Pub Date : 2001-01-01DOI: 10.1089/10915360152745821
A. Errejon, E. David Crawford, Judith Dayhoff, Colin O'Donnell, Ashutosh Tewari, James Finkelstein, E. Gamito
Artificial neural networks (ANNs) are a type of artificial intelligence software inspired by biological neuronal systems that can be used for nonlinear statistical modeling. In recent years, these applications have played an increasing role in predictive and classification modeling in medical research. We review the basic concepts behind ANNs and examine the role of this technology in selected applications in prostate cancer research.
{"title":"Use of artificial neural networks in prostate cancer.","authors":"A. Errejon, E. David Crawford, Judith Dayhoff, Colin O'Donnell, Ashutosh Tewari, James Finkelstein, E. Gamito","doi":"10.1089/10915360152745821","DOIUrl":"https://doi.org/10.1089/10915360152745821","url":null,"abstract":"Artificial neural networks (ANNs) are a type of artificial intelligence software inspired by biological neuronal systems that can be used for nonlinear statistical modeling. In recent years, these applications have played an increasing role in predictive and classification modeling in medical research. We review the basic concepts behind ANNs and examine the role of this technology in selected applications in prostate cancer research.","PeriodicalId":80296,"journal":{"name":"Molecular urology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/10915360152745821","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"60627538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2001-01-01DOI: 10.1089/10915360152745876
A. Porter, E. Ben-Josef, E. Crawford, S. Garde, I. Huhtaniemi, J. Pontes
Nonandrogenic hormones are implicated in the growth and function of the prostate, which is itself an endocrine gland that synthesizes and secretes hormones and growth factors, including follicle-stimulating hormone (FSH) and prostatic inhibin peptide (PIP). Findings of increased FSH concentrations and receptor expression in diseased prostate tissue suggest a role for FSH in prostate cancer growth. Not only does PIP suppress circulating levels of FSH, but it responds to and modulates prostatic FSH, suggesting a close interlinkage of these compounds in controlling both healthy and diseased prostate cells. Other focuses of endocrinologic research include androgen receptors, vitamin D, growth factors (including insulin-like growth factors I and II), and retinoids. Issues such as optimal therapy timing, intermittent administration, and the adoption of a multihormonal approach to the management of prostate cancer remain to be resolved.
{"title":"Advancing perspectives on prostate cancer: multihormonal influences in pathogenesis.","authors":"A. Porter, E. Ben-Josef, E. Crawford, S. Garde, I. Huhtaniemi, J. Pontes","doi":"10.1089/10915360152745876","DOIUrl":"https://doi.org/10.1089/10915360152745876","url":null,"abstract":"Nonandrogenic hormones are implicated in the growth and function of the prostate, which is itself an endocrine gland that synthesizes and secretes hormones and growth factors, including follicle-stimulating hormone (FSH) and prostatic inhibin peptide (PIP). Findings of increased FSH concentrations and receptor expression in diseased prostate tissue suggest a role for FSH in prostate cancer growth. Not only does PIP suppress circulating levels of FSH, but it responds to and modulates prostatic FSH, suggesting a close interlinkage of these compounds in controlling both healthy and diseased prostate cells. Other focuses of endocrinologic research include androgen receptors, vitamin D, growth factors (including insulin-like growth factors I and II), and retinoids. Issues such as optimal therapy timing, intermittent administration, and the adoption of a multihormonal approach to the management of prostate cancer remain to be resolved.","PeriodicalId":80296,"journal":{"name":"Molecular urology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/10915360152745876","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"60627843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2001-01-01DOI: 10.1089/109153601300177547
Y. Wada, A. Gotoh, T. Shirakawa, K. Hamada, S. Kamidono
BACKGROUND AND PURPOSE Bladder cancer is common. Current treatment for patients with superficial bladder cancer involves transurethral resection followed by adjuvant bacillus Calmette-Guérin (BCG) administration. Adjuvant BCG has been reported to be effective in 38% to 68% of patients; however, more than 30% of patients do not respond. Because p53 mutations are common among superficial bladder cancers, we tested the feasibility of using p53 as a gene therapy agent for targeting superficial tumors, which are easily accessible using an intravesical approach. MATERIALS AND METHODS Wild-type p53 was transduced into various human and murine bladder cancer cell lines (HTB9, KU-1, and MBT-2) using a recombinant adenoviral vector (Ad5CMV-p53) in vitro. Also, subcutaneous tumors were established and then treated with intratumoral injection of Ad5CMV-p53 or control viruses. RESULTS In vitro assays revealed significant growth suppression of target cells by Ad5CMV-p53 in comparison with those receiving the control Ad5-CMV-PA vector or untreated control cells. In vivo studies using subcutaneous bladder tumor models established in syngeneic mice demonstrated that the rate of tumor growth and volume was reduced to a greater extent by 14 days of intratumoral injection of Ad5CMV-p53 rather than Ad5CMV-PA. Furthermore, the survival of host animals bearing tumors that were infected with Ad5CMV-p53 was significantly longer than that of the control group treated with Ad5CMV-PA (P < 0.01). CONCLUSION Our data suggest that Ad5CMV-p53 is effective in suppressing bladder cancer growth and improving host survival.
