Cristian Acevedo - Academia.edu (original) (raw)

Papers by Cristian Acevedo

Research paper thumbnail of SCHU-49: Electrochemical Ablation of the Prostate: A Feasibility Study for the Treatment of Prostate Cancer and Benign Prostatic Hyperplasia

Research paper thumbnail of UP.69: Polymorphism of CYP1a1 MSP1 and Mortality in Patients with Prostatic Cancer: Seven-Year Follow-Up

Research paper thumbnail of Intraprostatic Injection of Alcohol Gel for the Treatment of Benign Prostatic Hyperplasia: Preliminary Clinical Results

TSW Urology, 2006

Benign prostatic hyperplasia (BPH) is one of the most common diseases ailing older men. Office-ba... more Benign prostatic hyperplasia (BPH) is one of the most common diseases ailing older men. Office-based procedures offer the advantage of being more effective than medications, while limiting the adverse effects, cost, and recovery of surgery. This study presents preliminary data on a new procedure that utilizes intraprostatic alcohol gel injection to ablate prostatic tissue. The purpose of this study is to evaluate the feasibility of using this gel as a treatment for BPH.

Research paper thumbnail of The lithotripsy table height: a novel predictor of outcome in shockwave lithotripsy

International braz j urol : official journal of the Brazilian Society of Urology

Outcome of Extracorporeal Shockwave Lithotripsy (SWL) is determined by physical factors that affe... more Outcome of Extracorporeal Shockwave Lithotripsy (SWL) is determined by physical factors that affect stone fragmentation and clearance. To evaluate the predictive value of the Lithotripsy Table Height (LTH) in SWL outcome. Lithotripsy Table Height (LTH) is a variable that represents skin to therapy head distance, and it is proportional to the energy that reaches the stone. A prospective study enrolled patients undergoing SWL for radiopaque urinary stones. All procedures were performed using a Modulith SLX (Karl Storz, Germany) Lithotripter. Patient weight, height and age; stone location and size; number of shock waves delivered, and LTH were recorded. One month post-procedure a KUB was obtained. Logistic regression analysis was used to evaluate the effects of these variables on stone-free outcome. A ROC curve was plotted. Fifty-six patients were enrolled. After one month follow-up, overall success rate (Stone Free) was 83.9% (n = 47). LTH was the only independent predictor of outcome...

Research paper thumbnail of Characterizing Prostiva TM RF Treatments of the Prostate for BPH with Gadolinium-Enhanced MRI

The Scientific World JOURNAL, 2009

Transurethral needle ablation (TUNA) is an accepted and effective therapy for the treatment of lo... more Transurethral needle ablation (TUNA) is an accepted and effective therapy for the treatment of lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH). Prostiva™ (Medtronic, Shoreview, MN) is the newest-generation device, which includes a new needle design and radio frequency (RF) generator. This device creates temperatures of 120°C and necrotic lesions in less than 2.5 min. Using previously described techniques, we analyzed dynamic, gadolinium-enhanced MRIs to characterize the ablative properties of the new Prostiva™ RF device.

Research paper thumbnail of Correlation Between Primary Tumor Pathologic Features and Presence of Clinical Metastasis at Diagnosis of Testicular Seminoma

Urology, 2007

To compare several risk factors in the testicular biopsy of patients with pure seminoma with and ... more To compare several risk factors in the testicular biopsy of patients with pure seminoma with and without clinical metastasis at diagnosis.

Research paper thumbnail of SCHU-08: Prognostic Factors in Transrectal Prostate Ultrasound-Guided Biopsy in Radical Prostatectomy Patients

Research paper thumbnail of SCHU-49: Electrochemical Ablation of the Prostate: A Feasibility Study for the Treatment of Prostate Cancer and Benign Prostatic Hyperplasia

Research paper thumbnail of SCHU-48: Impact of Body Mass Index in Patients Undergoing Transrectal Biopsy for Prostate Cancer Screening

Research paper thumbnail of Interstitial temperature mapping during Prolieve transurethral microwave treatment: Imaging reveals thermotherapy temperatures resulting in tissue necrosis and patent prostatic urethra

