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S S Chang

Publications and source records attributed to S S Chang.

At least 19 recordsLinked to original sources
PubMed2006

The association between body size, prostate volume and prostate-specific antigen.

Increasing prostate volume contributes to urinary tract symptoms and may obscure prostate cancer detection. We investigated the association between obesity and prostate volume, prostate-specific antigen (PSA) and PSA density among 753 men referred for prostate biopsy. Among men with a negative biopsy, prostate volume significantly increased approximately 25% from the lowest to highest body mass index (BMI), waist or hip circumference or height categories. PSA was 0.7 ng/ml lower with a high waist-to-hip ratio. These associations were less consistent among subjects diagnosed with high-grade prostatic intraepithelial neoplasia or cancer. Our data suggest that obesity and height are independently associated with prostate volume..

Abdomen↗
PubMed2001

Intrarectal lidocaine during transrectal prostate biopsy: results of a prospective double-blind randomized trial.

PURPOSE: Recent reports have indicated the benefit of anesthesia during prostate biopsy. To assess this finding objectively we performed a prospective randomized double-blind study to compare patient pain with and without local anesthesia during transrectal ultrasound guided prostate biopsies. MATERIALS AND METHODS: Between August 2000 and March 2001, 108 men undergoing transrectal ultrasound guided biopsy of the prostate were randomized in double-blind fashion to receive intrarectal 2% lidocaine gel or intrarectal lubricant alone. No patient received pre-procedure narcotics or sedation. Pain associated with biopsy was determined using a horizontal linear visual analog pain scale. Pain scores in the 2 treatment groups were compared and possible predictors of increased pain were examined. RESULTS: The 2 groups were similar in demographic characteristics. There was no significant difference in pain score in the 2% lidocaine and lubricant alone groups (28.3 versus 28.9 mm., p = 0.88). Previous biopsy, time since previous biopsy, physician, number of biopsies and prostate volume did not correlate with pain score, while age correlated negatively with the score (r = -0.27, p = 0.005). A single complication involving a vasovagal episode resolved spontaneously. CONCLUSIONS: Intrarectal lidocaine gel provides no significant therapeutic or analgesic benefit compared with lubricant alone for transrectal ultrasound guided biopsy of the prostate. In younger patients more discomfort is associated with this procedure.

Administration, Rectal↗
PubMed2001

Metastatic renal cell carcinoma neovasculature expresses prostate-specific membrane antigen.

OBJECTIVES: To determine whether the tumor-associated neovasculature of metastatic prostate and metastatic conventional (clear cell) renal carcinoma express prostate-specific membrane antigen (PSMA). PSMA is a type II integral membrane glycoprotein highly expressed in prostate cancer cells and also recently discovered to be expressed in the neovasculature of non-prostatic primary malignancies. METHODS: We examined metastatic prostate carcinoma (22 patients) and metastatic conventional (clear cell) renal carcinoma (20 patients) in various anatomic sites, including bone, lymph nodes, liver, lung, and soft tissue. Using the biotin-streptavidin method, we performed immunohistochemical reactions with the anti-PSMA monoclonal antibodies (mAbs) 7E11 and PM2J004.5 and with the anti-endothelial cell mAb CD34. RESULTS: Metastatic conventional (clear cell) renal carcinoma consistently expressed PSMA. The PM2J004.5 mAb was positive in 20 of 20 specimens, and the 7E11 mAb was positive in 15 of 20. The anti-PSMA immunoreactions with the neovasculature were confirmed by similar staining by the anti-CD34 mAb (20 of 20). Although the metastatic prostatic cancer cells expressed PSMA in all the specimens, only 2 of 22 had neovasculature PSMA expression. CONCLUSIONS: As in primary prostatic adenocarcinomas, the neovasculature of metastatic prostate cancer, regardless of site, rarely express PSMA. The neovascular endothelial cells of metastatic clear cell renal carcinoma, however, express PSMA. This expression may make PSMA an effective target for mAb-based antineovasculature therapy in metastatic renal carcinoma.