{"title":"Gene therapy for bladder cancer using adenoviral vector.","authors":"Y. Wada, A. Gotoh, T. Shirakawa, K. Hamada, S. Kamidono","doi":"10.1089/109153601300177547","DOIUrl":"https://doi.org/10.1089/109153601300177547","url":null,"abstract":"BACKGROUND AND PURPOSE Bladder cancer is common. Current treatment for patients with superficial bladder cancer involves transurethral resection followed by adjuvant bacillus Calmette-Guérin (BCG) administration. Adjuvant BCG has been reported to be effective in 38% to 68% of patients; however, more than 30% of patients do not respond. Because p53 mutations are common among superficial bladder cancers, we tested the feasibility of using p53 as a gene therapy agent for targeting superficial tumors, which are easily accessible using an intravesical approach. MATERIALS AND METHODS Wild-type p53 was transduced into various human and murine bladder cancer cell lines (HTB9, KU-1, and MBT-2) using a recombinant adenoviral vector (Ad5CMV-p53) in vitro. Also, subcutaneous tumors were established and then treated with intratumoral injection of Ad5CMV-p53 or control viruses. RESULTS In vitro assays revealed significant growth suppression of target cells by Ad5CMV-p53 in comparison with those receiving the control Ad5-CMV-PA vector or untreated control cells. In vivo studies using subcutaneous bladder tumor models established in syngeneic mice demonstrated that the rate of tumor growth and volume was reduced to a greater extent by 14 days of intratumoral injection of Ad5CMV-p53 rather than Ad5CMV-PA. Furthermore, the survival of host animals bearing tumors that were infected with Ad5CMV-p53 was significantly longer than that of the control group treated with Ad5CMV-PA (P < 0.01). CONCLUSION Our data suggest that Ad5CMV-p53 is effective in suppressing bladder cancer growth and improving host survival.","PeriodicalId":80296,"journal":{"name":"Molecular urology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/109153601300177547","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"60626839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2001-01-01DOI: 10.1089/109153601300177556
A. Irie, T. Uchida, H. Ishida, K. Matsumoto, M. Iwamura, S. Baba
BACKGROUND Altered expression of p53 has been described in nearly half of bladder cancers, and p53 mutations are presumed to play a role in the multistep progression of these tumors. MATERIALS AND METHODS The incidence of mutation in the p53 gene and its correlation with histopathologic findings and patient survival were evaluated in 105 Japanese patients with bladder cancer. Laboratory experiments were also performed to confirm the infectivity and efficacy in tumor growth inhibition of an adenovirus expressing wild-type p53 in EJ bladder cancer cells. RESULTS Mutations of p53 were observed in 38 bladder cancer specimens (36%), with a significantly higher incidence of mutation being seen in tumors of higher stage and grade. The overall survival was worse in patients with the p53 mutation. In laboratory experiments, adenoviral vectors infected bladder cancer cells in a dose- and cell density-dependent manner. The adenovirus-mediated transduction of wild-type p53 resulted in dose-dependent growth inhibition of bladder cancer cells in vitro. No significant cytotoxicity was observed after infection by a control adenovirus. CONCLUSION Transduction of wild-type p53 might be a potential therapeutic option for bladder cancer.
