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The present study aimed to determine whether grape seed extract (GSE) procyanidin mix, and its active constituent procyanidin B2 3,3â³-di-O-gallate (B2G2) have the potential to target cancer stem cells (CSCs) in prostate cancer (PCa). The CSC populations were isolated and purified based on CD44+ -α2ß1high surface markers in PCa cell lines LNCaP, C4-2B, 22Rv1, PC3, and DU145, and then subjected to prostasphere formation assays in the absence or presence of GSE or B2G2. Results indicated that at lower doses (<15 µg) , the GSE procyanidin mix produced activity in unsorted prostate cancer antigen (PCA) cells, but not in sorted; however, multiple treatments with low dose GSE over a course of time inhibited sphere formation by sorted PCA CSCs. Importantly, B2G2 demonstrated significant potential to target both unsorted and sorted CSCs at lower doses. As formation of spheroids, under specific in vitro conditions, is a measure of stemness, these results indicated the potential of both GSE and B2G2 to target the self-renewal of CSC in PCa cell lines, though B2G2 was more potent in its efficacy. Subsequent mechanistic studies revealed that both GSE procyanidins and B2G2 strongly decreased the constitutive as well as Jagged1 (Notch1 ligand)-induced activated Notch1 pathway. In totality, these in vitro studies warrant extensive dose-profiling-based assessments in vivo settings to conclusively determine the impact on CSC pool kinetics on the efficacy of both GSE and B2G2 to target PCa growth as well as tumor relapse.
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Antocianinas/farmacología , Antineoplásicos Fitogénicos/farmacología , Biflavonoides/farmacología , Catequina/farmacología , Extracto de Semillas de Uva/farmacología , Células Madre Neoplásicas/efectos de los fármacos , Proantocianidinas/farmacología , Neoplasias de la Próstata/tratamiento farmacológico , Apoptosis/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Humanos , Proteína Jagged-1/metabolismo , Masculino , Células Madre Neoplásicas/patología , Células PC-3 , Próstata/patología , Neoplasias de la Próstata/patología , Receptor Notch1/metabolismo , Esferoides Celulares/efectos de los fármacos , Células Tumorales CultivadasRESUMEN
BACKGROUND: The 4Kscore is a new commercially available blood-based diagnostic test which predicts risk for aggressive, clinically significant prostate cancer on prostate biopsy. The 4Kscore is currently restricted to patients who have not had a digital rectal exam (DRE) in the previous 96 h, owing to prior mixed data suggesting that prostate specific antigen (PSA) isoforms may increase by a statistically significant-if not necessarily clinically significant-amount shortly after DRE. Our primary objective was to determine if 4Kscore test results are affected by a preceding DRE. METHODS: Participants at a Prostate Cancer Awareness Week screening event sponsored by the Prostate Conditions Education Council filled out clinical history questionnaires and had blood samples for 4Kscore testing drawn prior to DRE, then 15-45 min following DRE. Patients with prior cancer diagnosis, 5-alpha reductase inhibitor medication use, or lower urinary tract procedures in the prior 6 months were excluded, resulting in a population of 162 participants for analysis. Values were then compared to determine if there was a significant difference in 4Kscore following DRE. RESULTS: A statistically significant increase was seen in levels of 3 kallikreins measured (total PSA, free PSA, and intact PSA; median <0.03 ng/mL for all). This resulted in a small but statistically significant decrease in post-DRE 4Kscore (median absolute score decrease 0.43%). Using a 4Kscore cutoff of 7.5% resulted in reclassification of 10 patients (6.2%), nine of whom were "downgraded" from above the cutoff to below. CONCLUSIONS: If the blood draw for the 4 K score is performed after a screening DRE, there is a statistically significant difference in the 4 K score results, but in the vast majority of cases it would not affect clinical decision making.