Adenocarcinoma, Clear Cell↗
PubMed2001

Comparison of anti-prostate-specific membrane antigen antibodies and other immunomarkers in metastatic prostate carcinoma.

OBJECTIVES: To compare the immunohistochemical properties of the 7E11 anti-prostate-specific membrane antigen (anti-PSMA) monoclonal antibody (mAb) with the recently developed anti-PSMA mAb, PM2J004.5, and with other common immunomarkers in metastatic prostate cancer. PSMA is a type II integral membrane glycoprotein highly expressed in prostate cancer cells. The mAb 7E11 is currently used in the radioisotopic evaluation of prostate cancer, and its immunohistochemical properties have been examined in primary prostate cancer specimens. METHODS: We examined 23 formalin-fixed, paraffin-embedded, metastatic prostate carcinoma specimens from various anatomic sites, including bone, lymph node, liver, lung, and soft tissue. Using the biotin-streptavidin method, we performed immunohistochemical reactions with the anti-PSMA mAbs 7E11 and PM2J004.5 and with antibodies to prostate-specific antigen and prostatic acid phosphatase. The immunoreactions were scored by pathologists unaware of the clinical and pathologic data according to a staining intensity scale and the percentage of cells stained. RESULTS: All four mAbs consistently stained the metastatic prostate cancer specimens. In 2 (8.7%) of 23 cases, however, the prostate-specific antigen immunoreaction was negative but the anti-PSMA mAbs had positive staining. Although 7E11 and PM2J004.5 had a similar staining intensity and percentage of cells stained for most specimens, in 3 (13%) of 23 specimens, 7E11 had less intense staining. None of the specimens were negative for all four antibodies. CONCLUSIONS: Anti-PSMA mAbs consistently immunoreacted with metastatic prostate cancer specimens and were positive in instances when prostate-specific antigen staining was negative. The anti-PSMA mAbs demonstrated similar staining patterns; however, in select cases, the PM2J004.5 mAb did show more intense staining. The anti-PSMA mAbs 7E11 and PM2J004.5 are useful in the pathologic evaluation of paraffin-embedded metastatic prostate cancer specimens.

Antibodies, Monoclonal↗
PubMed2001

Intraoperative nerve stimulation predicts postoperative potency.

OBJECTIVES: Intraoperative nerve stimulation has been used to map the course of cavernosal nerve bundles to aid in nerve-sparing radical prostatectomy (RP). We sought to determine whether the intraoperative nerve stimulation response after removal of the prostate specimen predicts postoperative potency. METHODS: We prospectively evaluated 63 consecutive patients undergoing RP. Among these 63 patients, 41 patients had a bilateral nerve-sparing procedure, and 22 underwent bilateral wide resection of the neurovascular bundles. Potency was determined at 1 year by direct patient interview. RESULTS: Of the 22 patients with wide resection, 16 (73%) had no observed stimulated response, 4 (18%) had a measurable tumescence response, and 2 (9%) had detumescence. All 22 patients were impotent postoperatively. At a minimum follow-up of 1 year, of the 41 patients who underwent nerve-sparing RP, 27 (66%) had postoperative erections sufficient for penetration. Of the 30 men with an intraoperative stimulated tumescence response, 24 (80%) were potent; of the 6 with a detumescence response, 2 (33%) were potent; and of the 5 with no stimulated nerve response, 1 (20%) was potent. A tumescence response was significantly more predictive of postoperative potency than no intraoperative response (P = 0.017). CONCLUSIONS: An intraoperative tumescence response with stimulation of the neurovascular bundles after prostate specimen removal is more likely to correspond to successful postoperative sexual function after nerve-sparing RP than is no response.

Adenocarcinoma↗
PubMed2001

Amyloidosis-induced gastrointestinal bleeding in a patient with multiple myeloma.