{"title":"p53 Mutation in bladder cancer patients in Japan and inhibition of growth by in vitro adenovirus-mediated wild-type p53 transduction in bladder cancer cells.","authors":"A. Irie, T. Uchida, H. Ishida, K. Matsumoto, M. Iwamura, S. Baba","doi":"10.1089/109153601300177556","DOIUrl":"https://doi.org/10.1089/109153601300177556","url":null,"abstract":"BACKGROUND Altered expression of p53 has been described in nearly half of bladder cancers, and p53 mutations are presumed to play a role in the multistep progression of these tumors. MATERIALS AND METHODS The incidence of mutation in the p53 gene and its correlation with histopathologic findings and patient survival were evaluated in 105 Japanese patients with bladder cancer. Laboratory experiments were also performed to confirm the infectivity and efficacy in tumor growth inhibition of an adenovirus expressing wild-type p53 in EJ bladder cancer cells. RESULTS Mutations of p53 were observed in 38 bladder cancer specimens (36%), with a significantly higher incidence of mutation being seen in tumors of higher stage and grade. The overall survival was worse in patients with the p53 mutation. In laboratory experiments, adenoviral vectors infected bladder cancer cells in a dose- and cell density-dependent manner. The adenovirus-mediated transduction of wild-type p53 resulted in dose-dependent growth inhibition of bladder cancer cells in vitro. No significant cytotoxicity was observed after infection by a control adenovirus. CONCLUSION Transduction of wild-type p53 might be a potential therapeutic option for bladder cancer.","PeriodicalId":80296,"journal":{"name":"Molecular urology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/109153601300177556","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"60626846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2001-01-01DOI: 10.1089/109153601750124249
Tatsunari Fukui, N. Nonomura, T. Tokizane, Eiichi Sato, Y. Ono, Y. Harada, K. Nishimura, S. Takahara, A. Okuyama
PURPOSE We examined the expression of mRNA of human telomerase reverse transcriptase (hTERT), a catalytic subunit of the telomerase complex, in bladder washings as a tumor marker for the detection of bladder cancer. MATERIALS AND METHODS Bladder washings were obtained from 63 patients. We examined the expression of hTERT mRNA by the nested reverse transcription-polymerase chain reaction (RT-PCR) method and also measured the relative expressions of hTERT mRNA and beta(2)-microglobulin (beta(2)-MG) in these samples by RT-PCR analysis. Correlations between the relative expression of hTERT mRNA and clinical features were analyzed. We also compared the sensitivity of this assay with that of urinary cytology. RESULTS By nested RT-PCR, we detected three false-positive cases (11%) in the control group. Therefore, the relative expression values of hTERT mRNA and beta(2)-MG correlated strongly with tumor size, but not with multiplicity or histologic grade. When the cut-off value of the expression was fixed at 0.27%, the sensitivity and specificity of this assay were 74% and 93%, respectively. This assay was more sensitive than urinary cytology for the detection of bladder cancer. CONCLUSION These results suggest that the relative expression of hTERT mRNA in bladder washings is useful in screening for bladder cancer. Relative expression is of assistance in diagnosing bladder cancer.
{"title":"Clinical evaluation of human telomerase catalytic subunit in bladder washings from patients with bladder cancer.","authors":"Tatsunari Fukui, N. Nonomura, T. Tokizane, Eiichi Sato, Y. Ono, Y. Harada, K. Nishimura, S. Takahara, A. Okuyama","doi":"10.1089/109153601750124249","DOIUrl":"https://doi.org/10.1089/109153601750124249","url":null,"abstract":"PURPOSE We examined the expression of mRNA of human telomerase reverse transcriptase (hTERT), a catalytic subunit of the telomerase complex, in bladder washings as a tumor marker for the detection of bladder cancer. MATERIALS AND METHODS Bladder washings were obtained from 63 patients. We examined the expression of hTERT mRNA by the nested reverse transcription-polymerase chain reaction (RT-PCR) method and also measured the relative expressions of hTERT mRNA and beta(2)-microglobulin (beta(2)-MG) in these samples by RT-PCR analysis. Correlations between the relative expression of hTERT mRNA and clinical features were analyzed. We also compared the sensitivity of this assay with that of urinary cytology. RESULTS By nested RT-PCR, we detected three false-positive cases (11%) in the control group. Therefore, the relative expression values of hTERT mRNA and beta(2)-MG correlated strongly with tumor