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1.
Korean J Parasitol ; 58(3): 217-227, 2020 Jun.
Article in English | MEDLINE | ID: mdl-32615735

ABSTRACT

Trichomonas vaginalis causes inflammation of the prostate and has been detected in tissues of prostate cancers (PCa), prostatitis and benign prostatic hyperplasia. Obesity is a risk factor for PCa and causes a chronic subclinical inflammation. This chronic inflammation further exacerbates adipose tissue inflammation as results of migration and activation of macrophages. Macrophages are the most abundant immune cells in the PCa microenvironment. M2 macrophages, known as Tumor-Associated Macrophages, are involved in increasing cancer malignancy. In this study, conditioned medium (TCM) of PCa cells infected with live trichomonads contained chemokines that stimulated migration of the mouse preadipocytes (3T3-L1 cells). Conditioned medium of adipocytes incubated with TCM (ATCM) contained Th2 cytokines (IL-4, IL-13). Macrophage migration was stimulated by ATCM. In macrophages treated with ATCM, expression of M2 markers increased, while M1 markers decreased. Therefore, it is suggested that ATCM induces polarization of M0 to M2 macrophages. In addition, conditioned medium from the macrophages incubated with ATCM stimulates the proliferation and invasiveness of PCa. Our findings suggest that interaction between inflamed PCa treated with T. vaginalis and adipocytes causes M2 macrophage polarization, so contributing to the progression of PCa.


Subject(s)
Adipocytes/immunology , Macrophages/immunology , Prostatic Neoplasms/etiology , Prostatic Neoplasms/parasitology , Trichomonas vaginalis , Animals , Cell Communication/immunology , Cell Line, Tumor , Chemokines/immunology , Inflammation , Male , Mice , Obesity , Prostatic Neoplasms/pathology , Risk Factors
2.
Prostate ; 79(11): 1316-1325, 2019 08.
Article in English | MEDLINE | ID: mdl-31212384

ABSTRACT

BACKGROUND: Urogenital infection with Schistosoma haematobium is a risk factor for the development of squamous cell carcinoma of the urinary bladder. The pathophysiology is thought to be mediated in part by inflammation, cellular damage, and bladder regeneration induced by the parasitic infection. Herein, we report an unusual case of schistosomiasis of the prostate that was found concurrent with prostate adenocarcinoma in a radical prostatectomy specimen from a man in the United States. METHODS: The infecting Schistosoma species was characterized via histomorphology and acid-fast stain. The concurrent Gleason score 6 prostate cancer was assessed for ETS transcription factor ERG (ERG), phosphatase and tensin homolog (PTEN), p27, and p53 status using immunohistochemistry (IHC). Cellular proliferation and the presence of intermediate cells in prostatic atrophy were assessed via immunostaining for Ki67 and CK903, respectively. RESULTS: Histomorphology and acid-fast stain of the infecting species were consistent with S. haematobium. We classified the Gleason score 6 prostate adenocarcinoma via IHC as ERG positive, PTEN intact, p27 intact, and without p53 nuclear accumulation. The prostatic epithelium immediately adjacent to the schistosomiasis-related granulomatous inflammation was atrophic and accompanied by increased cellular proliferation and the presence of intermediate cells. Upon literature review, we determined that prostate schistosomiasis is associated with a young age of prostate cancer diagnosis and highly aggressive prostate cancer. CONCLUSIONS: This is a rare case of prostate schistosomiasis in the United States; however, prostate schistosomiasis occurs frequently in endemic areas. The patient had traveled to a Schistosoma-endemic region, which was the likely location of exposure to the parasite. To our knowledge, this is the first report of the association of proliferative inflammatory atrophy and intermediate cells with schistosomiasis of the prostate. We propose that prostate schistosomiasis may be considered as a risk factor for the development of prostate cancer in geographic regions where Schistosoma species are endemic.


Subject(s)
Adenocarcinoma/parasitology , Carcinogenesis/pathology , Prostate/parasitology , Prostatic Neoplasms/parasitology , Schistosomiasis/pathology , Adenocarcinoma/pathology , Adenocarcinoma/surgery , Humans , Inflammation/parasitology , Inflammation/pathology , Male , Middle Aged , Prostate/pathology , Prostate/surgery , Prostatectomy , Prostatic Neoplasms/pathology , Prostatic Neoplasms/surgery , Schistosomiasis/complications
3.
Prostate ; 79(10): 1133-1146, 2019 07.
Article in English | MEDLINE | ID: mdl-31050003

