Search PubMed⌕ Search

Biomedical subjects

D M Ota

Publications and source records attributed to D M Ota.

At least 73 records · Page 4Linked to original sources
PubMed1988

Increased content of chondroitin sulfate proteoglycan in human colorectal carcinoma metastases compared with the primary tumor as determined by an anti-chondroitin-sulfate monoclonal antibody.

To determine if the amount of chondroitin sulfate proteoglycan (CSPG) in human colorectal tumor tissue correlates with the tumor's aggressiveness we immunochemically determined the CSPG levels in colorectal carcinomas at different stages. A total of 50 specimens--4 polyps, 15 stage B tumors, 9 stage C tumors, 12 stage D tumors, 7 liver metastases, and 3 lymph node metastases--were examined. Tumor tissues were extracted with 4 M guanidine hydrochloride containing protease inhibitors. The extracts were serially diluted and blotted onto nitrocellulose membranes. Reactivity of a chondroitin sulfate-specific mouse monoclonal antibody (CS-56) was determined by biotinylated goat antimouse Ig and avidin-biotin-peroxidase complex. After comparing tissues from tumors at different stages (classified by the presence or absence of metastasis), we could not find a positive or negative correlation between the amount of CSPG in primary colorectal carcinoma tissues and the tumor's metastatic potential. However, the metastatic foci in the liver or lymph node contained higher amounts of CSPG than the primary tumors did. Immunohistochemical staining of colon carcinoma tissue with CS-56 revealed that CSPG is predominantly localized in fibrotic portions in the tumor tissues. Two-year follow-up studies indicated that a high level of CSPG in primary tumors was not predictive of recurrence.

Adenocarcinoma↗
PubMed1988

Electrophoretic analysis of four high molecular weight sialoglycoproteins produced by metastatic human colon carcinoma cells.

We have found that polyacrylamide gel electrophoresis in 3% gels in the presence of sodium dodecyl sulfate is suitable for the separation of cellular glycoproteins having molecular weights ranging from 200,000 to 1,000,000. The gels secured on a rigid support (Gelbond) allow blotting techniques with lectins and antibodies for the detection of glycoproteins. Using these methods we have separated lysates of HT-29 human colon carcinoma cells and detected at least four distinct high molecular weight sialoglycoproteins having molecular weights of 900,000, 740,000, 560,000, and 450,000. The expression of the 900,000 component, as revealed by wheat germ agglutinin binding, was much higher in a subline of HT-29 cells established from liver metastases in a nude mouse than it was in the parental cells. The relative intensity of wheat germ agglutinin binding to these four sialoglycoprotein components differs depending upon their growth phase in vitro. These glycoproteins were also detectable by the binding of peanut agglutinin, provided the glycoproteins were previously treated in the gels with mild acid to remove the sialic acid from their carbohydrate chains, suggesting that mucin-type carbohydrate chains are present on these glycoproteins. The same set of glycoproteins can be detected by metabolic labeling of the cells with [3H]glucosamine in tissue culture. Very similar glycoprotein profiles are revealed by metabolic labeling of fresh colon carcinoma tissues with [3H]glucosamine in vitro.

Adenocarcinoma↗
PubMed1987

Bioavailability of estradiol as a marker for breast cancer risk assessment.

The search for a hormonal marker in breast cancer has centered on estrogens and their metabolites. However, direct measurements of total amounts of these steroids have shown no convincing or consistent differences between normal women and women with breast cancer. The purpose of this study was to measure the percentages of non-protein-bound estradiol (%NPBE) and of estradiol bound to albumin (%ABE) and the levels of sex hormone-binding globulin (SHBG) both in women with breast cancer and in those free of disease. Serum was collected and analyzed within 2 weeks, using an isodialysis method. The mean %NPBE and %ABE were significantly higher in 32 women with breast cancer (1.73 and 64.0%, respectively) than in 32 matched disease-free women (1.43 and 48.6%, respectively) (P less than 0.001). No significant difference was observed in the levels of plasma albumin when the above matched groups were compared. However, plasma levels of SHBG were significantly lower in the women with breast cancer than in either the control population or matched controls. In this finding we differ from previous studies which reported no significant differences in the mean plasma levels of SHBG. In our study, the increased %NPBE and %ABE in some patients with breast cancer may be related to a lower level of plasma SHBG; other factors, too, may affect the distribution of estradiol. Our results support the hypothesis than an increase in %NPBE and %ABE or both may indicate an increased risk of breast cancer.

