ABSTRACT
Many resected patients with locally advanced head and neck cancer are found on pathological assessment to have high-risk features for recurrence. We thus performed a feasibility trial of post-operative radiotherapy with paclitaxel and carboplatin in high-risk carcinoma of the head and neck. All patients were planned for 6 cycles of weekly paclitaxel (40 mg/m2) and carboplatin (AUC=1) and concomitant radiotherapy, 60 Gy in 6 weeks. The most common side effect was grade 3 and 4 mucositis in 5/6 patients and g-tube placement in 4/6 patients. Five out of 6 patients remain alive without evidence of disease at a mean time of 19 months since completion of therapy. Our pilot study treated 6 postoperative patients. Since 4 of 6 enrolled patients were unable to complete the treatment as prescribed, we conclude that this regimen is not feasible. With an 83% grade 3 or 4 mucositis rate and 67% of patients enrolled requiring feeding tube placement, this regimen is not tolerable.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/therapy , Head and Neck Neoplasms/pathology , Head and Neck Neoplasms/therapy , Neoplasm Recurrence, Local/prevention & control , Adult , Aged , Carboplatin/therapeutic use , Carcinoma, Squamous Cell/mortality , Chemotherapy, Adjuvant , Combined Modality Therapy , Female , Head and Neck Neoplasms/mortality , Humans , Male , Middle Aged , Neoplasm Staging , Paclitaxel/therapeutic use , Pilot Projects , Postoperative Care , Prognosis , Radiotherapy Dosage , Radiotherapy, Adjuvant , Risk Assessment , Survival Analysis , Treatment OutcomeABSTRACT
UNLABELLED: Ascorbic acid can be important in sickle cell anemia (SCA) because significant oxidative stress occurs in the disease. Ascorbate could contribute to reduction of the increased oxygen free radicals generated in sickle red blood cells (SRBC) and to the recycling of vitamin E in the cells, while renal loss could contribute to the low plasma levels. Evaluation of red blood cell (RBC) and urine ascorbate in SCA has not been reported. Results showed (1) ascorbate levels in SRBC were similar to those in normals; (2) urine ascorbate excretion was increased in 36% of patients; (3) plasma levels of ascorbate were decreased. CONCLUSIONS: (1) Ascorbate is present in SRBC, most likely due to ascorbate recycling, despite increased free-radical generation. (2) The increase in renal excretion may contribute to the low plasma levels of ascorbate. (3) The presence of ample ascorbate in SRBC and decreased plasma ascorbate suggests that ascorbate movement across the SRBC membrane may differ from normal RBC.
Subject(s)
Anemia, Sickle Cell/blood , Anemia, Sickle Cell/urine , Ascorbic Acid/blood , Ascorbic Acid/urine , Adult , Erythrocytes/chemistry , Humans , Matched-Pair Analysis , Middle Aged , Osmolar Concentration , Sodium/urineABSTRACT
The integrins are a supergene family of cell surface glycoproteins that promote cellular adhesion. Each member of the family is an alpha/beta heterodimer composed of a distinct alpha subunit noncovalently linked to one of at least six common beta subunits. These include the six beta 1 integrins (alpha 1-6/beta 1) which represent receptors for extracellular matrix proteins and the three beta 2 integrins (alpha L, alpha M, alpha X/beta 2) that are expressed by leukocytes and which bind to C3bi and/or endothelial ligands. Recently, it was reported that certain human tumor cells express the beta 1 integrins and that small cell lung cancer (SCLC) cell lines express the beta 2 integrin Mo1 (alpha M/beta 2). To extend these initial observations, we examined SCLC cell lines for integrin expression at the glycoprotein and mRNA levels and assessed the potential function of these integrins in promoting SCLC adhesion. An indirect immunofluorescence analysis of five SCLC cell lines (NCI-H187, H345, H146, H209, and N417) using alpha and beta subunit-specific monoclonal antibodies demonstrated the uniform expression of beta 1 (beta 1 much greater than beta 2 greater than or equal to beta 3 congruent to beta 4). Among the beta 1-associated alpha subunits, alpha 3 was uniformly expressed at high surface density by all five cell lines (as confirmed in H345 cells by sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of anti-beta 1 and anti-alpha 3 immunoprecipitates), while alpha 5 was not detected. The leukocyte (beta 2-associated) alpha M and alpha L subunits were also variably expressed by the five lines. Consistent with the surface expression of beta 1 integrin gene products, beta 1 (but not beta 2) mRNA was detected in SCLC cells by Northern blot analysis. That beta 1 integrin expression was involved in SCLC adhesion was suggested by the adherence of H345 cells to laminin, a known ligand for the alpha 3 beta 1 integrin. Moreover, an antibody specific for the beta 1 subunit inhibited this adhesion, indicating that the beta 1 subunit promotes adhesion to laminin. We conclude that beta 1 integrin molecules are expressed by human SCLC cells (with uniform expression of alpha 3/beta 1) and promote their adhesion to laminin.
Subject(s)
Carcinoma, Small Cell/metabolism , Integrins/metabolism , Lung Neoplasms/metabolism , Antibodies, Monoclonal , Blotting, Northern , Cell Adhesion/drug effects , Electrophoresis, Polyacrylamide Gel , Flow Cytometry , Gene Expression , Humans , Integrins/biosynthesis , Integrins/genetics , Laminin/metabolism , Precipitin Tests , RNA/analysis , Tumor Cells, CulturedABSTRACT
The action of starch, saccharose, lactose and glucose in the atherogenic rations containing a physiological (5 per cent) or an elevated (21 per cent of the ration's mass) amount of fat on the lipids metabolism and complex carbohydrates, as well as on the morphological structures in the aorta and coronary vessels was studied. It is found that of all the carbohydrates studied the most marked metabolic disorders are produced by rations with saccharose and lactose. Morphological changes in the vessels were in evidence only in rats fed on rations with lactose or saccharose and with an elevated proportion of fat.