PubMed Health⌕ Search

Biomedical subjects

C Begg

Publications and source records attributed to C Begg.

At least 19 recordsLinked to original sources
PubMed1995

Risk factors and p53 nuclear overexpression in early stage intestinal-type adenocarcinoma of the stomach.

In order to investigate the relationship between altered patterns of p53 expression and risk factors for stomach cancer, we have analyzed a group of 35 patients with early stage intestinal-type adenocarcinoma of the stomach. We assessed p53 nuclear overexpression by immunohistochemistry, using monoclonal antibody PAb 1801, and identified 15 out of 35 patients (43%) displaying nuclear overexpression of p53 protein. Significantly elevated odds ratios (O.R.) were observed for greater body mass index (highest quartile versus lowest quartile: O.R. = 7.9; 95% confidence interval (CI): 1.1 to 56.1) and younger age (< 60 vs. > or = 70 years: O.R. = 10; 95% CI, 1.43 to 50). The odds ratio for p53 overexpression in cigarette smokers was 2.8 (95% CI: 0.7 to 11.6) but not statistically significant. These data indicate that p53 mutations may be involved in the early stages of gastric carcinogenesis, especially in the development of intestinal-type adenocarcinoma.

Adenocarcinoma↗
PubMed1994

Prognostic factors for recurrence and survival in head and neck soft tissue sarcomas.

BACKGROUND: Soft tissue sarcomas of the head and neck represent uncommon malignant neoplasms. With the exception of orbital and parameningeal sites, the treatment of sarcomas in the head and neck has not been standardized. The authors used a prospectively collected database of adult soft tissue sarcomas to identify prognostic factors for local control and survival. METHODS: A prospectively collected database of adult soft tissue sarcoma from 1982 to 1989 was analyzed for the impact of prognostic factors on local control and survival. Factors examined included histologic type, tumor grade, size, and resection margins. RESULTS: The overall and disease free survival at 5 years was 71 and 60%, respectively. Local control was 70% at 5 years. On univariate analysis, grade and margin status were predictors for local control. Analysis based on the Cox proportional hazard model revealed that margin status was the only significant factor in predicting local control. Grade and margin status were significant prognostic indicators for survival both on univariate analysis and in the Cox proportional hazard model. CONCLUSION: Patients with head and neck sarcomas should undergo wide excision with the removal of all gross disease and the acquisition of negative, microscopic surgical margins. Patients with positive margins should receive adjuvant radiotherapy for local control. High grade lesions place patients at risk for local recurrence and distant dissemination. Investigational regimens designed to prevent metastatic disease should be performed.

Adolescent↗
PubMed1994

Post-therapy change in prostate-specific antigen levels as a clinical trial endpoint in hormone-refractory prostatic cancer: a trial with 10-ethyl-deaza-aminopterin.

OBJECTIVES: Serial changes in prostate-specific antigen (PSA) correlate with disease status in all stages of prostatic cancer. For hormone-refractory disease, post-therapy declines of 50% and 80% from baseline are associated with an improved survival. This study sought to evaluate edatrexate, a synthetic antifolate, in hormone-refractory prostatic cancer using post-therapy PSA change as the initial endpoint. METHODS: Fourteen patients with progression of disease despite castrate levels of testosterone received edatrexate. Serial changes in PSA were monitored and correlated with other parameters of outcome. RESULTS: Stabilization of a rising PSA level in parallel with clinical stabilization of disease was observed in one patient; disease in all others progressed. Toxic reactions were acceptable. CONCLUSIONS: With no objective evidence for antitumor activity as assessed by post-therapy PSA changes in any of the patients treated, edatrexate seems a poor candidate for future study. The use of post-therapy PSA change as the initial screening modality allows treatments to be evaluated rapidly in patients without measurable disease. The methodology proposed will require validation in prospective phase III investigations using survival as the endpoint.

Aged↗
PubMed1993

Identification of the L-tartrate dehydratase genes (ttdA and ttdB) of Escherichia coli and evolutionary relationship with the class I fumarase genes.

The genes encoding an oxygen-labile stereospecific L-tartrate dehydratase (L-Ttd, EC 4.2.1.32) have been identified as the orfZ1 and orfZ2 genes located upstream of the rpsU-dnaG-rpoD operon at 67 min in the Escherichia coli linkage map. They were previously cloned and sequenced by M. Nesin and others (Gene 51, 149-161, 1987) and have now been independently cloned, partially resequenced, and designated as an operon (ttdAB) containing two translationally coupled genes. The enzyme behaves as a tetramer (M(r) 105,000) containing two pairs of non-identical subunits, TtdA (M(r) 32589) and TtdB (M(r) 22641), which otherwise resembles the homodimeric iron-sulphur-containing Class I fumarases of E. coli and Bacillus stearothermophilus. The amino acid sequences of the TtdA-TtdB subunits are colinearly related to a single fumarase subunit, indicating a common evolutionary ancestry. E. coli can use L-, D- and meso-tartrates as aerobic growth substrates and as reducible substrates for supporting anaerobic growth on glycerol. L-Ttd was induced during anaerobic growth on glycerol plus L- and meso-tartrates, and a stereospecific D-tartrate dehydratase was induced by all three stereoisomers under comparable conditions. No meso-tartrate dehydratase was detected, nor were any dehydratases detected after aerobic growth on tartrate minimal media suggesting that different catabolic routes operate under aerobic conditions.