Adult↗
PubMed1987

The relationship of collagenolytic activity to stage of human colorectal carcinoma.

Collagenolytic enzymes produced by tumor cells are believed to play a significant role in the destruction of surrounding normal tissue and, in certain experimental animal systems, the ability of tumor cells to degrade type-IV collagen (basement membrane collagen) correlates positively with those cells' metastatic capacity. We measured collagenolytic activity levels of extracts from freshly excised colorectal carcinoma tissues and of conditioned media from primary organ culture (total of 114 tissues from 53 patients) by using purified radiolabelled type-I (rat tail) and type-IV (mouse Engelbreth-Holm-Swarm [EHS] sarcoma) collagens. Both type-IV and type-I collagenolytic activity levels of extracts from tumor and adjacent mucosa ranged from less than 1 to 80 ng/hr/mg wet tissue, and no significant differences between mucosa and carcinoma tissues were observed. In conditioned media, the type-IV collagenolytic activity was low for normal mucosa and benign tumors and slightly higher for carcinoma than for mucosa. In 5 of 32 primary tumors, collagenolytic activity levels were 2-5 times higher than in the rest of the tumors and mucosal tissues. There were no significant differences in collagenolytic activity levels of conditioned media and tissue extract from colorectal carcinoma of different Dukes' stages. Deep and superficial areas of primary tumors released similar type-IV collagenolytic activity levels, suggesting that there was little intratumoral heterogeneity in the release of this enzyme.

Collagen↗
PubMed1987

Differential production of high molecular weight sulfated glycoproteins in normal colonic mucosa, primary colon carcinoma, and metastases.

Sulfated macromolecules synthesized in tumor and mucosa tissues derived from colorectal cancer patients were labeled with [35S]sulfate and separated into two fractions on DEAE-Sephacel: the slightly acidic peak (peak I) was eluted with 0.2 M NaCl and the highly acidic peak (peak II) was eluted with 0.5 M NaCl. A total of 40 specimens, which included primary colon cancer, liver metastases, and normal mucosa obtained at surgery (16 patients), were examined regarding the amount of peak I and peak II. The amount of peak I significantly decreased in the order of normal mucosa greater than primary tumors greater than metastases, while the amount of peak II did not significantly change among the tissues. Peak I was mostly resistant to chondroitinase ABC and nitrous acid treatment under acidic conditions, whereas combined chondroitinase-sensitive materials and nitrous acid-sensitive materials were greater than 80% of the radioactivity in peak II. The major radioactive component of peak I migrated at a position corresponding to Mr greater than 300,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and became Mr less than 40,000 after alkaline borohydride treatment. The major component of peak I was likely to be a sulfated glycoprotein containing sulfate groups on alkaline labile carbohydrate chains. Peak II consisted of a mixture of heparan sulfate proteoglycans and chondroitin sulfate proteoglycans. Differential incorporation of [35S]sulfate into peak I among normal mucosa, primary colon carcinoma, and colon carcinoma metastasis was observed. Therefore, decreased peak I production may be a biochemical change associated with colorectal cancer progression and metastasis.

Chromatography, Ion Exchange↗
PubMed1987

Effect of intravenous alpha-difluoromethylornithine on the polyamine levels of normal tissue and a transplantable fibrosarcoma.

The effect of a continuous i.v. infusion of alpha-difluoromethylornithine (DFMO) on the polyamine metabolism of tumor and normal host tissue was determined. Non-tumor-bearing Fischer 344 rats or rats bearing a transplantable fibrosarcoma received continuous infusions of DFMO through a central venous catheter at three dose levels. Treatment with DFMO resulted in a time- and dose-dependent, cytostatic effect on the growth of the tumor. In fibrosarcoma-bearing rats the tumor putrescine levels were reduced after 6 and 12 days of DFMO treatment. Tumor spermidine levels were consistently reduced after 6 and 12 days of treatment with the reduction being dose dependent. The decrease in tumor ornithine decarboxylase activity was dose dependent. Erythrocyte putrescine levels were decreased in tumor- and non-tumor-bearing rats, suggesting that DFMO reduces the tumor contribution to the erythrocyte pool. Erythrocyte spermidine levels of fibrosarcoma- and non-tumor-bearing rats were elevated at the lower DFMO doses administered for 12 days but returned to normal as the dose was increased. Erythrocyte spermine levels were elevated in both groups of rats at all DFMO doses. Although normal host tissue weights were not affected by treatment with DFMO, the putrescine and spermidine levels of liver, spleen, and kidney and ornithine decarboxylase activity of the liver and kidney were decreased. These data demonstrate that i.v. DFMO has a cytostatic effect toward a rapidly growing fibrosarcoma associated with the depletion of both tumor putrescine and spermidine levels.

