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Biomedical subjects

S Saji

Publications and source records attributed to S Saji.

At least 55 records · Page 3Linked to original sources
PubMed2000

[Current status of "low-dose cisplatin-5-FU therapy" for solid tumors (2nd report)--from a nationwide questionnaire on its adverse effects].

A nationwide questionnaire survey was carried out on low-dose cisplatin-5-FU therapy for solid malignant tumors (mostly stomach and colon cancer) regarding its antitumor as well as adverse effects. The regimen was defined as 4 weeks administration of cisplatin 2-5 mg/body, 5 days a week, which was used in 47% of 82 institutions studied. Cases were classified into an Ab regimen (86 cases) with cisplatin 3-5 mg/body, and a Bb regimen (122 cases) with cisplatin 6-30 mg (mostly 10 mg)/body, both of which were given 5-FU 300-500 mg/body daily. The antitumor effect (CR + PR) was shown to be slightly higher in the Bb regimen than in the Ab regimen, and was 35% overall. Very few adverse effects appeared with either regimen for mostly major digestive, hepatic and renal functions, except for myelodepressions (leucopenia and thrombocytopenia), which were more than grade 3 in only a few percent with the Ab regimen, and a little more than 10% with the Bb regimen. The advantages and disadvantages of the A/Bb regimens appeared to be counter-balanced in terms of their antitumor and adverse effects. Most institutions using the Ab regimen favored repeating the regimen cycle as much as possible. Those using more than 6 cycles accounted for about 20% of hospitals.

Antimetabolites, Antineoplastic↗
PubMed2000

A dose-escalation and pharmacokinetic study of subcutaneously administered recombinant human interleukin 12 and its biological effects in Japanese patients with advanced malignancies.

A pilot dose-escalation study of recombinant human interleukin 12 (rhIL-12) was conducted in Japanese patients with advanced malignancies. Cohorts of three patients received escalating doses of rhIL-12 that increased from 50 to 300 ng/kg/day s.c. three times a week for 2 weeks followed by 1-week rest. The same dosage and schedule was repeated for two additional courses. Sixteen previously treated patients were registered, and 15 were evaluated. Common toxicities were fever and leukopenia; the abnormality of laboratory tests included elevations in aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, C-reactive protein, and beta2-microglobin. Dose-limiting toxicity was the grade 3 elevation of aminotransferases, and was observed in two of six patients at the 300-ng/kg dose level after the first course in one patient and after the third course in the other. Leukopenia was observed at all of the dose levels; two of six patients at 300 ng/kg experienced grade 3 leukopenia. Thus, 300 ng/kg was determined to be the maximum acceptable dose. Peak plasma levels of rhIL-12 decreased in the second courses, but the areas under the curve were almost the same in the first and second courses. Biological effects included increases of plasma levels of IFN-gamma, tumor necrosis factor-alpha, IL-6, IL-10, and neopterin. In two patients with renal cell carcinoma, complete response and partial response of metastatic tumors were observed with 50 and 300 ng/kg; the responses lasted for 5 and 3.5 months, respectively. Although immunological response to rhIL-12 varies depending on administration route and schedule and on patients' physiological conditions, the recommended dose for Phase II studies is 300 ng/kg s.c. three times a week for 2 weeks followed by 1-week rest.

Adult↗
PubMed1999

Identification of frequent impairment of the mitotic checkpoint and molecular analysis of the mitotic checkpoint genes, hsMAD2 and p55CDC, in human lung cancers.

The mitotic checkpoint is thought to be essential for ensuring accurate chromosome segregation by implementing mitotic delay in response to a spindle defect. To date, however, very little data has become available on the defects of the mitotic checkpoint in human cancer cells. In the present study, impaired mitotic checkpoint was found in four (44%) of nine human lung cancer cell lines. To our knowledge, this is the first demonstration of frequent impairment of the mitotic checkpoint in this leading cause of cancer deaths. As an initial step towards elucidation of the underlying mechanism, we further undertook a search for mutations in a key component of the mitotic checkpoint, known as hsMAD2, and its immediate downstream molecule, p55CDC. No such mutations were found, however, in either 21 lung cancer cell lines or 25 primary lung cancer cases, although we could identify silent polymorphisms and the transcribed and processed hsMAD2 pseudogene that was subsequently mapped at 14q21-q23. The present observations appear to warrant further investigations, such as search for alterations in other components, to better understand the molecular pathogenesis of this fatal disease, and warn against potential misinterpretation when performing mutational analyses for other cancer types based on cDNA templates.