Urology, 2006

Objectives. Temperature mapping of the prostate during transurethral microwave thermotherapy and ... more Objectives. Temperature mapping of the prostate during transurethral microwave thermotherapy and imaging of the resultant zones of tissue necrosis have been previously performed using several commercial systems. This study was performed using the Prolieve Thermodilatation System, which simultaneously compresses the prostate with a 46F balloon circulating heated fluid and delivering microwave energy into the prostate. Methods. Interstitial temperature mapping during Prolieve treatment was performed on 10 patients with benign prostatic hyperplasia using 24 temperature sensors arrayed throughout the prostate. Voiding cystourethrograms were performed on 3 additional patients treated without temperature mapping to document the patency of the prostatic urethra 1 hour after treatment. Gadolinium-enhanced magnetic resonance imaging studies were performed on all patients 1 week after treatment to determine the extent and pattern of tissue necrosis resulting from transurethral microwave thermotherapy. Results. Interstitial temperature mapping found that the heating pattern generated by the Prolieve system created average peak temperatures of 51.8°C an average of 7 mm away from the prostatic urethra. These temperatures were greater near the bladder neck and mid-gland than toward the prostatic apex. Subtherapeutic temperatures were seen adjacent to the urethra, consistent with the viable tissue seen on gadoliniumenhanced magnetic resonance imaging sequences. Magnetic resonance imaging also revealed necrotic zones that were consistent with sustained temperatures greater than 45°C. Voiding cystourethrograms showed widely patent prostatic urethras 1 hour after treatment. Conclusions. Transurethral microwave thermotherapy with the Prolieve Thermodilatation System produced sustained therapeutic temperatures that resulted in tissue necrosis while maintaining viable tissue surrounding a temporarily dilated prostatic urethra.

Research paper thumbnail of Impact of CYP1A1, GSTM1, and GSTT1 polymorphisms in overall and specific prostate cancer survival

Urologic Oncology: Seminars and Original Investigations, 2014

Objective: Prognostic biomarkers that distinguish between patients with good or poor outcome can ... more Objective: Prognostic biomarkers that distinguish between patients with good or poor outcome can be used to guide decisions of whom to treat and how aggressively. In this sense, several groups have proposed genetic polymorphisms as potential susceptibility and prognostic biomarkers; however, their validity has not been proven. Thus, the main goal of the present work was to investigate the potential role of single and combined CYP1A1, GSTM1, and GSTT1 genotypes as modifiers of cancer survival in Chilean patients with prostate cancer.

Research paper thumbnail of Positive correlation between single or combined genotypes of CYP1A1 and GSTM1 in relation to prostate cancer in Chilean people

The Prostate, 2003

BACKGROUND. The prostate cancer is a slowly progressing disease that begins decades prior to diag... more BACKGROUND. The prostate cancer is a slowly progressing disease that begins decades prior to diagnosis. It has been suggested that there might be differences in susceptibility due to genetic polymorphisms in biotransformation enzyme genes. In the present work, associations between CYP1A1(Msp1), GSTM1(À/À) polymorphisms, and prostate cancer were analyzed in a casecontrol study. METHODS. Genomic DNA was isolated from peripheral blood samples, collected on EDTA. PCR-RFLP was used to determine simultaneously Msp1 and GSTM1(À/À) polymorphisms. RESULTS. In cancer patients, frequency of m2 variant allele (0.377) and GSTM1(À/À) (0.362) showed statistically significant increases compared to the control group (0.262 and 0.227, respectively). The estimate relative risks (OR) were higher for individuals carrying combined CYP1A1 and GSTM1 rare genotypes, in relation to individuals carrying CYP1A1 or GSTM1 alone. Multivariate logistic regression analysis including confounding factors (age, digital examination, and PSA antigen) showed even higher risk for individuals carrying m2m2 genotype (OR ¼ 3.99; 95% CI, 1.27-12.54), GST(À/À) genotype (OR ¼ 2.75; 95% CI, 1.31-5.79), and m2m2/GST(À) genotype (OR ¼ 16.63; 95% CI, 1.67-165.48). CONCLUSIONS. Taken together, these findings suggest that Chilean people carrying single or combined GSTM1 and CYP1A1 polymorphisms are more susceptible to prostate cancer.

Research paper thumbnail of Gonadotropin releasing hormone analogs induce apoptosis by extrinsic pathway involving p53 phosphorylation in primary cell cultures of human prostatic adenocarcinomas

The Prostate, 2009

BACKGROUND. Gonadotropin-releasing-hormone (GnRH) analogs are widely used to block hypothalamic-p... more BACKGROUND. Gonadotropin-releasing-hormone (GnRH) analogs are widely used to block hypothalamic-pituitary-gonadal axis and inhibit blood androgen levels in patients with prostate cancer (PCa). In addition, GnRH analogs induce proliferation arrest and apoptosis through GnRH receptors expressed on the membrane of PCa cells. Possible molecular mechanisms involved in GnRH-mediated apoptosis on prostate cancer cells were studied. METHODS. Primary cultures from PCa and benign prostatic hyperplasia (BPH) (nonmalignant control) were derived from samples provided by our Institutional Hospital. Cell cultures were incubated for 24 hr with 20 ng/ml of GnRH agonist Leuprolide (Lp) or antagonist Cetrorelix (Cx). Apoptosis was evaluated by studying the expression of Bax and Bcl-2 and the activation of caspase-9 (intrinsic pathway), caspase-8 (extrinsic pathway), and caspase-3. Also, mRNA level, protein expression and phosphorylation of p53 were studied. RESULTS. Cleaved caspase-8 and -3, but not -9, increased in presence of Lp and Cx in PCa cell cultures. Bax and Bcl-2 mRNA levels showed no changes after GnRH-analog treatments. Only Bax protein showed an increase after Cx treatment in PCa cell cultures. p53 mRNA level was higher in PCa than in BPH cell cultures. Lp and Cx increased p53 expression and phosphorylation in PCa cell cultures. CONCLUSIONS. Apoptosis induced by GnRH analogs seems to be mediated by extrinsic pathway involving p53 phosphorylation. Phosphorylated-p53 might be associated with the increase in apoptotic NGF receptor, p75, previously reported by our laboratory. These findings reinforce the concept of clinical use of GnRH analogs for PCa suggesting that intraprostatic treatment may be more effective.