Animals↗
PubMed1987

Ulex europeus agglutinin I-reactive high molecular weight glycoproteins of adenocarcinoma of distal colon and rectum and their possible relationship with metastatic potential.

A Ulex europeus agglutinin I (UEAI)-reactive glycoprotein(s) with molecular weight higher than 300,000 was detected by direct binding of 125I-labeled UEAI to lysates of rectal or sigmoid colon cancer tissues separated by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. This was the major UEAI-reactive molecule in tumor tissues and different tumors possessed varying reactivities. Very little UEAI binding was detected to lower molecular weight components. Histochemical localization of UEAI confirmed that the UEAI-reactive molecules were mostly localized to the surface of carcinoma cells. A total of 135 fresh tissue samples, including those from adenocarcinoma, villous adenoma, and normal mucosa in surgical specimens (69 patients), were examined to determine the reactivities of UEAI to the high molecular weight component in the tissue extracts. The quantitative binding of 125I-UEAI was compared according to the stage of colorectal cancer at the time of surgery. The relative amount of UEAI-reactive high molecular weight substance was significantly higher in the carcinomas than in normal mucosa. UEAI binding to high molecular weight regions of the polyacrylamide gel was significantly lower in primary colorectal adenocarcinomas from stage C or D patients than in those from stage B1 patients. Therefore, increased expression of the UEAI-reactive molecule was related to transformation of colorectal epithelial cells and decreased expression appeared to be associated with progression and metastatic potential.

Adenocarcinoma↗
PubMed1987

Polyamine metabolism in carcinoma of the oral cavity compared with adjacent and normal oral mucosa.

In this study, polyamine biosynthesis required for cellular proliferation showed elevated levels in neoplastic cells. Putrescine, spermidine, and spermine, as well as the rate-limiting enzyme ornithine decarboxylase, were measured to evaluate differences in tissue concentration in squamous cell carcinoma of the oral cavity, and in the normal adjacent, buccal, and retromolar trigone tissues. Mean polyamine levels (nanomoles per gram of tissue +/- standard error of the mean) were significantly elevated in tumor tissue at 136 +/- 42 nmol/g for putrescine compared with 41 +/- 9 nmol/g in adjacent, 25 +/- 5 nmol/g in buccal, and 41 +/- 14 nmol/g in retromolar trigone tissues. Tumor spermidine was 415 +/- 41 nmol/g compared with 192 +/- 34 nmol/g in adjacent, 184 +/- 34 nmol/g in buccal, and 214 +/- 63 nmol/g in retromolar trigone tissues. Tumor spermine was 461 +/- 41 nmol/g compared with 236 +/- 30 nmol/g in adjacent, 233 +/- 35 nmol/g in buccal, and 269 +/- 59 nmol/g in retromolar trigone samples. Ornithine decarboxylase activity was highly variable in tumor tissues. High levels of polyamines appear to be specific for this malignancy, whereas ornithine decarboxylase activity is not. Measurement of polyamine content may be useful in evaluating epithelial changes in the oral cavity.

Carcinoma, Squamous Cell↗
PubMed1986

Red blood cell polyamine levels and host toxicity during continuous alpha-difluoromethylornithine infusion.

The dose effects of continuous alpha-difluoromethylornithine (DFMO) infusion on red blood cell (RBC) polyamine levels, host toxicity and tumor growth were determined. Male rats with and without a transplantable methylcholanthrene-induced sarcoma received intravenously either 0.45% NaCl or DFMO at 500 mg, 1,000 mg, or 2,000 mg/kg body wt/day for 6 or 12 days. Dose-related inhibition of tumor growth was noted after the 12-day treatment. There were no changes in host carcass weight, food intake, plasma albumin, hematocrit or white blood cell counts. Platelet suppression was associated with the 1,000- and 2,000-mg doses with the 12-day treatment. Morphometry of the small intestine revealed mild but significant shortening of villi in the duodenum and jejunum at the 2,000-mg dose, but none of the animals developed diarrhea. The 500-mg DFMO dose reduced the rate of tumor growth without inducing platelet suppression or altering intestinal morphology. A decrease in RBC putrescine levels was noted at all doses. RBC spermidine levels increased with the 500-mg dose. RBC spermine levels were higher at all doses compared with controls. These results suggest that thrombocytopenia is the major dose-limiting side-effect of continuous DFMO infusion but does not occur at a dose of 500 mg/kg body wt/day.

