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Biomedical subjects

D M Ota

Publications and source records attributed to D M Ota.

At least 91 records · Page 5Linked to original sources
PubMed1985

Effect of difluoromethylornithine on host and tumor polyamine metabolism during total parenteral nutrition.

Clinical and experimental data suggest that erythrocyte (RBC) polyamine (PA) levels are markers of tumor proliferation during total parenteral nutrition (TPN). The purpose of this experiment was to determine whether the inhibition of PA synthesis during TPN was greater in tumors than in normal host tissue. Rats bearing a subcutaneous fibrosarcoma were randomized to receive a chow diet (n = 5), TPN (n = 5), or TPN + difluoromethylornithine (DFMO) (an irreversible inhibitor of ornithine decarboxylase (ODC), at 1000 mg/kg body wt/day n = 4) for 6 days by continuous central venous infusion. TPN + DFMO resulted in a higher plasma albumin level and lower tumor ODC activity compared with chow feeding or TPN. Liver ODC activity was similar for the chow fed, TPN, and TPN + DFMO groups. RBC putrescine, tumor putrescine, and tumor spermidine levels were significantly lower in the TPN + DFMO group compared with the chow fed and TPN groups. RBC spermidine, RBC spermine, and tumor spermine levels were significantly increased with TPN + DFMO compared with TPN alone. DFMO did not produce diarrhea or weight loss. Increased RBC spermidine may indicate a toxic effect of DFMO on the tumor, resulting in leakage of tumor spermidine into the extracellular space. The data suggest that DFMO during TPN can selectively inhibit tumor PA synthesis and may improve host utilization of nutrients.

Animals↗
PubMed1985

Growth kinetics of human colorectal carcinoma.

In this study, we investigated the influence of some of the variables of the thymidine labeling index (TLI) in human colorectal carcinoma. These variables were: cell suspensions versus tissue fragments; incubation with 5-fluoro-2'-deoxyuridine; method of tissue procurement; location in the large bowel; and TLI distribution in different areas of the tumor. Mean TLI values for cell suspensions and tissue fragments were 3.4 (range, 0.1 to 7) and 1 (0.1 to 2.6), respectively. Incubation with 5-fluoro-2'-deoxyuridine significantly reduced tritiated thymidine incorporation. There were no differences in TLI values between biopsy and surgical samples and in different areas of the large intestine. Median TLI of cell suspensions in 47 tumors was 2.25 (0.1 to 10.1). These results show that the TLI of colorectal carcinoma is low and correlates with its slow growth. Cell suspension provides a more representative and unbiased sample than tissue fragments in cell kinetics studies.

Adenocarcinoma↗
PubMed1984

Nutritional parameters affecting erythrocyte polyamine levels in cancer patients.

Changes in erythrocyte polyamine levels during intravenous hyperalimentation in cancer and noncancer patients were determined, and the influence of host nutritional status on polyamine metabolism was analyzed. RBC putrescine (P less than .001), spermidine (P less than .01), and spermine (P less than .005) levels, and the putrescine-spermidine ratio (P less than .001) increased in the cancer group while no significant increases were noted in the noncancer group. The degree of malnutrition, based on body weight loss and plasma albumin, transferrin, prealbumin, and retinol-binding protein levels, was significantly greater in the cancer group than in the noncancer group, giving rise to the possibility that repletion of nutritional deficits in host tissues could have contributed to the rise in RBC polyamines. When cancer patients of similar nutritional status were matched with the noncancer group, increases in RBC putrescine level and putrescine-spermidine ratio were noted in the selected cancer patients. These results suggest that correction of nutritional deficits did not contribute significantly to the RBC polyamine pool and that increases in RBC polyamines during intravenous hyperalimentation were related to the presence of tumor.

Adult↗
PubMed1983

Modification of polycarbonate cages for individual housing of mice.

Polycarbonate cages were modified with clear plastic dividers so that up to four mice could be housed individually in one cage with ad libitum access to feed and water. The method used commercially available components and was applicable for use in any study when it was necessary to keep mice separate for an extended period of time.

Animal Husbandry↗
PubMed1979

Nutrition, cancer, and intravenous hyperalimentation.