ABSTRACT

BACKGROUND: Trichomonas vaginalis (Tv) is the most common sexually transmitted parasite. It is detected in prostatic tissue of benign prostatic hyperplasia, prostatitis, and prostate cancer (PCa) and has been suggested to cause chronic prostatitis. Moreover, up to 20% of all cancers worldwide are associated with chronic inflammation. Here, we investigated whether inflammatory mediators produced by normal human prostate epithelial cells (RWPE-1) stimulated with Tv could promote growth and invasiveness of PCa cells. METHODS: Conditioned medium of RWPE-1 cells was prepared by stimulating them with Tv (trichomonad-conditioned medium [TCM]) and without Tv (conditioned medium [CM]). Promotion of PCa cells (PC3, DU145, and LNCaP) was assessed by wound healing, proliferation, and invasion assays. RESULTS: We observed that the production of interleukin (IL)-1ß, IL-6, CCL2, CXCL8, prostaglandin-E2 (PGE2 ), and COX2 by RWPE-1 cells was increased by stimulating them with Tv. When PCa cells were incubated with TCM, their proliferation, invasion, and migration increased. Moreover, they showed increased epithelial-mesenchymal transition (EMT)-related markers by a reduction in epithelial markers and an increase in mesenchymal markers. In vivo, xenograft tumor tissues injected with TCM also showed increased expression of cyclin D1 and proliferating cell nuclear antigen, as well as induction of EMT. Receptors and signal molecules of PCa cells increased in response to exposure to TCM, and blocking receptors (CXCR1, CXCR2, C-C chemokine receptor 2, glycoprotein 130, EP2, and EP4) reduced the proliferation of PCa cells with decreased production of cytokines (CCL2, IL-6, and CXCL8) and PGE2 , and expression of NF-κB and Snail1. CONCLUSIONS: Our results suggest that Tv infection may be one of the factors creating the supportive microenvironment to promote proliferation and invasiveness of PCa cells.


Subject(s)
Cell Proliferation/physiology , Epithelial Cells/pathology , Neoplasm Invasiveness/pathology , Prostatic Neoplasms/pathology , Prostatitis/pathology , Trichomonas vaginalis , Chemokine CCL2/metabolism , Dinoprostone/metabolism , Epithelial Cells/metabolism , Epithelial Cells/parasitology , Humans , Inflammation/metabolism , Inflammation/parasitology , Inflammation/pathology , Interleukin-1beta/metabolism , Interleukin-6/metabolism , Interleukin-8/metabolism , Male , Prostate/metabolism , Prostate/parasitology , Prostate/pathology , Prostatic Neoplasms/metabolism , Prostatic Neoplasms/parasitology , Prostatitis/metabolism , Prostatitis/parasitology , Trichomonas Infections/metabolism , Trichomonas Infections/pathology
4.
Proc Natl Acad Sci U S A ; 116(12): 5687-5692, 2019 03 19.
Article in English | MEDLINE | ID: mdl-30842276

ABSTRACT

Melanoma differentiation-associated gene-7/interleukin-24 (mda-7/IL-24) is a multifunctional cytokine displaying broad-spectrum anticancer activity in vitro or in vivo in preclinical animal cancer models and in a phase 1/2 clinical trial in patients with advanced cancers. mda-7/IL-24 targets specific miRNAs, including miR-221 and miR-320, for down-regulation in a cancer-selective manner. We demonstrate that mda-7/IL-24, administered through a replication incompetent type 5 adenovirus (Ad.mda-7) or with His-MDA-7/IL-24 protein, down-regulates DICER, a critical regulator in miRNA processing. This effect is specific for mature miR-221, as it does not affect Pri-miR-221 expression, and the DICER protein, as no changes occur in other miRNA processing cofactors, including DROSHA, PASHA, or Argonaute. DICER is unchanged by Ad.mda-7/IL-24 in normal immortal prostate cells, whereas Ad.mda-7 down-regulates DICER in multiple cancer cells including glioblastoma multiforme and prostate, breast, lung, and liver carcinoma cells. MDA-7/IL-24 protein down-regulates DICER expression through canonical IL-20/IL-22 receptors. Gain- and loss-of-function studies confirm that overexpression of DICER rescues deregulation of miRNAs by mda-7/IL-24, partially rescuing cancer cells from mda-7/IL-24-mediated cell death. Stable overexpression of DICER in cancer cells impedes Ad.mda-7 or His-MDA-7/IL-24 inhibition of cell growth, colony formation, PARP cleavage, and apoptosis. In addition, stable overexpression of DICER renders cancer cells more resistant to Ad.mda-7 inhibition of primary and secondary tumor growth. MDA-7/IL-24-mediated regulation of DICER is reactive oxygen species-dependent and mediated by melanogenesis-associated transcription factor. Our research uncovers a distinct role of mda-7/IL-24 in the regulation of miRNA biogenesis through alteration of the MITF-DICER pathway.


