Biomedical subjects

Wael Sakr

Publications and source records attributed to Wael Sakr.

24 records · Page 2Linked to original sources

PubMed2002

Clinical significance of poor CD3 response in head and neck cancer.

PURPOSE: The objective of our investigation was to prospectively study what the implications of an unresponsive CD3 receptor are on clinical outcome in advanced-stage head and neck cancer patients. EXPERIMENTAL DESIGN: Lymph node mononuclear cells were purified from cancer patients and stimulated with immobilized anti-CD3 in vitro for 8 days. Two populations were identified, nonresponders (NRs) with [(3)H]thymidine-counts per min (cpm) <3500 and responders (Rs) with cpm >or=3500. NRs and Rs were prospectively followed for a minimum of 24 months, and clinical outcomes were compared. Postoperative complications, length of hospitalization, toxicities associated with chemotherapy or radiation therapy, survival, and disease-free status were measured. RESULTS: Twenty-six patients were followed, of which 19 Rs [[(3)H](X) = 37,819 +/- 24,979 cpm (mean proliferative count +/- SD)] and 7 NRs ([(3)H](X) = 1,375 +/- 1,102 cpm) were identified. There were no phenotypic differences in lymph node T-cell subpopulations (CD3, CD4, CD8, CD28, CD45RO) between groups. There was a 71% (5/7) incidence of recurrent cancer in NRs compared with 16% (3/19) in Rs; the median disease-free interval was significantly less in NRs (P = 0.03). The risk ratio of Rs to develop a recurrent cancer was 0.237 (95% confidence interval, 0.057-0.994), much less than for NRs. CONCLUSIONS: Patients with an unresponsive CD3 receptor as measured by in vitro response to anti-CD3 monoclonal antibodies had a significantly higher incidence of recurrent cancer. Analyses using Cox proportion hazards models demonstrated that CD3 response was the single greatest predictor of reduced disease-free interval. This is the first prospective study to confirm the importance of regional lymph node mononuclear cell CD3 receptor function in head and neck squamous cell carcinoma patients for tumor control.

CD3 Complex↗

PubMed2002

[Main grade of Gleason's 7 score of the surgical sample correlated with biologic progression in patients treated for total prostatectomy].

OBJECTIVES: To analyse the influence of the main grade of Gleason score 7 of the operative specimen correlated with the blood PSA level on the laboratory progression-free survival of patients treated by radical prostatectomy. MATERIALS AND METHODS: 331 patients consecutively treated by radical prostatectomy and presenting a Gleason score 7 were analysed. Exclusion criteria were the use of radiotherapy and/or preoperative and/or postoperative endocrine therapy. The main grade (3 or 4), histological stage, and blood PSA level were analysed for their predictive value of laboratory progression-free survival. The mean follow-up was 3.5 years (range: 13.6 to 72.8 months). Laboratory recurrence was defined by a PSA > 0.4 ng/ml. RESULTS: The main grade of Gleason score 7 was 3 in 199 (60%) patients and 4 in 132 (40%) patients with a mean follow-up of 3.6 years. Laboratory progression-free survival rates were 89% and 72% for main grades 3 and 4, respectively (p = 0.03). When the cancer was confined to the prostate, the progression-free survival rates were 96% and 88% for main grades 3 and 4, respectively (p = 0.01). For a PSA < 10 ng/ml, main grade 3 was associated with a better laboratory progression-free survival rate than main grade 4 (p = 0.0007). No difference in terms of laboratory progression was observed in the presence of extraprostatic extension or PSA > 10 ng/ml. CONCLUSION: A high correlation was observed between the main grade of Gleason score 7 and laboratory progression-free survival. Main grade 3 constituted a factor of better prognosis than main grade 4.

Disease Progression↗

PubMed1996

Prostate Cancer - Old Problems and New Approaches. (Part II. Diagnostic and Prognostic Markers, Pathology and Biological Aspects).