Animals↗
PubMed1986

Obesity, non-protein-bound estradiol levels, and distribution of estradiol in the sera of breast cancer patients.

This study attempted to determine the relationship of nutritional status, menopausal status, presence of breast cancer, stage of disease, and tumor estrogen receptor levels to percent non-protein-bound estradiol (%NPBE) and percent distribution of estradiol on sex hormone-binding globulin (SHBG) and albumin in breast cancer patients and control patients. Normal-weight controls had significantly lower %NPBE compared with overweight controls and normal-weight and overweight breast cancer patients. There was a significant shift in the percent distribution of estradiol from SHBG to albumin in breast cancer patients, independent of body weight. Elevated %NPBE and abnormal percent estradiol distribution on albumin persisted after mastectomy and were unrelated to menopausal status, presence and stage of disease, and tumor estrogen receptor levels. These results show that breast cancer patients have increased exposure to unbound circulating estradiol and an increased percentage of estradiol bound to albumin, which may influence the availability of estradiol, considering its low binding affinity to albumin. Because these abnormalities persist after mastectomy, the current results may be important in developing dietary intervention protocols that correct %NPBE and abnormal estradiol distribution on binding proteins.

Adult↗
PubMed1986

Active specific immunotherapy of Dukes B2 and C colorectal carcinoma: comparison of two doses of the vaccine.

The ability of active specific immunotherapy to enhance immune responses to autologous tumor-associated antigens (TAA) and to prolong the disease-free interval was evaluated in patients with Dukes B2 and C colorectal carcinoma who had undergone potentially curative resections. Patients were sensitized in the early postoperative period with irradiated autologous adenocarcinoma cells mixed with bacillus Calmette-Guérin (BCG) to yield either a low-dose vaccine (3 X 10(6) tumor cells) or a high-dose vaccine (1 X 10(7) tumor cells). Six of seven patients who received the low-dose vaccine developed delayed-type hypersensitivity (DTH) responses to autologous tumor cells upon completion of the vaccination, whereas all four patients receiving high-dose vaccine displayed a positive DTH response. However, DTH responses to autologous TAA waned within 3 months in all patients receiving the low-dose vaccine; DTH responses persisted for 3 months in three of the four high-dose vaccine patients. In vitro lymphoproliferative responses to TAA correlated with DTH responses to autologous tumor cells. Active specific immunotherapy appeared to induce specific immune responses either in vitro or in vivo to autologous TAA because it did not induce responses to autologous mucosa cells. There were no complications caused by BCG or tumor cells. This series demonstrates that active specific immunotherapy is a nontoxic treatment that augments immunity to autologous TAA.

Adult↗
PubMed1986

Erythrocyte polyamine levels during intravenous feeding of patients with colorectal carcinoma.

Changes in erythrocyte (RBC) polyamines were studied during total parenteral nutrition (TPN) in 16 colorectal carcinoma patients and six patients with noncancerous diseases. RBC putrescine (PTC), spermidine (SPD), and spermine (SPM) were analyzed before and at the completion of preoperative TPN in each patient. Before TPN, nutritional status, based on a history of weight loss and plasma albumin, prealbumin and retinol-binding protein levels, were similar for the two groups. Initial RBC PTC, SPD, and SPM levels were also similar for both groups. Preoperative TPN induced significant increases in RBC PTC levels (P less than 0.001) and RBC PTC:SPD ratios (P less than 0.005) of the cancer patients while no significant polyamine changes were observed in the other group. Host response to nutritional therapy was monitored with plasma prealbumin and retinol-binding protein levels which did not change significantly in either group.

Colonic Neoplasms↗
PubMed1986

Relationship of erythrocyte polyamine levels and growth rate of transplantable tumors in rats.

