6%, 100% and 36,6%, 69,2% and 62,2%. PSAD at a cut-off level of 0.08 or 0.10, and f/tPSA at a cut-off level of 20% were able to increase significantly tPSA specificity without loss on sensitivity. CONCLUSIONS: The tumor prevalence was higher in Non-White than in White phenotype. The association of tPSA at a cut-off level of 2.5 ng/ml with a PSAD of 0.08 or

  9. Disease-related effects of perioperative blood transfusions associated with 125I seed implantation for prostate carcinoma

    International Nuclear Information System (INIS)

    Petersen, J.P.; Schellhammer, P.F.; el-Mahdi, A.M.

    1990-01-01

    In some retrospective studies perioperative transfusions during oncologic surgery have been shown to decrease the time interval between surgery and local and/or distant recurrence of cancer. This study examines the disease-related effect, if any, of perioperative blood transfusions among 108 patients with localized carcinoma of the prostate treated by radioactive iodine-125 seed implantation of the prostate and lymphadenectomy. When all subjects were analyzed, there was no statistical difference of local and distant failure between the transfused and nontransfused groups. Patients with well-differentiated tumors had statistically fewer local recurrences (0% vs 22%, p = 0.036) if they were transfused perioperatively. However, the difference in distant metastases (0% vs 11%) was not statistically significant (p = 0.21). In contrast, patients with moderately and poorly differentiated disease receiving transfusions had more local recurrences and metastases, though this was not statistically significant. Our data suggest that there is no obvious evidence that perioperative blood transfusions have an adverse effect on local recurrence or distant metastases for iodine-125 seed implantation of carcinoma of the prostate

  10. Acute morbidity reduction using 3DCRT for prostate carcinoma; a randomised phase III study

    International Nuclear Information System (INIS)

    Koper, P.; Putten, W. van; Stroom, J.; Korevaar, G.; Heijmen, B.; Wijnmaalen, A.; Jansen, P.; Hanssens, P.; Griep, C.; Krol, A.; Samson, M.; Levendag, P.

    1997-01-01

    Purpose: A randomised phase III toxicity study (conventional vs conformal radiotherapy) was performed for prostatic carcinoma to study the effects on the (acute) morbidity of intestinal/rectosigmoid and bladder. The observed toxicity was compared with Dose Volume Histograms to reveal possible volume (reduction) effects. Methods: In the phase III study 266 T1-4 N0M0 prostate cancer patients were entered. Patients were randomised for conventional and conformal radiotherapy (total dose 66 Gy, minimum PTV dose 95% ICRU and a CTV-PTV margin of 10 mm in both study arms). The GTV was limited to the prostate only in T1 tumors. In all other patients the GTV was defined to be prostate and seminal vesicles for the complete treatment course. The CTV-PTV margin (10mm) was created by a automated program to ensure the minimum prescribed margin. The rectosigmoid was defined to be the rectum including the sigmoid within the Treatment Volume (ICRU). Acute toxicity was evaluated using the EORTC/RTOG morbidity score and weekly quality of life questionnaires. The radiation technique comparison was done by Dose volume Histogram analysis using the Area Under The Curve (AUC) for different dose levels. In this preliminary DVH analysis we present the data for the first 100 patients. Results: Patient and tumor characteristics were evenly distributed between both study groups. The maximum toxicity is reached at 75% of the tumordose (TD) (rectal grade I 59% grade II 26%, bladder grade I 48%, grade II 16% and grade III 1% [catheter for urinary retention]). Comparing both study arms there seems to be a reduction in intestinal morbidity (grade II and higher resp. 32% vs 19% p=0.02). Further analysis revealed a marked reduction in medication for anal symptoms; this accounts for a large part of the significant difference in intestinal toxicity (grade II conventional vs conformal rectosigmoid 18% vs 14% and anal 16% vs 8%). For bladder morbidity no difference for mobidity higher than grade I is

  11. Is Human Papillomavirus Associated with Prostate Cancer Survival?

    Directory of Open Access Journals (Sweden)

    Mariarosa Pascale

    2013-01-01

    Full Text Available The role of human papillomavirus (HPV in prostate carcinogenesis is highly controversial: some studies suggest a positive association between HPV infection and an increased risk of prostate cancer (PCa, whereas others do not reveal any correlation. In this study, we investigated the prognostic impact of HPV infection on survival in 150 primary PCa patients. One hundred twelve (74.67% patients had positive expression of HPV E7 protein, which was evaluated in tumour tissue by immunohistochemistry. DNA analysis on a subset of cases confirmed HPV infection and revealed the presence of genotype 16. In Kaplan-Meier analysis, HPV-positive cancer patients showed worse overall survival (OS (median 4.59 years compared to HPV-negative (median 8.24 years, P=0.0381. In multivariate analysis age (P<0.001, Gleason score (P<0.001, nuclear grading (P=0.002, and HPV status (P=0.034 were independent prognostic factors for OS. In our cohort, we observed high prevalence of HPV nuclear E7 oncoprotein and an association between HPV infection and PCa survival. In the debate about the oncogenic activity of HPV in PCa, our results further confirm the need for additional studies to clarify the possible role of HPV in prostate carcinogenesis.

  12. Neuroendocrine cells during human prostate development: does neuroendocrine cell density remain constant during fetal as well as postnatal life?

    NARCIS (Netherlands)

    Xue, Y.; van der Laak, J.; Smedts, F.; Schoots, C.; Verhofstad, A.; de la Rosette, J.; Schalken, J.

    2000-01-01

    Knowledge concerning differentiation of neuroendocrine (NE) cells during development of the human prostate is rather fragmentary. Using immunohistochemistry combined with a morphometric method, we investigated the distribution and density of NE cells in the developing human prostate, with special

  13. Analysis of the testicular dose in patients undergoing radiotherapy for carcinoma of the prostate; Analisis de las dosis testiculares en pacientes sometidos a tratamiento radioterapico de carcinoma de prostata

    Energy Technology Data Exchange (ETDEWEB)

    Bejar Navarro, M. J.; Ordonez Marquez, J.; Hervas Moron, A.; Alvarez Rodriguez, S.; Garcia-Galloway, E.; Sanchez Casanueva, R.; Polo Rubio, A.; Rodriguez-Patron, R.; Yanowsky, K.; Gomez Dos Santos, V.

    2013-07-01

    The objectives of this work are: -Studying comparatively the doses received in testes in patients undergoing radiotherapy of prostate carcinoma with external beam radiation and brachytherapy of low rate using I-125 seeds. -Compare doses due to images of verification using Cone Beam CT (CBCT), with doses of radiotherapy treatment itself. -Determine the seminal alterations and cytogenetic after treatment with ionizing radiation (RTE or BQT) in patients diagnosed with prostate cancer and its relation with testicular dose. (Author)

  14. 2,3,7,8-Tetrachlorodibenzo-p-dioxin has both pro-carcinogenic and anti-carcinogenic effects on neuroendocrine prostate carcinoma formation in TRAMP mice

    Energy Technology Data Exchange (ETDEWEB)

    Moore, Robert W., E-mail: robert.moore@wisc.edu [School of Pharmacy, 777 Highland Ave., University of Wisconsin-Madison, Madison, WI 53705 (United States); Molecular and Environmental Toxicology Center, 1400 University Ave., University of Wisconsin-Madison, Madison, WI 53706 (United States); Fritz, Wayne A., E-mail: Wayne.Fritz@covance.com [School of Pharmacy, 777 Highland Ave., University of Wisconsin-Madison, Madison, WI 53705 (United States); Molecular and Environmental Toxicology Center, 1400 University Ave., University of Wisconsin-Madison, Madison, WI 53706 (United States); Schneider, Andrew J., E-mail: ajschnei@wisc.edu [School of Pharmacy, 777 Highland Ave., University of Wisconsin-Madison, Madison, WI 53705 (United States); Lin, Tien-Min, E-mail: tlin1@facstaff.wisc.edu [School of Pharmacy, 777 Highland Ave., University of Wisconsin-Madison, Madison, WI 53705 (United States); Branam, Amanda M., E-mail: bran2117@hotmail.com [School of Pharmacy, 777 Highland Ave., University of Wisconsin-Madison, Madison, WI 53705 (United States); Molecular and Environmental Toxicology Center, 1400 University Ave., University of Wisconsin-Madison, Madison, WI 53706 (United States); Safe, Stephen, E-mail: SSAFE@cvm.tamu.edu [Department of Veterinary Physiology and Pharmacology, 4466 TAMU, Texas A& M University, College Station, TX 77843 (United States); Peterson, Richard E., E-mail: richard.peterson@wisc.edu [School of Pharmacy, 777 Highland Ave., University of Wisconsin-Madison, Madison, WI 53705 (United States); Molecular and Environmental Toxicology Center, 1400 University Ave., University of Wisconsin-Madison, Madison, WI 53706 (United States)

    2016-08-15

    It is well established that the prototypical aryl hydrocarbon receptor (AHR) agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) can both cause and protect against carcinogenesis in non-transgenic rodents. But because these animals almost never develop prostate cancer with old age or after carcinogen exposure, whether AHR activation can affect cancer of the prostate remained unknown. We used animals designed to develop this disease, Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) mice, to investigate the potential role of AHR signaling in prostate cancer development. We previously reported that AHR itself has prostate tumor suppressive functions in TRAMP mice; i.e., TRAMP mice in which Ahr was knocked out developed neuroendocrine prostate carcinomas (NEPC) with much greater frequency than did those with both Ahr alleles. In the present study we investigated effects of AHR activation by three different xenobiotics. In utero and lactational TCDD exposure significantly increased NEPC tumor incidence in TRAMP males, while chronic TCDD treatment in adulthood had the opposite effect, a significant reduction in NEPC incidence. Chronic treatment of adult TRAMP mice with the low-toxicity selective AHR modulators indole-3-carbinol or 3,3′-diindolylmethane did not significantly protect against these tumors. Thus, we demonstrate, for the first time, that ligand-dependent activation of the AHR can alter prostate cancer incidence. The nature of the responses depended on the timing of AHR activation and ligand structures. - Highlights: • TRAMP mice model aggressive neuroendocrine prostate carcinomas in men • In utero/lactational TCDD exposure raised prostate cancer incidence in TRAMP mice. • TCDD treatment in adulthood lowered prostate cancer incidence in TRAMP mice. • No significant protection was seen in TRAMP mice given I3C or DIM in adulthood. • This is the first report that TCDD alters prostate cancer incidence in lab animals.

  15. 2,3,7,8-Tetrachlorodibenzo-p-dioxin has both pro-carcinogenic and anti-carcinogenic effects on neuroendocrine prostate carcinoma formation in TRAMP mice

    International Nuclear Information System (INIS)

    Moore, Robert W.; Fritz, Wayne A.; Schneider, Andrew J.; Lin, Tien-Min; Branam, Amanda M.; Safe, Stephen; Peterson, Richard E.

    2016-01-01

    It is well established that the prototypical aryl hydrocarbon receptor (AHR) agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) can both cause and protect against carcinogenesis in non-transgenic rodents. But because these animals almost never develop prostate cancer with old age or after carcinogen exposure, whether AHR activation can affect cancer of the prostate remained unknown. We used animals designed to develop this disease, Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) mice, to investigate the potential role of AHR signaling in prostate cancer development. We previously reported that AHR itself has prostate tumor suppressive functions in TRAMP mice; i.e., TRAMP mice in which Ahr was knocked out developed neuroendocrine prostate carcinomas (NEPC) with much greater frequency than did those with both Ahr alleles. In the present study we investigated effects of AHR activation by three different xenobiotics. In utero and lactational TCDD exposure significantly increased NEPC tumor incidence in TRAMP males, while chronic TCDD treatment in adulthood had the opposite effect, a significant reduction in NEPC incidence. Chronic treatment of adult TRAMP mice with the low-toxicity selective AHR modulators indole-3-carbinol or 3,3′-diindolylmethane did not significantly protect against these tumors. Thus, we demonstrate, for the first time, that ligand-dependent activation of the AHR can alter prostate cancer incidence. The nature of the responses depended on the timing of AHR activation and ligand structures. - Highlights: • TRAMP mice model aggressive neuroendocrine prostate carcinomas in men • In utero/lactational TCDD exposure raised prostate cancer incidence in TRAMP mice. • TCDD treatment in adulthood lowered prostate cancer incidence in TRAMP mice. • No significant protection was seen in TRAMP mice given I3C or DIM in adulthood. • This is the first report that TCDD alters prostate cancer incidence in lab animals.

  16. Lack of detection of human papillomavirus infection by hybridization test in prostatic biopsies

    International Nuclear Information System (INIS)

    Gazzaz, Faten S; Mosli, Hisham A

    2009-01-01

    To explore the possibility of finding human papillomavirus (HPV) infection in the prostate tissue of a cohort of Saudi men presenting with benign prostatic hyperplasia (BPH) or prostate cancer. A cohort study on prospectively collected tissue samples was conducted at King Abdulaziz University Hospital (KAUH), Jeddah, Kingdom of Saudi Arabia from March 2007 to December 2008 on a total of 56 male patients, age range 50-93 years (average 68), diagnosed as having BPH or prostate cancer. The HPV DNA hybridization by hybrid capture 2 technology was performed on prostate biopsies of these patients to detect 18 types of HPV infection, and differentiate between 2 HPV DNA groups, the low-risk types, and the high/intermediate risk types.The tissues of all the prostatic biopsies were negative for HPV DNA. Our results, using the hybridization test, indicate that it is unlikely that HPV-16 or HPV-18, or the other tested subtypes, enhance the risk of prostate cancer. (author)

  17. Genomic instability in human actinic keratosis and squamous cell carcinoma

    Science.gov (United States)

    Cabral, Luciana Sanches; Neto, Cyro Festa; Sanches, José A; Ruiz, Itamar R G

    2011-01-01

    OBJECTIVE: To compare the repetitive DNA patterns of human actinic keratoses and squamous cell carcinomas to determine the genetic alterations that are associated with malignant transformation. INTRODUCTION: Cancer cells are prone to genomic instability, which is often due to DNA polymerase slippage during the replication of repetitive DNA and to mutations in the DNA repair genes. The progression of benign actinic keratoses to malignant squamous cell carcinomas has been proposed by several authors. MATERIAL AND METHODS: Eight actinic keratoses and 24 squamous cell carcinomas (SCC), which were pair-matched to adjacent skin tissues and/or leucocytes, were studied. The presence of microsatellite instability (MSI) and the loss of heterozygosity (LOH) in chromosomes 6 and 9 were investigated using nine PCR primer pairs. Random Amplified Polymorphic DNA patterns were also evaluated using eight primers. RESULTS: MSI was detected in two (D6S251, D9S50) of the eight actinic keratosis patients. Among the 8 patients who had squamous cell carcinoma-I and provided informative results, a single patient exhibited two LOH (D6S251, D9S287) and two instances of MSI (D9S180, D9S280). Two LOH and one example of MSI (D6S251) were detected in three out of the 10 patients with squamous cell carcinoma-II. Among the four patients with squamous cell carcinoma-III, one patient displayed three MSIs (D6S251, D6S252, and D9S180) and another patient exhibited an MSI (D9S280). The altered random amplified polymorphic DNA ranged from 70% actinic keratoses, 76% squamous cell carcinoma-I, and 90% squamous cell carcinoma-II, to 100% squamous cell carcinoma-III. DISCUSSION: The increased levels of alterations in the microsatellites, particularly in D6S251, and the random amplified polymorphic DNA fingerprints were statistically significant in squamous cell carcinomas, compared with actinic keratoses. CONCLUSION: The overall alterations that were observed in the repetitive DNA of actinic keratoses and

  18. SHBG is an important factor in stemness induction of cells by DHT in vitro and associated with poor clinical features of prostate carcinomas.

    Science.gov (United States)

    Ma, Yuanyuan; Liang, Dongming; Liu, Jian; Wen, Jian-Guo; Servoll, Einar; Waaler, Gudmund; Sæter, Thorstein; Axcrona, Karol; Vlatkovic, Ljiljana; Axcrona, Ulrika; Paus, Elisabeth; Yang, Yue; Zhang, Zhiqian; Kvalheim, Gunnar; Nesland, Jahn M; Suo, Zhenhe

    2013-01-01

    Androgen plays a vital role in prostate cancer development. However, it is not clear whether androgens influence stem-like properties of prostate cancer, a feature important for prostate cancer progression. In this study, we show that upon DHT treatment in vitro, prostate cancer cell lines LNCaP and PC-3 were revealed with higher clonogenic potential and higher expression levels of stemness related factors CD44, CD90, Oct3/4 and Nanog. Moreover, sex hormone binding globulin (SHBG) was also simultaneously upregulated in these cells. When the SHBG gene was blocked by SHBG siRNA knock-down, the induction of Oct3/4, Nanog, CD44 and CD90 by DHT was also correspondingly blocked in these cells. Immunohistochemical evaluation of clinical samples disclosed weakly positive, and areas negative for SHBG expression in the benign prostate tissues, while most of the prostate carcinomas were strongly positive for SHBG. In addition, higher levels of SHBG expression were significantly associated with higher Gleason score, more seminal vesicle invasions and lymph node metastases. Collectively, our results show a role of SHBG in upregulating stemness of prostate cancer cells upon DHT exposure in vitro, and SHBG expression in prostate cancer samples is significantly associated with poor clinicopathological features, indicating a role of SHBG in prostate cancer progression.

  19. SHBG is an important factor in stemness induction of cells by DHT in vitro and associated with poor clinical features of prostate carcinomas.

    Directory of Open Access Journals (Sweden)

    Yuanyuan Ma

    Full Text Available Androgen plays a vital role in prostate cancer development. However, it is not clear whether androgens influence stem-like properties of prostate cancer, a feature important for prostate cancer progression. In this study, we show that upon DHT treatment in vitro, prostate cancer cell lines LNCaP and PC-3 were revealed with higher clonogenic potential and higher expression levels of stemness related factors CD44, CD90, Oct3/4 and Nanog. Moreover, sex hormone binding globulin (SHBG was also simultaneously upregulated in these cells. When the SHBG gene was blocked by SHBG siRNA knock-down, the induction of Oct3/4, Nanog, CD44 and CD90 by DHT was also correspondingly blocked in these cells. Immunohistochemical evaluation of clinical samples disclosed weakly positive, and areas negative for SHBG expression in the benign prostate tissues, while most of the prostate carcinomas were strongly positive for SHBG. In addition, higher levels of SHBG expression were significantly associated with higher Gleason score, more seminal vesicle invasions and lymph node metastases. Collectively, our results show a role of SHBG in upregulating stemness of prostate cancer cells upon DHT exposure in vitro, and SHBG expression in prostate cancer samples is significantly associated with poor clinicopathological features, indicating a role of SHBG in prostate cancer progression.

  20. SHBG Is an Important Factor in Stemness Induction of Cells by DHT In Vitro and Associated with Poor Clinical Features of Prostate Carcinomas

    Science.gov (United States)

    Ma, Yuanyuan; Liang, Dongming; Liu, Jian; Wen, Jian-Guo; Servoll, Einar; Waaler, Gudmund; Sæter, Thorstein; Axcrona, Karol; Vlatkovic, Ljiljana; Axcrona, Ulrika; Paus, Elisabeth; Yang, Yue; Zhang, Zhiqian; Kvalheim, Gunnar; Nesland, Jahn M.; Suo, Zhenhe

    2013-01-01

    Androgen plays a vital role in prostate cancer development. However, it is not clear whether androgens influence stem-like properties of prostate cancer, a feature important for prostate cancer progression. In this study, we show that upon DHT treatment in vitro, prostate cancer cell lines LNCaP and PC-3 were revealed with higher clonogenic potential and higher expression levels of stemness related factors CD44, CD90, Oct3/4 and Nanog. Moreover, sex hormone binding globulin (SHBG) was also simultaneously upregulated in these cells. When the SHBG gene was blocked by SHBG siRNA knock-down, the induction of Oct3/4, Nanog, CD44 and CD90 by DHT was also correspondingly blocked in these cells. Immunohistochemical evaluation of clinical samples disclosed weakly positive, and areas negative for SHBG expression in the benign prostate tissues, while most of the prostate carcinomas were strongly positive for SHBG. In addition, higher levels of SHBG expression were significantly associated with higher Gleason score, more seminal vesicle invasions and lymph node metastases. Collectively, our results show a role of SHBG in upregulating stemness of prostate cancer cells upon DHT exposure in vitro, and SHBG expression in prostate cancer samples is significantly associated with poor clinicopathological features, indicating a role of SHBG in prostate cancer progression. PMID:23936228

  1. Effects of homeopathic preparations on human prostate cancer growth in cellular and animal models.

    Science.gov (United States)

    MacLaughlin, Brian W; Gutsmuths, Babett; Pretner, Ewald; Jonas, Wayne B; Ives, John; Kulawardane, Don Victor; Amri, Hakima

    2006-12-01

    The use of dietary supplements for various ailments enjoys unprecedented popularity. As part of this trend, Sabal serrulata (saw palmetto) constitutes the complementary treatment of choice with regard to prostate health. In homeopathy, Sabal serrulata is commonly prescribed for prostate problems ranging from benign prostatic hyperplasia to prostate cancer. The authors' work assessed the antiproliferative effects of homeopathic preparations of Sabal serrulata, Thuja occidentalis, and Conium maculatum, in vivo, on nude mouse xenografts, and in vitro, on PC-3 and DU-145 human prostate cancer as well as MDA-MB-231 human breast cancer cell lines. Treatment with Sabal serrulata in vitro resulted in a 33% decrease of PC-3 cell proliferation at 72 hours and a 23% reduction of DU-145 cell proliferation at 24 hours (PConium maculatum did not have any effect on human prostate cancer cell proliferation. In vivo, prostate tumor xenograft size was significantly reduced in Sabal serrulata-treated mice compared to untreated controls (P=.012). No effect was observed on breast tumor growth. Our study clearly demonstrates a biologic response to homeopathic treatment as manifested by cell proliferation and tumor growth. This biologic effect was (i)significantly stronger to Sabal serrulata than to controls and (ii)specific to human prostate cancer. Sabal serrulata should thus be further investigated as a specific homeopathic remedy for prostate pathology.

  2. CTP synthase forms the cytoophidium in human hepatocellular carcinoma.

    Science.gov (United States)

    Chang, Chia-Chun; Jeng, Yung-Ming; Peng, Min; Keppeke, Gerson Dierley; Sung, Li-Ying; Liu, Ji-Long

    2017-12-15

    CTP synthase (CTPS) can aggregate into an intracellular macrostructure, the cytoophidium, in various organisms including human cells. Previous studies have shown that assembly of human CTPS cytoophidia may be correlated with the cellular metabolic status, and is able to promote the activity of CTPS. A correlation between the cytoophidium and cancer metabolism has been proposed but not yet been revealed. In the current study we provide clear evidence of the presence of CTPS cytoophidia in various human cancers and some non-cancerous tissues. Moreover, among 203 tissue samples of hepatocellular carcinoma, 56 (28%) samples exhibited many cytoophidia, whereas no cytoophidia were detected in adjacent non-cancerous hepatocytes for all samples. Our findings suggest that the CTPS cytoophidium may participate in the adaptive metabolism of human hepatocellular carcinoma. Copyright © 2017. Published by Elsevier Inc.

  3. Expression of epidermal growth factor receptors in human endometrial carcinoma

    DEFF Research Database (Denmark)

    Nyholm, H C; Nielsen, Anette Lynge; Ottesen, B

    1993-01-01

    Little data exist on the expression of epidermal growth factor receptors (EGF-Rs) in human endometrial cancer. EGF-R status was studied in 65 patients with endometrial carcinomas and in 26 women with nonmalignant postmenopausal endometria, either inactive/atrophic endometrium or adenomatous...... hyperplasia. EGF-R was identified on frozen tissue sections by means of an indirect immunoperoxidase technique with a monoclonal antibody against the external domain of the EGF-R. Seventy-one percent of the carcinomas expressed positive EGF-R immunoreactivity. In general, staining was most prominent...

  4. Sr-89 therapy: Strontium kinetics in disseminated carcinoma of the prostate

    International Nuclear Information System (INIS)

    Blake, G.M.; Zivanovic, M.A.; McEwan, A.J.; Ackery, D.M.

    1986-01-01

    Strontium kinetics were investigated in a group of 14 patients receiving 89 Sr palliation for metastatic bone disease secondary to prostatic carcinoma. Using 85 Sr as a tracer, total body strontium retention R(t) was monitored for a 3 month period following 89 Sr administration, and at 90 days was found to vary from 11% to 88% and to correlate closely with the fraction of the skeleton showing scintigraphic evidence of osteoblastic metastatic involvement. Strontium renal plasma clearance varied from 1.6l/ day to 11.6l/day, and in nine patients was significantly reduced compared with values found in healthy adult men, probably due to increased renal tubular reabsorption associated with the disturbance of calcium homoeostasis. Renal clearance rate was the principal factor determining R(t) for t 30 (t/30) -b , with R 30 and b showing the close correlation expected from the effect of R(t) on strontium recycling. The correction of the data for this effect to determine the true skeletal release rate is described. Measurement of localized strontium turnover in individual metastatic deposits from whole body profiles and scintigraphic images gave retention curves that typically rose to a plateau by 10 days after therapy, and then decreased very slowly. In contrast, retention curves for adjacent normal trabecular bone showed more rapid turnover, peaking at 1 day and subsequently decreasing following a t -0.2 power law function. The changes in strontium kinetics found in metastatic bone disease are favourable to the objectives of 89 Sr therapy. (orig.)

  5. Sr-89 therapy: strontium kinetics in disseminated carcinoma of the prostate.

    Science.gov (United States)

    Blake, G M; Zivanovic, M A; McEwan, A J; Ackery, D M

    1986-01-01

    Strontium kinetics were investigated in a group of 14 patients receiving 89Sr palliation for metastatic bone disease secondary to prostatic carcinoma. Using 85Sr as a tracer, total body strontium retention R(t) was monitored for a 3 month period following 89Sr administration, and at 90 days was found to vary from 11% to 88% and to correlate closely with the fraction of the skeleton showing scintigraphic evidence of osteoblastic metastatic involvement. Strontium renal plasma clearance varied from 1.6 l/day to 11.6 l/day, and in nine patients was significantly reduced compared with values found in healthy adult men, probably due to increased renal tubular reabsorption associated with the disturbance of calcium homoeostasis. Renal clearance rate was the principal factor determining R(t) for t less than 6 days, and was an important secondary factor at later times. Over the interval 30 days less than t less than 90 days, R(t) was closely fitted by the power law function R(t) = R30 (t/30)-b, with R30 and b showing the close correlation expected from the effect of R(t) on strontium recycling. The correction of the data for this effect to determine the true skeletal release rate is described. Measurement of localized strontium turnover in individual metastatic deposits from whole body profiles and scintigraphic images gave retention curves that typically rose to a plateau by 10 days after therapy, and then decreased very slowly. In contrast, retention curves for adjacent normal trabecular bone showed more rapid turnover, peaking at 1 day and subsequently decreasing following a t-0.2 power law function.(ABSTRACT TRUNCATED AT 250 WORDS)

  6. Urtica dioica Induces Cytotoxicity in Human Prostate Carcinoma ...

    African Journals Online (AJOL)

    In order to evaluate the involvement of caspases in UD-AQ induced cytotoxicity, the activities of caspase 3 and 9 were measured using a colorimetric assay. Following treatment of. LNCaP cells with UD-AQ extract (50 µg/ml) in 6- well plates, cells were collected by centrifugation and lysed with lysis buffer (1 % Triton X-100,.

  7. Use of complementary and alternative medicine by patients with localized prostate carcinoma. Study at a single institute in Japan

    Energy Technology Data Exchange (ETDEWEB)

    Yoshimura, Koji; Ichioka, Kentaro; Terada, Naoki; Terai, Akito [Kurashiki Central Hospital, Okayama (Japan); Arai, Yoichi [Tohoku Univ., Sendai (Japan). Graduate School of Medicine

    2003-02-01

    The use of complementary/alternative medicine (CAM) has recently received considerable attention throughout the world. We evaluated the prevalence and predictors of CAM use among Japanese patients with localized prostate cancer. A total of 177 patients with localized prostate carcinoma underwent radical retropubic prostatecotomy or external beam radiation therapy between January 1994 and January 2001. Of them, 138 (78%) answered a self-administered questionnaire on CAM use and were eligible for this study. The overall prevalence, types of CAM used, and costs of CAM were assessed. The effects of age, prostate-specific antigen (PSA) level, clinical stage, pretreatment Gleason score, patients' income, patients' final educational status, and general health-related quality of life at baseline and 1 year after treatment, as estimated using the European Organization for Research and Treatment of Cancer Prostate Cancer Quality of Life Questionnaire on the prevalence of CAM use, were evaluated. Twenty-seven patients (20%) had once used or had been using some types of CAM. Herbal medicine and vitamins were the most common types of CAM used. Preoperative Gleason score was significantly associated with CAM use, as determined by the {chi}''2 test (P0.0198), and PSA level and posttreatment physical function domain were marginally associated with CAM use, as determined by the Mann-Whitney U-test (P=0.0734 and P=0.0597, respectively). Patient age, income, and final educational status had no impact on CAM use. A relatively small proportion of Japanese patients with localized prostate cancer have tried CAM compared with the proportions of patients described in previous reports from Western countries. (author)

  8. Use of complementary and alternative medicine by patients with localized prostate carcinoma. Study at a single institute in Japan

    International Nuclear Information System (INIS)

    Yoshimura, Koji; Ichioka, Kentaro; Terada, Naoki; Terai, Akito; Arai, Yoichi

    2003-01-01

    The use of complementary/alternative medicine (CAM) has recently received considerable attention throughout the world. We evaluated the prevalence and predictors of CAM use among Japanese patients with localized prostate cancer. A total of 177 patients with localized prostate carcinoma underwent radical retropubic prostatecotomy or external beam radiation therapy between January 1994 and January 2001. Of them, 138 (78%) answered a self-administered questionnaire on CAM use and were eligible for this study. The overall prevalence, types of CAM used, and costs of CAM were assessed. The effects of age, prostate-specific antigen (PSA) level, clinical stage, pretreatment Gleason score, patients' income, patients' final educational status, and general health-related quality of life at baseline and 1 year after treatment, as estimated using the European Organization for Research and Treatment of Cancer Prostate Cancer Quality of Life Questionnaire on the prevalence of CAM use, were evaluated. Twenty-seven patients (20%) had once used or had been using some types of CAM. Herbal medicine and vitamins were the most common types of CAM used. Preoperative Gleason score was significantly associated with CAM use, as determined by the χ''2 test (P0.0198), and PSA level and posttreatment physical function domain were marginally associated with CAM use, as determined by the Mann-Whitney U-test (P=0.0734 and P=0.0597, respectively). Patient age, income, and final educational status had no impact on CAM use. A relatively small proportion of Japanese patients with localized prostate cancer have tried CAM compared with the proportions of patients described in previous reports from Western countries. (author)

  9. Comparative analysis of three- and two-antibody cocktails to AMACR and basal cell markers for the immunohistochemical diagnosis of prostate carcinoma

    Directory of Open Access Journals (Sweden)

    Dabir Parag

    2012-07-01

    Full Text Available Abstract Background Immunohistochemistry using antibody cocktails against basal cell specific and cancer-associated markers is important in the diagnosis of prostate carcinoma in needle biopsies. We compared the usefulness for detecting prostate carcinoma of a three-marker cocktail of antibodies to α-methylacyl-CoA racemase (AMACR, p63 and cytokeratin (CK 5 with a traditional two-marker cocktail of AMACR and p63. Methods Sixty-six prostate needle biopsies were analysed prospectively. Serial sections were immunostained with the two- and three- antibody cocktails. Blinded slides were assessed individually by two pathologists and sensitivity, specificity and kappa statistics were calculated. Results Both antibody cocktails contributed to the detection of prostate carcinoma in needle biopsies. There was an acceptable level of agreement between the pathologists for both the cocktails. Sensitivity was similar for one pathologist comparing both the cocktails (76.4% and 75.7%, but was slightly lower comparing the three-antibody with the two-antibody cocktail for the other pathologist (66.6% vs. 77.4%, respectively. Higher specificity values of 90.3% were achieved by both pathologists using three-antibody as compared with two-antibody cocktails (68.7% and 71.8%. Conclusions Antibody cocktails are important in diagnosing prostate carcinoma in needle biopsies. Adding an extra basal cell marker to the traditional two-antibody cocktail improves the specificity of detecting prostate carcinoma in limited needle biopsy material, and should be considered for routine diagnostic use. Virtual slides The virtual slide(s for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2492231327330327

  10. Epidermal growth factor and its receptors in human pancreatic carcinoma

    International Nuclear Information System (INIS)

    Chen, Y.F.; Pan, G.Z.; Hou, X.; Liu, T.H.; Chen, J.; Yanaihara, C.; Yanaihara, N.

    1990-01-01

    The role of epidermal growth factor (EGF) in oncogenesis and progression of malignant tumors is a subject of vast interest. In this study, radioimmunoassay and radioreceptor assay of EGF were established. EGF contents in malignant and benign pancreatic tumors, in normal pancreas tissue, and in culture media of a human pancreatic carcinoma cell line were determined. EGF receptor binding studies were performed. It was shown that EGF contents in pancreatic carcinomas were significantly higher than those in normal pancreas or benign pancreatic tumors. EGF was also detected in the culture medium of a pancreatic carcinoma cell line. The binding of 125I-EGF to the pancreatic carcinoma cells was time and temperature dependent, reversible, competitive, and specific. Scatchard analysis showed that the dissociation constant of EGF receptor was 2.1 X 10(-9) M, number of binding sites was 1.3 X 10(5) cell. These results indicate that there is an over-expression of EGF/EGF receptors in pancreatic carcinomas, and that an autocrine regulatory mechanism may exist in the growth-promoting effect of EGF on tumor cells

  11. Notch activation is dispensable for D, L-sulforaphane-mediated inhibition of human prostate cancer cell migration.

    Directory of Open Access Journals (Sweden)

    Eun-Ryeong Hahm

    Full Text Available D, L-Sulforaphane (SFN, a synthetic racemic analog of broccoli constituent L-sulforaphane, is a highly promising cancer chemopreventive agent with in vivo efficacy against chemically-induced as well as oncogene-driven cancer in preclinical rodent models. Cancer chemopreventive effect of SFN is characterized by G(2/M phase cell cycle arrest, apoptosis induction, and inhibition of cell migration and invasion. Moreover, SFN inhibits multiple oncogenic signaling pathways often hyperactive in human cancers, including nuclear factor-κB, Akt, signal transducer and activator of transcription 3, and androgen receptor. The present study was designed to determine the role of Notch signaling, which is constitutively active in many human cancers, in anticancer effects of SFN using prostate cancer cells as a model. Exposure of human prostate cancer cells (PC-3, LNCaP, and/or LNCaP-C4-2B to SFN as well as its naturally-occurring thio-, sulfinyl-, and sulfonyl-analogs resulted in cleavage (activation of Notch1, Notch2, and Notch4, which was accompanied by a decrease in levels of full-length Notch forms especially at the 16- and 24-hour time points. The SFN-mediated cleavage of Notch isoforms was associated with its transcriptional activation as evidenced by RBP-Jk-, HES-1A/B- and HEY-1 luciferase reporter assays. Migration of PC-3 and LNCaP cells was decreased significantly by RNA interference of Notch1 and Notch2, but not Notch4. Furthermore, SFN-mediated inhibition of PC-3 and LNCaP cell migration was only marginally affected by knockdown of Notch1 and Notch2. Strikingly, SFN administration to Transgenic Adenocarcinoma of Mouse Prostate transgenic mice failed to increase levels of cleaved Notch1, cleaved Notch2, and HES-1 proteins in vivo in prostatic intraepithelial neoplasia, well-differentiated carcinoma or poorly-differentiated prostate cancer lesions. These results indicate that Notch activation is largely dispensable for SFN-mediated inhibition of cell

  12. Leptin Regulates Proliferation and Apoptosis in Human Prostate

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    Eduardo Leze

    2012-01-01

    Full Text Available This paper aimed to evaluate the leptin role on the cellular proliferation and the expression of fibroblast growth factor 2, aromatase enzyme, and apoptotic genes in the human prostate tissue. Methods. Fifteen samples of hyperplasic prostate tissue were divided in four symmetric parts maintained in RPMI medium supplemented with 10% fetal bovine serum, 1 ng/mL of gentamicin, and added with 50 ng/mL leptin (L or not (C. After 3 hours of incubation, gene expression was evaluated by real time RT-PCR. Cellular proliferation was evaluated by immunohistochemistry for PCNA. Results. The leptin treatment led to an increase cellular proliferation (C=21.8±0.5; L=64.8±0.9; P<0.0001 and in the expression of Bax (C=0.4±0.1; L=0.9±0.2; P<0.05 while Bcl-2 (C=19.9±5.6; L=5.6±1.8; P<0.05, Bcl-x (C=0.2±0.06; L=0.07±0.02; P<0.05, and aromatase expressions (C=1.9±0.6; L=0.4±0.1; P<0.04 were significantly reduced. Conclusion. Leptin has an important role in maintaining the physiological growth of the prostate since it stimulates both cellular proliferation and apoptosis, with the decrement in the aromatase gene expression.

