Search PubMed⌕ Search

Biomedical subjects

J A Califano

Publications and source records attributed to J A Califano.

At least 19 recordsLinked to original sources
PubMed2000

Two distinct regions of loss on chromosome arm 4q in primary head and neck squamous cell carcinoma.

OBJECTIVE: To more clearly define the frequency and the regions of chromosome arm 4q loss in head and neck squamous cell carcinoma. DESIGN: A retrospective microsatellite analysis of DNA from previously microdissected primary tumor samples. SETTING: Academic medical center. PATIENTS AND METHODS: One hundred primary tumor samples from patients with head and neck squamous cell carcinoma were analyzed for loss of heterozygosity on the long arm of chromosome 4. The Kaplan-Meier method was used to estimate survival for 97 patients for whom clinical data were available. The Cox proportional hazards model was used to compare survival, and logistic regression was used to search for associations between clinical tumor characteristics and 4q status. RESULTS: Analysis of 33 polymorphic microsatellite markers identified 51 samples (51%) exhibiting loss of heterozygosity of 4q in at least 1 locus. Eighteen tumors revealed loss at all informative markers, indicating monosomy or complete deletion of 4q. Thirty-three tumors displayed partial loss of heterozygosity and delineated 2 minimal areas of loss at 4q2324 and 4q2829. Eleven tumors displayed loss solely at the 4q2324 region, 13 tumors displayed deletions confined to the 4q2829 region, and 9 tumors displayed selective loss at both regions. A separate analysis in a subset of 94 primary head and neck tumors was done to further delineate the minimal area of chromosomal loss at 4q2324. Analysis of 8 markers in this region allowed us to identify the smallest region of loss between markers D4S2986 and D4S1564 (a distance of 2 centimorgans). Review of the clinical records of 97 patients revealed no statistically significant association between 4q status and any clinical variable, including survival. CONCLUSION: These results confirm a high frequency of chromosome arm 4q loss in primary head and neck squamous cell carcinoma and might demarcate 2 novel putative suppressor loci involved in progression of this carcinoma.

Adult↗
PubMed1997

Comparison of oncogene mutation detection and telomerase activity for the molecular staging of non-small cell lung cancer.

Novel oncogene mutation detection techniques have demonstrated that standard histopathological examination may fail to detect clinically significant metastatic cancer cells. Recently, telomerase activity has been detected in most immortal cell lines and human tumors, potentially providing a novel diagnostic marker. We compared standard histopathological examination with the telomeric repeat amplification protocol assay and either a p53 plaque hybridization or a K-ras mutation ligation assay in the lymph nodes of 12 patents with surgically resectable non-small cell lung cancer. Telomerase activity was detected in 10 of 10 (100%) evaluable tumors. Eight of 9 (89%) histopathologically positive lymph nodes were telomerase positive, and 26 of 48 (54%) histopathologically negative lymph nodes were telomerase positive. In comparison, oligonucleotide plaque hybridization detected metastases in all 3 histopathologically positive nodes and in 3 of 27 histopathologically negative nodes. Similarly, the K-ras mutation ligation assay detected metastases in all 6 histopathologically positive lymph nodes examined and in 1 of 21 histopathologically negative lymph nodes. Thus, most of the "positive" nodes by telomerase assay did not harbor occult neoplastic cells that shared the same genetic alteration as the primary tumor. The high rate of false positives associated with the telomeric repeat amplification protocol assay limits its role in staging lymph nodes in patients with non-small cell lung cancer.

Adult↗
PubMed1996

An allelotype of papillary thyroid cancer.

Although papillary carcinoma accounts for approximately 70% of all thyroid cancers, preliminary studies of allelic loss have thus far not identified any areas of chromosomal deletion. We evaluated 30 papillary thyroid carcinomas for chromosomal loss/allelic imbalance by testing at least 2 microsatellite markers from every autosomal arm. Fifteen of the 30 tumors tested exhibited loss of heterozygosity/allelic imbalance (LOH/AI) at one or more loci. Chromosomal arms with frequent LOH/AI included 4q, 5p, 7p and 11p. An average of 1.1 chromosomal arms displayed LOH/AI in each individual tumor. Therefore, 4q, 5p, 7p and, to a lesser extent, 11p display significant LOH/AI in papillary thyroid cancer, which indicates the presence of putative tumor-suppressor gene loci at these chromosomal arms.

Alleles↗
PubMed1996

Allelotype of salivary gland tumors.

To elucidate the genetic alterations that occur in salivary gland tumors, we screened every autosomal arm (and the X-chromosome) of 29 primary human salivary gland neoplasms (11 pleomorphic adenomas, 10 adenoid cystic carcinomas, 5 mucopidermoid carcinomas, and 3 carcinomas ex-mixed tumors) for allelic loss using 86 microsatellite markers. A minimum of two microsatellite markers were used per chromosomal arm to achieve informativity of at least 60% (excluding X). The pleomorphic adenomas demonstrated few areas of allelic loss; the most prominent chromosomal arm involved was 12q, lost in more than 35% of informative cases. The most significant allelic losses in adenoid cystic carcinoma were 1p, 2p, 6q, 17p, and 20p (>20% of informative cases) and 19q (40% of informative cases). Mucoepidermoid carcinoma showed 50% or greater loss at 2q, 5p, 12p, and 16q. Although losses at 9p, 3p, and 17p are common in squamous cell carcinoma of the head and neck, only the carcinoma ex-mixed tumors demonstrated loss at these loci, consistent with progression to a more aggressive phenotype. Salivary gland tumors display allelic loss patterns different from many other tumor types, suggesting distinct genetic pathways in the progression of these tumors.

