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Biomedical subjects

K Inokuchi

Publications and source records attributed to K Inokuchi.

At least 19 recordsLinked to original sources
PubMed1992

Randomized adjuvant trial to evaluate the addition of tamoxifen and PSK to chemotherapy in patients with primary breast cancer. 5-Year results from the Nishi-Nippon Group of the Adjuvant Chemoendocrine Therapy for Breast Cancer Organization.

BACKGROUND: A randomized adjuvant trial was conducted from October 1982 to January 1985 to evaluate the addition of tamoxifen (TAM) to combination chemotherapy with perioperative mitomycin C (MMC) and ftorafur (FT) for patients with estrogen receptor (ER)-positive tumors and the addition of PSK, a biologic response modifier, to MMC+FT chemotherapy for patients with ER-negative tumors in operable Stage IIA, IIB, and IIIA cancer. The doses used were 20 mg of oral TAM daily, 600 mg of oral FT daily, and 3 g of oral PSK daily for 2 years. Intravenous MMC (13 mg/m2) was given on the day of operation. METHODS: A total of 967 patients were entered and randomized by stratification based on ER status and staging (1978 International Union Against Cancer [UICC] criteria at the time of trial execution). Of 967 patients, 914 (94.5%) were evaluable. At 5-year follow-up, significant prolonged overall survival (OS) and relapse-free survival (RFS) times were seen with the addition of TAM in patients with ER-positive and Stage IIIA T3N0 cancer (1987 UICC-American Joint Committee on Cancer [AJCC] criteria); however, no significant survival benefit from TAM was seen in patients with ER-positive and Stage IIA T2N1 cancer. There was no significant difference between regimens, with or without PSK, in patients with ER-negative disease. RESULTS: Results of subset analyses suggested a benefit from TAM in postmenopausal patients with ER-positive and Stage IIA T2N1 cancer and a benefit from PSK in patients with node-negative, ER-negative, and Stage IIA T2N1 cancer. CONCLUSIONS: The 5-year results of the current trial showed a survival advantage by the addition of TAM to chemotherapy in patients with ER-positive and Stage IIIA T3N0 cancer.

Adjuvants, Immunologic↗
PubMed1992

Relationship of the type of bcr-abl hybrid mRNA to clinical course and transforming activity in Philadelphia-positive chronic myelogenous leukemia.

We studied the type of bcr-abl mRNA for 34 patients with chronic myelogenous leukemia and analyzed for correlations among the mRNA type, the clinical outcome and the transforming activity using the tumorigenicity assay. There was no difference in the distribution of the mRNA-types (b2-a2 and b3-a2) between clinical phases. We found no correlation between the two types of bcr-abl mRNA and the chronic phase duration or survival. The DNA from 12 of 20 chronic phase patients and all five blastic phase patients showed transforming activity. Although there was no difference in the positive rate of transforming activity among the two mRNA-type groups, the blastic phase patients showed a tendency to have higher transforming activity.

3T3 Cells↗
PubMed1992

Histochemical analysis of sialomucin in Paget cells of mammary and extramammary Paget's disease.

The cytoplasmic sialomucin in Paget cells of both mammary and extramammary Paget's diseases was examined, using a new method proposed by Volz et al. (1987a, b). The staining methods used involved an electrolyte-Alcian Blue (pH = 5.8) and periodic acid Schiff. Oxidation was performed with 0.4 mmol/l periodate in 1 mol/l HCl at 4 degrees C or 50 mmol/l periodate in distilled water at room temperature for 1 h. Methylation, saponification, borohydride reduction, and digestion with diastase, neuraminidase (Vibrio cholerae) or chondroitinase ABC, were also employed. The cytoplasmic mucin was found to exhibit positive reaction for the above staining which were variously altered by the chemical modification procedures and diminished in intensity or abolished by digestion with neuraminidase. These results suggest that the cytoplasmic mucin in Paget cells is sialomucin without side-chain substituent in genital Paget's disease, and that with a substituent at C7 in mammary Paget's disease.