Antineoplastic Agents↗
PubMed1999

Impact of splenectomy and immunochemotherapy on survival following gastrectomy for carcinoma: covariate interaction with immunosuppressive acidic protein, a serum marker for the host immune system. Tumor Marker Committee for the Study Group of Immunochemotherapy with PSK for Gastric Cancer.

The role of the spleen in tumor immunology is still controversial in that it can either enhance or suppress the antitumor immune response depending on the tumor-bearing host. To clarify this biphasic effect of the spleen, a clinical evaluation of splenectomy in conjunction with immunotherapy and the host immune status was performed in gastric cancer patients. The effect of splenectomy and immunotherapy in 253 gastric cancer patients enrolled in a prospective randomized trial (SIP) was analyzed using the Cox's proportional hazards model in terms of the covariate interaction of the preoperative immunosuppressive acidic protein (IAP) level. In patients with high IAP levels (>580 microg/ml) with predicted negative antitumor immune reactions, splenectomy improved the prognosis. In patients with lower IAP values, conversely, the preservation of the spleen and immunotherapy demonstrated a significant benefit to survival. The spleen was shown to have a biphasic activity in terms of its antitumor immune response depending on the IAP level of the patient. The effect of immunotherapy is significantly influenced by the activity of spleen cells. The preoperative IAP level is therefore considered to be a possible indicator for the effectiveness of splenectomy and immunotherapy in curatively resected gastric cancer patients.

Aged↗
PubMed1999

Solitary fibrous benign mesothelioma of the peritoneum: report of a case.

A 66-year-old Japanese man who had undergone a subtotal gastrectomy for gastric cancer 1 year earlier, and was asymptomatic, underwent a computed tomography scan during a detailed follow-up examination, which revealed a pancreatic mass. Abdominal ultrasonography showed a solid tumor containing a cystic lesion, and abdominal magnetic resonance demonstrated a tumor with low intensity on T1-weighted images and high intensity on T2-weighted images. Although an abdominal angiography added no new information to help in establishing a preoperative diagnosis, it showed an avascular mass. An endoscopic retrograde pancreatograhy showed compression and deviation of the body part of the pancreatic duct, and dilatation of its caudal part. At laparotomy, an elastic soft tumor was found to originate from the peritoneum of the omental bursa in front of the pancreas. The tumor was encapsulated and solid. The solid lesion consisted of spindle-shaped cells, but no atypical cells were observed. The histological findings were diagnostic of a benign solitary fibrous mesothelioma, which is extremely rare. The patient is currently well and disease-free more than 5 years after this operation.

Aged↗
PubMed1999

An abdominal desmoid tumor involving the xyphoid and costal chondrium associated with pregnancy: report of a case.

We report herein the case of a 27-year-old woman found to have an abdominal desmoid tumor involving the xyphoid and costal chondrium associated with pregnancy. The patient was referred to our department on the third day after delivery for investigation of a fist-sized, firm tumor in the infrasternal angle, first noticed during the eighth month of gestation. Computed tomography and magnetic resonance imaging revealed a well-defined mass, 9 x 7.5 cm in size, invading the xyphoid. The tumor could be radically excised with the xyphoid, a lower part of sternum, and the chondrium of the bilateral sixth and seventh ribs, including 1.5 cm of free margin. The resected specimen measured 10 x 11.5 x 11.5 cm and weighed 395 g. Histological examination revealed the lesion to be a desmoid tumor consisting of spindle cells with small, elongated nuclei infiltrating dense collagenous fibers. The patient had an uneventful postoperative course and was discharged on the 11th postoperative day. There has been no evidence of recurrence in the 6 months since her operation. This case is of interest with regard to the possible contribution of sex hormones, especially estrogen, to desmoid tumor development.

Adult↗
PubMed1999

Molecular cloning, mapping, and characterization of a novel human gene, MTA1-L1, showing homology to a metastasis-associated gene, MTA1.

Through large-scale sequencing of clones randomly selected from libraries of human cDNAs, we have isolated a novel human gene encoding a product with 59.6% identity in amino acid sequence to human MTA1, a protein associated with tumor invasion and metastasis. This cDNA, named MTA1-L1 (MTA1 like 1), consists of 2736 nucleotides with an open reading frame encoding 668 amino acids. A single 3.0-kb transcript of MTA1-L1 was expressed ubiquitously on Northern blots. Structural analysis of the MTA1-L1 gene revealed 18 exons spanning 8.1 kb of genomic DNA. We assigned the MTA1-L1 locus to chromosomal band 11q12-13.1 by fluorescence in situ hybridization.