Alleles↗
PubMed1995

Estimating the costs of substance abuse to the Medicaid hospital care program.

OBJECTIVES: The purpose of this study was to develop a model, using the epidemiologic tool of attributable risk, for estimating the cost of substance abuse to Medicaid. METHODS: Based on prior substance-use and morbidity research, population attributable risks for substance abuse-related diseases were calculated. (These risks measure the proportion of total disease cases attributable to smoking, drinking, and drug use.) The risks for each disease were applied to Medicaid hospital discharges and days on the 1991 National Hospital Discharge Survey that had these diseases as primary diagnoses. The cost of these substance abuse-related days were added to Medicaid hospital costs for direct treatment of substance abuse. RESULTS: More than 60 medical conditions involving 1100 diagnoses were identified, at least in part, as attributable to substance abuse. Factoring these substance abuse-related conditions into hospital costs, 1 out of 5 Medicaid hospital days, or 4 million days, were spent on substance abuse-related care in 1991. In 1994, this would account for almost $8 billion in Medicaid expenditures. CONCLUSIONS: The use of tobacco, alcohol, and drugs contributes significantly to hospital costs. To address rising costs, substance abuse treatment and prevention should be an integral part of any health care reform effort.

Alcoholism↗
PubMed1993

Joseph A. Califano Jr. A former HEW secretary looks at health care reform. Interview by Terese Hudson.

Joseph A. Califano Jr. was secretary of Health, Education and Welfare in the Carter administration and is now president of the Center on Addiction and Substance Abuse at Columbia University, an independent not-for-profit research center. He also serves as an adjunct professor of public health at Columbia University. Califano has written eight books, including America's Health Care Revolution: Who Lives? Who Dies? Who Pays?, published in 1986. He will speak at the American Society for Healthcare Marketing and Public Relations 15th annual meeting, Sept. 11-14 in San Francisco. He spoke recently with Senior Editor Terese Hudson about the possibilities and problems in the current move to reform health care.

Cost Control↗
PubMed1991

Tumor growth dependent on Kaposi's sarcoma-derived fibroblast growth factor inhibited by pentosan polysulfate.

A neoangiogenic response is critical for the unrestricted growth of solid tumors beyond a few millimeters in diameter. Release of adequate growth-stimulating activity from tumor cells is obviously required for the stimulation of blood vessel growth, and blockade of such stimulatory activity should repress tumor growth at the microscopic level. To test this hypothesis and to study appropriate inhibitors, we used a human adrenal cancer cell line (SW-13/K-fgf) engineered to secrete Kaposi's sarcoma-derived fibroblast growth factor (K-FGF), which we previously showed to induce growth of highly vascularized subcutaneous tumors in animals by autocrine and paracrine stimuli. In the present study, we tested different polysulfates for their selective inhibition of proliferation induced by K-FGF versus proliferation independent of K-FGF. Suramin and dextran sulfate showed slight selective inhibition of K-FGF-induced proliferation, ie, inhibition three- and five-fold greater, respectively, than the inhibition of proliferation independent of K-FGF. In contrast, heparin was inactive. The heparin analogue pentosan polysulfate (PPS), however, showed selective inhibition that was more than 2000-fold greater. The inhibitory effects of PPS on growth of SW-13/K-fgf cells, as well as endothelial cells, were fully reversible by an excess of added FGF. Daily intraperitoneal injections of PPS were tolerated well by athymic nude mice and prevented growth of subcutaneous SW-13/K-fgf tumor xenografts. PPS will be a useful tool to elucidate the effects of FGFs in vitro and in vivo and appears to be a prototype for the development of tumoricidal therapy based on targeting of growth factors.

Adrenal Gland Neoplasms↗
PubMed1989

The Chrysler experience, and forecasts.

Using his experience with Chrysler Motors as an example, the author tells how waste, inefficiency, and greed shaped a corporate health care system that, if it continued, could have blocked the corporation's recovery. An intense investigation of the use and abuse of this plan resulted in savings of about $100 million over an initial two-year period, with an additional $250 million savings projected over the following five years. In considering future changes in the country's health care system, he comments on the need for hospital cutbacks; reduction in unwarranted variations in medical practice; dissemination of necessary information to both individual and corporate purchasers of health care; increasing utilization of nurses in the medical arts; changes in the medical malpractice system; an increase in corporation case management systems; and competition among providers, which, by reducing costs, will most likely result in an efficient health care system for all people.

Cost Control↗