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Biomedical subjects

S Saji

Publications and source records attributed to S Saji.

At least 109 records · Page 6Linked to original sources

Transposition of the maize Ds element from a viral vector to the rice genome.

The geminivirus miscanthus streak virus (MiSV) was used as a gene vector to study the transposition of the maize Ds element in rice protoplasts. Efficient excision of the Ds from the MiSV vector was observed only when the MiSV vector was allowed to replicate and the plasmid expressing the transposase gene encoded by Ac was co-transfected. Under the same condition, the Ds carrying a hygromycin phosphotransferase gene (Ds::HPT) was also efficiently excised. Hygromycin-resistant calli were obtained by culturing these transfected protoplasts in order to examine the transposition of the excised Ds::HPT into the rice genome. In five out of 16 calli examined, the Ds::HPT, but not the vector sequence, was integrated into the rice genome and 8 bp target site duplication typical of Ac/Ds transposition was generated. These results show that the Ds::HPT inserted in the MiSV vector transposed directly into the rice genome. This demonstrates the direct transposition of a cloned plant transposable element into the plant genome. Implications of these finding are discussed.

Base Sequence↗

[Studies on adjuvant chemotherapy using subserosal or submucosal administration of neocarzinostatin for gastric cancer and colorectal cancer].

The significance and effectiveness of adjuvant intraoperative chemotherapy using subserosal or submucosal administration of Neocarzinostatin (NCS) and CH 40 for gastric cancer and colorectal cancer were studied. Tissue NCS concentration of proximal lymph nodes were higher than for distant lymph nodes, while the immunocompetency of distant lymph nodes (lower NCS concentration) showed slightly higher activity than that of proximal lymph nodes. From these results, it is suggested that loco-regional administration of NCS might be effective for chemical lymph node cleaning of the cancer.

Carbon↗

Spontaneous Ca2+ release from a caffeine and ryanodine-sensitive intracellular Ca2+ store in freshly prepared hepatocytes.

A considerable fraction of freshly prepared hepatocytes loaded with the fluorescent [Ca2+]i indicator fura-2 exhibited spontaneous rhythmic fluctuations that tended to decrease with increasing length of incubation after isolation. These oscillations were dependent on the external Ca2+. They could no longer be observed when a Ca2+ chelator-(ethylenebis [oxyethylenenitrilo]) tetraacetic acid--was added to medium. Addition of thapsigargin, which is known to release Ca2+ from inositol 1,4,5-trisphosphate-sensitive and -insensitive Ca2+ stores, induced a large transient increase in [Ca2+]i and abolished the fluctuations. When the cells were treated with 2 mmol/L caffeine, frequency was increased, whereas 10 mmol/L caffeine induced a single large peak followed by a persistent plateau. Moreover, addition of dibutyryl cAMP led to decreased frequency of fluctuations. Ryanodine caused larger fluctuations; thereafter the [Ca2+]i level became much higher and the spikes ceased. These results suggest that spontaneous rhythmic fluctuations in freshly prepared hepatocytes are driven by Ca2+ release from a caffeine- and ryanodine-sensitive calcium-induced calcium release pool.

Animals↗

[A comparative study among ftorafur, ftorafur plus tamoxifen, and tamoxifen in adjuvant therapy for breast cancer. The Chubu Cooperative Study Group of Adjuvant Chemoendocrine Therapy for Breast Cancer, Japan].

A randomized study assessing the efficacy of three treatment of ftorafur (FT), ftorafur plus Tamoxifen (TAM), and Tamoxifen in patients diagnosed as having stage II (N1b) or stage III breast cancer was carried out at 90 institutions in the Chubu district of Japan. After 10 mg of MMC administration on the day of surgery and the next day, patients were allocated to one of three treatments: FT 600 mg/day for 2 years, FT 600 mg/day plus TAM 20 mg/day for 2 years, or TAM 20 mg/day for 2 years. A total of 647 cases were analyzed. No significant differences were observed in the 5-year disease-free survival rates or in the 5-year survival rates. In the stratified analysis, however, a beneficial effect of adding FT to TAM was observed in the patients with ER-positive tumors in the 5-year survival rate, and FT plus TAM treatment was favorable compared with the other two treatments for postmenopausal patients with ER-positive tumors.

Adult↗

[Immunological effects of locoregional immunochemotherapy for liver metastases of gastric cancer].

