Biomedical subjects

Iman Osman

Publications and source records attributed to Iman Osman.

24 records · Page 2Linked to original sources

PubMed2002

Evaluation of the proliferation marker MIB-1 in the prognosis of cutaneous malignant melanoma.

BACKGROUND: The proliferation marker MIB-1, which recognizes the Ki-67 antigen, provides independent prognostic information in several tumor types. Its utility in melanoma has been evaluated mostly in studies of thick primary tumors. Its usefulness in thinner lesions has not been assessed adequately. METHODS: A well characterized cohort of 137 patients diagnosed with primary cutaneous melanoma at the New York University School of Medicine between 1972 and 1982 was studied based on the availability of representative tissues and adequate clinical follow-up. Twenty-one tumors were less than or equal to 1.0 mm thick, 94 were between 1.01 and 4.0 mm thick, and 22 were thicker than 4.0 mm. Tumor cell proliferation was assessed by immunohistochemistry using the monoclonal antibody MIB-1. MIB-1 expression was correlated with baseline clinicopathologic parameters, as well as recurrence (RR), disease-free (DFS), and overall survival (OS) rates. Median follow-up among survivors was 6.5 years (range, 5.6-17.5). RESULTS: High proliferative index, defined as 20% or more of tumor cells showing nuclear immunoreactivity, was observed in 65 of 137 (47.4%) cases. High proliferative index was significantly correlated with increased tumor thickness (P < 0.001) and higher stage (P = 0.03). Trends approaching statistical significance were observed with ulceration of the primary tumor (P = 0.09), male gender (P = 0.06), and shorter DFS (P = 0.12). No significant associations were seen between high proliferative index and RR or OS. In multivariate analyses, tumor thickness was the strongest predictor of clinical outcome. CONCLUSIONS: In primary cutaneous melanoma, a high proliferative index is associated with clinicopathologic parameters predictive of worse clinical outcomes. However, it was not an independent predictor of clinical outcome.

Cohort Studies↗

PubMed2002

Alteration of p53 pathway in squamous cell carcinoma of the head and neck: impact on treatment outcome in patients treated with larynx preservation intent.

PURPOSE: To identify the role of p53 pathway alteration(s) as predictors of treatment outcome in patients with advanced, resectable, squamous cell carcinoma (SCC) of the larynx and pharynx treated with larynx preservation (LP) intent. PATIENTS AND METHODS: Seventy-one patients treated on two consecutive LP protocols were studied based on availability of representative tissues. We analyzed the expression pattern of p53, its upstream regulator mdm2, and downstream transcriptional target p21/WAF1 by immunohistochemistry. Positive phenotype was defined as >or= 20% of tumor cells showing nuclear immunoreactivity. Results were correlated with treatment outcomes. RESULTS: Positive phenotype was observed in 35 (49%) of 71 cases for p53, in 52 (74%) of 70 for mdm2, and in 37 (54%) of 68 for p21. There was no correlation between p53 phenotype and p21 nuclear accumulation. The mdm2-negative phenotype was most predictive of major response at the primary tumor site (P =.088). p53-positive phenotype was associated with worse local control with LP (LCLP; 49% v 23%, P =.053) and inferior overall survival (OS; 51% v 29%, P =.017) at 5 years. On Cox regression analysis, p53-positive phenotype predicted inferior OS (P =.033) and showed a trend for worse LCLP (P =.102). When analyzed in a multivariate model as continuous variables, p53 showed a stronger correlation with inferior OS (P <.01), and mdm2 was associated with worse OS (P <.01). CONCLUSION: Among the three markers studied, our data support p53 phenotype as the most informative predictor of unfavorable outcomes in the LP setting, and suggest a role for mdm2 phenotype that requires further exploration. Our analysis does not support a p53-dependent mechanism for p21 expression. Prospective and larger studies are necessary before integration of these molecular markers as part of molecular staging and predictors for organ preservation or other outcomes.

Adult↗

PubMed2002

HER-2 profiling and targeting in prostate carcinoma.