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Tacto Rectal/métodos , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/diagnóstico , Juego de Reactivos para Diagnóstico , Anciano , Biopsia , Detección Precoz del Cáncer/métodos , Humanos , Calicreínas/sangre , Masculino , Persona de Mediana Edad , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/patología , Calicreínas de Tejido/sangreRESUMEN
BACKGROUND: Testicular stromal tumors (TSTs) are rare. In adult men with TSTs, various pathologic risk factors have been identified in patients with clinically localized disease that increase the risk of occult metastatic disease (OMD). We systematically reviewed existing literature to analyze the impact of these risk factors on OMD in prepubertal (0 to 12 y) and postpubertal (13 to 21 y) patients. METHODS: A literature search was conducted using the combination of terms: "testicular stromal tumors," "testicular leydig cell tumors," "testicular sertoli tumors," "testicular interstitial tumors," "testicular granulosa tumor," and "testicular sex cord tumors." Studies of patients 0 to 21 years with clinical stage I TSTs were included. RESULTS: A total of 100 patients from 31 publications were included with a median age at diagnosis of 5.7 years (range, 1.2 mo to 21 y). Seventy-nine patients were 12 years and below (median 7.2 mo) and 21 patients were 13 to 21 years (median 16 y). No patients in either group were identified to have OMD at retroperitoneal lymph node dissection or during follow-up surveillance (median follow-up 45.6 y; range, 4 to 360 mo). 99% of those 12 years and below versus 95% of those above 12 years had 0 to 1 pathologic risk factors, and 1% versus 5% had 2+ pathologic risk factors (P=0.38). CONCLUSIONS: Clinical stage I TSTs in adolescent, postpubertal patients appear to behave in a benign manner with few pathologic risk factors, similar to prepubertal patients. Given the low risk of relapse in this population, low-impact surveillance strategies are paramount. Prospective study of these patients is needed, and entry into a tumor registry such as the International Ovarian and Testicular Stromal Tumor Registry is important to learning more about this rare disease.
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Tumores de los Cordones Sexuales y Estroma de las Gónadas/epidemiología , Neoplasias Testiculares/epidemiología , Adolescente , Niño , Preescolar , Estrógenos/biosíntesis , Feminización/etiología , Humanos , Incidencia , Lactante , Recién Nacido , Masculino , Índice Mitótico , Metástasis de la Neoplasia , Estadificación de Neoplasias , Orquiectomía , Pronóstico , Factores de Riesgo , Tumores de los Cordones Sexuales y Estroma de las Gónadas/metabolismo , Tumores de los Cordones Sexuales y Estroma de las Gónadas/patología , Tumores de los Cordones Sexuales y Estroma de las Gónadas/cirugía , Neoplasias Testiculares/metabolismo , Neoplasias Testiculares/patología , Neoplasias Testiculares/cirugía , Testosterona/metabolismo , Adulto JovenRESUMEN
BACKGROUND: Extended transrectal ultrasound guided biopsies (TRUSB) of the prostate may not accurately convey true morphometric information and Gleason score (GS) of prostate cancer (PCa) and the clinical use of template-guided (5-mm grid) transperineal mapping biopsies (TPMBs) remains controversial. METHODS: We correlated the clinical-pathologic results of 1,403 TPMB cores obtained from 25 men diagnosed with PCa with 64 cancer lesions found in their corresponding radical prostatectomy (RP) specimens. Special computer models of three-dimensional, whole-mounted radical prostatectomy (3D-WMRP) specimens were generated and used as gold standard to determine tumor morphometric data. Between-sample rates of upgrade and downgrade (highest GS and a novel cumulative GS) and upstage and downstage (laterality) were determined. Lesions ≥ 0.5 cm(3) or GS ≥ 7 were considered clinically significant. RESULTS: From 64 separate 3D-WMRP lesions, 25 had significant volume (mean 1.13 cm(3)) and 39 were insignificant (mean 0.09 cm(3)) (P < 0.0001); 18/64 lesions were missed by TPMB, but only one was clinically significant with GS-8 (0.02 cm(3)). When comparing the cumulative GS of TPMB versus RP, 72% (n = 18) had identical scores, 12% (n = 3) were upgraded, and only 16% (n = 4) were downgraded. Laterality of TPMB and RP was strongly correlated, 80% same laterality, 4% were up-staged, and 16% down-staged. CONCLUSIONS: Our clinical-pathology correlation showed very high accuracy of TPMB with a 5-mm grid template to detect clinically significant PCa lesions as compared with 3D-WMRP, providing physicians and patients with a reliable assessment of grade and stage of disease and the opportunity to choose the most appropriate therapeutic options.