Amino Acid Sequence↗
PubMed1992

DNA-flow cytometry of head and neck carcinoma: the importance of uniform tissue sampling and tumor sites.

Flow cytometric DNA ploidy measurements using deparaffinized tumor specimens were performed on 46 squamous cell carcinomas of the head and neck, including 22 carcinomas of the oropharynx, 18 carcinomas of the larynx and six carcinomas of the oral cavity. Aneuploidy was found in 14 of these tumors with carcinomas of the larynx and oral cavity showing almost equal percentages of DNA aneuploidy (10/18 and 3/6, respectively). In contrast, only 1 of the oropharyngeal carcinomas was aneuploid. Accurate microscopy-controlled sampling of tumor tissue from the histological tissue blocks was found to be mandatory in order to obtain reliable ploidy measurements.

Carcinoma, Squamous Cell↗
PubMed1992

Prognostic factors in differentiated carcinoma of the thyroid gland.

A retrospective review of a consecutive series of 931 previously untreated patients with differentiated thyroid carcinoma treated over a 50-year period was undertaken to analyze prognostic factors. Data pertaining to demographic status, clinical, operative, and pathologic findings, and survival were analyzed. Univariate statistical analysis was performed based on the Kaplan-Meier method and the log-rank test. Multivariate analysis was performed to assess the independent effect of these variables using the Cox model. There were 630 female and 301 male patients, with an average age of 43 years. A total of 532 patients were younger than 45 years. Seven hundred thirty-one patients had either pure or mixed papillary carcinoma, and 200 had follicular carcinoma. In 153 patients, lesions were larger than 4 cm. Extrathyroidal extension was noted in 71 patients. Multifocal lesions were present in 159 patients. Regional lymph node metastasis was present on admission in 451 patients, and distant metastases were noted on presentation in 45 patients. Determinate survival for all patients was 87% at 10 years. Favorable prognostic factors using univariate analysis included female gender, multifocal primary tumors, and regional lymph node metastases. Adverse prognostic factors included age over 45 years, follicular histology, extrathyroidal extension, tumor size exceeding 4 cm, and the presence of distant metastases. On multivariate analysis, the only factors that affected the prognosis were patient age, histology, tumor size, extrathyroidal extension, and distant metastases. These observations support findings of reports from the Mayo Clinic and Lahey Clinic regarding the significance of prognostic factors for differentiated carcinoma of the thyroid gland.

Adenocarcinoma↗
PubMed1990

High-dose thiotepa alone and in combination regimens with bone marrow support.

Curative treatment regimens for leukemias, lymphomas, and testicular cancer have been based on laboratory observations of a clear relationship (generally linear-log) between increasing doses of chemotherapeutic agents and tumor cytotoxicity and on recognition of the need for combination chemotherapy to avoid the emergence of drug resistance. Chemotherapeutic agents have been selected for combinations based on cytotoxic activity, different mechanisms of action (to avoid cross-resistance), and different dose-limiting toxicities (to avoid additive toxicity). The ideal combinations use the highest tolerable doses of active non-cross-resistant agents to minimize the potential for drug resistance and achieve optimum cytotoxicity. Dose escalation is often limited by myelosuppression. Hematologic stem cell support from bone marrow or peripheral blood allows the administration of significantly higher doses of chemotherapy. In 1977, Thomas and colleagues in Seattle reported that 13 of 100 patients who underwent bone marrow transplantation for relapsed acute leukemia were disease-free 1 to 4.5 years later. Today, almost 50% of selected patients with acute myelogenous leukemia who undergo transplantation with human leukocyte antigen-matched sibling donor marrow during first remission are cured. Between 20% and 50% of lymphoma patients who undergo transplantation after failing conventional treatment have survived; those whose disease is responding to standard-dose therapy at the time of transplant have the best prognosis. Conditioning regimens that are sufficiently cytoreductive are not currently available for patients with solid tumors. The diversity of solid tumors makes it likely that a variety of regimens will be required. In a sequence of laboratory and clinical studies, we have constructed and evaluated a regimen comprising 6 g/m2 of cyclophosphamide, 500 mg/m2 of N,N',N''-triethylenethiophosphoramide (thiotepa), and 800 mg/m2 of carboplatin. The response rate in women with measurable breast cancer was 81%. While profound myelosuppression was noted, organ toxicity has been rare. This regimen, designed to exploit the principles of curative cancer chemotherapy, is associated with low morbidity and high cytoreductive efficacy. The regimen is currently being evaluated in a phase II trial in patients with previously untreated metastatic breast cancer who are responsive to conventional-dose chemotherapy. Of 29 patients entered in the study, only one has died of toxicity, confirming the low incidence of treatment-related toxicity associated with the regimen.

