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C H Bangma

Publications and source records attributed to C H Bangma.

At least 37 records · Page 2Linked to original sources
PubMed2000

Targeting of adenoviral vectors for gene therapy of prostate cancer.

The transduction of cytotoxic genes by adenoviral vectors into prostatic cells offers a new entity for the treatment of prostate cancer. Current adenoviral vectors cannot infect prostatic cells selectively, and expression of therapeutic genes is often too low to be efficient. Bispecific antibodies may alter the natural tropism of adenoviral vectors towards prostatic cells, and increase the efficacy of infection (transductional targeting). The transcription of transgenes can be placed under the control of prostate-specific promoters (transcriptional targeting), and the combination of this with transductional targeting may be warranted to construct targeted vectors that are adequate for gene therapy of the prostate. Prostate Cancer and Prostatic Diseases (2000) 3, 308-312

Journal Article↗
PubMed2000

Prostate cancer gene therapy: comparison of adenovirus-mediated expression of interleukin 12 with interleukin 12 plus B7-1 for in situ gene therapy and gene-modified, cell-based vaccines.

We have documented previously that adenovirus-mediated interleukin 12 (IL-12) gene therapy is effective for orthotopic tumor control and suppression of pre-established metastases in a preclinical prostate cancer model (Y. Nasu et al., Gene Ther., 6: 338-349, 1999). In this report, we directly compare the effectiveness of an adenovirus that expresses both IL-12 and the costimulatory molecule B7-1 (AdmIL12/B7) with one that expresses IL-12 alone (AdmIL-12) using the poorly immunogenic RM-9 orthotopic murine model of prostate cancer. We document AdmIL-12/B7-mediated secretion of IL-12 and increased surface expression of B7-1 in infected RM-9 tumor cells. A significant reduction in orthotopic tumor size and increased survival was demonstrated in mice treated with a single orthotopic injection of AdmIL-12/B7 compared with AdmIL-12 or controls. Six of 19 animals treated with AdmIL-12/B7 survived long term with apparent eradication of the primary tumor in contrast to one of 38 animals in the AdmIL-12-treated group. Orthotopic treatment of tumors with both vectors led to an infiltration of both CD4+ and CD8+ immunoreactive cells, with AdmIL-12/B7 treatment having a more prolonged infiltration of CD8+ cells. AdmIL-12/B7 was also more effective than AdmIL-12 or controls at suppression of pre-established metastases. We further developed a vaccine model based on s.c. injection of infected, irradiated RM-9 cells and found that both AdmIL-12 and AdmIL-12/B7 are effective at suppressing the development and growth of challenge orthotopic tumors using this protocol.

Adenoviridae↗
PubMed1999

Adenovirus-mediated interleukin-12 gene therapy for prostate cancer: suppression of orthotopic tumor growth and pre-established lung metastases in an orthotopic model.

Interleukin-12 (IL-12) can elicit potent antitumoral effects that involve the recruitment of specific immune effector cells. We investigated the efficacy of a single injection of a recombinant adenovirus expressing murine IL-12 (AdmIL-12) directly into orthotopic mouse prostate carcinomas generated from a poorly immunogenic cell line (RM-9) derived from the mouse prostate reconstitution system. Significant growth suppression (> 50% reduction of tumor weight) and increased mean survival time (23.4 to 28.9 days) were observed compared with controls. Suppression of pre-established lung metastases was also observed following the injection of AdmIL-12 into the orthotopic tumor. Cytolytic natural killer cell activity was markedly enhanced 1-2 days after virus injection. Immunohistochemical analysis showed significantly elevated intratumoral infiltration of CD4+ and CD8+ T cells 7 days after virus injection. However, splenocyte-derived cytotoxic T lymphocytes were not detected during the 14 days following treatment. Increased numbers of nitric oxide synthase-positive macrophages were seen in the AdmIL-12 treated group 7 days following injection. Systemic inhibition of natural killer cells with antiasialo-GM1 serum led to increased numbers of lung metastases in AdmIL-12-treated orthotopic tumors but did not affect local tumor growth. In this model system the antitumor effects of a single injection of adenovirus-mediated IL-12 appears to be based to a large extent on the activation of nitric oxide synthase in macrophages and possibly T cell activities, whereas the relatively early cytolytic activity of natural killer cells are largely but not exclusively responsible for the antimetastatic effects.

Adenoviridae↗
PubMed1999

Metastasis-related genes in prostate cancer.