Subject(s)
DEAD-box RNA Helicases/metabolism , Interleukins/metabolism , MicroRNAs/metabolism , Microphthalmia-Associated Transcription Factor/metabolism , Ribonuclease III/metabolism , Animals , Apoptosis/physiology , Cell Differentiation/physiology , Cell Line, Tumor , Cell Proliferation/physiology , DEAD-box RNA Helicases/biosynthesis , DEAD-box RNA Helicases/genetics , Down-Regulation , Genes, Tumor Suppressor , Humans , Interleukins/genetics , Male , Mice , Mice, Nude , MicroRNAs/biosynthesis , Microphthalmia-Associated Transcription Factor/genetics , Neoplasms/genetics , Neoplasms/metabolism , Neoplasms/pathology , Prostatic Neoplasms/genetics , Prostatic Neoplasms/metabolism , Prostatic Neoplasms/parasitology , Reactive Oxygen Species/metabolism , Ribonuclease III/biosynthesis , Ribonuclease III/genetics , Signal Transduction , Xenograft Model Antitumor Assays/methods
5.
Int J Cancer ; 144(10): 2377-2380, 2019 05 15.
Article in English | MEDLINE | ID: mdl-30242839

ABSTRACT

We previously observed a positive association between seropositivity for the parasite Trichomonas vaginalis and risk of clinically significant prostate cancer at diagnosis. Here, we examined whether T. vaginalis seropositivity was associated with increased prostate cancer-specific or all-cause mortality among prostate cancer patients. We studied 736 men with prostate cancer from the Physicians' Health Study (PHS) and 749 men with prostate cancer from the Health Professionals Follow-Up Study (HPFS). We used Cox proportional hazards regression models to estimate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of the association between T. vaginalis serostatus and progression to death from prostate cancer and from all causes. In PHS, 423 men died of any cause during a median follow-up of 13.8 years from the date of cancer diagnosis, among whom 131 died of prostate cancer. In HPFS, there were 287 deaths, including 77 deaths from prostate cancer, during a median follow-up of 12.8 years. We found no association between T. vaginalis serostatus and either prostate cancer mortality or all-cause mortality in either the PHS or HPFS. While previous studies suggest a possible role for T. vaginalis in the development of clinically significant prostate cancer, our findings do not support the hypothesis that T. vaginalis serostatus is associated with mortality among prostate cancer patients.


Subject(s)
Prostatic Neoplasms/etiology , Prostatic Neoplasms/mortality , Trichomonas Vaginitis/complications , Trichomonas vaginalis/pathogenicity , Aged , Case-Control Studies , Disease Progression , Female , Follow-Up Studies , Humans , Male , Middle Aged , Prospective Studies , Prostate/parasitology , Prostate/pathology , Prostatic Neoplasms/parasitology , Prostatic Neoplasms/pathology , Risk Factors , Trichomonas Vaginitis/pathology
6.
Clin Genitourin Cancer ; 17(1): 32-37, 2019 Feb.
Article in English | MEDLINE | ID: mdl-30348512

ABSTRACT

BACKGROUND: Inflammation and infections have been associated with prostate cancer progression. We assessed whether elevated serum cytokines or T. vaginalis seropositivity at the time of diagnosis was associated with higher grade or lethal prostate cancer. PATIENTS AND METHODS: Men with localized or metastatic prostate cancer were included in this study. Cytokine serum levels including interleukin (IL)-1α, IL-1ß, IL-2, IL-6, IL-8, monocyte chemotactic protein 1 (CCL-2), tumor necrosis factor α, and growth-regulated oncogene α (CXCL-1) using a multiplex enzyme-linked immunosorbent assay and T. vaginalis serology were measured in blood samples at diagnosis. RESULTS: A total of 324 patients were identified at time of localized disease and 118 at time of metastatic disease. Of the 189 patients with localized disease and clinical follow-up data (median, 73 months), 28 developed lethal disease. There was no association between circulating cytokine levels above median concentrations nor T. vaginalis seropositivity and risk of intermediate- to high-risk or lethal prostate cancer. CONCLUSION: Higher levels of serum cytokine levels and T. vaginalis seropositivity at diagnosis are not associated with high-grade or lethal prostate cancer and do not aid risk stratification of localized prostate cancer.


Subject(s)
Biomarkers, Tumor/analysis , Cytokines/blood , Neoplasm Grading , Prostatic Neoplasms/pathology , Trichomonas Infections/complications , Aged , Cohort Studies , Follow-Up Studies , Humans , Male , Middle Aged , Prognosis , Prostatic Neoplasms/blood , Prostatic Neoplasms/epidemiology , Prostatic Neoplasms/parasitology , Seroepidemiologic Studies , Trichomonas Infections/parasitology , Trichomonas vaginalis/physiology
7.
Rev Esp Patol ; 52(1): 54-56, 2019.
Article in English | MEDLINE | ID: mdl-30583833

ABSTRACT

The presence of foreign bodies in a prostate transurethral resection may pose a histopathological challenge. A 65-year-old white man with urinary obstructive symptoms was subjected to a transurethral resection. Histopathology showed a squamous cell carcinoma affecting prostatic ducts and multiple foreign bodies; their differential diagnosis was between iodine-125 seeds and Schistosoma sp. eggs, as both can show oval morphology and terminal spines. The seeds are irregular, homogeneous and solid, unlike Schistosoma eggs that are heterogeneous, with a lytic appearance and some embryonated or calcified. The seeds are located in prostatic ducts inducing periductal fibrosis whereas the Schistosoma sp. eggs are found in the stroma inducing desmoplasia and granulomas. The seeds are associated with a lymphoplasmacytic infiltrate while the eggs are surrounded by eosinophils.


