Biomedical subjects

Amnon Zisman

Publications and source records attributed to Amnon Zisman.

At least 19 recordsLinked to original sources

PubMed2006

Combined "periprostatic and periapical" local anesthesia is not superior to "periprostatic" anesthesia alone in reducing pain during Tru-Cut prostate biopsy.

OBJECTIVES: To evaluate, in a prospective study, the benefit of adding local periapical prostatic anesthesia to routine periprostatic infiltration to the prostate-seminal vesicle junction in a randomized fashion. Transrectal ultrasound-guided biopsy is the reference standard in the diagnosis of prostate cancer. Although well tolerated by most patients, it can be associated with discomfort. METHODS: A total of 120 consecutive evaluable patients with an elevated total prostate-specific antigen (tPSA) level, increased tPSA velocity, and/or abnormal digital rectal examination findings were enrolled. The patients were randomized into two groups. Group 1 received periprostatic infiltration of 6 mL 1% lidocaine. Group 2 received periprostatic and apical infiltration: 4 mL 1% lidocaine at the prostate-seminal vesicle junction and 2-mL infiltration at the prostatic apex 15 minutes before transrectal ultrasound-guided biopsy. Pain was assessed using a 10-point modified visual analog scale. RESULTS: The mean patient age was 63.7 +/- 1.2 years and 64.2 +/- 1.1 years, the mean tPSA level was 12.1 +/- 1.5 ng/mL and 13.6 +/- 2.7 ng/mL, the mean biopsy duration was 6.2 +/- 2.5 minutes and 6.1 +/- 2.2 minutes, and the mean visual analog scale pain score was 1.26 +/- 0.1 and 1.23 +/- 0.1 for groups 1 and 2, respectively. No statistically significant difference was observed with respect to age, tPSA level, mean biopsy duration, or pain score between the two groups. CONCLUSIONS: Periprostatic lidocaine infiltration provides local anesthesia that results in improved visual analog scale pain scores. Additional apical infiltration did not improve patient discomfort further. However, comparative evidence has indicated that increasing the time elapsed between the anesthetic infiltration and the biopsy procedure may further improve pain control.

Aged↗

PubMed2006

[Multivariate analysis on radical retropubic prostatectomy associated blood loss: importance of prostate size, pelvic lymph-node dissection and percentage of carcinoma].

BACKGROUND: Radical retropubic prostatectomy (RRP) has been associated with blood loss requiring blood transfusion. AIM: To define risk factors for blood transfusion. STUDY DESIGN AND METHODS: The charts of 303 patients who underwent RRP between the years 1992 and 2002 were prospectively reviewed. Blood loss, blood requirements and correlative clinical data were recorded and a multivariate analysis model was applied. RESULTS: Data was available in 293 cases (97%). A total of 122 patients were transfused (42%) with a median of 2 units of packed cells. Median estimated blood loss was 766 ml (range 150-2800). Blood loss declined progressively during the study period (1220 ml in 1992 to 826 ml in 2002). Multivariate analysis reveals that estimated blood loss and transfusion rate are related to performance of pelvic lymph node dissection, prostate size and percentage of cancer in the prostatectomy specimen. CONCLUSION: Our series indicates that blood preparation may be spared in patients who are not candidates for pelvic lymph node dissection with prostate smaller than 57 gr. and with less than 77% in the biopsy specimen (equivalent to < 66% of cancer in the prostatectomy specimen).

Blood Loss, Surgical↗

PubMed2006

[Comparative morbidity for different accesses in percutaneous nephrolithotripsy].