The identification of genes specifically related to the development of metastatic disease in prostate cancer is complicated by tumor cell heterogeneity and the presence of expressed sequences that are not related to metastasis. A system was designed to minimize these complications using differential display-polymerase chain reaction (DD-PCR) together with genetically paired cell lines derived from primary mouse prostate cancer and their associated metastases generated in vivo by the metastatic mouse prostate cancer reconstitution model. Using this system, a number of metastasis-related sequences were identified, including a cDNA that encodes caveolin-1.

Animals↗
PubMed1998

Comparison of prostate-specific antigen corrected for total prostate volume and transition zone volume in a population-based screening study.

OBJECTIVES: To compare the discriminatory potential between prostate cancer and benign conditions of the prostate in a population-based screening study, of serum prostate-specific antigen levels (PSA) and PSA corrected for both the total prostate volume (PSA-D) and the transition zone volume (PSA-T). METHODS: In a randomized population-based screening study (Rotterdam section of the European Randomized Study of Screening for Prostate Cancer), in which 10,865 men have been screened, the biopsy results of 1202 men with PSA levels of 4 ng/mL or more were evaluated. Planimetric and prolate ellipsoid volumes of the total prostate as well as of the transition zone were measured. The measured volumes were compared with the volumes of 57 radical prostatectomy specimens through Spearman's rank correlation coefficient and agreement tests. A receiver operating characteristic (ROC) curve analysis was done of sensitivity and specificity of biopsy indications through PSA and PSA corrected for the volumes measured with transrectal ultrasound. RESULTS: In the 1202 men studied, 361 cases of prostate cancer were diagnosed. Both PSA-D and PSA-T showed a significantly higher area under the ROC curve (0.77 and 0.79, respectively) than PSA alone (area 0.65). There was no significant difference between PSA-D and PSA-T. The use of a PSA-D threshold value of 0. 10 ng/mL/cc would have avoided 28% of biopsies at the cost of 10% of detectable cancers. A PSA-D threshold of 0.15 ng/mL/cc would have avoided 73.8% of biopsies at the cost of not diagnosing 43.8% of detectable cancers. CONCLUSIONS: The planimetrically obtained prostate volume showed a more favorable agreement with the radical prostatectomy volume than the prolate ellipsoid volume. The discriminatory potential of the corrected PSA value is better at predicting the results of needle biopsy of the prostate when compared with PSA alone. The use of the transition zone volume for this correction results in a higher discriminatory potential when compared to the use of the total prostate volume; however, the observed difference was not statistically significant.

Aged↗
PubMed1998

Suppression of caveolin expression induces androgen sensitivity in metastatic androgen-insensitive mouse prostate cancer cells.

Although prostate cancer cells are often initially sensitive to androgen ablation, they eventually lose this response and continue to survive, grow and spread in the absence of androgenic steroids. The mechanism(s) that underlie resistance to androgen ablation therapy remain mostly unknown. We have demonstrated that elevated caveolin protein levels are associated with human prostate cancer progression in pathological specimens. Here we show that suppression of caveolin expression by a stably transfected antisense caveolin-1 cDNA vector converted androgen-insensitive metastatic mouse prostate cancer cells to an androgen-sensitive phenotype. Orthotopically grown tumors and low-density cell cultures derived from antisense caveolin clones had increased apoptosis in the absence of androgenic steroids, whereas similarly grown tumors and cells from vector (control) clones and parental cells were not sensitive to androgens. Studies using a representative antisense caveolin clone showed that selection for androgen resistance in vivo correlated with increased caveolin levels, and that adenovirus-mediated caveolin expression blocked androgen sensitivity. Our results identify a new candidate gene for hormone-resistant prostate cancer in man and indicate that androgen insensitivity can be an inherent property of metastatic prostate cancer.

Androgens↗
PubMed1998

Repeat screening for prostate cancer after 1-year followup in 984 biopsied men: clinical and pathological features of detected cancer.

PURPOSE: We describe the yield of a repeat examination and biopsy procedure 1 year after initial biopsy was negative. We also assessed the parameters responsible for the failure to diagnose these cancers at the primary screening. MATERIALS AND METHODS: We screened 8,103 men randomized to the screening arm of the Rotterdam section of the European Randomized Study of Screening for Prostate Cancer using prostate specific antigen measurement, digital rectal examination and transrectal ultrasound. At the primary screening biopsy of 1,875 men was positive for prostate cancer in 374. Of the remaining 1,501 men 984 underwent repeat screening. RESULTS: Biopsy at repeat screening diagnosed prostate cancer in 49 of 442 men (11%), a rate significantly lower than the 19.9% true positive biopsy rate at the primary screening. Pathological characteristics of the tumors diagnosed were not significantly different in the 2 groups. However, prostate volume in men diagnosed with prostate cancer was significantly greater at repeat versus primary screening (mean 42.6 versus 34.9 cc, p = 0.003). The clinical characteristics were more favorable because of an increased proportion of stage T1C tumors. Prostate volume in men with stage T1C cancer was significantly greater than in those with palpable or visible tumors in whom prostate specific antigen values were in the same range. CONCLUSIONS: The most important factor responsible for the failure to diagnose these cancers at the primary screening was significantly greater prostate volume. Tumor characteristics were not significantly different in the groups. If prostate cancer screening were to become a routine health care policy, efforts would have to be made to improve the chances of diagnosing prostate cancer in larger prostates by repeat biopsy or by increasing the number of cores obtained.