  13. 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.

  14. Induction of Human Squamous Cell-Type Carcinomas by Arsenic

    International Nuclear Information System (INIS)

    Martinez, V. D.; Becker-Santos, D. D.; Vucic, E. A.; Lam, S.; Lam, W. L.

    2011-01-01

    Arsenic is a potent human carcinogen. Around one hundred million people worldwide have potentially been exposed to this metalloid at concentrations considered unsafe. Exposure occurs generally through drinking water from natural geological sources, making it difficult to control this contamination. Arsenic biotransformation is suspected to have a role in arsenic-related health effects ranging from acute toxicities to development of malignancies associated with chronic exposure. It has been demonstrated that arsenic exhibits preference for induction of squamous cell carcinomas in the human, especially skin and lung cancer. Interestingly, keratins emerge as a relevant factor in this arsenic-related squamous cell-type preference. Additionally, both genomic and epi genomic alterations have been associated with arsenic-driven neoplastic process. Some of these aberrations, as well as changes in other factors such as keratins, could explain the association between arsenic and squamous cell carcinomas in humans.

  15. Met-Independent Hepatocyte Growth Factor-mediated regulation of cell adhesion in human prostate cancer cells

    Directory of Open Access Journals (Sweden)

    Davis Rodney

    2006-07-01

    Full Text Available Abstract Background Prostate cancer cells communicate reciprocally with the stromal cells surrounding them, inside the prostate, and after metastasis, within the bone. Each tissue secretes factors for interpretation by the other. One stromally-derived factor, Hepatocyte Growth Factor (HGF, was found twenty years ago to regulate invasion and growth of carcinoma cells. Working with the LNCaP prostate cancer progression model, we found that these cells could respond to HGF stimulation, even in the absence of Met, the only known HGF receptor. The new HGF binding partner we find on the cell surface may help to clarify conflicts in the past literature about Met expression and HGF response in cancer cells. Methods We searched for Met or any HGF binding partner on the cells of the PC3 and LNCaP prostate cancer cell models, using HGF immobilized on agarose beads. By using mass spectrometry analyses and sequencing we have identified nucleolin protein as a novel HGF binding partner. Antibodies against nucleolin (or HGF were able to ameliorate the stimulatory effects of HGF on met-negative prostate cancer cells. Western blots, RT-PCR, and immunohistochemistry were used to assess nucleolin levels during prostate cancer progression in both LNCaP and PC3 models. Results We have identified HGF as a major signaling component of prostate stromal-conditioned media (SCM and have implicated the protein nucleolin in HGF signal reception by the LNCaP model prostate cancer cells. Antibodies that silence either HGF (in SCM or nucleolin (on the cell surfaces eliminate the adhesion-stimulatory effects of the SCM. Likewise, addition of purified HGF to control media mimics the action of SCM. C4-2, an LNCaP lineage-derived, androgen-independent human prostate cancer cell line, responds to HGF in a concentration-dependent manner by increasing its adhesion and reducing its migration on laminin substratum. These HGF effects are not due to shifts in the expression levels of

  16. Met-Independent Hepatocyte Growth Factor-mediated regulation of cell adhesion in human prostate cancer cells

    International Nuclear Information System (INIS)

    Tate, Amanda; Isotani, Shuji; Bradley, Michael J; Sikes, Robert A; Davis, Rodney; Chung, Leland WK; Edlund, Magnus

    2006-01-01

    Prostate cancer cells communicate reciprocally with the stromal cells surrounding them, inside the prostate, and after metastasis, within the bone. Each tissue secretes factors for interpretation by the other. One stromally-derived factor, Hepatocyte Growth Factor (HGF), was found twenty years ago to regulate invasion and growth of carcinoma cells. Working with the LNCaP prostate cancer progression model, we found that these cells could respond to HGF stimulation, even in the absence of Met, the only known HGF receptor. The new HGF binding partner we find on the cell surface may help to clarify conflicts in the past literature about Met expression and HGF response in cancer cells. We searched for Met or any HGF binding partner on the cells of the PC3 and LNCaP prostate cancer cell models, using HGF immobilized on agarose beads. By using mass spectrometry analyses and sequencing we have identified nucleolin protein as a novel HGF binding partner. Antibodies against nucleolin (or HGF) were able to ameliorate the stimulatory effects of HGF on met-negative prostate cancer cells. Western blots, RT-PCR, and immunohistochemistry were used to assess nucleolin levels during prostate cancer progression in both LNCaP and PC3 models. We have identified HGF as a major signaling component of prostate stromal-conditioned media (SCM) and have implicated the protein nucleolin in HGF signal reception by the LNCaP model prostate cancer cells. Antibodies that silence either HGF (in SCM) or nucleolin (on the cell surfaces) eliminate the adhesion-stimulatory effects of the SCM. Likewise, addition of purified HGF to control media mimics the action of SCM. C4-2, an LNCaP lineage-derived, androgen-independent human prostate cancer cell line, responds to HGF in a concentration-dependent manner by increasing its adhesion and reducing its migration on laminin substratum. These HGF effects are not due to shifts in the expression levels of laminin-binding integrins, nor can they be linked to

  17. Radiosensitization of human prostate cell line LNCAP by [6]- gingerol

    Energy Technology Data Exchange (ETDEWEB)

    Silva, Josias Paulino Leal; Bellini, Maria Helena [Instituto de Pesquisas Energéticas e Nucleares (IPEN/CNEN-SP), São Paulo, SP (Brazil)

    2017-07-01

    Full text: Introduction: Prostate cancer is the second most prevalent malignancy and second leading cause of cancer-related deaths among men in the world. Several different diagnostic and therapeutic approaches have been developed in order to decrease the death rates. A number of experimental and clinical studies have showed antiproliferative, pro-apoptotic, anti-metastatic and anti-angiogenic effects of several phytochemicals. [6]-Gingerol (1-[4'-hydroxy-3'-methoxyphenyl]-5-hydroxy-3- decanone), the major pungent principle of ginger, has anti-oxidant, anti-inflammation and antitumor promoting activities. Aim: The purpose of this study was to evaluate the radiosensitizing activity of [6]-Gingerol in the human prostate cancer cells. Methods: The viability was assessed (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) tetrazolium (MTS) assay. The prostate human cells (LNCAP) (2,5×103 cells/well) were seeded into 96-well plates, after 24 hr they were treated with 150 and 300μg/mL of [6]-Gingerol or vehicle alone (0.1% DMSO) in serum containing media. After incubation, MTS solution was added to the plate at a final concentration of 0.5 mg/mL. The cells were incubated for 2 hr in dark at 37. The resulting MTS-products were determined by measuring the absorbance at 490 nm with ELISA reader. In the clonogenic cell survival assay, the cells were divided into two groups: A) control, B) treated with [6]-Gingerol, C) irradiated control and D) treated with [6]-Gingerol and irradiated. The cells were irradiated by 60Co source in the range from 0 to 15 Gy, using the GammaCell 220 - Irradiation Unit of Canadian-Atomic Energy Commision Ltd. (CTR-IPEN). After 10-14 days of culture in normoxia conditions, cell colonies were fixed and stained with methanol 20% and crystal violet 0.5% and counted. Multiple comparisons were assessed by One-way ANOVA followed by Bonferroni´s tests with GraphPad Prism version 6.0 software. p< 0.05 was considered statistically

  18. Radiosensitization of human prostate cell line LNCAP by [6]- gingerol

    International Nuclear Information System (INIS)

    Silva, Josias Paulino Leal; Bellini, Maria Helena

    2017-01-01

    Full text: Introduction: Prostate cancer is the second most prevalent malignancy and second leading cause of cancer-related deaths among men in the world. Several different diagnostic and therapeutic approaches have been developed in order to decrease the death rates. A number of experimental and clinical studies have showed antiproliferative, pro-apoptotic, anti-metastatic and anti-angiogenic effects of several phytochemicals. [6]-Gingerol (1-[4'-hydroxy-3'-methoxyphenyl]-5-hydroxy-3- decanone), the major pungent principle of ginger, has anti-oxidant, anti-inflammation and antitumor promoting activities. Aim: The purpose of this study was to evaluate the radiosensitizing activity of [6]-Gingerol in the human prostate cancer cells. Methods: The viability was assessed (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) tetrazolium (MTS) assay. The prostate human cells (LNCAP) (2,5×103 cells/well) were seeded into 96-well plates, after 24 hr they were treated with 150 and 300μg/mL of [6]-Gingerol or vehicle alone (0.1% DMSO) in serum containing media. After incubation, MTS solution was added to the plate at a final concentration of 0.5 mg/mL. The cells were incubated for 2 hr in dark at 37. The resulting MTS-products were determined by measuring the absorbance at 490 nm with ELISA reader. In the clonogenic cell survival assay, the cells were divided into two groups: A) control, B) treated with [6]-Gingerol, C) irradiated control and D) treated with [6]-Gingerol and irradiated. The cells were irradiated by 60Co source in the range from 0 to 15 Gy, using the GammaCell 220 - Irradiation Unit of Canadian-Atomic Energy Commision Ltd. (CTR-IPEN). After 10-14 days of culture in normoxia conditions, cell colonies were fixed and stained with methanol 20% and crystal violet 0.5% and counted. Multiple comparisons were assessed by One-way ANOVA followed by Bonferroni´s tests with GraphPad Prism version 6.0 software. p< 0.05 was considered statistically

  19. Human RecQL4 helicase plays critical roles in prostate carcinogenesis

    DEFF Research Database (Denmark)

    Su, Yanrong; Meador, Jarah A; Calaf, Gloria M

    2010-01-01

    Prostate cancer is the second leading cause of cancer-associated deaths among men in the western countries. Here, we report that human RecQL4 helicase, which is implicated in the pathogenesis of a subset of cancer-prone Rothmund-Thomson syndrome, is highly elevated in metastatic prostate cancer c...

  20. Cell-autonomous intracellular androgen receptor signaling drives the growth of human prostate cancer initiating cells.

    Science.gov (United States)

    Vander Griend, Donald J; D'Antonio, Jason; Gurel, Bora; Antony, Lizamma; Demarzo, Angelo M; Isaacs, John T

    2010-01-01

    The lethality of prostate cancer is due to the continuous growth of cancer initiating cells (CICs) which are often stimulated by androgen receptor (AR) signaling. However, the underlying molecular mechanism(s) for such AR-mediated growth stimulation are not fully understood. Such mechanisms may involve cancer cell-dependent induction of tumor stromal cells to produce paracrine growth factors or could involve cancer cell autonomous autocrine and/or intracellular AR signaling pathways. We utilized clinical samples, animal models and a series of AR-positive human prostate cancer cell lines to evaluate AR-mediated growth stimulation of prostate CICs. The present studies document that stromal AR expression is not required for prostate cancer growth, since tumor stroma surrounding AR-positive human prostate cancer metastases (N = 127) are characteristically AR-negative. This lack of a requirement for AR expression in tumor stromal cells is also documented by the fact that human AR-positive prostate cancer cells grow equally well when xenografted in wild-type versus AR-null nude mice. AR-dependent growth stimulation was documented to involve secretion, extracellular binding, and signaling by autocrine growth factors. Orthotopic xenograft animal studies documented that the cellautonomous autocrine growth factors which stimulate prostate CIC growth are not the andromedins secreted by normal prostate stromal cells. Such cell autonomous and extracellular autocrine signaling is necessary but not sufficient for the optimal growth of prostate CICs based upon the response to anti-androgen plus/or minus preconditioned media. AR-induced growth stimulation of human prostate CICs requires AR-dependent intracellular pathways. The identification of such AR-dependent intracellular pathways offers new leads for the development of effective therapies for prostate cancer. (c) 2009 Wiley-Liss, Inc.

  1. Sexual steroids in serum and prostatic tissue of human non-cancerous prostate (STERPROSER trial).

    Science.gov (United States)

    Neuzillet, Yann; Raynaud, Jean-Pierre; Radulescu, Camélia; Fiet, Jean; Giton, Franck; Dreyfus, Jean-François; Ghoneim, Tarek P; Lebret, Thierry; Botto, Henry

    2017-11-01

    The specific involvement of the sex steroids in the growth of the prostatic tissue remains unclear. Sex steroid concentrations in plasma and in fresh surgical samples of benign central prostate were correlated to prostate volume. Monocentric prospective study performed between September 2014 and January 2017. Age, obesity parameters, and both serum and intraprostatic concentrations of sex steroids were collected complying with the latest Endocrine Society guidelines and the steroids assessed by GC/MS. Statistical calculations were adjusted for age and body mass index (BMI). Thirty-two patients, equally divided between normal- and high-volume prostate groups, were included in the analysis. High-volume prostate patients were older, heavier and had higher BMI. Comparison adjusted for age and BMI showed higher DHT concentrations in high-volume prostate. Both normal- and high-volume prostate tissues concentrate sex steroids in a similar way. Comparison of enzymatic activity surrogate marker ratios within tissue highlighted similar TT/E1 and TT/E2 ratios, and higher DHT/E1 ratio and lower DHT/PSA ratio in the high-volume prostates. STERPROSER trial provides evidence for higher DHT concentration in highvolume prostates, that could reflect either higher 5-alpha reductase expression or lower expression of downstream metabolizing enzymes such as 3a-hydoxysteroid dehydrogenase. © 2017 Wiley Periodicals, Inc.

  2. Mechanism of cisplatin resistance in human urothelial carcinoma cells.

    Science.gov (United States)

    Yu, Hui-Min; Wang, Tsing-Cheng

    2012-05-01

    An isogenic pair of cisplatin-susceptible (NTUB1) and -resistant (NTUB1/P) human urothelial carcinoma cell lines was used to elucidate the mechanism of cisplatin resistance. The significantly lower intracellular platinum (IP) concentration, which resulted from the decreased cisplatin uptake, was found in NTUB1/P cells. The enhancement of IP concentration did not increase the susceptibility of NTUB1/P cells to cisplatin treatment. The reduction of IP concentration as well was unable to enhance the cisplatin-resistance in susceptible NTUB1 cells. This indicated that reduction of IP concentration was not the account for the development of cisplatin resistance here. Instead, the over expression of anti-apoptotic Bcl-2, anti-oxidative heme oxygenase-1 (HO-1) and cell cycle regulator p16INK4 seemed to be more important for the gaining of cisplatin in these human urothelial carcinoma cell. Copyright © 2012 Elsevier Ltd. All rights reserved.

  3. Palladium-103 brachytherapy for clinical T1/T2 prostate carcinomas

    International Nuclear Information System (INIS)

    Dattoli, M.J.; Wallner, K.E.; Cash, J.C.; Ross, R.E.; Koval, J.M.; Sorace, R.A.

    1997-01-01

    Purpose: To evaluate the efficacy of Pd-103 brachytherapy as sole modality for patients having clinical T1/T2 prostate carcinomas Materials and Methods: The initial 103 consecutive patients treated at our hospital are available for biochemical failure and toxicity data following Pd-103 brachytherapy. Minimum peripheral target dose of 11,500cGy (median) was prescribed. Follow-up range: 4-6 years (56 months median). Mean pre-treatment PSA = 11.7ng/ml. All patients have been followed in prospective fashion with respect to PSA response, clinical evidence of disease progression and complications. Criteria for biochemical failure was relatively strict, and was analyzed using PSA>1.0. Patients whose PSA was still decreasing at last follow-up were censored at that time. Freedom from failure rates were calculated by the method of Kaplan and Meier. Differences between groups were determined by the Log-rank method. Sexual potency was defined as the ability to attain and maintain an erection sufficient for intercourse. Results: Actuarial freedom from biochemical failure at 6 years after treatment is 68%. Toxicity has been low with no patient developing rectal ulceration or incontinence (despite 16 pts having prior TURP). The impotency rate is 12%. Of the 33 pts with a post treatment PSA >1.0, 29 pts actually had one or more adverse features determined to be PSA>10 (26 pts), Gleason's score ≥ 7 (5 pts), AJC clinical stage≥T2b (10 pts). Mean pre-treatment PSA's of the 33 failures = 18.3ng/ml. For the 74 pts without high risk features, the actuarial 6 years biochemical freedom from progression rate using PSA<1.0 as an endpoint for success is 93%. Conclusion: This biochemical freedom from progression rate compares favorably to other modalities and supports the use of Pd-103 brachytherapy as sole modality in properly selected patients. Morbidity has been relatively low. Pd-103 implant alone is currently being used in patients having PSA<10, Gleason's score<7, and clinical stage

  4. The expression of xenobiotic-metabolizing enzymes in human prostate and in prostate epithelial cells (PECs) derived from primary cultures.

    Science.gov (United States)

    Al-Buheissi, S Z; Cole, K J; Hewer, A; Kumar, V; Bryan, R L; Hudson, D L; Patel, H R; Nathan, S; Miller, R A; Phillips, D H

    2006-06-01

    Dietary heterocyclic amines (HCAs) are carcinogenic in rodent prostate requiring activation by enzymes such as cytochrome P450 (CYP) and N-acetyltransferase (NAT). We investigated by Western blotting and immunohistochemistry the expression of CYP1A1, CYP1A2, and NAT1 in human prostate and in prostate epithelial cells (PECs) derived from primary cultures and tested their ability to activate the dietary carcinogen 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and its N-hydroxy metabolite (N-OH-IQ) to DNA-damaging moieties. Western blotting identified CYP1A1, CYP1A2, and NAT1. Immunohistochemistry localized NAT1 to the cytoplasm of PECs. Inter-individual variation was observed in the expression levels of CYP1A1, 1A2, and NAT1 (11, 75, and 35-fold, respectively). PECs expressed CYP1A1 and NAT1 but not CYP1A2. When incubated with IQ or N-OH-IQ, PECs formed DNA adducts indicating their ability to metabolically activate these compounds. Prostate cells possess the capacity to activate dietary carcinogens. PECs may provide a useful model system to study their role in prostate carcinogenesis.

  5. Androgen receptor signaling is required for androgen-sensitive human prostate cancer cell proliferation and survival

    Directory of Open Access Journals (Sweden)

    Day Wanda V

    2005-04-01

    Full Text Available Abstract Background Androgens and androgen receptors (AR regulate normal prostate development and growth. They also are involved in pathological development of prostatic diseases, including benign prostatic hyperplasia (BPH and prostate cancer (PCa. Antiandrogen therapy for PCa, in conjunction with chemical or surgical castration, offers initial positive responses and leads to massive prostate cell death. However, cancer cells later appear as androgen-independent PCa. To investigate the role of AR in prostate cell proliferation and survival, we introduced a vector-based small interfering RNA (siRNA. This siRNA targeted 5'-untranslated region of AR mRNA for extended suppression of AR expression in androgen-sensitive human prostate LNCaP cells. Results The siRNA design successfully suppressed endogenous AR expression, as revealed by western blotting and immunofluorescence staining in LNCaP cells. LNCaP cells did not proliferate in the absence of AR and underwent apoptosis, based on elevated phospho-Histone H2B expression and higher number of apoptotic body as compared to control cells. Conclusion We demonstrated that AR is vital for prostate cell proliferation and survival in this androgen-sensitive prostate cell line. These results further strengthen the hypothesis that AR can be a therapeutic target for treating androgen-sensitive stages of PCa. Unlike antiandorgens, however, siRNA targeting AR provides a direct inactivation of AR function through the suppression of AR protein expression.

  6. Aminomethylphosphonic acid inhibits growth and metastasis of human prostate cancer in an orthotopic xenograft mouse model.

    Science.gov (United States)

    Parajuli, Keshab Raj; Zhang, Qiuyang; Liu, Sen; You, Zongbing

    2016-03-01

    Aminomethylphosphonic acid (AMPA) has been shown to inhibit prostate cancer cell growth in vitro. The purpose of the present study was to determine if AMPA could inhibit growth and metastasis of prostate cancer in vivo. Human prostate cancer PC-3-LacZ-luciferase cells were implanted into the ventral lateral lobes of the prostate in 39 athymic Nu/Nu nude male mice. Seven days later, mice were randomized into the control group (n = 14, treated intraperitoneally with phosphate buffered saline), low dose group (n = 10, treated intraperitoneally with AMPA at 400 mg/kg body weight/day), and high dose group (n = 15, treated intraperitoneally with AMPA at 800 mg/kg body weight/day). Tumor growth and metastasis were examined every 4-7 days by bioluminescence imaging of live mice. We found that AMPA treatment significantly inhibited growth and metastasis of orthotopic xenograft prostate tumors and prolonged the survival time of the mice. AMPA treatment decreased expression of BIRC2 and activated caspase 3, leading to increased apoptosis in the prostate tumors. AMPA treatment decreased expression of cyclin D1. AMPA treatment also reduced angiogenesis in the prostate tumors. Taken together, these results demonstrate that AMPA can inhibit prostate cancer growth and metastasis, suggesting that AMPA may be developed into a therapeutic agent for the treatment of prostate cancer.

  7. d -Limonene sensitizes docetaxel-induced cytotoxicity in human prostate cancer cells: Generation of reactive oxygen species and induction of apoptosis

    Directory of Open Access Journals (Sweden)

    Rabi Thangaiyan

    2009-01-01

    Full Text Available Background: Clinical trials have shown that docetaxel combined with other novel agents can improve the survival of androgen-independent prostate cancer patients. d -Limonene, a non-nutrient dietary component, has been found to inhibit various cancer cell growths without toxicity. We sought to characterize whether a non-toxic dose of d -limonene may enhance tumor response to docetaxel in an in vitro model of metastatic prostate cancer. Materials and Methods: Human prostate carcinoma DU-145 and normal prostate epithelial PZ-HPV-7 cells were treated with various concentrations of d -limonene, docetaxel or a combination of both, and cell viability was determined by MTT assay. Intracellular reactive oxygen species (ROS, reduced glutathione (GSH and caspase activity were measured. Apoptosis and apoptosis-related proteins were studied by enzyme-linked immunosorbent assay and Western blotting, respectively. Results: d -Limonene and docetaxel in combination significantly enhanced the cytotoxicity to DU-145 cells than PZ-HPV-7 cells. Exposure of DU-145 cells to a combined d -limonene and docetaxel resulted in higher ROS generation, depletion of GSH, accompanied by increased caspase activity than docetaxel alone. It also triggered a series of effects involving cytochrome c , cleavages of caspase-9, 3 and poly (ADP-ribose polymerase, and a shift in Bad:Bcl-xL ratio in favor of apoptosis. Apoptotic effect was significantly blocked on pretreatment with N -acetylcystein, indicating that antitumor effect is initiated by ROS generation, and caspase cascades contribute to the cell death. Conclusion: Our results show, for the first time, that d -limonene enhanced the antitumor effect of docetaxel against prostate cancer cells without being toxic to normal prostate epithelial cells. The combined beneficial effect could be through the modulation of proteins involved in mitochondrial pathway of apoptosis. d -Limonene could be used as a potent non-toxic agent to

  8. Deep RNA-Seq analysis reveals unexpected features of human prostate basal epithelial cells

    Directory of Open Access Journals (Sweden)

    Dingxiao Zhang

    2016-03-01

    Full Text Available Prostate cancer is the second leading cause of cancer-related deaths among American men [1]. The prostate gland mainly contains basal and luminal cells, which are constructed as a pseudostratified epithelium. Annotation of prostate epithelial transcriptomes provides a foundation for discoveries that can impact disease understanding and treatment. Here, for the first time, we describe a whole-genome transcriptome analysis of human benign prostatic basal and luminal populations by using deep RNA sequencing (GSE67070 [2]. Combined with comprehensive molecular and biological characterizations, we show that the differential gene expression profiles account for their distinct functional phenotypes. Strikingly, in contrast to luminal cells, basal cells preferentially express gene categories associated with stem cells, neural and neuronal development, and RNA processing. Of clinical relevance, the treatment failed castration-resistant and anaplastic prostate cancers molecularly resemble a basal-like phenotype. We also identified genes associated with patient clinical outcome. Therefore, we provide a gene expression resource for understanding human prostate epithelial lineages, and link the cell-type specific gene signatures to subtypes of prostate cancer development. Keywords: Prostate epithelial cells, Basal cells, Luminal cells, RNA-seq

  9. Temporal morphologic changes in human colorectal carcinomas following xenografting.

    Science.gov (United States)

    Barkla, D H; Tutton, P J

    1983-03-01

    The temporal morphologic changes of human colorectal carcinomas following xenografting into immunosuppressed mice were investigated by the use of light and transmission electron microscopy. The results show that colorectal carcinomas undergo a series of morphologic changes during the initial 30-day period following transplantation. During the initial 1-5-day period the majority of tumor cells die, and during the following 5-10-day period the necrotic debris created during the 1-5-day period is removed by host-supplied inflammatory cells. Only small groups of peripherally placed tumor cells survived at the end of the first 10 days. During the 10-20-day period the tumor cell populations of xenografts were reestablished by a morphologically heterogeneous population of tumor cells, and during the 20-30 day period consolidation of this process continued and some xenografts showed macroscopic evidence of growth. The authors hypothesize that human colorectal carcinomas, like the antecedent epithelium, contain subpopulations of undifferentiated cells that give rise to populations of more-differentiated cells.

  10. Tuft (caveolated) cells in two human colon carcinoma cell lines.

    Science.gov (United States)

    Barkla, D H; Whitehead, R H; Foster, H; Tutton, P J

    1988-09-01

    The presence of an unusual cell type in two human colon carcinoma cell lines is reported. The cells show the same morphology as "tuft" (caveolated) cells present in normal gastrointestinal epithelium. Tuft cells were seen in cell line LIM 1863 growing in vitro and in human colon carcinoma cell line LIM 2210 growing as subcutaneous solid tumour xenografts in nude mice. Characteristic morphologic features of tuft cells included a wide base, narrow apex and a tuft of long microvilli projecting from the apical surface. The microvilli are attached by a core of long microfilaments passing deep into the apical cytoplasm. Between the microvilli are parallel arrays of vesicles (caveoli) containing flocculent material. Two different but not mutually exclusive explanations for the presence of tuft cells are proposed. The first explanation is that tuft cells came from the resected tumour and have survived by mitotic division during subsequent passages. The second explanation suggests that tuft cells are the progeny of undifferentiated tumour cells. Descriptions of tuft cells in colon carcinomas are uncommon and possible reasons for this are presented. The morphology of tuft cells is consistent with that of a highly differentiated cell specialised for absorption, and these new models provide an opportunity to further investigate the structure and function of tuft cells.

  11. Exoftalmo unilateral por metástase orbitária de carcinoma de próstata Unilateral exophthalmos secondary to orbital metastatic carcinoma of the prostate: a case report

    Directory of Open Access Journals (Sweden)

    José Carlos Corrêa Barbosa

    1972-06-01

    Full Text Available É relatado um caso de exoftalmo ou proptose unilateral direita, causado por metástase orbitária de carcinoma da próstata em paciente negro, na 6.ª década de vida, com evolução de 9 meses. O exame neuro-ocular revelou acentuada diminuição da agudeza visual, perturbação para visão de cores, perda da convergência, diminuição dos reflexos à luz e acomodação e restrição dos movimentos oculares. O paciente apresentava discreta disbasia esquerda por metástase no fêmur. Exames laboratoriais, radiológicos e a biópsia confirmaram a etiologia carcinomatosa da manifestação ocular.A case of right unilateral exophthalmos secondary to metastatic carcinoma of the prostate, in a 68 years old negro patient in which the ocular manifestation lasted 9 months is reported The extrinsic movements of the eye were limited. Pupils reacted slightly to light and accommodation. There was no ocular convergence. The vision of the right eye was blurred and there was mild color vision. The prostate was found to be petrous by touch specially in the right portion. The laboratory findings pointed to a prostatic carcinoma. Bone X-rays were strongly suggestive of metastatic tumour. The histological examination of the orbital tumour showed prostatic tumour cells.

  12. 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

  13. Expression of ERG Protein and TMRPSS2-ERG Fusion in Prostatic Carcinoma in Egyptian Patients

    Directory of Open Access Journals (Sweden)

    Ahmed Abdel-Hady

    2017-03-01

    CONCLUSION: Our findings emphasise that only malignant and pre-malignant cells and not benign cells from the prostate stain positive. ERG expression may offer a simpler, accurate and less costly alternative for evaluation of ERG fusion status in PCa.

  14. Tetranucleotide repeat polymorphism at the human prostatic acid phosphatase (ACPP) gene

    Energy Technology Data Exchange (ETDEWEB)

    Polymeropoulos, M H; Xiao, Hong; Rath, D S; Merril, C R [National Inst. of Mental Health Neuroscience Center, Washington, DC (United States)

    1991-09-11

    The polymorphic (AAAT){sub n} repeat begins at base pair 2342 of the human prostatic acid phosphatase gene on chromosome 3q21-qter. The polymorphism can be typed using the polymerase chain reaction (PCR) as described previously. The predicted length of the amplified sequence was 275 bp. Co-dominant segregation was observed in two informative families. The human prostatic acid phosphatase gene has been assigned to chromosome 3q21-qter.

  15. Human Papilloma Virus and Esophageal Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Hayedeh Haeri

    2013-04-01

    Full Text Available Human papilloma virus (HPV has been suggested as an etiology of esophageal squamous cell carcinoma (SCC. The aim of this study was to investigate the prevalence of HPV infection in esophageal SCCs in our region with strict contamination control to prevent false positive results. Thirty cases of esophageal squamous cell carcinomas were chosen by simple random selection in a period of two years. PCR for target sequence of HPV L1 gene was performed on nucleic acid extracted from samples by means of GP5+/GP6+ primers. All tissue samples in both case and control groups were negative for HPV-DNA. Although the number of cases in this study was limited, the contribution of HPV in substantial number of esophageal SCCs in our region is unlikely.

  16. Human papilloma virus and esophageal squamous cell carcinoma.

    Directory of Open Access Journals (Sweden)

    Hayedeh Haeri

    2014-03-01

    Full Text Available Human papillomavirus (HPV has also been suggested as an etiology of esophageal squamous cell carcinoma (SCC. The aim of this study was to investigate the prevalence of HPV infection in esophageal SCCs in our region with strict contamination control to prevent false positive results. Thirty cases of esophageal squamous cell carcinomas were chosen by simple random selection in a period of two years. PCR for target sequence of HPV L1 gene was performed on nucleic acid extracted from samples by means of GP5+/GP6+ primers. All tissue samples in both case and control groups were negative for HPV-DNA. Although the number of cases in this study was limited, the contribution of HPV in the substantial number of esophageal SCCs in our region is unlikely.

  17. An Embryonic Growth Pathway is Reactivated in Human Prostate Cancer

    National Research Council Canada - National Science Library

    Bushman, Wade

    2005-01-01

    .... This research postulates that prostate cancer cells commandeer this normal epithelial-mesenchymal signaling pathway to recruit stromal cells to support abnormal tumor growth and tests the hypothesis...

  18. An Embryonic Growth Pathway is Reactivated in Human Prostate Cancer

    National Research Council Canada - National Science Library

    Bushman, Wade

    2003-01-01

    .... This research postulates that prostate cancer cells commandeer this normal epithelial-mesenchymal signaling pathway to recruit stromal cells to support abnormal tumor growth and tests the hypothesis...

  19. 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.

  20. Plasma membrane proteomics of human embryonic stem cells and human embryonal carcinoma cells.

    NARCIS (Netherlands)

    Dormeyer, W.; van Hoof, D.; Braam, S.R.; Heck, A.J.R.; Mummery, C.L.; Krijgsveld, J.

    2008-01-01

    Human embryonic stem cells (hESCs) are of immense interest in regenerative medicine as they can self-renew indefinitely and can give rise to any adult cell type. Human embryonal carcinoma cells (hECCs) are the malignant counterparts of hESCs found in testis tumors. hESCs that have acquired

  1. Snail regulates cell survival and inhibits cellular senescence in human metastatic prostate cancer cell lines.

    Science.gov (United States)

    Emadi Baygi, Modjtaba; Soheili, Zahra Soheila; Schmitz, Ingo; Sameie, Shahram; Schulz, Wolfgang A

    2010-12-01

    The epithelial-mesenchymal transition (EMT) is regarded as an important step in cancer metastasis. Snail, a master regulator of EMT, has been recently proposed to act additionally as a cell survival factor and inducer of motility. We have investigated the function of Snail (SNAI1) in prostate cancer cells by downregulating its expression via short (21-mer) interfering RNA (siRNA) and measuring the consequences on EMT markers, cell viability, death, cell cycle, senescence, attachment, and invasivity. Of eight carcinoma cell lines, the prostate carcinoma cell lines LNCaP and PC-3 showed the highest and moderate expression of SNAI1 mRNA, respectively, as measured by quantitative RT-PCR. Long-term knockdown of Snail induced a severe decline in cell numbers in LNCaP and PC-3 and caspase activity was accordingly enhanced in both cell lines. In addition, suppression of Snail expression induced senescence in LNCaP cells. SNAI1-siRNA-treated cells did not tolerate detachment from the extracellular matrix, probably due to downregulation of integrin α6. Expression of E-cadherin, vimentin, and fibronectin was also affected. Invasiveness of PC-3 cells was not significantly diminished by Snail knockdown. Our data suggest that Snail acts primarily as a survival factor and inhibitor of cellular senescence in prostate cancer cell lines. We therefore propose that Snail can act as early driver of prostate cancer progression.

  2. Isorhynchophylline, a Potent Plant Alkaloid, Induces Apoptotic and Anti-Metastatic Effects in Human Hepatocellular Carcinoma Cells through the Modulation of Diverse Cell Signaling Cascades.

    Science.gov (United States)

    Lee, Hanwool; Baek, Seung Ho; Lee, Jong Hyun; Kim, Chulwon; Ko, Jeong-Hyeon; Lee, Seok-Geun; Chinnathambi, Arunachalam; Alharbi, Sulaiman Ali; Yang, Woong Mo; Um, Jae-Young; Sethi, Gautam; Ahn, Kwang Seok

    2017-05-19

    Isorhynchophylline (Rhy) is an active pharmacological component of Uncaria rhynchophylla that has been reported previously to exert significant antihypertensive and neuroprotective effects. However, very little is known about its potential anti-cancer activities. This study was carried out to evaluate the anticancer effects of Rhy against various human carcinoma cell lines. We found that Rhy exhibited substantial cytotoxic effect against human hepatocellular carcinoma HepG2 cells when compared with other human carcinoma cell lines including those of lung, pancreas, prostate, head and neck, breast, multiple myeloma, brain and renal cell carcinoma. Rhy induced apoptosis as characterized by accumulation of cells in sub G1 phase; positive Annexin V binding; activation of caspase-8, -9, and -3; and cleavage of PARP (poly-ADP ribose polymerase). This effect of Rhy correlated with the down-regulation of various proteins that mediated cell proliferation, cell survival, metastasis, and angiogenesis. Moreover, cell proliferation, migration, and constitutive CXCR4 (C-X-C chemokine receptor type 4), MMP-9 (Matrix metallopeptidase-9), and MMP-2 expression were inhibited upon Rhy treatment. We further investigated the effect of Rhy on the oncogenic cell signaling cascades through phospho-kinase array profiling assay. Rhy was found to abrogate phospho-p38, ERK, JNK, CREB, c-Jun, Akt, and STAT3 signals, but interestingly enhanced phospho-p53 signal. Overall, our results indicate, for the first time, that Rhy could exert anticancer and anti-metastatic effects through regulation of multiple signaling cascades in hepatocellular carcinoma cells.