In over 1000 cancer patients treated with intravenous hyperalimentation (IVH), tumor growth has not been identified and catheter-related sepsis has been minimal. Studies in rats demonstrated that the host benefits more than the tumor during nutritional repletion, and any stimulation of tumor growth in the rat-tumor model could be manipulated with DNA specific drugs to benefit the host. A study of 65 malnourished cancer patients undergoing oncologic therapy and treated with IVH indicated that much of the immune suppression in these patients was the result of malnutrition coincident with or secondary to oncologic treatment. Conclusions reached in this study were that nutritional repletion resulted in a return of skin test reactivity, proper wound healing in the surgical patient, and possibly an increase in response to chemotherapy. Certainly, the use of IVH allowed specific oncologic therapy to be administered to a group of malnourished patients who otherwise might not have been acceptable candidates for intensive antineoplastic therapy.

Animals↗
PubMed1979

The effects of nutrition and treatment of cancer on host immunocompetence.

Conventional approaches to therapy for cancer, such as chemotherapy, operative therapy and radiation therapy, can produce profound changes in host immunity. The effects of chemotherapy upon immune responses are related both to the dosage and duration of therapy and are readily reversible. Operative therapy likewise suppresses both humoral and cell-mediated immunity for two to three weeks, as manifested by in vitro and in vivo tests of these functions. Radiation therapy, however, seems to decrease host immune responses for more prolonged periods of time, up to ten years. Nutritional status may also affect both limbs of the immune system, and malnutrition is being recognized with increasing frequency as a clinical problem in patients with advanced primary malignant or metastatic disease, especially during antineoplastic therapy. Intravenous hyperalimentation is a safe and effective method for correcting nutritional deficits in patients with cancer; moreover, immunocompetence may be enhanced during adequate nutritional rehabilitation.

Animals↗
PubMed1978

The effects of a 10% soybean oil emulsion on lymphocyte transformation.

Free essential fatty acids (EFA) are reported to suppress cell-mediated immunity. Because Intralipid contains a high concentration of esterified EFA, the effects of this emulsion on in vitro lymphocyte transformation were studied. Intralipid concentrations of 11.5, 115, and 230 mg% in lymphocyte cultures increased phytohemagglutinin (PHA) stimulation by an average of 8.2% (not significant [NS]), 18.1% (p < 0.01), and 11.8% (NS), respectively. These same concentrations also increased Varidase stimulation in lymphocyte cultures by an average of 11.3 (p < 0.02), 18.9 (p < 0.02), and 4.4% (NS), respectively. Control wells did not demonstrate allergic reactions to Intralipid. These data demonstrate that Intralipid can significantly increase the mitogenic response of human thymic lymphocytes and the antigenic response of human lymphocytes, in vitro.

Antigens↗
PubMedDate not supplied

Potentially resectable gastric carcinoma: current approaches to staging and preoperative therapy.

The incidence of gastric carcinoma has declined worldwide during the past several decades, and yet this cancer remains the most common malignancy in several countries around the world, particularly Japan, Chile, and Costa Rica. Gastric carcinoma, although not as common in the United States as it was in the past, is still the eighth most frequent cause of cancer death. For patients with localized gastric carcinoma, surgery remains the most effective therapy, resulting in a consistent but low rate of cure. Unresectable gastric carcinoma is an incurable disease with the exception of a small fraction of patients who are salvaged with chemoradiotherapy. In Western countries curative resection rates have been dismal because of the lack of early diagnosis. Additionally, postoperative adjuvant strategies in the United States and Europe have been ineffective. Even patients with curative resection frequently develop intraperitoneal and systemic carcinoma in addition to locoregional relapses. Many investigators have therefore embarked on the therapeutic strategies of preoperative chemotherapy and postoperative intraperitoneal chemotherapy. The preoperative chemotherapy strategy has particular appeal because of its potential to reduce the size of the primary tumor, thereby allowing a higher rate of curative resection; early systemic therapy of micrometastases might prove biologically more effective. To date, several studies using preoperative chemotherapy have demonstrated its feasibility. The effectiveness of repeated courses of postoperative intraperitoneal chemotherapy remains unsettled mainly owing to the inadequacy of peritoneal drug distribution and the associated toxic effects. Additional investigations are necessary to improve preoperative staging with the use of endoscopic ultrasonography and laparoscopy (peritoneal staging).(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Agents↗
PubMedDate not supplied

Metastatic behavior and cell surface properties of HT-29 human colon carcinoma variant cells selected for their differential expression of sialyl-dimeric Le(x)-antigen.

