Biomedical subjects

Melania Pintilie

Publications and source records attributed to Melania Pintilie.

44 records · Page 3Linked to original sources

PubMed2003

Expression and prognostic significance of kit, protein kinase B, and mitogen-activated protein kinase in patients with small cell lung cancer.

PURPOSE: The Kit receptor has been proposed as a key molecular target for the treatment of small cell lung cancer (SCLC). Protein kinase B (PKB/Akt) and mitogen-activated protein kinase (MAPK) are intracellular kinases that regulate cell survival and proliferation and may play a role in Kit signal transduction. This study was designed to examine the expression and importance of Kit, PKB/Akt, and MAPK relative to standard clinical prognostic factors in SCLC. EXPERIMENTAL DESIGN: Kit, PKB/Akt, and MAPK expression was assessed by immunohistochemistry in SCLC biopsies. Clinical data were collected on tumor stage, weight loss, hematology, biochemistry, response to treatment, and survival. Univariate and multivariate analyses were performed to evaluate prognostic significance. RESULTS: Biopsies from 42 patients were evaluable, and significant Kit expression (>/=35% cells) was detected in 51% of the tumors, phosphorylated PKB/Akt was detected in 62% of the tumors, and phosphorylated MAPK was detected in 48% of the tumors. Neither Kit nor PKB/Akt expression predicted for survival. Only increased expression of cytoplasmic MAPK was prognostic for survival (median, 1 year for negative staining versus 1.8 years for positive staining; P = 0.0054). CONCLUSIONS: Kit, PKB/Akt, and MAPK are expressed in a high percentage of SCLCs, and our data suggest that MAPK is an independent positive predictive factor in this malignancy.

Adult↗

PubMed2002

Dealing with competing risks: testing covariates and calculating sample size.

It is universally agreed that Kaplan-Meier estimates overestimate the probability of the event of interest in the presence of competing risks. Kalbfleisch and Prentice recommend using the cumulative incidence as an estimate of the probability of an event of interest. However, there is no consensus on how to test the effect of a covariate in the presence of competing risks. Using simulations, this paper illustrates that the Cox proportional hazards model gives valid results when employed in testing the effect of a covariate on the hazard rate and when estimating the hazard ratio. A method to calculate the sample size for testing the effect of a covariate on outcome in the presence of competing risks is also provided.

Breast Neoplasms↗

PubMed2002

Expression of hypoxia-inducible factor-1alpha in cervical carcinomas: correlation with tumor oxygenation.

PURPOSE: To investigate the relations between hypoxia-inducible factor-1 (HIF-1), tumor oxygenation, and clinical correlates in patients with locally advanced carcinoma of the uterine cervix. METHODS AND MATERIALS: Biopsies from 42 patients with invasive cervical carcinoma and previous polarographic O2 measurements were assessed for the expression of HIF-1alpha using digitized microscopic imaging and analysis. RESULTS: The HIF-1alpha expression levels ranged from <0.1% to 10.7% of the total tumor area; the positive staining was localized exclusively to the nuclei. Three distinct arrangement patterns of HIF-1alpha-positive cells in relation to blood vessels were identified using spatial image mapping: (1) most HIF-1alpha-positive cells were located within the typical oxygen diffusion distance in tissue (< or =150 microm to the nearest blood vessel); (2) most HIF-1alpha-positive cells were located in the vicinity (< or =60 microm) of the blood vessels; and (3) no apparent spatial relationship was found between HIF-1alpha-positive cells and blood vessels. A statistically significant association was found between HIF-1alpha expression and tumor oxygenation (Spearman correlation coefficient = 0.4, p <0.01), as determined with the Eppendorf pO2 histograph. No correlation was found between the level of HIF-1alpha expression and patient outcome, using disease-free survival as the end point. CONCLUSION: Our results suggest that HIF-1alpha expression may represent a useful biologic marker for hypoxia in uterine cervical cancer.