  3. Prophylactic irradiation of the male mammary gland - prevention of gynaecomastia as caused by endocrine treatment of carcinomas of the prostate

    International Nuclear Information System (INIS)

    Eggerath, E.M.

    1983-01-01

    During the period between 1975 and 1980 bilateral irradiation of the mammary glands was carried out in a total of 72 bearers of carcinomas of the prostate that had previously been confirmed on a histological basis. In no less than 35 (90%) out of the 39 patients where radiotherapy was started prior to the beginning of endocrine treatment the follow-up checks revealed a prevention or suppression of gynaecomastia as a result of radiation. The effectiveness of this treatment is described in the literature as being in the order 81% and its beneficial influences are confirmed by the data of our study. If gynaecomastia has already become established, radiotherapy holds out little promise of success and a relief of the associated discomfort is the best to be expected here. (orig./MG) [de

  4. Expression of biomarkers modulating prostate cancer angiogenesis: Differential expression of annexin II in prostate carcinomas from India and USA

    Directory of Open Access Journals (Sweden)

    Dinda Amit K

    2003-10-01

    Full Text Available Abstract Background Prostate cancer (PCa incidences vary with genetic, geographical and ethnic dietary background of patients while angiogenesis is modulated through exquisite interplay of tumor-stromal interactions of biological macromolecules. We hypothesized that comprehensive analysis of four biomarkers modulating angiogenesis in PCa progression in two diverse populations might explain the variance in the incidence rates. Results Immunohistochemical analysis of 42 PCa biopsies reveals that though Anx-II expression is lost in both the Indian and American population with Gleason scores (GS ranging between 6 and 10, up to 25 % of cells in the entire high grade (GS > 8 PD PCa samples from US show intense focal membrane staining for Anx-II unlike similarly graded specimens from India. Consistent with this observation, the prostate cancer cell lines PC-3, DU-145 and MDA PCa 2A, but not LNCaP-R, LNCAP-UR or MDA PCa 2B cell lines, express Anx-II. Transcriptional reactivation of Anx-II gene with Aza-dC could not entirely account for loss of Anx-II protein in primary PCa. Cyclooxygenase-2 (COX-2 was moderately expressed in most of high grade PIN and some MD PCa and surrounding stroma. COX-2 was not expressed in PD PCa (GS ~7–10, while adjacent smooth muscles cells stained weakly positive. Decorin expression was observed only in high grade PIN but not in any of the prostate cancers, atrophy or BPH while stromal areas of BPH stained intensively for DCN and decreased with advancing stages of PCa. Versican expression was weak in most of the MD PCa, moderate in all of BPH, moderately focal in PD PC, weak and focal in PIN, atrophy and adjacent stroma. Conclusions Expression of pro- and anti-angiogenic modulators changes with stage of PCa but correlates with angiogenic status. Focal membrane staining of Anx-II reappears in high grade PCa specimens only from US indicating differential expression of Anx-II. COX-2 stained stronger in American specimens

  5. Radiotherapy of intensity modulated VS conformational in the treatment of carcinoma of the prostate. A dosimetric comparison; Radioterapia de intensidad modulada VS conformacional en el tratamiento de carcinoma de prostata. Una camparacion dosimetrica

    Energy Technology Data Exchange (ETDEWEB)

    Rodriguez Martin, G.; Garcia Vicente, F.; Zapatero Laborda, A.; Bermudez Luna, R.; Roch Gonzalez, M.; Perez Gonzalez, L.; Torres Escobar, J. J.

    2013-07-01

    The intensity modulated (IMRT) radiation therapy is a technique of high conformation which, by its nature, has as one of its main directions prostate cancer radiotherapy treatment. The purpose of this work is presents results of the dosimetric indicators collected in our hospital a number of patients of carcinoma of the prostate with standard three-dimensional Conformal technique (3D-CRT) and IMRT. Aims to demonstrate and quantify with a statistical methodology that, establishing an adequate Protocol of IMRT, significant reductions in risk organ doses can be obtained by keeping the same prescription to the white volume. (Author)

  6. Non-THC cannabinoids inhibit prostate carcinoma growth in vitro and in vivo: pro-apoptotic effects and underlying mechanisms.

    Science.gov (United States)

    De Petrocellis, Luciano; Ligresti, Alessia; Schiano Moriello, Aniello; Iappelli, Mariagrazia; Verde, Roberta; Stott, Colin G; Cristino, Luigia; Orlando, Pierangelo; Di Marzo, Vincenzo

    2013-01-01

    Cannabinoid receptor activation induces prostate carcinoma cell (PCC) apoptosis, but cannabinoids other than Δ(9) -tetrahydrocannabinol (THC), which lack potency at cannabinoid receptors, have not been investigated. Some of these compounds antagonize transient receptor potential melastatin type-8 (TRPM8) channels, the expression of which is necessary for androgen receptor (AR)-dependent PCC survival. We tested pure cannabinoids and extracts from Cannabis strains enriched in particular cannabinoids (BDS), on AR-positive (LNCaP and 22RV1) and -negative (DU-145 and PC-3) cells, by evaluating cell viability (MTT test), cell cycle arrest and apoptosis induction, by FACS scans, caspase 3/7 assays, DNA fragmentation and TUNEL, and size of xenograft tumours induced by LNCaP and DU-145 cells. Cannabidiol (CBD) significantly inhibited cell viability. Other compounds became effective in cells deprived of serum for 24 h. Several BDS were more potent than the pure compounds in the presence of serum. CBD-BDS (i.p.) potentiated the effects of bicalutamide and docetaxel against LNCaP and DU-145 xenograft tumours and, given alone, reduced LNCaP xenograft size. CBD (1-10 µM) induced apoptosis and induced markers of intrinsic apoptotic pathways (PUMA and CHOP expression and intracellular Ca(2+)). In LNCaP cells, the pro-apoptotic effect of CBD was only partly due to TRPM8 antagonism and was accompanied by down-regulation of AR, p53 activation and elevation of reactive oxygen species. LNCaP cells differentiated to androgen-insensitive neuroendocrine-like cells were more sensitive to CBD-induced apoptosis. These data support the clinical testing of CBD against prostate carcinoma. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

  7. The Isolation and Characterization of Human Prostate Cancer Stem Cells

    Science.gov (United States)

    2015-05-01

    migration as a result of PSA screening, the vast majority of prostate cancers in prostatectomy specimens today are often of low grade and stage and...epithelial interactions—I. Induction of prostatic phenotype in urothelium of testicular feminized (Tfm/y) mice. J Steroid Biochem. 1981; 14(12):1317–1324

  8. Fluorescence (FISH) and chromogenic (CISH) in situ hybridisation in prostate carcinoma cell lines: comparison and use of virtual microscopy.

    Science.gov (United States)

    Elliott, K; Hamilton, P W; Maxwell, P

    2008-01-01

    Chromogenic in situ hybridisation (CISH) has become an attractive alternative to fluorescence in situ hybridisation (FISH) due to its permanent stain which is more familiar to pathologists and because it can be viewed using light microscopy. The aim of the present study is to examine reproducibility in the assessment of abnormal chromosome number by CISH in comparison to FISH. Using three prostate cell lines--PNT1A (derived from normal epithelium), LNCAP and DU145 (derived from prostatic carcinoma), chromosomes 7 and 8 were counted in 40 nuclei in FISH preparations (x100 oil immersion) and 100 nuclei in CISH preparations (x40) by two independent observers. The CISH slides were examined using standard light microscopy and virtual microscopy. Reproducibility was examined using paired Student's t-test (PCISH. No significant differences in chromosome count were seen between the techniques. Chromosomes 7 and 8 showed disomic status for each cell line except LNCAP, which proved to be heterogeneous (disomic/aneusomic), particularly for chromosome 8. Virtual microscopy proved to be easy to use and gave no significant differences from standard light microscopy. These results support the hypothesis that there is no significant difference between FISH and CISH techniques.

  9. Human prostatic cancer cells, PC3, elaborate mitogenic activity which selectively stimulates human bone cells

    International Nuclear Information System (INIS)

    Perkel, V.S.; Mohan, S.; Herring, S.J.; Baylink, D.J.; Linkhart, T.A.

    1990-01-01

    Prostatic cancer typically produces osteoblastic metastases which are not attended by marrow fibrosis. In the present study we sought to test the hypothesis that prostatic cancer cells produce factor(s) which act selectively on human osteoblasts. Such a paracrine mechanism would explain the observed increase in osteoblasts, unaccompanied by an increase in marrow fibroblasts. To test this hypothesis we investigated the mitogenic activity released by the human prostatic tumor cell line, PC3. PC3 cells have been reported previously to produce mitogenic activity for cells that was relatively specific for rat osteoblasts compared to rat fibroblasts. However, the effects of this activity on human cells has not been examined previously. PC3-conditioned medium (CM) (5-50 micrograms CM protein/ml) stimulated human osteoblast proliferation by 200-950% yet did not stimulate human fibroblast proliferation ([3H]thymidine incorporation). PC3 CM also increased cell numbers in human osteoblast but not fibroblast cell cultures. To determine whether the osteoblast-specific mitogenic activity could be attributed to known bone growth factors, specific assays for these growth factors were performed. PC3 CM contained 10 pg insulin-like growth factor (IGF) I, less than 2 pg IGF II, 54 pg basic fibroblast growth factor, and 16 pg transforming growth factor beta/microgram CM protein. None of these growth factors alone or in combination could account for the observed osteoblast-specific PC3 cell-derived mitogenic activity. Furthermore, when 5 micrograms/ml PC3 CM was tested in combination with maximally effective concentrations of either basic fibroblast growth factor, IGF I, IGF II, or transforming growth factor beta, it produced an additive effect suggesting that PC3 CM stimulates osteoblast proliferation by a mechanism independent of these bone mitogens

  10. Conversion of 3H-testosterone to dihydrotestosterone in human hypertrophic prostatic tissue

    International Nuclear Information System (INIS)

    Baranowska, B.; Zgliczynski

    1979-01-01

    The aim of the study was to develop a simple method for the determination of the conversion of testosterone to 5α-dihydrotestosterone (5α-DHT) after incubation of human hypertrophic prostatic tissue with 3 H-testosterone. The mean conversion rate of 3 H-testosterone to 5α-DHT in hypertrophic prostatic tissue was found to be higher than in normal and carcinomatous tissue. The results indicate that androgen metabolism in the hypertrophic prostatic gland is enhanced. (orig.) [de

  11. Conversion of /sup 3/H-testosterone to dihydrotestosterone in human hypertrophic prostatic tissue

    Energy Technology Data Exchange (ETDEWEB)

    Baranowska, B; Zgliczynski, [Centre of Postgraduate Medical Education, Warsaw (Poland). Clinic of Endocrinology

    1979-12-01

    The aim of the study was to develop a simple method for the determination of the conversion of testosterone to 5..cap alpha..-dihydrotestosterone (5..cap alpha..-DHT) after incubation of human hypertrophic prostatic tissue with /sup 3/H-testosterone. The mean conversion rate of /sup 3/H-testosterone to 5..cap alpha..-DHT in hypertrophic prostatic tissue was found to be higher than in normal and carcinomatous tissue. The results indicate that androgen metabolism in the hypertrophic prostatic gland is enhanced.

  12. Possible application of tumor marker radioimmunoassay in diagnosis of testicular and prostatic carcinomas

    Energy Technology Data Exchange (ETDEWEB)

    Kausitz, J

    1988-10-01

    Determinations of alpha fetoprotein and chorionic gonadotropin levels by radioimmunoassay in 340 patients with germ cell tumors of the testes have confirmed that tumor markers are suitable prognostic parameters, facilitate assessment of the clinical stage, are sensitive parameters of the efficacy of chemotherapy and enable early detection of relapses. In a group of 71 patients with prostate cancer, systematic determination of prostate specific antigen levels proved to be a reliable method of monitoring and a sensitive method of detecting remote metastases. (author). 5 figs., 13 tabs., 23 refs.

  13. The role of nuclear medicine diagnostic technology in prediction of prostate carcinoma in Sudanese individuals

    International Nuclear Information System (INIS)

    Auhamed, H. S. H.

    2011-03-01

    Prostate cancer is one of the most common malignancies worldwide, with an estimated 40,000 new case diagnosed annually. Insulin-like growth factor-1 (IGF-1) is important to the growth and function of prostate gland, but its incidence and mortality have been associated with increased circulating IGF-1 levels and this causes a high risk to the prostate gland cells in development of cancer. To fulfill these hypotheses we do a prospective study of prostate gland in Sudanese men at the Physicians Urology Health department in Khartoum State hospitals (2004-2009) to assayed circulating levels of IGF-1, PSA, E2 and testosterone among 110 known cases of prostate cancer (Ca.P), 110 benign prostate hyperplasia (BPH) and 110 matched controls subjects (CG). Using non isotopic enzyme methods of Enzyme Linked Sorbent Assay (ELISA), kits produced from Germany DRG company and sensitive micro plate reader and SPSS and ANOVAS one way statistic programme to analysis the data. So when we compare these three groups with ages, types of cancers, and the IGF-1, PSA, E2 and testosterone parameters, there was significant (p=0.04) and the associations between these hormones parameters was (p=0.01). Also when we compare the IGF-1 levels at 95% of upper quartiles of confidence interval in CG group (180ng/ml) with the IGF-1 levels at 25% of lower quartiles of confidence interval in the (Ca.P) and (BPH) group (165ng/ml) and (134ng/ml) respectively, the CG-IGF-1 group was higher than (Ca.P and BPH) groups at these percentiles, with associations between them of (p=0.05). This apparent discrepancy of the risk fallen to the normal (CG) group can be explained using the risk ratio (RR), odds ratio (OR) and confidence interval (CI) with Ca.P patients groups, (OR 2.4, 95% CI 0.71-7.9) (RR 2.3, 95% C10.7-7.1), showing that the risk fallen to the (CG) group was ten (10) times higher than the known cancer patients of the Ca.P, with significant of (p=0.05). So there were associations between high circulating

  14. LAT1 acts as a crucial transporter of amino acids in human thymic carcinoma cells

    Directory of Open Access Journals (Sweden)

    Keitaro Hayashi

    2016-11-01

    Full Text Available L-type amino acid transporter 1 (LAT1, SLC7A5 incorporates essential amino acids into cells. Recent studies have shown that LAT1 is a predominant transporter in various human cancers. However, the function of LAT1 in thymic carcinoma remains unknown. Here we demonstrate that LAT1 is a critical transporter for human thymic carcinoma cells. LAT1 was strongly expressed in human thymic carcinoma tissues. LAT1-specific inhibitor significantly suppressed leucine uptake and growth of Ty82 human thymic carcinoma cell lines, suggesting that thymic carcinoma takes advantage of LAT1 as a quality transporter and that LAT1-specific inhibitor might be clinically beneficial in therapy for thymic carcinoma.

  15. The diet as a cause of human prostate cancer.

    Science.gov (United States)

    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

  16. Incidence and mortality of prostate cancer and their relationship with the Human Development Index worldwide

    OpenAIRE

    Hassanipour-Azgomi, S.; Mohammadian-Hafshejani, Abdollah; Ghoncheh, Mahshid; Towhidi, Farhad; Jamehshorani, Saeid; Salehiniya, Hamid

    2016-01-01

    Background: The aim of this study was to evaluate the incidence and mortality of prostate cancer and their relationship with the Human Development Index (HDI) and its components in Asia in 2012. Methods: This study was an ecological study conducted based on the GLOBOCAN project of the World Health Organization. The correlation between standardized incidence rate (SIR) and standardized mortality rate (SMR) of prostate cancer with HDI and its components was assessed using SPSS Inc Version 18...

  17. Exogenous fatty acid binding protein 4 promotes human prostate cancer cell progression.

    Science.gov (United States)

    Uehara, Hisanori; Takahashi, Tetsuyuki; Oha, Mina; Ogawa, Hirohisa; Izumi, Keisuke

    2014-12-01

    Epidemiologic studies have found that obesity is associated with malignant grade and mortality in prostate cancer. Several adipokines have been implicated as putative mediating factors between obesity and prostate cancer. Fatty acid binding protein 4 (FABP4), a member of the cytoplasmic fatty acid binding protein multigene family, was recently identified as a novel adipokine. Although FABP4 is released from adipocytes and mean circulating concentrations of FABP4 are linked with obesity, effects of exogenous FABP4 on prostate cancer progression are unclear. In this study, we examined the effects of exogenous FABP4 on human prostate cancer cell progression. FABP4 treatment promoted serum-induced prostate cancer cell invasion in vitro. Furthermore, oleic acid promoted prostate cancer cell invasion only if FABP4 was present in the medium. These promoting effects were reduced by FABP4 inhibitor, which inhibits FABP4 binding to fatty acids. Immunostaining for FABP4 showed that exogenous FABP4 was taken up into DU145 cells in three-dimensional culture. In mice, treatment with FABP4 inhibitor reduced the subcutaneous growth and lung metastasis of prostate cancer cells. Immunohistochemical analysis showed that the number of apoptotic cells, positive for cleaved caspase-3 and cleaved PARP, was increased in subcutaneous tumors of FABP4 inhibitor-treated mice, as compared with control mice. These results suggest that exogenous FABP4 might promote human prostate cancer cell progression by binding with fatty acids. Additionally, exogenous FABP4 activated the PI3K/Akt pathway, independently of binding to fatty acids. Thus, FABP4 might be a key molecule to understand the mechanisms underlying the obesity-prostate cancer progression link. © 2014 UICC.

  18. Rare ADAR and RNASEH2B variants and a type I interferon signature in glioma and prostate carcinoma risk and tumorigenesis.

    Science.gov (United States)

    Beyer, Ulrike; Brand, Frank; Martens, Helge; Weder, Julia; Christians, Arne; Elyan, Natalie; Hentschel, Bettina; Westphal, Manfred; Schackert, Gabriele; Pietsch, Torsten; Hong, Bujung; Krauss, Joachim K; Samii, Amir; Raab, Peter; Das, Anibh; Dumitru, Claudia A; Sandalcioglu, I Erol; Hakenberg, Oliver W; Erbersdobler, Andreas; Lehmann, Ulrich; Reifenberger, Guido; Weller, Michael; Reijns, Martin A M; Preller, Matthias; Wiese, Bettina; Hartmann, Christian; Weber, Ruthild G

    2017-12-01

    In search of novel germline alterations predisposing to tumors, in particular to gliomas, we studied a family with two brothers affected by anaplastic gliomas, and their father and paternal great-uncle diagnosed with prostate carcinoma. In this family, whole-exome sequencing yielded rare, simultaneously heterozygous variants in the Aicardi-Goutières syndrome (AGS) genes ADAR and RNASEH2B co-segregating with the tumor phenotype. AGS is a genetically induced inflammatory disease particularly of the brain, which has not been associated with a consistently increased cancer risk to date. By targeted sequencing, we identified novel ADAR and RNASEH2B variants, and a 3- to 17-fold frequency increase of the AGS mutations ADAR,c.577C>G;p.(P193A) and RNASEH2B,c.529G>A;p.(A177T) in the germline of familial glioma patients as well as in test and validation cohorts of glioblastomas and prostate carcinomas versus ethnicity-matched controls, whereby rare RNASEH2B variants were significantly more frequent in familial glioma patients. Tumors with ADAR or RNASEH2B variants recapitulated features of AGS, such as calcification and increased type I interferon expression. Patients carrying ADAR or RNASEH2B variants showed upregulation of interferon-stimulated gene (ISG) transcripts in peripheral blood as seen in AGS. An increased ISG expression was also induced by ADAR and RNASEH2B variants in tumor cells and was blocked by the JAK inhibitor Ruxolitinib. Our data implicate rare variants in the AGS genes ADAR and RNASEH2B and a type I interferon signature in glioma and prostate carcinoma risk and tumorigenesis, consistent with a genetic basis underlying inflammation-driven malignant transformation in glioma and prostate carcinoma development.

  19. A phase III trial of zoladex and flutamide versus orchiectomy in the treatment of patients with advanced carcinoma of the prostate

    DEFF Research Database (Denmark)

    Iversen, P; Christensen, M G; Friis, E

    1990-01-01

    In a multicenter Phase III trial 264 patients with advanced prostatic cancer were randomized to either bilateral orchiectomy or treatment with zoladex supplemented by flutamide. Presently, median follow-up time is 30 months. A small difference in objective response was recorded in favor of the co......In a multicenter Phase III trial 264 patients with advanced prostatic cancer were randomized to either bilateral orchiectomy or treatment with zoladex supplemented by flutamide. Presently, median follow-up time is 30 months. A small difference in objective response was recorded in favor...... of the combination therapy, whereas no statistically significant difference was found in subjective response to therapy, time to progression, and overall survival. Adverse effects were more commonly encountered in the pharmacologically treated patients. It is concluded that the combination of zoladex plus flutamide...... is not clinically superior to orchiectomy in the treatment of patients with advanced carcinoma of the prostate....

  20. Taxifolin enhances andrographolide-induced mitotic arrest and apoptosis in human prostate cancer cells via spindle assembly checkpoint activation.

    Directory of Open Access Journals (Sweden)

    Zhong Rong Zhang

    Full Text Available Andrographolide (Andro suppresses proliferation and triggers apoptosis in many types of cancer cells. Taxifolin (Taxi has been proposed to prevent cancer development similar to other dietary flavonoids. In the present study, the cytotoxic and apoptotic effects of the addition of Andro alone and Andro and Taxi together on human prostate carcinoma DU145 cells were assessed. Andro inhibited prostate cancer cell proliferation by mitotic arrest and activation of the intrinsic apoptotic pathway. Although the effect of Taxi alone on DU145 cell proliferation was not significant, the combined use of Taxi with Andro significantly potentiated the anti-proliferative effect of increased mitotic arrest and apoptosis by enhancing the cleavage of poly(ADP-ribose polymerase, and caspases-7 and -9. Andro together with Taxi enhanced microtubule polymerization in vitro, and they induced the formation of twisted and elongated spindles in the cancer cells, thus leading to mitotic arrest. In addition, we showed that depletion of MAD2, a component in the spindle assembly checkpoint (SAC, alleviated the mitotic block induced by the two compounds, suggesting that they trigger mitotic arrest by SAC activation. This study suggests that the anti-cancer activity of Andro can be significantly enhanced in combination with Taxi by disrupting microtubule dynamics and activating the SAC.

  1. Taxifolin Enhances Andrographolide-Induced Mitotic Arrest and Apoptosis in Human Prostate Cancer Cells via Spindle Assembly Checkpoint Activation

    Science.gov (United States)

    Wong, Matthew Man-Kin; Chiu, Sung-Kay; Cheung, Hon-Yeung

    2013-01-01

    Andrographolide (Andro) suppresses proliferation and triggers apoptosis in many types of cancer cells. Taxifolin (Taxi) has been proposed to prevent cancer development similar to other dietary flavonoids. In the present study, the cytotoxic and apoptotic effects of the addition of Andro alone and Andro and Taxi together on human prostate carcinoma DU145 cells were assessed. Andro inhibited prostate cancer cell proliferation by mitotic arrest and activation of the intrinsic apoptotic pathway. Although the effect of Taxi alone on DU145 cell proliferation was not significant, the combined use of Taxi with Andro significantly potentiated the anti-proliferative effect of increased mitotic arrest and apoptosis by enhancing the cleavage of poly(ADP-ribose) polymerase, and caspases-7 and -9. Andro together with Taxi enhanced microtubule polymerization in vitro, and they induced the formation of twisted and elongated spindles in the cancer cells, thus leading to mitotic arrest. In addition, we showed that depletion of MAD2, a component in the spindle assembly checkpoint (SAC), alleviated the mitotic block induced by the two compounds, suggesting that they trigger mitotic arrest by SAC activation. This study suggests that the anti-cancer activity of Andro can be significantly enhanced in combination with Taxi by disrupting microtubule dynamics and activating the SAC. PMID:23382917

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

    Directory of Open Access Journals (Sweden)

    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.

  3. Carcinoma-specific Ulex europaeus agglutinin-I binding glycoproteins of human colorectal carcinoma and its relation to carcinoembryonic antigen.

    Science.gov (United States)

    Matsushita, Y; Yonezawa, S; Nakamura, T; Shimizu, S; Ozawa, M; Muramatsu, T; Sato, E

    1985-08-01

    Glycoproteins binding to Ulex europaeus agglutinin-I (UEA-I) lectin, which recognizes the terminal alpha-L-fucose residue, were analyzed in 18 cases of human colorectal carcinoma by sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by the Western blotting method. In the distal large bowel (descending and sigmoid colon and rectum), high-molecular-weight glycoproteins binding to UEA-I existed in carcinoma tissue but not in normal mucosa. In the proximal large bowel (ascending and transverse colon), high-molecular-weight glycoproteins binding to UEA-I were found both in normal mucosa and in carcinoma tissue, whereas those from the carcinoma tissue had an apparently lower molecular weight as compared to the weight of those from the normal mucosa. Thus there is a biochemical difference in UEA-I binding glycoproteins between the normal mucosa and the carcinoma tissue, although in our previous histochemical study no difference was observed in UEA-I binding glycoproteins of the proximal large bowel between the carcinoma tissue and the normal mucosa. Furthermore, carcinoembryonic antigen from the carcinoma tissue was found to have the same electrophoretical mobility as the UEA-I binding glycoproteins.

  4. Hypofractionated stereotactic body radiotherapy in low- and intermediate-risk prostate carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hun Jung; Phak, Jeong Hoon; Kim, Woo Chul [Dept. of Radiation Oncology, Inha University Hospital, Inha University School of Medicine, Incheon (Korea, Republic of)

    2016-12-15

    Stereotactic body radiotherapy (SBRT) takes advantage of low α/β ratio of prostate cancer to deliver a large dose in few fractions. We examined clinical outcomes of SBRT using CyberKnife for the treatment of low- and intermediate-risk prostate cancer. This study was based on a retrospective analysis of the 33 patients treated with SBRT using CyberKnife for localized prostate cancer (27.3% in low-risk and 72.7% in intermediate-risk). Total dose of 36.25 Gy in 5 fractions of 7.25 Gy were administered. The acute and late toxicities were recorded using the Radiation Therapy Oncology Group scale. Prostate-specific antigen (PSA) response was monitored. Thirty-three patients with a median 51 months (range, 6 to 71 months) follow-up were analyzed. There was no biochemical failure. Median PSA nadir was 0.27 ng/mL at median 33 months and PSA bounce occurred in 30.3% (n = 10) of patients at median at median 10.5 months after SBRT. No grade 3 acute toxicity was noted. The 18.2% of the patients had acute grade 2 genitourinary (GU) toxicities and 21.2% had acute grade 2 gastrointestinal (GI) toxicities. After follow-up of 2 months, most complications had returned to baseline. There was no grade 3 late GU and GI toxicity. Our experience with SBRT using CyberKnife in low- and intermediate-risk prostate cancer demonstrates favorable efficacy and toxicity. Further studies with more patients and longer follow-up duration are required.

  5. Molecular Signaling Pathways Mediating Osteoclastogenesis Induced by Prostate Cancer Cells

    International Nuclear Information System (INIS)

    Rafiei, Shahrzad; Komarova, Svetlana V

    2013-01-01

    Advanced prostate cancer commonly metastasizes to bone leading to osteoblastic and osteolytic lesions. Although an osteolytic component governed by activation of bone resorbing osteoclasts is prominent in prostate cancer metastasis, the molecular mechanisms of prostate cancer-induced osteoclastogenesis are not well-understood. We studied the effect of soluble mediators released from human prostate carcinoma cells on osteoclast formation from mouse bone marrow and RAW 264.7 monocytes. Soluble factors released from human prostate carcinoma cells significantly increased viability of naïve bone marrow monocytes, as well as osteoclastogenesis from precursors primed with receptor activator of nuclear factor κ-B ligand (RANKL). The prostate cancer-induced osteoclastogenesis was not mediated by RANKL as it was not inhibited by osteoprotegerin (OPG). However inhibition of TGFβ receptor I (TβRI), or macrophage-colony stimulating factor (MCSF) resulted in attenuation of prostate cancer-induced osteoclastogenesis. We characterized the signaling pathways induced in osteoclast precursors by soluble mediators released from human prostate carcinoma cells. Prostate cancer factors increased basal calcium levels and calcium fluctuations, induced nuclear localization of nuclear factor of activated t-cells (NFAT)c1, and activated prolonged phosphorylation of ERK1/2 in RANKL-primed osteoclast precursors. Inhibition of calcium signaling, NFATc1 activation, and ERK1/2 phosphorylation significantly reduced the ability of prostate cancer mediators to stimulate osteoclastogenesis. This study reveals the molecular mechanisms underlying the direct osteoclastogenic effect of prostate cancer derived factors, which may be beneficial in developing novel osteoclast-targeting therapeutic approaches

  6. Expression and role of the angiotensin II AT2 receptor in human prostate tissue: in search of a new therapeutic option for prostate cancer.

    Science.gov (United States)

    Guimond, Marie-Odile; Battista, Marie-Claude; Nikjouitavabi, Fatemeh; Carmel, Maude; Barres, Véronique; Doueik, Alexandre A; Fazli, Ladan; Gleave, Martin; Sabbagh, Robert; Gallo-Payet, Nicole

    2013-07-01

    Evidence shows that angiotensin II type 1 receptor (AT1R) blockers may be associated with improved outcome in prostate cancer patients. It has been proposed that part of this effect could be due to angiotensin II type 2 receptor (AT2R) activation, the only active angiotensin II receptor in this situation. This study aimed to characterize the localization and expression of AT2R in prostate tissues and to assess its role on cell morphology and number in prostatic epithelial cells in primary culture. AT2R and its AT2R-interacting protein (ATIP) expression were assessed on non-tumoral and tumoral human prostate using tissue microarray immunohistochemistry, binding assay, and Western blotting. AT2R effect on cell number was measured in primary cultures of epithelial cells from non-tumoral human prostate. AT2R was localized at the level of the acinar epithelial layer and its expression decreased in cancers with a Gleason score 6 or higher. In contrast, ATIP expression increased with cancer progression. Treatment of primary cell cultures from non-tumoral prostate tissues with C21/M024, a selective AT2R agonist, alone or in co-incubation with losartan, an AT1R antagonist, significantly decreased cell number compared to untreated cells. AT2R and ATIP are present in non-tumoral human prostate tissues and differentially regulated according to Gleason score. The decrease in non-tumoral prostate cell number upon selective AT2R stimulation suggests that AT2R may have a protective role against prostate cancer development. Treatment with a selective AT2R agonist could represent a new approach for prostate cancer prevention or for patients on active surveillance. Copyright © 2013 Wiley Periodicals, Inc.

  7. Calculated organ doses using Monte Carlo simulations in a reference male phantom undergoing HDR brachytherapy applied to localized prostate carcinoma

    International Nuclear Information System (INIS)

    Candela-Juan, Cristian; Perez-Calatayud, Jose; Ballester, Facundo; Rivard, Mark J.

    2013-01-01

    Purpose: The aim of this study was to obtain equivalent doses in radiosensitive organs (aside from the bladder and rectum) when applying high-dose-rate (HDR) brachytherapy to a localized prostate carcinoma using 60 Co or 192 Ir sources. These data are compared with results in a water phantom and with expected values in an infinite water medium. A comparison with reported values from proton therapy and intensity-modulated radiation therapy (IMRT) is also provided. Methods: Monte Carlo simulations in Geant4 were performed using a voxelized phantom described in International Commission on Radiological Protection (ICRP) Publication 110, which reproduces masses and shapes from an adult reference man defined in ICRP Publication 89. Point sources of 60 Co or 192 Ir with photon energy spectra corresponding to those exiting their capsules were placed in the center of the prostate, and equivalent doses per clinical absorbed dose in this target organ were obtained in several radiosensitive organs. Values were corrected to account for clinical circumstances with the source located at various positions with differing dwell times throughout the prostate. This was repeated for a homogeneous water phantom. Results: For the nearest organs considered (bladder, rectum, testes, small intestine, and colon), equivalent doses given by 60 Co source were smaller (8%–19%) than from 192 Ir. However, as the distance increases, the more penetrating gamma rays produced by 60 Co deliver higher organ equivalent doses. The overall result is that effective dose per clinical absorbed dose from a 60 Co source (11.1 mSv/Gy) is lower than from a 192 Ir source (13.2 mSv/Gy). On the other hand, equivalent doses were the same in the tissue and the homogeneous water phantom for those soft tissues closer to the prostate than about 30 cm. As the distance increased, the differences of photoelectric effect in water and soft tissue, and appearance of other materials such as air, bone, or lungs, produced

  8. p16 expression is not associated with human papillomavirus in urinary bladder squamous cell carcinoma.

    Science.gov (United States)

    Alexander, Riley E; Hu, Yingchuan; Kum, Jennifer B; Montironi, Rodolfo; Lopez-Beltran, Antonio; Maclennan, Gregory T; Idrees, Muhammad T; Emerson, Robert E; Ulbright, Thomas M; Grignon, David G; Eble, John N; Cheng, Liang

    2012-11-01

    Squamous cell carcinoma of the urinary bladder is unusual and of unknown etiology. There is a well-established association between human papillomavirus (HPV) infection and the development of cervical and head/neck squamous cell carcinomas. However, the role of HPV in the pathogenesis of squamous cell carcinoma of the urinary bladder is uncertain. The purposes of this study were to investigate the possible role of HPV in the development of squamous cell carcinoma of the urinary bladder and to determine if p16 expression could serve as a surrogate marker for HPV in this malignancy. In all, 42 cases of squamous cell carcinoma of the urinary bladder and 27 cases of urothelial carcinoma with squamous differentiation were investigated. HPV infection was analyzed by both in situ hybridization at the DNA level and immunohistochemistry at the protein level. p16 protein expression was analyzed by immunohistochemistry. HPV DNA and protein were not detected in 42 cases of squamous cell carcinoma (0%, 0/42) or 27 cases of urothelial carcinoma with squamous differentiation (0%, 0/15). p16 expression was detected in 13 cases (31%, 13/42) of squamous cell carcinoma and 9 cases (33%, 9/27) of urothelial carcinoma with squamous differentiation. There was no correlation between p16 expression and the presence of HPV infection in squamous cell carcinoma of the bladder or urothelial carcinoma with squamous differentiation. Our data suggest that HPV does not play a role in the development of squamous cell carcinoma of the urinary bladder or urothelial carcinoma with squamous differentiation. p16 expression should not be used as a surrogate marker for evidence of HVP infection in either squamous cell carcinoma of the urinary bladder or urothelial carcinoma with squamous differentiation as neither HVP DNA nor protein is detectable in these neoplasms.

  9. 3-Bromopyruvate induces rapid human prostate cancer cell death by affecting cell energy metabolism, GSH pool and the glyoxalase system.

    Science.gov (United States)

    Valenti, Daniela; Vacca, Rosa A; de Bari, Lidia

    2015-12-01

    3-bromopyruvate (3-BP) is an anti-tumour drug effective on hepatocellular carcinoma and other tumour cell types, which affects both glycolytic and mitochondrial targets, depleting cellular ATP pool. Here we tested 3-BP on human prostate cancer cells showing, differently from other tumour types, efficient ATP production and functional mitochondrial metabolism. We found that 3-BP rapidly induced cultured androgen-insensitive (PC-3) and androgen-responsive (LNCaP) prostate cancer cell death at low concentrations (IC(50) values of 50 and 70 μM, respectively) with a multimodal mechanism of action. In particular, 3-BP-treated PC-3 cells showed a selective, strong reduction of glyceraldeide 3-phosphate dehydrogenase activity, due to the direct interaction of the drug with the enzyme. Moreover, 3-BP strongly impaired both glutamate/malate- and succinate-dependent mitochondrial respiration, membrane potential generation and ATP synthesis, concomitant with the inhibition of respiratory chain complex I, II and ATP synthase activities. The drastic reduction of cellular ATP levels and depletion of GSH pool, associated with significant increase in cell oxidative stress, were found after 3-BP treatment of PC-3 cells. Interestingly, the activity of both glyoxalase I and II, devoted to the elimination of the cytotoxic methylglyoxal, was strongly inhibited by 3-BP. Both N-acetylcysteine and aminoguanidine, GSH precursor and methylglyoxal scavenger, respectively, prevented 3-BP-induced PC-3 cell death, showing that impaired cell antioxidant and detoxifying capacities are crucial events leading to cell death. The provided information on the multi-target cytotoxic action of 3-BP, finally leading to PC-3 cell necrosis, might be useful for future development of 3-BP as a therapeutic option for prostate cancer treatment.