Subject(s)
Carcinoma, Squamous Cell/pathology , Foreign Bodies/diagnosis , Iodine Radioisotopes/analysis , Ovum , Prostatic Neoplasms/pathology , Schistosoma , Aged , Animals , Brachytherapy/instrumentation , Carcinoma, Squamous Cell/parasitology , Carcinoma, Squamous Cell/radiotherapy , Carcinoma, Squamous Cell/surgery , Case-Control Studies , Humans , Iodine Radioisotopes/therapeutic use , Male , Prostate/parasitology , Prostate/pathology , Prostatic Neoplasms/parasitology , Prostatic Neoplasms/radiotherapy , Prostatic Neoplasms/surgery
8.
Cancer Causes Control ; 26(10): 1461-6, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26223890

ABSTRACT

PURPOSE: Previous epidemiologic studies have observed positive associations between Trichomonas vaginalis (Tv) serostatus and both prostate cancer (PCa) risk and mortality. However, only a few small older studies have examined Tv antibody persistence over time, all of which were composed mainly of female patients. Therefore, we examined Tv antibody persistence over time, as well as intra-individual variability, among middle- to older-aged men in the Southern Community Cohort Study (SCCS). METHODS: We tested baseline and repeat plasma specimens (collected 1-3 years later) from 248 male participants for Tv antibodies. We used the same enzyme-linked immunosorbent assay as in previous studies of Tv serostatus and PCa. RESULTS: At baseline, 46 (18.5 %) participants were seropositive for Tv infection. Seventy-six percent of these men were still seropositive 1-3 years later. A similar proportion of men "seroconverted" (4.0 %) as "seroreverted" (4.4 %), all of whom had absorbance values near the cutoff point for seropositivity. Overall, substantial agreement was observed between baseline and repeat serostatus (κ = 0.72, 95 % confidence interval 0.60-0.83). CONCLUSION: Tv seropositivity was largely persistent between plasma specimens collected 1-3 years apart from middle- to older-aged men. These high levels of persistence are similar to those observed for other sexually transmitted infections frequently investigated in relation to PCa.


Subject(s)
Antibodies, Protozoan/blood , Trichomonas vaginalis/immunology , Adult , Aged , Cohort Studies , Enzyme-Linked Immunosorbent Assay , Humans , Male , Middle Aged , Prostatic Neoplasms/parasitology , Risk Factors , Sex Factors , Time Factors , Trichomonas Infections/immunology
9.
Aktuelle Urol ; 45(3): 209-17, 2014 May.
Article in German | MEDLINE | ID: mdl-24806028

ABSTRACT

BACKGROUND: The aim of this study is the construction of a questionnaire which determines uro-oncological patients' attitudes to their own bodies. The questionnaire will be tested by means of psychometric criteria for suitability. In this way, the emotional-affective and perceptual--cognitive characteristics of the body concept will be detected more effectively. PARTICIPANTS AND METHODS: For the construction, 12 interviews with patients were conducted and items from four body concept questionnaires were analysed. Subsequently, a draft version, containing 133 items, was written. A total of 305 participants (PCa n=205; healthy n=100) were questioned in 2 studies. Thereafter the suitability of the items could be checked by psychometric and factor analytical criteria. RESULTS: The psychometric testing of the statements led to a selection of the items. 40 items could be established as applicable and were therefore accepted for the final questionnaire. CONCLUSION: The indentified scales show good psychometric characteristics and also differentiate between the healthy and the clinical samples. Preliminary analyses prove the validity of the scales, although this should be subjected to further testing for assurance.


Subject(s)
Body Image , Postoperative Complications/psychology , Prostatectomy/psychology , Prostatic Neoplasms/parasitology , Prostatic Neoplasms/surgery , Surveys and Questionnaires , Aged , Humans , Interview, Psychological , Male , Middle Aged , Psychometrics/statistics & numerical data , Reference Values , Reproducibility of Results
10.
Proc Natl Acad Sci U S A ; 111(22): 8179-84, 2014 Jun 03.
Article in English | MEDLINE | ID: mdl-24843155