Aged↗

PubMed2002

Molecular profiling of non-small cell lung cancer and correlation with disease-free survival.

Recent studies have suggested that information from gene expression profiles could be used to develop molecular classifications of cancer. We hypothesized that expression levels of specific genes in operative specimens could be correlated to recurrence risk in non-small cell lung cancer (NSCLC). We performed expression profiling using 19.2 K cDNA microarrays on tumor specimens from a total of 39 NSCLC patients with known clinical follow-up information. Statistical analysis and clustering approaches were used to determine patterns of gene expression segregating with clinical outcome. The results provide evidence that molecular subtyping of NSCLC can identify distinct profiles of gene expression correlating with disease-free survival.

Adult↗

PubMed2002

Assessment of coronary heart disease morbidity and mortality after radiation therapy for early breast cancer.

PURPOSE: To assess the risk of fatal and nonfatal myocardial infarction (MI) after breast-conserving surgery (BCS) and radiation therapy (RT) for left-sided breast cancer. PATIENTS AND METHODS: A hospital-based retrospective cohort linkage study of all breast cancer patients registered at the Princess Margaret Hospital (PMH), Toronto, Canada, between 1982 and 1988 who were treated with postlumpectomy RT was performed. Available identifiers for the study cohort were linked to two province-wide health files: the Canadian Institute for Health Information Hospitalization File and the Ontario Mortality Database. Admissions to hospital for MI and deaths attributable to MI were identified. The relevant original health records were abstracted to verify the diagnosis of MI according to diagnostic criteria used in the World Health Organization multinational monitoring of trends and determinants in cardiovascular disease (MONICA) project. We compared incidence of MI in the study cohort with the general population and incidence of MI after therapy for left- versus right-sided breast cancer. RESULTS: A cohort of 2,128 patients was identified. The median length of follow-up was 10.2 years. The incidence of MI in the study cohort was comparable to that in an age-matched general population of women in Ontario. There were 70 coronary events among 56 patients after breast irradiation. According to MONICA criteria, 53 and six events were characterized as definite and possible MIs, respectively. Eleven events did not satisfy MONICA criteria for MI. Twenty-six patients treated for left-sided and 23 patients treated for right-sided breast cancer experienced at least one definite or possible MI (log-rank test, P =.66). There were eight fatal MIs among the left-sided group and six among the right-sided group. There was no excess of other cardiac diseases among patients who received left-sided radiotherapy compared to the right-sided group. CONCLUSION: We have found no evidence for excess morbidity and mortality from coronary artery disease among women treated with RT to the left breast after BCS at 10.2 years of follow-up. Longer follow-up is required to confirm that excess cardiac disease has been completely avoided.

Adult↗

PubMed2002

Factors influencing risk of acute urinary retention after TRUS-guided permanent prostate seed implantation.

PURPOSE: To look for factors predictive of acute urinary retention (AUR) after permanent seed prostate brachytherapy. METHODS AND MATERIALS: From March 1999 to February 2001, 150 permanent seed prostate implants were performed at Princess Margaret Hospital (Stage T1c, n = 113; T2a, n = 37; mean prostate-specific antigen level 5.9 ng/mL, prescription dose 145 Gy per Task Group No. 43). alpha-Blockers were used routinely after implantation. Dosimetry was based on the 1-month postimplant CT scan. The International Prostate Symptom Score (IPSS) and catheterization were recorded at 1 month and 3 months and then every 3 months. The following variables were examined: age, baseline IPSS, prior androgen ablation, prostate transrectal ultrasound volume, number of seeds, D(90), V(100), V(200), and urethral dose. RESULTS: Twenty patients (13%) experienced AUR. No difference was seen in the mean D(90) (149 Gy vs. 152 Gy, p = 0.6), V(100) (90% vs. 91%, p = 0.6), V(200) (23% vs. 25% p = 0.4), IPSS (6.4 vs. 5.9, p = 0.8), or maximal urethral dose (204 Gy vs. 210 Gy, p = 0.5). The prostate volume was significantly larger in men with AUR (39.8 cm(3) vs. 34.3 cm(3), p = 0.003), and the mean number of seeds was higher (112 vs. 103, p = 0.006). Of the 20 patients experiencing AUR, 11 (55%) had received prior antiandrogen therapy to downsize their prostates vs. 35 (27%) of the 130 who did not have AUR (p = 0.02). Multivariate analysis showed prostate volume and prior hormone use to be independent predictors of AUR. CONCLUSIONS: Implant quality as determined by D(90), V(100), V(200), and urethral dose did not predict AUR. Prostate size was the major determinant of AUR. For any given prostate size, prior androgen ablation increased the risk of AUR. Men with larger prostates should be aware of the increased risk when contemplating brachytherapy.