size, but not with multiplicity or histologic grade. When the cut-off value of the expression was fixed at 0.27%, the sensitivity and specificity of this assay were 74% and 93%, respectively. This assay was more sensitive than urinary cytology for the detection of bladder cancer. CONCLUSION These results suggest that the relative expression of hTERT mRNA in bladder washings is useful in screening for bladder cancer. Relative expression is of assistance in diagnosing bladder cancer.","PeriodicalId":80296,"journal":{"name":"Molecular urology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/109153601750124249","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"60627878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2001-01-01DOI: 10.1089/109153601300177538
H. Kumon
GENE THERAPY in the new century has begun in the face of both tragic and encouraging news. Since the death of an 18-year-old man on September 17, 1999 after injection of an adenoviral vector intended to correct his ornithine transcarbamylase deficiency, clinical gene therapy in general and adenoviral vectors in particular have received an unprecedented barrage of bad publicity. This painful experience provided some hard lessons for the advancement of gene therapy. The first lesson is that a gene therapy program should be scrutinized to ensure that the system is open and clear in all aspects from the manufacture of vectors and preparation of a protocol to monitoring and evaluation of clinical trial. The second lesson is that gene therapy researchers should make every possible effort to educate the general public and the press regarding what we do and why we do it. Current gene therapy is regarded as translational research, it is at a point between the bench and the bedside. We must go back to the bench after reviewing the clinical data obtained from early phase trials in order to establish more effective and reliable strategies for the future. The completion of human genome sequencing is excellent news in the field of gene therapy. It is evident that we will soon identify a number of new potential target genes based on this spectacular project. Successful application in SCID-X1 patients (Science 288:669–672, 2000) and hemophilia patients (Nature Genetics 24:257–261, 2000) was very encouraging for gene therapy scientists. Of great importance is the variety of gene therapy protocols for advanced localized tumors including urogenital malignancies that have been conducted, demonstrating its feasibility and safety. The Japanese Society for Urological Gene Therapy was founded in 1999 in order to stimulate our communication and collaboration with other physicians and basic scientists. There is an urgent and increasing need for our urologists to have an understanding of the basic concepts of gene therapy, its potential applications, and its shortcomings. The second meeting of the Society was held on November 18th, 2000 in Okayama, Japan; a guest speaker, Prof. Kaneda, Professor and Chairman of the Gene Therapy Science Division, Graduate School of Medicine, Osaka University, and 15 active urologists reported the current status and future prospects of their gene therapy approaches. Among them, eight articles were selected for the publication of this issue including Dr. Kaneda’s special article. Dr. Kaneda originally developed HVJ (Hemagglutinating Virus of Japan; Sendai virus)-liposomes that are efficient in vitro and in vivo as gene delivery vehicles using fusion-mediated gene delivery. And further studies have resulted in the creation of HVJ-cationic liposomes with increased transfection efficiency. He has discussed the improvement of gene therapy technology with regard to his current research outcomes. Developed by Dr. Kaneda and his colleagues, the firs
{"title":"Gene therapy in the 21st century.","authors":"H. Kumon","doi":"10.1089/109153601300177538","DOIUrl":"https://doi.org/10.1089/109153601300177538","url":null,"abstract":"GENE THERAPY in the new century has begun in the face of both tragic and encouraging news. Since the death of an 18-year-old man on September 17, 1999 after injection of an adenoviral vector intended to correct his ornithine transcarbamylase deficiency, clinical gene therapy in general and adenoviral vectors in particular have received an unprecedented barrage of bad publicity. This painful experience provided some hard lessons for the advancement of gene therapy. The first lesson is that a gene therapy program should be scrutinized to ensure that the system is open and clear in all aspects from the manufacture of vectors and preparation of a protocol to monitoring and evaluation of clinical