Diagnostic and prognostic markers for prostatic cancer (PCa) include conventional protein markers (e.g., PAP, PSA, PSMA, PIP, OA-519, Ki-67, PCNA, TF, collagenase, and TIMP 1), angiogenesis indicator (e.g., factor VIII), neuroendocrine differentiation status, adhesion molecules (E-cadherin, integrin), bone matrix degrading products (e.g., ICPT), as well as molecular markers (e.g., PSA, PSMA, p53, 12-LOX, and MSI). Currently, only PSA is used clinically for early diagnosis and monitoring of PCa. The histological differential diagnosis of prostatic adenocarcinoma includes normal tissues such as Cowper's gland, paraganglion tissue and seminal vesicle or ejaculatory duct as well as pathological conditions such as atypical adenomatous hyperplasia, atrophy, basal cell hyperplasia and sclerosing adenosis. A common PCa is characterized by a remarkable heterogeneity in terms of its differentiation, microscopic growth patterns and biological aggressiveness. Most PCa are multifocal with signi ficant variations in tumor grade between anatomically separated tumor foci. The Gleason grading system which recognizes five major grades defined by patterns of neoplastic growth has gained almost uniform acceptance. In predicting the biologic behavior of PCa clinical and pathological stages are used as the major prognostic indicators. Among the cell proliferation and death regulators androgens are critical survival factors for normal prostate epithelial cells as well as for the androgen-dependent human prostatic cancer cells. The androgen ablation has been shown to increase the apoptotic index in prostatic cancer patients and castration also promotes apoptotic death of human prostate carcinoma grown in mice. The progression of PCa, similarly to other malignancies, is a multistep process, accompanied by genetic and epigenetic changes, involving phenomenons as adhesion, invasion and angiogenesis (without prostate specific features).

Journal Article↗

PubMed1996

Prostate Cancer Old Problems and New Approaches. Part III. Prevention and Treatment.

In Part Three of this review, we begin with an analysis of prevention strategies for prostate cancer followed by a discussion of the clinical use of molecular techniques for the evaluation and treatment of patients with clinically localized prostate cancer. New developments in neutron and photon therapy of prostate cancer are addressed as well as the use of systemic radiotherapy for the treatment of bone metastases. Finally, we conclude with the role of hormonal therapy in the treatment of prostate cancer and the current status of development of chemo therapeutic regimens for the treatment of prostate cancer.

Journal Article↗

PubMedDate not supplied

High frequency of allelic losses in high-grade prostate cancer is associated with biochemical progression after radical prostatectomy.

Loss of heterozygosity (LOH) is the most consistent genetic change in prostate cancer (CaP). We aimed, to correlate specific LOH and the overall LOH frequency, to disease progression after radical prostatectomy (RP) in high-grade CaP. Between January 1990 through December 1998, 126 patients who underwent RP (cT1-T2), Gleason 8-10, were pT3, or pN1, or SM(+) (surgical margins). Nine were lost of follow-up, 39/117 (33%) had no biochemical progression (mean follow-up: 45 months). After exclusion for preoperative PSA >50 ng/mL, a case-control study was designed by matching 26 of these cases with 26 similar patients without biochemical progression (criteria: pT, pN, year of surgery). Using microsatellite markers, LOH were assessed on six chromosomal regions (7q31, 8p22, 12p13, 13q14, 16q23.2, 18q21). No prognostic value was associated with LOH at any one specific locus. However, the overall LOH frequency (five classes, cutoff of 60%), was significantly higher if progression (P = 0.02; P = 0.03) in SM(+) patients, and was near statistical significance (P = 0.08; P = 0.07) for the overall case-control population. In multivariate analysis (overall population), the overall LOH rate > or =60% was independently associated with progression [P = 0.035; Odds Ratio (OR) = 5.54]. An overall LOH rate > or =60% predicted poor outcome in 85% of SM(+) patients and 69% of the whole population. Our results suggest that the overall rate of LOH at chromosomal "hot spots" is more likely to be predictive of recurrence than the presence of LOH at any one particular locus. Moreover, the identification of a threshold of LOH could help in predicting patients with poor outcome who may be candidates for local or systemic adjuvant therapies.

Aged↗

PubMedDate not supplied

Pathologic features the urologist should expect on a prostate biopsy.

In recent years, the pathological evaluation of prostate biopsy specimens has made great improvements in diagnostic accuracy and comprehensiveness. In this article, we review major pathological findings on prostate biopsy, their interpretation and reporting, as well as their clinical significance and utility. We discuss especially the clinically relevant histological features in either a positive or negative biopsy. We emphasize that both Gleason score and extent of cancer involvement in a needle core biopsy are important predictors of clinical outcome after either radical prostatectomy or radiation. Special issues regarding diagnosis and grading of minimal cancer on needle core biopsies are discussed. We also highlight the current standards on high-grade prostatic intraepithelial neoplasia and atypical small acinar proliferation on needle core biopsies. In summary, the pathology reports on needle biopsies are far beyond the simple presence or absence of cancer; they contain invaluable information to clinicians on patient management and counseling.

Biopsy, Needle↗