  10. 5-Fluorouracil modulation of radiosensitivity in cultured human carcinoma cells

    International Nuclear Information System (INIS)

    Smalley, S.R.; Kimler, B.F.; Evans, R.G.

    1991-01-01

    We evaluated conventional pulse exposure versus continuous exposure models of 5-fluorouracil (5-FU) radiosensitization in HT-29 (human colon adenocarcinoma) and DU-145 (human prostate cancer adenocarcinoma) cell lines. Cell survival following treatment with drug and/or radiation was determined by colony formation assays. Radiation was delivered either by itself, approximately midway through a 1-hr exposure to 5-FU (10 micrograms/ml), or at various times following initiation of exposure to 5-FU (0.5 microgram/ml) present throughout the entire period of incubation. Drug concentrations were selected to approximate those achieved in vivo in humans. HT-29 cells showed a plating efficiency of 87% and similar cytotoxicity (survival reduced to 0.57-0.71) for all 5-FU conditions. The Do's of the radiation survival curves were not different for 1 hr of 5-FU exposure versus radiation alone. However, continuous exposure conditions demonstrated statistically significantly different Do's from radiation alone and pulse 5-FU exposure. DU-145 cells displayed a plating efficiency of 17% and cytotoxicities of 0.10-0.91 for the 5-FU conditions. DU-145 cells showed different radiation 5-FU interactions: 5-FU produced statistically significant changes in Do well as the differences between cell lines insofar as their radiosensitization by 5-FU underscore the caution required in extrapolating these radiobiologic models to the clinical setting

  11. Detection and localization of carcinoma within the prostate using high resolution transrectal gamma imaging (TRGI) of monoclonal antibody directed at prostate specific membrane antigen (PSMA)—Proof of concept and initial imaging results

    International Nuclear Information System (INIS)

    Franc, Benjamin L.; Cho, Steve Y.; Rosenthal, Seth A.; Cui, Yonggang; Tsui, Benjamin; Vandewalker, Kristen M.N.; Holz, Andrew L.; Poonamallee, Uday; Pomper, Martin G.; James, Ralph B.

    2013-01-01

    Purpose: Molecular imaging methods may identify primary prostate cancer foci and potentially guide biopsy and optimal management approaches. In this exploratory study, safety and first human imaging experience of a novel solid state endocavity transrectal gamma-imaging (TRGI) device was evaluated. Methods: Twelve patients received 5 ± 0.5 mCi In-111 capromab pendetide (ProstaScint ® ) intravenously and the prostate of each was imaged 4 days later transrectally using an endoluminal cadmium zinc telluride (CZT)-based compact gamma camera (ProxiScan™, Hybridyne Imaging Technologies, Inc.). Immediate and 5–7-day post imaging safety assessments were performed. In those patients with a prostate cancer diagnosis (N = 10), single photon emission computed tomography (SPECT-CT) and magnetic resonance imaging (MRI) of the pelvis were also acquired. Images were reviewed and sites of suspected cancer were localized by prostate quadrant by consensus of two nuclear medicine physicians. Pathology from TRUS biopsy, or surgical pathology following prostatectomy (N = 3) when available, served as the gold standard. Results: There were no serious adverse events associated with TRGI. No focal signal was detected in patients without a diagnosis of prostate cancer (N = 2). Of 40 quadrants evaluated in the cancer cohort (N = 10), 22 contained malignancy. In 8 of these 10 patients, the most focal site of uptake on TRGI corresponded to a prostatic quadrant with biopsy-proven malignancy. In 6 cancer-containing quadrants, TRGI was positive where SPECT-CT was negative; MRI showed a detectable abnormality in only 1 of these 6 quadrants. Qualitative image review of the planar TRGI images for prostate cancer localization was severely limited in some cases by scatter artifact within the vicinity of the prostate gland arising from physiologic urine and blood pool activity from nearby structures. Conclusions: TRGI is a safe imaging method that can potentially detect radiopharmaceutical uptake

  12. Photoaffinity labeling of the progesterone receptor from human endometrial carcinoma

    International Nuclear Information System (INIS)

    Clarke, C.L.; Satyaswaroop, P.G.

    1985-01-01

    A nude mouse model for the growth of human endometrial carcinoma and hormonal modulation of the progesterone receptor (PR) was established previously. This study describes the effect of 17 beta-estradiol and tamoxifen (TAM) on growth rate and PR concentration in a hormonally responsive human endometrial tumor (EnCa 101) grown in this experimental system and presents the first characterization of human endometrial carcinoma PR. EnCa 101 was transplanted subcutaneously into ovariectomized, BALB/c, nu/nu athymic mice and grown under 17 beta-estradiol-stimulated, TAM-stimulated, and control conditions. Both 17 beta-estradiol and TAM increased the growth rate of EnCa 101 in nude mice, and a parallel increase in the cytosol PR concentration was observed. PR was partially purified by phosphocellulose and DEAE cellulose chromatography, and the DEAE eluate was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and photoaffinity labeling with [17 alpha-methyl- 3 H]promegestone ([ 3 H]R5020). Two PR-negative tumors (EnCa K and EnCa V) were also examined in parallel. Photolabeling and sodium dodecyl sulfate-polyacrylamide gel electrophoresis of EnCa 101 grown in the presence of 17 beta-estradiol or TAM revealed incorporation of [3H]R5020 into proteins of molecular weight approximately 116,000 and 85,000. Labeled proteins of molecular weight 66,000, 45,000, and 35,000 were also observed. No incorporation of [ 3 H]R5020 was observed in EnCa 101 grown in the absence of estrogen, nor was any observed in EnCa K or EnCa V

  13. Neural protein gamma-synuclein interacting with androgen receptor promotes human prostate cancer progression

    International Nuclear Information System (INIS)

    Chen, Junyi; Jiao, Li; Xu, Chuanliang; Yu, Yongwei; Zhang, Zhensheng; Chang, Zheng; Deng, Zhen; Sun, Yinghao

    2012-01-01

    Gamma-synuclein (SNCG) has previously been demonstrated to be significantly correlated with metastatic malignancies; however, in-depth investigation of SNCG in prostate cancer is still lacking. In the present study, we evaluated the role of SNCG in prostate cancer progression and explored the underlying mechanisms. First, alteration of SNCG expression in LNCaP cell line to test the ability of SNCG on cellular properties in vitro and vivo whenever exposing with androgen or not. Subsequently, the Dual-luciferase reporter assays were performed to evaluate whether the role of SNCG in LNCaP is through AR signaling. Last, the association between SNCG and prostate cancer progression was assessed immunohistochemically using a series of human prostate tissues. Silencing SNCG by siRNA in LNCaP cells contributes to the inhibition of cellular proliferation, the induction of cell-cycle arrest at the G1 phase, the suppression of cellular migration and invasion in vitro, as well as the decrease of tumor growth in vivo with the notable exception of castrated mice. Subsequently, mechanistic studies indicated that SNCG is a novel androgen receptor (AR) coactivator. It interacts with AR and promotes prostate cancer cellular growth and proliferation by activating AR transcription in an androgen-dependent manner. Finally, immunohistochemical analysis revealed that SNCG was almost undetectable in benign or androgen-independent tissues prostate lesions. The high expression of SNCG is correlated with peripheral and lymph node invasion. Our data suggest that SNCG may serve as a biomarker for predicting human prostate cancer progression and metastasis. It also may become as a novel target for biomedical therapy in advanced prostate cancer

  14. Prostate cancer

    International Nuclear Information System (INIS)

    Bey, P.; Beckendorf, V.; Stines, J.

    2001-01-01

    Radiation therapy of prostate carcinoma with a curative intent implies to treat the whole prostate at high dose (at least 66 Gy). According to clinical stage, PSA level, Gleason's score, the clinical target volume may include seminal vesicles and less often pelvic lymph nodes. Microscopic extra-capsular extension is found in 15 to 60% of T1-T2 operated on, specially in apex tumors. On contrary, cancers developing from the transitional zone may stay limited to the prostate even with a big volume and with a high PSA level. Zonal anatomy of the prostate identifies internal prostate, including the transitional zone (5% of the prostate in young people). External prostate includes central and peripheral zones. The inferior limit of the prostate is not lower than the inferior border of the pubic symphysis. Clinical and radiological examination: ultrasonography, nuclear magnetic resonance (NMR), CT-scan identify prognostic factors as tumor volume, capsule effraction, seminal vesicles invasion and lymph node extension. The identification of the clinical target volume is now done mainly by CT-Scan which identifies prostate and seminal vesicles. NMR could be helpful to identify more precisely prostate apex. The definition of margins around the clinical target volume has to take in account daily reproducibility and organ motion and of course the maximum tolerable dose for organs at risk. (authors)

  15. Using an AMACR (P504S)/34betaE12/p63 cocktail for the detection of small focal prostate carcinoma in needle biopsy specimens.

    Science.gov (United States)

    Jiang, Zhong; Li, Cuizhen; Fischer, Andrew; Dresser, Karen; Woda, Bruce A

    2005-02-01

    We assessed the usefulness of immunohistochemical analysis with a 3-antibody cocktail (alpha-methylacyl coenzyme A racemase [AMACR, or P504S], 34betaE12, p63) and a double-chromogen reaction for detection of limited prostate cancer in 138 needle biopsy specimens, including 82 with small foci of prostatic adenocarcinoma and 56 benign prostates. When carcinoma was present, red cytoplasmic granular staining (AMACR) in the malignant glands and cells and dark brown nuclear (p63) and cytoplasmic (34betaE12) staining in basal cells of adjacent nonmalignant glands were found. Of 82 cases of small foci of prostatic adenocarcinoma, 78 (95%) expressed AMACR; all malignant glands were negative for basal cell staining. All benign glands adjacent to malignant glands were recognized easily by basal cell marker positivity and little or no AMACR expression. No benign glands were simultaneously positive for AMACR and negative for basal cell markers (specificity, 100%). There were no differences in intensity and numbers of positive glands with double-chromogen staining compared with using 1-color staining. Our results indicate that immunohistochemistry with a 3-antibody cocktail and double chromogen is a simple and easy assay that can be used as a routine test, which overcomes the problems of studying small lesions in prostate needle biopsies with multiple immunohistochemical stains.

  16. Expression profiling of human renal carcinomas with functional taxonomic analysis

    Science.gov (United States)

    2002-01-01

    Background Molecular characterization has contributed to the understanding of the inception, progression, treatment and prognosis of cancer. Nucleic acid array-based technologies extend molecular characterization of tumors to thousands of gene products. To effectively discriminate between tumor sub-types, reliable laboratory techniques and analytic methods are required. Results We derived mRNA expression profiles from 21 human tissue samples (eight normal kidneys and 13 kidney tumors) and two pooled samples using the Affymetrix GeneChip platform. A panel of ten clustering algorithms combined with four data pre-processing methods identified a consensus cluster dendrogram in 18 of 40 analyses and of these 16 used a logarithmic transformation. Within the consensus dendrogram the expression profiles of the samples grouped according to tissue type; clear cell and chromophobe carcinomas displayed distinctly different gene expression patterns. By using a rigorous statistical selection based method we identified 355 genes that showed significant (p Matrix Organization and Adhesion. Conclusions Affymetrix GeneChip profiling differentiated clear cell and chromophobe carcinomas from one another and from normal kidney cortex. Clustering methods that used logarithmic transformation of data sets produced dendrograms consistent with the sample biology. Functional taxonomy provided a practical approach to the interpretation of gene expression data. PMID:12356337

  17. Expression profiling of human renal carcinomas with functional taxonomic analysis

    Directory of Open Access Journals (Sweden)

    Madore Steven J

    2002-09-01

    Full Text Available Abstract Background Molecular characterization has contributed to the understanding of the inception, progression, treatment and prognosis of cancer. Nucleic acid array-based technologies extend molecular characterization of tumors to thousands of gene products. To effectively discriminate between tumor sub-types, reliable laboratory techniques and analytic methods are required. Results We derived mRNA expression profiles from 21 human tissue samples (eight normal kidneys and 13 kidney tumors and two pooled samples using the Affymetrix GeneChip platform. A panel of ten clustering algorithms combined with four data pre-processing methods identified a consensus cluster dendrogram in 18 of 40 analyses and of these 16 used a logarithmic transformation. Within the consensus dendrogram the expression profiles of the samples grouped according to tissue type; clear cell and chromophobe carcinomas displayed distinctly different gene expression patterns. By using a rigorous statistical selection based method we identified 355 genes that showed significant (p Conclusions Affymetrix GeneChip profiling differentiated clear cell and chromophobe carcinomas from one another and from normal kidney cortex. Clustering methods that used logarithmic transformation of data sets produced dendrograms consistent with the sample biology. Functional taxonomy provided a practical approach to the interpretation of gene expression data.

  18. Carcinoma of the prostate: the treatment of bone metastases by radioactive phosphorus (32P)

    International Nuclear Information System (INIS)

    Ariel, I.M.; Hassouna, H.

    1985-01-01

    The administration of radioactive phosphorus and testosterone benefitted two-thirds of thirty patients with prostate cancer treated. Subjective relief of bone pain occurred in 73% of cases and measurable objective improvement occurred in 50%. Hematopoietic depression occurred in 30% of the patients necessitating readmission to hospital for transfusion. This method of treatment is advocated for patients with widespread osseous metastasis, especially those with severe pain

  19. Immunohistochemical expression of alpha methylacyl-coa racemase (amacr) in carcinoma prostate in pakistani population

    International Nuclear Information System (INIS)

    Tariq, H.; Ahmed, R.; Muhammad, I.; Afzal, M.S.; Hashmi, S.N.; Hamdani, S.N.R.; Shahid, A.

    2017-01-01

    Objective: To determine the frequency of expression of positive diagnostic marker alpha methylacyl-COA RACEMES (AMACR) in the examination of prostate needle biopsy specimens from patients of adenocarcinoma prostate from a subset of Pakistani population. Study design: Cross-sectional study. Place and Duration of Study: Department of Histopathology, Armed Forces Institute of Pathology, Rawalpindi from Apr 2015 to Oct 2015. Material and Methods: All specimens of adenocarcinoma prostate diagnosed at Armed forces institute of pathology on the basis of immunohistochemistry and routine histopathology irrespective of age of patient, histological type or grade of the tumor were analyzed. Mean and Standard deviation were calculated for quantitative variables like patient's age and frequencies along with percentages were calculated for qualitative variables like AMACR expression. Results: Out of the total 80 cases, 68 (85%) were positive for AMACR while 12 (15%) were negative. Among the cases that were negative 9 (11.3%) showed 1 +- staining (Weak, non-circumferential) and 3 cases (3.8%) displayed 0 staining (No cytoplasmic staining). Conclusion: Positive staining for AMACR can be used to support a diagnosis of cancer on prostate needle core biopsies when the focus in question is <1mm in maximum dimension. The results of AMACR expression in a subset of Pakistani population are comparable to the western studies. AMACR staining must be interpreted in the context of basic haematoxylin and eosin criteria for malignancy along with the results expansion of other supportive markers, such as a basal cell specific marker like p63 or 34 beta E12. (author)

  20. Prostate carcinoma: results of radiation therapy in the French Cancer Centres

    International Nuclear Information System (INIS)

    Allain, Y.M.; Bolla, M.; Douchez, J.; Gary-Bobo, J.; Geslin, J.; Huart, J.; Mazeron, J.J.; Mathieu, G.

    1985-01-01

    From 1975 to 1982, 597 patients with localized prostatic adenocarcinoma were treated using external beam irradiation in one of 6 cooperating centers. The mean patient age was 67 years. The 5 and 10 years actuarial survivals (including all causes of death) were 70% and 40% respectively. The adjusted survival rates become 86% at 5 years and 61% at 10 years when only death due to cancer is taken into consideration. Despite the fact that patients with stage A1 and A2 disease show different patterns of lymphatic spread, the actuarial and adjusted 8 years survivals were identical for both staging groups, in this study, 57% and 90% respectively. It is significant that the majority of patients in both group A1 and in group A2 received irradiation to the pelvic lymph nodes as well as the prostate. Patients with stage B1 disease showed a 7 years actuarial survival of 53% and an 82% survival adjusted for death due to cancer only. Patients in both group B2 and group C, showed an identical 10 year actuarial survival rate of 49%. However, without CT scanning, it is difficult to differentiate between these 2 staging groups. Patients with stage C2 disease showed 10 years actuarial and adjusted survival rates of 20% and 40% respectively. The local recurrence rate after primary radiation therapy did not exceed 11% in any patient group. These data demonstrate, once again, that the dogma pertaining to the radioresistance of prostatic cancer is outdated [fr

  1. The role of CD133 in normal human prostate stem cells and malignant cancer-initiating cells.

    Science.gov (United States)

    Vander Griend, Donald J; Karthaus, Wouter L; Dalrymple, Susan; Meeker, Alan; DeMarzo, Angelo M; Isaacs, John T

    2008-12-01

    Resolving the specific cell of origin for prostate cancer is critical to define rational targets for therapeutic intervention and requires the isolation and characterization of both normal human prostate stem cells and prostate cancer-initiating cells (CIC). Single epithelial cells from fresh normal human prostate tissue and prostate epithelial cell (PrEC) cultures derived from them were evaluated for the presence of subpopulations expressing stem cell markers and exhibiting stem-like growth characteristics. When epithelial cell suspensions containing cells expressing the stem cell marker CD133+ are inoculated in vivo, regeneration of stratified human prostate glands requires inductive prostate stromal cells. PrEC cultures contain a small subpopulation of CD133+ cells, and fluorescence-activated cell sorting-purified CD133+ PrECs self-renew and regenerate cell populations expressing markers of transit-amplifying cells (DeltaNp63), intermediate cells (prostate stem cell antigen), and neuroendocrine cells (CD56). Using a series of CD133 monoclonal antibodies, attachment and growth of CD133+ PrECs requires surface expression of full-length glycosylated CD133 protein. Within a series of androgen receptor-positive (AR+) human prostate cancer cell lines, CD133+ cells are present at a low frequency, self-renew, express AR, generate phenotypically heterogeneous progeny negative for CD133, and possess an unlimited proliferative capacity, consistent with CD133+ cells being CICs. Unlike normal adult prostate stem cells, prostate CICs are AR+ and do not require functional CD133. This suggests that (a) AR-expressing prostate CICs are derived from a malignantly transformed intermediate cell that acquires "stem-like activity" and not from a malignantly transformed normal stem cell and (b) AR signaling pathways are a therapeutic target for prostate CICs.

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

    Energy Technology Data Exchange (ETDEWEB)

    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

  3. Overexpression of peroxiredoxin I and thioredoxin1 in human breast carcinoma

    Directory of Open Access Journals (Sweden)

    Kim Il-Han

    2009-06-01

    Full Text Available Abstract Background Peroxiredoxins (Prxs are a novel group of peroxidases containing high antioxidant efficiency. The mammalian Prx family has six distinct members (Prx I-VI in various subcellular locations, including peroxisomes and mitochondria, places where oxidative stress is most evident. The function of Prx I in particular has been implicated in regulating cell proliferation, differentiation, and apoptosis. Since thioredoxin1 (Trx1 as an electron donor is functionally associated with Prx I, we investigated levels of expression of both Prx I and Trx1. Methods We investigated levels of expression of both Prx I and Trx1 in breast cancer by real-time polymerase chain reaction (RT-PCR and Western blot. Results Levels of messenger RNA (mRNA for both Prx I and Trx1 in normal human breast tissue were very low compared to other major human tissues, whereas their levels in breast cancer exceeded that in other solid cancers (colon, kidney, liver, lung, ovary, prostate, and thyroid. Among members of the Prx family (Prx I-VI and Trx family (Trx1, Trx2, Prx I and Trx1 were preferentially induced in breast cancer. Moreover, the expression of each was associated with progress of breast cancer and correlated with each other. Western blot analysis of different and paired breast tissues revealed consistent and preferential expression of Prx I and Trx1 protein in breast cancer tissue. Conclusion Prx I and Trx1 are overexpressed in human breast carcinoma and the expression levels are associated with tumor grade. The striking induction of Prx I and Trx1 in breast cancer may enable their use as breast cancer markers.

  4. 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.

  5. A basal stem cell signature identifies aggressive prostate cancer phenotypes

    Science.gov (United States)

    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

  6. Comparison of PSMA-HBED and PSMA-I and T as diagnostic agents in prostate carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    McCarthy, Michael; Langton, Tiffany; Kumar, Divesh [Fiona Stanley Hospital, Molecular Imaging and Therapy Service (Nuclear Medicine), Perth (Australia); Royal Perth Hospital, Molecular Imaging and Therapy Service (Nuclear Medicine), Perth (Australia); Campbell, Andrew [Fiona Stanley Hospital, Molecular Imaging and Therapy Service (Nuclear Medicine), Perth (Australia); Royal Perth Hospital, Molecular Imaging and Therapy Service (Nuclear Medicine), Perth (Australia); Royal Perth Hospital, Medical Engineering and Physics, Perth (Australia)

    2017-08-15

    Gallium(68)-labelled prostate-specific membrane antigen (PSMA) radiopharmaceuticals can be used to detect prostate cancer (PCa) cells due the their over expression of PSMA. The {sup 68}Ga HBED-PSMA (PSMA-HBED) ligand has been most widely used and can be considered the current gold standard agent. Further PSMA ligands based on the DOTAGA and DOTA conjugates have more recently been developed. These agents (PSMA-I and T and PSMA-617) have potential theranostic capabilities as they can be conjugated with therapeutic radioisotopes. In this study, we examine whether PSMA-I and T has comparative efficacy, such that it could replace PSMA-HBED as a diagnostic agent in prostate carcinoma. 19 patients with PCa referred for {sup 68}Ga-PSMA imaging were imaged with PSMA-HBED and PSMA-I and T PET-CT imaging within a 2-week period. The two pharmaceuticals were synthesised using click chemistry. Imaging was performed using the same standardised methodology on a Siemens Biograph mCT. All sites of PSMA binding thought to represent PCa (probable or definite) were included in a lesion analysis that examined lesion concordance and lesional binding efficiency (SUV{sub peak}) between the two radiopharmaceuticals. For each patient, SUV{sub mean} of the LV cavity blood pool, bone, muscle and liver were determined as image background measures. Across all patients, PSMA uptake was observed in 47 lesions (10 bone lesions, 19 nodal lesions, 18 high-grade intraprostatic binding). Lesions were concordant between the agents in all except for two small (<4 mm) nodal lesions which were not visualised with PSMA-I and T. SUV{sub peak} assessment showed significantly greater overall lesion binding with HBED (paired t test, p = 0.0001). LV blood pool and bone marrow SUV{sub mean} were significantly higher for I and T than HBED (paired t test, blood pool p < 1 x 10-5, bone marrow p < 0.005). Intra-patient comparative imaging demonstrates higher lesional PSMA-HBED binding than PSMA-I and T and that the

  7. Potential downstream target genes of aberrant ETS transcription factors are differentially affected in Ewing's sarcoma and prostate carcinoma.

    Directory of Open Access Journals (Sweden)

    Maria J Camões

    Full Text Available FLI1 and ERG, the major ETS transcription factors involved in rearrangements in the Ewing's sarcoma family of tumors (ESFT and in prostate carcinomas (PCa, respectively, belong to the same subfamily, having 98% sequence identity in the DNA binding domain. We therefore decided to investigate whether the aberrant transcription factors in both malignancies have some common downstream targets. We crossed a publicly available list of all putative EWSR1-FLI1 target genes in ESFT with our microarray expression data on 24 PCa and 6 non-malignant prostate tissues (NPT and choose four genes among the top-most differentially expressed between PCa with (PCa ERG+ and without (PCa ETS- ETS fusion genes (HIST1H4L, KCNN2, ECRG4 and LDOC1, as well as four well-validated direct targets of the EWSR1-FLI1 chimeric protein in ESFT (NR0B1, CAV1, IGFBP3 and TGFBR2. Using quantitative expression analysis in 16 ESFT and seven alveolar rhabdomyosarcomas (ARMS, we were able to validate the four genes previously described as direct targets of the EWSR1-FLI1 oncoprotein, showing overexpression of CAV1 and NR0B1 and underexpression of IGFBP3 and TGFBR2 in ESFT as compared to ARMS. Although none of these four genes showed significant expression differences between PCa ERG+ and PCa ETS-, CAV1, IGFBP3 and TGFBR2 were less expressed in PCa in an independent series of 56 PCa and 15 NPT, as also observed for ECRG4 and LDOC1, suggesting a role in prostate carcinogenesis in general. On the other hand, we demonstrate for the first time that both HIST1H4L and KCNN2 are significantly overexpressed in PCa ERG+ and that ERG binds to the promoter of these genes. Conversely, KCNN2 was found underexpressed in ESFT relative to ARMS, suggesting that the EWSR1-ETS oncoprotein may have the opposite effect of ERG rearrangements in PCa. We conclude that aberrant ETS transcription factors modulate target genes differently in ESFT and PCa.

  8. AR-Signaling in Human Malignancies: Prostate Cancer and Beyond

    Directory of Open Access Journals (Sweden)

    Michael T. Schweizer

    2017-01-01

    Full Text Available In the 1940s Charles Huggins reported remarkable palliative benefits following surgical castration in men with advanced prostate cancer, and since then the androgen receptor (AR has remained the main therapeutic target in this disease. Over the past couple of decades, our understanding of AR-signaling biology has dramatically improved, and it has become apparent that the AR can modulate a number of other well-described oncogenic signaling pathways. Not surprisingly, mounting preclinical and epidemiologic data now supports a role for AR-signaling in promoting the growth and progression of several cancers other than prostate, and early phase clinical trials have documented preliminary signs of efficacy when AR-signaling inhibitors are used in several of these malignancies. In this article, we provide an overview of the evidence supporting the use of AR-directed therapies in prostate as well as other cancers, with an emphasis on the rationale for targeting AR-signaling across tumor types.

  9. Epigenetic Regulation of Vitamin D 24-Hydroxylase/CYP24A1 in Human Prostate Cancer

    Science.gov (United States)

    Luo, Wei; Karpf, Adam R.; Deeb, Kristin K.; Muindi, Josephia R.; Morrison, Carl D.; Johnson, Candace S.; Trump, Donald L.

    2010-01-01

    Calcitriol, a regulator of calcium homeostasis with antitumor properties, is degraded by the product of the CYP24A1 gene which is downregulated in human prostate cancer by unknown mechanisms. We found that CYP24A1 expression is inversely correlated with promoter DNA methylation in prostate cancer cell lines. Treatment with the DNA methyltransferase inhibitor 5-aza-2′-deoxycytidine (DAC) activates CYP24A1 expression in prostate cancer cells. In vitro methylation of the CYP24A1 promoter represses its promoter activity. Furthermore, inhibition of histone deacetylases by trichostatin A (TSA) enhances the expression of CYP24A1 in prostate cancer cells. ChIP-qPCR reveals that specific histone modifications are associated with the CYP24A1 promoter region. Treatment with TSA increases H3K9ac and H3K4me2 and simultaneously decreases H3K9me2 at the CYP24A1 promoter. ChIP-qPCR assay reveals that treatment with DAC and TSA increases the recruitment of VDR to the CYP24A1 promoter. RT-PCR analysis of paired human prostate samples reveals that CYP24A1 expression is down-regulated in prostate malignant lesions compared to adjacent histologically benign lesions. Bisulfite pyrosequencing shows that CYP24A1 gene is hypermethylated in malignant lesions compared to matched benign lesions. Our findings indicate that repression of CYP24A1 gene expression in human prostate cancer cells is mediated in part by promoter DNA methylation and repressive histone modifications. PMID:20587525

  10. A study of prostate delineation referenced against a gold standard created from the visible human data

    International Nuclear Information System (INIS)

    Gao Zhanrong; Wilkins, David; Eapen, Libni; Morash, Christopher; Wassef, Youssef; Gerig, Lee

    2007-01-01

    Purpose: To measure inter- and intra-observer variation and systematic error in CT based prostate delineation, where individual delineations are referenced against a gold standard produced from photographic anatomical images from the Visible Human Project (VHP). Materials and methods: The CT and anatomical images of the VHP male form the basic data set for this study. The gold standard was established based on 1 mm thick anatomical photographic images. These were registered against the 3 mm thick CT images that were used for target delineation. A total of 120 organ delineations were performed by six radiation oncologists. Results: The physician delineated prostate volume was on average 30% larger than the 'true' prostate volume, but on average included only 84% of the gold standard volume. Our study found a systematic delineation error such that posterior portions of the prostate were always missed while anteriorly some normal tissue was always defined as target. Conclusions: Our data suggest that radiation oncologists are more concerned with the unintentional inclusion of rectal tissue than they are in missing prostate volume. In contrast, they are likely to overextend the anterior boundary of the prostate to encompass normal tissue such as the bladder

  11. Adenoma clear cell carcinoma of prostatic utricle. Report of a case. Literature Review

    International Nuclear Information System (INIS)

    Cataldi, S.; Castillo, L.; Rodrígue, R.

    2004-01-01

    The prostatic utricle (UP) is a rudimentary structure derived from the Müllerian ducts (paramesonephric), which gives rise to the female genital tract in its portion flow and Wollfianos products (mesonephric), which causes the male seminal tubes urogenital sinus and in the caudal segment. It is located in the central portion of the prostatic urethra. UP pathology is rare in the literature and only few isolated cases have been reported and rare reviews. UP neoplasms are extremely rare. The first report on the literature is the year 1967 in a man 66 years in which the diagnosis was incidental in a piece of prostatectomy. Objective: The aim of this paper is to review the literature on this rare condition from the report of a clinical case. Case report: Male patient, 15 years who presented with hematuria. the tomography showed right renal agenesis, hypertrophic left kidney and a solid mass retrovesical in prostate topography. The transrectal ultrasound guided biopsy remains informed embryonic kidney blastoma and immunohistochemical profile is specific to urothelial epithelium and glomerular (BPM CK7 strongly positive). It is involved, resecting the tumor whose pelvic pathology (AP) corresponded to clear cell adenocarcinoma UP. Pursuing a post-operative complications and remains without clinical tomographic control locoregional relapse was diagnosed 5 months after. Get chemotherapy type adriamycin-cisplatin with complete clinical response after the 2nd cycle of treatment and rapid lesion progression at the end of the 6th cycle. Was re hospitalized resecting one laterovesical mass right, leaving in situ a left laterovesical similar mass. the AP was similar to the original. Currently, the patient underwent a left nephrostomy is planned initiation of palliative chemotherapy of weekly Docetaxel type. Conclusions: Given the rarity of the disease, and little literature there is no data on evolution and sensitivity to treatment. In the case of this patient highlight the high

  12. Alterations in Lipoxygenase and Cyclooxygenase-2 Catalytic Activity and mRNA Expression in Prostate Carcinoma

    Directory of Open Access Journals (Sweden)

    Scott B. Shappell

    2001-01-01

    Full Text Available Recent studies in prostate tissues and especially cell lines have suggested roles for arachidonic acid (AA metabolizing enzymes in prostate adenocarcinoma (Pca development or progression. The goal of this study was to more fully characterize lipoxygenase (LOX and cyclooxygenase-2 (COX-2 gene expression and AA metabolism in benign and malignant prostate using snap-frozen tissues obtained intraoperatively and mRNA analyses and enzyme assays. Formation of 15-hydroxyeicosatetraenoic acid (15-HETE was detected in 23/29 benign samples and 15-LOX-2 mRNA was detected in 21/25 benign samples. In pairs of pure benign and Pca from the same patients, 15-HETE production and 15-LOX-2 mRNA were reduced in Pca versus benign in 9/14 (P=.04 and 14/17 (P=.002, respectively. Under the same conditions, neither 5HETE nor 12-HETE formation was detectable in 29 benign and 24 tumor samples; with a more sensitive assay, traces were detected in some samples, but there was no clear association with tumor tissue. COX-2 mRNA was detected by nuclease protection assay in 7/16 benign samples and 5/16 tumors. In benign and tumor pairs from 10 patients, COX-2 was higher in tumor versus benign in only 2, with similar results by in situ hybridization. Paraffin immunoperoxidase for COX2 was performed in whole mount sections from 87 additional radical prostatectomy specimens, with strong expression in ejaculatory duct as a positive control and corroboration with in situ hybridization. No immunostaining was detected in benign prostate or tumor in 45% of cases. Greater immunostaining in tumor versus benign was present in only 17% of cases, and correlated with high tumor grade (Gleason score 8 and 9 vs. 5 to 7. In conclusion, reduced 15-LOX-2 expression and 15-HETE formation is the most characteristic alteration of AA metabolism in Pca. Increased 12-HETE and 5-HETE formation in Pca were not discernible. Increased COX-2 expression is not a typical abnormality in Pca in general, but

  13. Glucocorticoid receptor antagonism reverts docetaxel resistance in human prostate cancer

    NARCIS (Netherlands)

    Kroon, Jan; Kroon, Jan; Puhr, M.; Buijs, J.T.; van der Horst, G.; Hemmer, D.M.; Marijt, K.A.; Hwang, M.S.; Masood, M.; Grimm, S.; Storm, Gerrit; Metselaar, Josbert Maarten; Meijer, O.C.; Culig, Z.; van der Pluijm, M.

    2016-01-01

    Resistance to docetaxel is a major clinical problem in advanced prostate cancer (PCa). Although glucocorticoids (GCs) are frequently used in combination with docetaxel, it is unclear to what extent GCs and their receptor, the glucocorticoid receptor (GR), contribute to the chemotherapy resistance.

  14. Glucocorticoid receptor antagonism reverts docetaxel resistance in human prostate cancer

    NARCIS (Netherlands)

    Kroon, Jan; Puhr, Martin; Buijs, Jeroen T.; Van Der Horst, Geertje; Lemhemmer, Daniël; Marijt, Koen A.; Hwang, Ming S.; Masood, Motasim; Grimm, Stefan; Storm, Gert; Metselaar, Josbert M.|info:eu-repo/dai/nl/244207690; Meijer, Onno C.; Culig, Zoran; Van Der Pluijm, Gabri

    2016-01-01

    Resistance to docetaxel is a major clinical problem in advanced prostate cancer (PCA). Although glucocorticoids (GCs) are frequently used in combination with docetaxel, it is unclear to what extent GCs and their receptor, the glucocorticoid receptor (GR), contribute to the chemotherapy resistance.

  15. The role of Rad 51 protein in radioresistance of spheroid model of Du 145 prostate carcinoma cell line

    International Nuclear Information System (INIS)

    Taghizadeh, M.; Khoei, S.; Nikoofar, A. R.; Ghamsari, L.; Goliaei, B.

    2009-01-01

    Rad 51 is a protein with critical role in double strand break repair. Down-regulation of this protein has a significant effect in radiosensitivity of some cell lines like prostate carcinoma. Compared to monolayer cell culture model, the spheroids are more resistant to radiation. The aim of the current study was to determine the Rad 51 protein level in Du 145 spheroids, and monolayer cells before and after exposure to gamma irradiation. Materials and Methods: In the present study, western blot was used to determine the level of Rad 51 protein in Du 145 cell line grown as monolayer and spheroid. Results: Western blot analysis showed that in the spheroid cells, Rad 51 had an elevated level before and after radiation in comparison with monolayer cells. Higher doses of radiation induced elevated expression of Rad 51 protein in both culture models.The level of at protein after exposure to gamma rays had been time-dependent. Conclusion: Rad 51 might act as a mediator of radiation resistance in tumor cells. Repression of Rad 51 activity could be a prominent strategy to overcome radiation resistance of tumors.