We present a case of multiple myeloma (MM) complicated by recurrent amyloidosis-induced gastrointestinal bleeding. The patient presented with episodes of coffee-ground vomitus or massive hematochezia. No bleeding focus could be identified using endoscopy, a red blood cell scan, or angiography. Finally, a tissue biopsy taken at the irregular mucosa beside protruding vessels in the duodenum confirmed the diagnosis of gastrointestinal amyloidosis. As this case illustrates, the absence of systemic symptoms of amyloidosis and nonspecific endoscopic findings in gastrointestinal amyloidosis may make diagnosis difficult. Therefore, we recommend that a diagnosis of amyloidosis-induced gastrointestinal bleeding should be considered in patients with MM with an obscure hemorrhage.

Aged↗
PubMed2001

The clinical features and prognostic factors of hepatocellular carcinoma patients with spinal metastasis.

OBJECTIVE: Hepatocellular carcinoma is the most common malignancy in Taiwan, and spinal metastasis is a serious complication in cancer patients. In this study, we aimed to delineate the clinical features, evaluate the radiotherapy response and analyse the prognostic features in hepatocellular carcinoma subjects with spinal metastasis. METHODS: From 1981 to 1997, 102 patients with spinal metastasis were enrolled, taken from the 5887 documented hepatocellular carcinoma patients treated at Taipei Veterans General Hospital. All the clinical and laboratory data were recorded, including: age; gender; liver biochemistry; tumour characteristics; Child-Pugh's score; performance status; number and location of vertebral metastasis; motor capacity; neurological symptoms and signs; response to radiotherapy of the spinal lesion; and survival. Prognostic factors in hepatocellular carcinoma patients with spinal metastasis were analysed using Cox's regression model. RESULTS: The most common symptoms in hepatocellular carcinoma patients with spinal metastasis were lower back pain (74.5%), thoracic numbness (52.9%) and lower limb weakness (51.0%). Of the 102 patients, 84 received palliative radiotherapy using 3000 cGy for spinal lesions. Of these 84 patients, 32.1% showed a complete response, 26.2% a partial response and 41.7% a non-response to the radiotherapy. Multivariate Cox's regression analysis revealed that responsive radiotherapy (complete response + partial response) and good performance status (score <or= 2) were significant positive prognostic factors for survival in hepatocellular carcinoma patients with spinal metastasis. CONCLUSIONS: Responsive radiotherapy can improve a hepatocellular carcinoma patient's quality of life by ameliorating the neurological condition and relieving pain, and can prolong survival in hepatocellular carcinoma patients with spinal metastasis.

Adolescent↗
PubMed2001

Adrenal insufficiency in critically ill emergency department patients: a Taiwan preliminary study.

OBJECTIVE: Unrecognized adrenal insufficiency can have serious consequences in critically ill emergency department (ED) patients. This prospective pilot study of adrenal function in patients with severe illness was undertaken to determine the prevalence of adrenal dysfunction and any relation to prior herbal drug use. METHODS: In a high-volume urban tertiary care ED, adult patients with sepsis or acute myocardial infarction (AMI) were eligible for the study. Over a two-month period, a convenience sample was enrolled by the authors on arrival to the ED. Inclusion criteria were systemic inflammatory response syndrome (SIRS) criteria plus evidence of at least one organ dysfunction or cardiac marker plus electrocardiogram-proven AMI. Exclusion criteria included known corticosteroid use. Serum cortisol was measured on arrival and for those patients with a level of <15 microg/dL (<414 nmol/L), an adrenocorticotropic hormone (ACTH) stimulation test was performed. RESULTS: Of the 30 enrolled patients, 23 (77%) were suffering from severe sepsis and the other seven (23%) had an AMI. Thirteen of the 30 patients (43%; 95% CI = 25% to 65%) had serum cortisol levels of <15 microg/dL, consistent with adrenal insufficiency, nine with severe sepsis and four with an AMI. Eight (62%; 95% CI = 32% to 86%) of the 13 patients with low cortisol levels reported using herbal medications, while only two (12%; 95% CI = 1% to 36%) of the 17 with normal cortisol levels reported taking herb drugs (p = 0.01). Only two (15%; 95% CI = 2% to 45%) of the patients with low cortisol levels failed their corticotropin stimulation test, suggestive of true adrenocortical insufficiency. Both reported using herbal preparations. CONCLUSIONS: These results indicate that adrenal dysfunction is common among a group of critically ill patients seen in this Taiwanese ED. Moreover, the use of herbal drugs was high in the patients with low serum cortisols. Further studies are required to both confirm these findings and clarify whether a number of herbal medications contain corticosteroids.