BACKGROUND: Over the last decades percutaneous nephrolithotripsy (PCNL) has been developed as an alternative for open renal operations in the treatment of complex renal stones. Currently, different approaches are used for the collecting system. OBJECTIVES: To estimate the overall morbidity of different approaches to the collecting system during PCNL; to compare the complication rates for PCNL through the upper pole of the kidney with lower pole access and multiple access approaches. METHODS: We retrospectively reviewed 174 patients (178 renal units) who underwent PCNL. They formed three groups according to surgical access: upper pole (n = 107), lower pole (n = 51) and multiple (n = 20). Inter-group data on procedure related complications were compared. RESULTS: Postoperative fever was more frequent in the upper pole group (34%) compared to the other two groups (25% each, p < 0.49). There was a higher rate of pulmonary complications in the upper pole and multiple access groups (21% and 20%, respectively) compared with the lower pole group (2%, p=0.007). The rate of bleeding and need for blood transfusion was significantly higher in the multiple access group than in the other groups (20% vs 5% and 6%, respectively, p < 0.05). CONCLUSIONS: The upper and multiple access approaches were associated with a higher overall incidence of pleural effusion compared with the lower pole access. The incidence of bleeding and transfusion rates were similar using the upper and lower pole accesses but higher in the multiple access group. Provision of an enhanced surgical field and greater maneuverability together with 'the treatable nature of the associated complications favor an upper pole access, especially for removing a large stone burden.

Fever↗

PubMed2006

[Percutaneous diagnostic biopsy of solid renal masses in adults].

Most solid renal masses are presumed to represent renal cell carcinoma. Percutaneous biopsies of renal cell carcinoma have been discouraged because traditionally it was believed that surgery provides tissue diagnosis, staging, and grading as well as definitive treatment. Percutaneous renal mass biopsy was shown to be inaccurate and finally, beside rare complications such as bleeding and pneumothorax, biopsy may facilitate tumor seeding along the needle tract. In recent years, due to an increased use of cross-sectional imaging, more renal masses are being detected. The size of renal masses in contemporary series is smaller than in historical cohorts. On the basis of our findings and according to reports by others, approximately 20% of small renal masses are benign. We reviewed the indications, techniques, success rates, accuracy and complications of percutaneous biopsy of solid renal masses in adults in order to debate whether it is currently indicated to reconsider the role of renal mass biopsy in the diagnostic flowchart of small renal masses workup. Such a modification, if proven to be justified, may spare a substantial number of patients the risk and morbidity of nephrectomy or partial nephrectomy.

Adult↗

PubMed2006

[Management of prostate cancer with indolent biological potential: from watchful waiting to active surveillance].

Prostate cancer is the most common malignancy among elderly men. Due to its indolent course and the fact that the majority of contemporary patients are diagnosed early, disease progression to metastasis often occurs many years after the initial diagnosis. Elderly men who have concurrent severe illnesses may not experience progression to metastasis during their lifetime. Therefore, it is reasonable to withhold active therapy in some patients avoiding the associated risks, and impact on patient quality of life. Watchful waiting (WW) is an adequate approach in such cases, and has been shown to be associated with a similar overall survival when compared with radical prostatectomy. However, the disease-specific survival was better in patients who had undergone surgery. Prostate cancer patients often find it hard to persist on a WW policy. This is due to their expectation to be treated, to fight, and win the battle over cancer. Consequently, many patients who start on WW drop out and seek active treatment within several years, mostly when PSA elevation is noted. Active surveillance for prostate cancer is a novel approach consisting of avoiding the risks of therapy, while allowing the early detection of those who are prone to progress. In these high-risk individuals delayed active treatment is offered. Active surveillance consists of periodic monitoring of the PSA serum level, digital rectal exam and repeated prostate biopsies. Threshold values for these parameters are pre-defined and active therapy is instituted when such threshold values are met. Preliminary results of active surveillance show that more patients remain on a surveillance regimen as compared with the traditional WW; it is possible to offer curative treatment to individuals who were defined as having high risk by active surveillance parameters, and the disease-specific mortality is similar to that with WW. Active surveillance for prostate cancer is a novel and fascinating approach that may improve our ability to distinguish between patients who have a higher risk and need active therapy, and others in whom the risk for progression remains low and avoiding the risks of therapy is warranted.

Aged↗

PubMed2005

Prognostic value of histologic subtypes in renal cell carcinoma: a multicenter experience.