Research paper thumbnail of In Vivo Temperature Mapping of Prostate during Treatment with TherMatrx TMx-2000 Device: Heat Field and MRI Determinations of Necrotic Lesions

Journal of Endourology, 2005

The effectiveness of any thermotherapy device is determined by the temperatures created and how l... more The effectiveness of any thermotherapy device is determined by the temperatures created and how long they are applied. Understanding the heating characteristics of a thermotherapy device is vital to its correct implementation. Interstitial temperature mapping was used to determine the heat field created within the prostate by the TherMatrx TMx-2000 transurethral microwave thermotherapy (TUMT) device. Gadolinium-enhanced MRI was used to determine the extent, type, and pattern of coagulation necrosis caused by TUMT. Interstitial temperature mapping was performed during treatment in five patients with benign prostatic hyperplasia using 24 temperature sensors inserted through the perineum and arrayed throughout the prostate under ultrasound and X-ray guidance. Gadolinium-enhanced MRI scans were performed on all patients 1 week after treatment. Interstitial temperature mapping found the heat field created to peak at the urethral surface near the central part of the catheter antenna. Temperatures decreased at consistent rates of 1 to 1.4 degrees C/mm radially and 0.1 to 0.5 degrees C/mm longitudinally from the peak area. Gadolinium-enhanced MRI showed minimal dispersed necrosis and only in the periurethral area. The TMx-2000 can create temperatures >45 degrees C in areas 3 to 4 mm from the antenna. However, the heat pattern and protocol of the TMx-2000 produce necrosis-generating conditions only within a few millimeters of the urethra.

Research paper thumbnail of Evaluation of MENT on primary cell cultures from benign prostatic hyperplasia and prostate carcinoma

International Journal of Andrology, 2009

Research paper thumbnail of Relationship among metabolizing genes, smoking and alcohol used as modifier factors on prostate cancer risk: Exploring some gene?gene and gene?environment interactions

European Journal of Epidemiology, 2005

Background: Prostate cancer (PCa) is one of the most common male cancers, but the burden of this ... more Background: Prostate cancer (PCa) is one of the most common male cancers, but the burden of this disease shows remarkable worldwide variation. The role of susceptibility low penetrance genes and environmental factors in the etiology of (PCa) is unclear, but may involve, in some cases, multiple alleles at multiple loci and environmental factors. Study Objectives: To assess whether CYP1A1, GSTM1, GSTT1 susceptibility genotypes, smoking status and alcohol consumption factors contribute to PCa risk, gene-gene and gene-environment interactions were analyzed. Design and Participants: We explored interactions on a multiplicative scale conducting a population-based case-control and a case-only study on 103 incident PCa patients and 132 unrelated controls. Main Results: The interaction odds ratios (IOR) for PCa risk were increased in men who had both susceptibility genotypes GST (M1; T1) null and CYP1A1-M1* in a case-control and case-only design (IOR cc : 1.11; 95% CI: 0.12-10.02; IOR cc : 6.23; 95%, CI: 0.51-75.89; IOR co : 2.80; 95% CI: 0.44-17.45 and IOR co : 2.65; 95%, CI: 0.30-25.40). No clear evidence for interaction on a multiplicative scale between smoking status, alcohol consumption and genetic polymorphisms in PCa risk was observed. Conclusions: Our findings suggest that the interaction between genetic polymorphisms in GST (T1; M1) and CYP1A1-M1* would play a significant role as a modifying factor on PCa risk in Chilean people. However, these preliminary exploratory results should be confirmed in a larger study.