Adrenal Insufficiency↗
PubMed2001

Clinical under staging of high risk nonmuscle invasive urothelial carcinoma treated with radical cystectomy.

PURPOSE: The role of radical cystectomy in patients with nonmuscle invasive urothelial carcinoma of the bladder remains controversial. The risk of overtreatment must be balanced against the potential benefit of aggressive therapy. We reviewed our results in these patients with a particular emphasis on clinical under staging. MATERIALS AND METHODS: We reviewed the records of 214 consecutive patients who underwent radical cystectomy for urothelial carcinoma between April 1995 and August 1999, focusing on those with nonmuscle invasive, stages T1 or less disease. We assessed clinical and pathological data as well as outcomes based on pathological disease extent. RESULTS: A total of 78 patients (36%) underwent radical cystectomy for clinical stages T1 or less disease. Indications included disease refractory to intravesical therapy in 29 cases (37%), pathological findings reflective of high grade stage T1 or multifocal disease in 26 (33%), radiographic suspicion of invasive disease in 15 (20%) and severe symptoms in 8 (10%). Cancer was clinically under staged with stages pT2 or greater disease in 31 patients (40%) according to final pathology results. Under staging was most pronounced in the 10 patients (67%) with suspicious radiography and in the 18 (64%) with absent muscle in the biopsy specimen. Of the 78 patients with pathological stages pT1 disease or less 98% had no evidence of disease compared to 65% with stages pT2 or greater disease (p <0.01). CONCLUSIONS: Despite the intent to perform early cystectomy a significant percent of patients harbored occult muscle invasive and/or metastatic disease. In clinical and pathological, superficial stages T1 or less cases disease-free survival was excellent. Due to these results, the selection of high risk superficial transitional cell carcinoma cases for continued bladder sparing treatment should include uninvolved muscle on biopsy and absent radiographic suspicion of invasion.

Adult↗
PubMed2001

Radical cystectomy is safe in elderly patients at high risk.

PURPOSE: Radical cystectomy is standard treatment for bladder cancer in healthy individuals. We determined the safety of radical cystectomy in elderly patients at high risk. MATERIALS AND METHODS: We reviewed the records of all patients who underwent radical cystectomy at our institution between January 1994 and June 2000. Of these 382 patients we identified 44 who were elderly and at high risk, as defined by age 75 years or greater and American Society of Anesthesiologists classification 3 or greater. We examined postoperative care, perioperative minor/major complications, the mortality rate and the need for rehospitalization. RESULTS: Median age of the 44 patients was 77.5 years (range 75 to 87). American Society of Anesthesiologists class was 3 in 40 patients and 4 in 4. Median hospitalization was 7 days (range 4 to 20). Postoperatively 31 of the 44 patients (70%) were transferred directly to the general urology floor, while cardiac monitoring was required postoperatively in 30%. Nine of these patients were transferred to a step-down unit and the remaining 4 required surgical intensive care unit admission. Minor and major complications developed in 10 (22.7%) and 2 (4.5%) cases, respectively. No patients died in the perioperative period and 4 patients were hospitalized within 6 months of discharge home. CONCLUSIONS: Our results support the safety of radical cystectomy in elderly patients at high risk. Acceptable perioperative morbidity and mortality may be achieved without routine intensive monitoring postoperatively.

Age Factors↗
PubMed2001

Estimated blood loss and transfusion requirements of radical cystectomy.