  16. Retrospective evaluation of dosimetric quality for prostate carcinomas treated with 3D conformal, intensity modulated and volumetric modulated arc radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Crowe, Scott B [Science and Engineering Faculty, Queensland University of Technology, Brisbane, Queensland (Australia); Kairn, Tanya [Science and Engineering Faculty, Queensland University of Technology, Brisbane, Queensland (Australia); Premion, Wesley Medical Centre, Brisbane, Queensland (Australia); Middlebrook, Nigel; Hill, Brendan; Christie, David R H; Knight, Richard T [Premion, Wesley Medical Centre, Brisbane, Queensland (Australia); Kenny, John [Australian Clinical Dosimetry Services, Australian Radiation Protection and Nuclear Safety Agency, Melbourne, Victoria (Australia); Langton, Christian M; Trapp, Jamie V [Science and Engineering Faculty, Queensland University of Technology, Brisbane, Queensland (Australia)

    2013-12-15

    This study examines and compares the dosimetric quality of radiotherapy treatment plans for prostate carcinoma across a cohort of 163 patients treated across five centres: 83 treated with three-dimensional conformal radiotherapy (3DCRT), 33 treated with intensity modulated radiotherapy (IMRT) and 47 treated with volumetric modulated arc therapy (VMAT). Treatment plan quality was evaluated in terms of target dose homogeneity and organs at risk (OAR), through the use of a set of dose metrics. These included the mean, maximum and minimum doses; the homogeneity and conformity indices for the target volumes; and a selection of dose coverage values that were relevant to each OAR. Statistical significance was evaluated using two-tailed Welch's T-tests. The Monte Carlo DICOM ToolKit software was adapted to permit the evaluation of dose metrics from DICOM data exported from a commercial radiotherapy treatment planning system. The 3DCRT treatment plans offered greater planning target volume dose homogeneity than the other two treatment modalities. The IMRT and VMAT plans offered greater dose reduction in the OAR: with increased compliance with recommended OAR dose constraints, compared to conventional 3DCRT treatments. When compared to each other, IMRT and VMAT did not provide significantly different treatment plan quality for like-sized tumour volumes. This study indicates that IMRT and VMAT have provided similar dosimetric quality, which is superior to the dosimetric quality achieved with 3DCRT.

  17. Radiation therapy in carcinoma of the prostate: a contributing cause of urinary incontinence

    International Nuclear Information System (INIS)

    Kaufman, J.J.; Smith, R.B.; Raz, S.

    1984-01-01

    The authors believe that radiation therapy as a postoperative adjuvant or preceding salvage prostatectomy for carcinoma is particularly conducive to the complication of urinary incontinence by virtue of its sclerosing effect on residual sphincter mechanisms. Obviously, such dual therapy will continue to prevail in the foreseeable future but patients should be notified of the added risk and be prepared for further treatment of the incontinence. Unfortunately, these patients have an extra risk of complications and failure from anti-incontinence operations

  18. Gastrin-releasing peptide receptor imaging in human breast carcinoma versus immunohistochemistry

    NARCIS (Netherlands)

    de Wiele, Christophe Van; Phonteyne, Philippe; Pauwels, Patrick; Goethals, Ingeborg; Van den Broecke, Rudi; Cocquyt, Veronique; Dierckx, Rudi Andre

    This study reports on the uptake of (99m)Tc-RP527 by human breast carcinoma and its relationship to gastrin-releasing peptide receptor (GRIP-R) expression as measured by immunohistochemistry (IHC). Methods: Nine patients referred because of a clinical diagnosis suggestive of breast carcinoma and 5

  19. [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.

  20. Image Guided Hypofractionated Radiotherapy by Helical Tomotherapy for Prostate Carcinoma: Toxicity and Impact on Nadir PSA

    Directory of Open Access Journals (Sweden)

    Salvina Barra

    2014-01-01

    Full Text Available Aim. To evaluate the toxicity of a hypofractionated schedule for primary radiotherapy (RT of prostate cancer as well as the value of the nadir PSA (nPSA and time to nadir PSA (tnPSA as surrogate efficacy of treatment. Material and Methods. Eighty patients underwent hypofractionated schedule by Helical Tomotherapy (HT. A dose of 70.2 Gy was administered in 27 daily fractions of 2.6 Gy. Acute and late toxicities were graded on the RTOG/EORTC scales. The nPSA and the tnPSA for patients treated with exclusive RT were compared to an equal cohort of 20 patients treated with conventional fractionation and standard conformal radiotherapy. Results. Most of patients (83% did not develop acute gastrointestinal (GI toxicity and 50% did not present genitourinary (GU toxicity. After a median follow-up of 36 months only grade 1 of GU and GI was reported in 6 and 3 patients as late toxicity. Average tnPSA was 30 months. The median value of nPSA after exclusive RT with HT was 0.28 ng/mL and was significantly lower than the median nPSA (0.67 ng/mL of the conventionally treated cohort (P=0.02. Conclusions. Hypofractionated RT schedule with HT for prostate cancer treatment reports very low toxicity and reaches a low level of nPSA that might correlate with good outcomes.

  1. Prognosis in patients with local recurrence after definitive irradiation for prostatic carcinoma

    International Nuclear Information System (INIS)

    Kuban, D.A.; el-Mahdi, A.M.; Schellhammer, P.F.

    1989-01-01

    Of 414 patients with Stage A2-C disease, all with a minimum follow-up period of 3 years, who have been definitively irradiated by external beam therapy or iodine-125 (I-125) implantation for biopsy-proven prostatic adenocarcinoma, 83 patients (20%) have experienced local recurrences. The incidence of distant metastasis was significantly higher in patients with local tumor recurrence (56 of 83; 68%), as compared with those with local control (64 of 331; 19%; P less than 0.001). This difference remained significant within each tumor grade and stage. Subsequently, survival in patients with local recurrence was significantly shorter than in those with local tumor control (66% vs. 89% at 5 years; P = 0.001). Of the 83 patients with local tumor recurrence, 56 had local recurrence and distant metastasis, and 27 had local failure alone, with a median follow-up of 76 months for the latter group. Fifteen of 83 patients with local recurrence (18%) developed major complications secondary to local disease. Three of the 83 (4%) patients were known to die of prostatic recurrence alone and another 11 of 83 (13%) as a result of some combination of local and distant disease. Therefore, in reference to the entire group of definitively irradiated patients, only 0.72% expired solely of complications associated with local tumor recurrence and an additional 2.7% expired of a combination of both local and distant disease

  2. Isolation and functional interrogation of adult human prostate epithelial stem cells at single cell resolution.

    Science.gov (United States)

    Hu, Wen-Yang; Hu, Dan-Ping; Xie, Lishi; Li, Ye; Majumdar, Shyama; Nonn, Larisa; Hu, Hong; Shioda, Toshi; Prins, Gail S

    2017-08-01

    Using primary cultures of normal human prostate epithelial cells, we developed a novel prostasphere-based, label-retention assay that permits identification and isolation of stem cells at a single cell level. Their bona fide stem cell nature was corroborated using in vitro and in vivo regenerative assays and documentation of symmetric/asymmetric division. Robust WNT10B and KRT13 levels without E-cadherin or KRT14 staining distinguished individual stem cells from daughter progenitors in spheroids. Following FACS to isolate label-retaining stem cells from label-free progenitors, RNA-seq identified unique gene signatures for the separate populations which may serve as useful biomarkers. Knockdown of KRT13 or PRAC1 reduced sphere formation and symmetric self-renewal highlighting their role in stem cell maintenance. Pathways analysis identified ribosome biogenesis and membrane estrogen-receptor signaling enriched in stem cells with NF-ĸB signaling enriched in progenitors; activities that were biologically confirmed. Further, bioassays identified heightened autophagy flux and reduced metabolism in stem cells relative to progenitors. These approaches similarly identified stem-like cells from prostate cancer specimens and prostate, breast and colon cancer cell lines suggesting wide applicability. Together, the present studies isolate and identify unique characteristics of normal human prostate stem cells and uncover processes that maintain stem cell homeostasis in the prostate gland. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  3. Isolation and functional interrogation of adult human prostate epithelial stem cells at single cell resolution

    Directory of Open Access Journals (Sweden)

    Wen-Yang Hu

    2017-08-01

    Full Text Available Using primary cultures of normal human prostate epithelial cells, we developed a novel prostasphere-based, label-retention assay that permits identification and isolation of stem cells at a single cell level. Their bona fide stem cell nature was corroborated using in vitro and in vivo regenerative assays and documentation of symmetric/asymmetric division. Robust WNT10B and KRT13 levels without E-cadherin or KRT14 staining distinguished individual stem cells from daughter progenitors in spheroids. Following FACS to isolate label-retaining stem cells from label-free progenitors, RNA-seq identified unique gene signatures for the separate populations which may serve as useful biomarkers. Knockdown of KRT13 or PRAC1 reduced sphere formation and symmetric self-renewal highlighting their role in stem cell maintenance. Pathways analysis identified ribosome biogenesis and membrane estrogen-receptor signaling enriched in stem cells with NF-ĸB signaling enriched in progenitors; activities that were biologically confirmed. Further, bioassays identified heightened autophagy flux and reduced metabolism in stem cells relative to progenitors. These approaches similarly identified stem-like cells from prostate cancer specimens and prostate, breast and colon cancer cell lines suggesting wide applicability. Together, the present studies isolate and identify unique characteristics of normal human prostate stem cells and uncover processes that maintain stem cell homeostasis in the prostate gland.

  4. Photodynamic therapy in prostate cancer: optical dosimetry and response of normal tissue

    Science.gov (United States)

    Chen, Qun; Shetty, Sugandh D.; Heads, Larry; Bolin, Frank; Wilson, Brian C.; Patterson, Michael S.; Sirls, Larry T., II; Schultz, Daniel; Cerny, Joseph C.; Hetzel, Fred W.

    1993-06-01

    The present study explores the possibility of utilizing photodynamic therapy (PDT) in treating localized prostate carcinoma. Optical properties of ex vivo human prostatectomy specimens, and in vivo and ex vivo dog prostate glands were studied. The size of the PDT induced lesion in dog prostate was pathologically evaluated as a biological endpoint. The data indicate that the human normal and carcinoma prostate tissues have similar optical properties. The average effective attenuation depth is less in vivo than that of ex vivo. The PDT treatment generated a lesion size of up to 16 mm in diameter. The data suggest that PDT is a promising modality in prostate cancer treatment. Multiple fiber system may be required for clinical treatment.

  5. Prostate carcinoma (PC) - an organ-related specific pathological neoplasm; Prostatakarzinom (PC) - eine organspezifische Neoplasie aus der Sicht der Pathologie

    Energy Technology Data Exchange (ETDEWEB)

    Massmann, J.; Funk, A. [Gemeinschaftspraxis Pathologie Massmann-Funk-Dettmar, Muenchen (Germany); Altwein, J. [Krankenhaus der Barmherzigen Brueder, Muenchen (Germany); Praetorius, M.

    2003-06-01

    The organ- and tumour-related specific characteristics of prostate carcinoma (PC) are presented in an overview under various aspects. It is the key for understanding pathological changes, including PC, to consider the subdivision of the prostate into anatomically and functionally distinguishable zones, especially the transitional zone (TZ) and the peripheral zone (PZ). The pseudoneoplastic hyperplasia of the TZ, combined with inflammatory consequences and age-related changes, forms a differential diagnostic challenge to both clinico-radiological diagnosis and macroscopic and microscopic examination. High-degree prostatic intra-epithelial neoplasia (PIN III) and atypical adenomatous hyperplasia (AAH) are presented as precursor lesions of PC with varying significance and assessment. Moreover, there are discussed the following characteristic features of PC: localisation types, focality, volume, progression, double-graduation according to Gleason, tumour stage, and prognosis. The most important prognosis factors of PC (category I) include the categories of the TNM system, such as stage, surgical marginal situation, degree and also the preoperative PSA level as a (poor) substitute for the tumour volume. Potential prognosis parameters (category II) show the tumour volume and the DNS ploidy, while there continues to exist a large number of non-established parameters (category III). The prognostic validity of the pathological examinations depends, on the one hand, on the tissue extent (needle biopsy, transurethral resection (TURP), so-called simple prostatectomy, radical prostatectomy (RPE)) and the prostate zones covered. On the other hand, the prognostic certainty also depends on the tumour-adequate macroscopic and microscopic assessment of an RPE that can only be a partial or complete handling in transversal large-area sections. (orig.) [German] Die organ- und tumorspezifischen Besonderheiten des Prostatakarzinoms (PC) werden in einer Uebersicht unter verschiedenen

  6. Human papillomavirus-mediated carcinogenesis and HPV-associated oral and oropharyngeal squamous cell carcinoma. Part 2: Human papillomavirus associated oral and oropharyngeal squamous cell carcinoma

    Science.gov (United States)

    2010-01-01

    Human papillomavirus (HPV) infection of the mouth and oropharynx can be acquired by a variety of sexual and social forms of transmission. HPV-16 genotype is present in many oral and oropharyngeal squamous cell carcinomata. It has an essential aetiologic role in the development of oropharyngeal squamous cell carcinoma in a subset of subjects who are typically younger, are more engaged with high-risk sexual behaviour, have higher HPV-16 serum antibody titer, use less tobacco and have better survival rates than in subjects with HPV-cytonegative oropharyngeal squamous cell carcinoma. In this subset of subjects the HPV-cytopositive carcinomatous cells have a distinct molecular profile. In contrast to HPV-cytopositive oropharyngeal squamous cell carcinoma, the causal association between HPV-16 and other high-risk HPV genotypes and squamous cell carcinoma of the oral mucosa is weak, and the nature of the association is unclear. It is likely that routine administration of HPV vaccination against high-risk HPV genotypes before the start of sexual activity will bring about a reduction in the incidence of HPV-mediated oral and oropharyngeal squamous cell carcinoma. This article focuses on aspects of HPV infection of the mouth and the oropharynx with emphasis on the link between HPV and squamous cell carcinoma, and on the limitations of the available diagnostic tests in identifying a cause-and-effect relationship of HPV with squamous cell carcinoma of the mouth and oropharynx. PMID:20633288

  7. Biosynthesis and metabolism of steroid hormones by human adrenal carcinomas

    OpenAIRE

    Brown, J.W.; Fishman, L.M.

    2000-01-01

    Over a 15-year period, our university-based laboratory obtained 125 adrenal tumors, of which 15 (12%) were adrenal cortical carcinomas. Of these, 6 (40% of the carcinomas) occurred in patients with clear clinical manifestations of steroid hormone excess. Adrenal cortical carcinoma cells derived from the surgically resected tumors in 4 of these patients were isolated and established in primary culture. Radiotracer steroid interconversion studies were carried out with these cultures and also on...

  8. EXPRESSION AND SIGNIFICANCE OF ERK PROTEIN IN HUMAN BREAST CARCINOMA

    Institute of Scientific and Technical Information of China (English)

    张秀梅; 李柏林; 宋敏; 宋继谒

    2004-01-01

    Objective: To investigate the expression of ERK and p-ERK protein in human breast cancer and their corresponding tissue, to assess the significance of ERK signal pathway in tumorigenesis and progression of breast carcinoma. Methods: 40 breast cancer cases were used in S-P immunohistochemistry technique and Western Blot study. Results: The expression of ERK1, ERK2, and p- ERK protein levels increased remarkably in breast cancer tissues in comparison to normal tissues (P<0.01). The expression was upregulated by 1.32-, 1.53-and 4.27-fold, respectively. The overexpressions of ERK1, ERK2, and p- ERK proteins were obviously correlated with clinical stage of breast cancer. Protein levels of ERK and p-ERK were higher in stage III patients than in stage I and stage II patients (P<0.05). These proteins were strongly related with axillary lymph node metastasis of breast cancer, but not correlated with histopathological type and status of ER and PR of breast cancer. Expression of ERK1, and ERK2, protein showed a positive linear correlation. Conclusion: ERK signal transduction pathway is a key factor during human breast tumorigenesis and breast cancer progression.

  9. Human prostate supports more efficient replication of HIV-1 R5 than X4 strains ex vivo

    Directory of Open Access Journals (Sweden)

    Denis Hélène

    2008-12-01

    Full Text Available Abstract Background In order to determine whether human prostate can be productively infected by HIV-1 strains with different tropism, and thus represent a potential source of HIV in semen, an organotypic culture of prostate from men undergoing prostatic adenomectomy for benign prostate hypertrophy (BPH was developed. The presence of potential HIV target cells in prostate tissues was investigated using immunohistochemistry. The infection of prostate explants following exposures with HIV-1 R5, R5X4 and X4 strains was analyzed through the measure of RT activity in culture supernatants, the quantification of HIV DNA in the explants and the detection of HIV RNA+ cells in situ. Results The overall prostate characteristics were retained for 21/2 weeks in culture. Numerous potential HIV-1 target cells were detected in the prostate stroma. Whilst HIV-1 R5SF162 strain consistently productively infected prostatic T lymphocytes and macrophages, the prototypic X4IIIB strain and a primary R5X4 strain showed less efficient replication in this organ. Conclusion The BPH prostate is a site of HIV-1 R5 replication that could contribute virus to semen. A limited spreading of HIV-1 X4 and R5X4 in this organ could participate to the preferential sexual transmission of HIV-1 R5 strains.

  10. Variations of Human DNA Polymerase Genes as Biomarkers of Prostate Cancer Progression

    Science.gov (United States)

    2011-07-01

    Pesche S, Latil A, Muzeau F, Cussenot O, Fournier G, Longy M, Eng C, Lidereau R. 1998. PTEN/MMAC1/TEP1 involvement in primary prostate cancers. Oncogene 16...skin fibroblasts from heterozygotes for the Lesch-Nyhan syndrome : a sensitive marker for carrier detection. Hum Hered 29:64–68. 48 HUMAN MUTATION, Vol

  11. Pathogenetic Influences of Human Herpesvirus 8 (HHV-8) in Prostate Cancer Progression

    Science.gov (United States)

    2012-05-25

    Science 1974;186:1213-1215. 11. Wilson JD, Griffin JE, Leshin M, George FW. Role of gonadal hormones in development of the sexual phenotypes. Hum Genet... Cantor A, Muro-Cacho C, Livingston S, Karras J, Pow-Sang J, Jove R. Constitutive activation of Stat3 in human prostate tumors and cell lines: direct

  12. Antiproliferative effect of a polysaccharide fraction of a 20% methanolic extract of stinging nettle roots upon epithelial cells of the human prostate (LNCaP).

    Science.gov (United States)

    Lichius, J J; Lenz, C; Lindemann, P; Müller, H H; Aumüller, G; Konrad, L

    1999-10-01

    In Germany, plant extracts are often used in the treatment of early stages of benign prostate hyperplasia (BPH). The effects of different concentrations of the polysaccharide fraction of the 20% methanolic extract of stinging nettle roots (POLY-M) on the cellular proliferation of lymph node carcinoma of the prostate (LNCaP) cells were determined by measurement of the genomic DNA content of the samples. All concentrations of POLY-M showed an inhibitory effect on the growth of the LNCaP cells during 7 days except the two lowest concentrations. The reduced proliferation of POLY-M treated LNCaP cells was significantly (p < 0.05) different from the untreated control. The inhibition was time- and concentration-dependent with the maximum suppression (50%) on day 6 and at concentrations of 1.0E-9 and 1.0E-11 mg/ml. No cytotoxic effect of POLY-M on cell proliferation was observed. The in vitro results show for the first time an antiproliferative effect of Urtica compounds on human prostatic epithelium and confirm our previous in vivo findings.

  13. Radiation therapy of a metastatic tumour of the orbit caused by prostatic carcinoma

    International Nuclear Information System (INIS)

    Daniel, F.; Langmann, G.; Faulborn, J.; Poschauko, J.

    1994-01-01

    We report a case of metastatic carcinoma to the apex of the orbit in a 66-year old patient. Orbital metastasis occurred while the patient suffered from another metastatic activity especially in his bony structures. The orbital tumour caused rapid visual impairment because of compression of the optic nerve. The metastasis was treated by radiation therapy. With CT-scan, electrophysiological examination, visual field examination, and visual function we demonstrate the regression of the tumour. One year after therapy the tumor was no longer detectable. Visual function had recovered and visual fields were normally. Radiation therapy prolonged high quality life for our patient due to preservation of visual function. (authors)

  14. Evaluation of IMRT plans of prostate carcinoma from four treatment planning systems based on Monte Carlo

    International Nuclear Information System (INIS)

    Chi Zifeng; Han Chun; Liu Dan; Cao Yankun; Li Runxiao

    2011-01-01

    Objective: With the Monte Carlo method to recalculate the IMRT dose distributions from four TPS to provide a platform for independent comparison and evaluation of the plan quality.These results will help make a clinical decision as which TPS will be used for prostate IMRT planning. Methods: Eleven prostate cancer cases were planned with the Corvus, Xio, Pinnacle and Eclipse TPS. The plans were recalculated by Monte Carlo using leaf sequences and MUs for individual plans. Dose-volume-histograms and isodose distributions were compared. Other quantities such as D min (the minimum dose received by 99% of CTV/PTV), D max (the maximum dose received by 1% of CTV/PTV), V 110% , V 105% , V 95% (the volume of CTV/PTV receiving 110%, 105%, 95% of the prescription dose), the volume of rectum and bladder receiving >65 Gy and >40 Gy, and the volume of femur receiving >50 Gy were evaluated. Total segments and MUs were also compared. Results: The Monte Carlo results agreed with the dose distributions from the TPS to within 3%/3 mm. The Xio, Pinnacle and Eclipse plans show less target dose heterogeneity and lower V 65 and V 40 for the rectum and bladder compared to the Corvus plans. The PTV D min is about 2 Gy lower for Xio plans than others while the Corvus plans have slightly lower female head V 50 (0.03% and 0.58%) than others. The Corvus plans require significantly most segments (187.8) and MUs (1264.7) to deliver and the Pinnacle plans require fewest segments (82.4) and MUs (703.6). Conclusions: We have tested an independent Monte Carlo dose calculation system for dose reconstruction and plan evaluation. This system provides a platform for the fair comparison and evaluation of treatment plans to facilitate clinical decision making in selecting a TPS and beam delivery system for particular treatment sites. (authors)

  15. Lysophosphatidic Acid Regulation and Roles in Human Prostate Cancer

    Science.gov (United States)

    2006-08-01

    IGF-II ( insulin -like growth factor-II), and hormones have been implicated in the growth and survival of prostate cancer cells [1]. A recent addition to...sphingomyelin. In the synthesis of sphingomyelin, a phosphocholine group is transferred from phosphatidylcholine to ceramide. Sphin- gomyelin synthesis...cytotoxicity of TNF-α [78]. A phosphatidylcholine -specific phospholipase C activity was also required for aSMase activa- tion [79,80]. It is assumed that

  16. Development of a new in vivo kit for detection of prostate specific antigen in human serum using immunoradiometric assay method

    International Nuclear Information System (INIS)

    Babaei, M. H.; Behradkia, P.; Shafii, M.; Movla, M.; Forutan, H.; Najafi, R.

    2006-01-01

    Prostate is a leading site for the cancer incidence, accounted for 31.0% of new cancer cases in men. Prostate-specific antigen is widely used in the detection and monitoring of the prostate cancer. Currently, immunoassay is used to detect Prostate-specific antigen in human serum. This technique is based on the interaction between antibody and antigen. The varied immunoassay formats and equipment to run the assays allow the users to measure the analytes rapidly, with the flexibility to run a small or a large number of samples. Among different immunoassay methods, immunoradiometric assay is a more sensitive and valuable detection approach. This study has been made in 4 parts: (1) purification of Prostate-specific antigen from seminal fluid; (2) preparation of hybridoma cells which secrete monoclonal antibody (mAb) against Prostate-specific antigen , (3) selection of pair monoclonal antibody among those antibodies, and finally (4) design of an immunoradiometric assay kit and it's quality control . The results of this study were: (1) obtaining a huge amount of Prostate-specific antigen as semi-purified and purified, that is a valuable material for preparation of standard kits; (2) preparation of 8 kinds of monoclonal antibodies; (3) finding 4 pairs of monoclonal antibodies which react with different epitopes on Prostate-specific antigen molecule; and (4) preparation of immunoradiometric assay kit for measuring Prostate-specific antigen concentration in human serum

  17. Hydrogen sulfide mediates the anti-survival effect of sulforaphane on human prostate cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Pei, Yanxi [Department of Biology, Lakehead University, Thunder Bay (Canada); College of Life Science, Shanxi University, Taiyuan (China); Wu, Bo [Department of Biology, Lakehead University, Thunder Bay (Canada); Department of Pathophysiology, Harbin Medical University, Harbin (China); Cao, Qiuhui [Department of Biology, Lakehead University, Thunder Bay (Canada); Wu, Lingyun [Department of Pathophysiology, Harbin Medical University, Harbin (China); Department of Pharmacology, University of Saskatchewan, Saskatoon (Canada); Yang, Guangdong, E-mail: gyang@lakeheadu.ca [The School of Kinesiology, Lakehead University, Thunder Bay (Canada)

    2011-12-15

    Hydrogen sulfide (H{sub 2}S) is a novel gasotransmitter that regulates cell proliferation and other cellular functions. Sulforaphane (SFN) is a sulfur-containing compound that exhibits anticancer properties, and young sprouts of broccoli are particularly rich in SFN. There is consistent epidemiological evidence that the consumption of sulfur-containing vegetables, such as garlic and cruciferous vegetables, may help reduce the occurrence of prostate cancer. Here we found that a large amount of H{sub 2}S is released when SFN is added into cell culture medium or mixed with mouse liver homogenates, respectively. Both SFN and NaHS (a H{sub 2}S donor) decreased the viability of PC-3 cells (a human prostate cancer cell line) in a dose-dependent manner, and supplement of methemoglobin or oxidized glutathione (two H{sub 2}S scavengers) reversed SFN-reduced cell viability. We further found both cystathionine gamma-lyase (CSE) and cystathionine beta-synthase are expressed in PC-3 cells and mouse prostate tissues. H{sub 2}S production in prostate tissues from CSE knockout mice was only 20% of that from wild-type mice, suggesting CSE is a major H{sub 2}S-producing enzyme in prostate. CSE overexpression enhanced H{sub 2}S production and inhibited cell viability in PC-3 cells. In addition, both SFN and NaHS activated p38 mitogen-activated protein kinases (MAPK) and c-Jun N-terminal kinase (JNK). Pre-treatment of PC-3 cells with methemoglobin decreased SFN-stimulated MAPK activities. Suppression of both p38 MAPK and JNK reversed H{sub 2}S- or SFN-reduced viability of PC-3 cells. Our results demonstrated that H{sub 2}S mediates the inhibitory effect of SFN on the proliferation of PC-3 cells, which suggests that H{sub 2}S-releasing diet or drug might be beneficial in the treatment of prostate cancer. Highlights: Black-Right-Pointing-Pointer A large amount of H{sub 2}S is released from sulforaphane. Black-Right-Pointing-Pointer H{sub 2}S mediates the anti-survival effect of

  18. Hydrogen sulfide mediates the anti-survival effect of sulforaphane on human prostate cancer cells

    International Nuclear Information System (INIS)

    Pei, Yanxi; Wu, Bo; Cao, Qiuhui; Wu, Lingyun; Yang, Guangdong

    2011-01-01

    Hydrogen sulfide (H 2 S) is a novel gasotransmitter that regulates cell proliferation and other cellular functions. Sulforaphane (SFN) is a sulfur-containing compound that exhibits anticancer properties, and young sprouts of broccoli are particularly rich in SFN. There is consistent epidemiological evidence that the consumption of sulfur-containing vegetables, such as garlic and cruciferous vegetables, may help reduce the occurrence of prostate cancer. Here we found that a large amount of H 2 S is released when SFN is added into cell culture medium or mixed with mouse liver homogenates, respectively. Both SFN and NaHS (a H 2 S donor) decreased the viability of PC-3 cells (a human prostate cancer cell line) in a dose-dependent manner, and supplement of methemoglobin or oxidized glutathione (two H 2 S scavengers) reversed SFN-reduced cell viability. We further found both cystathionine gamma-lyase (CSE) and cystathionine beta-synthase are expressed in PC-3 cells and mouse prostate tissues. H 2 S production in prostate tissues from CSE knockout mice was only 20% of that from wild-type mice, suggesting CSE is a major H 2 S-producing enzyme in prostate. CSE overexpression enhanced H 2 S production and inhibited cell viability in PC-3 cells. In addition, both SFN and NaHS activated p38 mitogen-activated protein kinases (MAPK) and c-Jun N-terminal kinase (JNK). Pre-treatment of PC-3 cells with methemoglobin decreased SFN-stimulated MAPK activities. Suppression of both p38 MAPK and JNK reversed H 2 S- or SFN-reduced viability of PC-3 cells. Our results demonstrated that H 2 S mediates the inhibitory effect of SFN on the proliferation of PC-3 cells, which suggests that H 2 S-releasing diet or drug might be beneficial in the treatment of prostate cancer. Highlights: ► A large amount of H 2 S is released from sulforaphane. ► H 2 S mediates the anti-survival effect of sulforaphane on human prostate cancer cells. ► Cystathionine gamma-lyase is a major H 2 S

  19. Proliferative activity and branching morphogenesis in the human prostate: a closer look at pre- and postnatal prostate growth

    NARCIS (Netherlands)

    Xue, Y.; Sonke, G.; Schoots, C.; Schalken, J.; Verhofstad, A.; de la Rosette, J.; Smedts, F.

    2001-01-01

    To gain further insight into the molecular cell biologic features of prostate development, we investigated the proliferative activity of prostate epithelial and stromal cells and their topographic relationship with neuroendocrine (NE) cell distribution and regional heterogeneity. Consecutive

  20. Proliferative activity and branching morphogenesis in the human prostate: a closer look at pre- and postnatal prostate growth.

    NARCIS (Netherlands)

    Xue, Y.; Sonke, G.S.; Schoots, C.; Schalken, J.A.; Verhofstad, A.A.J.; Rosette, J.J.M.H.C. de la; Smedts, F.

    2001-01-01

    BACKGROUND: To gain further insight into the molecular cell biologic features of prostate development, we investigated the proliferative activity of prostate epithelial and stromal cells and their topographic relationship with neuroendocrine (NE) cell distribution and regional heterogeneity.

  1. Association of human papilloma virus infection and oral squamous cell carcinoma in Bangladesh.

    Science.gov (United States)

    Akhter, Mahmuda; Ali, Liaquat; Hassan, Zahid; Khan, Imran

    2013-03-01

    Oral squamous cell carcinoma is the sixth most common malignancy worldwide. In Bangladesh, it comprises 20% of the whole body malignancies. Several studies found that 15% to 25% of oropharyngeal cancer cases are associated with human papilloma virus (HPV). This study is done to find the association of human papilloma virus subtypes, particularly HPV type 16 and HPV type 18, with the oral squamous cell carcinoma in Bangladeshi patients. In total, 34 diagnosed patients of oral squamous cell carcinoma were included in the study. Extracted DNA from the cancerous tissues was checked for PCR reaction to detect the subtypes of human papilloma virus. Data of the present study suggest that oral squamous cell carcinoma are almost absent in Bangladeshi patients with human papilloma virus, particularly HPV 16 and 18.

  2. Association of Human Papilloma Virus Infection and Oral Squamous Cell Carcinoma in Bangladesh

    Science.gov (United States)

    Ali, Liaquat; Hassan, Zahid; Khan, Imran

    2013-01-01

    Oral squamous cell carcinoma is the sixth most common malignancy worldwide. In Bangladesh, it comprises 20% of the whole body malignancies. Several studies found that 15% to 25% of oropharyngeal cancer cases are associated with human papilloma virus (HPV). This study is done to find the association of human papilloma virus subtypes, particularly HPV type 16 and HPV type 18, with the oral squamous cell carcinoma in Bangladeshi patients. In total, 34 diagnosed patients of oral squamous cell carcinoma were included in the study. Extracted DNA from the cancerous tissues was checked for PCR reaction to detect the subtypes of human papilloma virus. Data of the present study suggest that oral squamous cell carcinoma are almost absent in Bangladeshi patients with human papilloma virus, particularly HPV 16 and 18. PMID:23617206

  3. Lobaplatin arrests cell cycle progression in human hepatocellular carcinoma cells

    Directory of Open Access Journals (Sweden)

    Chen Chang-Jie

    2010-10-01

    Full Text Available Abstract Background Hepatocellular carcinoma (HCC still is a big burden for China. In recent years, the third-generation platinum compounds have been proposed as potential active agents for HCC. However, more experimental and clinical data are warranted to support the proposal. In the present study, the effect of lobaplatin was assessed in five HCC cell lines and the underlying molecular mechanisms in terms of cell cycle kinetics were explored. Methods Cytotoxicity of lobaplatin to human HCC cell lines was examined using MTT cell proliferation assay. Cell cycle distribution was determined by flow cytometry. Expression of cell cycle-regulated genes was examined at both the mRNA (RT-PCR and protein (Western blot levels. The phosphorylation status of cyclin-dependent kinases (CDKs and retinoblastoma (Rb protein was also examined using Western blot analysis. Results Lobaplatin inhibited proliferation of human HCC cells in a dose-dependent manner. For the most sensitive SMMC-7721 cells, lobaplatin arrested cell cycle progression in G1 and G2/M phases time-dependently which might be associated with the down-regulation of cyclin B, CDK1, CDC25C, phosphorylated CDK1 (pCDK1, pCDK4, Rb, E2F, and pRb, and the up-regulation of p53, p21, and p27. Conclusion Cytotoxicity of lobaplatin in human HCC cells might be due to its ability to arrest cell cycle progression which would contribute to the potential use of lobaplatin for the management of HCC.

  4. Recurrent chimeric RNAs enriched in human prostate cancer identified by deep sequencing

    Science.gov (United States)

    Kannan, Kalpana; Wang, Liguo; Wang, Jianghua; Ittmann, Michael M.; Li, Wei; Yen, Laising

    2011-01-01

    Transcription-induced chimeric RNAs, possessing sequences from different genes, are expected to increase the proteomic diversity through chimeric proteins or altered regulation. Despite their importance, few studies have focused on chimeric RNAs especially regarding their presence/roles in human cancers. By deep sequencing the transcriptome of 20 human prostate cancer and 10 matched benign prostate tissues, we obtained 1.3 billion sequence reads, which led to the identification of 2,369 chimeric RNA candidates. Chimeric RNAs occurred in significantly higher frequency in cancer than in matched benign samples. Experimental investigation of a selected 46 set led to the confirmation of 32 chimeric RNAs, of which 27 were highly recurrent and previously undescribed in prostate cancer. Importantly, a subset of these chimeras was present in prostate cancer cell lines, but not detectable in primary human prostate epithelium cells, implying their associations with cancer. These chimeras contain discernable 5′ and 3′ splice sites at the RNA junction, indicating that their formation is mediated by splicing. Their presence is also largely independent of the expression of parental genes, suggesting that other factors are involved in their production and regulation. One chimera, TMEM79-SMG5, is highly differentially expressed in human cancer samples and therefore a potential biomarker. The prevalence of chimeric RNAs may allow the limited number of human genes to encode a substantially larger number of RNAs and proteins, forming an additional layer of cellular complexity. Together, our results suggest that chimeric RNAs are widespread, and increased chimeric RNA events could represent a unique class of molecular alteration in cancer. PMID:21571633

  5. Anticancer effect of triterpenes from Ganoderma lucidum in human prostate cancer cells.

    Science.gov (United States)

    Qu, Lijun; Li, Sumei; Zhuo, Yumin; Chen, Jianfan; Qin, Xiaoping; Guo, Guoqing

    2017-12-01

    Ganoderma lucidum , within the Polyporaceae family of Basidiomycota, is a popular traditional remedy medicine used in Asia to promote health and longevity. Compounds extracted from G. lucidum have revealed anticancer, antioxidant and liver protective effects. G. lucidum has been associated with prostate cancer cells. G. lucidum extracts contain numerous bioactive components; however, the exact functional monomer is unknown and the role of triterpenes from G. lucidum (GLT) in prostate cancer remain obscure. The present study investigated the effects of GLT on cell viability, migration, invasion and apoptosis in DU-145 human prostate cancer cells. The results demonstrated that a high dose (2 mg/ml) of GLT inhibits cell viability in a dose- and time-dependent manner by the regulation of matrix metalloproteases. Furthermore, GLT induced apoptosis of DU-145 cells. In general, GLT exerts its effect on cancer cells via numerous mechanisms and may have potential therapeutic use for the prevention and treatment of cancer.