Research paper thumbnail of GENE-GENE AND GENE-ENVIRONMENT INTERACTIONS AS MODIFIER FACTORS OF PROSTATIC CANCER RISK: ???A CASE-ONLY??? DESIGN STUDY

Epidemiology, 2005

The role of susceptibility low penetrance genes and environmental factors in the etiology of pros... more The role of susceptibility low penetrance genes and environmental factors in the etiology of prostate cancer (PCa) is unclear, but may involve in some cases multiple alleles at multiple loci. Aim: To evaluate the association of gene-gene and gene-environment interactions with PCa. Patients and methods: One hundred three subjects with biopsy proven PCa were studied, using a case-only design. All were interrogated about smoking habits. Polymorphisms for Glutathione-S-transferase (GST) and Cytochrome P4501A1 (CYP1A1), were measured in DNA extracted from peripheral Iymphocytes, using a restriction fragment length polymorphism analysis. Results: Our findings suggest that gene-gene interactions between GSTT1 and CYP1A1 high risk genotypes were positive modifiers and had a high predictive value for the presence of PCa, compared with non-susceptibility genotypes. The interaction between susceptibility genotypes and smoking did not modify the risk for PCa. Conclusions: Gene-gene interactions may play a role modulating the susceptibility to PCa in a proportion of affected individuals (Rev Méd Chile 2004; 132: 961-66). (

Research paper thumbnail of Joint effect among p53, CYP1A1, GSTM1 polymorphism combinations and smoking on prostate cancer risk: an exploratory genotype-environment interaction study

Asian Journal of Andrology, 2006

To assess the role of several genetic factors in combination with an environmental factor as modu... more To assess the role of several genetic factors in combination with an environmental factor as modulators of prostate cancer risk. We focus on allele variants of low-penetrance genes associated with cell control, the detoxification processes and smoking. Methods: In a case-control study we compared people carrying p53cd72 Pro allele, CYP1A1 M1 allele and GSTM1 null genotypes with their prostate cancer risk. Results: The joint risk for smokers carrying Pro* and M1*, Pro* and GSTM1null or GSTM1 null and CYP1A1 M1* variants was significantly higher (odds ratio [OR]: 13.13, 95% confidence interval [CI]: 2.41-71.36; OR: 3.97, 95% CI: 1.13-13.95 and OR: 6.87, 95% CI: 1.68-27.97, respectively) compared with that for the reference group, and for non-smokers was not significant. OR for combinations among p53cd72, GSTM1 and CYP1A1 M1 in smokers were positively and significantly associated with prostate cancer risk compared with non-smokers and compared with the putative lowest risk group (OR: 8.87, 95% CI: 1.25-62.71). Conclusion: Our results suggest that a combination of p53cd72, CYP1A1, GSTM1 alleles and smoking plays a significant role in modified prostate cancer risk on the study population, which means that smokers carrying susceptible genotypes might have a significantly higher risk than those carrying non-susceptible genotypes.

Research paper thumbnail of CYP1A1, CYP2E1 and GSTM1 genetic polymorphisms. The effect of single and combined genotypes on lung cancer susceptibility in Chilean people

Cancer Letters, 2001

CYP1A1, CYP2E1 and GSTM1 polymorphisms were evaluated in Chilean healthy controls and lung cancer... more CYP1A1, CYP2E1 and GSTM1 polymorphisms were evaluated in Chilean healthy controls and lung cancer patients. In the Chilean healthy group, frequencies of CYP1A1 variant alleles for MspI (m2 or CYP1A1*2A) and ile/val (val or CYP1A1*2B) polymorphisms were 0.25 and 0.33, respectively. Frequencies of variant alleles C (CYP2E1*6) and c2 (CYP2E1*5B) for CYP2E1 were 0.21 and 0.16, respectively and frequency for GSTM1(2) was 0.24. The presence of variant alleles for GSTM1, MspI and Ile/val polymorphisms was more frequent in cases than in controls. However, frequencies for the c2 and C alleles were not significantly different in controls and in cases. The estimated relative risk for lung cancer associated to a single mutated allele in CYP1A1, CYP2E1 or GSTM1 was 2.41 for m2, 1.69 for val, 1.16 for C, 0.71 for c2 and 2.46 for GSTM1(2). The estimated relative risk was higher for individuals carrying combined CYP1A1 and GSTM1 mutated alleles (m2/val, OR ¼ 6.28; m2/GSTM1(2), OR ¼ 3.56) and lower in individuals carrying CYP1A1 and CYP2E1 mutated alleles (m2/ C, OR ¼ 1.39; m2/c2, OR ¼ 2.00; val/C, OR ¼ 1.45; val/c2, OR ¼ 0.48; not significant). The OR values considering smoking were 4.37 for m2, 4.05 for val, 3.47 for GSTM1(2), 7.38 for m2/val and 3.68 for m2/GSTM1(2), higher values than those observed without any stratification by smoking. Taken together, these findings suggest that Chilean people carrying single or combined GSTM1 and CYP1A1 polymorphisms could be more susceptible to lung cancer induced by environmental pollutants such as polycyclic aromatic hydrocarbons. q