Immunochemical studies of human colorectal carcinoma with various monoclonal antibodies against Le(X)-related carbohydrate antigens previously revealed that the amount of sialyl-dimeric Le(X) antigen (NeuAc alpha 2-3Gal beta 1-4(Fuc alpha 1-3)GlcNAc beta 1-3Gal beta 1-4(Fuc alpha 1-3)GlcNAc beta 1-R: SLX) associated with metastatic lesions was greater than in the primary tumors. To assess whether an experimental model can be used to study the direct relationship between this carbohydrate antigen and the tumor cell's metastatic behavior, we selected variant cells with increased surface SLX from established human colon carcinoma cell line HT-29. The cells in the upper 5% or lower 5% population in fluorescence intensity after reacting with a monoclonal antibody, FH6, were retrieved separately by a fluorescence-activated cell sorter and propagated. After three- or four-times selection, we obtained stable cell lines with low and high cell surface SLX antigens (HT-29 M1 and HT-29 M2, respectively). Binding of monoclonal antibody FH6 was detected to glycolipids extracted from HT-29 M2 cells but not from HT-29 M1 cells. Glycoprotein components having reactivity with monoclonal antibody FH6 were below the detectable level. HT-29 M2 cells injected intrasplenically into nude mice showed a slightly reduced incidence of metastasis to lung, liver and lymph nodes than did HT-29 M1 cells. Subsequently we found that SLX antigen was not detectable by immunohistochemical examination of these tumor cells grown in nude mice. Re-established cell line from nude mice xenografts expressed SLX antigen in vitro.

Animals↗
PubMedDate not supplied

Immune function during intravenous administration of a soybean oil emulsion.

The effect of a continuous infusion of a soybean oil emulsion on immune function was evaluated in 40 malnourished patients who were randomized to receive preoperatively either a 25% glucose-5% amino acid solution (group G) or a 15% glucose-3.3% Intralipid-5% amino acid solution (group G-F). Average length of total parenteral nutrition (TPN) was 10.3 +/- 0.9 days for group G and 9.0 +/- 0.8 days for group G-F. Initial nutritional status and response to TPN were similar for both groups. Immune function was assessed before TPN and after nutritional repletion prior to surgery for each patient. The levels of immunoglobulins, C3, C4, circulating B lymphocytes and T lymphocytes, suppressor T lymphocytes, natural killer cell activity, and monocytes were normal before TPN and after nutritional therapy. However, the total number of T cells and helper T cells were low before TPN and remained so after TPN. In addition, lymphocyte function measured by the lymphocyte blastogenic response to phytohemagglutinin and pokeweed mitogen was depressed prior to TPN and was not improved by either regimen. Neutrophil chemotaxis and bactericidal activity were not affected by either nutritional regimen while neutrophil phagocytosis was enhanced before TPN and remained elevated throughout TPN with either regimen. There were no differences in infection rates during TPN. The addition of Intralipid to the TPN regimen did not alter immune function in these patients who showed depressed cell-mediated immunity before TPN compared with the standard glucose TPN regimen.

B-Lymphocytes↗
PubMedDate not supplied

Influence of total parenteral nutrition on tumor growth and polyamine biosynthesis of fibrosarcoma-bearing rats after induced cachexia.

The effect of a protein-free diet (PF) or a restricted intake of chow (RI) and subsequent host repletion with total parenteral nutrition (PF-TPN, RI-TPN) on tumor growth and polyamine metabolism of fibrosarcoma-bearing rats was examined. Host weight was significantly reduced by PF and RI. Tumor growth was reduced in malnourished rats with the PF regimen resulting in the greatest decrease. Rats receiving TPN after 14 days of the RI or PF regimens had higher host weight and plasma albumin levels than malnourished rats. Tumor growth during TPN was evaluated as the percent increase and compared with that of the respective malnourished rats. The percent increase for RI-TPN rats was significantly greater although a trend toward an increase was also evident for PF-TPN rats. Tumor ornithine decarboxylase (ODC) activity and putrescine levels were increased for PF rats and decreased for RI rats while tumor ODC activity was consistently increased by TPN. Tumor growth, ODC activity, and putrescine levels were simultaneously increased only for those rats fed the RI regimen prior to TPN. These results show a disparity in tumor ODC activity, putrescine levels, and tumor growth in malnourished rats. The results of this study suggest that the nutritional origin of cachexia influences the response of the tumor to TPN and emphasizes the importance of considering the methods to induce malnutrition in designing therapuetic regimens.

Animals↗