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Biomedical subjects

K Sawai

Publications and source records attributed to K Sawai.

At least 73 records · Page 4Linked to original sources
PubMed1997

Prevention of peritoneal metastasis of cancer with dextran sulfate--an experimental study in mice.

Peritoneal metastases occur most often in the greater omentum, where tumor implantation sites are densely distributed. We used dextran sulfate (S-Dex) as an anti-cell-adherence agent to prevent i.p. seeded malignant cells from causing peritoneal metastases. S-Dex was tested for its anti-adherent activity against B-16 melanoma cells on plastic, and was examined for its ability to prevent implantation in the omentum and to improve survival in mice after B-16 melanoma was inoculated i.p. S-Dex prevented B-16 melanoma cells from adhering to the plastic wall. S-Dex reduced the number of B-16 melanoma cells implanted into the greater omentum and improved the survival of mice inoculated with B-16 melanoma cells. We conclude that S-Dex attenuated peritoneal metastases when B-16 melanoma cells were seeded i.p.

Animals↗
PubMed1997

Chronologic changes in the clinicopathologic findings and survival of gastric cancer patients.

PURPOSE: To determine the chronologic changes in the clinicopathologic features of gastric cancer patients. PATIENTS AND METHODS: The clinicopathologic findings of 1,795 patients with gastric cancer were examined retrospectively from hospital records obtained between 1969 and 1995. The patients were divided into three generations on the basis of chronologic order. The first generation included patients treated over the period 1969 to 1977; the second generation, 1978 to 1986; and the third generation, 1987 to 1995. RESULTS: The chronologic changes in the clinicopathologic findings for all gastric cancers included increases in the superficial type based on macroscopic appearance (P < .005), small-sized tumor (P < .025), superficial depth of invasion (P < .005), and earlier histologic stages (P < .005), in addition to a decrease in lymph node metastasis (P < .005). Overall, the postoperative survival rate has improved over time in gastric cancer patients, with 5-year survival rates of 36.0%, 53.3%, and 68.6% in the first, second, and third generations, respectively. In stages 1,2, and 3, the survival rate in the third generation was the highest of the three generations, whereas in stage 4, the survival rate did not differ between the three generations. Patients who underwent a D2 dissection showed a higher survival rate than those with D1 or D3 dissections, but there was no statistical difference in the survival of patients with D1, D2, and D3 dissections when stage 4 patients were excluded. CONCLUSION: The chronologic changes in gastric cancer patients over the past 27 years have included an increase in the incidence of earlier-staged gastric cancers, which has had a significant impact on the improved postoperative survival rate.

Adult↗
PubMed1997

Chorioamnionitis reduces placental endocrine functions: the role of bacterial lipopolysaccharide and superoxide anion.

Chorioamnionitis has been shown to be one of the most important factors in inducing preterm delivery. The present study was undertaken to examine the effects of chorioamnionitis on placental endocrine functions. Preterm placentas with histologic chorioamnionitis produced smaller amounts of human chorionic gonadotropin (hCG) and human placental lactogen (hPL) than those without chorioamnionitis (P < 0.001). To examine the mechanism involved in the suppression of placental endocrine functions induced by chorioamnionitis, we initially confirmed the expression of lipopolysaccharide (LPS) receptor, i.e. the CD14 molecule, on trophoblasts by Northern blot analysis and immunohistochemistry. We then stimulated purified trophoblasts with LPS, which is the major agent which induces inflammatory responses in the host via the LPS receptor. The trophoblasts stimulated with LPS produced reduced amounts of hCG, hPL, and progesterone in a time- and dose-dependent fashion in spite of the induced manganese-superoxide dismutase (SOD) synthesis. Stimulation of trophoblasts with hypoxanthine and xanthine oxidase resulted in suppressed hCG production, while the simultaneous addition of SOD into the culture medium reversed the suppression of hCG production. LPS in the placenta with chorioamnionitis might directly stimulate trophoblasts through the LPS receptor (CD14), thus reducing placental endocrine functions. Superoxide anions which exogenously act on trophoblasts might be generated by simultaneous stimulation of neutrophils and monocytes at the feto-maternal interface by LPS, and additively reduce placental endocrine functions.