Research paper thumbnail of SCHU-49: Electrochemical Ablation of the Prostate: A Feasibility Study for the Treatment of Prostate Cancer and Benign Prostatic Hyperplasia

Research paper thumbnail of UP.69: Polymorphism of CYP1a1 MSP1 and Mortality in Patients with Prostatic Cancer: Seven-Year Follow-Up

Research paper thumbnail of Intraprostatic Injection of Alcohol Gel for the Treatment of Benign Prostatic Hyperplasia: Preliminary Clinical Results

TSW Urology, 2006

Benign prostatic hyperplasia (BPH) is one of the most common diseases ailing older men. Office-ba... more Benign prostatic hyperplasia (BPH) is one of the most common diseases ailing older men. Office-based procedures offer the advantage of being more effective than medications, while limiting the adverse effects, cost, and recovery of surgery. This study presents preliminary data on a new procedure that utilizes intraprostatic alcohol gel injection to ablate prostatic tissue. The purpose of this study is to evaluate the feasibility of using this gel as a treatment for BPH.

Research paper thumbnail of The lithotripsy table height: a novel predictor of outcome in shockwave lithotripsy

International braz j urol : official journal of the Brazilian Society of Urology

Outcome of Extracorporeal Shockwave Lithotripsy (SWL) is determined by physical factors that affe... more Outcome of Extracorporeal Shockwave Lithotripsy (SWL) is determined by physical factors that affect stone fragmentation and clearance. To evaluate the predictive value of the Lithotripsy Table Height (LTH) in SWL outcome. Lithotripsy Table Height (LTH) is a variable that represents skin to therapy head distance, and it is proportional to the energy that reaches the stone. A prospective study enrolled patients undergoing SWL for radiopaque urinary stones. All procedures were performed using a Modulith SLX (Karl Storz, Germany) Lithotripter. Patient weight, height and age; stone location and size; number of shock waves delivered, and LTH were recorded. One month post-procedure a KUB was obtained. Logistic regression analysis was used to evaluate the effects of these variables on stone-free outcome. A ROC curve was plotted. Fifty-six patients were enrolled. After one month follow-up, overall success rate (Stone Free) was 83.9% (n = 47). LTH was the only independent predictor of outcome...

Research paper thumbnail of Characterizing Prostiva TM RF Treatments of the Prostate for BPH with Gadolinium-Enhanced MRI

The Scientific World JOURNAL, 2009

Transurethral needle ablation (TUNA) is an accepted and effective therapy for the treatment of lo... more Transurethral needle ablation (TUNA) is an accepted and effective therapy for the treatment of lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH). Prostiva™ (Medtronic, Shoreview, MN) is the newest-generation device, which includes a new needle design and radio frequency (RF) generator. This device creates temperatures of 120°C and necrotic lesions in less than 2.5 min. Using previously described techniques, we analyzed dynamic, gadolinium-enhanced MRIs to characterize the ablative properties of the new Prostiva™ RF device.

Research paper thumbnail of Correlation Between Primary Tumor Pathologic Features and Presence of Clinical Metastasis at Diagnosis of Testicular Seminoma

Urology, 2007

To compare several risk factors in the testicular biopsy of patients with pure seminoma with and ... more To compare several risk factors in the testicular biopsy of patients with pure seminoma with and without clinical metastasis at diagnosis.

Research paper thumbnail of SCHU-08: Prognostic Factors in Transrectal Prostate Ultrasound-Guided Biopsy in Radical Prostatectomy Patients

Research paper thumbnail of SCHU-49: Electrochemical Ablation of the Prostate: A Feasibility Study for the Treatment of Prostate Cancer and Benign Prostatic Hyperplasia

Research paper thumbnail of SCHU-48: Impact of Body Mass Index in Patients Undergoing Transrectal Biopsy for Prostate Cancer Screening

Research paper thumbnail of Interstitial temperature mapping during Prolieve transurethral microwave treatment: Imaging reveals thermotherapy temperatures resulting in tissue necrosis and patent prostatic urethra