Breast Neoplasms↗
PubMed1992

Expression of growth hormone (GH)-releasing factor gene in GH-producing pituitary adenoma.

Pituitary cells synthesize various neuropeptides that influence pituitary hormone secretion. GH-releasing factor (GRF) may also be produced by normal or pituitary tumor cells. We examined GRF gene expression in pituitary tumors. Standard techniques for the analysis of GRF gene expression did not appear to be suitable. Highly sensitive reverse transcription coupled to polymerase chain reaction was used. Specimens of pituitary adenoma were obtained by transsphenoidal adenomectomy from six patients with acromegaly and three patients with no clinical evidence of pituitary hormone overproduction; non-functioning adenoma. Pituitary glands were collected at autopsy from three patients who died from nonendocrine disorders. A specific GRF gene transcript was detected in five out of six GH-producing pituitary adenomas, whereas this was not found in three separate specimens of nonfunctioning pituitary adenoma or anterior and posterior pituitary tissue. The data suggest that GRF is synthesized as an intrinsic product in human GH-producing pituitary adenoma.

Acromegaly↗
PubMed1992

N-RAS activation in the terminal stage of undifferentiated chronic myeloproliferative disease.

The relationship between activation of the N-RAS gene and the leukemic progression of undifferentiated chronic myeloproliferative disease (UCMPD) was investigated in a 71-year-old male. Hematologically, it was difficult to differentiate the UCMPD from chronic myelogenous leukemia. Chromosomal analysis revealed no Philadelphia chromosome (Ph1-), and DNA analysis revealed no BCR rearrangement (BCR-) either at the beginning or in the terminal stages of the disease. We performed a tumorigenicity assay, using NIH3T3 cells, and molecular analysis, using the polymerase chain reaction (PCR) and direct sequencing. The DNA of leukemic cells at the beginning of the leukemic progression did not show any abnormalities, but at the terminal stage of the disease the DNA showed a point mutation in codon 12 (GGT----GCT) of the N-RAS gene. Interestingly, a codon 13 mutation (GGT----GTT) was also detected by tumorigenicity assay. These observations suggest that the activated N-RAS gene contributes to the hematologic progression of UCMPD.

Aged↗
PubMed1992

[DCC gene and leukemia].

The deleted in colorectal carcinomas (DCC) gene, located in human chromosome band 18q21, was identified as a potential tumor suppressor gene by Fearon et al. in 1990. The DCC gene encodes a protein which is highly similar to neural cell adhesion molecules and other related cell surface glycoproteins. In colorectal carcinoma, the expression of the DCC gene is reduced or absent in 88% of cases. We examined the expression of the DCC gene using reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. Its expression was reduced or absent in some leukemias. Our findings suggest the possibility that this gene may play a role in leukemogenesis.

Base Sequence↗
PubMed1991

A possible correlation between the type of bcr-abl hybrid messenger RNA and platelet count in Philadelphia-positive chronic myelogenous leukemia.

The Philadelphia (Ph1) chromosome, in which the hybrid bcr-abl gene is formed, is thought to be the initial event in chronic myelogenous leukemia (CML). The position of the breakpoint within the breakpoint cluster region (bcr) on Ph1 chromosome and the splicing pattern determine the species of the fused bcr-abl messenger RNA (mRNA). We tried to detect the two types of fused mRNAs in 57 chronic-phase cases of Ph1-positive CML using the polymerase chain reaction procedure (RT-PCR). The bcr exon 2/abl exon 2 fused mRNA (b2-a2) was detected in 17 patients, the bcr exon 3/abl exon 2 fused mRNA (b3-a2) was detected in 34 patients, and both types of mRNA were detected in six patients. The platelet counts of patients who expressed b3-a2 mRNA or both types were significantly higher than those of patients who expressed only b2-a2 (841.5 v 373.5 x 10(9)/L; P less than .015), although there was no significant difference in the white blood cell counts or hemoglobin. This finding suggests a possibility that the type of bcr-abl mRNA may affect the thrombopoietic activity in CML.