BACKGROUND: The clinical effects of targeting HER-2 in prostate carcinoma are not known. This study explored the feasibility of molecular profiling to determine the correlation between HER-2 expression, hormonal sensitivity, and the antitumor effects of trastuzumab and paclitaxel in patients with prostate carcinoma. METHODS: Patients with progressive androgen dependent (AD) and androgen independent (AI) prostate carcinoma were eligible to participate in the study. HER-2 expression was assessed on pretreatment tissue specimens, and patients were then assigned to one of four treatment groups: AD HER-2 positive, AD HER-2 negative, AI HER-2 positive, and AI HER-2 negative. They were treated with weekly trastuzumab at a dose of 2 mg/kg (after a 4 mg/kg loading dose) until they experienced disease progression, when weekly paclitaxel at 100 mg/m(2) was added. RESULTS: The authors screened 130 patients for HER-2 expression. In total, 23 patients were treated. Six eligible patients had HER-2 positive disease; therefore, only the AI HER-2 negative arm accrued to completion. All patients (100%) experienced disease progression on trastuzumab alone at or before the first 12 weeks of treatment. Fifteen patients received combined therapy: Seven patients (47%) experienced disease progression, 5 patients (33%) had stable disease, and 3 patients (20%) had a decline > or = 50% in prostate specific antigen PSA level or in soft tissue disease. HER-2 overexpression was found in significant proportions only in AI metastatic tissue samples (42% HER-2 positive; 95% confidence interval, 14-60%). In three of nine matched pairs, the AD prostate biopsy was HER-2 negative, and the AI metastatic sample was HER-2 positive. CONCLUSIONS: Trastuzumab is not effective as a single agent for the treatment of patients with AI HER-2 negative tumors. HER-2 expression varies by clinical state in patients with prostate carcinoma: Accurate HER-2 profiling requires sampling metastatic tissue in patients with metastatic disease. Further development of trastuzumab for the treatment of patients with metastatic prostate carcinoma is not feasible until more reliable and practical methods of sampling metastatic disease are developed to identify patients with HER-2 positive tumors.

Aged↗

PubMed2002

Fluorinated deoxyglucose positron emission tomography imaging in progressive metastatic prostate cancer.

OBJECTIVES: To correlate the abnormalities on computed tomography, magnetic resonance imaging, and bone scan with fluorinated deoxyglucose positron emission tomography (FDG-PET) in patients with progressive metastatic prostate cancer, using a lesion-by-lesion analysis, and to preliminarily explore post-treatment changes in standard uptake value (SUV) with changes in prostate-specific antigen (PSA). METHODS: A lesional analysis compared abnormalities on FDG-PET with those on CT/MRI or bone scan. Patients had rising PSA levels and progressive disease according to the imaging findings. Changes in the SUV were compared with the PSA changes in patients who had serial scans after treatment. RESULTS: One hundred fifty-seven lesions in 17 patients were examined; 134 osseous lesions were evident on PET and/or bone scan, 95 lesions (71%) were evident on both, 31 (23%) were seen only on bone scan, and 8 (6%) were seen only on PET (adjusted McNemar's chi-square = 8.32, P = 0.004). All but one of the lesions seen only on bone scan were "stable" compared with the previous bone scans. All lesions seen only on PET proved to be active disease on subsequent bone scans. Twenty-three soft-tissue lesions were present on CT/MRI or PET, or both; 9 (39%) lesions were evident on both and 14 (61%) were evident only on one imaging modality. In 9 (75%) of 12 cases in which serial PET scans were available, the SUV changed in parallel with the PSA level. CONCLUSIONS: FDG-PET can discriminate active osseous disease from scintigraphically quiescent lesions in patients with progressive metastatic prostate cancer, but it is limited in detecting soft-tissue metastases. Post-treatment changes in the SUV tend to correlate with changes in PSA.

Aged↗

PubMed2002

Combined 18F-FDG and 11C-methionine PET scans in patients with newly progressive metastatic prostate cancer.