Urology, 2006

Objectives. Temperature mapping of the prostate during transurethral microwave thermotherapy and ... more Objectives. Temperature mapping of the prostate during transurethral microwave thermotherapy and imaging of the resultant zones of tissue necrosis have been previously performed using several commercial systems. This study was performed using the Prolieve Thermodilatation System, which simultaneously compresses the prostate with a 46F balloon circulating heated fluid and delivering microwave energy into the prostate. Methods. Interstitial temperature mapping during Prolieve treatment was performed on 10 patients with benign prostatic hyperplasia using 24 temperature sensors arrayed throughout the prostate. Voiding cystourethrograms were performed on 3 additional patients treated without temperature mapping to document the patency of the prostatic urethra 1 hour after treatment. Gadolinium-enhanced magnetic resonance imaging studies were performed on all patients 1 week after treatment to determine the extent and pattern of tissue necrosis resulting from transurethral microwave thermotherapy. Results. Interstitial temperature mapping found that the heating pattern generated by the Prolieve system created average peak temperatures of 51.8°C an average of 7 mm away from the prostatic urethra. These temperatures were greater near the bladder neck and mid-gland than toward the prostatic apex. Subtherapeutic temperatures were seen adjacent to the urethra, consistent with the viable tissue seen on gadoliniumenhanced magnetic resonance imaging sequences. Magnetic resonance imaging also revealed necrotic zones that were consistent with sustained temperatures greater than 45°C. Voiding cystourethrograms showed widely patent prostatic urethras 1 hour after treatment. Conclusions. Transurethral microwave thermotherapy with the Prolieve Thermodilatation System produced sustained therapeutic temperatures that resulted in tissue necrosis while maintaining viable tissue surrounding a temporarily dilated prostatic urethra.

Research paper thumbnail of Impact of CYP1A1, GSTM1, and GSTT1 polymorphisms in overall and specific prostate cancer survival

Urologic Oncology: Seminars and Original Investigations, 2014

Objective: Prognostic biomarkers that distinguish between patients with good or poor outcome can ... more Objective: Prognostic biomarkers that distinguish between patients with good or poor outcome can be used to guide decisions of whom to treat and how aggressively. In this sense, several groups have proposed genetic polymorphisms as potential susceptibility and prognostic biomarkers; however, their validity has not been proven. Thus, the main goal of the present work was to investigate the potential role of single and combined CYP1A1, GSTM1, and GSTT1 genotypes as modifiers of cancer survival in Chilean patients with prostate cancer.

Research paper thumbnail of Positive correlation between single or combined genotypes of CYP1A1 and GSTM1 in relation to prostate cancer in Chilean people

The Prostate, 2003

BACKGROUND. The prostate cancer is a slowly progressing disease that begins decades prior to diag... more BACKGROUND. The prostate cancer is a slowly progressing disease that begins decades prior to diagnosis. It has been suggested that there might be differences in susceptibility due to genetic polymorphisms in biotransformation enzyme genes. In the present work, associations between CYP1A1(Msp1), GSTM1(À/À) polymorphisms, and prostate cancer were analyzed in a casecontrol study. METHODS. Genomic DNA was isolated from peripheral blood samples, collected on EDTA. PCR-RFLP was used to determine simultaneously Msp1 and GSTM1(À/À) polymorphisms. RESULTS. In cancer patients, frequency of m2 variant allele (0.377) and GSTM1(À/À) (0.362) showed statistically significant increases compared to the control group (0.262 and 0.227, respectively). The estimate relative risks (OR) were higher for individuals carrying combined CYP1A1 and GSTM1 rare genotypes, in relation to individuals carrying CYP1A1 or GSTM1 alone. Multivariate logistic regression analysis including confounding factors (age, digital examination, and PSA antigen) showed even higher risk for individuals carrying m2m2 genotype (OR ¼ 3.99; 95% CI, 1.27-12.54), GST(À/À) genotype (OR ¼ 2.75; 95% CI, 1.31-5.79), and m2m2/GST(À) genotype (OR ¼ 16.63; 95% CI, 1.67-165.48). CONCLUSIONS. Taken together, these findings suggest that Chilean people carrying single or combined GSTM1 and CYP1A1 polymorphisms are more susceptible to prostate cancer.

Research paper thumbnail of Gonadotropin releasing hormone analogs induce apoptosis by extrinsic pathway involving p53 phosphorylation in primary cell cultures of human prostatic adenocarcinomas

The Prostate, 2009

BACKGROUND. Gonadotropin-releasing-hormone (GnRH) analogs are widely used to block hypothalamic-p... more BACKGROUND. Gonadotropin-releasing-hormone (GnRH) analogs are widely used to block hypothalamic-pituitary-gonadal axis and inhibit blood androgen levels in patients with prostate cancer (PCa). In addition, GnRH analogs induce proliferation arrest and apoptosis through GnRH receptors expressed on the membrane of PCa cells. Possible molecular mechanisms involved in GnRH-mediated apoptosis on prostate cancer cells were studied. METHODS. Primary cultures from PCa and benign prostatic hyperplasia (BPH) (nonmalignant control) were derived from samples provided by our Institutional Hospital. Cell cultures were incubated for 24 hr with 20 ng/ml of GnRH agonist Leuprolide (Lp) or antagonist Cetrorelix (Cx). Apoptosis was evaluated by studying the expression of Bax and Bcl-2 and the activation of caspase-9 (intrinsic pathway), caspase-8 (extrinsic pathway), and caspase-3. Also, mRNA level, protein expression and phosphorylation of p53 were studied. RESULTS. Cleaved caspase-8 and -3, but not -9, increased in presence of Lp and Cx in PCa cell cultures. Bax and Bcl-2 mRNA levels showed no changes after GnRH-analog treatments. Only Bax protein showed an increase after Cx treatment in PCa cell cultures. p53 mRNA level was higher in PCa than in BPH cell cultures. Lp and Cx increased p53 expression and phosphorylation in PCa cell cultures. CONCLUSIONS. Apoptosis induced by GnRH analogs seems to be mediated by extrinsic pathway involving p53 phosphorylation. Phosphorylated-p53 might be associated with the increase in apoptotic NGF receptor, p75, previously reported by our laboratory. These findings reinforce the concept of clinical use of GnRH analogs for PCa suggesting that intraprostatic treatment may be more effective.