Aged↗
PubMed1998

Elevated expression of caveolin is associated with prostate and breast cancer.

To identify genes associated with prostate cancer progression, we developed a strategy involving the use of differential display-PCR with a panel of genetically matched primary tumor- and metastasis-derived mouse prostate cancer cell lines. We isolated a cDNA fragment with homology to the mouse caveolin-1 gene. Northern blotting with this fragment revealed increased caveolin expression in metastasis-derived cell lines relative to primary tumor-derived cell lines. Western blotting with a polyclonal caveolin antibody confirmed increased caveolin protein in metastasis-derived mouse cell lines and expression in three of four human prostate cancer cell lines. Immunohistochemical analysis of a human prostate cancer cell line demonstrated a prominent granular pattern of caveolin accumulation. Subsequent analysis of mouse and human prostate specimens revealed minimal caveolin expression in normal epithelium with abundant staining of smooth muscle and endothelium. The frequency of caveolin-positive cells was increased in prostate cancer with markedly increased accumulation of caveolin and a granular staining pattern in lymph node metastatic deposits. In human breast cancer specimens, increased caveolin staining was detected in intraductal and infiltrating ductal carcinoma as well as nodal disease. Caveolin therefore appears to be associated with human prostate cancer progression and is also present in primary and metastatic human breast cancer.

Animals↗
PubMed1997

Prostate-specific antigen as a screening test. The Netherlands experience.

At the Rotterdam site of the ERSPC approximately 9600 men between 54 and 76 years old have been randomized at the time of writing, of which 50% for screening by PSA (Hybritech Tandem E), DRE, and TRUS until March 1996. The cancer detection rate is 4.3%, and the overall biopsy-to-carcinoma rate is 5.1. By clinical staging 91% of cancers are organ-confined (T2c or less), by pathologic staging after radical prostatectomy 64% of tumors are specimen-confined. The best sole predictor of a positive biopsy is total serum PSA, followed by DRE. The specificity of PSA in the intermediate PSA range between 4 and 10 ng/mL can be improved significantly by application of the f-PSA/t-PSA ratio, PSA density and age-specific reference ranges. The f-PSA/t-PSA ratio with a cut-off value of 0.20 appears to be the most effective parameter and reduces in combination with DRE the number of biopsies in the intermediate PSA range by 38% with 12% of carcinomas undetected. This leads to an overall biopsy-to-carcinoma ratio of 4.6. The evaluation of TRUS-, DRE-, and PSA-driven biopsies will lead to a change of the screening procedure within the study.

Aged↗
PubMed1997

Free and total prostate-specific antigen in a screened population.

OBJECTIVES: To determine whether the ratio of free to total (F/T) prostate-specific antigen (PSA) can differentiate between men with prostate carcinoma or benign conditions in a screened population. SUBJECTS AND METHODS: Total and free serum PSA (measured using Delfia PSA assays, Abbott IMx and Hybritech Tandem E methods) were determined retrospectively in 1726 men aged 55-77 years, in whom 67 prostate carcinomas were detected by screening with a digital rectal examination, transrectal ultrasonography, and total serum PSA level. Predictors for a positive biopsy result were estimated as a function of total PSA, free PSA and the combination of both. RESULTS: There was an excellent correlation between the Delfia ProStatus, the Abbott IMx and the Hybritech Tandem E assays. Compared with the total serum PSA level, the F/T ratio improved the specificity significantly only in those men with a total PSA of > or = 7 ng/mL. Using the information given by the total and free PSA values, a maximum sensitivity of 75% at a specificity of 74% was obtained for the whole PSA range from 4 to 10 ng/mL; the maximum sensitivity was 79% with a specificity of 71%. CONCLUSION: The optimal mathematical combination of free and total serum PSA improves the specificity of total serum PSA level in detecting prostate carcinoma more than the does the F/T PSA ratio.

Aged↗
PubMed1997

The free-to-total serum prostate specific antigen ratio for staging prostate carcinoma.

