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J Jett

Publications and source records attributed to J Jett.

10 recordsLinked to original sources
PubMed1998

Bcl-2 immunohistochemistry in a surgical series of non-small cell lung cancer patients.

The bcl-2 gene is implicated in oncogenesis by its ability to prolong cell survival through the inhibition of apoptosis, without increasing cell proliferation. An association between immunohistochemical staining for bcl-2 protein and the histological type and prognosis of non-small cell carcinoma was hypothesized by Pezzella et al. (N Engl J Med 329:690-694, 1993). In a case series, we stained formalin-fixed, paraffin-embedded tumor tissue from 106 surgical non-small cell lung cancer patients with an antibody to bcl-2 protein (DAKO clone 124, Carpinteria, CA). The resulting bcl-2 staining data were evaluated for associations with demographic, histological, immunohistochemical, and genetic features, including p53 mutations. Bcl-2 staining was observed in tumors from 29 of 106 (27%) of subjects, but was significantly less frequent in subjects' adenocarcinoma histology (8 of 55, 14.6%) (P = .007). This finding persisted after adjustment for age, gender, stage, grade, smoking history, and disease-free survival. In univariate analyses, no association was seen with age, weight, body mass index, gender, or pack-years smoking; tumor grade, stage, or patient performance status; p53 or c-erbB2 immunohistochemical staining, or p53 mutations. These data agree with earlier reports that bcl-2 staining is less common in adenocarcinomas; however, our data do not support the hypothesis that bcl-2 staining confers a better prognosis overall, in squamous cell carcinoma, or in an older patient population.

Adenocarcinoma↗
PubMed1998

Considerations in optimizing radiation therapy for non-small cell lung cancer.

Irradiation therapy for lung cancer is mostly restricted to conventional methods. To improve therapeutic ratio, we have combined a treatment planning and a gene therapy approach. Three-dimensional conformal radiotherapy is described as carried out by methods of gene therapy for radiation protection using the manganese-superoxide-dismutase transgene delivered by inhalation gene transfer. These methods may improve therapeutic outcomes in lung cancer.

Animals↗
PubMed1996

p53 mutations and occupational exposures in a surgical series of lung cancers.

p53 mutations are frequent in malignant lung tumors. Of 88 surgically treated lung cancers from cigarette smokers previously evaluated for p53 mutations, 45 tumors (51.1%) had mutations in exons 5-8 (D. G. Guinee, Jr. et al., Carcinogenesis (Lond.), 16: 993-1002, 1995). We report here the examination of 13 occupational exposures and 13 high-risk occupations in relation to these p53 mutations. Two molecular abnormalities were associated with occupational exposures: (a) G:C-->T:A transversions on the coding (nontranscribed) strand (n = 13) were associated with chromate exposure and employment in the metal industry (P < 0.05) and marginally associated with nickel exposure (P = 0.056); and (b) G:C-->A:T transitions at non-CpG sites (n = 9) were associated with work in the petrochemical industry (P = 0.05). No association was found between p53 mutations and gender, cigarette pack-years, tumor histology, age at diagnosis, or family history of lung cancer. Because all three chromate-exposed subjects had large cell carcinomas exhibiting G: C-->T:A coding-strand transversions, follow-up of a cohort with this exposure should clarify the association with the p53 gene.

Adult↗
PubMed1996

Chemoradiotherapy in non-small cell lung cancer: paclitaxel/carboplatin/radiotherapy in regionally advanced disease.

Based on superior results observed with combined-modality therapy over radiotherapy alone and on the authors' previous work with carboplatin and standard daily thoracic radiotherapy in patients with advanced, unresectable non-small cell lung cancer, a phase II study was designed to incorporate radiosensitizing doses of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) into the carboplatin/radiotherapy regimen, to improve the therapeutic index and define the toxicities. Thirty-two patients have been entered. Paclitaxel 45 mg/m2/wk was administered over 3 hours prior to carboplatin (100 mg/m2/wk) and thoracic radiotherapy (1.8 Gy/d 5 days a week; total dose, 60 to 65 Gy). No grade 4 toxicities occurred. Seven patients had chemotherapy doses delayed because of grade 3 neutropenia, and one patient had grade 3 mucositis/esophagitis that required hospitalization. Median survival has not yet been reached, and all patients are being followed. These preliminary data demonstrate the feasibility of combined concurrent chemoradiotherapy, with acceptable toxicities. Further investigation is needed to optimize carboplatin dosage with adaptive control using formulas based on pharmacokinetics and pharmacodynamics. Full-dose induction chemotherapy regimens to maximize the systemic effects of chemotherapy should precede concurrent chemoradiotherapy in future studies.

Adult↗
PubMed1995

Gender comparisons in human lung cancer: analysis of p53 mutations, anti-p53 serum antibodies and C-erbB-2 expression.

Little is known about the molecular mechanisms of lung carcinogenesis in women. We initiated an investigation of the role of gender in pulmonary carcinogenesis by analysis of p53 mutations, immunohistochemistry, serum antibodies and c-erbB-2 expression in a series of 63 male and 44 female lung cancer patients whose tumors were resected at the Mayo Clinic between 1991 and 1992. There were 102 smokers and 5 never smoked. Adenocarcinoma was the more frequent histological type in women (62%) than in men (41%). Sequence analysis of exons 5-8 in 42 females and 49 males identified 44 p53 mutations in 42 tumors (46%). Base substitution mutations showed a preponderance of G:C-->T:A transversions, which were more frequent in women than men (40 versus 25%) and in individuals exposed to asbestos. c-erbB-2 immunohistochemical staining was identified more frequently in females (nine cases) than males (two cases). Marked immunohistochemical staining for p53 positively correlated with the presence of missense mutations in exons 5-8 (81%, P < 0.001). Seven missense mutations (four in exon 5, two in exon 6, one in exon 8) were identified in five of nine patients who had serum antibodies recognizing p53; tumors from these patients were also strongly positive for p53 by immunohistochemistry. These and other results indicate gender differences in the genetic and biochemical alterations in lung cancer and generate hypothesis regarding gender differences in lung cancer susceptibility.

Adenocarcinoma↗
PubMed1976

Study of in vivo tumor state and response to therapy by analysis of DNA distribution.

The growth characteristics of an in vivo tumor model were studied. This tumor offers an intermediate system useful for the study of tumor cells in the intact animal, but does not have the complexities of solid tumors. DNA distribution was correlated with macromolecular DNA synthesis. Mechlorethamine, BCNU, radiation, and hydroxyurea were studied and produced perturbation in stationary phase-cell kinetics. There was a redistribution of cell ages consistent with induced cycling activity with most, but not all, of the above agents. This indicated a recruitment from a stationary phase by cancer therapeutic agents, although subsequent cell-cycle traverse may also be greatly perturbed. A number of considerations important to the interpretation of this type of data are discussed.

Animals↗