PURPOSE: Radical cystectomy has been associated with significant blood loss and/or transfusion requirement. We defined and characterized blood loss and transfusion parameters in this population. MATERIALS AND METHODS: We reviewed the records of 304 consecutive patients who underwent radical cystectomy and urinary diversion between October 1995 and July 2000. Charts were examined, and univariate and multivariate logistic regression analysis was performed to evaluate estimated blood loss and the transfusion requirement. RESULTS: Complete blood loss data were available in 297 cases. Overall 45% of patients had anemia preoperatively. Median estimated blood loss was 600 ml. (range 100 to 3,000). On univariate analysis increased estimated blood loss was related to patient age, American Society of Anesthesiologists score, longer operative time and paralytic ileus. Overall transfusion was done in 88 of 297 cases (30%) with a median requirement of 2 units (range 1 to 10). The transfusion rate in male and female patients was 26% and 40%, respectively (p <0.05). On univariate analysis female gender, ileal conduit diversion and lower preoperative hematocrit correlated with transfusion need (p = 0.04, <0.001 and <0.001, respectively). On multivariate logistic regression analysis lower preoperative hematocrit, increased estimated blood loss, major complications and ileal conduit diversion type correlated with a higher transfusion rate (odds ratio 8.34, 5.88 and 4.60, respectively). CONCLUSIONS: Acute blood loss anemia is common in patients undergoing radical cystectomy, and predicting blood loss and transfusion requirements remains difficult. These data indicate the need for continued refinement in surgical techniques to decrease blood loss as well as for strategies designed to decrease the need for blood transfusion.

Adult↗
PubMed2000

Short term neoadjuvant androgen deprivation therapy does not affect prostate specific membrane antigen expression in prostate tissues.

BACKGROUND: Prostate specific membrane antigen (PSMA) is a transmembrane glycoprotein highly expressed in benign prostate secretory-acinar epithelium and prostate carcinoma. The results of several studies suggest that PSMA expression is increased in prostate carcinoma cell lines subjected to androgen deprivation and in androgen-independent tumors. The authors studied the effects of short term (3-month) androgen deprivation on PSMA expression in prostate carcinoma specimens using two anti-PSMA monoclonal antibodies (mAbs), 7E11 and PM2J004.5. METHODS: The study included patients with clinically localized prostate carcinoma who were prospectively randomized into 1 of 2 treatment groups: 3 months of neoadjuvant androgen deprivation therapy followed by radical prostatectomy (ADT/RP), or radical prostatectomy (RP) alone. Representative formalin fixed, paraffin embedded prostate sections were immunostained with the anti-PSMA mAbs 7E11 and PM2J004.5 by the streptavidin-biotin method. The authors recorded the staining intensity and the percentage of positive cells stained in benign epithelium, high grade prostatic intraepithelial neoplasia (PIN), and prostate carcinoma. They compared the results of 7E11 with those of PM2J004.5 in benign epithelium, high grade prostate, and carcinoma and also compared the results between the two treatment groups (ADT/RP vs. RP alone). RESULTS: Both anti-PSMA mAbs stained benign secretory-acinar epithelium, high grade PIN, and prostate carcinoma. In both treatment groups, PM2J004.5 reacted with a significantly greater percentage of cells (P < 0.001) and with significantly greater intensity (P < 0.001) compared with 7E11 in benign epithelium and prostate carcinoma. With both anti-PSMA mAbs, the percentage of cells stained and the intensity of staining in high grade PIN was similar to that in prostate carcinoma. In the group that received RP alone, the percentage of cells stained and the intensity of staining with 7E11 were significantly greater in high grade PIN and prostate carcinoma compared with benign epithelium (P < 0.001), and the intensity of staining with the PM2J004.5 was significantly greater in high grade PIN and prostate carcinoma compared with benign epithelium (P < 0.001). In the ADT/RP group, the percentage of cells stained and the intensity of staining with 7E11 and PM2J004.5 were significantly greater in prostate carcinoma compared with benign epithelium (P < 0.006). PSMA staining did not correlate with either Gleason score (in the group that received RP alone) or pathologic stage (in both the RP-alone and ADT/RP groups) and did not differ between the two treatment groups. CONCLUSIONS: Short term neoadjuvant ADT does not affect PSMA expression in benign prostate secretory-acinar epithelium, high grade PIN, or prostate carcinoma. Prostate carcinoma and high grade PIN express significantly higher levels of PSMA than benign prostate secretory-acinar epithelium. Compared with 7E11, the PM2J004.5 anti-PSMA mAb is a more sensitive immunohistochemical marker of prostate carcinoma in formalin fixed, paraffin embedded tissue.