Base Sequence↗
PubMed1991

Lack of a requirement for strict rotational alignment among transcription factor binding sites in yeast.

The MF alpha 1 gene of Saccharomyces cerevisiae is an alpha specific gene whose expression is regulated by two upstream activation sites (UASMF alpha 1S), which are the binding sites for activator proteins, MAT alpha 1 and MCM1. UASMF alpha 1 elements act in a synergistic fashion; lack of either element causes reduced expression levels that are 6- to 45-fold less than that of intact promoter in alpha cells. We investigated the effect of manipulating rotational alignments among transcription factor binding sites of MF alpha 1 on the expression of the gene. The expression level of MF alpha 1 decreased with the spacing between the two UASMF alpha 1S and no synergism was observed when the distance of the two elements was longer than 90 base pairs. No strict rotational alignment was required for their synergistic action. We also show that the spacing between UASMF alpha 1 elements and TFIID binding site, the TATA box, had little, if any, effect on MF alpha 1 expression. We chose a sufficient number of positions for UASMF alpha 1S to ensure that, in several of these positions, MAT alpha 1 and MCM1 were on the opposite side of the DNA helix with respect to the TATA box.

Base Sequence↗
PubMed1991

Transforming genes and chromosome aberrations in therapy-related leukemia and myelodysplastic syndrome.

The presence of activated transforming genes was investigated in four patients with therapy-related leukemia and in three with therapy-related myelodysplastic syndrome. DNA of bone marrow cells from six of the patients exhibited transforming activity in the tumorigenicity assay. Five of the six patients who were positive in the tumorigenicity assay contained activated N-ras oncogenes, and three contained activated K-ras oncogenes. Thus, concurrent activation of N-ras and K-ras oncogenes was observed in two patients. In vitro DNA amplification followed by oligonucleotide dot-blot analysis was used to investigate mutations in codons 12, 13, and 61 of the N-ras and K-ras oncogenes. Two patients exhibited an N-ras mutation, substituting aspartic acid (GAT) for glycine (GGT), and three patients exhibited an N-ras codon 13 mutation, substituting valine (GTT) for glycine. Two patients exhibited K-ras codon 12 mutations, substituting aspartic acid (GAT) or cysteine (TGT) for glycine (GGT), respectively, and one case exhibited a K-ras codon 61 mutation, substituting lysine (AAA) for glutamic acid (CAA). Cytogenetic analysis revealed that loss of chromosome 7 was frequent (four patients: 57%). Our data indicate that activation of N-ras and K-ras genes, as well as loss of heterozygosity for specific alleles on chromosome 7, plays a more important role in the leukemogenesis of both therapy-related leukemia and myelodysplastic syndrome.

Aged↗
PubMed1991

The relationship between the site of breakpoints within the bcr gene and thrombopoiesis of Philadelphia-positive chronic myelocytic leukemia.

We determined the position of the breakpoint within the bcr gene in 22 patients with Philadelphia-positive chronic myelocytic leukemia using conventional Southern-blots and analyzed its relationship to thrombopoiesis. After DNA digestion with restriction endonucleases (Hind III, Bam HI and Bgl II), we localized the breakpoint in bcr using two genomic probes. The location of the breakpoint within the bcr was assigned to one of five zones. Breakpoints in zones 1 and 2 were grouped as "5"', and those in zones 3, 4 and 5 as "3'". Thus we subdivided patients with bcr rearrangements into those with genomic breaks at either 5' or 3' of the Bam HI site, just upstream of exon 3. Nine patients had 5' breakpoints and 13 patients had 3' breakpoints. The platelet counts of 3' patients were significantly higher than those of 5' patients (1395 vs 274 x 10(9)/l; p less than 0.03). The megakaryocyte counts from bone marrow histological sections in 3' patients (n = 12) and 5' patients (n = 7) were 63.4/mm2 and 19.5/mm2, respectively, with a significant difference of p less than 0.006. The mean number of megakaryocyte progenitor cells assayed by in vitro cloning was 128.3/2 x 10(5) bone marrow cells for 3' patients (n = 7) compared with 46.3 for 5' patients (n = 4). These results suggest that Philadelphia-positive CML patients with 3' breakpoints have higher thrombopoietic activity than patients with 5' breakpoints.