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Próstata/patología , Neoplasias de la Próstata/patología , Anciano , Humanos , Biopsia Guiada por Imagen/métodos , Imagenología Tridimensional , Masculino , Persona de Mediana Edad , Clasificación del Tumor/métodos , Próstata/cirugía , Prostatectomía , Neoplasias de la Próstata/cirugía , Estudios RetrospectivosRESUMEN
Pediatric hypertension represents a rare though increasingly common medical problem. When encountered, a workup to determine the etiology should be conducted. In this report, we detail an unusual case in which a teenager presenting with hypertension was found to have multifocal primary paragangliomas. We illustrate important considerations in management which include appropriate preoperative labs and imaging, collaboration with endocrinology for preoperative alpha-blockade, surgical management with close perioperative hemodynamic control, and genetic evaluation for all patients with paragangliomas.
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Neoplasias de las Glándulas Suprarrenales , Hipertensión , Paraganglioma , Humanos , Adolescente , Niño , Paraganglioma/complicaciones , Paraganglioma/diagnóstico , Paraganglioma/genética , Diagnóstico por Imagen , Hipertensión/complicaciones , Neoplasias de las Glándulas Suprarrenales/cirugíaRESUMEN
INTRODUCTION: We evaluated primary testicular tumor characteristics associated with nongerm cell tumor histology and potential appropriateness for testis sparing surgery in selected patients from our institution. METHODS: We retrospectively reviewed medical records of patients undergoing surgery for testicular masses between 2003 and 2015. We included patients with unilateral testicular tumors, normal preoperative serum tumor markers and no preoperative evidence of metastatic spread. Demographic and clinical information were extracted. The primary outcome studied was tumor pathology, germ cell tumor histology vs nongerm cell histology. We compared patients in these cohorts based on the testicular tumor size. RESULTS: A total of 48 patients met study criteria, 18 (37.5%) of whom had a final pathology consistent with nongerm cell histology. In general, the median tumor size was less in the nongerm cell group (11 mm vs 27 mm, p=0.001). Tumor size less than 2 cm was associated with increased likelihood of nongerm cell histology (p=0.003) with 61.9% of those with tumors less than 2 cm harboring nongerm cell tumors and therefore likely appropriate for organ-sparing surgery. A receiver operating characteristic analysis demonstrated a maximum sensitivity and specificity for selecting masses with normal tumor markers as having nongerm cell histology at a size cutoff of 18 mm. CONCLUSIONS: It appears that a majority of patients with localized small testicular masses and nonelevated tumor markers will have nongerm cell histology, which makes them potentially eligible for testicular sparing surgery at centers with expertise in intraoperative frozen section analysis.