Varying levels of polyamines in the urine, plasma, and erythrocytes (RBC) of cancer patients have been demonstrated. The growth rate of the tumor has been suggested as a primary factor which determines whether the polyamine levels in urine are elevated. To further evaluate tumor size and growth rate as variables affecting polyamine levels in physiological fluids, the effect of a transplantable fibrosarcoma and colon tumor on the RBC polyamine levels of Fischer 344 rats was determined. The tumors were implanted s.c. and grew without metastasis or spontaneous regression. The fibrosarcoma grew exponentially up to a weight of approximately 69 +/- 15 (SD) g and was associated with a linear increase in RBC polyamine levels compared with that of non-tumor-bearing rats. RBC putrescine, spermidine, and spermine levels were significantly elevated at tumor weights of 12.5 +/- 1.4, 20.4 +/- 3.8, and 33.2 +/- 5.0 g, respectively. The respective polyamines increased consistently thereafter until the tumor weight was 57.8 +/- 5.8 g. In contrast with the fibrosarcoma, the colon tumor grew exponentially only to a weight of 9.2 +/- 4.7 g, at which time the growth rate of the tumor began to decrease (time T of the Gompertz model). RBC polyamine levels of rats with the colon tumor showed only a transient increase. RBC putrescine levels were significantly increased at a tumor weight of 12.9 +/- 1.2 g and spermidine at a tumor weight of 17.4 +/- 0.2 g. RBC spermine levels were significantly elevated at both tumor weights; thereafter, all RBC polyamine levels returned to normal. Host cachexia was evident when the fibrosarcoma and colon tumors weighed 12.5 +/- 0.9 and 7.2 +/- 2.6 g, respectively. The polyamine levels of the fibrosarcoma differed significantly from that of the colon tumor. These levels, however, did not correlate with the exponential growth rates. The results suggest that the tumor is the major source of elevated RBC polyamines. The data also suggest that the tumors must be rapidly growing for the elevation in polyamines to occur. This may partly explain why patients with extensive neoplastic disease that may have surpassed time T in the Gompertz model do not manifest abnormal polyamine levels.

Animals↗
PubMed1985

Plasma proteins as indices of response to nutritional therapy in cancer patients.

The use of plasma albumin (ALB), transferrin (TFN), prealbumin (TBPA), retinol-binding protein (RBP), triceps skin fold (TSF), and midarm muscle circumference (MAMC) as determinants of response to nutritional therapy (TPN) was investigated in 40 cancer patients during preoperative TPN. Thirty-one patients received 90% or more of their anabolic caloric requirement (Harris-Benedict equation) by means of TPN. During this study period (average 11.1 +/- 4.7 days) nutritional assessments were completed before TPN and on the last day of TPN before surgery. Average weight loss based on usual body wt (UBW) and ideal body wt (IBW) was 19 +/- 11% and 9 +/- 15%, respectively (not significant, NS). Weight loss (UBW) correlated with ALB (P less than 0.001), TBPA (P less than 0.005) and RBP (P less than 0.02) but did not correlate with TFN (P less than 0.06), TSF, and MAMC. Weight loss (IBW) correlated with TSF (P less than 0.01) and MAMC (P less than 0.03) but did not correlate with plasma protein (PP). During TPN the average percent increases for PP were 0.1% (ALB, NS), 20% (TFN, NS), 60% (TBPA, P less than 0.02), and 116% (RBP, P less than 0.005). These results suggest that plasma TBPA and RBP are significant parameters of response to short-term nutritional therapy in cancer patients.

Adult↗
PubMed1985

A surgical oncology perspective on AIDS.

During the summer of 1981 reports of unusual opportunistic infections among male homosexuals first began to appear in the literature and by December 1983, 3000 cases has been reported to the Center for Disease Control in Atlanta, Georgia. Homosexual and bisexual men comprise 71% of the reported cases, while 17% are known intravenous drug users, and the remaining 12% made up of persons with other risk factors. Approximately 80% of AIDS patients with Kaposi's sarcoma have identifiable gastrointestinal lesions. Specific risk factors for Kaposi's sarcoma in AIDS patients have not been exclusively identified, but it is thought that repeated sexual involvement with multiple partners exposes the victim to the immunosuppressive effect of cytomegalovirus and allogenic sperm, which may in turn impair lymphoid cells. The immunological abnormalities associated with AIDS have included striking changes in T-cell ratios, with more profound changes in the Kaposi-AIDS groups. Increases in IgG, decreased antibody production by B-cells to challenge antigen, decreased B-cell proliferative responses to B-cell mitogens, abnormalities in macrophage function, and increased serum thymosin levels have been found. Various opportunistic infections afflict the patient with AIDS. Antimicrobial therapy, various interferons, interleukin-2, and immunomodulation with thymosin have all been used without much success. The distribution and transmission of AIDS parallels hepatitis B virus infection which is transmitted sexually and parenterally. On the whole the same precautions as for hepatitis B should be taken for AIDS. Health care personnel treating patients with AIDS should also wear masks and eye protection against the splatter of body fluids and secretions.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