Research paper thumbnail of In Vivo Temperature Mapping of Prostate during Treatment with TherMatrx TMx-2000 Device: Heat Field and MRI Determinations of Necrotic Lesions

Journal of Endourology, 2005

The effectiveness of any thermotherapy device is determined by the temperatures created and how l... more The effectiveness of any thermotherapy device is determined by the temperatures created and how long they are applied. Understanding the heating characteristics of a thermotherapy device is vital to its correct implementation. Interstitial temperature mapping was used to determine the heat field created within the prostate by the TherMatrx TMx-2000 transurethral microwave thermotherapy (TUMT) device. Gadolinium-enhanced MRI was used to determine the extent, type, and pattern of coagulation necrosis caused by TUMT. Interstitial temperature mapping was performed during treatment in five patients with benign prostatic hyperplasia using 24 temperature sensors inserted through the perineum and arrayed throughout the prostate under ultrasound and X-ray guidance. Gadolinium-enhanced MRI scans were performed on all patients 1 week after treatment. Interstitial temperature mapping found the heat field created to peak at the urethral surface near the central part of the catheter antenna. Temperatures decreased at consistent rates of 1 to 1.4 degrees C/mm radially and 0.1 to 0.5 degrees C/mm longitudinally from the peak area. Gadolinium-enhanced MRI showed minimal dispersed necrosis and only in the periurethral area. The TMx-2000 can create temperatures >45 degrees C in areas 3 to 4 mm from the antenna. However, the heat pattern and protocol of the TMx-2000 produce necrosis-generating conditions only within a few millimeters of the urethra.

Research paper thumbnail of Evaluation of MENT on primary cell cultures from benign prostatic hyperplasia and prostate carcinoma

International Journal of Andrology, 2009

Research paper thumbnail of Relationship among metabolizing genes, smoking and alcohol used as modifier factors on prostate cancer risk: Exploring some gene?gene and gene?environment interactions

European Journal of Epidemiology, 2005

Background: Prostate cancer (PCa) is one of the most common male cancers, but the burden of this ... more Background: Prostate cancer (PCa) is one of the most common male cancers, but the burden of this disease shows remarkable worldwide variation. The role of susceptibility low penetrance genes and environmental factors in the etiology of (PCa) is unclear, but may involve, in some cases, multiple alleles at multiple loci and environmental factors. Study Objectives: To assess whether CYP1A1, GSTM1, GSTT1 susceptibility genotypes, smoking status and alcohol consumption factors contribute to PCa risk, gene-gene and gene-environment interactions were analyzed. Design and Participants: We explored interactions on a multiplicative scale conducting a population-based case-control and a case-only study on 103 incident PCa patients and 132 unrelated controls. Main Results: The interaction odds ratios (IOR) for PCa risk were increased in men who had both susceptibility genotypes GST (M1; T1) null and CYP1A1-M1* in a case-control and case-only design (IOR cc : 1.11; 95% CI: 0.12-10.02; IOR cc : 6.23; 95%, CI: 0.51-75.89; IOR co : 2.80; 95% CI: 0.44-17.45 and IOR co : 2.65; 95%, CI: 0.30-25.40). No clear evidence for interaction on a multiplicative scale between smoking status, alcohol consumption and genetic polymorphisms in PCa risk was observed. Conclusions: Our findings suggest that the interaction between genetic polymorphisms in GST (T1; M1) and CYP1A1-M1* would play a significant role as a modifying factor on PCa risk in Chilean people. However, these preliminary exploratory results should be confirmed in a larger study.