ABSTRACT

The human-infective parasite Trichomonas vaginalis causes the most prevalent nonviral sexually transmitted infection worldwide. Infections in men may result in colonization of the prostate and are correlated with increased risk of aggressive prostate cancer. We have found that T. vaginalis secretes a protein, T. vaginalis macrophage migration inhibitory factor (TvMIF), that is 47% similar to human macrophage migration inhibitory factor (HuMIF), a proinflammatory cytokine. Because HuMIF is reported to be elevated in prostate cancer and inflammation plays an important role in the initiation and progression of cancers, we have explored a role for TvMIF in prostate cancer. Here, we show that TvMIF has tautomerase activity, inhibits macrophage migration, and is proinflammatory. We also demonstrate that TvMIF binds the human CD74 MIF receptor with high affinity, comparable to that of HuMIF, which triggers activation of ERK, Akt, and Bcl-2-associated death promoter phosphorylation at a physiologically relevant concentration (1 ng/mL, 80 pM). TvMIF increases the in vitro growth and invasion through Matrigel of benign and prostate cancer cells. Sera from patients infected with T. vaginalis are reactive to TvMIF, especially in males. The presence of anti-TvMIF antibodies indicates that TvMIF is released by the parasite and elicits host immune responses during infection. Together, these data indicate that chronic T. vaginalis infections may result in TvMIF-driven inflammation and cell proliferation, thus triggering pathways that contribute to the promotion and progression of prostate cancer.


Subject(s)
Macrophages/immunology , Prostatic Neoplasms/immunology , Prostatic Neoplasms/parasitology , Protozoan Proteins/immunology , Trichomonas Infections/immunology , Trichomonas vaginalis/immunology , Amino Acid Sequence , Cell Line, Tumor , Cells, Cultured , Conserved Sequence , Humans , Intramolecular Oxidoreductases/genetics , Intramolecular Oxidoreductases/immunology , MAP Kinase Signaling System/immunology , Macrophage Migration-Inhibitory Factors/genetics , Macrophage Migration-Inhibitory Factors/immunology , Macrophages/cytology , Macrophages/parasitology , Male , Molecular Sequence Data , Prostate/immunology , Prostate/parasitology , Prostate/pathology , Prostatic Neoplasms/pathology , Protozoan Proteins/genetics , Protozoan Proteins/metabolism , Sequence Homology , Trichomonas Infections/complications , Trichomonas Infections/parasitology , Trichomonas vaginalis/genetics , Trichomonas vaginalis/metabolism
12.
J Natl Cancer Inst ; 101(20): 1406-11, 2009 Oct 21.
Article in English | MEDLINE | ID: mdl-19741211

ABSTRACT

BACKGROUND: A recent nested case-control study found that the presence of antibodies against Trichomonas vaginalis, a common nonviral sexually transmitted infection, was positively associated with subsequent incidence of prostate cancer. We confirmed these findings in an independent population and related serostatus for antibodies against T vaginalis to prostate cancer incidence and mortality. METHODS: We conducted a case-control study nested within the Physicians' Health Study that included 673 case subjects with prostate cancer and 673 individually matched control subjects who had available plasma samples. Plasma from blood samples collected at baseline was assayed for antibodies against T vaginalis with an enzyme-linked immunosorbent assay. We used conditional logistic regression to estimate the odds ratios (ORs) of incident prostate cancer, extraprostatic prostate cancer, and cancer that would ultimately progress to bony metastases or prostate cancer-specific death. RESULTS: Although not statistically significant, the magnitude of the association between T vaginalis-seropositive status and overall prostate cancer risk (OR = 1.23, 95% confidence interval [CI] = 0.94 to 1.61) was similar to that reported previously. Furthermore, a seropositive status was associated with statistically significantly increased risks of extraprostatic prostate cancer (OR = 2.17, 95% CI = 1.08 to 4.37) and of cancer that would ultimately progress to bony metastases or prostate cancer-specific death (OR = 2.69, 95% CI = 1.37 to 5.28). CONCLUSIONS: This large prospective case-control study obtained further support for an association between a seropositive status for antibodies against T vaginalis and the risk of prostate cancer, with statistically significant associations identified for the risk of extraprostatic prostate cancer and for clinically relevant, potentially lethal prostate cancer.


Subject(s)
Antibodies, Protozoan/blood , Prostatic Neoplasms/epidemiology , Prostatic Neoplasms/parasitology , Trichomonas Infections/complications , Trichomonas vaginalis/isolation & purification , Aged , Animals , Bone Neoplasms/secondary , Case-Control Studies , Disease Progression , Enzyme-Linked Immunosorbent Assay , Humans , Incidence , Logistic Models , Male , Middle Aged , Odds Ratio , Physicians/statistics & numerical data , Prospective Studies , Prostatic Neoplasms/mortality , Prostatic Neoplasms/pathology , Research Design , Trichomonas vaginalis/immunology
13.
Int J Cancer ; 124(9): 2082-7, 2009 May 01.
Article in English | MEDLINE | ID: mdl-19117055