PURPOSE: To analyze to what extent histologic subtype is of prognostic importance in renal cell carcinoma based on a large, international, multicenter experience. PATIENTS AND METHODS: Four thousand sixty-three patients from eight international centers were included in this retrospective study. Histologic subtype (1997 International Union Against Cancer [UICC] criteria of tumor response), age, sex, TNM stage, Fuhrman grade, tumor size, Eastern Cooperative Oncology Goup performance status (ECOG PS), and overall survival were determined in all cases. The prognostic values of clear cell, papillary, and chromophobe histologic features were assessed by uni- and multivariate analysis using the Kaplan-Meier method and Cox model, respectively. RESULTS: Clear cell, papillary, and chromophobe carcinomas accounted for 3,564 (87.7%), 396 (9.7%) and 103 (2.5%) cases, respectively. In univariate analysis, a trend toward a better survival was observed when clear cell, papillary, and chromophobe histologies were considered prognostic categories (log-rank P = .0007). However, in multivariate analysis, TNM stage, Fuhrman grade and ECOG PS, but not histology, were retained as independent prognostic variables (P < .001). CONCLUSION: The stratification in three main renal cell carcinoma histologic subtypes as defined by the 1997 UICC-American Joint Committee on Cancer consensus should not be considered a major prognostic variable comparable to TNM stage, Fuhrman grade and ECOG PS.

Adolescent↗

PubMed2005

Retropubic radical prostatectomy: associated blood loss and transfusion requirements--a two-decade perspective review.

Bleeding during retropubic radical prostatectomy arises from venous structures in the majority of cases. Since its introduction two decades ago, the nerve-sparing procedure with surgical control of the dorsal venous complex has led to a reduction in blood loss and blood transfusion rate. The reducton in blood loss is a result of better understanding of the prostatic blood vessel anatomy, extensive surgical experience over time, and reduction in transfusion triggers with an acceptance of lower postoperative hemoglobin values. Increased blood loss during RRP is associated with poorer outcomes most probably due to surgical difficulties. But as for now, there are no decisive risk factors for clinically significant bleeding during RRP although newer technologies for hemostasis of the dorsal vein complex are being utilized.

Blood Transfusion↗

PubMed2005

[Long-term follow-up of radical retropubic prostatectomy for prostate cancer in 400 consecutive patients].

PURPOSE: To evaluate the long-term outcomes following radical retropubic prostatectomy for localized prostate cancer. STUDY DESIGN AND METHODS: The charts of 401 patients who underwent radical retropubic prostatectomy between 1992 and 2004 were reviewed. RESULTS: The average age was 63 years with a median PSA of 8.5 and median Gleason score of 5. Ninety one percent of the cases were diagnosed by a single prostate biopsy set (average 7 cores, range 3-16). Pelvic lymph node dissection was performed in 84 patients (21.7%). Nodal involvement was noted in 5 (6%). Capsular invasion was found in 91 patients (24%), positive surgical margin in 78 (20.1%) and seminal vesicle involvement in 37 (9.5%). The average admission stay was 5.2 days (3-22). Fever (11.4%), urine leakage (8%), wound infection (4%) and pulmonary embolism (1.5%) were the most common early complications. One year after the operation 72% of the patients were fully continent. Of the 172 patients who underwent nerve-sparing procedure, 80 patients (46.5%) regained their sexual potency one year after the operation and did not require pharmacological assistance. Median follow-up time was 84 months. The five and eight years overall survival rates were 85% and 73%, respectively. Ten years survival of 136 patients (35%) with clinical stage T1C was 95%. Biochemical failure was observed in 68 patients (18%). The average time to biochemical failure was 12.5 months (range 0-76. median 12). Forty five patients (12%) died, twenty one (5.4%) due to metastatic disease. Mortality correlated to pre-operative PSA, clinical stage and Gleason score. CONCLUSION: At one year follow up, most of the patients are continent and 46.5% have spontaneous erection following nerve-sparing procedure. The overall survival and the long-term outcomes of radical retropubic prostatectomy are equal to those reported in the current literature.

Follow-Up Studies↗

PubMed2005

[Endourological treatment of ureteropelvic obstruction using holmium YAG laser].