trial. The second lesson is that gene therapy researchers should make every possible effort to educate the general public and the press regarding what we do and why we do it. Current gene therapy is regarded as translational research, it is at a point between the bench and the bedside. We must go back to the bench after reviewing the clinical data obtained from early phase trials in order to establish more effective and reliable strategies for the future. The completion of human genome sequencing is excellent news in the field of gene therapy. It is evident that we will soon identify a number of new potential target genes based on this spectacular project. Successful application in SCID-X1 patients (Science 288:669–672, 2000) and hemophilia patients (Nature Genetics 24:257–261, 2000) was very encouraging for gene therapy scientists. Of great importance is the variety of gene therapy protocols for advanced localized tumors including urogenital malignancies that have been conducted, demonstrating its feasibility and safety. The Japanese Society for Urological Gene Therapy was founded in 1999 in order to stimulate our communication and collaboration with other physicians and basic scientists. There is an urgent and increasing need for our urologists to have an understanding of the basic concepts of gene therapy, its potential applications, and its shortcomings. The second meeting of the Society was held on November 18th, 2000 in Okayama, Japan; a guest speaker, Prof. Kaneda, Professor and Chairman of the Gene Therapy Science Division, Graduate School of Medicine, Osaka University, and 15 active urologists reported the current status and future prospects of their gene therapy approaches. Among them, eight articles were selected for the publication of this issue including Dr. Kaneda’s special article. Dr. Kaneda originally developed HVJ (Hemagglutinating Virus of Japan; Sendai virus)-liposomes that are efficient in vitro and in vivo as gene delivery vehicles using fusion-mediated gene delivery. And further studies have resulted in the creation of HVJ-cationic liposomes with increased transfection efficiency. He has discussed the improvement of gene therapy technology with regard to his current research outcomes. Developed by Dr. Kaneda and his colleagues, the firs","PeriodicalId":80296,"journal":{"name":"Molecular urology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/109153601300177538","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"60626833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2001-01-01DOI: 10.1089/10915360152745830
C. Porter, C. O’Donnell, E. Crawford, E. Gamito, A. Errejon, E. Genega, T. Sotelo, A. Tewari
BACKGROUND Biochemical failure, defined here as a rise in the serum prostate specific antigen (PSA) concentration to >0.3 ng/mL or the initiation of adjuvant therapy, is thought to be an adverse prognostic factor for men who undergo radical prostatectomy (RP) as definitive treatment for clinically localized cancer of the prostate (CAP). We have developed an artificial neural network (ANN) to predict biochemical failure that may benefit clinicians and patients choosing among the definitive treatment options for CAP. MATERIALS AND METHODS Clinical and pathologic data from 196 patients who had undergone RP at one institution between 1988 and 1999 were utilized. Twenty-one records were deleted because of missing outcome, Gleason sum, PSA, or clinical stage data. The variables from the 175 remaining records were analyzed for input variable selection using principal component analysis, decision tree analysis, and stepped logistic regression. The selected variables were age, PSA, primary and secondary Gleason grade, and Gleason sum. The records were randomized and split into three bootstrap training and validation sets of 140 records (80%) and 35 records (20%), respectively. RESULTS Forty-four percent of the patients suffered biochemical failure. The average duration of follow up was 2.5 years (range 0-11.5 years). Forty-two percent of the patients had pathologic evidence of non-organ-confined disease. The average area under the receiver operator characteristic (ROC) curve for the validation sets was 0.75 +/- 0.07. The ANN with the highest area under the ROC curve (0.80) was used for prediction and had a sensitivity of 0.74, a specificity of 0.78, a positive predictive value of 0.71, and a negative predictive value of 0.81. CONCLUSION These results suggest that ANN models can predict PSA failure using readily available preoperative variables. Such predictive models may offer assistance to patients and physicians deciding on definitive therapy for CaP.