ABSTRACT

We previously observed a positive association between a history of trichomonosis, a sexually transmitted infection caused by the protozoan, Trichomonas vaginalis, and prostate cancer risk in the Health Professionals Follow-up Study. To determine the reproducibility of this finding, we conducted a second, prospective investigation of trichomonosis and prostate cancer in the Prostate Cancer Prevention Trial. Participants were men (>or=55 years of age) with no evidence of prostate cancer at enrollment (n = 18,882). Men were screened annually for prostate cancer, and if not diagnosed during the trial, were offered an end-of-study prostate biopsy. Cases were a sample of men diagnosed with prostate cancer on any biopsy after visit 2 or on their end-of-study biopsy (n = 616). Controls were men not diagnosed with prostate cancer during the trial or on their end-of-study biopsy (n = 616). Controls were frequency-matched to cases by age, treatment arm, and family history of prostate cancer. Serum from visit 2 was tested for anti-T. vaginalis IgG antibodies. No association was observed between T. vaginalis serostatus and prostate cancer. 21.5% of cases and 24.8% of controls had low seropositivity, and 15.2% and 15.0% had high seropositivity. Compared to seronegative men, the odds ratio of prostate cancer for men with low seropositivity was 0.83 [95% confidence interval (CI): 0.63-1.09), and that for men with high seropositivity was 0.97 (95% CI: 0.70-1.34). Given the original strong biologic rationale and potential for prevention, additional studies are warranted to help resolve discrepancies between study findings and to further investigate this hypothesis from a variety of different approaches.


Subject(s)
Antibodies, Protozoan/blood , Prostatic Neoplasms/parasitology , Sexually Transmitted Diseases/parasitology , Trichomonas Infections/parasitology , Trichomonas vaginalis/pathogenicity , Animals , Case-Control Studies , Follow-Up Studies , Humans , Immunoglobulin G/blood , Incidence , Male , Middle Aged , Neoplasm Staging , Prospective Studies , Risk Factors , Sexually Transmitted Diseases/epidemiology , Trichomonas vaginalis/immunology
14.
Rev Soc Bras Med Trop ; 40(3): 341-2, 2007.
Article in Portuguese | MEDLINE | ID: mdl-17653473

ABSTRACT

In endemic regions, Mansoni schistosomiasis is responsible for high morbidity-mortality rates due to diseases associated with infestation of the hepatic system. Genital involvement caused by Mansoni schistosomiasis is rare. We report the first case of Mansoni schistosomiasis in the seminal vesicle, which was diagnosed incidentally by means of histopathological study of the prostate and seminal vesicles after surgical removal.


Subject(s)
Genital Diseases, Male/parasitology , Schistosomiasis mansoni/diagnosis , Seminal Vesicles/parasitology , Animals , Genital Diseases, Male/diagnosis , Genital Diseases, Male/pathology , Humans , Incidental Findings , Male , Middle Aged , Prostatic Neoplasms/parasitology , Prostatic Neoplasms/pathology , Schistosoma mansoni/isolation & purification , Schistosomiasis mansoni/pathology , Seminal Vesicles/pathology
15.
Clin Cancer Res ; 12(20 Pt 1): 6116-24, 2006 Oct 15.
Article in English | MEDLINE | ID: mdl-17062688

ABSTRACT

PURPOSE: Bcl-2 inhibits apoptosis, and its overexpression is associated with hormone refractory prostate cancer (HRPC). Bak and Bax are in the Bcl-2 family and counteract the antiapoptotic function of Bcl-2. Taxane-induced (paclitaxel and its analogue docetaxel) phosphorylation of Bcl-2 abolishes the potential antiapoptotic effect of Bcl-2. We hypothesized that (a) survival benefit in HRPC patients treated with taxanes is determined by the presence of Bcl-2 protein and (b) altered expression of Bak and Bax protein caused by genetic mutation is associated with biological aggressiveness of prostate cancer. EXPERIMENTAL DESIGN: Forty localized prostate cancer and 30 HRPC cases were used in this study. Surgical specimens of localized prostate cancer and biopsy specimens of HRPC were used for immunostaining of Bcl-2, Bak, and Bax as well as DNA extraction. Mutations in the Bak and Bax genes were screened by single-strand conformational polymorphism, and confirmed by direct DNA sequencing. RESULTS: Bcl-2-positive HRPC showed longer cause-specific survival in comparison with the counterparts. Multivariate analysis revealed that the level of Bcl-2 expression before treatment with taxane-based chemotherapy was an independent predictor for cause-specific survival (P < 0.01) and baseline prostate-specific antigen level was an independent predictor for progression-free survival (P < 0.01). Bax gene mutation was found in only one HRPC specimen. CONCLUSIONS: Bcl-2 expression in addition to prostate-specific antigen measurement before treatment could identify HRPC patients who may benefit from taxane-based chemotherapy. Mutation of the Bak and Bax genes is a rare event in prostate cancer.