  6. The regulation of adiponectin receptors in human prostate cancer cell lines

    International Nuclear Information System (INIS)

    Mistry, T.; Digby, J.E.; Chen, J.; Desai, K.M.; Randeva, H.S.

    2006-01-01

    Obesity is a risk factor for prostate cancer, and plasma levels of the adipokine, adiponectin, are low in the former but high in the latter. Adiponectin has been shown to modulate cell proliferation and apoptosis, suggesting that adiponectin and its receptors (Adipo-R1, Adipo-R2) may provide a molecular association between obesity and prostate carcinogenesis. We show for First time, the protein distribution of Adipo-R1 and Adipo-R2 in LNCaP and PC3 cells, and in human prostate tissue. Using real-time RT-PCR we provide novel data demonstrating the differential regulation of Adipo-R1 and Adipo-R2 mRNA expression by testosterone, 5-α dihydrotestosterone, β-estradiol, tumour necrosis factor-α, leptin, and adiponectin in LNCaP and PC3 cells. Our findings suggest that adiponectin and its receptors may contribute to the molecular association between obesity and prostate cancer through a complex interaction with other hormones and cytokines that also play important roles in the pathophysiology of obesity and prostate cancer

  7. Isorhynchophylline, a Potent Plant Alkaloid, Induces Apoptotic and Anti-Metastatic Effects in Human Hepatocellular Carcinoma Cells through the Modulation of Diverse Cell Signaling Cascades

    Directory of Open Access Journals (Sweden)

    Hanwool Lee

    2017-05-01

    Full Text Available Isorhynchophylline (Rhy is an active pharmacological component of Uncaria rhynchophylla that has been reported previously to exert significant antihypertensive and neuroprotective effects. However, very little is known about its potential anti-cancer activities. This study was carried out to evaluate the anticancer effects of Rhy against various human carcinoma cell lines. We found that Rhy exhibited substantial cytotoxic effect against human hepatocellular carcinoma HepG2 cells when compared with other human carcinoma cell lines including those of lung, pancreas, prostate, head and neck, breast, multiple myeloma, brain and renal cell carcinoma. Rhy induced apoptosis as characterized by accumulation of cells in sub G1 phase; positive Annexin V binding; activation of caspase-8, -9, and -3; and cleavage of PARP (poly-ADP ribose polymerase. This effect of Rhy correlated with the down-regulation of various proteins that mediated cell proliferation, cell survival, metastasis, and angiogenesis. Moreover, cell proliferation, migration, and constitutive CXCR4 (C-X-C chemokine receptor type 4, MMP-9 (Matrix metallopeptidase-9, and MMP-2 expression were inhibited upon Rhy treatment. We further investigated the effect of Rhy on the oncogenic cell signaling cascades through phospho-kinase array profiling assay. Rhy was found to abrogate phospho-p38, ERK, JNK, CREB, c-Jun, Akt, and STAT3 signals, but interestingly enhanced phospho-p53 signal. Overall, our results indicate, for the first time, that Rhy could exert anticancer and anti-metastatic effects through regulation of multiple signaling cascades in hepatocellular carcinoma cells.

  8. Isorhynchophylline, a Potent Plant Alkaloid, Induces Apoptotic and Anti-Metastatic Effects in Human Hepatocellular Carcinoma Cells through the Modulation of Diverse Cell Signaling Cascades

    Science.gov (United States)

    Lee, Hanwool; Baek, Seung Ho; Lee, Jong Hyun; Kim, Chulwon; Ko, Jeong-Hyeon; Lee, Seok-Geun; Chinnathambi, Arunachalam; Alharbi, Sulaiman Ali; Yang, Woong Mo; Um, Jae-Young; Sethi, Gautam; Ahn, Kwang Seok

    2017-01-01

    Isorhynchophylline (Rhy) is an active pharmacological component of Uncaria rhynchophylla that has been reported previously to exert significant antihypertensive and neuroprotective effects. However, very little is known about its potential anti-cancer activities. This study was carried out to evaluate the anticancer effects of Rhy against various human carcinoma cell lines. We found that Rhy exhibited substantial cytotoxic effect against human hepatocellular carcinoma HepG2 cells when compared with other human carcinoma cell lines including those of lung, pancreas, prostate, head and neck, breast, multiple myeloma, brain and renal cell carcinoma. Rhy induced apoptosis as characterized by accumulation of cells in sub G1 phase; positive Annexin V binding; activation of caspase-8, -9, and -3; and cleavage of PARP (poly-ADP ribose polymerase). This effect of Rhy correlated with the down-regulation of various proteins that mediated cell proliferation, cell survival, metastasis, and angiogenesis. Moreover, cell proliferation, migration, and constitutive CXCR4 (C-X-C chemokine receptor type 4), MMP-9 (Matrix metallopeptidase-9), and MMP-2 expression were inhibited upon Rhy treatment. We further investigated the effect of Rhy on the oncogenic cell signaling cascades through phospho-kinase array profiling assay. Rhy was found to abrogate phospho-p38, ERK, JNK, CREB, c-Jun, Akt, and STAT3 signals, but interestingly enhanced phospho-p53 signal. Overall, our results indicate, for the first time, that Rhy could exert anticancer and anti-metastatic effects through regulation of multiple signaling cascades in hepatocellular carcinoma cells. PMID:28534824

  9. Association of Human Papilloma Virus Infection and Oral Squamous Cell Carcinoma in Bangladesh

    OpenAIRE

    Akhter, Mahmuda; Ali, Liaquat; Hassan, Zahid; Khan, Imran

    2013-01-01

    Oral squamous cell carcinoma is the sixth most common malignancy worldwide. In Bangladesh, it comprises 20% of the whole body malignancies. Several studies found that 15% to 25% of oropharyngeal cancer cases are associated with human papilloma virus (HPV). This study is done to find the association of human papilloma virus subtypes, particularly HPV type 16 and HPV type 18, with the oral squamous cell carcinoma in Bangladeshi patients. In total, 34 diagnosed patients of oral squamous cell car...

  10. Co-existent Paget’s Disease of the Bone, Prostate Carcinoma Skeletal Metastases and Fracture on Skeletal Scintigraphy-Lessons to be Learned

    Directory of Open Access Journals (Sweden)

    Luke I Sonoda

    2013-08-01

    Full Text Available Bone scintigraphy, despite being non-specific, is a very sensitive and simple investigation for patients with active Paget’s disease of the bone. Skeletal metastases and Paget’s disease may co-exist in the elderly patients as both conditions are commonly seen in this age group. Clinical and radiological correlation may help to improve the diagnostic specificity of a bone scintigram. We report a patient in whom concurrent Paget’s disease and a rib fracture became evident only on repeat scintigraphy following successful treatment of prostate carcinoma skeletal metastases.

  11. Androgen-Sensitized Apoptosis of HPr-1AR Human Prostate Epithelial Cells.

    Directory of Open Access Journals (Sweden)

    Congcong Chen

    Full Text Available Androgen receptor (AR signaling is crucial to the development and homeostasis of the prostate gland, and its dysregulation mediates common prostate pathologies. The mechanisms whereby AR regulates growth suppression and differentiation of luminal epithelial cells in the prostate gland and proliferation of malignant versions of these cells have been investigated in human and rodent adult prostate. However, the cellular stress response of human prostate epithelial cells is not well understood, though it is central to prostate health and pathology. Here, we report that androgen sensitizes HPr-1AR and RWPE-AR human prostate epithelial cells to cell stress agents and apoptotic cell death. Although 5α-dihydrotestosterone (DHT treatment alone did not induce cell death, co-treatment of HPr-1AR cells with DHT and an apoptosis inducer, such as staurosporine (STS, TNFt, or hydrogen peroxide, synergistically increased cell death in comparison to treatment with each apoptosis inducer by itself. We found that the synergy between DHT and apoptosis inducer led to activation of the intrinsic/mitochondrial apoptotic pathway, which is supported by robust cleavage activation of caspase-9 and caspase-3. Further, the dramatic depolarization of the mitochondrial membrane potential that we observed upon co-treatment with DHT and STS is consistent with increased mitochondrial outer membrane permeabilization (MOMP in the pro-apoptotic mechanism. Interestingly, the synergy between DHT and apoptosis inducer was abolished by AR antagonists and inhibitors of transcription and protein synthesis, suggesting that AR mediates pro-apoptotic synergy through transcriptional regulation of MOMP genes. Expression analysis revealed that pro-apoptotic genes (BCL2L11/BIM and AIFM2 were DHT-induced, whereas pro-survival genes (BCL2L1/BCL-XL and MCL1 were DHT-repressed. Hence, we propose that the net effect of these AR-mediated expression changes shifts the balance of BCL2-family proteins

  12. Downregulation of CCR1 inhibits human hepatocellular carcinoma cell invasion

    International Nuclear Information System (INIS)

    Wu Xiaofeng; Fan Jia; Wang Xiaoying; Zhou Jian; Qiu Shuangjian; Yu Yao; Liu Yinkun; Tang Zhaoyou

    2007-01-01

    CC chemokine receptor 1 (CCR1) has an important role in the recruitment of leukocytes to the site of inflammation. The migration and metastasis of tumor cells shares many similarities with leukocyte trafficking, which is mainly regulated by chemokine receptor-ligand interactions. CCR1 is highly expressed in hepatocellular carcinoma (HCC) cells and tissues with unknown functions. In this study, we silenced CCR1 expression in the human HCC cell line HCCLM3 using artificial microRNA (miRNA)-mediated RNA interference (RNAi) and examined the invasiveness and proliferation of CCR1-silenced HCCLM3 cells and the matrix metalloproteinase (MMP) activity. The miRNA-mediated knockdown expression of CCR1 significantly inhibited the invasive ability of HCCLM3 cells, but had only a minor effect on the cellular proliferation rate. Moreover, CCR1 knockdown significantly reduced the secretion of MMP-2. Together, these findings indicate that CCR1 has an important role in HCCLM3 invasion and that CCR1 might be a new target of HCC treatment

  13. The influence of human papillomavirus on nasopharyngeal carcinoma in Japan.

    Science.gov (United States)

    Kano, Makoto; Kondo, Satoru; Wakisaka, Naohiro; Moriyama-Kita, Makiko; Nakanishi, Yosuke; Endo, Kazuhira; Murono, Shigeyuki; Nakamura, Hiroyuki; Yoshizaki, Tomokazu

    2017-06-01

    Although Japan is a non-endemic area with nasopharyngeal carcinoma (NPC), the proportion of WHO type I NPC in Japan are different from that in non-endemic areas such as North America and Europe. Recently, it is said that not only Epstein-Barr virus (EBV) but also human papillomavirus (HPV) has an influence on NPC in non-endemic areas. The aim of this study is to clarify the influence of HPV on NPC in Japan. Paraffin-embedded tumor specimens were available for 59 patients with NPC diagnosed between 1996 and 2015. We detected the virus status by p16 immunohistochemistry, HPV PCR, and in situ hybridization for Epstein-Barr virus (EBV)-encoded RNA. Kaplan-Meier curves were used to compare the overall survival by viral status. Among the 59 patients, 49 (83%) were EBV-positive/HPV-negative, 2 (3%) were EBV-positive/HPV-positive, and 8 (16%) were EBV-negative/HPV-negative. All HPV-positive NPCs were co-infected with EBV. There were no significant differences between the overall survival in the three groups (p=0.111). In Japan, HPV was detected in a few patients with NPC, and we suggest that HPV has no influence on NPC carcinogenesis in this population. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  14. Phenotypic characterization of telomerase-immortalized primary non-malignant and malignant tumor-derived human prostate epithelial cell lines

    International Nuclear Information System (INIS)

    Gu Yongpeng; Li Hongzhen; Miki, Jun; Kim, Kee-Hong; Furusato, Bungo; Sesterhenn, Isabell A.; Chu, Wei-Sing; McLeod, David G.; Srivastava, Shiv; Ewing, Charles M.; Isaacs, William B.; Rhim, Johng S.

    2006-01-01

    In vitro human prostate cell culture models are critical for clarifying the mechanism of prostate cancer progression and for testing preventive and therapeutic agents. Cell lines ideal for the study of human primary prostate tumors would be those derived from spontaneously immortalized tumor cells; unfortunately, explanted primary prostate cells survive only short-term in culture, and rarely immortalize spontaneously. Therefore, we recently have generated five immortal human prostate epithelial cell cultures derived from both the benign and malignant tissues of prostate cancer patients with telomerase, a gene that prevents cellular senescence. Examination of these cell lines for their morphologies and proliferative capacities, their abilities to grow in low serum, to respond to androgen stimulation, to grow above the agar layer, to form tumors in SCID mice, suggests that they may serve as valid, useful tools for the elucidation of early events in prostate tumorigenesis. Furthermore, the chromosome alterations observed in these immortalized cell lines expressing aspects of the malignant phenotypes imply that these cell lines accurately recapitulate the genetic composition of primary tumors. These novel in vitro models may offer unique models for the study of prostate carcinogenesis and also provide the means for testing both chemopreventive and chemotherapeutic agents

  15. Trichostatin A (TSA) sensitizes the human prostatic cancer cell line DU145 to death receptor ligands treatment.

    Science.gov (United States)

    Taghiyev, Agshin F; Guseva, Natalya V; Sturm, Mary T; Rokhlin, Oskar W; Cohen, Michael B

    2005-04-01

    The human prostatic carcinoma cell line DU145 has previously been found to be resistant to treatment with TNF-family ligands. However, TRAIL, TNF-alpha and anti-Fas antibodies (Ab) treatment in combination with the histone deacetylase inhibitor Trichostatin A (TSA) converted the phenotype of DU145 from resistant to sensitive. TSA induced 15% cell death but simultaneous treatment with TRAIL, TNF-alpha and anti-Fas Ab resulted in 55%, 70% and 40% cell death, respectively. Simultaneous treatment did not increase the level of TSA-induced histone acetylation, but induced the release of acetylated histones from chromatin into the cytosol. This release was caspase dependent since it was abrogated by Z-VAD-fmk. In addition, treatment with TSA induced caspase-9 activation and resulted in the release of cytochrome c and Smac/DIABLO from mitochondria. To further investigate the role of caspase-9 in TSA-mediated apoptosis we used two different approaches: (1) cells were pretreated with the caspase-9 inhibitor Z-LEHD-fmk, and (2) cells were transfected with a dominant-negative form of caspase-9. Both approaches gave similar results: cells became resistant to treatment with TSA. These data indicate that TSA mediates its effect via the mitochondrial pathway. This was confirmed by examining DU145 overexpressing Bcl-2. These transfectants were resistant to TSA treatment. Taken together, our data shows that only simultaneous treatment with TNF-family ligands and TSA in DU145 resulted in caspase activity sufficient to induce apoptosis. The combination of TSA and TNF-family ligands could potentially be the basis for the treatment of prostate cancer.

  16. Targeting MEK5 Enhances Radiosensitivity of Human Prostate Cancer and Impairs Tumor-Associated Angiogenesis

    Science.gov (United States)

    2016-09-01

    analysis of tumor necrosis factor - alpha resistant human breast cancer cells reveals a MEK5/Erk5-mediated epithelial-mesenchymal transition phenotype...AWARD NUMBER: W81XWH-15-1-0296 TITLE: Targeting MEK5 Enhances Radiosensitivity of Human Prostate Cancer and Impairs Tumor - Associated...Cancer and Impairs Tumor -Associated Angiogenesis 5b. GRANT NUMBER W81XWH-15-1-0296 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER

  17. Cellular and molecular effects of the liposomal mTHPC derivative Foslipos in prostate carcinoma cells in vitro.

    Science.gov (United States)

    Gyenge, Emina Besic; Hiestand, Seraina; Graefe, Susanna; Walt, Heinrich; Maake, Caroline

    2011-06-01

    Meso-tetra-hydroxyphenyl-chlorine (mTHPC) is among the most powerful photosensitizers available for photodynamic therapy (PDT). However, the mechanisms leading to cell death are poorly understood. We here focused on changes at DNA and RNA levels after treatment with the liposomal mTHPC derivative Foslipos in vitro. After determination of darktoxicity, laser conditions and uptake kinetics, PC-3 prostate carcinoma cells were subjected to PDT with Foslipos, followed by assessment of cell numbers directly (TP0) or 1h (TP1), 2h (TP2), 5h (TP5) and 24h (TP24) after illumination. Nucleic acids had been extracted for evaluation of RNA amounts and integrity as well as for estimation of abasic sites as a measure for DNA damage. Furthermore, expression changes of 84 genes related to oxidative stress were investigated by quantitative polymerase chain reaction. Already at TP0, the number of dead cells was significantly higher after PDT versus controls and at TP24 more than 90% of cells had been destroyed. PDT resulted in a severe damage of both RNA and DNA. Gene expression analyses revealed an impact of PDT on pathways for oxidative and metabolic stress, heat shock, proliferation and carcinogenesis, growth arrest, inflammation, DNA repair and apoptosis signaling. Mechanisms of Foslipos-mediated PDT comprise a combination of acute and delayed lethal effects in PC-3 cells. The latter may include death processes initiated by nucleic acid damage, activation of stress and growth arrest genes in combination with a reduced capability to adequately cope with oxidative toxicity. Our results will help to better understand molecular photodynamic effects. Copyright © 2011 Elsevier B.V. All rights reserved.

  18. Argon Plasma Coagulation Therapy Versus Topical Formalin for Intractable Rectal Bleeding and Anorectal Dysfunction After Radiation Therapy for Prostate Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Yeoh, Eric, E-mail: eric.yeoh@health.sa.gov.au [Department of Radiation Oncology, Royal Adelaide Hospital, Adelaide (Australia); School of Medicine, University of Adelaide, Adelaide (Australia); Tam, William; Schoeman, Mark [School of Medicine, University of Adelaide, Adelaide (Australia); Department of Gastroenterology, Royal Adelaide Hospital, Adelaide (Australia); Moore, James; Thomas, Michelle [School of Medicine, University of Adelaide, Adelaide (Australia); Department of Colorectal Surgery, Royal Adelaide Hospital, Adelaide (Australia); Botten, Rochelle; Di Matteo, Addolorata [Department of Radiation Oncology, Royal Adelaide Hospital, Adelaide (Australia)

    2013-12-01

    Purpose: To evaluate and compare the effect of argon plasma coagulation (APC) and topical formalin for intractable rectal bleeding and anorectal dysfunction associated with chronic radiation proctitis. Methods and Materials: Thirty men (median age, 72 years; range, 49-87 years) with intractable rectal bleeding (defined as ≥1× per week and/or requiring blood transfusions) after radiation therapy for prostate carcinoma were randomized to treatment with APC (n=17) or topical formalin (n=13). Each patient underwent evaluations of (1) anorectal symptoms (validated questionnaires, including modified Late Effects in Normal Tissues–Subjective, Objective, Management, and Analytic and visual analogue scales for rectal bleeding); (2) anorectal motor and sensory function (manometry and graded rectal balloon distension); and (3) anal sphincteric morphology (endoanal ultrasound) before and after the treatment endpoint (defined as reduction in rectal bleeding to 1× per month or better, reduction in visual analogue scales to ≤25 mm, and no longer needing blood transfusions). Results: The treatment endpoint was achieved in 94% of the APC group and 100% of the topical formalin group after a median (range) of 2 (1-5) sessions of either treatment. After a follow-up duration of 111 (29-170) months, only 1 patient in each group needed further treatment. Reductions in rectal compliance and volumes of sensory perception occurred after APC, but no effect on anorectal symptoms other than rectal bleeding was observed. There were no differences between APC and topical formalin for anorectal symptoms and function, nor for anal sphincteric morphology. Conclusions: Argon plasma coagulation and topical formalin had comparable efficacy in the durable control of rectal bleeding associated with chronic radiation proctitis but had no beneficial effect on anorectal dysfunction.

  19. Argon Plasma Coagulation Therapy Versus Topical Formalin for Intractable Rectal Bleeding and Anorectal Dysfunction After Radiation Therapy for Prostate Carcinoma

    International Nuclear Information System (INIS)

    Yeoh, Eric; Tam, William; Schoeman, Mark; Moore, James; Thomas, Michelle; Botten, Rochelle; Di Matteo, Addolorata

    2013-01-01

    Purpose: To evaluate and compare the effect of argon plasma coagulation (APC) and topical formalin for intractable rectal bleeding and anorectal dysfunction associated with chronic radiation proctitis. Methods and Materials: Thirty men (median age, 72 years; range, 49-87 years) with intractable rectal bleeding (defined as ≥1× per week and/or requiring blood transfusions) after radiation therapy for prostate carcinoma were randomized to treatment with APC (n=17) or topical formalin (n=13). Each patient underwent evaluations of (1) anorectal symptoms (validated questionnaires, including modified Late Effects in Normal Tissues–Subjective, Objective, Management, and Analytic and visual analogue scales for rectal bleeding); (2) anorectal motor and sensory function (manometry and graded rectal balloon distension); and (3) anal sphincteric morphology (endoanal ultrasound) before and after the treatment endpoint (defined as reduction in rectal bleeding to 1× per month or better, reduction in visual analogue scales to ≤25 mm, and no longer needing blood transfusions). Results: The treatment endpoint was achieved in 94% of the APC group and 100% of the topical formalin group after a median (range) of 2 (1-5) sessions of either treatment. After a follow-up duration of 111 (29-170) months, only 1 patient in each group needed further treatment. Reductions in rectal compliance and volumes of sensory perception occurred after APC, but no effect on anorectal symptoms other than rectal bleeding was observed. There were no differences between APC and topical formalin for anorectal symptoms and function, nor for anal sphincteric morphology. Conclusions: Argon plasma coagulation and topical formalin had comparable efficacy in the durable control of rectal bleeding associated with chronic radiation proctitis but had no beneficial effect on anorectal dysfunction

  20. Identification of Sarcosine as a Target Molecule for the Canine Olfactory Detection of Prostate Carcinoma.

    Science.gov (United States)

    Pacik, Dalibor; Plevova, Mariana; Urbanova, Lucie; Lackova, Zuzana; Strmiska, Vladislav; Necas, Alois; Heger, Zbynek; Adam, Vojtech

    2018-03-21

    The hypothesis that dogs can detect malignant tumours through the identification of specific molecules is nearly 30 years old. To date, several reports have described the successful detection of distinct types of cancer. However, is still a lack of data regarding the specific molecules that can be recognized by a dog's olfactory apparatus. Hence, we performed a study with artificially prepared, well-characterized urinary specimens that were enriched with sarcosine, a widely reported urinary biomarker for prostate cancer (PCa). For the purposes of the study, a German shepherd dog was utilized for analyses of 60 positive and 120 negative samples. Our study provides the first evidence that a sniffer dog specially trained for the olfactory detection of PCa can recognize sarcosine in artificial urine with a performance [sensitivity of 90%, specificity of 95%, and precision of 90% for the highest amount of sarcosine (10 µmol/L)] that is comparable to the identification of PCa-diagnosed subjects (sensitivity of 93.5% and specificity of 91.6%). This study casts light on the unrevealed phenomenon of PCa olfactory detection and opens the door for further studies with canine olfactory detection and cancer diagnostics.

  1. Prediction of Aggressive Human Prostate Cancer by Cathepsin B

    Science.gov (United States)

    2008-03-01

    Cancer Res 2004;10(12 Pt 1):4118-4124. 28. Munoz E, Gomez F, Paz JI, Casado I, Silva JM, Corcuera MT, Alonso MJ. Ki-67 immunolabeling in pre...detected prostate cancer. J Pathol 2002;197(2):148-154. 34. Claudio PP, Zamparelli A, Garcia FU, Claudio L, Ammirati G, Farina A, Bovicelli A, Russo G...JA. Distinct roles for cysteine cathepsin genes in multistage tumorigenesis. Genes Dev 2006;20(5):543-556. 47. Fernandez PL, Farre X, Nadal A

  2. 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.

  3. Selective expression of myosin IC Isoform A in mouse and human cell lines and mouse prostate cancer tissues.

    Directory of Open Access Journals (Sweden)

    Ivanna Ihnatovych

    Full Text Available Myosin IC is a single headed member of the myosin superfamily. We recently identified a novel isoform and showed that the MYOIC gene in mammalian cells encodes three isoforms (isoforms A, B, and C. Furthermore, we demonstrated that myosin IC isoform A but not isoform B exhibits a tissue specific expression pattern. In this study, we extended our analysis of myosin IC isoform expression patterns by analyzing the protein and mRNA expression in various mammalian cell lines and in various prostate specimens and tumor tissues from the transgenic mouse prostate (TRAMP model by immunoblotting, qRT-PCR, and by indirect immunohistochemical staining of paraffin embedded prostate specimen. Analysis of a panel of mammalian cell lines showed an increased mRNA and protein expression of specifically myosin IC isoform A in a panel of human and mouse prostate cancer cell lines but not in non-cancer prostate or other (non-prostate- cancer cell lines. Furthermore, we demonstrate that myosin IC isoform A expression is significantly increased in TRAMP mouse prostate samples with prostatic intraepithelial neoplasia (PIN lesions and in distant site metastases in lung and liver when compared to matched normal tissues. Our observations demonstrate specific changes in the expression of myosin IC isoform A that are concurrent with the occurrence of prostate cancer in the TRAMP mouse prostate cancer model that closely mimics clinical prostate cancer. These data suggest that elevated levels of myosin IC isoform A may be a potential marker for the detection of prostate cancer.

  4. Novel Monoclonal Antibodies Recognizing Human Prostate-Specific Membrane Antigen (PSMA) as Research and Theranostic Tools.

    Science.gov (United States)

    Nováková, Zora; Foss, Catherine A; Copeland, Benjamin T; Morath, Volker; Baranová, Petra; Havlínová, Barbora; Skerra, Arne; Pomper, Martin G; Barinka, Cyril

    2017-05-01

    Prostate-specific membrane antigen (PSMA) is a validated target for the imaging and therapy of prostate cancer. Here, we report the detailed characterization of four novel murine monoclonal antibodies (mAbs) recognizing human PSMA as well as PSMA orthologs from different species. Performance of purified mAbs was assayed using a comprehensive panel of in vitro experimental setups including Western blotting, immunofluorescence, immunohistochemistry, ELISA, flow cytometry, and surface-plasmon resonance. Furthermore, a mouse xenograft model of prostate cancer was used to compare the suitability of the mAbs for in vivo applications. All mAbs demonstrate high specificity for PSMA as documented by the lack of cross-reactivity to unrelated human proteins. The 3F11 and 1A11 mAbs bind linear epitopes spanning residues 226-243 and 271-288 of human PSMA, respectively. 3F11 is also suitable for the detection of PSMA orthologs from mouse, pig, dog, and rat in experimental setups where the denatured form of PSMA is used. 5D3 and 5B1 mAbs recognize distinct surface-exposed conformational epitopes and are useful for targeting PSMA in its native conformation. Most importantly, using a mouse xenograft model of prostate cancer we show that both the intact 5D3 and its Fab fragment are suitable for in vivo imaging. With apparent affinities of 0.14 and 1.2 nM as determined by ELISA and flow cytometry, respectively, 5D3 has approximately 10-fold higher affinity for PSMA than the clinically validated mAb J591 and, therefore, is a prime candidate for the development of next-generation theranostics to target PSMA. Prostate 77:749-764, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  5. Quantification of Mesenchymal Stem Cells (MSCs) at sites of human prostate cancer.

    Science.gov (United States)

    Brennen, W Nathaniel; Chen, Shuangling; Denmeade, Samuel R; Isaacs, John T

    2013-01-01

    Circulating bone marrow-derived Mesenchymal Stem Cells (BM-MSCs) have an innate tropism for tumor tissue in response to the inflammatory microenvironment present in malignant lesions. The prostate is bombarded by numerous infectious and inflammatory insults over a lifetime. Chronic inflammation is associated with CXCL12, CCL5, and CCL2, which are highly overexpressed in prostate cancer. Among other cell types, these chemoattractant stimuli recruit BM-MSCs to the tumor. MSCs are minimally defined as plastic-adhering cells characterized by the expression of CD90, CD73, and CD105 in the absence of hematopoietic markers, which can differentiate into osteoblasts, chondrocytes, and adipocytes. MSCs are immunoprivileged and have been implicated in tumorigenesis through multiple mechanisms, including promoting proliferation, angiogenesis, and metastasis, in addition to the generation of an immunosuppressive microenvironment. We have demonstrated that MSCs represent 0.01-1.1% of the total cells present in core biopsies from primary human prostatectomies. Importantly, these analyses were performed on samples prior to expansion in tissue culture. MSCs in these prostatectomy samples are FAP-, CD90-, CD73-, and CD105-positive, and CD14-, CD20-, CD34-, CD45-, and HLA-DR-negative. Additionally, like BM-MSCs, these prostate cancer-derived stromal cells (PrCSCs) were shown to differentiate into osteoblasts, adipocytes and chondrocytes. In contrast to primary prostate cancer-derived epithelial cells, fluorescently-labeled PrCSCs and BM-MSCs were both shown to home to CWR22RH prostate cancer xenografts following IV injection. These studies demonstrate that not only are MSCs present in sites of prostate cancer where they may contribute to carcinogenesis, but these cells may also potentially be used to deliver cytotoxic or imaging agents for therapeutic and/or diagnostic purposes.

  6. Are prostate carcinoma clinical stages T1C and T2 similar?

    Directory of Open Access Journals (Sweden)

    Athanase Billis

    2006-04-01

    Full Text Available PURPOSE: A recent study has found that PSA recurrence rate for clinical T1c tumors is similar to T2 tumors, indicating a need for further refinement of clinical staging system. To test this finding we compared clinicopathologic characteristics and the time to PSA progression following radical retropubic prostatectomy of patients with clinical stage T1c tumors to those with stage T2, T2a or T2b tumors. MATERIALS AND METHODS: From a total of 186 consecutive patients submitted to prostatectomy, 33.52% had clinical stage T1c tumors, 45.45% stage T2a tumors and 21.02% stage T2b tumors. The variables studied were age, preoperative PSA, prostate weight, Gleason score, tumor extent, positive surgical margins, extraprostatic extension (pT3a, seminal vesicle invasion (pT3b, and time to PSA progression. Tumor extent was evaluated by a point-count method. RESULTS: Patients with clinical stage T1c were younger and had the lowest mean preoperative PSA. In the surgical specimen, they had higher frequency of Gleason score < 7 and more organ confined cancer. In 40.54% of the patients with clinical stage T2b tumors, there was extraprostatic extension (pT3a. During the study period, 54 patients (30.68% developed a biochemical progression. Kaplan-Meier product-limit analysis revealed no significant difference in the time to PSA progression between men with clinical stage T1c versus clinical stage T2 (p = 0.7959, T2a (p = 0.6060 or T2b (p = 0.2941 as well as between men with clinical stage T2a versus stage T2b (p = 0.0994. CONCLUSION: Clinicopathological features are not similar considering clinical stage T1c versus clinical stages T2, T2a or T2b.

  7. Androgen receptor-negative human prostate cancer cells induce osteogenesis in mice through FGF9-mediated mechanisms.

    Science.gov (United States)

    Li, Zhi Gang; Mathew, Paul; Yang, Jun; Starbuck, Michael W; Zurita, Amado J; Liu, Jie; Sikes, Charles; Multani, Asha S; Efstathiou, Eleni; Lopez, Adriana; Wang, Jing; Fanning, Tina V; Prieto, Victor G; Kundra, Vikas; Vazquez, Elba S; Troncoso, Patricia; Raymond, Austin K; Logothetis, Christopher J; Lin, Sue-Hwa; Maity, Sankar; Navone, Nora M

    2008-08-01

    In prostate cancer, androgen blockade strategies are commonly used to treat osteoblastic bone metastases. However, responses to these therapies are typically brief, and the mechanism underlying androgen-independent progression is not clear. Here, we established what we believe to be the first human androgen receptor-negative prostate cancer xenografts whose cells induced an osteoblastic reaction in bone and in the subcutis of immunodeficient mice. Accordingly, these cells grew in castrated as well as intact male mice. We identified FGF9 as being overexpressed in the xenografts relative to other bone-derived prostate cancer cells and discovered that FGF9 induced osteoblast proliferation and new bone formation in a bone organ assay. Mice treated with FGF9-neutralizing antibody developed smaller bone tumors and reduced bone formation. Finally, we found positive FGF9 immunostaining in prostate cancer cells in 24 of 56 primary tumors derived from human organ-confined prostate cancer and in 25 of 25 bone metastasis cases studied. Collectively, these results suggest that FGF9 contributes to prostate cancer-induced new bone formation and may participate in the osteoblastic progression of prostate cancer in bone. Androgen receptor-null cells may contribute to the castration-resistant osteoblastic progression of prostate cancer cells in bone and provide a preclinical model for studying therapies that target these cells.

  8. The Contributions of 8P Loss and 8Q Gain to the Malignant Phenotype in Human Prostate Tumors

    National Research Council Canada - National Science Library

    Kant, Rajiv

    2002-01-01

    .... In order to overcome this limitation, the Nl5C6 epithelial and the Nl fibroblastic cell lines were developed through immortalization of explanted human prostate tissue with the HPV and E6 and E7 proteins...

  9. Effects of cholera toxin on human colon carcinoma cell lines.

    Science.gov (United States)

    Barkla, D H; Whitehead, R H; Hayward, I P

    1992-10-01

    This study reports on changes in morphology and membrane transport in 5 human colon carcinoma cell lines treated with cholera toxin (CT). Three of the cell lines that grew as monolayers (LIM 1215, LIM 1899, LIM 2099) and 1 that grew as floating clumps (LIM 2408) did not show morphological changes after CT treatment. However, cell line LIM 1863 that grows as floating "crypt-like" organoids showed rapid and distinctive changes in morphology and membrane transport after CT treatment. At 1 and 6 hrs after CT treatment, light and transmission electron microscopy revealed rapid dilatation of the central lumen of organoids and the appearance of 2 populations of apical vesicular inclusions. The first population was unusual in being non-membrane bound and limited by fuzzy filamentous material. The second population was membrane bound. Scanning electron microscopy at 1-6 hr after CT treatment showed swelling and loss of surface microvilli on some, but not all, cells. At 24 hr after CT treatment the majority of organoids showed evidence of fluid accumulation and small apical vesicles coalesced to form large single vacuoles that obliterated normal cell morphology. By 48 hr, continued swelling produced extreme attenuation of the plasma membrane with cells taking on an "endothelial cell-like" appearance. The response to CT was dose-dependent. Uptake studies using 86Rubidium and blocking studies using ouabain and amiloride indicated that CT is acting on the Na+/K+ ATPase membrane pump to cause the increased fluid uptake by LIM 1863 cells. This study is the first to report specific morphological changes in intestine-derived cells in response to CT.(ABSTRACT TRUNCATED AT 250 WORDS)

  10. Automated quantification of aligned collagen for human breast carcinoma prognosis

    Directory of Open Access Journals (Sweden)

    Jeremy S Bredfeldt

    2014-01-01

    Full Text Available Background: Mortality in cancer patients is directly attributable to the ability of cancer cells to metastasize to distant sites from the primary tumor. This migration of tumor cells begins with a remodeling of the local tumor microenvironment, including changes to the extracellular matrix and the recruitment of stromal cells, both of which facilitate invasion of tumor cells into the bloodstream. In breast cancer, it has been proposed that the alignment of collagen fibers surrounding tumor epithelial cells can serve as a quantitative image-based biomarker for survival of invasive ductal carcinoma patients. Specific types of collagen alignment have been identified for their prognostic value and now these tumor associated collagen signatures (TACS are central to several clinical specimen imaging trials. Here, we implement the semi-automated acquisition and analysis of this TACS candidate biomarker and demonstrate a protocol that will allow consistent scoring to be performed throughout large patient cohorts. Methods: Using large field of view high resolution microscopy techniques, image processing and supervised learning methods, we are able to quantify and score features of collagen fiber alignment with respect to adjacent tumor-stromal boundaries. Results: Our semi-automated technique produced scores that have statistically significant correlation with scores generated by a panel of three human observers. In addition, our system generated classification scores that accurately predicted survival in a cohort of 196 breast cancer patients. Feature rank analysis reveals that TACS positive fibers are more well-aligned with each other, are of generally lower density, and terminate within or near groups of epithelial cells at larger angles of interaction. Conclusion: These results demonstrate the utility of a supervised learning protocol for streamlining the analysis of collagen alignment with respect to tumor stromal boundaries.