Adult↗
PubMed1997

[Endoscopic local injection of anticancer drugs bound to carbon particles for treatment of upper digestive tract cancers--clinical trials].

A new dosage formulation consisting of anticancer drugs bound to carbon particles was developed for treating cancers of the upper digestive tract, and is designed to distribute higher levels of anticancer drug to the regional lymph nodes and at the injection site, as compared to a drug in aqueous solution form. Thirteen patients with histologically proven carcinoma (8 with superficial esophageal cancer and 5 with early or proper muscle layer-infiltrating gastric cancer), in whom surgical treatment was contraindicated, received intra- and peritumoral injection of the new dosage formulation (total dose of 35-100 mg of peplomycin or 250-500 mg of methotrexate) guided by esophago- or gastro-fiberscope. Eleven of these 13 patients are currently alive, 12-64 months after therapy, or they died without evidence of recurrence 12-98 months after the treatment. One patient has remained cancer-free for 37 months after a second course of the therapy given to treat a recurrence found 26 months after the first treatment. Another patient has a recurrent tumor 9 months after the therapy and is now going to undergo a second course of treatment. Side effects were not severe and well-tolerable.

Adenocarcinoma↗
PubMed1997

[Visualising lymph nodes by aclarubicin bound to activated carbon particles in breast cancer surgery].

A new dosage formulation (ACR-CH), composed of aclarubicin (ACR) bound to fine activated carbon particles, has been developed for the treatment of lymph node metastases in breast cancer. ACR-CH is designed to (a) adsorb a great amount of aclarubicin and desorb in a free state; (b) distribute a greater amount of ACR for a longer period of time selectively to the regional lymph nodes; (c) be decreased in the systemic toxicity; and (d) enhance its therapeutic effect on lymph node metastases. In this clinical trial in 20 patients with breast cancer, ACR-CH was injected intra- and peritumorally just before operation for breast cancer, and we examined the extent of blackened nodes produced by ACR-CH. ACR-CH blackened about 70% of the axillary lymph nodes with cancer metastasis as well as the nodes without metastasis. In conclusion, ACR-CH will be useful for dissection of lymph nodes by visualizing the nodes during operation for breast cancer.

Aclarubicin↗
PubMed1997

[Traditional remedy-induced Chinese herbs nephropathy showing rapid deterioration of renal function].

A 19-year-old female was referred to our hospital for azotemia and anemia. She had been taking a health food for atopic dermatitis for about three years. Urinalysis showed proteinuria, glycosuria and microscopic hematuria. Generalized aminoaciduria was observed. Moreover, severe anemia, azotemia, hypokalemia and hypophosphatemia were also observed. Renal biopsy specimen disclosed hypocellular interstitial fibrosis and degeneration of the proximal tubular epithelial cells. No remarkable changes were observed in the glomeruli. Aristolochic acid was detected in the health food. From these findings, she was diagnosed as having Chinese herbs nephropathy (CHN). Although consumption of the food intake was stopped, her renal function deteriorated rapidly. Previously, we reported that certain kinds of Chinese herbal drugs contain aristolochic acid and that the drugs should be prohibited if aristolochic acid is identified. However, we experienced a patient of CHN arising from traditional remedy, which was not proved to be safe. It should be awared that health foods may contain aristolochic acid.

Adult↗
PubMed1996

Methotrexate bound to carbon particles used for treating cancers with lymph node metastases in animal experiments and a clinical pilot study.

BACKGROUND: A new dosage formulation, methotrexate adsorbed onto activated carbon particles (MTX-CH), was developed for treating cancer patients with lymph node metastases. METHODS: MTX-CH injected subcutaneously into the left hind foot pad of rats delivered greater amounts of methotrexate selectively to the regional lymph nodes and to the injection site for longer periods than did the same dose of methotrexate in aqueous solution. Seven days after mice received a subcutaneous inoculation with 5 x 10(5) P388 leukemia cells in the left hind foot pad, when metastasis had occurred in the left popliteal lymph node, methotrexate was injected subcutaneously into the left hind foot pad in the form of either MTX-CH or methotrexate aqueous solution. In clinical trials, patients with cancers in relatively early stages (5 patients with gastric cancer and 1 with esophageal cancer) each received local injections of MTX-CH doses of 250 to 500 mg under fiberscope. RESULTS: MTX-CH extended the survival time better than did methotrexate aqueous solution. In mice who received an inoculation of P388 leukemia cells and drug treatment using the same procedures, the treatment effects on metastases to the regional lymph nodes were significantly greater in mice treated with the MTX-CH than in those given methotrexate aqueous solution. MTX-CH controlled the disease well for 25 to 35 months. CONCLUSIONS: Local injection of MTX-CH is apparently useful for treating digestive cancers with lymph node metastases in patients who have difficulty tolerating surgery.