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BACKGROUND: Prostate-derived Ets factor (PDEF) is expressed in tissues of high epithelial content including prostate, although its precise function has not been fully established. Conventional therapies produce a high rate of cure for patients with localized prostate cancer, but there is, at present, no effective treatment for intervention in metastatic prostate cancer. These facts underline the need to develop new approaches for early diagnosis of aggressive prostate cancer patients, and mechanism based anti-metastasis therapies that will improve the outlook for hormone-refractory prostate cancer. In this study we evaluated role of prostate-derived Ets factor (PDEF) in prostate cancer. RESULTS: We observed decreased PDEF expression in prostate cancer cell lines correlated with increased aggressive phenotype, and complete loss of PDEF protein in metastatic prostate cancer cell lines. Loss of PDEF expression was confirmed in high Gleason Grade prostate cancer samples by immuno-histochemical methods. Reintroduction of PDEF profoundly affected cell behavior leading to less invasive phenotypes in three dimensional cultures. In addition, PDEF expressing cells had altered cell morphology, decreased FAK phosphorylation and decreased colony formation, cell migration, and cellular invasiveness. In contrast PDEF knockdown resulted in increased migration and invasion as well as clonogenic activity. Our results also demonstrated that PDEF downregulated MMP9 promoter activity, suppressed MMP9 mRNA expression, and resulted in loss of MMP9 activity in prostate cancer cells. These results suggested that loss of PDEF might be associated with increased MMP9 expression and activity in aggressive prostate cancer. To confirm results we investigated MMP9 expression in clinical samples of prostate cancer. Results of these studies show increased MMP9 expression correlated with advanced Gleason grade. Taken together our results demonstrate decreased PDEF expression and increased MMP9 expression during the transition to aggressive prostate cancer. CONCLUSIONS: These studies demonstrate for the first time negative regulation of MMP9 expression by PDEF, and that PDEF expression was lost in aggressive prostate cancer and was inversely associated with MMP9 expression in clinical samples of prostate cancer. Based on these exciting results, we propose that loss of PDEF along with increased MMP9 expression should serve as novel markers for early detection of aggressive prostate cancer.
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Metaloproteinasa 9 de la Matriz/metabolismo , Neoplasias de la Próstata/patología , Proteínas Proto-Oncogénicas c-ets/fisiología , Secuencia de Bases , Western Blotting , Línea Celular Tumoral , Cartilla de ADN , Humanos , Inmunohistoquímica , Masculino , Fenotipo , Neoplasias de la Próstata/enzimología , Neoplasias de la Próstata/metabolismo , Proteínas Proto-Oncogénicas c-ets/genética , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
INTRODUCTION: Retroperitoneal lymph node dissection for low volume, clinical stage II testicular seminoma may provide an alternative to radiation therapy or chemotherapy for local control, preserving the high rate of cure while reducing exposure to long-term side effects. In this study we determined the willingness of patients and providers to participate in a clinical trial with this approach. METHODS: We distributed 2 surveys, with one going to patients with testicular seminoma and one to providers who treat testicular cancer. This study included patients with pure seminoma and providers currently in clinical practice. Logistic regression analysis was performed to identify factors associated with willingness to participate in the proposed trial. RESULTS: Overall 193 patients with testicular seminoma and 178 actively practicing providers responded to the surveys. Of these respondents 148 patients (76.7%) and 167 providers (81.9%) reported that they would be willing to participate in the proposed clinical trial. For patients, on univariate analysis age, stage, management after orchiectomy and relapse status did not impact willingness to enroll. For providers, on univariate analysis years in practice, number of patients with testicular cancer evaluated annually, practice setting and association with a Comprehensive Cancer Center did not impact willingness to offer enrollment. CONCLUSIONS: The majority of patients and providers would be willing to participate in a trial of retroperitoneal lymph node dissection as an alternative treatment strategy for low volume, clinical stage II testicular seminoma.
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Altering the effects of testosterone on prostate cancer cells by blocking androgen production or action is a critical part of treating this malignancy. The appropriate timing of androgen blockade for advanced prostate cancer is controversial. Despite many phase-III studies, gaps in clinical information still remain, and some questions are still not conclusively answered. This review concentrates on high-level evidence to address common clinical situations in advanced and metastatic prostate cancer. Additionally, the side-effects of androgen blockade have become increasingly visible and relevant.