PURPOSE: We analyzed the relationship between the free-to-total PSA ratio and prostate cancer tumor stage and grade compared to total serum PSA. MATERIALS AND METHODS: In 123 patients clinical and pathological grade and stage were related to total serum PSA and free-to-total PSA ratio. RESULTS: Total serum PSA paralleled clinical staging of prostate cancer. The distributions of total serum PSA and the free-to-total PSA ratio were significantly different between benign and malignant diseases (any stage), and between any T category and nodal disease. For serum PSA significant differences were noted between the distributions of men with locally confined (stages T1 and T2) and locally extended (stage T3) disease, and between all T categories and systemic metastatic disease. This finding was not noted for the free-to-total PSA ratio. CONCLUSIONS: The free-to-total PSA ratio has no additional value in clinical staging of prostate carcinoma compared to serum PSA. The free-to-total PSA ratio may be considered the result of cell differentiation and not an indicator of tumor load.

Humans↗
PubMed1997

Analytical evaluation of the new Prostatus PSA Free/Total assay for prostate-specific antigen as part of a screening study for prostate cancer.

In this communication a limited analytical study is described on the new Prostatus PSA Free/Total assay. The study is considered as a side study of the European Randomized Study of Screening for Prostate Cancer. The between-day imprecision with 8 control samples for free prostate-specific antigen ranged from 10.3% at 0.17 microg/l to 3.7% at a concentration of 35.5 microg/l, while for total prostate-specific antigen we found 7.3% at 0.69 microg/l and 4.3% at 70.7 microg/l. For total prostate-specific antigen we found excellent agreement between the new assay and well-established assays like Abbott IMx and Hybritech Tandem-E, both for prostate cancer and benign prostate hyperplasia specimens. The age-specific reference ranges proved to be well-comparable with the literature data both for free and total prostate-specific antigen.

Adult↗
PubMed1997

The free-to-total prostate specific antigen ratio improves the specificity of prostate specific antigen in screening for prostate cancer in the general population.

PURPOSE: The ratio between free and total prostate specific antigen (PSA) in serum improves the specificity of total serum PSA for the detection of prostate carcinoma in select populations. The value of the free-to-total PSA ratio for a PSA of 4.0 to 10.0 ng./ml. was analyzed in a screening population. MATERIALS AND METHODS: From 4,800 participants 55 to 76 years old 977 biopsies were obtained because of an abnormal digital rectal examination, suspicious transrectal ultrasonography and total serum PSA 4.0 ng./ml. or more. Of 191 patients with prostate carcinoma detected 101 had a serum PSA of 4.0 to 10.0 ng./ml. and 54 of them underwent radical prostatectomy. A free-to-total PSA ratio of 0.20, age specific PSA reference ranges and a PSA density of 0.12 ng./ml./cc were evaluated for the ability to increase the specificity of total serum PSA in predicting positive prostate biopsy results. RESULTS: Receiver operating characteristics curves for the free-to-total PSA ratio showed a significant increase in specificity compared to PSA. Retrospective application of age specific PSA reference ranges, the free-to-total PSA ratio and the PSA density decreased the number of biopsies significantly by up to 40% in our study, with a decrease in cancer detection rate of 12%. When used in combination with digital rectal examination, the pathological stage of undetected carcinomas appeared favorable. CONCLUSIONS: The free-to-total PSA ratio may be used to decrease biopsies in patients with an intermediate PSA of 4.0 to 10.0 ng./ml.

Aged↗
PubMed1996

Transrectal ultrasonic volumetry of the prostate: in vivo comparison of different methods.

In order to assess the accuracy of various volumetric methods for screening and follow-up of prostatic disease, total prostate volume and inner zone volume were measured by transrectal ultrasonography in a screening population of 716 men. Semiplanimetric and caliper formula methods were compared with step section planimetry as the gold standard. Planimetric volumetry of the prostate is regarded as the most reproducible method for individual follow-up of total gland and inner zone volume. The prolate spheroid formula is the most reproducible of caliper formula methods for both volumes. In this study the elliptical volume was, however, more accurate than the prolate spheroid volume of the total gland, as the correlation coefficient between total elliptical volume and planimetry was higher compared to the prolate spheroid volume (0.89 vs. 0.83), and the standard deviation of the mean volumetric difference smaller. The mean total prolate spheroid volume resembled the mean total planimetric volume better than the elliptical volume did, as the mean volumetric difference was smaller. For measurement of the inner zone volume the prolate spheroid volume was more accurate that the elliptical volume. The correlation coefficient between length and planimetric volume was similar to that of width and height, which accounted for more accuracy of the elliptical volume that of the prolate spheroid volume in larger prostates. The elliptical volume might be used for incidental volumetric measurements of the total gland, and for comparison of different individuals, e.g., in preoperative evaluation or screening studies.

Aged↗