BACKGROUND: Ureteropelvic junction obstruction (UPJO) is defined as an impairment of urine outflow from the pelvis to the ureter. Several treatment approaches are in use. OBJECTIVES: To present the different endo-urological approaches--retrograde and antegrade techniques --for UPJO using the holmium: YAG laser. METHODS: We followed 67 patients who underwent endopyelotomy between 1994 - 1997 and compared the different approaches for the treatment of UPJO. RESULTS: A total of 67 patients were operated, 52 patients using retrograde approach and 15 using antegrade approach. In the retrograde approach success was achieved in 48 patients (93%) and in 14 patients (94%) in the antegrade approach. Complications rate was 10% and 40%, respectively. Hospital stay was 2.2 days in the retrograde approach and 4.6 in the antegrade approach. CONCLUSIONS: The success rate in the different endourologic approaches was high and no difference between the two approaches was identified. From our experience, lower complication rate and shorter hospital stay make the retrograde approach more advantageous.

Endoscopy↗

PubMed2005

[Tissue microarray--an infrastructure for prostate cancer outcome research].

UNLABELLED: In tissue microarray (TMA) approximately 500 clinical formalin fixed and paraffin embedded tissue cores are reorganized into a new recipient block. Each recipient block may be sectioned up to 200 times. MATERIAL AND METHODS: Radical prostatectomy specimens of 405 patients operated for prostate cancer (CaP) between 1992 and 2004 were considered. A large database was created incorporating clinical and pathological data. Median follow-up time was 84 months. A full pathological revision was performed. We allocated and marked sites of interest on patients' slides: CaP, normal prostate, capsular or seminal vesicles invasion and the appropriate controls. The corresponding paraffin blocks served as donor blocks for harvesting tissue cores sequentially incorporated into the TMA recipient block. RESULTS: The specimens of 264 patients out of 405 qualified for inclusion into the TMA (yield 65%). Two TMA copies were prepared containing 4 blocks each. Each copy includes approximately 2000 tissue cores. CONCLUSIONS: We have constructed a large scale TMA associated with a detailed clinical database. This TMA will serve for prostate cancer outcome studies by using immunohistochemical as well as other molecular staining. Our TMA is unique because it contains sites of interest for CaP local invasiveness and metastasis.

Biopsy↗

PubMed2004

Use of the University of California Los Angeles integrated staging system to predict survival in renal cell carcinoma: an international multicenter study.

PURPOSE: To evaluate ability of the University of California Los Angeles Integrated Staging System (UISS) to stratify patients with localized and metastatic renal cell carcinoma (RCC) into risk groups in an international multicenter study. PATIENTS AND METHODS: 4,202 patients from eight international academic centers were classified according to the UISS, which combines TNM stage, Fuhrman grade, and Eastern Cooperative Oncology Group performance status. Distribution of the UISS categories was assessed in the overall population and in each center. RESULTS: The UISS stratified both localized and metastatic RCC into three different risk groups (P <.001). For localized RCC, the 5-year survival rates were 92%, 67%, and 44% for low-, intermediate-, and high-risk groups, respectively. A trend toward a higher risk of death was observed in all centers for increasing UISS risk category. For metastatic RCC, the 3-year survival rates were 37%, 23%, and 12% for low-, intermediate-, and high-risk groups, respectively; in 6 of 8 centers, a trend toward a higher risk of death was observed for increasing UISS risk category. A greater variability in survival rates among centers was observed for high-risk patients. CONCLUSION: This study defines the general applicability of the UISS for predicting survival in patients with RCC. The UISS is an accurate predictor of survival for patients with localized RCC applicable to external databases. Although the UISS may be useful for patients with metastatic RCC, it may be less accurate in this subset of patients due to the heterogeneity of patients and treatments.

Adult↗

PubMed2004

Prognostic significance of venous thrombus in renal cell carcinoma. Are renal vein and inferior vena cava involvement different?