Adult↗
PubMed1989

A phase I clinical and pharmacokinetic study of carboplatin and autologous bone marrow support.

A series of 33 patients were treated with a four-day continuous infusion of carboplatin in a phase I study to determine the maximum-tolerated dose (MTD) of this agent when used with autologous bone marrow reinfusion. Doses were escalated from 375 to 2,400 mg/m2; autologous bone marrow reinfusion was added to the regimen at doses of 1,600 mg/m2 and above. The MTD was determined to be 2,000 mg/m2. Dose-limiting toxicity consisting of reversible hepatotoxicity, renal dysfunction, and moderate to severe ototoxicity was observed with a dose of 2,400 mg/m2. There were ten responses in 31 heavily pretreated patients, including six responses in 11 patients with recurrent ovarian cancer. Pharmacokinetic studies revealed a systemic clearance (Clss) of 4.5 L/m2/h. This value is consistent with clearances reported for carboplatin administered at lower doses and by different schedules. No evidence for saturation of systemic clearance at higher doses was observed. Carboplatin appears to be an active drug that can undergo considerable dose escalation when used in conjunction with autologous bone marrow support.

Adult↗
PubMed1987

The effect of age on the care of women with breast cancer in community hospitals.

We studied the process of care received by 1,680 female breast cancer patients treated in 17 community hospitals. The probability of receiving various diagnostic, consultation, therapy, or rehabilitation services was almost always significantly associated with patient age for one or more disease stages. Most often there was a linear trend for older patients to receive fewer services (e.g., biopsies prior to definitive treatment, number of lymph nodes examined, chemotherapy, radiation therapy) but other age patterns also were found. Age was not significantly associated with clinical staging or estrogen receptors.

Adult↗
PubMed1987

Human hypervariable sequences in risk assessment: rare Ha-ras alleles in cancer patients.

A variable tandem repeat (VTR) is responsible for the hyperallelism one kilobase 3' to the human c-Ha-ras-1 (Ha-ras) gene. Thirty-two distinct restriction fragments, comprising 3 allelic classes by frequency of occurrence, have thus far been detected in a sample size of approximately 800 caucasians. Rare Ha-ras alleles, 21 in all, are almost exclusively confined to the genomes of cancer patients (p less than 0.001). From our data we have computed the relative cancer risk associated with possession of a rare Ha-ras allele to be 27. To understand the molecular basis for this phenomenon, we have begun to clone Ha-ras fragments from nontumor DNA of cancer patients. We report here the weak activation, as detected by transfection and transformation of NIH 3T3 mouse cells, of two Ha-ras genes which were obtained from lymphocyte DNA of a melanoma patient. We have mapped the regions that confer this transforming activity to the fragment containing the VTR in one Ha-ras clone and the fragment containing gene coding sequences in the other.

Alleles↗
PubMed1987

Pharmacokinetics of continuous-infusion high-dose thiotepa.

The pharmacokinetics of thiotepa administered as a continuous infusion over 4 days have been studied in 18 patients receiving high-dose thiotepa, cyclophosphamide, and autologous bone marrow reinfusion as treatment for advanced neoplasms. Patients received cyclophosphamide at a total dose of 6 g/m2 and thiotepa at a total dose of 180-900 mg/m2 over the 4-day infusion. Samples of plasma were obtained during and following infusion, and the plasma concentration of thiotepa was determined by the method of Egorin et al. For many patients (72%), peak concentrations of plasma thiotepa were achieved during the initial 24 hours of infusion and then declined an average of 29% by the end of the 96-hour infusion. The average total systemic clearance of thiotepa was 16.7 +/- 7.4 (SD) L/m2/hour [or 420 +/- 162 (SD) ml/kg/hr]. An inverse correlation between the average total systemic clearance and the dose of thiotepa was observed (P less than 0.01).

Adult↗
PubMed1980

Prognostic effect of weight loss prior to chemotherapy in cancer patients. Eastern Cooperative Oncology Group.

The prognostic effect of weight loss prior to chemotherapy was analyzed using data from 3,047 patients enrolled in 12 chemotherapy protocols of the Eastern Cooperative Oncology Group. The frequency of weight loss ranged from 31 percent for favorable non-Hodgkin's lymphoma to 87 percent in gastric cancer. Median survival was significantly shorter in nine protocols for the patients with weight loss compared to the patients with no weight loss. Chemotherapy response rates were lower in the patients with weight loss, but only in patients with breast cancer was this difference significant. Decreasing weight was correlated with decreasing performance status except for patients with pancreatic and gastric cancer. Within performance status categories, weight loss was associated with decreased median survival. The frequency of weight loss increased with increasing number of anatomic sites involved with metastases, but within categories of anatomic involvement, weight loss was associated with decreased median survival. These observations emphasize the prognostic effect of weight loss, especially in patients with a favorable performance status or a limited anatomic involvement with tumor.

Activities of Daily Living↗