Aged↗
PubMed1996

Overexpression of bax sensitizes human breast cancer MCF-7 cells to radiation-induced apoptosis.

Resistance to apoptosis plays an important role in tumors that are refractory to chemotherapy and ionizing radiation (IR). bax, which forms a heterodimer with bcl-2 and accelerates apoptosis, is not, or only weakly, expressed in most human breast cancer cells, and weak bax expression is considered to be related to the resistance of breast cancer cells to apoptosis. bax expression vector was introduced to human breast cancer MCF-7 cells, which exhibit weak expression of bax, to demonstrate its role of modulating radiation-induced apoptosis. bax overexpression in MCF-7 cells by stable transfection does not affect viability by itself, but each stable transfectant was more sensitive to IR than the parental MCF-7 cells. The degree of enhancement in radiosensitivity was dependent on the expression level of bax. IR upregulated p53 and p21WAF1 about 5- to 10-fold and downregulated bcl-2 and bcl-XL by 80-90% at 6 hr in both parent and bax stably transfected MCF-7 cells to the same degree. FACS analysis and DNA electrophoresis revealed that this sensitization was due to apoptosis. We suggest that exogenous bax expression might be one of the factors determining cellular radiosensitivity in MCF-7 breast cancer cells and may have therapeutic applications for enhancing radiation sensitivity in breast cancer cells.

Apoptosis↗
PubMed1996

Analysis of numerical aberrations of specific chromosomes by fluorescent in situ hybridization as a diagnostic tool in breast cancer.

BACKGROUND: Biopsy by fine-needle, aspiration has become a routine technique for the diagnosis of a dominant breast mass. In this study, fluorescent in situ, hybridization (FISH) analysis of interphase nuclei allowed the authors to detect genetic aberrations that are difficult to identify by conventional cytology. METHODS: To investigate ways of minimizing misdiagnosis of the cytology of breast tumors, and detecting genetic aberrations preoperatively, the authors performed FISH with specimens obtained by fine-needle aspiration biopsies of 106 primary breast tumors (78 primary breast cancers, 2 phyllodes tumors, and 26 benign breast tumors). Numerical chromosome aberrations were investigated using 3-color FISH performed with (peri)centromere-specific probes for chromosomes 1, 11, and 17. RESULTS: Sufficient materials for FISH analysis were obtained with aspiration biopsy from 98 of the 106 breast tumors (93.4%). None of the benign tumors nor phyllodes tumors showed evidence of aneusomy for any of the 3 chromosomes. However, 71 of the 74 breast cancers (95.9%) for which sufficient material was available demonstrated aneusomy of at least 1 of the 3 chromosomes tested. The FISH analysis also suggested a possible correlation between aneusomy of chromosome 17 and metastasis to regional lymph nodes (chi-square test = 7.78; P < 0.05). CONCLUSIONS: FISH analysis of fine-needle aspiration biopsies can be a practical and useful method for the preoperative diagnosis of breast carcinoma.

Biopsy, Needle↗
PubMed1996

Prognostic evaluation of preoperative combined treatment for advanced cancer in the lower rectum with radiation, intraluminal hyperthermia, and 5-fluorouracil suppository.