  11. Physician resource utilization in radiation oncology: a model based on management of carcinoma of the prostate

    International Nuclear Information System (INIS)

    Kobeissi, Beverly J.; Gupta, Mahendra; Perez, Carlos A.; Dopuch, Nicholas; Michalski, Jeff M.; Antwerp, George van; Gerber, Russell; Wasserman, Todd H.

    1998-01-01

    Purpose: To develop a methodology to estimate the comparative cost of physician time in treating patients with localized prostate cancer, using as an example two-dimensional (2D) vs. three-dimensional (3D) conformal irradiation techniques, and to illustrate how current cost-accounting techniques can be used to quantify the cost of physician time and effort of any treatment. Methods and Materials: Activity-based costing, a recent innovation in accounting, widely recommended for estimating and managing the costs of specific activities, was used to derive physician resource utilization costs (actual cost of the physician services and related support services consumed). Results: Patients treated with 3D conformal irradiation consume about 50% more physician time than patients receiving 2D conventional radiation therapy. The average professional reimbursement for the 3D conformal irradiation is only about 26% more than for the 2D treatment. Substantial variations in cost are found depending on the total available physician working hours. In an academic institution, a physician working 40 hours a week would have to spend an average of about 60% of available time on clinical services to break even on a 2D treatment process and over 74% of available time on clinical work to break even on a 3D treatment process. The same physician working 50 hours a week would have to spend an average of about 48% of available time on 2D clinical services and about 60% of available time on 3D clinical work to break even. Current Medicare reimbursement for 3D treatment falls short of actual costs, even if physicians work 100% of a 50-hour week. Medicare reimbursement for 2D barely allows the department to break even for 2D treatments. Conclusions: Costs based on estimates of resource use can be substantially under- or overestimated. A consistent language (method) is needed to obtain and describe the costs of radiation therapy. The methodology described here can help practitioners and

  12. Urethral dose sparing in squamous cell carcinoma of anal canal using proton therapy matching electrons with prior brachytherapy for prostate cancer: A case study.

    Science.gov (United States)

    Apinorasethkul, Ontida; Lenards, Nishele; Hunzeker, Ashley

    2016-01-01

    The purpose of this case study is to communicate a technique on treating the re-irradiation of squamous cell carcinoma (SCC) of anal canal with proton fields matched with electron fields to spare prostatic urethra. A 76-year old male presented with a secondary radiation-induced malignancy as a result of prostate brachytherapy seeds irradiation 10 years prior. A rectal examination revealed a bulky tumor at the top of the anal canal involving the left superior-most aspect of the anal canal extending superiorly into the rectum. The inferior extent was palpable approximately 3cm from the anal verge and the superior extent of the mass measured greater than 5cm in the superior-inferior dimension. Chemoradiation was suggested since the patient was opposed to abdominoperineal resection (APR) and colostomy. The use of proton therapy matching with electron fields in the re-irradiation setting could help reduce the complications. A 2 lateral proton beams were designed to treat the bulky tumor volume with 2 electron beams treating the nodal volumes. This complication of treatment fields helped spare the prostatic urethra and reduced the risk of urinary obstruction in the future. Copyright © 2016 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

  13. Smoking increased the risk of prostate cancer with grade group ≥ 4 and intraductal carcinoma in a prospective biopsy cohort.

    Science.gov (United States)

    Tang, Bo; Han, Cheng-Tao; Gan, Hua-Lei; Zhang, Gui-Ming; Zhang, Cui-Zhu; Yang, Wei-Yi; Shen, Ying; Zhu, Yao; Ye, Ding-Wei

    2017-06-01

    To investigate the association between smoking and different prostate cancer (PCa) pathological subtypes incidence in Chinese men. We prospectively included 1795 patients who underwent prostate biopsies in one tertiary center between March 2013 and April 2016. Clinical data and biopsy outcomes were collected. Logistic regression was used to evaluate the association between cigarette smoking and PCa incidence. A total of 737 men, 480 men and 58 men were diagnosed with PCa, high-grade PCa (HGPCa, grade group ≥ 4 as accepted by the 2014 ISUP) and intraductal carcinoma of the prostate (IDC-P), respectively. Current smokers had a significantly higher risk of HGPCa than never smokers (OR = 1.89, 95%CI: 1.44-2.48). No such association was observed for low-grade disease and cigarette smoking (OR = 0.84, 95%CI: 0.61-1.16). In a sub-analysis, men who had smoked longer than 30 years had a higher risk of HGPCa, compared with men who had smoked fewer than 30 years (OR = 1.50, 95%CI: 1.09-2.06). Current smokers were more likely to develop IDC-P than never smokers (OR = 2.29, 95%CI: 1.14-4.59). Among men in this Chinese biopsy cohort, current smoking was associated with highly malignant PCa incidence, such as HGPCa and IDC-P. The duration of smoking may be associated with HGPCa. © 2017 Wiley Periodicals, Inc.

  14. Urethral dose sparing in squamous cell carcinoma of anal canal using proton therapy matching electrons with prior brachytherapy for prostate cancer: A case study

    Energy Technology Data Exchange (ETDEWEB)

    Apinorasethkul, Ontida, E-mail: ontida.a@gmail.com [Medical Dosimetry Graduate Program, University of Wisconsin, La Crosse, WI (United States); Department of Radiation Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA (United States); Lenards, Nishele; Hunzeker, Ashley [Medical Dosimetry Graduate Program, University of Wisconsin, La Crosse, WI (United States)

    2016-10-01

    The purpose of this case study is to communicate a technique on treating the re-irradiation of squamous cell carcinoma (SCC) of anal canal with proton fields matched with electron fields to spare prostatic urethra. A 76-year old male presented with a secondary radiation-induced malignancy as a result of prostate brachytherapy seeds irradiation 10 years prior. A rectal examination revealed a bulky tumor at the top of the anal canal involving the left superior-most aspect of the anal canal extending superiorly into the rectum. The inferior extent was palpable approximately 3 cm from the anal verge and the superior extent of the mass measured greater than 5 cm in the superior-inferior dimension. Chemoradiation was suggested since the patient was opposed to abdominoperineal resection (APR) and colostomy. The use of proton therapy matching with electron fields in the re-irradiation setting could help reduce the complications. A 2 lateral proton beams were designed to treat the bulky tumor volume with 2 electron beams treating the nodal volumes. This complication of treatment fields helped spare the prostatic urethra and reduced the risk of urinary obstruction in the future.

  15. Enteric-coated and highly standardized cranberry extract reduces antibiotic and nonsteroidal anti-inflammatory drug use for urinary tract infections during radiotherapy for prostate carcinoma

    Directory of Open Access Journals (Sweden)

    Bonetta A

    2017-04-01

    Full Text Available Alberto Bonetta,1 Giandomenico Roviello,2,3 Daniele Generali,3,4 Laura Zanotti,3 Maria Rosa Cappelletti,3 Chiara Pacifico,5 Francesco Di Pierro6 1Oncological Radiotherapy Operative Unit, ASST, Cremona, 2Department of Molecular and Translational Medicine, University of Brescia, Brescia, 3Molecular Therapy and Pharmacogenomics Unit, ASST, Cremona, 4Department of Medical, Surgery and Health Sciences, University of Trieste, Trieste, 5Department of Medical, Surgical and Neurological Sciences, University Hospital of Siena, Siena, 6Velleja Research Scientific Department, Milan, Italy Introduction: Worldwide, bacterial resistance to antibiotic therapy is a major concern for the medical community. Antibiotic resistance mainly affects Gram-negative bacteria that are an important cause of lower urinary tract infections (LUTIs. Pelvic irradiation for prostate cancer is a risk factor for LUTIs. Cranberry extract is reported to reduce the incidence of LUTIs. The prophylactic role of an enteric-coated, highly standardized cranberry extract (VO370® in reducing LUTI episodes, urinary discomfort, and nonsteroidal anti-inflammatory drug (NSAID and antibiotic use during radiotherapy for prostate carcinoma was evaluated. Methods: A total of 924 patients with prostate carcinoma treated by radiotherapy to the prostatic and pelvic areas were randomized to receive (n=489 or not (n=435 the enteric-coated, highly standardized cranberry extract for 6–7 weeks concurrently with irradiation. Outcomes were analyzed by using Mann–Whitney U test and Pearson’s X2 test. Primary endpoint was the number of patients with LUTI; secondary endpoints were incidence of recurrence, days of treatment with antibiotics and number of subjects treated with NSAIDs, and incidence of dysuria. Results: The treatment was very well tolerated, and there were no serious side effects. All enrolled patients completed the study. Urinary infections were detected in 53 of the 489 patients (10

  16. Endostar, a recombined humanized endostatin, enhances the radioresponse for human nasopharyngeal carcinoma and human lung adenocarcinoma xenografts in mice

    International Nuclear Information System (INIS)

    Wen Qinglian; Meng Maobin; Tu Lingli; Jia Li; Zhou Lin; Xu Yong; Lu You; Yang Bo

    2009-01-01

    The purpose of this paper is to determine the efficacy of combining radiation therapy with endostar, a recombined humanized endostatin, in human nasopharyngeal carcinoma and human lung adenocarcinoma xenografts. Tumor xenografts were established in the hind limb of male athymic nude mice (BALB/c-nu) by subcutaneous transplantation. The tumor-bearing mice were assigned into four treatment groups: sham therapy (control), endostar (20 mg/kg, once daily for 10 days), radiation therapy (6 Gray per day to 30 Gray, once a day for 1 week), and endostar plus radiation therapy (combination). The experiment was repeated and mice were killed at days 3, 6, and 10 after initiation therapy, and the tumor tissues and blood samples were collected to analyze the kinetics of antitumor, antiangiogenesis, and antivascularization responses of different therapies. In human nasopharyngeal carcinoma and human lung adenocarcinoma xenografts, endostar significantly enhanced the effects of tumor growth inhibition, endothelial cell and tumor cell apoptosis induction, and improved tumor cell hypoxia of radiation therapy. Histological analyses demonstrated that endostar plus radiation also induced a significant reduction in microvascular density, microvascular area, and vascular endothelial growth factor and matrix metalloproteinase-2 expression compared with radiation and endostar alone respectively. We concluded that endostar significantly sensitized the function of radiation in antitumor and antiangiogenesis in human nasopharyngeal carcinoma and human lung adenocarcinoma xenografts by increasing the apoptosis of the endothelial cell and tumor cell, improving the hypoxia of the tumor cell, and changing the proangiogenic factors. These data provided a rational basis for clinical practice of this multimodality therapy. (author)

  17. The classification of benign and malignant human prostate tissue by multivariate analysis of {sup 1}H magnetic resonance spectra

    Energy Technology Data Exchange (ETDEWEB)

    Hahn, P.; Smith, I.; Leboldus, L.; Littman, C.; Somorjai, L.; Bezabeh, T. [Institute for Biodiagnostic, National Research Council, Manitoba (Canada)

    1998-04-01

    {sup 1}H magnetic resonance spectroscopy studies (360 MHz) were performed on specimens of benign (n = 66) and malignant (n = 21) human prostate tissue from 50 patients and the spectral data were subjected to multivariate analysis, specifically linear-discriminant analysis. On the basis of histopathological assessments, an overall classification accuracy of 96.6 % was achieved, with a sensitivity of 100 % and a specificity of 95.5 % in classifying benign prostatic hyperplasia from prostatic cancer. Resonances due to citrate, glutamate, and taurine were among the six spectral subregions identified by our algorithm as having diagnostic potential. Significantly higher levels of citrate were observed in glandular than in stromal benign prostatic hyperplasia (P < 0.05). This method shows excellent promise for the possibility of in vivo assessment of prostate tissue by magnetic resonance. (author)

  18. The study of the androgen receptor profile and changes of level of serum testosterone in human prostatic cancer

    Energy Technology Data Exchange (ETDEWEB)

    Zhining, Gui; Xiaoke, Hu; Hanping, Lu; Wei, Fan; Naiyun, Wu; Jinhui, Gao [Zhongshan University of Medical Sciences, Guangzhou, GD (China); Hua, Mei; Jinyun, Zeng [First Affiliated Hospital of Zhongshan Univ. of Medical Sciences, Guangzhou, GD (China)

    1993-11-01

    The androgen receptors in biopsy specimens of 22 cases of human prostatic cancer (PC) were studied by radioligand binding assay. The cytoplasmic androgen receptor (AcR) and nuclear androgen receptor (AnR) densities were 305.70 +- 461.68 and 363.04 +- 391.44 pmol/g protein respectively, both were significantly higher than those of 36 benign prostatic hypertrophy (BPH) and 9 normal prostate (NP). Among the prostatic cancers, the AnR/AcR ratios were significantly different between metastatic and primary cancers. This result suggested that there might be migration of AR from nucleus to cytosol in the process of metastasis. The serum testosterone studied by RIA method are significantly lower than that of BPH and NP. Thawmounted autoradiography demonstrated that AR were mainly located in epithelial cells of the glandular tissue of prostate.

  19. Human Papilloma Virus (HPV) Induced Head & Neck Squamous Cell Carcinoma: A Comprehensive Retrospect

    Science.gov (United States)

    Nishat, Roquaiya; Ramachandra, Sujatha; Kumar, Harish; Bandyopadhyay, Alokenath

    2015-01-01

    Head and Neck Squamous Cell Carcinoma accounts for the sixth most common malignancy occurring worldwide with tobacco and alcohol being the two well established risk factors. In the recent years, substantial evidence has been obtained that Human Papilloma Virus (HPV) associated head and neck cancers are on the rise. This article provides an insight into the structure of HPV genome, molecular pathogenesis, detection methods and clinical implications of HPV positive Head and Neck Squamous Cell Carcinoma. PMID:26266234

  20. 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 ...

  1. Albumin Suppresses Human Hepatocellular Carcinoma Proliferation and the Cell Cycle

    Directory of Open Access Journals (Sweden)

    Shunsuke Nojiri

    2014-03-01

    Full Text Available Many investigations have revealed that a low recurrence rate of hepatocellular carcinoma (HCC is associated with high serum albumin levels in patients; therefore, high levels of serum albumin are a major indicator of a favorable prognosis. However, the mechanism inhibiting the proliferation of HCC has not yet been elucidated, so we investigated the effect of serum albumin on HCC cell proliferation. Hep3B was cultured in MEM with no serum or containing 5 g/dL human albumin. As control samples, Prionex was added to generate the same osmotic pressure as albumin. After 24-h incubation, the expressions of α-fetoprotein (AFP, p53, p21, and p57 were evaluated with real-time PCR using total RNA extracted from the liver. Protein expressions and the phosphorylation of Rb (retinoblastoma were determined by Western blot analysis using total protein extracted from the liver. For flow cytometric analysis of the cell cycle, FACS analysis was performed. The percentages of cell cycle distribution were evaluated by PI staining, and all samples were analyzed employing FACScalibur (BD with appropriate software (ModFit LT; BD. The cell proliferation assay was performed by counting cells with using a Scepter handy automated cell counter (Millipore. The mRNA levels of AFP relative to Alb(−: Alb(−, Alb(+, and Prionex, were 1, 0.7 ± 0.2 (p < 0.001 for Alb(−, and 1 ± 0.3, respectively. The mRNA levels of p21 were 1, 1.58 ± 0.4 (p = 0.007 for Alb(− and p = 0.004 for Prionex, and 0.8 ± 0.2, respectively. The mRNA levels of p57 were 1, 4.4 ± 1.4 (p = 0.002 for Alb(− and Prionex, and 1.0 ± 0.1, respectively. The protein expression levels of Rb were similar in all culture media. The phosphorylation of P807/811 and P780 of Rb protein was reduced in Alb(+. More cells in the G0/G1 phase and fewer cells in S and G2/M phases were obtained in Alb(+ than in Alb(− (G0/G1: 60.9%, 67.7%, 61.5%; G2/M: 16.5%, 13.1%, 15.6%; S: 22.6%, 19.2%, 23.0%, Alb(−, Alb

  2. The Expression of MTUS1/ATIP and Its Major Isoforms, ATIP1 and ATIP3, in Human Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Louis, Simon N.S., E-mail: simonnsl@unimelb.edu.au; Chow, Laurie T.C.; Varghayee, Naghmeh; Rezmann, Linda A.; Frauman, Albert G.; Louis, William J. [Clinical Pharmacology and Therapeutics Unit, Department of Medicine, University of Melbourne, Austin Health, Heidelberg 3084, Victoria (Australia)

    2011-10-11

    Angiotensin II (Ang II), the main effector of the renin angiotensin system, acts upon two distinct transmembrane receptors, the Ang II type 1 and the type 2 (AT{sub 2}-) receptor, to induce promotion and inhibition of ERK2 phosphorylation. The AT{sub 2}-receptor, through an interaction with its putative signaling partner MTUS1/ATIP (AT{sub 2}-receptor interacting protein), inhibits the mitogenic effects of EGF in prostate cancer cell lines representing both early and late stage disease. This is the first report on the expression of ATIP in normal and malignant human prostatic biopsies. The expression of ATIP and its major isoforms, ATIP1 and ATIP3, in normal prostatic cells and three prostate cancer cell lines was examined using QPCR and immunohistochemistry. Human biopsies containing benign prostatic hyperplasia (BPH), high grade prostatic intraepithelial neoplasia (HGPIN) and well, moderately and poorly differentiated prostate cancer were also examined. Overall, ATIP1 and ATIP3 mRNA expression was increased in malignant compared to normal tissues and cell lines. ATIP immunostaining was low or absent in both the basal and columnar epithelial cell layers surrounding BPH acini; however, it was observed in high concentration in neoplastic epithelial cells of HGPIN and was clearly evident in cytoplasms of malignant cells in all prostate cancer grades. ATIP immunostaining was also identified in the cytoplasms of LNCaP and PC3 prostate cancer cells. As the AT{sub 2}-receptor/ATIP inhibitory signaling pathway exists in malignant cells in all grades of prostate cancer, enhancement of this pathway may be a therapeutic target even after the development of androgen-independence.

  3. The Expression of MTUS1/ATIP and Its Major Isoforms, ATIP1 and ATIP3, in Human Prostate Cancer

    International Nuclear Information System (INIS)

    Louis, Simon N.S.; Chow, Laurie T.C.; Varghayee, Naghmeh; Rezmann, Linda A.; Frauman, Albert G.; Louis, William J.

    2011-01-01

    Angiotensin II (Ang II), the main effector of the renin angiotensin system, acts upon two distinct transmembrane receptors, the Ang II type 1 and the type 2 (AT 2 -) receptor, to induce promotion and inhibition of ERK2 phosphorylation. The AT 2 -receptor, through an interaction with its putative signaling partner MTUS1/ATIP (AT 2 -receptor interacting protein), inhibits the mitogenic effects of EGF in prostate cancer cell lines representing both early and late stage disease. This is the first report on the expression of ATIP in normal and malignant human prostatic biopsies. The expression of ATIP and its major isoforms, ATIP1 and ATIP3, in normal prostatic cells and three prostate cancer cell lines was examined using QPCR and immunohistochemistry. Human biopsies containing benign prostatic hyperplasia (BPH), high grade prostatic intraepithelial neoplasia (HGPIN) and well, moderately and poorly differentiated prostate cancer were also examined. Overall, ATIP1 and ATIP3 mRNA expression was increased in malignant compared to normal tissues and cell lines. ATIP immunostaining was low or absent in both the basal and columnar epithelial cell layers surrounding BPH acini; however, it was observed in high concentration in neoplastic epithelial cells of HGPIN and was clearly evident in cytoplasms of malignant cells in all prostate cancer grades. ATIP immunostaining was also identified in the cytoplasms of LNCaP and PC3 prostate cancer cells. As the AT 2 -receptor/ATIP inhibitory signaling pathway exists in malignant cells in all grades of prostate cancer, enhancement of this pathway may be a therapeutic target even after the development of androgen-independence

  4. Antimetastatic Effects of a Novel Telomerase Inhibitor, GRN163L, on Human Prostate Cancer

    Science.gov (United States)

    2010-05-01

    Human Papilloma Virus Type 18 (HPV-18) DNA. PZ-HPV-7 cells are generally considered as non-tumorigenic in subcutaneous xenograft animal models...6481. [39] H.J. Sommerfeld, A.K. Meeker, M.A. Piatyszek, G.S. Bova, J.W. Shay, D.S. Coffey, Telomerase activity: a prevalent marker of malignant human ...6:192–8. 31. Sommerfeld HJ, Meeker AK, Piatyszek MA, Bova GS, Shay JW, Coffey DS. Telomerase activity: a prevalent marker of malignant human prostate

  5. Antiproliferative effect on human prostate cancer cells by a stinging nettle root (Urtica dioica) extract.

    Science.gov (United States)

    Konrad, L; Müller, H H; Lenz, C; Laubinger, H; Aumüller, G; Lichius, J J

    2000-02-01

    In the present study the activity of a 20% methanolic extract of stinging nettle roots (Urtica dioica L., Urticaceae) on the proliferative activity of human prostatic epithelial (LNCaP) and stromal (hPCPs) cells was evaluated using a colorimetric assay. A concentration-dependent and significant (p nettle roots observed both in an in vivo model and in an in vitro system clearly indicates a biologically relevant effect of compounds present in the extract.

  6. Effect of resveratrol and zinc on intracellular zinc status in normal human prostate epithelial cells

    Science.gov (United States)

    To evaluate the influence of resveratrol on cellular zinc status, normal human prostate epithelial (NHPrE) cells were treated with 6 levels of resveratrol (0, 0.5, 1, 2.5, 5 and 10 microM) and 4 levels of zinc [0, 4, 16, and 32 microM for zinc-deficient (ZD), zinc-normal (ZN), zinc-adequate (ZA), an...

  7. 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)

  8. Role of human papillomavirus in oropharyngeal squamous cell carcinoma: A review

    Science.gov (United States)

    Woods, Robbie SR; O’Regan, Esther M; Kennedy, Susan; Martin, Cara; O’Leary, John J; Timon, Conrad

    2014-01-01

    Human papillomavirus (HPV) has been implicated in the pathogenesis of a subset of oropharyngeal squamous cell carcinoma. As a result, traditional paradigms in relation to the management of head and neck squamous cell carcinoma have been changing. Research into HPV-related oropharyngeal squamous cell carcinoma is rapidly expanding, however many molecular pathological and clinical aspects of the role of HPV remain uncertain and are the subject of ongoing investigation. A detailed search of the literature pertaining to HPV-related oropharyngeal squamous cell carcinoma was performed and information on the topic was gathered. In this article, we present an extensive review of the current literature on the role of HPV in oropharyngeal squamous cell carcinoma, particularly in relation to epidemiology, risk factors, carcinogenesis, biomarkers and clinical implications. HPV has been established as a causative agent in oropharyngeal squamous cell carcinoma and biologically active HPV can act as a prognosticator with better overall survival than HPV-negative tumours. A distinct group of younger patients with limited tobacco and alcohol exposure have emerged as characteristic of this HPV-related subset of squamous cell carcinoma of the head and neck. However, the exact molecular mechanisms of carcinogenesis are not completely understood and further studies are needed to assist development of optimal prevention and treatment modalities. PMID:24945004

  9. Genetic and cellular studies highlight that A Disintegrin and Metalloproteinase 19 is a protective biomarker in human prostate cancer

    International Nuclear Information System (INIS)

    Hoyne, Gerard; Rudnicka, Caroline; Sang, Qing-Xiang; Roycik, Mark; Howarth, Sarah; Leedman, Peter; Schlaich, Markus; Candy, Patrick; Matthews, Vance

    2016-01-01

    Prostate cancer is the second most frequently diagnosed cancer in men worldwide. Current treatments include surgery, androgen ablation and radiation. Introduction of more targeted therapies in prostate cancer, based on a detailed knowledge of the signalling pathways, aims to reduce side effects, leading to better clinical outcomes for the patient. ADAM19 (A Disintegrin And Metalloproteinase 19) is a transmembrane and soluble protein which can regulate cell phenotype through cell adhesion and proteolysis. ADAM19 has been positively associated with numerous diseases, but has not been shown to be a tumor suppressor in the pathogenesis of any human cancers. Our group sought to investigate the role of ADAM19 in human prostate cancer. ADAM19 mRNA and protein levels were assessed in well characterised human prostate cancer cohorts. ADAM19 expression was assessed in normal prostate epithelial cells (RWPE-1) and prostate cancer cells (LNCaP, PC3) using western blotting and immunocytochemistry. Proliferation assays were conducted in LNCaP cells in which ADAM19 was over-expressed. In vitro scratch assays were performed in PC3 cells over-expressing ADAM19. Immunohistochemical studies highlighted that ADAM19 protein levels were elevated in normal prostate tissue compared to prostate cancer biopsies. Results from the clinical cohorts demonstrated that high levels of ADAM19 in microarrays are positively associated with lower stage (p = 0.02591) and reduced relapse (p = 0.00277) of human prostate cancer. In vitro, ADAM19 expression was higher in RWPE-1 cells compared to LNCaP cells. In addition, human ADAM19 over-expression reduced LNCaP cell proliferation and PC3 cell migration. Taken together, our immunohistochemical and microarray results and cellular studies have shown for the first time that ADAM19 is a protective factor for human prostate cancer. Further, this study suggests that upregulation of ADAM19 expression could be of therapeutic potential in human prostate cancer

  10. Facial nerve palsy as a primary presentation of advanced carcinoma ...

    African Journals Online (AJOL)

    A. Abdulkadir

    2016-07-02

    Jul 2, 2016 ... advanced carcinoma of the prostate: An unusual occurrence. A. Abdulkadira,∗ ... PSA was 116 ng/ml and the six cores of the digital guided prostate biopsy taken all .... Benign prostatic hyperplasia and prostate carcinoma in ...

  11. The 2014 International Society of Urological Pathology (ISUP) Consensus Conference on Gleason Grading of Prostatic Carcinoma: Definition of Grading Patterns and Proposal for a New Grading System.

    Science.gov (United States)

    Epstein, Jonathan I; Egevad, Lars; Amin, Mahul B; Delahunt, Brett; Srigley, John R; Humphrey, Peter A

    2016-02-01

    In November, 2014, 65 prostate cancer pathology experts, along with 17 clinicians including urologists, radiation oncologists, and medical oncologists from 19 different countries gathered in a consensus conference to update the grading of prostate cancer, last revised in 2005. The major conclusions were: (1) Cribriform glands should be assigned a Gleason pattern 4, regardless of morphology; (2) Glomeruloid glands should be assigned a Gleason pattern 4, regardless of morphology; (3) Grading of mucinous carcinoma of the prostate should be based on its underlying growth pattern rather than grading them all as pattern 4; and (4) Intraductal carcinoma of the prostate without invasive carcinoma should not be assigned a Gleason grade and a comment as to its invariable association with aggressive prostate cancer should be made. Regarding morphologies of Gleason patterns, there was clear consensus on: (1) Gleason pattern 4 includes cribriform, fused, and poorly formed glands; (2) The term hypernephromatoid cancer should not be used; (3) For a diagnosis of Gleason pattern 4, it needs to be seen at 10x lens magnification; (4) Occasional/seemingly poorly formed or fused glands between well-formed glands is insufficient for a diagnosis of pattern 4; (5) In cases with borderline morphology between Gleason pattern 3 and pattern 4 and crush artifacts, the lower grade should be favored; (6) Branched glands are allowed in Gleason pattern 3; (7) Small solid cylinders represent Gleason pattern 5; (8) Solid medium to large nests with rosette-like spaces should be considered to represent Gleason pattern 5; and (9) Presence of unequivocal comedonecrosis, even if focal is indicative of Gleason pattern 5. It was recognized by both pathologists and clinicians that despite the above changes, there were deficiencies with the Gleason system. The Gleason grading system ranges from 2 to 10, yet 6 is the lowest score currently assigned. When patients are told that they have a Gleason score 6 out

  12. Detection of the E7 transform gene of human papilloma virus type 16 in human oral squamous cell carcinoma.

    Science.gov (United States)

    Wang, J; Li, J; Huang, H; Fu, Y

    1998-12-01

    To determine, with the use of polymerase chain reaction, the prevalence of human papillomavirus (HPV) 16 in 30 patients with primary oral squamous cell carcinoma (OSCC) and 30 healthy control patients. DNA was extracted from freshly frozen tumor tissues of 30 patients with primary oral squamous cell carcinoma and from the oral mucosa of 30 controls. A pair of specific primers of the E7 early gene of HPV 16 were designed. PCR products were run by 1.5% agarose gel and the results of electrophoresis were photographed. HPV 16 was detected in 36.7% (11/30) of oral squamous cell carcinoma patients and 11.1% (4/30) of controls. HPV 16 has a significant association with oral squamous cell carcinoma. However, the role HPV 16 plays in the tumorigenesis of oral cancer and its clinical significance remain to be investigated.

  13. Expression of Anti-apoptotic Protein BAG3 in Human Sebaceous Gland Carcinoma of the Eyelid.

    Science.gov (United States)

    Yunoki, Tatsuya; Tabuchi, Yoshiaki; Hayashi, Atsushi

    2017-04-01

    Bcl-2-associated athanogene 3 (BAG3), a co-chaperone of heat shock protein 70 (HSP70), has been shown to play a role in anti-apoptosis of various malignant tumors. In this study, the expression of BAG3 was examined in human sebaceous gland carcinoma of the eyelid. The expression of BAG3 was evaluated by immunohistochemistry of surgical samples from 5 patients with sebaceous gland carcinoma in the eyelid. BAG3 was positive diffusely in the cytoplasm in all patients. The average positive rate of BAG3 was 73.0±26.0% in tumor cells of all patients. BAG3 was highly expressed in sebaceous gland carcinoma of the eyelid. BAG3 may play an important role in the pathogenesis and progression of sebaceous gland carcinoma of the eyelid. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  14. 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.

  15. Prostate-specific antigen (PSA/hK3): a further player in the field of breast cancer diagnostics?

    OpenAIRE

    Mannello, Ferdinando; Gazzanelli, Giancarlo

    2001-01-01

    Since its identification, much information has been obtained about prostate-specific antigen (PSA, or human glandular kallikrein 3 [hK3]), a kallikrein-like serine protease that is the most valuable tumour marker for the screening, diagnosis and management of human prostate carcinoma. Recently, it has become widely accepted that PSA is also present in many nonprostatic sources, casting doubts about the specificity of its tissue expression. Here we summarize the findings on the biomolecular ex...

  16. High-dose-rate stereotactic body radiation therapy for postradiation therapy locally recurrent prostatic carcinoma: Preliminary prostate-specific antigen response, disease-free survival, and toxicity assessment.

    Science.gov (United States)

    Fuller, Donald B; Wurzer, James; Shirazi, Reza; Bridge, Stephen S; Law, Jonathan; Mardirossian, George

    2015-01-01

    Patients with locally recurrent adenocarcinoma of the prostate following radiation therapy (RT) present a challenging problem. We prospectively evaluated the use of "high-dose-rate-like" prostate stereotactic body RT (SBRT) salvage for this circumstance, evaluating prostate-specific antigen response, disease-free survival, and toxicity. Between February 2009 and March 2014, 29 patients with biopsy-proven recurrent locally prostate cancer >2 years post-RT were treated. Median prior RT dose was 73.8 Gy and median interval to SBRT salvage was 88 months. Median recurrence Gleason score was 7 (79% was ≥7). Pre-existing RT toxicity >grade 1 was a reason for exclusion. Magnetic resonance imaging-defined prostate volume including any suspected extraprostatic extension, comprising the planning target volume. A total of 34 Gy/5 fractions was given, delivering a heterogeneous, high-dose-rate-like dose-escalation pattern. Toxicities were assessed using Common Terminology Criteria for Adverse Events, version 3.0, criteria. Twenty-nine treated patients had a median 24-month follow-up (range, 3-60 months). A median pre-SBRT salvage baseline prostate-specific antigen level of 3.1 ng/mL decreased to 0.65 ng/mL and 0.16 ng/mL at 1 and 2 years, respectively. Actuarial 2-year biochemical disease-free survival measured 82%, with no local failures. Toxicity >grade 1 was limited to the genitourinary domain, with 18% grade 2 or higher and 7% grade 3 or higher. No gastrointestinal toxicity >grade 1 occurred. Two-year disease-free survival is encouraging, and the prostate-specific antigen response kinetic appears comparable with that seen in de novo patients treated with SBRT, albeit still a preliminary finding. Grade ≥2 genitourinary toxicity was occasionally seen with no obvious predictive factor. Noting that our only brachytherapy case was 1 of the 2 cases with ≥grade 3 genitourinary toxicity, caution is recommended treating these patients. SBRT salvage of post-RT local recurrence

  17. Alterations of the Human Skin N- and O-Glycome in Basal Cell Carcinoma and Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Uwe Möginger

    2018-03-01

    Full Text Available The glycome of one of the largest and most exposed human organs, the skin, as well as glycan changes associated with non-melanoma skin cancers have not been studied in detail to date. Skin cancers such as basal cell carcinoma (BCC and squamous cell carcinoma (SCC are among the most frequent types of cancers with rising incidence rates in the aging population. We investigated the healthy human skin N- and O-glycome and its changes associated with BCC and SCC. Matched patient samples were obtained from frozen biopsy and formalin-fixed paraffin-embedded tissue samples for glycomics analyses using two complementary glycomics approaches: porous graphitized carbon nano-liquid chromatography electro spray ionization tandem mass spectrometry and capillary gel electrophoresis with laser induced fluorescence detection. The human skin N-glycome is dominated by complex type N-glycans that exhibit almost similar levels of α2-3 and α2-6 sialylation. Fucose is attached exclusively to the N-glycan core. Core 1 and core 2 type O-glycans carried up to three sialic acid residues. An increase of oligomannose type N-glycans and core 2 type O-glycans was observed in BCC and SCC, while α2-3 sialylation levels were decreased in SCC but not in BCC. Furthermore, glycopeptide analyses provided insights into the glycoprotein candidates possibly associated with the observed N-glycan changes, with glycoproteins associated with binding events being the most frequently identified class.

  18. Tuberculous prostatitis: mimicking a cancer.

    Science.gov (United States)

    Aziz, El Majdoub; Abdelhak, Khallouk; Hassan, Farih Moulay

    2016-01-01

    Genitourinary tuberculosis is a common type of extra-pulmonary tuberculosis . The kidneys, ureter, bladder or genital organs are usually involved. Tuberculosis of the prostate has mainly been described in immune-compromised patients. However, it can exceptionally be found as an isolated lesion in immune-competent patients. Tuberculosis of the prostate may be difficult to differentiate from carcinoma of the prostate and the chronic prostatitis when the prostate is hard and nodular on digital rectal examination and the urine is negative for tuberculosis bacilli. In many cases, a diagnosis of tuberculous prostatitis is made by the pathologist, or the disease is found incidentally after transurethral resection. Therefore, suspicion of tuberculous prostatitis requires a confirmatory biopsy of the prostate. We report the case of 60-year-old man who presented a low urinary tract syndrome. After clinical and biological examination, and imaging, prostate cancer was highly suspected. Transrectal needle biopsy of the prostate was performed and histological examination showed tuberculosis lesions.