PURPOSE: The prognostic significance of the level of venous involvement in renal cell carcinoma (RCC) is controversial. It has been suggested that the 1997 TNM classification of venous involvement system should be revised. MATERIALS AND METHODS: The records of 226 patients who underwent a nephrectomy and tumor thrombectomy, 117 for renal vein (RV) and 109 for inferior vena cava (IVC) involvement, between 1989 and 2001 were reviewed and compared to those of 654 patients undergoing nephrectomy without venous involvement. RESULTS: In patients with localized RCC (N0M0), the risk of recurrence after nephrectomy was significantly increased in patients with venous thrombus compared to patients without venous thrombus (p = 0.005). However, the difference was not significant in a multivariate analysis including T stage (1, 2, 3 or 4), Fuhrman grade and Eastern Cooperative Oncology Group performance status. In patients with localized RCC disease specific survival was similar (p = 0.536) in patients with RV (T3b) and IVC involvement below the diaphragm (T3b). However, patients with IVC involvement above the diaphragm (T3c) had a significantly worse survival rate even after controlling for Fuhrman grade and Eastern Cooperative Oncology Group performance status in a multivariate analysis (p = 0.020). All patients treated for metastatic RCC had a similar prognosis regardless of the level of venous involvement. CONCLUSIONS: For patients with pT3b disease, local tumor stage and grade are better predictors of prognosis than extent of venous involvement. Based on our data we support the current TNM classification of venous involvement with RV and IVC invasion categorized as T3b and IVC involvement above the diaphragm categorized as T3c.

Carcinoma, Renal Cell↗

PubMed2004

Cachexia-like symptoms predict a worse prognosis in localized t1 renal cell carcinoma.

PURPOSE: Although cachexia is a common sequela of advanced and metastatic renal cell carcinoma (RCC), cachexia-like symptoms may also represent a paraneoplastic finding. We assessed the prognostic significance of these symptoms in patients with stage T1 RCC. MATERIALS AND METHODS: Using the kidney cancer database at our institution 250 patients were identified who underwent partial or radical nephrectomy for T1N0M0 RCC between 1989 and 2001. The prognostic significance of the symptoms present at diagnosis and findings on preoperative laboratory evaluation were examined. RESULTS: Mean and median followup was 33 and 43 months, respectively. Malaise, weight loss, anorexia and hypoalbuminemia were cachexia related findings that were significant predictors of worse disease specific survival (DSS). DSS in patients with 1 vs greater than 1 cachexia related symptoms was not significantly different (p = 0.077). Therefore, any patient with at least 1 cachexia related finding was considered to be positive for cachexia and cachexia occurred in 37 (14.8%). Cachexia was associated with significantly worse recurrence-free survival (HR 3.03, p = 0.032) and DSS (HR 4.39, p = 0.011) even after controlling for tumor size, grade and performance status. The 5-year survival rate in patients with low grade (1 or 2) tumors with and without cachexia was 91% and 81%, respectively. The 5-year survival rate in patients with high grade (3 or 4) tumors with and without cachexia was 75% and 55%, respectively. CONCLUSIONS: Cachexia-like symptoms independently predict a worse prognosis in patients with T1 RCC. Patients with cachexia (malaise, weight loss, anorexia and hypoalbuminemia), especially when associated with high grade tumors, should be considered for clinical trials of adjuvant therapies.

Aged↗

PubMed2004

Adverse effects of cystoscopy and its impact on patients' quality of life and sexual performance.

BACKGROUND: Cystoscopy, the principal means of diagnosis and surveillance of bladder tumors, is invasive and associated with unpleasant side effects. OBJECTIVES: To determine the early complications of rigid cystoscopy and the impact on patients' quality of life and sexual performance. METHODS: One hundred consecutive patients undergoing diagnostic rigid cystoscopy filled in questionnaires that included anxiety and pain levels (0-5 visual analogue scale), adverse events, Short-Form Health Survey, International Prostate Symptom Score, and functional sexual performance. Questionnaires were administered before, immediately after, and 1, 2 days, 2 and 4 weeks following cystoscopy. RESULTS: The pre-cystoscopy anxiety level was 2.01. The average pain during the examination was 1.41. SF-36 score was not affected by cystoscopy. The subjective impact on patients' quality of life was 0.51. The mean IPSS increased following cystoscopy (6.75 vs. 5.43, P = 0.001) and returned to baseline 2 weeks later. A decline in libido was reported by 55.6% (25/45) and 50% (3/6) of the sexually active men and women, respectively. Cystoscopy was associated with a decreased Erectile Dysfunction Intensity Score, from 15.6 to 9.26 during the first 2 weeks (P = 0.04). The overall complication rate was 15% and included urethrorrhagia and dysuria, None of the patients had fever or urinary retention and none was hospitalized. The complication rate was higher in patients with benign prostatic hyperplasia (24% vs. 9.7%, P = 0.001). CONCLUSIONS: Rigid cystoscopy is well tolerated by most patients and has only a minor impact on quality of life. However, cystoscopy transiently impairs sexual performance and libido. The early complications are mild and correlate with a diagnosis of BPH.

