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S Ichii

Publications and source records attributed to S Ichii.

At least 37 records · Page 2Linked to original sources
PubMed1996

[Genetic steps in colorectal cancer].

Though colorectal tumorigenesis has long been thought to be a multistep mechanisms, recently has it become possible to identify the molecular events that underlie the initiation and progression of colorectal carcinoma. Though the analysis of mutations in colorectal tumors at various stages of their development allows definition of a model for colorectal tumorigenesis, because the progression is the result of a series of genetic changes that accumulate activation of oncogene (K-ras), inactivation of tumor-suppressor gene (two-hit mutation of APC, Pla2s, p53, suppressor gene on chromosome 8p22 locus, NF2 and DCC) and mismatch repair gene (hMSH2, hMLH1 hPMS family and TGF beta II receptor linked DNA repair). These accumulation of genetic alterations contribute to tumor development and/or progression in primary colorectal carcinoma.

Colorectal Neoplasms↗
PubMed1995

A new type of human calcitonin receptor isoform generated by alternative splicing.

There are three isoforms of calcitonin receptors (CTRs). The first type (type 1) has 479 amino acids in rat and 482 amino acids in porcine. The second type (type 2) has a 39 amino acid insertion in the second extracellular domain. The third type (type 3) has a 16 amino acid insertion in the first intracellular domain. The CTR which has been isolated from a human ovarian carcinoma cell line belongs to type 3. Using RT-PCR with primers whose sequences correspond to the human CTR cDNA, we analyzed the expression of the CTR transcripts in seven human tumor cell lines and surgical specimens. The CTR m-RNA were found in all samples. Transcripts which were 48bp shorter than that of the type 3 human CTR were detected, but not transcripts of type 2 and type 3. Since the structure of this CTR is same as that of the type 1 rat and porcine CTRs, we termed it the human type 1 CTR. PCR studies using human genomic DNA as a template revealed that the 48bp sequence constitutes an exon. These results indicate that the type 1 and the type 3 human CTRs are generated by alternative splicing and a majority of human CTR transcripts is type 1.

Alternative Splicing↗
PubMed1995

Detection of K-ras mutations in DNAs isolated from feces of patients with colorectal tumors by mutant-allele-specific amplification (MASA).

K-ras mutations are found in approximately half of all colorectal tumors examined. To explore the possibility of detecting mutated K-ras rapidly and efficiently in DNAs isolated from fecal material, we applied the mutant allele specific amplification (MASA)-PCR method to DNA from feces of patients with colorectal tumors. Among 55 colorectal adenocarcinomas or adenomas examined, 19 were found to carry K-ras mutations in codons 12 or 13. We were able to PCR-amplify DNAs isolated from feces of 15 of these 19 patients, but in only three of the fecal samples, we were able to detect the K-ras mutations corresponding to tumor DNA by MASA and ethidiumbromide staining of the gel. The carcinomas in these three cases were more than 40 mm x 40 mm in size and located in the sigmoid colon or rectum. However, we identified the K-ras mutations in fecal DNAs of additional seven patients by MASA when the gels were blotted and probed with a radio-labeled oligonucleotide; the tumors in those patients had arisen in the distal half of the colon and the smallest of these tumors was only 7 mm x 5 mm. No K-ras mutations were detectable in feces of the remaining five cases, whose tumors were relatively small and/or located in the proximal region. The results suggested that the MASA-PCR system has potential for development as a simple, rapid and noninvasive method for diagnosing the presence of colorectal tumors that carry mutant K-ras alleles, particularly tumors located in the distal colon.

Adenocarcinoma↗
PubMed1993

Detection of K-ras mutation in sputum by mutant-allele-specific amplification (MASA).

From 10 to 30% of lung carcinomas examined to date contain mutant K-ras genes. We report here that the mutant-allele-specific amplification (MASA) method may be useful for detection of the K-ras mutations in cells obtained from the sputum of patients with lung cancer. The PCR product from one of five patients revealed an alteration when mixed oligonucleotides representing variants of the second letter at codon 12 of this gene were used as 5' primers, and further experiments showed a mutation of GGT (Gly) to GAT (Asp) at codon 12. The MASA system could also be applied to an examination of metastatic lung carcinomas, particularly from adenocarcinomas in colon and pancreas in which frequent K-ras mutations are detected, and to mass-screening for colorectal tumors using DNA isolated from feces as template.

Alleles↗
PubMed1993

Multiple forms of the APC gene transcripts and their tissue-specific expression.

We have detected multiple forms of RNA transcript from APC, the gene which is responsible for familial adenomatous polyposis (FAP). Transcriptional initiation occurs at three sites in two distinct non-translating exons at the 5' end of the gene. At least five different forms of 5' non-coding sequences, generated by alternative splicing, exist. The splicing mechanism seems to be regulated in a tissue-specific fashion, and one type of transcript contained an additional exon, which was transcribed specifically in brain. Analyses of mRNAs from two colorectal-tumor cell lines by reverse-transcriptase polymerase chain reaction (RT-PCR) revealed that one or another of the transcriptional forms was absent in both cell lines. This observation suggested the presence of mutations in the control region or the first exon of APC, or that mutation(s) could have affected the splicing efficiency or transcriptional initiation of the gene in these tumors. Furthermore, we found that the alternative splicing involving the 19 kDa protein of signal recognition particle (SRP19) gene, that is known to occur at exon 14 of APC, is also controlled in a tissue-specific manner, and one type of transcript lacked in some organs.