{"title":"Artificial neural network model to predict biochemical failure after radical prostatectomy.","authors":"C. Porter, C. O’Donnell, E. Crawford, E. Gamito, A. Errejon, E. Genega, T. Sotelo, A. Tewari","doi":"10.1089/10915360152745830","DOIUrl":"https://doi.org/10.1089/10915360152745830","url":null,"abstract":"BACKGROUND Biochemical failure, defined here as a rise in the serum prostate specific antigen (PSA) concentration to >0.3 ng/mL or the initiation of adjuvant therapy, is thought to be an adverse prognostic factor for men who undergo radical prostatectomy (RP) as definitive treatment for clinically localized cancer of the prostate (CAP). We have developed an artificial neural network (ANN) to predict biochemical failure that may benefit clinicians and patients choosing among the definitive treatment options for CAP. MATERIALS AND METHODS Clinical and pathologic data from 196 patients who had undergone RP at one institution between 1988 and 1999 were utilized. Twenty-one records were deleted because of missing outcome, Gleason sum, PSA, or clinical stage data. The variables from the 175 remaining records were analyzed for input variable selection using principal component analysis, decision tree analysis, and stepped logistic regression. The selected variables were age, PSA, primary and secondary Gleason grade, and Gleason sum. The records were randomized and split into three bootstrap training and validation sets of 140 records (80%) and 35 records (20%), respectively. RESULTS Forty-four percent of the patients suffered biochemical failure. The average duration of follow up was 2.5 years (range 0-11.5 years). Forty-two percent of the patients had pathologic evidence of non-organ-confined disease. The average area under the receiver operator characteristic (ROC) curve for the validation sets was 0.75 +/- 0.07. The ANN with the highest area under the ROC curve (0.80) was used for prediction and had a sensitivity of 0.74, a specificity of 0.78, a positive predictive value of 0.71, and a negative predictive value of 0.81. CONCLUSION These results suggest that ANN models can predict PSA failure using readily available preoperative variables. Such predictive models may offer assistance to patients and physicians deciding on definitive therapy for CaP.","PeriodicalId":80296,"journal":{"name":"Molecular urology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/10915360152745830","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"60627159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2001-01-01DOI: 10.1089/10915360152745858
P. Snow, J. Brandt, R. L. Williams
An artificial neural network (ANN) has been developed to predict the presence or absence of cancer following debulking laparotomy and chemotherapy in patients with stages III and IV ovarian cancer. The presence or absence of a residual gross tumor or microscopic disease was determined by a second-look laparotomy. The ANN was trained and tested using detailed operative findings and related surgical procedures associated with the debulking surgery. The ANN predictive results were compared with linear and logistic regression. The ANN significantly outperformed both logistic and linear regression analyses, but additional cases are needed to validate the network.
{"title":"Neural network analysis of the prediction of cancer recurrence following debulking laparotomy and chemotherapy in stages III and IV ovarian cancer.","authors":"P. Snow, J. Brandt, R. L. Williams","doi":"10.1089/10915360152745858","DOIUrl":"https://doi.org/10.1089/10915360152745858","url":null,"abstract":"An artificial neural network (ANN) has been developed to predict the presence or absence of cancer following debulking laparotomy and chemotherapy in patients with stages III and IV ovarian cancer. The presence or absence of a residual gross tumor or microscopic disease was determined by a second-look laparotomy. The ANN was trained and tested using detailed operative findings and related surgical procedures associated with the debulking surgery. The ANN predictive results were compared with linear and logistic regression. The ANN significantly outperformed both logistic and linear regression analyses, but additional cases are needed to validate the network.","PeriodicalId":80296,"journal":{"name":"Molecular urology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/10915360152745858","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"60627959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2001-01-01DOI: 10.1089/109153601750124267
Y. Ono, N. Nonomura, Y. Harada, T. Fukui, T. Tokizane, E. Sato, M. Nakayama, K. Nishimura, S. Takahara, A. Okuyama
BACKGROUND Cisplatin (CDDP) plays an important role in the treatment of transitional-cell carcinoma (TCC), but resistance develops. The mechanism is not entirely understood. METHODS To assess acquired resistance to CDDP, we established a CDDP-resistant subclone, CL8-2, of T24, which is a bladder cancer cell line. We examined the changes in the various pathways leading to apoptosis in the parent line and CL8-2. RESULTS The drug caused apoptosis of T24 cells but not CL8-2 cells. The CL8-2 cells were 6.4 times more resistant to CDDP than was T24. In both cell lines, the mismatch repair genes hMLH-1 and hMSH-2 were expressed at high levels. The p53 protein was not detected in either cell line but p73 protein was induced by CDDP treatment in T24 cells, which was followed by activation of caspases 3, 8, and 9. This phenomenon was not observed in CL8-2 cells. CONCLUSION These results suggest that loss of p73 induction may lead to CDDP resistance of TCC.