Amino Acid Sequence↗
PubMed1999

Overexpression of MDM2 in MCF-7 promotes both growth advantage and p53 accumulation in response to estradiol.

The overexpression of the oncogene product MDM2 is often observed in human breast cancer cells, especially in estrogen receptor (ER)-positive ones. To study the role of MDM2 protein in ER-positive breast cancer, we have established cell lines derived from MCF-7 which stably express increased and decreased levels of MDM2 by transfection of a mammalian expression vector containing human mdm2 cDNA in sense and antisense orientations, respectively. Interestingly, MDM2 overexpression in MCF-7 cells afforded a remarkable growth advantage under estradiol (E2)-supplemented condition. Then, we analyzed the expression of p53, which is an important regulator of growth and the cell cycle. Unexpectedly, the p53 accumulation induced by E2 was remarkably higher in MCF-7 cells stably overexpressing MDM2 than in the parent MCF-7 cells. On the other hand, reduction of MDM2 suppressed the E2-induced increase in p53 protein. Moreover, mdm2 antisense oligonucleotides prevented E2-induced accumulation of p53. In the steady state, the cellular levels of p53 were also correlated with those of MDM2. These interactions are not consistent with the well-known role of MDM2, which acts as a negative regulator for p53 by inhibiting its function and promoting its rapid degradation. These results suggest that MDM2 may regulate the expression of p53 in the steady state and in response to E2 in breast cancer cells, and imply a novel and important role of MDM2 during breast carcinogenesis.

Breast Neoplasms↗
PubMed1999

Application of restriction fragment fingerprinting with a rice microsatellite sequence to assembling rice YAC clones.

To refine the current physical map of rice, we have established a restriction fragment fingerprinting method for identifying overlap between pairs of rice yeast artificial chromosome (YAC) clones and defining the physical arrangement of YACs within contiguous fragments (contigs). In this method, Southern blots of rice YAC DNAs digested with a restriction endonuclease are probed with a rice microsatellite probe, (GGC)5. The probe produces a unique fingerprint profile characteristic of each YAC clone. The profile is then digitized, processed in a computer, and a statistic that represents the degree of overlap between two YACs is calculated. The statistics have been used to detect overlaps among YAC clones, thereby filling a gap between two neighbouring contigs and organizing overlapping rice YAC clones into contiguous fragments. We applied this method to rearranging YACs that had previously been assigned to rice chromosome 6 by anchoring with RFLP markers.

Chromosomes, Artificial, Yeast↗
PubMed1999

[Recent progress in biological therapies for cancer].

After approval of national health insurance for non-specific immunomodulation such as OK-432 (1978) and PSK (1980), lentinan, SPG, bestatin and dried BCG vaccine have been tried. Including cytokines such as IL-2, IL-12, IFN, TNF or monoclonal antibodies, they have been widely used as biological response modifiers (BRM). Progress in BRM therapy may be broken down into the first 10 years as development, the next 10 years as disappointment and the most recent 5 years as dream-like progress owing to molecular biological techniques. An interdisciplinary approach has been taken by the Japanese Research Society for Surgical Cancer Immunology, founded in 1980, and the Japanese Society of BRM founded in 1988. Many investigations have been performed on issues such as the clinical evaluation or criteria for responder cases, host immunocompetency, post-operative adjuvant immuno-chemotherapy, locoregional immunotherapy, cytokine therapy, adoptive immunotherapy, and tumor specific immunotherapy. Attention has also focused on malignant tumor injury, surgical stress, the advantages or disadvantages of splenectomy, and discussions of the current status and future prospects in the next century for new BRM therapy.

Antibodies, Monoclonal↗
PubMed1999

[Clinical evaluation of intermittent hepatic arterial infusion therapy with CDDP and 5-FU for liver metastasis of colorectal cancer].