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Antagonistas de Andrógenos/uso terapéutico , Terapia Neoadyuvante , Neoplasias de la Próstata/tratamiento farmacológico , Antagonistas de Andrógenos/efectos adversos , Andrógenos/metabolismo , Antineoplásicos Hormonales/efectos adversos , Antineoplásicos Hormonales/uso terapéutico , Quimioterapia Adyuvante/efectos adversos , Terapia Combinada , Humanos , Metástasis Linfática , Masculino , Terapia Neoadyuvante/efectos adversos , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/patología , Neoplasias Hormono-Dependientes/tratamiento farmacológico , Neoplasias de la Próstata/mortalidad , Neoplasias de la Próstata/patología , Análisis de Supervivencia , Factores de Tiempo , Resultado del TratamientoRESUMEN
INTRODUCTION: Testicular germ cell tumors (GCTs) are the most common solid tumor among adolescent and young adult (AYA) males. AYA patients with GCTs most typically have non-seminoma compared with seminoma, and accordingly there are fewer data reported on the AYA experience with testicular seminoma. OBJECTIVE: To evaluate national trends in postoperative treatment and overall survival (OS) outcomes in testicular seminoma by age group, specifically comparing AYAs with older adults. STUDY DESIGN: The National Cancer Data Base (NCDB) was queried for patients with testicular seminoma diagnosed between 2004 and 2012, who underwent orchiectomy followed by observation or adjuvant therapy (chemotherapy, radiation (RT), or both). Patients were grouped by age: AYA (15-39 years), adults between 40 and 55 years, and adults >55 years. Overall survival (OS) was presented using Kaplan-Meier curves and groups compared via a log-rank test. Univariate (UVA) and multivariate (MVA) analyses were performed using Cox proportional hazards regression models. Binary multiple logistic regression identified differences in variables by age category. RESULTS: Of the total 22,361 patients the majority were AYAs (12,880, 57.6%), followed by adults 40-55 years (8,022, 35.9%), and >55 years (1,459, 6.5%). Unadjusted 5-year OS was significantly better for AYAs versus adults 40-55 years and >55 years (98.0%, 96.4%, 87.7%; p < 0.001), as was 10-year OS (96.1%, 91.8%, 71.3% respectively; p < 0.001). The Table shows that on a MVA, OS was significantly better for AYAs versus adults 40-55 years and adults >55 years. AYA patients were also more commonly treated at centers with greater clinical volume. Additionally, AYA patients were less likely to present with metastatic disease. Accordingly, AYA patients were less likely to undergo retroperitoneal lymph node dissection (OR 0.81; p = 0.001) and were less often managed with adjuvant therapy including chemotherapy (OR 0.91; p = 0.027), RT (OR 0.93; p = 0.025), or both (OR 0.68; p = 0.020). DISCUSSION: AYA patients with testicular seminoma present with earlier stage disease and in the clinical Stage I setting are more often are managed with active surveillance following orchiectomy when compared with older adults in this population-based analysis. Among AYA patients, OS was modestly better when compared with adults 40-55 years and significantly better when compared with adults >55 years. CONCLUSION: Our objective to describe the patterns of care and survival outcomes for AYA patients with testicular seminoma in the USA was met by reviewing this large national dataset. These results may inform future guidelines for management of AYA seminoma.