BACKGROUND: Since 1977, we have studied preoperative treatments using 5-fluorouracil (5-FU) suppositories alone or in combination with radiation to reduce local recurrence and improve survival of patients with rectal cancer. PATIENTS AND METHODS: We developed a novel preoperative therapy combining radiation, intraluminal hyperthermia, and 5-FU suppositories. Thirty-five patients with rectal cancer underwent surgery after this treatment, and 41 patients underwent surgery without pretreatment. RESULTS: The patients who underwent preoperative combination treatment showed significant tumor reduction; 2 achieved microscopically complete regression. In comparison with the patients who underwent surgery without pretreatment, the preoperative treatment group had a 16.7% lower local recurrence rate (10.4% versus 27.1%) and an improved survival rate (81.8% versus 67.6%). CONCLUSIONS: Preoperative combination therapy is a promising modality for the patients with respectable advanced cancer in the lower rectum.

Adult↗
PubMed1996

End results of simultaneous splenectomy in patients undergoing total gastrectomy for gastric carcinoma.

BACKGROUND: Splenectomy often is performed simultaneously with total gastrectomy for gastric carcinoma to facilitate dissection of splenic hilar lymph nodes. Splenectomy, however, should be avoided as frequently as possible because of its important role in the reticuloendothelial system and because of its sometimes severe complications. We evaluated the end results of simultaneous splenectomy with total gastrectomy. METHODS: The effect of splenectomy on survival was examined by retrospective analysis of 245 patients undergoing total gastrectomy for gastric carcinoma. Of these, 154 underwent splenectomy, and 91 did not. Prognostic factors for patients undergoing total gastrectomy were determined. The relationship to postoperative complications also was analyzed. RESULTS: No significant differences overall were found between the 5-year survival of the patients undergoing total gastrectomy with or without splenectomy. No correlation to any prognostic factor was seen with splenectomy. In contrast, splenectomy was independently associated with postoperative complications. CONCLUSIONS: In this retrospective study simultaneous splenectomy at total gastrectomy for gastric cancer did not have an effect on the survival rate of patients undergoing total gastrectomy, and it sometimes caused severe complications.

Female↗
PubMed1996

Clinicopathological characteristics of gastric cancer in the elderly.

The clinicopathological features of 380 elderly patients 70 years of age or older with gastric cancer were reviewed retrospectively from hospital records between 1969 and 1993. They were then compared with 1134 middle-aged patients between 40 and 69 years. The elderly constituted 18.4% of all gastric cancer patients 20 years ago but now comprise 24.4% of all patients in the most recent decade, despite the overall decrease in the rate of gastric cancer. The distinguishing histological features of gastric cancer in the elderly were an intestinal type of cancer, expansive tumour growth and synchronous multiplicity of the lesions. Elderly patients had a similar rate of tumour extension but had poorer survival as compared with the middle-aged patients. Post-operative death within 30 days after surgery was also higher in the elderly than in the middle-aged patients.

Adolescent↗
PubMed1996

Pharmacological effects of 5-fluorouracil microspheres on peritoneal carcinomatosis in animals.

A new delivery formulation (5FU-MS) of 5-fluorouracil (5FU), 5FU incorporated in microspheres composed of poly(glycolide-co-lactide) matrix, has been developed for the treatment of peritoneal carcinomatosis, and is designed to slowly release the incorporated 5FU for 3 weeks. Intraperitoneal 5FU-MS distributed higher concentrations of 5FU to the intraperitoneal tissues, such as the omentum and the mesentery, for a longer period with lower blood plasma concentrations than did the aqueous 5FU solution in rats. In experiments using mice, the lethal toxicity, determined by the probit method, in 5FU-MS was reduced to less than half that in aqueous 5FU solution. We evaluated the therapeutic effects on peritoneal carcinomatosis induced by the intraperitoneal inoculation of B-16 PC melanoma cells. The therapeutic effects of 5FU-MS were enhanced when compared with both the equivalent doses and same toxicity doses of the aqueous 5FU solution.

Animals↗
PubMed1996

New formulation of 5-fluorouracil in microspheres reduces toxicity in mice.

A new dosage formulation of 5-fluorouracil incorporated in microspheres (5-FU-MS) was developed for the treatment of peritoneal carcinomatosis. We studied the acute toxicity and side effects of i.p. 5-FU-MS in mice. The 50% lethal dose value for 5-FU-MS was 535.4 mg/kg of 5-FU, which was 2.22 times that of the aqueous 5-FU solution. Deaths occurred 12-17 days after the administration of 5-FU-MS, but within 11 days after the administration of aqueous 5-FU. Thus, lethal toxicity appeared later with 5-FU-MS than with aqueous 5-FU. There were no differences in pathologic findings on autopsy between mice given the two dosage formulations.