Twenty-seven patients with liver metastasis from colorectal cancer were treated with intermittent intra-arterial infusion chemotherapy for 5 years starting from 1993. Five to ten mg of CDDP, 250 mg of 5-FU and/or 3-6 mg of Leucovorin were administered weekly. In the case of nonresponders, the dose of 5-FU was allowed to increase toward 500 mg. The above schedule was repeated as long as possible. The average number of administrations in 12 out of 27 unresectable patients was 28.7. The response rate was 50% (CR; 4 cases, PR; 2), with 2 NC and 3 PD. Four patients given 500 mg of 5-FU showed some response. The 50% survival period was 466 days, and the 1- and 3-year survival rates were 66.7% and 18.3%, respectively. The average number of administrations in the group of patients who underwent prophylactic treatment and resection of the metastasis was 33.1. During an average observational period 681 days, 7 patients (46.7%) had a recurrence in the liver. The 5-year survival rate was 85.7%. The patients who were treated with 250 mg 5-FU experienced no severe side effects, but one who was given 500 mg 5-FU developed a duodenal ulcer.

Adult↗
PubMed1999

[A recurrent case of esophageal cancer in which metastatic skin tumor disappeared after local injection of activated lymphocytes with tumor-pulsed dendritic cells].

We examined the effect of activated lymphocytes stimulated with tumor-pulsed dendritic cells (DC-K), and found that such stimulation enhanced the cytotoxity of the activated lymphocytes. Furthermore, in applying DC-K to a recurrent case of esophageal cancer, the skin tumors disappeared after local injection of DC-K. The only adverse effect of this treatment was pyrexia. Although no general effect was observed, the local effect was satisfactory. This suggests that DC-K might be useful for local treatment or postoperative adjuvant therapy.

Aged↗
PubMed1998

Spread of colorectal cancer micrometastases in regional lymph nodes by reverse transcriptase-polymerase chain reactions for carcinoembryonic antigen and cytokeratin 20.

BACKGROUND AND OBJECTIVES: Lymph node metastasis is known as a significant predictor of prognosis in colorectal cancer patients. Recently, reverse transcriptase polymerase chain reaction (RT-PCR) has been applied to detecting micrometastasis. To assess the risk of recurrence and accurately determine the spread of tumor cells, we examined lymph node micrometastases in a series of colorectal cancer patients. METHODS: We examined 202 lymph nodes obtained from 13 colorectal cancer patients who underwent curative operation and were histologically diagnosed to be node-negative, using RT-PCR to amplify mRNAs for two epithelial markers, carcinoembryonic antigen (CEA) and cytokeratin 20 (CK-20). RESULTS: All the cases, including early stage patients, had micrometastases. A total of 102 among 202 lymph nodes (50.5%) were positive for either CEA or CK-20, or both (47.0, 40.1, and 36.6% respectively). Positive lymph nodes were spread along the courses of vascular trunks as well as being located in more distant regions. CONCLUSIONS: Even in histologically negative lymph nodes, there is a considerable possibility that micrometastases may exist. Their detection by RT-PCR may improve clinical staging and indications for cancer therapy. We should also take care in the choice of surgical approach.

Adult↗
PubMed1998

Sustained induction of hepatocyte growth factor by sensitization with freeze-thawed hepatic tissue.

Hepatocyte growth factor (HGF) is a mitogen for hepatocytes, and has therapeutic potential for fibrotic/cirrhotic liver. Therefore, the induction of HGF in vivo is considered to be useful in the treatment of liver dysfunction caused by cirrhosis, chronic hepatitis, or extensive surgical resection. In this study, we examined the sustained induction of HGF by inoculation of freeze-thawed hepatic tissue (FTHT). Serum from rats inoculated with FTHT increased [3H]thymidine incorporation i.e., increased DNA synthesis, in primary cultured rat hepatocytes. The DNA synthesis was significantly promoted by the addition of the FTHT-sensitized serum, while this DNA synthesis was inhibited by neutralizing anti-rat HGF antibody. The concentration of HGF in the FTHT-sensitized serum was increased by day 3 after the inoculation. The time of HGF induction was dependent on the inoculated volume of FTHT, but peaks of HGF concentration were found on day 5 with different volumes of FTHT. Injurins, inducers of HGF, were also induced in the FTHT-sensitized rats, with their peak levels on day 3. The FTHT inoculated tissue showed inflammatory cell infiltration, which was gradually absorbed, and had completely disappeared by day 14 after the inoculation. Although mild inflammatory cell infiltration was observed in non-freeze-thawed inoculated hepatic tissue (NFHT) a tight capsule formed around the NFHT, and was scarcely phagocytized on day 14. These results suggest that FTHT inoculation induces HGF sustainedly through the increased synthesis of injurins, and that freeze-thawed tissue, which is easily phagocytized, is important for the sustained induction of HGF.

Animals↗