Nine gastric cancer patients with simultaneous liver metastases were given intermittent transarterial administration of chemotherapeutics (adriamycin, mitomycin C or 5-fluorouracil) and biological response modifiers (BRM; OK-432 and interleukin (IL) -2) after gastrectomy. In terms of direct antitumor effect on liver metastases, a partial response was observed in 4 of 9 cases (44%). In addition, the concentration of 3 kinds of cytokines such as IL-6, tumor necrosis factor (TNF) -alpha and interferon (IFN) -gamma in the peripheral blood sera was measured immediately before and after transarterial administration of agents. While the concentration of IL-6 increased by BRM, chemotherapeutics could not alter the level of IL-6. As for TNF-alpha and IFN-gamma, no particular changing pattern was observed after transarterial administration. Furthermore, natural killer (NK) activity of peripheral blood mononuclear cells was measured. Administration of either BRM or BRM in combination with chemotherapeutics caused a decrease in NK activity, whereas chemotherapeutics did not. Flow cytometric analysis using 3 kinds of monoclonal antibodies (Anti-CD16, CD56 and CD57) revealed that the proportion of subset of both highly activated NK cells (CD16+.CD56+.CD57-) and moderately activated NK cells (CD16+.CD56+.CD57+) reduced after administration of BRM.

Antineoplastic Combined Chemotherapy Protocols↗

[A case of secondary leukemia induced by chemotherapy with a CDDP-based regimen for gastric cancer 5 years following radical resection].

Cisplatin, mitomycin C and 5-fluorouracil were given a 55-year-old woman for an unresectable gastric cancer, and successful radical gastrectomy was performed. Postoperative adjuvant immunochemotherapy using UFT and PSK was continued for about 4 years and 4 months. Pancytopenia was observed at 5 years after the treatment and then marked leucocytosis was noted. She also showed complications of general fatigue, appetite loss etc. A secondary acute leukemia associated with eosinophilia was diagnosed by peripheral blood examinations, showing WBC, 122,400: blast, 37.5 % and eosinophil, 41%. Results also showed atypia and pseudo-Pelger nuclear abnormality of eosinophil, high positive stain of cell myelogenic cell surface marker, many numeral and structural abnormalities of chromosomal analysis, etc. From the above results, it was suggested that the leukemia might be induced by previously performed chemotherapy. The patient died about 2 months following its onset.

Antineoplastic Combined Chemotherapy Protocols↗

Cytosolic calcium oscillations induced by hepatocyte growth factor (HGF) in single fura-2-loaded cultured hepatocytes: effects of extracellular calcium and protein kinase C.

Hepatocyte growth factor (HGF) induced the periodic fluctuations of cytosolic calcium concentration ([Ca2+]i) in primary cultured rat hepatocytes, which were dependent on extracellular calcium. The HGF-induced [Ca2+]i oscillations were suppressed by the pretreatment with phorbol 12-myristate 13-acetate (PMA). Administration of PMA during oscillations also caused their blockade, but the subsequent addition of protein kinase C (PKC) inhibitor H-7 reversed the inhibitory effects of PMA, thereby resulting in the resumption of the oscillatory responses. Moreover, the prior exposure to H-7 caused apparent increases in [Ca2+]i spike peaks elicited by HGF. These results suggest a negative modulation via PKC in HGF-induced repetitive [Ca2+]i transients. The absence of HGF-induced oscillations after the thapsigargin treatment indicates that the agonist-sensitive intracellular Ca2+ pool plays a crucial role in the [Ca2+] oscillations.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Hepatocyte growth factor (HGF) mediates the sustained formation of 1,2-diacylglycerol via phosphatidylcholine-phospholipase C in cultured rat hepatocytes.

The addition of hepatocyte growth factor (HGF) to rat hepatocytes in primary culture resulted in the formation of inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) and 1,2-diacylglycerol (DG) by a phosphoinositide-specific phospholipase C (PI-PLC). DG showed a biphasic increase; the first phase, corresponding with the peak of Ins(1,4,5)P3 and a second larger and prolonged phase. The HGF stimulates the phosphatidylcholine (PC)-derived prolonged DG formation by a phospholipase C pathway (PC-PLC) but not by a phospholipase D pathway. HGF also was found to elicit [Ca2+] oscillations which may be associated with the prolonged DG production from PC via the PC-PLC phospholipase C pathway.

Animals↗

Preoperative serum immunosuppressive acidic protein (IAP) test for the prognosis of gastric cancer: a statistical study of the threshold level and evaluation of the effect of the biological response modifier PSK.