Aged↗
PubMed2000

Effect of a calcium channel blocker and antispasmodic in diarrhoea-predominant irritable bowel syndrome.

BACKGROUND: Irritable bowel syndrome (IBS) is a colonic function disorder. Both pinaverlum bromide (a selective calcium channel blocker) and mebeverine (an antispasmodic) are reported to be effective in the long-term (12-16 weeks) treatment of IBS patients. Their efficacy in the short-term treatment of IBS patients and colonic transit time is unclear. Furthermore, substance P and neuropeptide Y have either excitatory or inhibitory effects on colonic motility. Whether the efficacy of both drugs is mediated through these neuropeptides remains unknown. METHODS AND RESULTS: A clinical trial was conducted with 91 patients with diarrhoea-predominant IBS. After basal measurement of the total colonic transit time, IBS patients were randomized to receive either pinaverlum bromide (50 mg, t.i.d.) or mebeverine (100 mg, t.i.d.) for 2 weeks. The symptomatic scores regarding defaecation, total colonic transit time and serum levels of substance P and neuropeptide Y were measured before and after treatments. The daily defaecation frequency was markedly decreased after treatment (pinaverlum bromide, 2.9+/-1.2 vs 2.0+/-1.0, P< 0.05; mebeverine, 2.7+/-1.1 vs 2.1+/-1.0, P< 0.05). The stool consistency became well formed after both treatments (P< 0.05). Both drugs similarly improved the global well-being in these IBS patients (pinaverlum bromide vs mebeverine 73.4 vs 71.8%, P> 0.05). The total colonic transit time was significantly prolonged only after pinaverlum bromide treatment (21.4+/-15.5 vs 30.8+/-14.8 h, P< 0.01). Neither substance P nor neuropeptide Y serum level was significantly changed after either treatments. CONCLUSION: Pinaverlum bromide and mebeverine have similar therapeutic efficacies on diarrhoea-predominant IBS patients. Prolonged colonic transit time may be one of the factors responsible for the efficacy of pinaverlum bromide on the IBS patients. Substance P and neuropeptideY appear less important in the pathogenesis of diarrhoea-predominant IBS.

Calcium Channel Blockers↗
PubMed2000

Pseudogastroparesis as a presentation of small-bowel malignancy.

Establishing the diagnosis of small-bowel malignancy is sometimes an extremely difficult challenge owing to its non-specific symptoms. The mainstay of treatment is early recognition, diagnosis and surgical resection. The prognosis depends primarily on the degree of spread and stage at presentation. We present two cases with initially obscure presentations of a small-bowel tumour. One was a jejunal adenocarcinoma, but an initial upper gastrointestinal and small-bowel series did not disclose the lesion; the other was a primary ileal lymphoma, first thought to be diabetes mellitus gastroparesis. Therefore, a negative small-bowel series or presentation of a systemic disease-associated intestinal pseudo-obstruction or gastroparesis does not exclude the possibility of a small-bowel malignancy, if the clinical symptoms are not alleviated after prokinetic medications. The clinicians should further pursue the possibility of an obstructing lesion.

Adenocarcinoma↗
PubMed2000

Repeated episodes of spontaneous intracystic hemorrhage of hepatic cysts mimicking malignancy.

Repeated episodes of spontaneous intracystic hemorrhage in the liver are very rare. We present the case of a patient with spontaneous intracystic hemorrhage mimicking hepatic malignancy, following an episode of spontaneous hemorrhage of a cyst in the left lobe of the liver. Sonography revealed a heterogenous mass with amorphous material in one episode and a cystic mass with internal papillary projections and septations in the other. The patient experienced acute abdominal pain in the first episode and remained asymptomatic during the two-year follow-up period. With an accurate diagnosis, spontaneous hemorrhage of a hepatic cyst may follow a benign course and be treated conservatively.