Aged↗

PubMed2002

Radiotherapy alone in patients with advanced nasopharyngeal cancer: comparison with an intergroup study. Is combined modality treatment really necessary?

PURPOSE: To examine the outcome of radiotherapy (RT) alone in patients with advanced nasopharyngeal cancer (NPC) and to compare the results with those reported by the Intergroup study 0099 (IGS) comparing RT to combined modality therapy (CMT). MATERIALS AND METHODS: During the period 1985-1992, 198 NPC patients presenting without distant metastatic disease were treated for cure. Of these, 172 had stage III/IV (UICC 1987, 1992). Planned RT was 2 Gy/day fraction to 60-66 Gy to the primary tumor, with 50 and 60 Gy to the node negative and to palpable nodes, respectively. Outcomes included overall survival (OS) and disease-free survival (DFS), defined from the time of registration at our institution. RESULTS: The TNM categories and other prognostic factors were similar to the IGS, though 80% had stage IV compared to 91% in IGS. The 5 year OS and DFS for the 172 patients with stage III/IV disease were 62 and 48%, respectively, as compared to the IGS results of OS 37% and DFS 29% for RT alone, and OS 67% and DFS 58% for the CMT arm of IGS. When the distribution of adverse prognostic factors was balanced between both studies the comparative results were unchanged. CONCLUSIONS: The early results for RT alone of this single institution experience are superior to those of the IGS control arm (RT), while somewhat inferior to those reported in the chemo-radiotherapy arm. The surprisingly poor outcome of the IGS/RT control arm may have resulted by chance, suggesting the need for a confirmatory randomized trial to fully establish the role of combined chemotherapy and radiation, as used in the IGS.

Adolescent↗

PubMedDate not supplied

Stability and heterogeneity of expression profiles in lung cancer specimens harvested following surgical resection.

One of the major concerns in microarray profiling studies of clinical samples is the effect of tissue sampling and RNA extraction on data. We analyzed gene expression in lung cancer specimens that were serially harvested from tumor mass and snap-frozen at several intervals up to 120 minutes after surgical resection. Global gene expression was profiled on cDNA microarrays, and selected stress and hypoxia-activated genes were evaluated using real-time reverse transcription polymerase chain reaction (RT-PCR). Remarkably, similar gene expression profiles were obtained for the majority of samples regardless of the time that had elapsed between resection and freezing. Real-time RT-PCR studies showed significant heterogeneity in the expression levels of stress and hypoxia-activated genes in samples obtained from different areas of a tumor specimen at one time point after resection. The variations between multiple samplings were significantly greater than those of elapsed time between sampling/freezing. Overall samples snap-frozen within 30 to 60 minutes of surgical resection are acceptable for gene expression studies, thus making sampling and snap-freezing of tumor samples in a routine surgical pathology laboratory setting feasible. However, sampling and pooling from multiple sites of each tumor may be necessary for expression profiling studies to overcome the molecular heterogeneity present in tumor specimens.

Carcinoma, Non-Small-Cell Lung↗