Subject(s)
Gene Expression Regulation, Neoplastic , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/genetics , Proto-Oncogene Proteins c-bcl-2/genetics , Taxoids/therapeutic use , Aged , Antineoplastic Agents/therapeutic use , DNA, Neoplasm/genetics , Drug Resistance, Neoplasm , Exons/genetics , Humans , Magnetic Resonance Spectroscopy , Male , Middle Aged , Polymerase Chain Reaction , Polymorphism, Single-Stranded Conformational , Prostatic Neoplasms/parasitology , bcl-2 Homologous Antagonist-Killer Protein/genetics , bcl-2-Associated X Protein/genetics
16.
Cancer Epidemiol Biomarkers Prev ; 15(5): 939-45, 2006 May.
Article in English | MEDLINE | ID: mdl-16702374

ABSTRACT

BACKGROUND: Although several previous case-control studies have investigated associations between sexually transmitted infections (STI) and prostate cancer, most have focused on gonorrhea and syphilis, two well-recognized, symptomatic STIs. Another STI of interest for prostate carcinogenesis is trichomonosis, a less well recognized and frequently asymptomatic STI with known prostate involvement. We investigated this infection in relation to incident prostate cancer in a nested case-control study within the Health Professionals Follow-up Study. METHODS: Prostate cancer cases were men diagnosed with prostate cancer between the date of blood draw (1993-1995) and 2000 (n = 691). Controls were men who had had at least one prostate-specific antigen test and who were free of prostate cancer and alive at the time of case diagnosis. One control was individually matched to each case by age (n = 691). Serologic evidence of a history of trichomonosis was assessed by a recombinant Trichomonas vaginalis alpha-actinin IgG ELISA. RESULTS: Thirteen percent of cases and 9% of controls were seropositive for trichomonosis (adjusted odds ratio, 1.43; 95% confidence interval, 1.00-2.03). This association persisted after additional adjustment for such factors as a history of other STIs, and was strongest among men who used aspirin infrequently over the course of their lives (odds ratio, 2.05; 95% confidence interval, 1.05-4.02, P(interaction) = 0.11). CONCLUSIONS: Serologic evidence of a history of trichomonosis was positively associated with incident prostate cancer in this large, nested case-control study of male health professionals. As this study is the first, to our knowledge, to investigate associations between T. vaginalis serology and prostate cancer, additional studies are necessary before conclusions can be made.


Subject(s)
Antibodies, Protozoan/blood , Prostatic Neoplasms/parasitology , Sexually Transmitted Diseases/parasitology , Trichomonas Infections/complications , Trichomonas vaginalis , Adult , Aged , Animals , Case-Control Studies , Enzyme-Linked Immunosorbent Assay , Humans , Immunoglobulin G/blood , Incidence , Logistic Models , Male , Middle Aged , Prospective Studies , Prostatic Neoplasms/epidemiology , Sexually Transmitted Diseases/epidemiology , Statistics, Nonparametric , Surveys and Questionnaires , Trichomonas Infections/epidemiology
17.
Ann Med ; 36(4): 273-7, 2004.
Article in English | MEDLINE | ID: mdl-15224653

ABSTRACT

BACKGROUND: Cancer is a complex multi-factorial disorder that may commonly show abnormal angiogenesis in such patients. Recently, platelets have been postulated to have a major role in both these processes, suggesting that antiplatelet strategies may be useful in cancer treatment. MATERIALS AND METHODS: To further investigate the role of platelets in angiogenesis, we used a novel platelet lysate assay to analyse platelet contents in breast cancer (n = 30) and prostate cancer (n = 30) patients and age- and sex-matched controls (n = 60). Markers of angiogenesis (vascular endothelial growth factor (VEGF), angiopoietin-1 and-2 (Ang-1, -2), and their respective receptors (Flt-1 and Tie-2) plus a marker of platelet activation (P-selectin (P-sel)), were all measured in platelet lysate by enzyme-linked immunsorbent assay. RESULTS: Platelet lysate from breast cancer patients contained higher levels of VEGF (P < 0.0001). Ang-1 (P = 0.0186) and P-sel (P = 0.0002), compared to healthy controls. Platelet lysate from prostate cancer patients had elevated VEGF (P = 0.008) but not Ang-1 or P-sel. There were no significant differences between levels of Fit-1 between patients and controls, and both Ang-2 and Tie-2 were undetectable in both patient groups and control platelet lysate. CONCLUSION: We have shown that our previously developed platelet lysate technique could be used to measure indices of angiogenesis, and their respective receptors, and that this assay can be applied to patients with cancer. Our study also provides further evidence that platelets may influence angiogenic abnormalities in human cancer. The platelet may be a useful target in anti-cancer strategies.


Subject(s)
Biomarkers, Tumor/analysis , Blood Platelets/metabolism , Breast Neoplasms/metabolism , Prostatic Neoplasms/metabolism , Aged , Angiopoietin-1/analysis , Blood Platelets/physiology , Breast Neoplasms/blood supply , Breast Neoplasms/pathology , Case-Control Studies , Enzyme-Linked Immunosorbent Assay , Extracellular Matrix Proteins/analysis , Female , Humans , Male , Middle Aged , Neovascularization, Pathologic/physiopathology , P-Selectin/analysis , Prostatic Neoplasms/parasitology , Prostatic Neoplasms/pathology , Vascular Endothelial Growth Factor A/analysis , Vascular Endothelial Growth Factor Receptor-1
18.
Int J Androl ; 23 Suppl 2: 34-6, 2000.
Article in English | MEDLINE | ID: mdl-10849490