UNLABELLED: Metastatic prostate cancer may respond initially to hormone suppression, with involution of tumor sites, but ultimate tumor progression is inevitable. Our aim was to detect the proportion of bone and soft-tissue lesions that represent metabolically active tumor sites in patients with progressive metastatic prostate cancer. METHODS: In a prospective study, we compared 18F-FDG and L-methyl-11C-methionine (11C-methionine) PET with conventional imaging modalities (CIM), which included the combination of 99mTc-methylene diphosphonate scintigraphy, CT, or MRI. Twelve patients with prostate cancer, increasing levels of prostate-specific antigen (PSA), and at least 1 site (index lesion) with new or increasing disease on CIM were studied. The total numbers of soft-tissue and bone-tissue lesions, in a site-by-site comparison, were calculated for all imaging modalities. RESULTS: The sensitivities of 18F-FDG PET and 11C-methionine PET were 48% (167/348 lesions) and 72.1% (251/348 lesions), respectively, with CIM being used as the 100% reference (348/348). 11C-Methionine PET identified significantly more lesions than 18F-FDG PET (P < 0.01). All 12 patients with progressive metastatic prostate cancer had at least 1 lesion site of active metabolism for 18F-FDG or 11C-methionine, which could be used as an index lesion to monitor the metabolic response to therapy. A significant proportion of lesions (26%) had no detectable metabolism of 18F-FDG or 11C-methionine. Although technical factors cannot be totally excluded, we believe that metabolically inactive sites may be necrotic or dormant. More than 95% (251/258) of metabolically active sites (72% of the total number of lesions detected by CIM) metabolize 11C-methionine. 18F-FDG uptake is more variable, with 65% of metabolically active sites (48% of the total number of lesions detected by CIM). CONCLUSION: These findings reflect the different biologic characteristics of the lesions in a heterogeneous tumor such as prostate cancer and suggest that a time-dependent metabolic cascade may occur in advanced prostate cancer, with initial uptake of 11C-methionine in dormant sites followed by increased uptake of 18F-FDG during progression of disease.

Adenocarcinoma↗

PubMed1999

Differential Metabolism and Pharmacokinetics of L-[1-(11)C]-Methionine and 2-[(18)F] Fluoro-2-deoxy-D-glucose (FDG) in Androgen Independent Prostate Cancer.

Metabolic imaging with positron emission tomography (PET) for the staging and monitoring of treatment response has important implications in clinical oncology. The choice of radiotracer is likely to be critically important. The objective of our study was to compare the pharmacokinetics of C-11-methionine with FDG in a group of androgen independent patients with metastatic prostate cancer, to determine the differential metabolism of the two tracers, and to determine the optimal time of imaging after injection in treated and untreated patients. A total of 29 dynamic scans (19 pretreatment and 10 posttreatment) were performed in 10 patients with progressive or new lesions on bone scans (index lesions). A total of 13 index lesions were identified in baseline scans. Patients were infused with 370 MBq C-11-methionine on the couch and 32 dynamic images acquired over 60 minutes. After at least 5 half-lives of C-11, patients were then dynamically imaged (15 frames) for 45 minutes with FDG. Index lesions demonstrated both C-11-methionine (13/13) and FDG uptake (12/13). The plateau of methionine uptake in tumor was reached by 10 minutes, and thereafter remained constant. FDG tumor uptake was slower and for some patients continued to rise beyond 45 minutes. The clearance of blood activity for C-11-methionine was more rapid than FDG and the plateau was 10 and 45 minutes respectively. In 5 patients scanned after therapy, 4 responded to treatment, which was reflected by a corresponding decrease in C-11-methionine and FDG tumor uptake. No change was observed in the relative shape of the uptake curves however, between the C-11-methionine and the FDG uptake, either in the 4 who responded to treatment or for one patient who did not respond. The SUV of C-11-methionine was significantly higher than for FDG (P <.008). Both C-11-methionine and FDG are taken up in index lesions in patients with progressive prostate cancer. The advantages of C-11-methionine over FDG are the higher tumor to blood ratio, the more rapid tumor uptake allowing earlier imaging, and a flatter plateau rendering lesion activity on whole body images more uniform and less susceptible to gradual change than FDG. This indicates the feasibility of whole body PET imaging with decay corrected C-11-methionine. Additional studies are planned to define optimal imaging times after different therapies in comparison to FDG and bone scans.

Journal Article↗