Aged↗

PubMed2003

LABAZ1: A metastatic tumor model for renal cell carcinoma expressing the carbonic anhydrase type 9 tumor antigen.

A metastatic renal cell carcinoma (RCC) tumor model xenograft that expresses the targetable, membrane-bound tumor-associated antigen carbonic anhydrase type 9 (CA IX) is described. The xenograft, established from a high-grade type-2 chromophil RCC (cRCC), has been serially transplanted in immune compromised mice, in which it grows orthotopically under the renal capsule, doubling its size every 9 weeks and sending metastases to the lung and liver at approximately 20 weeks. Tumors were capable of being imaged using a micro-PET (micro-positron emission tomograph) with an 18-fluorodeoxyglucose (18-FDG) tracer. Subsequent xenograft generations have conserved immunohistochemical and ultrastructural properties typical for malignant renal epithelium-derived neoplasia (vimentin+, CK-19+, CA IX+ with hypoxia-inducible factor (HIF)-1 alpha constitutive expression) and have demonstrated extensive proliferation, lack of apoptosis, severe genetic alterations, and molecular expression alterations; transforming growth factor beta 1 (TGF-beta 1), hepatocyte growth factor (HGF), proto-oncogene (c-met), matrix metalloproteinase (MMP)-1, and vascular endothelial growth factor (VEGF) C and D were overexpressed, whereas human epidermal growth factor receptor (HER)-2, MMP-2 and MMP-9, VEGF-R3, p53, and p27 were severely down-regulated, suggesting a proangiogenic environment, local invasiveness, and facilitated lymphatic metastasis. Altogether, LABAZ1 provides a relevant and flexible model to study the biology of cRCC, the role of CA IX in RCC tumorigenesis, progression, and metastasis, and a platform for testing new targeted therapeutic strategies.

Aged↗

PubMed2003

Renal cell carcinoma with retroperitoneal lymph nodes. Impact on survival and benefits of immunotherapy.

BACKGROUND: The current study was performed to determine the impact of the presence of retroperitoneal lymphadenopathy on the survival and response to immunotherapy of patients with metastatic renal cell carcinoma (RCC). METHODS: A retrospective cohort study was performed with outcome assessment based on the chart review of demographic, clinical, and pathologic data from 1087 patients. Patients with RCC who did not present with metastatic disease, who did not undergo nephrectomy as part of their cancer treatment, and those in whom either the lymph node (N) or metastatic (M) status was unknown, were excluded. A total of 322 M1 patients who met these criteria and who underwent nephrectomy for unilateral RCC formed the principal study population. RESULTS: Two hundred thirty-six patients presented with N0M1 disease and 86 patients presented with N+M1 disease. In M1 patients, the presence of positive regional lymph nodes was associated with larger sized, higher grade, locally advanced primary tumors that were more commonly associated with sarcomatoid features. N0M1 patients were more likely to achieve an objective response to systemic immunotherapy compared with N+M1 patients (P = 0.01). N+M1 patients overall had worse short-term and long-term survival compared with N0M1 patients, with a median survival of 10.5 months compared with 20.4 months, respectively. The median survival of N0M1 patients was improved to 28 months in those who received adjunctive immunotherapy (P = 0.0008), whereas the median survival of patients with N+M1 disease was the same in those treated with and those treated without adjunctive immunotherapy (P = 0.18). CONCLUSIONS: Even in the modern era of systemic immunotherapy, the presence of regional lymphadenopathy exerts a detrimental effect on the survival of patients with metastatic RCC. Lymph node status is a strong predictor of the failure to achieve either an objective immunotherapy response or an improvement in survival when immunotherapy is given as an adjunctive treatment after cytoreductive nephrectomy. However, in multivariate analysis, including both clinical and pathologic variables, lymph node status was found to have less of an impact on survival than primary tumor stage and grade and patient performance status.