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Seminoma/mortalidad , Seminoma/terapia , Neoplasias Testiculares/mortalidad , Neoplasias Testiculares/terapia , Adolescente , Adulto , Factores de Edad , Bases de Datos Factuales , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pautas de la Práctica en Medicina , Seminoma/patología , Tasa de Supervivencia , Neoplasias Testiculares/patología , Estados Unidos/epidemiología , Adulto JovenRESUMEN
OBJECTIVE: To systematically review the existing literature to analyze the impact of previously identified pathologic risk factors on harboring occult metastatic disease (OMD) in patients with Clinical Stage I testicular stromal tumors (TSTs). MATERIALS AND METHODS: A literature search using PubMed was conducted using the following terms: "testicular stromal tumors," "testicular Leydig cell tumors," "testicular Sertoli tumors," "testicular interstitial tumors," "testicular granulosa tumor," and "testicular sex cord tumors." For analysis, we included only studies with data on available recurrence, survival, and time-to-event. We hypothesized that patients with ≥2 risk factors would experience lower 5-year OMD-free survival (OMDFS) than those with <2 risk factors. RESULTS: Two hundred ninety-two patients from 47 publications were included with a median age at diagnosis of 35 years (range 12-76). Five-year OMDFS and overall survival in patients with Stage I TSTs were 91.2% and 93.2%, respectively. When comparing those who harbored OMD to those who did not, we observed an increased risk of OMD for each additional risk factor (P < .001). Five-year OMDFS was 98.1% for those with <2 risk factors vs 44.9% for those with ≥2 risk factors (P < .001). CONCLUSION: The existing literature on pathologic risk factors for OMD in this population is insufficient to make broad clinical recommendations. However, these factors appear to risk-stratify patients and may be useful for future research investigating adjuvant therapy in higher-risk patients. This review indicates that such a stratification system has a rational basis.
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Causas de Muerte , Tumor de Células de Sertoli-Leydig/mortalidad , Tumor de Células de Sertoli-Leydig/patología , Neoplasias Testiculares/mortalidad , Neoplasias Testiculares/patología , Adulto , Factores de Edad , Anciano , Supervivencia sin Enfermedad , Humanos , Estimación de Kaplan-Meier , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Invasividad Neoplásica/patología , Metástasis de la Neoplasia , Estadificación de Neoplasias , Orquiectomía/métodos , Pronóstico , Medición de Riesgo , Tumor de Células de Sertoli-Leydig/cirugía , Análisis de Supervivencia , Neoplasias Testiculares/cirugía , Adulto JovenRESUMEN
BACKGROUND: In adolescents, approximately 90% of testicular germ cell tumors (T-GCTs) are non-seminomas (NS T-GCTs). Few studies have evaluated the impact of age, specifically in adolescence, on outcomes of NS T-GCTs. OBJECTIVE: The purpose of this study was to review all patients diagnosed with NS T-GCTs in the Surveillance, Epidemiology, and End Results (SEER) database to evaluate the association between age (adolescents vs. adults) and survival outcomes. METHOD: The SEER database was queried for individuals ≥13 years old diagnosed with NS T-GCTs from 1995 to 2012. Patients were categorized into adolescent (13-19 years) and adult (≥20 years) cohorts. A Cox proportional hazards model was used for multivariate analysis (MVA). RESULTS: A total of 13,963 patients (1496 adolescents, 12,467 adults) was included. Median follow-up was 71 months (range 1-215). Five-year overall survival (OS) for adolescent and adult patients was 94% and 92%, respectively (p = 0.007); 5-year cancer-specific survival (CSS) was 95% and 94%, respectively (p = 0.139). Under MVA, adolescent patients had improved OS (HR 0.61; 95% CI 0.50-0.75; p < 0.001) and CSS (HR 0.65; 95% CI 0.51-0.82; p < 0.001), when compared with adults (Table). In a logistic regression analysis adjusting for demographics, adolescent patients were more likely to present with regional or distant metastatic disease (OR 1.16; 95% CI 1.01-1.35; p = 0.039), undergo an orchiectomy (OR 2.44; 95% CI 1.50-4.00; p < 0.001) or tumor excision (OR 2.43; 95% CI 1.57-3.77; p < 0.001), and receive other adjuvant surgery (OR 5.87; 95% CI 2.25-15.30; p < 0.001). CONCLUSIONS: To our knowledge, this is the largest population-based comparative analysis in NS T-GCTs comparing outcomes between these two age groups. Adolescent patients with NS T-GCTs had slightly improved survival compared with adults, despite presenting with more advanced disease. While adolescent patients present at more advanced stage, they achieve excellent survival outcomes possibly at the cost of a greater therapeutic burden.