The prognostic value of immunosuppressive acidic protein (IAP), which is known to suppress various immune responses in cancer patients, was studied in a prospective randomized trial of advanced gastric cancer patients, designed to evaluate the effect of PSK, a kind of biological response modifier with protein-bound polysaccharides. Preoperative serum IAP levels were determined in 228 patients who received radical gastric resection and tests conducted in one laboratory by the single radial immunodiffusion (SRID) method. All patients were followed up for 24 months or more. There was an overall significant difference in disease-free survival time in favour of the PSK-treated group compared with the control group. Preoperative IAP values were strongly associated with disease-free survival time. The statistical analysis to define an appropriate cut-off level for IAP was performed using Cox's proportional hazards model. The most significant difference was observed at the threshold value of 580 micrograms/ml, the hazard ratio being 2.13 with a 95% confidence interval [1.17, 3.88] (P = 0.013). Patients in the PSK-treated group with a preoperative IAP of lower than 580 micrograms/ml showed improved disease-free survival (P = 0.029), however, no significant difference was seen between the two groups when the preoperative IAP exceeded the threshold level. From these results, 580 micrograms/ml is postulated to be the most appropriate threshold value for predicting the prognosis of advanced gastric cancer patients, and it is suggested that PSK would be most effective in patients whose preoperative IAP level is lower than the threshold level.

Biomarkers, Tumor↗

[Experimental studies on antitumor effects of endogenously induced LAK (CTL) therapy for metastatic liver tumor].

UNLABELLED: Antitumor effects of endogenously induced LAK (CTL) therapy by trans-hepatic arterial administration with OK-432 and rIL-2 for metastatic liver tumor were examined. RESULTS: The number of metastatic nodules (NMN) showed a significant correlation with the number of inoculated tumor cells. NMN of the treated group was significantly reduced over that of the saline group in cases of 2.5 x 10(6) VX2 cells inoculation, while the survival day showed no prolongation even in the treated group. On the other hand, when 1 x 10(5) tumor cells were inoculated the survival day was slightly more prolonged in the treated group than in the saline group. The PHA-induced blastogenesis of peripheral blood was significantly increased at 10 days after the therapy in case of non-tumor bearer, while in cases of tumor bearer it was decreased at 7 days after the therapy.

Animals↗

[Significance of antitumor effects and immunological response on endogenously induced LAK therapy for primary or metastatic liver tumor].

Nineteen patients with metastatic liver tumor (9 of gastric cancer, 5 of colon cancer, 2 of pancreatic cancer, one each of mammary cancer, cholecystic cancer, carcinoid of biliary tract) and one patient with primary liver cancer were treated by endogenously induced LAK therapy consisting of transhepatic arterial infusion with ADM or MMC for induction therapy and OK-432 and rIL-2 (TGP-3) for immunotherapy. The following results were obtained. 1) Clinical response for liver tumor showed no CR but 8 cases of PR, for an overall response rate of 42.1%. 2) Reduced tumor marker value was noted in 76.5% cases, and 50% survival term became 349 days after the therapy. 3) Many CD4 and CD8 positive mononuclear cells had infiltrated around liver tumor after therapy by immuno-histochemical staining of surface marker. 4) NK activity of peripheral blood lymphocytes was markedly reduced soon after the therapy and continued for about 4-7 days, while in cases of combined subcutaneous administration with OK-432, NK activity showed only a slight decrease.

Antineoplastic Combined Chemotherapy Protocols↗

[Clinical studies on locoregional immunochemotherapy of peritonitis carcinomatosa].

Although 58 patients with peritonitis carcinomatosa underwent multidisciplinary therapy over the last 5 years in our department, about half of them died within 3 months after treatment. In addition, the prognosis was poor for gastric and colon cancer patients, who had macroscopic peritoneal dissemination. Therefore intraoperative intraperitoneal administration of either BRM or anticancer drugs was performed for the microscopic peritoneal dissemination of the cancer, and the immunological response in the peritoneal cavity was examined. In terms of subpopulation of peritoneal exudate cells, neutrophil leucocytes were predominant and thereafter lymphocytes increased. As for the cytokines in the exudate from peritoneal cavity, the concentration of interleukin-6 peaked within 24 hours after administration, followed by a gradual decrease, while the concentration of interferon-gamma was detectable at more than 24 hours after operation, followed by a gradual increase. Tumor necrosis factor-alpha was also detectable in the exudate. Its concentration decreased when both OK-432 and MMC were administered, but it increased when CDDP was administered. The above results indicated that preventive intraoperative intraperitoneal administration of BRM and anticancer drugs should bring about individual immunokinetic modulation in tumor bearing host and both cytokines and immunocytes could play an important role in locoregional tumor immunity.