ABSTRACT

The incidence of prostate cancer (PC) has been rapidly increasing in the past 10 years in Taiwan. It became the sixth common cancer in males in 1996 and resulted in 540 deaths in 1998. It was estimated that the incidence of PC would be up to 14 per 105 in the year 2000, 3-fold higher than that in 1990. Three factors may be responsible for the increase of PC in Taiwan: use of prostate specific antigen, population aging and high fat diet. A case-control study on the risk factors of PC in a patient population comprised mainly of veterans (63%) in Taiwan showed that PC patients tended to have engaged in more physical activity (adjusted odds ratio (OR): 2.16), have a lower body mass index (OR 2.0) and be less likely to consume vegetables cooked with pork lard (OR 0.47). About half of our patients had locally advanced or metastatic diseases upon diagnosis. This staging distribution was consistent in most major institutions in Taiwan and was fairly unchanged over time in the past two decades. The incidence of latent PC in Taiwan was not investigated until a pathological review of 49 cystoprostatectomy specimens recently revealed unsuspected PC in 32.7% and high-grade prostate intra epithelial neoplasia in 49% of the prostates removed. As the incidence of PC grows rapidly in Taiwan, this disease warrants more attention from the public and the authorities. More efforts should also be directed to the investigation on the risk factors for PC in the new millennium.


Subject(s)
Prostatic Neoplasms/genetics , Aged , Humans , Incidence , Male , Prevalence , Prostatic Neoplasms/mortality , Prostatic Neoplasms/parasitology , Risk Factors , Taiwan/epidemiology
19.
J Natl Cancer Inst ; 90(12): 925-31, 1998 Jun 17.
Article in English | MEDLINE | ID: mdl-9637143

ABSTRACT

BACKGROUND: Population-based screening for prostate cancer is currently being evaluated in randomized clinical trials in the United States and in Europe. Side effects arising from the process of screening and from the earlier treatment of screen-detected prostate cancer may be important factors in the evaluation. To examine health-related quality of life (or health status) among men screened for prostate cancer, we conducted a longitudinal study of 626 attenders to the Rotterdam (The Netherlands) prostate cancer screening program and of 500 nonparticipants. METHODS: Attenders of the screening program and nonparticipants completed self-assessment questionnaires (SF-36 [i.e., Medical Outcomes Study 36-Item Short-Form Health Survey] and EQ-5D [i.e., EuroQol measure for health-related quality of life] health surveys) to measure generic health status, as well as an additional questionnaire for anxiety and items relating to prostate cancer screening. RESULTS: Physical discomfort during digital rectal examination and during transrectal ultrasound was reported by 181 (37%) of 491 men and by 139 (29%) of 487 men, respectively; discomfort during prostate biopsy was reported by 64 (55%) of 116 men. Mean scores for health status and anxiety indicated that the participants did not experience relevant changes in physical, psychological, and social functioning during the screening procedure. However, high levels of anxiety were observed throughout the screening process among men with a high predisposition to anxiety. Similar scores for anxiety predisposition were observed among attenders and nonparticipants. CONCLUSIONS: At the group level, we did not find evidence that prostate cancer screening induced important short-term health-status effects, despite the short-lasting side effects related to the biopsy procedure. However, subgroups may experience high levels of anxiety. The implication is that unfavorable health-status effects of prostate cancer screening occur mainly in the treatment phase.


Subject(s)
Health Status , Mass Screening/adverse effects , Prostatic Neoplasms/parasitology , Quality of Life , Anxiety/etiology , Humans , Longitudinal Studies , Male , Netherlands , Prostatic Neoplasms/psychology , Surveys and Questionnaires
20.
Z Urol Nephrol ; 83(9): 495-503, 1990 Sep.
Article in German | MEDLINE | ID: mdl-1702572

ABSTRACT

1100 patients with pathological findings of the prostate, urothelium and lymph-nodes underwent cytological examination with histological control. Prostatic cytology showed a sensitivity of 81% in detecting cancer. Through reassessment of originally false negative or only suspicious aspirates a specificity rate of 90% was achieved while the rate of unsatisfactory smears were doubled. In urothelial tumors evidence of lavage cytology was significantly higher than exfoliative cytology and depends on grading and staging of the tumor. Tumors with a low grade of malignancy were rarely detected cytologically. Topical chemotherapy seems to change the accuracy of cytological examinations because of the difficulty to separate malignancy associated cell changes from therapy induced cellular features. Transperitoneal aspiration cytology of retroperitoneal lymph-nodes has no evidence.


Subject(s)
Cytological Techniques , Female Urogenital Diseases/pathology , Male Urogenital Diseases , Carcinoma, Transitional Cell/pathology , Female , Humans , Kidney Diseases, Cystic/pathology , Lymph Nodes/pathology , Male , Prostatic Hyperplasia/pathology , Prostatic Neoplasms/parasitology , Urinary Bladder Neoplasms/pathology
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