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Neoplasias de Células Germinales y Embrionarias/mortalidad , Neoplasias Testiculares/mortalidad , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de Células Germinales y Embrionarias/terapia , Tasa de Supervivencia , Neoplasias Testiculares/terapia , Adulto JovenRESUMEN
Prostate tumors are graded by the revised Gleason Score (GS) which is the sum of the two predominant Gleason grades present ranging from 6-10. GS 6 cancer exclusively with Gleason grade 3 is designated as low grade (LG) and correlates with better clinical prognosis for patients. GS >7 cancer with at least one of the Gleason grades 4 and 5 is designated as HG indicate worse prognosis for patients. Current transrectal ultrasound guided prostate biopsies often fail to correctly diagnose HG prostate cancer due to sampling errors. Diffuse reflectance spectra (DRS) of biological tissue depend on tissue morphology and architecture. Thus, DRS could potentially differentiate between HG and LG prostatic carcinoma. A 15-gauge optical biopsy needle was prototyped to take prostate biopsies after measuring DRS with a laboratory fluorometer. This needle has an optical sensor that utilizes 8×100 µm optical fibers for tissue excitation and a single 200 µm central optical fiber to measure DRS. Tissue biopsy cores were obtained from 20 surgically excised prostates using this needle after measuring DRS at 5 nm intervals between 500-700 nm wavelengths. Tissue within a measurement window was histopathologically classified as either benign, LG, or HG and correlated with DRS. Partial least square analysis of DRS identified principal components (PC) as potential classifiers. Statistically significant PCs (p<;0.05) were tested for their ability to classify biopsy tissue using support vector machine and leave-one-out cross validation method. There were 29 HG and 49 LG cancers among 187 biopsy cores included in the study. Study results show 76% sensitivity, 80% specificity, 93% negative predictive value, and 50% positive predictive value for HG versus benign, and 76%, 73%, 84%, and 63%, for HG versus LG prostate tissue classification. DRS failed to diagnose 7/29 (24%) HG cancers. This study demonstrated that an optical biopsy needle guided by DRS has sufficient accuracy to differentiate HG from LG carcinoma and benign tissue. It may allow precise targeting of HG prostate cancer providing more accurate assessment of the disease and improvement in patient care.
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Neoplasias de la Próstata/patología , Análisis Espectral , Anciano , Biopsia con Aguja , Humanos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Pronóstico , Neoplasias de la Próstata/diagnóstico , Sensibilidad y Especificidad , Máquina de Vectores de SoporteRESUMEN
Vestibular tissues (cristae ampullares, macular otolithic organs, and Scarpa's ganglia) in chinchilla, rat, and guinea pig were examined for immunoreactivity to the alpha9 nicotinic acetylcholine receptor (nAChR) subunit. The alpha9 antibody was generated against a conserved peptide present in the intracellular loop of the predicted protein sequence of the guinea pig alpha9 nAChR subunit. In the vestibular periphery, staining was observed in calyces around type I hair cells, at the synaptic pole of type II hair cells, and in varying levels in Scarpa's ganglion cells. Ganglion cells were also triply labeled to detect alpha9, calretinin, and peripherin. Calretinin labels calyx-only afferents. Peripherin labels bouton-only afferents. Dimorphic afferents, which have both calyx and bouton endings, are not labeled by calretinin or peripherin. In these experiments, alpha9 was expressed in both calyx and dimorphic afferents. A subpopulation of small ganglion cells did not contain the alpha9 nAChR but did stain for peripherin. We surmise that these are bouton-only afferents. Bouton (regularly discharging) afferents also show efferent responses, although they are qualitatively different from those in irregularly discharging (calyx and dimorphic) afferents, much slower and longer lasting. Thus, regular afferents are probably more affected via a muscarinic cholinergic or a peptidergic mechanism, with a much smaller superimposed fast nicotinic-type response. This latter response could be due to one of the other nicotinic receptors that have been described in studies from other laboratories.