Animals↗
PubMed1996

Elevated nitric oxide concentration in the seminal plasma of infertile males: nitric oxide inhibits sperm motility.

PROBLEM: To evaluate the effect of nitric oxide in the seminal plasma on sperm motility. METHOD: Seminal plasma concentrations of NO2-, a stable end product of nitric oxide, of 108 males of infertile couples and 15 proven fertile donors were measured and compared with spermatogram parameters. Motile sperm was incubated with a nitric oxide-generating drug, sodium nitroprusside, for 6 hr in the absence or presence of oxyhemoglobin, an inhibitor of nitric oxide. RESULTS: The NO2- concentration in the seminal plasma was 6.58 +/- 0.5.6 microM in 26 infertile males with leukocytospermia, 5.51 +/- 0.25 microM in 82 infertile males without leukocytospermia, and 3.91 +/- 0.16 microM in 15 controls. There was a significant correlation between the NO2- concentration and sperm motility. Sodium nitroprusside reduced the sperm motility in a dose- and time-dependent manner and its reduction was completely inhibited by the addition of oxyhemoglobin. CONCLUSION: These findings indicate that nitric oxide concentration in the seminal plasma of infertile males is elevated and that nitric oxide is an inhibitor of sperm motion.

Cell Survival↗
PubMed1996

Maintenance of imprinting of the insulin-like growth factor II gene (IGF2) and the small nuclear ribonucleoprotein polypeptide N gene (SNRPN) in the human uterus and leiomyoma.

The insulin-like growth factor II gene (IGF2) is thought to be involved in the growth of uterine smooth muscle tumors. We studied the allele-specific expression of IGF2 in 20 patients with uterine leiomyomas by analyzing restriction fragment length polymorphisms (RFLP), because IGF2 is a maternally imprinted gene and only the paternal allele is exclusively expressed in human somatic tissue. We also studied the allelic expression of the small nuclear ribonucleoprotein polypeptide N gene (SNRPN), which is reportedly maternally imprinted in humans, and compared the imprinting status with that of IGF2. Nine patients (45%) were heterozygous at the ApaI site of IGF2, nine (45%) were heterozygous at the possible AccII polymorphic site of SNRPN, and three (15%) showed polymorphism in both genes. The genomic DNA of 15 patients showed heterozygosity in either or both of these genes, and the mRNA of these was expressed monoallelically in myometrial tissues and leiomyomas of these patients. These results demonstrated that IGF2 and SNRPN imprinting is completely maintained in human uteri and leiomyomas and that increased expression of IGF2 is not due to biallelic expression.

Autoantigens↗
PubMed1996

Rationale of lymph node dissection for breast cancer--from the viewpoint of analysis of axillary lymphatic flow using activated carbon particle CH40.

In order to rationalize lymph node dissection for breast cancer, we reviewed regional lymphatic flow from the mesial and outer half of the breast using intra-tumoral injection of activated carbon particles (CH40). Seventy patients with breast cancer were included in this study. Cancers were located in the mesial half of the breast in 25 cases and in its outer half in 41 cases. Since regional lymph nodes were blackened by CH40, lymph node dissection was performed easily and small lymph nodes could be readily examined. The average number of resected nodes in each case was 29.4. When CH40 was injected into the mesial half of the breast, the rates of blackened nodes (number of macroscopically blackened lymph nodes/number of total removed lymph nodes) in the stations were 46.6% (No. 1a), 41.4% (No. 1b), 62.1% (No. 1c), 61.8% (No. 2), 69.2.% (No. 2h), and 65.6% (No. 3). When CH40 was injected into outer half of the breast, those were 62.0% (No. 1a), 64.3% (No. 1b), 68.7% (No. 1c), 75.3% (No. 2), and 67.8% (No. 2h). Regardless of tumor location, the rates of blackened nodes were high in each station. In conclusion, regardless of tumor location it is impossible to determine the level of axillary dissection for breast cancer. It should be all or nothing.

Axilla↗