Adult↗
PubMed1991

Cell-mediated cyclic thrombocytopenia treated with azathioprine.

We studied a male patient with cyclic thrombocytopenia whose bone marrow megakaryocyte count showed cyclic fluctuations in synchrony with cyclic changes of platelet count. He failed to respond to either prednisolone or bolus methylprednisolone therapy, but subsequently he was successfully treated with azathioprine. To investigate the underlying pathogenesis of the cyclic fluctuations in the platelet count, we studied the kinetics of megakaryocyte progenitor cells (CFU-Meg) and the effects of the patient's peripheral blood mononuclear cells on CFU-Meg. In one cycle of the platelet fluctuation, the increase in the CFU-Meg number preceded an increase in the bone marrow megakaryocyte count and then the platelet count. In the latter half of the cycle, CFU-Meg, bone marrow megakaryocytes and platelets began to decrease in that order. Peripheral blood mononuclear cells obtained from the patient in the thrombocytopenic phase suppressed megakaryocyte colony formation from normal bone marrow cells in a dose-dependent manner. In contrast, these cells obtained in the phase of a normal platelet count did not suppress megakaryocyte colony formation at all. These findings indicate that the cause of platelet fluctuation is periodic failure of megakaryocytopoiesis at the stage of CFU-Meg and that the patient's peripheral mononuclear cells are responsible for periodically suppressing the CFU-Meg.

Azathioprine↗
PubMed1991

[Cooperative study of surgical adjuvant chemotherapy for colorectal cancer (third report): five-year results. Cooperative Study Group of Surgical Adjuvant Chemotherapy for Colorectal Cancer in Japan].

A randomized controlled study was carried out by the envelope method with 491 institutions in participation across the country in order to find an optimal surgical adjuvant chemotherapy for curatively resected colorectal cancer. The schedules for drug administration were different in four districts: ACNU + Futraful (FT) group and FT alone group in the Hokkaido-Shikoku district; the same schedule groups plus untreated group in the Chubu-Kinki district; MMC+FT group, FT alone group in the Tohoku-Kanto district; and ADM+FT group and FT alone group in the Chugoku-Kyushu district. The numbers of patients admitted to this study were 2,450 cases with colon cancer and 2,456 cases met the evaluation criteria of this study. The 5-year survival rate on the whole did not differ from combination therapy to single drug therapy in either colon cancer or rectal cancer, but in Dukes C rectal cancer the five-year survival rate tended to be higher with the combination therapies. In n2 (+) or a2(s) rectal cancer in particular, combination therapies with MMC and FT and with ADM and FT achieved significantly higher five-year survival rate, and the rate of local recurrence was significantly lower with ADM+FT.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

[The preoperative and postoperative carcinoembryonic antigen test in the diagnosis, staging, and prognosis of gastric cancer. Tumor Marker Committee, Japanese Foundation for Multidisciplinary Treatment of Cancer].

Preoperative and postoperative carcinoembryonic antigen (CEA) levels were studied in 3,532 patients with Surgically treated gastric cancer in 52 institutions from 1980 to 1981. These patients had disease resectable with curative intent and were followed for a minimum of 5 years or until death. Among 2,749 Stage I cases, 33 had recurrence and proved to be histologically stage I. A pair matching case control study between these 33 cases and matched 33 stage I controls without recurrence proved that the preoperative CEA level was relatively higher in cases with recurrence (p = 0.079). In Stage II and III cases, an analysis of variance using a cut off level as a block factor was performed. Among 315 Stage II cases, preoperative CEA levels were significantly higher in cases with recurrence than in cases without recurrence. In 468 Stage III cases, no correlations between preoperative CEA levels and high risks of cancer recurrence were detected. In Stage I and Stage II cases, CEA levels significantly increased at the time of recurrence. In conclusion, preoperative high serum CEA levels might be considered one of the risk factors for recurrence of Stage I and II gastric cancers, and monitoring the postoperative CEA levels might be useful in early detection of recurrence.