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Oído Interno , Receptores Nicotínicos/metabolismo , Animales , Chinchilla , Oído Interno/citología , Oído Interno/metabolismo , Cobayas , Inmunohistoquímica , Neuronas/citología , Neuronas/metabolismo , RatasRESUMEN
Oxalate, a metabolic end product and a major constituent of the majority of renal stones, has been shown to be toxic to renal epithelial cells of cortical origin. However, it is unknown whether inner medullary collecting duct (IMCD) cells that are physiologically exposed to higher concentrations of oxalate also behave in a similar manner. In the present study, we examined the effects of oxalate on IMCD cells. IMCD cells from the mouse were maintained in DMEM/F12 media supplemented with fetal bovine serum and antibiotics. Exposure of IMCD cells to oxalate produced time- and concentration-dependent changes in the light microscopic appearance of the cells. Long-term exposure to oxalate resulted in alterations in cell viability, with net cell loss after exposure to concentrations of 2 mM or greater. The production of free radicals was directly related to the exposure time and the concentration of oxalate. Crystal formation occurred in less than 1 h and cells in proximity to crystals would lose membrane integrity. Compared with IMCD cells, LLC-PK1 cells as well as HK-2 cells showed significant toxicity starting at lower oxalate concentrations (0.4 mM or greater). These results provide the first direct demonstration of toxic effects of oxalate in IMCD cells, a line of renal epithelial cells of the inner medullary collecting duct, and suggest that the cells lining the collecting duct are relatively resistant to oxalate toxicity.
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Médula Renal/efectos de los fármacos , Ácido Oxálico/farmacología , Animales , Línea Celular , Médula Renal/citología , RatonesRESUMEN
Prostate cancer is the second leading cause of cancer deaths in men. Conventional therapies produce a high rate of cure for patients with localized prostate cancer, but there is no cure once the disease has spread beyond the prostate. Androgen withdrawal remains the only treatment for these men with clinically advanced disease; however, most of these men, who initially respond to hormone ablation therapy, fail and the disease progresses. There is at present no effective treatment for hormone-independent prostate cancer. Several lines of evidence suggest a role of p42/p44 mitogen-activated protein kinase (p42/p44 MAP kinase) signal transduction pathways in prostate cancer. At the molecular level, a variety of genetic alterations lead to an epigenetic mechanism by which a feedback autocrine loop between membrane receptors and associated ligands serves as an essential component of the growth, proliferation, and metastasis of prostate cancer at an advanced and androgen-independent stage. Peptide growth factors are known to exert their effects by a complex array of mechanisms primarily mediated by the p42/p44 MAP kinase signal transduction pathway. Thus, we hypothesized that MAP kinase signal transduction pathways could serve as new and novel targets in prostate cancer therapy. In this article we provide an overview of the role played by MAP kinase signal transduction in the prostate.
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Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Neoplasias de la Próstata/tratamiento farmacológico , Transducción de Señal , Humanos , Masculino , Neoplasias de la Próstata/enzimologíaRESUMEN
The biochemistry of the mitogen activated protein kinases ERK, JNK, and p38 have been studied in prostate physiology in an attempt to elucidate novel mechanisms and pathways for the treatment of prostatic disease. We reviewed articles examining mitogen-activated protein kinases using prostate tissue or cell lines. As with other tissue types, these signaling modules are links/transmitters for important pathways in prostate cells that can result in cellular survival or apoptosis. While the activation of the ERK pathway appears to primarily result in survival, the roles of JNK and p38 are less clear. Manipulation of these pathways could have important implications for the treatment of prostate cancer and benign prostatic hypertrophy.