Cisplatin↗

[A long-term survival case of advanced gastric cancer undergoing radical gastrectomy by second-look operation after successful chemotherapy (CDDP, MMC, 5-FU)].

A 55-year-old woman with gastric cancer underwent laparotomy and was found to have an unresectable tumor characterized by S3 (invasion of the pancreas), N3, P0 and H0. She was then treated by combined administration of cisplatinum, mitomycin C and 5-fluorouracil. A remarkable response (CR) was confirmed by upper gastrointestinal roentgenography and endoscopy. Upon reoperation about 8 weeks after chemotherapy, a successful radical total gastrectomy with R2 (partially R3) lymphnode dissection was performed. Histological examination of the specimens, including the stomach and lymphnodes, revealed no cancer cells in any region (pCR). She had been given UFT and PSK for 4 years 4 months after reoperation. She has lived for 5 years 2 months after reoperation without any signs of recurrence or metastases.

Adenocarcinoma↗

[Therapeutic effect of transarterial infusion immunochemotherapy for metastatic liver cancer].

In order to improve therapeutic efficacy for metastatic liver cancer, intermittent transarterial administration of BRM in combination with anticancer drugs was performed by use of reservoir apparatus. A total of 22 patients (12 cases of gastric cancer, 6 of colon cancer, 2 of pancreas cancer, 1 of gall bladder cancer and 1 of biliary tract carcinoid) were treated according to the following schedule: both 10 mg of ADM (or MMC) and 0.5 KE (or 1.0 KE) of OK-432 were administered on day 1 and 40 x 10(4) JRU of recombinant interleukin 2 (r-IL 2) on day 4, 7 and 11. The treatment was repeated as many times as possible. In terms of direct antitumor effect and decrease of tumor marker, the response rate was 43% (6 cases out of 14) and 75% (9 cases out of 12), respectively. As for performance status, improvement, no change and deterioration were seen in 4 cases, 8 cases and 3 cases, respectively. Even though 13 patients died, 8 of them survived more than 300 days. In the case of gastric cancer patients with liver metastasis, 50% survival time of 12 cases was 334 days, while that of 30 cases, who were administered anticancer drugs only systemically, was 144 days. In 3 cases the decrease in the size of tumors located in both liver and the other metastases also was seen. Every case developed high grade fever, but an antifebrile was effective. Otherwise severe side effects were not seen. These results indicated that intermittent arterial infusion immunochemotherapy was feasible for the treatment of metastatic liver cancer.

Antineoplastic Combined Chemotherapy Protocols↗

[Recent advance and its problem of postoperative immunotherapy on gastric cancer--with references to effects and host dependent factors].

The effects of immunotherapy such as PSK, Bestatine and OK-432 (oral administration) in combination with various chemotherapy were reviewed in the patients who underwent gastrectomy for gastric cancer from the Japanese references. The immunotherapy might lead to better prognosis about 10% or more, however, if it is administered for such a selected patient who show a lower preoperative serum IAP value (580 micrograms/ml), higher total protein (6.5g/dl), better performance status (0, 1 or 2) and etc, the survival rate could be increased. The usefulness of immunotherapy was also noted in such a case which showed severe side effects of chemotherapy and bad performance status. Moreover, the pre- and post-operative immunotherapy was advisable for prevention of surgical stress and enhancement of tumor metastases.

Humans↗

Neurogenic stress ulceration caused by laparotomy under anesthesia plus restraint. The device of a new rat model.

We report herein, a new method devised of producing neurogenic stress ulceration in rats. An experimental subarachnoid hemorrhage (SAH) was produced in rats by injecting 0.2 ml of arterial blood from other rats into the cisterna magna. Three days later, the rats were laparotomized for 1 hour under ether anesthesia, followed by restraint for 3 hours in wakefulness. The SAH rats were found to develop stress ulcers (UL-I) in the glandular stomach, which were significantly (p less than 0.001) more marked than those in non-SAH rats. Measurements were performed on gastric acid secretion, an important aggressive factor. It was found that the SAH rats undergoing the laparotomy-restraint stress showed a more marked increase in gastric acid secretion and a more marked reduction in MBF, than the non-SAH rats. The effects of bilateral vagotomy, upper abdominal sympathectomy and bilateral adrenalectomy were examined, and it was revealed that the SAH rats were under the condition of hyperreactivity both in the sympathetic and parasympathetic systems and, on this basis, the laparotomy-restraint stress caused the stress gastric ulceration. In this rat model, the laparotomy stress was applied under anesthesia and any exposure to low temperatures which may have interfered with blood circulation was avoided.

Anesthesia, General↗