  19. Vanadate monomers and dimers both inhibit the human prostatic acid phosphatase.

    Science.gov (United States)

    Crans, D C; Simone, C M; Saha, A K; Glew, R H

    1989-11-30

    A combination of enzyme kinetics and 51V NMR spectroscopy was used to identify the species of vanadate that inhibits acid phosphatases. Monomeric vanadate was shown to inhibit wheat germ and potato acid phosphatases. At pH 5.5, the vanadate dimer inhibits the human prostatic acid phosphatase whereas at pH 7.0 it is the vanadate monomer that inhibits this enzyme. The pH-dependent shift in the affinity of the prostatic phosphatase for vanadate is presumably due to deprotonation of an amino acid side chain in or near the binding site resulting in a conformational change in the protein. pH may be a subtle effector of the insulin-like vanadate activity in biological systems and may explain some of the differences in selectivity observed with the protein phosphatases.

  20. Everyman's prostate phantom: kiwi-fruit substitute for human prostates at magnetic resonance imaging, diffusion-weighted imaging and magnetic resonance spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Mueller-Lisse, Ullrich G.; Murer, Sophie; Kuhn, Marissa [University of Munich (' ' Ludwig-Maximilians-Universitaet' ' , LMU), Department of Radiology, Faculty of Medicine, Muenchen (Germany); Mueller-Lisse, Ulrike L. [University of Munich (' ' Ludwig-Maximilians-Universitaet' ' , LMU), Department of Urology, Faculty of Medicine, Muenchen (Germany); Interdisciplinary Oncology Centre Munich (IOZ), Department of Urology, Munich (Germany); Scheidler, Juergen [University of Munich (' ' Ludwig-Maximilians-Universitaet' ' , LMU), Department of Radiology, Faculty of Medicine, Muenchen (Germany); Radiology Centre Munich (RZM), Muenchen (Germany); Scherr, Michael [University of Munich (' ' Ludwig-Maximilians-Universitaet' ' , LMU), Department of Radiology, Faculty of Medicine, Muenchen (Germany); BG Unfallklinik Murnau, Department of Radiology, Murnau am Staffelsee (Germany)

    2017-08-15

    To apply an easy-to-assemble phantom substitute for human prostates in T2-weighted magnetic resonance imaging (T2WI), diffusion-weighted imaging (DWI) and 3D magnetic resonance spectroscopy (MRS). Kiwi fruit were fixed with gel hot and cold compress packs on two plastic nursery pots, separated by a plastic plate, and submerged in tap water inside a 1-L open-spout plastic watering can for T2WI (TR/TE 7500/101 ms), DWI (5500/61 ms, ADC b50-800 s/mm{sup 2} map) and MRS (940/145 ms) at 3.0 T, with phased array surface coils. One green kiwi fruit was additionally examined with an endorectal coil. Retrospective comparison with benign peripheral zone (PZ) and transitional zone (TZ) of prostate (n = 5), Gleason 6-7a prostate cancer (n = 8) and Gleason 7b-9 prostate cancer (n = 7) validated the phantom. Mean contrast between central placenta (CP) and outer pericarp (OP, 0.346-0.349) or peripheral placenta (PP, 0.364-0.393) of kiwi fruit was similar to Gleason 7b-9 prostate cancer and PZ (0.308) in T2WI. ADC values of OP and PP (1.27 ± 0.07-1.37 ± 0.08 mm{sup 2}/s x 10{sup -3}) resembled PZ and TZ (1.39 ± 0.17-1.60 ± 0.24 mm{sup 2}/s x 10{sup -3}), while CP (0.91 ± 0.14-0.99 ± 0.10 mm{sup 2}/s x 10{sup -3}) resembled Gleason 7b-9 prostate cancer (1.00 ± 0.25 mm{sup 2}/s x 10{sup -3}). MR spectra showed peaks of citrate and myo-inositol in kiwi fruit, and citrate and ''choline+creatine'' in prostates. The phantom worked with an endorectal coil, too. The kiwi fruit phantom reproducibly showed zones similar to PZ, TZ and cancer in human prostates in T2WI and DWI and two metabolite peaks in MRS and appears suitable to compare different MR protocols, coil systems and scanners. (orig.)

  1. High-risk human papillomavirus (HPV) DNA sequences in metaplastic breast carcinomas of Mexican women

    International Nuclear Information System (INIS)

    Herrera-Goepfert, Roberto; Vela-Chávez, Teresa; Carrillo-García, Adela; Lizano-Soberón, Marcela; Amador-Molina, Alfredo; Oñate-Ocaña, Luis F; Hallmann, Rita Sotelo-Regil

    2013-01-01

    Metaplastic carcinoma, an uncommon subtype of breast cancer, is part of the spectrum of basal-like, triple receptor-negative breast carcinomas. The present study examined 20 surgical specimens of metaplastic breast carcinomas, for the presence of high-risk Human papillomavirus (HPV), which is suspected to be a potential carcinogenic agent for breast carcinoma. Mastectomy specimens from patients harboring metaplastic breast carcinoma, as defined by the World Health Organization (WHO), and who attended the Instituto Nacional de Cancerologia in Mexico City, were retrieved from the files of the Department of Pathology accumulated during a 16-year period (1995–2008). Demographic and clinical information was obtained from patients’ medical records. DNA was extracted from formalin-fixed, paraffin-embedded tumors and HPV type-specific amplification was performed by means of Polymerase chain reaction (PCR). Quantitative Real-time (RT) PCR was conducted in HPV positive cases. Statistically, the association of continuous or categorical variables with HPV status was tested by the Student t, the Chi square, or Fisher’s exact tests, as appropriate. High-risk HPV DNA was detected in eight (40%) of 20 metaplastic breast carcinomas: seven (87.5%) HPV-16 and one (12.5%) HPV-18. Mean age of patients with HPV-positive cases was 49 years (range 24–72 years), the same as for HPV-negative cases (range, 30–73 years). There were not striking differences between HPV + and HPV– metaplastic carcinomas regarding clinical findings. Nearly all cases were negative for estrogen, progesterone and Human epidermal growth factor receptor 2 (HER2), but positive for Epidermal growth factor receptor (EGFR). High-risk HPV has been strongly associated with conventional breast carcinomas, although the subtle mechanism of neoplastic transformation is poorly understood. In Mexican patients, the prevalence of HPV infection among metaplastic breast carcinomas is higher than in non-metaplastic ones

  2. Enhanced induction of apoptosis by combined treatment of human carcinoma cells with X rays and death receptor agonists

    International Nuclear Information System (INIS)

    Hamasu, Taku; Inanami, Osamu; Asanuma, Taketoshi; Kuwabara, Mikinori

    2005-01-01

    The death receptors Fas and DR5 are known to be expressed not only in immune cells but also in various tumor cells. The aim of the present study was to determine whether X irradiation enhanced induction of apoptosis in Tp53 wild type and Tp53-mutated tumor cell lines treated with agonists against these death receptors. We showed that 5 Gy of X irradiation significantly up-regulated the expression of death receptors Fas and DR5 on the plasma membrane in gastric cancer cell lines MKN45 and MKN28, lung cancer cell line A549, and prostate cancer cell line DU145, and that subsequent treatments with agonistic molecules for these death receptors, Fas antibody CHl1 and TRAIL, increased the formation of active fragment p20 of caspase 3 followed by the induction of apoptosis. This death-receptor-mediated apoptosis was independent of Tp53 status since MKN28 and DU145 were Tp53-mutated. The post-irradiation treatment of the cells with N-acetyl-L-cysteine (NAC) abolished the up-regulation of the expression of Fas and DR5 on the plasma membrane. NAC also attenuated the increase in the formation of p20 and the induction of apoptosis by agonistic molecules. These results suggested that the increase in the induction of apoptosis by combined treatment with X irradiation and CHl1 or TRAIL occurred through a change of the intracellular redox state independent of Tp53 status in human carcinoma cell lines. (author)

  3. [Primary study on fluro [ 19F] berberine derivative for human hepatocellular carcinoma targetting in vitro].

    Science.gov (United States)

    Zhang, Tong; Wu, Xiaoai; Cai, Huawei; Liang, Meng; Fan, Chengzhong

    2017-04-01

    [ 18 F]HX-01, a Fluorine-18 labeled berberine derivative, is a potential positron emission tomography (PET) tumor imaging agent, while [ 19 F]HX-01 is a nonradioactive reference substance with different energy state and has the same physical and chemical properties. In order to collect data for further study of [ 18 F]HX-01 PET imaging of hepatocellular carcinoma in vivo , this study compared the uptake of [ 19 F]HX-01 by human hepatocellular carcinoma and normal hepatocytes in vitro . The target compound, [ 19 F]HX-01, was synthesized in one step using berberrubine and 3-fluoropropyl 4-methylbenzenesulfonate. Cellular uptake and localization of [ 19 F]HX-01 were performed by a fluorescence microscope in human hepatocellular carcinoma HepG2, SMMC-7721 and human normal hepatocyte HL-7702. Cellular proliferation inhibition and cell cytotoxicity assay of the [ 19 F]HX-01 were conducted using cell counting kit-8 (CCK-8) on HepG2, SMMC-7721 and HL-7702 cells. Fluorescent microscopy showed that the combining ability of [ 19 F]HX-01 to the carcinoma SMMC-7721 and HepG2 was higher than that to the normal HL-7702. Cellular proliferation inhibition assay demonstrated that [ 19 F]HX-01 leaded to a dose-dependent inhibition on SMMC-7721, HepG2, and HL-7702 proliferation. Cell cytotoxicity assay presented that the cytotoxicity of [ 19 F]HX-01 to SMMC-7721 and HepG2 was obviously higher than that to HL-7702. This in vitro study showed that [ 19 F]HX-01 had a higher selectivity on human hepatocellular carcinoma cells (SMMC-7721, HepG2) but has less toxicity to normal hepatocytes (HL-7702). This could set up the idea that the radioactive reference substance [ 18 F]HX-01 may be worthy of further development as a potential molecular probe targeting human hepatocellular carcinoma using PET.

  4. Biosynthesis and metabolism of steroid hormones by human adrenal carcinomas

    Directory of Open Access Journals (Sweden)

    Brown J.W.

    2000-01-01

    Full Text Available Over a 15-year period, our university-based laboratory obtained 125 adrenal tumors, of which 15 (12% were adrenal cortical carcinomas. Of these, 6 (40% of the carcinomas occurred in patients with clear clinical manifestations of steroid hormone excess. Adrenal cortical carcinoma cells derived from the surgically resected tumors in 4 of these patients were isolated and established in primary culture. Radiotracer steroid interconversion studies were carried out with these cultures and also on mitochondria isolated from homogenized tissues. Large tumors had the lowest steroidogenic activities per weight, whereas small tumors had more moderately depressed enzyme activities relative to cells from normal glands. In incubations with pregnenolone as substrate, 1 mM metyrapone blocked the synthesis of corticosterone and cortisol and also the formation of aldosterone. Metyrapone inhibition was associated with a concomitant increase in the formation of androgens (androstenedione and testosterone from pregnenolone. Administration of metyrapone in vivo before surgery in one patient resulted in a similar increase in plasma androstenedione, though plasma testosterone levels were not significantly affected. In cultures of two of four tumors examined, dibutyryl cAMP stimulated 11ß-hydroxylase activity modestly; ACTH also had a significant stimulatory effect in one of these tumors. Unlike results obtained with normal or adenomatous adrenal cortical tissues, mitochondria from carcinomatous cells showed a lack of support of either cholesterol side-chain cleavage enzyme complex or steroid 11ß-hydroxylase activity by Krebs cycle intermediates (10 mM isocitrate, succinate or malate. This finding is consistent with the concept that these carcinomas may tend to function predominantly in an anaerobic manner, rather than through the oxidation of Krebs cycle intermediates.

  5. Scanned ion beam therapy for prostate carcinoma. Comparison of single plan treatment and daily plan-adapted treatment

    International Nuclear Information System (INIS)

    Hild, Sebastian; Graeff, Christian; Rucinski, Antoni; Zink, Klemens; Habl, Gregor; Durante, Marco; Herfarth, Klaus; Bert, Christoph

    2016-01-01

    Intensity-modulated particle therapy (IMPT) for tumors showing interfraction motion is a topic of current research. The purpose of this work is to compare three treatment strategies for IMPT to determine potential advantages and disadvantages of ion prostate cancer therapy. Simulations for three treatment strategies, conventional one-plan radiotherapy (ConvRT), image-guided radiotherapy (IGRT), and online adaptive radiotherapy (ART) were performed employing a dataset of 10 prostate cancer patients with six CT scans taken at one week intervals. The simulation results, using a geometric margin concept (7-2 mm) as well as patient-specific internal target volume definitions for IMPT were analyzed by target coverage and exposure of critical structures on single fraction dose distributions. All strategies led to clinically acceptable target coverage in patients exhibiting small prostate motion (mean displacement < 4 mm), but IGRT and especially ART led to significant sparing of the rectum. In 20 % of the patients, prostate motion exceeded 4 mm causing insufficient target coverage for ConvRT (V95 mean = 0.86, range 0.63-0.99) and IGRT (V95 mean = 0.91, range 0.68-1.00), while ART maintained acceptable target coverage. IMPT of prostate cancer demands consideration of rectal sparing and adaptive treatment replanning for patients exhibiting large prostate motion. (orig.) [de

  6. Clinical Implication of Elevated Human Cervical Cancer Oncogene-1 Expression in Esophageal Squamous Cell Carcinoma

    OpenAIRE

    Liu, Ying; Li, Ke; Ren, Zhonghai; Li, Shenglei; Zhang, Hongyan; Fan, Qingxia

    2012-01-01

    The human cervical cancer oncogene 1 (HCCR-1), a novel human oncoprotein, has been shown to be upregulated in various human tumors and plays a critical role in tumorigenesis and tumor progression. Here, the authors investigated HCCR-1 level in esophageal squamous cell carcinoma (ESCC) tissues and assessed the correlation between HCCR-1 level and prognosis of the patients with ESCC. HCCR-1 levels were investigated by immunohistochemistry, in situ hybridization, real-time quantit...

  7. Influence of human papillomavirus on the clinical presentation of oropharyngeal carcinoma in the United States.

    Science.gov (United States)

    Stenmark, Matthew H; Shumway, Dean; Guo, Cui; Vainshtein, Jeffrey; Mierzwa, Michelle; Jagsi, Reshma; Griggs, Jennifer J; Banerjee, Mousumi

    2017-10-01

    Much of what is known about the significance of human papillomavirus (HPV) in oropharyngeal squamous cell carcinoma is derived from single-institution retrospective studies, post hoc analyses of tissue specimens from clinical trials, and tissue bank studies with a small sample size. The objective of this study is to investigate the impact of HPV on the frequency and clinical presentation of oropharyngeal carcinoma in a large, national sample with information from patients who underwent HPV testing. Retrospective, cross-sectional study. We identified a comprehensive national sample of 8,359 patients with oropharyngeal carcinoma and known HPV status diagnosed between 2010 and 2011 within the National Cancer Database. Multivariable logistic regression was used to assess correlates of patient and tumor characteristics on HPV status. Among patients with oropharyngeal carcinoma, the frequency of HPV-related squamous cell carcinoma in the United States was 65.4%. HPV-related oropharyngeal carcinoma was associated with younger age, male sex, and white race (P presentation (P clinical profile, supporting efforts to re-evaluate the staging and treatment paradigm for HPV-associated oropharyngeal cancer. 4. Laryngoscope, 127:2270-2278, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

  8. [Human papilloma viruses: other risk factor of head and neck carcinoma].

    Science.gov (United States)

    Woto-Gaye, G; M'Farrej, M K; Doh, K; Thiam, I; Touré, S; Diop, R; Dial, C

    2016-08-01

    Head and neck carcinoma (HNC) occupy the sixth place as the most frequent type of cancer worldwide. Next to alcohol and tobacco intoxication, other risk factors (RF) are suspected, including the human papilloma viruses (HPVs). The aim of this study was to highlight the prevalence of HPVs and histo-epidemiological characteristics of HNC HPV+ in Senegal. This is a prospective, multicenter preliminary study of 18 months (January 1, 2012-June 30, 2014). The cases of HNC histologically confirmed in Senegal were then sent to the bio-pathology department of the Curie Institute in Paris to search HPVs. In the 90 included cases, the PCR technique was successful in 54 cases (60%). HPVs were found in seven cases, that is, a prevalence of 13%. HPVs were associated with 5 cases of hypopharyngeal carcinoma and 2 cases of carcinoma of the oral cavity. Patients with HNC HPV+ had a median age of 42 years against 49 years for HPV-patients. Three patients (42.8%) with HPV+ carcinomas were smokers. Of the 47 HPV-patients, 40 patients (87.1%) had alcohol intoxication and/or smoking. The concept of oral sex was refuted by all our patients. Squamous cell carcinoma was the only histological type found. HPV+ cell carcinoma showed no specific histological appearance. HPVs are another certain RF of HNC in Senegal. The major therapeutic and prognostic impact of HPVinduced cancers requires the systematic search of the viruses by the PCR technique.

  9. Systematic gene microarray analysis of the lncRNA expression profiles in human uterine cervix carcinoma.

    Science.gov (United States)

    Chen, Jie; Fu, Ziyi; Ji, Chenbo; Gu, Pingqing; Xu, Pengfei; Yu, Ningzhu; Kan, Yansheng; Wu, Xiaowei; Shen, Rong; Shen, Yan

    2015-05-01

    The human uterine cervix carcinoma is one of the most well-known malignancy reproductive system cancers, which threatens women health globally. However, the mechanisms of the oncogenesis and development process of cervix carcinoma are not yet fully understood. Long non-coding RNAs (lncRNAs) have been proved to play key roles in various biological processes, especially development of cancer. The function and mechanism of lncRNAs on cervix carcinoma is still rarely reported. We selected 3 cervix cancer and normal cervix tissues separately, then performed lncRNA microarray to detect the differentially expressed lncRNAs. Subsequently, we explored the potential function of these dysregulated lncRNAs through online bioinformatics databases. Finally, quantity real-time PCR was carried out to confirm the expression levels of these dysregulated lncRNAs in cervix cancer and normal tissues. We uncovered the profiles of differentially expressed lncRNAs between normal and cervix carcinoma tissues by using the microarray techniques, and found 1622 upregulated and 3026 downregulated lncRNAs (fold-change>2.0) in cervix carcinoma compared to the normal cervical tissue. Furthermore, we found HOXA11-AS might participate in cervix carcinogenesis by regulating HOXA11, which is involved in regulating biological processes of cervix cancer. This study afforded expression profiles of lncRNAs between cervix carcinoma tissue and normal cervical tissue, which could provide database for further research about the function and mechanism of key-lncRNAs in cervix carcinoma, and might be helpful to explore potential diagnosis factors and therapeutic targets for cervix carcinoma. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  10. Prophylactic tamsulosin (Flomax) in patients undergoing prostate 125I brachytherapy for prostate carcinoma: Final report of a double-blind placebo-controlled randomized study

    International Nuclear Information System (INIS)

    Elshaikh, Mohamed A.; Ulchaker, James C.; Reddy, Chandana A.; Angermeier, Kenneth W.; Klein, Eric A.; Chehade, Nabil; Altman, Andrew; Ciezki, Jay P.

    2005-01-01

    Purpose: To evaluate the effectiveness of prophylactic tamsulosin (Flomax) in reducing the urinary symptoms in patients undergoing 125 I prostate implantation (PI) for prostate adenocarcinoma. Methods and materials: This is a single-institution, double-blind, placebo-controlled, randomized trial for patients undergoing PI for prostate adenocarcinoma comparing prophylactic tamsulosin versus placebo. Eligibility criteria included patients not taking tamsulosin or other α-blockers treated with PI. The patients were randomly assigned to either tamsulosin (0.8 mg, orally once a day) or matched placebo. All patients started the medication 4 days before PI and continued for 60 days. The American Urologic Association (AUA) symptom index questionnaire was used to assess urinary symptoms. The AUA questionnaire was administered before PI for a baseline score and weekly for 8 weeks after PI. Patients were taken off the study if they developed urinary retention, had intolerable urinary symptoms, or wished to discontinue with the trial. Results: One hundred twenty-six patients were enrolled in this study from November 2001 to January 2003 (118 were evaluable: 58 in the tamsulosin arm and 60 in the placebo group). Pretreatment and treatment characteristics were comparably matched between the two groups. The urinary retention rate was 17% (10 patients) in the placebo group compared with 10% (6 patients) in the tamsulosin group (p = 0.3161). Eighty-eight percent (14 patients) of those who developed urinary retention experienced it within 2 weeks after the PI. Intolerable urinary symptoms were reported equally (10 patients in each group) with 70% occurring in the first 2 weeks after PI. There was a significant difference in mean AUA score in favor of tamsulosin at Week 5 after PI (p = 0.03). Conclusions: Prophylactic tamsulosin (0.8 mg/day) before prostate brachytherapy did not significantly affect urinary retention rates, but had a positive effect on urinary morbidity at Week 5

  11. A randomized, controlled trial of aerobic exercise for treatment-related fatigue in men receiving radical external beam radiotherapy for localized prostate carcinoma.

    Science.gov (United States)

    Windsor, Phyllis M; Nicol, Kathleen F; Potter, Joan

    2004-08-01

    Advice to rest and take things easy if patients become fatigued during radiotherapy may be detrimental. Aerobic walking improves physical functioning and has been an intervention for chemotherapy-related fatigue. A prospective, randomized, controlled trial was performed to determine whether aerobic exercise would reduce the incidence of fatigue and prevent deterioration in physical functioning during radiotherapy for localized prostate carcinoma. Sixty-six men were randomized before they received radical radiotherapy for localized prostate carcinoma, with 33 men randomized to an exercise group and 33 men randomized to a control group. Outcome measures were fatigue and distance walked in a modified shuttle test before and after radiotherapy. There were no significant between group differences noted with regard to fatigue scores at baseline (P = 0.55) or after 4 weeks of radiotherapy (P = 0.18). Men in the control group had significant increases in fatigue scores from baseline to the end of radiotherapy (P = 0.013), with no significant increases observed in the exercise group (P = 0.203). A nonsignificant reduction (2.4%) in shuttle test distance at the end of radiotherapy was observed in the control group; however, in the exercise group, there was a significant increase (13.2%) in distance walked (P = 0.0003). Men who followed advice to rest and take things easy if they became fatigued demonstrated a slight deterioration in physical functioning and a significant increase in fatigue at the end of radiotherapy. Home-based, moderate-intensity walking produced a significant improvement in physical functioning with no significant increase in fatigue. Improved physical functioning may be necessary to combat radiation fatigue.

  12. Association of anorectal dose-volume histograms and impaired fecal continence after 3D conformal radiotherapy for carcinoma of the prostate

    International Nuclear Information System (INIS)

    Vordermark, Dirk; Schwab, Michael; Ness-Dourdoumas, Rhea; Sailer, Marco; Flentje, Michael; Koelbl, Oliver

    2003-01-01

    Purpose: The late toxicity of fecal incontinence after pelvic radiotherapy is now frequently recognized but the etiology poorly understood. We therefore investigated associations between dose-volume histogram (DVH) parameters of the rectum and the anal canal with fecal continence as measured by an established 10-item questionnaire. Methods and materials: Forty-four patients treated for carcinoma of the prostate with 58-72 Gy of 3D conformal radiotherapy between 1995 and 1999 who completed the questionnaire formed the study population. Total continence scores of treated patients obtained 1.5 years (median) after radiotherapy were compared to a control group of 30 patients before radiotherapy. Median, mean, minimum and maximum doses as well as the volume (% and ml) treated to 40, 50, 60 and 70 Gy were determined separately for anal canal and rectum. DVH parameters were correlated with total continence score (Spearman rank test) and patients grouped according to observed continence were compared regarding DVH values (Mann-Whitney U-test). Results: Median fecal continence scores were significantly worse in the irradiated than in the control group (31 vs. 35 of a maximum 36 points). In treated patients, 59%/27%/14% were classified as fully continent, slightly incontinent and severely incontinent. Continence was similar in the 58-to-62-Gy, 66-Gy and 68-to-72-Gy dose groups. No DVH parameter was significantly correlated with total continence score, but severely incontinent patients had a significantly higher minimum dose to the anal canal than fully continent/slightly incontinent, accompanied by portals extending significantly further inferiorly with respect to the ischial tuberosities. Conclusions: Excluding the inferior part of the anal canal from the treated volume in 3D conformal therapy for carcinoma of the prostate appears to be a promising strategy to prevent radiation-induced fecal incontinence

  13. The effect of local control on metastatic dissemination in carcinoma of the prostate: Long-term results in patients treated with 125I implantation

    International Nuclear Information System (INIS)

    Fuks, Z.; Leibel, S.A.; Wallner, K.E.; Begg, C.B.; Fair, W.R.; Anderson, L.L.; Hilaris, B.S.; Whitmore, W.F.

    1991-01-01

    The study evaluates the effect of the locally recurring tumor on the incidence of metastatic disease in early stage carcinoma of the prostate. The probability of distant metastases was studied in 679 patients with Stage B-C/N0 carcinoma of the prostate treated at MSKCC between 1970 and 1985 (median follow-up of 97 months). Patients were staged with pelvic lymph node dissection and treated with retropubic 125I implantation. The actuarial distant metastases free survival (DMFS) for patients at risk at 15 years after initial therapy was 37%. Cox proportional hazard regression analysis of covariates affecting the metastatic outcome showed that local failure, used in the model as a time dependent variable, was the most significant covariate, although stage, grade, and implant volume were also found to be independent variables. The relative risk of metastatic spread subsequent to local failure was 4-fold increased compared to the risk without evidence of local relapse. The 15-year actuarial DMFS in 351 patients with local control was 77% compared to 24% in 328 patients who developed local relapses (p less than 0.00001). The relation of distant spread to the local outcome was observed regardless of stage, grade, or implant dose. Even stage B1/N0-Grade I patient with local control showed a 15-year actuarial DMFS of 82%, compared to 22% in patients with local relapse (p less than 0.00001). The median local relapse-free survival (LRFS) in the 268 patients with local recurrences who did not receive hormonal therapy before distant metastases were detected was 51 months, compared to a median of 71 months for DMFS in the same patients (p less than 0.001), consistent with the possibility that distant dissemination may develop secondary to local failure

  14. JS-K promotes apoptosis by inducing ROS production in human prostate cancer cells.

    Science.gov (United States)

    Qiu, Mingning; Chen, Lieqian; Tan, Guobin; Ke, Longzhi; Zhang, Sai; Chen, Hege; Liu, Jianjun

    2017-03-01

    Reactive oxygen species (ROS) are chemical species that alter redox status, and are responsible for inducing carcinogenesis. The purpose of the present study was to assess the effects of the glutathione S transferase-activated nitric oxide donor prodrug, JS-K, on ROS accumulation and on proliferation and apoptosis in human prostate cancer cells. Cell proliferation and apoptosis, ROS accumulation and the activation of the mitochondrial signaling pathway were measured. The results demonstrated that JS-K may inhibit prostate cancer cell growth in a dose- and time-dependent manner, and induce ROS accumulation and apoptosis in a dose-dependent manner. With increasing concentrations of JS-K, expression of pro-apoptotic proteins increased, but Bcl-2 expression decreased. Additionally, the antioxidant N-acetylcysteine reversed JS-K-induced cell apoptosis; conversely, the pro-oxidant glutathione disulfide exacerbated JS-K-induced apoptosis. In conclusion, the data suggest that JS-K induces prostate cancer cell apoptosis by increasing ROS levels.

  15. Subcellular distribution of zinc in the benign and malignant human prostate

    International Nuclear Information System (INIS)

    Leake, A.; Chrisholm, G.D.; Busuttil, A.; Habib, F.K

    1984-01-01

    The subcellular distribution of zinc and its interaction with androgens has been examined in the benign and malignant human prostate. Endogenously, most of the zinc was associated with the nuclear fraction but signigicant concentrations were also found in the cytosol. Furthermore, the epithelium contained more zinc than that found in either the stroma or the intact gland. Zinc concentrations were lower in the subcellular fractions of the cancerous tissue when compared to hyperplastic specimens. In vitro uptake of zinc into prostatic homogenates was rapid and at equilibrium the binding was stable for both the 4degC and the 37degC incubations. At low zinc concentrations (<5mM) the uptake was higher in the nucleus, whereas at higher concentraions, the cancerous tissue exhibited a greater capacity for the metal which was predominantly retained by the cytosol. Our data suggest the presence of a saturable zinc retention mechanism in the nucleus. The zinc uptake was found to be independent of any added androgen. In contrast, the total androgen uptake by the prostate was significantly enhanced by the addition of zinc. This effect was not due to increases in the nuclear and cytosolic receptor binding since zinc inhibited the binding of the androgen to these receptors. (author)

  16. p,p'-Dichlorodiphenyltrichloroethane (p,p'-DDT) and p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) repress prostate specific antigen levels in human prostate cancer cell lines.

    Science.gov (United States)

    Wong, Lilian I L; Labrecque, Mark P; Ibuki, Naokazu; Cox, Michael E; Elliott, John E; Beischlag, Timothy V

    2015-03-25

    Despite stringent restrictions on their use by many countries since the 1970s, the endocrine disrupting chemicals, DDT and DDE are still ubiquitous in the environment. However, little attention has been directed to p,p'-DDT and the anti-androgen, p,p'-DDE on androgen receptor (AR) target gene transcription in human cells. Inhibitors of androgenic activity may have a deleterious clinical outcome in prostate cancer screens and progression, therefore we determined whether environmentally relevant concentrations of p,p'-DDT and p,p'-DDE negatively impact AR-regulated expression of prostate-specific antigen (PSA), and other AR target genes in human LNCaP and VCaP prostate cancer cells. Quantitative real-time PCR and immuno-blotting techniques were used to measure intracellular PSA, PSMA and AR mRNA and protein levels. We have shown for the first time that p,p'-DDT and p,p'-DDE repressed R1881-inducible PSA mRNA and protein levels in a dose-dependent manner. Additionally, we used the fully automated COBAS PSA detection system to determine that extracellular PSA levels were also significantly repressed. These chemicals achieve this by blocking the recruitment of AR to the PSA promoter region at 10 μM, as demonstrated by the chromatin immunoprecipitation (ChIP) in LNCaP cells. Both p,p'-DDT and p,p'-DDE repressed R1881-inducible AR protein accumulation at 10 μM. Thus, we conclude that men who have been exposed to either DDT or DDE may produce a false-negative PSA test when screening for prostate cancer, resulting in an inaccurate clinical diagnosis. More importantly, prolonged exposure to these anti-androgens may mimic androgen ablation therapy in individuals with prostate cancer, thus exacerbating the condition by inadvertently forcing adaptation to this stress early in the disease. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  17. Anti-Inflammatory (IL-10 Levels and Affects the Survival of Prostate Carcinoma Patients: An Explorative Study in North Indian Population

    Directory of Open Access Journals (Sweden)

    Shailendra Dwivedi

    2014-01-01

    Full Text Available Objective. Inflammation is an important hallmark of all cancers and net inflammatory response is determined by a delicate balance between pro- and anti-inflammatory cytokines, which may be affected by tobacco exposure, so the present study was designed to explore the effect of various modes of tobacco exposure on interleukin-12 (IL-12 and interleukin-10 (IL-10 inflammatory cytokine levels and survival in prostate carcinoma (PCa patients. Methods. 285 cancer patients and equal controls with 94 BPH (benign prostatic hyperplasia were recruited; baseline levels of serum IL-12 and IL-10 were measured and analyzed in various tobacco exposed groups by appropriate statistical tool. Five-year survivals of patients were analyzed by Log-rank (Mantel-Cox test (graph pad version 5. Results. The expression of serum proinflammatory (IL-12 and anti-inflammatory (IL-10 cytokines was correlated with tobacco exposed group as smokers, chewers, and alcohol users have shown significantly higher levels (P<0.001 with significantly lower median survivals (27.1 months, standard error = 2.86, and 95% CI: 21.4–32.62; than nonusers. Stages III and IV of tobacco addicted patients have also shown significantly increased levels of IL-12 and IL-10. Conclusions. IL-12 and IL-10 seem to be affected by various modes of tobacco exposure and inflammation also affects median survival of cancer patients.

  18. Activated α2-macroglobulin binding to human prostate cancer cells triggers insulin-like responses.

    Science.gov (United States)

    Misra, Uma Kant; Pizzo, Salvatore Vincent

    2015-04-10

    Ligation of cell surface GRP78 by activated α2-macroglobulin (α2M*) promotes cell proliferation and suppresses apoptosis. α2M*-treated human prostate cancer cells exhibit a 2-3-fold increase in glucose uptake and lactate secretion, an effect similar to insulin treatment. In both α2M* and insulin-treated cells, the mRNA levels of SREBP1-c, SREBP2, fatty-acid synthase, acetyl-CoA carboxylase, ATP citrate lyase, and Glut-1 were significantly increased together with their protein levels, except for SREBP2. Pretreatment of cells with α2M* antagonist antibody directed against the carboxyl-terminal domain of GRP78 blocks these α2M*-mediated effects, and silencing GRP78 expression by RNAi inhibits up-regulation of ATP citrate lyase and fatty-acid synthase. α2M* induces a 2-3-fold increase in lipogenesis as determined by 6-[(14)C]glucose or 1-[(14)C]acetate incorporation into free cholesterol, cholesterol esters, triglycerides, free fatty acids, and phosphatidylcholine, which is blocked by inhibitors of fatty-acid synthase, PI 3-kinase, mTORC, or an antibody against the carboxyl-terminal domain of GRP78. We also assessed the incorporation of [(14)CH3]choline into phosphatidylcholine and observed similar effects. Lipogenesis is significantly affected by pretreatment of prostate cancer cells with fatostatin A, which blocks sterol regulatory element-binding protein proteolytic cleavage and activation. This study demonstrates that α2M* functions as a growth factor, leading to proliferation of prostate cancer cells by promoting insulin-like responses. An antibody against the carboxyl-terminal domain of GRP78 may have important applications in prostate cancer therapy. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  19. Immunocytochemical characterization of explant cultures of human prostatic stromal cells

    NARCIS (Netherlands)

    A. Kooistra (Anko); A.M.J. Elissen (Arianne ); J.J. Konig (Josee); M. Vermey; Th.H. van der Kwast (Theo); J.C. Romijn (Johannes); F.H. Schröder (Fritz)

    1995-01-01

    textabstractThe study of stromal-epithelial interactions greatly depends on the ability to culture both cell types separately, in order to permit analysis of their interactions under defined conditions in reconstitution experiments. Here we report the establishment of explant cultures of human

  20. Preclinical evaluation of transcriptional targeting strategy for human hepatocellular carcinoma in an orthotopic xenograft mouse model.

    Science.gov (United States)

    Sia, Kian Chuan; Huynh, Hung; Chung, Alexander Yaw Fui; Ooi, London Lucien Peng Jin; Lim, Kiat Hon; Hui, Kam Man; Lam, Paula Yeng Po

    2013-08-01

    Gene regulation of many key cell-cycle players in S-, G(2) phase, and mitosis results from transcriptional repression in their respective promoter regions during the G(0) and G(1) phases of cell cycle. Within these promoter regions are phylogenetically conserved sequences known as the cell-cycle-dependent element (CDE) and cell-cycle genes homology regions (CHR) sites. Thus, we hypothesize that transcriptional regulation of cell-cycle regulation via the CDE/CHR region together with liver-specific apolipoprotein E (apoE)-hAAT promoter could bring about a selective transgene expression in proliferating human hepatocellular carcinoma. We show that the newly generated vector AH-6CC-L2C could mediate hepatocyte-targeted luciferase gene expression in tumor cells and freshly isolated short-term hepatocellular carcinoma cultures from patient biopsy. In contrast, normal murine and human hepatocytes infected with AH-6CC-L2C expressed minimal or low luciferase activities. In the presence of prodrug 5-fluorocytosine (5-FC), AH-6CC-L2C effectively suppressed the growth of orthotopic hepatocellular carcinoma patient-derived xenograft mouse model via the expression of yeast cytosine deaminase (yCD) that converts 5-FC to anticancer metabolite 5-fluoruracil. More importantly, we show that combination treatment of AH-6CC-L2C with an EZH2 inhibitor, DZNep, that targets EpCAM-positive hepatocellular