{"title":"Loss of p73 induction in a cisplatin-resistant bladder cancer cell line.","authors":"Y. Ono, N. Nonomura, Y. Harada, T. Fukui, T. Tokizane, E. Sato, M. Nakayama, K. Nishimura, S. Takahara, A. Okuyama","doi":"10.1089/109153601750124267","DOIUrl":"https://doi.org/10.1089/109153601750124267","url":null,"abstract":"BACKGROUND Cisplatin (CDDP) plays an important role in the treatment of transitional-cell carcinoma (TCC), but resistance develops. The mechanism is not entirely understood. METHODS To assess acquired resistance to CDDP, we established a CDDP-resistant subclone, CL8-2, of T24, which is a bladder cancer cell line. We examined the changes in the various pathways leading to apoptosis in the parent line and CL8-2. RESULTS The drug caused apoptosis of T24 cells but not CL8-2 cells. The CL8-2 cells were 6.4 times more resistant to CDDP than was T24. In both cell lines, the mismatch repair genes hMLH-1 and hMSH-2 were expressed at high levels. The p53 protein was not detected in either cell line but p73 protein was induced by CDDP treatment in T24 cells, which was followed by activation of caspases 3, 8, and 9. This phenomenon was not observed in CL8-2 cells. CONCLUSION These results suggest that loss of p73 induction may lead to CDDP resistance of TCC.","PeriodicalId":80296,"journal":{"name":"Molecular urology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/109153601750124267","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"60628216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2001-01-01DOI: 10.1089/10915360152559585
Hideaki Miyake, S. Hara, Tobias Zellweger, Sadao Kamidono, Martin E. Gleave, I. Hara
Recent studies have shown the antiapoptotic activity of clusterin against a wide variety of stimuli; however, the functional role of clusterin in Fas-mediated apoptosis has not been well characterized. We transfected the clusterin cDNA into human renal-cell carcinoma (RCC) ACHN cells that scarcely express clusterin protein in order to examine whether overexpression of clusterin inhibits the Fas-mediated signal pathway for apoptotic cell death. No significant difference was observed in the in vitro cell growth rates between the clusterin-transfected cell line (ACHN/CL) and the vector-only-transfected control cell line (ACHN/C), whereas the colony-forming efficiency in soft agar of ACHN/CL was significantly higher than that of ACHAN/C. The anti-Fas monoclonal antibody CH11 induced apoptosis in ACHAN/C cells in a dose-dependent manner; however, the growth-inhibitory effect of CH11 on ACHN/CL cells was markedly suppressed, with corresponding increases in p53 expression and decrease in the fraction of cells in the sub-G(1) phase of the cell cycle. Furthermore, the cytotoxic effect of CH11 on ACHN/CL cells was augmented by treatment with interferon-gamma, but a corresponding effect on ACHN/C cells was not observed. These findings suggest that overexpression of clusterin may contribute to a phenotype resistant to Fas-mediated apoptosis, and that if interferon-gamma treatment is added according to the clusterin expression level, Fas-mediated therapy could be a novel approach to RCC.
{"title":"Acquisition of resistance to Fas-mediated apoptosis by overexpression of clusterin in human renal-cell carcinoma cells.","authors":"Hideaki Miyake, S. Hara, Tobias Zellweger, Sadao Kamidono, Martin E. Gleave, I. Hara","doi":"10.1089/10915360152559585","DOIUrl":"https://doi.org/10.1089/10915360152559585","url":null,"abstract":"Recent studies have shown the antiapoptotic activity of clusterin against a wide variety of stimuli; however, the functional role of clusterin in Fas-mediated apoptosis has not been well characterized. We transfected the clusterin cDNA into human renal-cell carcinoma (RCC) ACHN cells that scarcely express clusterin protein in order to examine whether overexpression of clusterin inhibits the Fas-mediated signal pathway for apoptotic cell death. No significant difference was observed in the in vitro cell growth rates between the clusterin-transfected cell line (ACHN/CL) and the vector-only-transfected control cell line (ACHN/C), whereas the colony-forming efficiency in soft agar of ACHN/CL was significantly higher than that of ACHAN/C. The anti-Fas monoclonal antibody CH11 induced apoptosis in ACHAN/C cells in a dose-dependent manner; however, the growth-inhibitory effect of CH11 on ACHN/CL cells was markedly suppressed, with corresponding increases in p53 expression and decrease in the fraction of cells in the sub-G(1) phase of the cell cycle. Furthermore, the cytotoxic effect of CH11 on ACHN/CL cells was augmented by treatment with interferon-gamma, but a corresponding effect on ACHN/C cells was not observed. These findings suggest that overexpression of clusterin may contribute to a phenotype resistant to Fas-mediated apoptosis, and that if interferon-gamma treatment is added according to the clusterin expression level, Fas-mediated therapy could be a novel approach to RCC.","PeriodicalId":80296,"journal":{"name":"Molecular urology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/10915360152559585","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"60626919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：