Aged↗
PubMed2000

Overview of evolving strategies incorporating prostate-specific membrane antigen as target for therapy.

Prostate-specific membrane antigen (PSMA) is a potential target in prostate cancer patients because it is very highly expressed and because it has been reported to be upregulated by androgen deprivation. This overview addresses the expression of the PSMA gene in terms of the promoter and enhancer and how that may play a role in gene therapy. We also review PSMA as a target for antibodies for imaging and treatment and the development of a novel hybrid T-cell receptor that combines the specificity of anti-PSMA antibodies with that of T-cell receptor activation when introduced into primary lymphocytes by retroviral-mediated gene transfer. We also discuss our recent findings on the expression of a PSMA-like gene and how that understanding allows specific targeting of PSMA.

Animals↗
PubMed1999

Five different anti-prostate-specific membrane antigen (PSMA) antibodies confirm PSMA expression in tumor-associated neovasculature.

Prostate-specific membrane antigen (PSMA) is a type II integral membrane glycoprotein that was initially characterized by the monoclonal antibody (mAb) 7E11. PSMA is highly expressed in prostate secretory-acinar epithelium and prostate cancer as well as in several extraprostatic tissues. Recent evidence suggests that PSMA is also expressed in tumor-associated neovasculature. We examined the immunohistochemical characteristics of 7E11 and those of four recently developed anti-PSMA mAbs (J591, J415, and Hybritech PEQ226.5 and PM2J004.5), each of which binds a distinct epitope of PSMA. Using the streptavidin-biotin method, we evaluated these mAbs in viable prostate cancer cell lines and various fresh-frozen benign and malignant tissue specimens. In the latter, we compared the localization of the anti-PSMA mAbs to that of the anti-endothelial cell mAb CD34. With rare exceptions, all five anti-PSMA mAbs reacted strongly with the neovasculature of a wide spectrum of malignant neoplasms: conventional (clear cell) renal carcinoma (11 of 11 cases), transitional cell carcinoma of the urinary bladder (6 of 6 cases), testicular embryonal carcinoma (1 of 1 case), colonic adenocarcinoma (5 of 5 cases), neuroendocrine carcinoma (5 of 5 cases), glioblastoma multiforme (1 of 1 cases), malignant melanoma (5 of 5 cases), pancreatic duct carcinoma (4 of 4 cases), non-small cell lung carcinoma (5 of 5 cases), soft tissue sarcoma (5 of 6 cases), breast carcinoma (5 of 6 cases), and prostatic adenocarcinoma (2 of 12 cases). Localization of the anti-PSMA mAbs to tumor-associated neovasculature was confirmed by CD34 immunohistochemistry in sequential tissue sections. Normal vascular endothelium in non-cancer-bearing tissue was consistently PSMA negative. The anti-PSMA mAbs reacted with the neoplastic cells of prostatic adenocarcinoma (12 of 12 cases) but not with the neoplastic cells of any other tumor type, including those of benign and malignant vascular tumors (0 of 3 hemangiomas, 0 of 1 hemangioendothelioma, and 0 of 1 angiosarcoma). The mAbs to the extracellular PSMA domain (J591, J415, and Hybritech PEQ226.5) bound viable prostate cancer cells (LNCaP and PC3-PIP), whereas the mAbs to the intracellular domain (7E11 and Hybritech PM2J004.5) did not. All five anti-PSMA mAbs reacted with fresh-frozen benign prostate secretory-acinar epithelium (28 of 28 cases), duodenal columnar (brush border) epithelium (11 of 11 cases), proximal renal tubular epithelium (5 of 5 cases), colonic ganglion cells (1 of 12 cases), and benign breast epithelium (8 of 8 cases). A subset of skeletal muscle cells was positive with 7E11 (7 of 7 cases) and negative with the other four anti-PSMA mAbs. PSMA was consistently expressed in the neovasculature of a wide variety of malignant neoplasms and may be an effective target for mAb-based antineovasculature therapy.

Antibodies, Monoclonal↗