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Biomedical subjects

S Graziano

Publications and source records attributed to S Graziano.

25 records · Page 2Linked to original sources
PubMed1990

Integrating technology assessment and medical practice evaluation into hospital operations.

The Johns Hopkins Program for Medical Technology and Practice Assessment, established in 1986, assesses the clinical efficacy, safety, and cost of specific technologies; evaluates the costs and benefits of alternative approaches to management of clinical problems; and examines the clinical and economic impact of health care program innovations. For example, program faculty have conducted analyses of clinical economic, and health policy issues related to radiographic contrast media. The director of the program chairs a committee that formulates guidelines for the appropriate use of low-osmolality contrast media and that will develop a mechanism to ensure compliance with guidelines. Program faculty are currently studying variations in the pre-, intra-, and postoperative management of patients with cataract and the relationship between such variations and outcomes. Faculty are also attempting to develop an improved mechanism for paying health maintenance organizations that enroll Medicare beneficiaries. Program activities have had a direct impact on decision making within the Johns Hopkins Health System.

Baltimore↗
PubMed1990

Mechlorethamine, vincristine, and procarbazine chemotherapy for recurrent high-grade glioma in adults: a phase II study.

We undertook a phase II study of combination chemotherapy with mechlorethamine (nitrogen mustard) 6 mg/m2 intravenously day 1 and day 8, vincristine 2 mg intravenously day 1 and day 8, and procarbazine 100 mg/m2 orally days 1 through 14 (MOP) in adults with recurrent high-grade glioma. There were 31 patients entered and 27 patients assessable for response. The median age was 49 years old. All patients had prior maximal radiotherapy, and eight had previous chemotherapy. Responses were determined based on clinical and computed tomographic (CT) scan/magnetic resonance imaging (MRI) criteria. The response rate (partial response [PR] plus objective qualitative response [OQR] plus complete response [CR]) was 52% with one CR. The response rate was higher in patients with anaplastic astrocytoma as compared with glioblastoma multiforme (P less than .05). The median duration of response was 42 weeks. Median survival for all assessable patients was 30 weeks, and for responders, it was 60 weeks. Response was correlated with ability to decrease dexamethasone doses and improved performance status. Toxicity was mainly hematologic with leukopenia being common. There was one treatment-related death from listeria meningitis, and two patients developed Pneumocystis carinii pneumonia. There were three episodes of neutropenic fever. We conclude that MOP is active and merits further investigation in adult high-grade glioma.

Adult↗
PubMed1989

Cooperation of c-raf-1 and c-myc protooncogenes in the neoplastic transformation of simian virus 40 large tumor antigen-immortalized human bronchial epithelial cells.

Overexpression of c-raf-1 and the myc family of protooncogenes is primarily associated with small cell carcinoma, which accounts for approximately 25% of human lung cancer. To determine the functional significance of the c-raf-1 and/or c-myc gene expression in lung carcinogenesis and to delineate the relationship between protooncogene expression and tumor phenotype, we introduced both protooncogenes, alone or in combination, into human bronchial epithelial cells. Two retroviral recombinants, pZip-raf and pZip-myc, containing the complete coding sequences of the human c-raf-1 and murine c-myc genes, respectively, were constructed and transfected into simian virus 40 large tumor antigen-immortalized bronchial epithelial cells (BEAS-2B); this was followed by selection for G418 resistance. BEAS-2B cells expressing both the transfected c-raf-1 and c-myc sequences formed large cell carcinomas in athymic nude mice with a latency of 4-21 weeks, whereas either pZip-raf- or pZip-myc-transfected cells were nontumorigenic after 12 months. Cell lines established from tumors (designated RMT) revealed the presence of the cotransfected c-raf-1 and c-myc sequences and expressed morphological, chromosomal, and isoenzyme markers, which identified BEAS-2B cells as the progenitor line of the tumors. A significant increase in the mRNA levels of neuron-specific enolase was detected in BEAS-2B cells containing both the c-raf-1 and c-myc genes and derived tumor cell lines. The data demonstrate that the concomitant expression of the c-raf and c-myc protooncogenes causes neoplastic transformation of human bronchial epithelial cells resulting in large cell carcinomas with certain neuroendocrine markers. The presented model system should be useful in studies of molecular events involved in multistage lung carcinogenesis.

Animals↗
PubMed1988

Phase II trial of 4'-deoxydoxorubicin (DxDx) in non-small cell lung cancer: a Cancer and Leukemia Group B Trial.

Eighty-seven patients with histologically or cytologically proven non-small-cell carcinoma of the lung were treated with 4'-deoxydoxorubicin (DxDx) 30 mg/m2 every 3 weeks. Three responses (4%), all partial, were observed. All responses occurred in patients with large-cell anaplastic lung cancer and none in squamous or adenocarcinoma histologies (P less than 0.01). The durations of partial response for these three responders were 70, 198+ and 209+ days. The side effects noted were predominantly neutropenia, anemia, and weight loss. In three patients, declines in cardiac ejection fraction of 7%, 12%, and 23% occurred after cumulative drug doses of 150 mg/m2, 150 mg/m2, and 233 mg/m2, respectively. 4'-Deoxydoxorubicin had little activity in non-small-cell lung cancer at the dose used in this study.

Carcinoma, Non-Small-Cell Lung↗
PubMed1987

Molecular analysis of the short arm of chromosome 3 in small-cell and non-small-cell carcinoma of the lung.

Previous studies have suggested that the loss of DNA sequences on the short arm of chromosome 3 (3p) is associated with small-cell lung carcinoma. We therefore looked for loss of 3p alleles in tumor tissue from 42 patients with either small-cell or non-small-cell lung carcinoma. All 13 patients with small-cell lung carcinoma who were heterozygous for one or more alleles at 3p in normal tissue had the loss of at least one codominant allele in the tumor tissue. Cell lines of small-cell lung carcinoma from an additional eight patients were homozygous for 3p alleles; this result was significantly different from the predicted frequency of homozygosity. The tumor tissue studied included cell lines of small-cell lung carcinoma obtained from biopsy specimens, an autopsy sample, and an excised lymph node containing tumor cells. Loss of alleles at 3p was observed in tumor samples obtained before and after chemotherapy. Four of 15 evaluable patients with non-small-cell carcinoma of the lung had loss of 3p alleles. We conclude that loss of alleles at 3p is a change found consistently in small-cell lung carcinoma and occasionally in non-small-cell lung carcinoma.

Alleles↗
PubMed1987

Carboplatin or iproplatin in advanced non-small cell lung cancer: a Cancer and Leukemia Group B Study.

The effect of the cisplatin analogs carboplatin (CBDCA) or iproplatin (CHIP) was evaluated in patients with extensive non-small cell lung cancer. The randomized phase II design was used to achieve balance between patient groups and comparison of response rates was not a primary objective of the study. CBDCA (400 mg/m2 iv) or CHIP (270 mg/m2 iv) was administered every 4 weeks until relapse of disease. Overall, 11 of 70 patients (16%; 95% confidence interval: 7%-25%) responded to CBDCA and five of 71 patients (7%; 95% confidence interval: 1%-13%) responded to CHIP. There were two complete responses to CHIP and none to CBDCA. The most frequent severe or life-threatening toxic effects were thrombocytopenia and leukopenia. Median survival for patients receiving CBDCA was 6.5 months; for those on CHIP it was 5.0 months (P = 0.59). CBDCA is probably active in patients with non-small cell lung cancer whereas CHIP has limited activity. Further evaluation of CBDCA as part of combination chemotherapy for non-small cell lung cancer is warranted.

Adult↗