Analysis of Variance↗
PubMed1990

Improved survival after prophylactic portal nondecompression surgery for esophageal varices: a randomized clinical trial. Cooperative Study Group of Portal Hypertension of Japan.

To evaluate prophylactic surgery for esophageal varices, a prospective randomized controlled trial was begun in 1980 by the Japanese Research Society for Portal Hypertension. Methods of operation included selective shunts and nonshunting interruption procedures. One hundred and twelve Japanese patients, in whom endoscopic findings suggested risk of bleeding but who had no bleeding episode, were randomly allocated to the operated group of 60 patients or nonoperated group of 52 patients. Nine patients with idiopathic portal hypertension, histologically proven noncirrhotic disease, which all fell in the operated group, were excluded from the study and the remaining 103 patients (51 operated and 52 nonoperated) were analyzed. Long-term follow-up of patients for a median of 49 mo with a maximum of 73 mo showed a total of 11 (22%) deaths, including 2 operative deaths, in the operated group compared with 23 (49%) deaths in the nonoperated group. The cumulative survival rate at 5 yr in the operated group was 72%, which was significantly higher than the 45% of the nonoperated group (p less than 0.05). The cumulative variceal bleeding rate at 5 yr was 7% in the operated group, which was significantly lower than that of the nonoperated group of 46% (p less than 0.001). It was concluded that portal nondecompression surgery was effective in preventing the variceal bleeding and in improving survival.

Esophageal and Gastric Varices↗
PubMed1990

The selective shunt for variceal bleeding: a personal perspective.

It has been proved that selective decompression of esophageal varices can occur by way of the left gastric venous route or the transsplenic route. The left gastric venacaval shunt functions well over a long postoperative period, if the shunt is technically satisfactory; however, the distal splenorenal shunt (DSRS) can be problematic. Unless the proximal and distal portions of the splenic vein are both entirely isolated from the pancreas, blood flow will be diverted from the portal vein to the distal splenic vein, where the pressure has been lowered by the shunt. This portal malcirculation may lead to portal thrombosis or stenosis on occasion. To prevent this adverse effect, complete isolation of the splenic vein (splenopancreatic disconnection) is necessary. Extensive gastric disconnection is irrelevant in this regard. Although the conventional DSRS has been viewed with disfavor, we must realize that splenopancreatic disconnection makes the DSRS a satisfactory technique. The clinical evidence and theoretic basis of the selective shunt for esophageal varices are described herein.

Esophageal and Gastric Varices↗
PubMed1990

[Intraoperative intraperitoneal administration of CDDP against gastric cancer with peritoneal dissemination].

This study was undertaken in order to evaluate the effect of intraoperative intraperitoneal (i.p.) administration of CDDP on patients who underwent gastrectomy for gastric cancer with peritoneal dissemination, compared with MMC or OK-432 i.p. administration group and untreated group. The median survival time was 11 months in CDDP i.p. group (35 patients), 8 months in MMC or OK-432 Ip group (33 patients) and 7 months in untreated group (25 patients). 1- and 2-year survival rates were 30.4% and 12.1% for MMC or OK-432 i.p. group, and 28% and 8% for untreated group, while in CDDP i.p. group, the rates were higher at 46.4% and 14.7%, respectively (CDDP i.p. group vs. untreated group, p less than 0.05). In vitro chemosensitivity test by succinate dehydrogenase inhibition (SDI) test supported the clinical results. CDDP had higher sensitivities than MMC and ADM on poorly differentiated cases as well as peritoneal dissemination cases. Our results suggest that intraoperative i.p. administration of CDDP was useful for the treatment of gastric cancer with peritoneal dissemination.

Adult↗