Research paper thumbnail of GENE-GENE AND GENE-ENVIRONMENT INTERACTIONS AS MODIFIER FACTORS OF PROSTATIC CANCER RISK: ???A CASE-ONLY??? DESIGN STUDY

Epidemiology, 2005

The role of susceptibility low penetrance genes and environmental factors in the etiology of pros... more The role of susceptibility low penetrance genes and environmental factors in the etiology of prostate cancer (PCa) is unclear, but may involve in some cases multiple alleles at multiple loci. Aim: To evaluate the association of gene-gene and gene-environment interactions with PCa. Patients and methods: One hundred three subjects with biopsy proven PCa were studied, using a case-only design. All were interrogated about smoking habits. Polymorphisms for Glutathione-S-transferase (GST) and Cytochrome P4501A1 (CYP1A1), were measured in DNA extracted from peripheral Iymphocytes, using a restriction fragment length polymorphism analysis. Results: Our findings suggest that gene-gene interactions between GSTT1 and CYP1A1 high risk genotypes were positive modifiers and had a high predictive value for the presence of PCa, compared with non-susceptibility genotypes. The interaction between susceptibility genotypes and smoking did not modify the risk for PCa. Conclusions: Gene-gene interactions may play a role modulating the susceptibility to PCa in a proportion of affected individuals (Rev Méd Chile 2004; 132: 961-66). (

Research paper thumbnail of Joint effect among p53, CYP1A1, GSTM1 polymorphism combinations and smoking on prostate cancer risk: an exploratory genotype-environment interaction study

Asian Journal of Andrology, 2006

To assess the role of several genetic factors in combination with an environmental factor as modu... more To assess the role of several genetic factors in combination with an environmental factor as modulators of prostate cancer risk. We focus on allele variants of low-penetrance genes associated with cell control, the detoxification processes and smoking. Methods: In a case-control study we compared people carrying p53cd72 Pro allele, CYP1A1 M1 allele and GSTM1 null genotypes with their prostate cancer risk. Results: The joint risk for smokers carrying Pro* and M1*, Pro* and GSTM1null or GSTM1 null and CYP1A1 M1* variants was significantly higher (odds ratio [OR]: 13.13, 95% confidence interval [CI]: 2.41-71.36; OR: 3.97, 95% CI: 1.13-13.95 and OR: 6.87, 95% CI: 1.68-27.97, respectively) compared with that for the reference group, and for non-smokers was not significant. OR for combinations among p53cd72, GSTM1 and CYP1A1 M1 in smokers were positively and significantly associated with prostate cancer risk compared with non-smokers and compared with the putative lowest risk group (OR: 8.87, 95% CI: 1.25-62.71). Conclusion: Our results suggest that a combination of p53cd72, CYP1A1, GSTM1 alleles and smoking plays a significant role in modified prostate cancer risk on the study population, which means that smokers carrying susceptible genotypes might have a significantly higher risk than those carrying non-susceptible genotypes.

Research paper thumbnail of CYP1A1, CYP2E1 and GSTM1 genetic polymorphisms. The effect of single and combined genotypes on lung cancer susceptibility in Chilean people

Cancer Letters, 2001

CYP1A1, CYP2E1 and GSTM1 polymorphisms were evaluated in Chilean healthy controls and lung cancer... more CYP1A1, CYP2E1 and GSTM1 polymorphisms were evaluated in Chilean healthy controls and lung cancer patients. In the Chilean healthy group, frequencies of CYP1A1 variant alleles for MspI (m2 or CYP1A1*2A) and ile/val (val or CYP1A1*2B) polymorphisms were 0.25 and 0.33, respectively. Frequencies of variant alleles C (CYP2E1*6) and c2 (CYP2E1*5B) for CYP2E1 were 0.21 and 0.16, respectively and frequency for GSTM1(2) was 0.24. The presence of variant alleles for GSTM1, MspI and Ile/val polymorphisms was more frequent in cases than in controls. However, frequencies for the c2 and C alleles were not significantly different in controls and in cases. The estimated relative risk for lung cancer associated to a single mutated allele in CYP1A1, CYP2E1 or GSTM1 was 2.41 for m2, 1.69 for val, 1.16 for C, 0.71 for c2 and 2.46 for GSTM1(2). The estimated relative risk was higher for individuals carrying combined CYP1A1 and GSTM1 mutated alleles (m2/val, OR ¼ 6.28; m2/GSTM1(2), OR ¼ 3.56) and lower in individuals carrying CYP1A1 and CYP2E1 mutated alleles (m2/ C, OR ¼ 1.39; m2/c2, OR ¼ 2.00; val/C, OR ¼ 1.45; val/c2, OR ¼ 0.48; not significant). The OR values considering smoking were 4.37 for m2, 4.05 for val, 3.47 for GSTM1(2), 7.38 for m2/val and 3.68 for m2/GSTM1(2), higher values than those observed without any stratification by smoking. Taken together, these findings suggest that Chilean people carrying single or combined GSTM1 and CYP1A1 polymorphisms could be more susceptible to lung cancer induced by environmental pollutants such as polycyclic aromatic hydrocarbons. q