Carcinoma, Renal Cell↗

PubMed2003

Heterogeneity of molecular targets on clonal cancer lines derived from a novel hormone-refractory prostate cancer tumor system.

OBJECTIVE: We recently described a new hormone refractory prostate cancer cell line, CL1, derived from LNCaP via in vitro androgen deprivation. To study gene expression during prostate cancer progression and to identify molecular targets for therapy, a pure clonal tumor system was generated. METHODS: Limiting dilution of CL1 stably transfected with a green fluorescent protein, generated 35 single-cell clones, which were expanded into stable cell lines. In vitro responses to various therapeutic modalities were assessed in each clone. Gene expression was determined using reverse transcriptase-polymerase chain reaction and oligonucleotide microarrays. In vivo biology was assessed following orthotopic injection into intact and castrated severe combined immunodeficient mice. RESULTS: In vitro, all clones demonstrated similar resistance to traditional therapeutic efforts including chemotherapy and radiation therapy, but differential sensitivity to cell-mediated cytotoxicity. The clones demonstrated differential gene expression relative to each other and to the parental CL1 and LNCaP cell lines. Following orthotopic injection into mice, three distinct growth patterns were observed: fast growth with widespread metastasis; slower grower with widespread metastasis; and no tumor formation. Using oligonucleotide microarrays, several genes were identified as differentially expressed between the most aggressive and the nontumorigenic clone. CONCLUSIONS: We have described a novel fluorescent-labeled clonal hormone refractory prostate cancer tumor system that exhibited marked heterogeneity in its response to various therapeutic modalities, gene expression, and in vivo biology. Our data suggests that given the marked clonal heterogeneity, multi-modality approaches directed against multiple molecular targets rather than single agent therapy will be necessary to adequately eradicate the entire malignant cell population. Clonal tumor lines may allow more accurate examination of molecular pathways involved in tumor progression and resistance to treatment.

Animals↗

PubMed2003

Loss of CD10 (neutral endopeptidase) is a frequent and early event in human prostate cancer.

BACKGROUND: We hypothesized that the aggressive LNCaP-derived androgen-independent cell line, CL1, might differ from LNCaP in their repertoire of cell surface markers and that these differences might typify changes that occur during clinical prostate cancer progression. METHODS: The cell surface marker expression profiles of CL1 and LNCaP were examined using flow cytometry. Markedly differential gene expression was confirmed using RT-PCR and further examined using immunohistochemistry among the prostate cancer cell lines LAPC-4, LNCaP, CL1, CL2, DU145, and PC-3. The expression of the most markedly differentially expressed surface marker, CD10, was further explored in a tissue microarray containing radical prostatectomy samples from 219 hormone naïve prostate cancer patients. RESULTS: There were marked differences in the expression of CD10, CD13, CD26, CD33, CD44, CD54, CD55, and CD104 between CL1 and LNCaP. Results from both the RT-PCR and immunohistochemistry confirmed the differential expression and found that CD10 demonstrated a pattern of expression in hormone sensitive but not hormone refractory cell lines. When CD10 expression was examined in a tissue microarray, CD10 expression was below the 25th percentile of matched normal prostate tissue in 68% of prostate cancers, below the median expression of matched normal prostate tissue in 86% of cancers, and completely absent in 34% of cancers. Samples of prostatic intraepithelial neoplasia demonstrated CD10 expression that was intermediate between normal prostatic tissue and prostate cancer. Among prostate cancer patients, CD10 expression did not correlate with Gleason score, pathological stage, or biochemical recurrence following radical prostatectomy. CONCLUSIONS: These findings demonstrate that loss or decreased expression of CD10 is an early and frequent event in human prostate cancer and implicates CD10 as a potential therapeutic target for early stage hormone sensitive prostate cancer.

Aged↗