Adenomatous Polyposis Coli↗
PubMed1993

Somatic mutations of the APC gene in precancerous lesion of the stomach.

The adenomatous polyposis coli (APC) gene, responsible for familial adenomatous polyposis, is also associated with development of sporadic tumors in digestive system as colon, stomach, or pancreas. In order to investigate whether or not APC mutations occur as an early genetic event during gastric carcinogenesis, we examined somatic mutations of APC in flat adenomas of the stomach. DNAs isolated from flat adenomas were examined by means of an RNase protection analysis coupled with polymerase chain reaction (PCR) followed by DNA sequencing of the PCR products. By screening a mutation cluster region (MCR: codons between 1286 and 1513) of APC in which two-thirds of somatic mutations were detected in colorectal tumors, somatic mutations were found in four of ten flat adenomas: three of which caused truncation of the gene product due to a nonsense mutation or 4-bp deletion; one other was a point mutation that altered amino acid from alanine to threonine. Our results imply that APC plays a crucial role in an early step of gastric carcinogenesis, as was observed in colorectal carcinogenesis.

Adenoma↗
PubMed1993

[Acute mixed lineage leukemia showing resistance to AML and ALL therapy].

A 51-year-old female was who admitted complaining of cough and slight fever and lower limb petechia. The laboratory examinations revealed leukocytosis (49,400/microliters) with blasts (71%) in the peripheral blood. The NCC was 30 x 10(4)/microliters with 84.8% blasts in the bone marrow. Myeloperoxidase staining was positive for 6% of blasts. Auer rods were not seen in some blasts. Thus, acute myeloblastic leukemia (M1) was diagnosed according to FAB classification. In the peripheral blood, 43.3% of blasts expressed CD19, 10.3% of blasts expressed CD20 and 55.6% of blasts expressed CD33 on admission. Though she received two courses of DCMP according to the DCMP-85 protocol, and one combined course of mitoxantrone, etoposide, and Ara-C. The NCC was 20.0 x 10(4)/microliters with 70% blasts in the bone marrow. CD19 was expressed by 72.4% of blasts and 35.0% expressed CD20. The ALL-90 protocol was started, but remission was not achieved. Thus this case was considered to be acute mixed lineage leukemia.

Antigens, CD↗
PubMed1993

Detailed analysis of genetic alterations in colorectal tumors from patients with and without familial adenomatous polyposis (FAP).

To examine early genetic events during colorectal carcinogenesis, we searched for genetic alterations in 75 adenomas from seven patients with familial polyposis coli (FAP) and in 64 sporadic colorectal tumors (63 carcinomas and one adenoma). We investigated germ-line and somatic mutations in the APC gene, somatic mutations in the K-ras and p53 genes, and loss of heterozygosity (LOH) on chromosome 8p21-22. Thirty-two FAP adenomas carried detectable somatic mutations in the APC gene. The frequency of somatic APC mutations among adenomas was the same regardless of differences in size or histopathological classification. On the other hand, K-ras mutation was very rare in small adenomas where dysplasia was mild or moderate but frequent in large adenomas with severe dysplasia. Mutation of the p53 gene was observed in only two adenomas and LOH on 8p22 was detected in none. These results imply that a second 'hit' in the APC gene, but not necessarily mutation in K-ras or p53, is an important and critical event for formation of a colorectal adenoma.

Adenomatous Polyposis Coli↗
PubMed1992

Frequent somatic mutations of the APC gene in human pancreatic cancer.

The APC (adenomatous polyposis coli) gene is responsible for familial adenomatous polyposis and is also associated with the development of sporadic tumors of the colon and stomach. To investigate whether or not mutations of APC play any role in tumors arising in other organs, we examined somatic mutations of this gene in sporadic (nonfamilial) renal cell carcinomas, hepatocellular carcinomas, and cancers of the lung and pancreas. DNAs isolated from tumors were examined by means of a RNase protection analysis, coupled with the polymerase chain reaction followed by DNA sequencing of the polymerase chain reaction products. By screening a part of the APC coding region, we detected somatic mutations in four of ten pancreatic cancers; each of these mutations would yield a truncated APC product due to a 1- or 5-base pair deletion. These results imply that mutations in APC contribute to carcinogenesis in the pancreas.

Base Sequence↗
PubMed1992

The APC gene, responsible for familial adenomatous polyposis, is mutated in human gastric cancer.

Although gastric cancer is the most common cancer in the world, genetic changes during its carcinogenesis are not well understood. Since some gastric cancers are considered to originate from the intestinal metaplasia, it is likely that the adenomatous polyposis coli (APC) gene, the mutation of which causes adenomatous polyps in the colon, is associated with carcinogenesis of gastric cancer. Based on this idea, DNAs isolated from gastric cancers were examined by means of a RNase protection analysis coupled with polymerase chain reaction followed by sequencing of the polymerase chain reaction products. By screening nearly one-half of the coding region of the APC gene in 44 tumors, somatic mutations were detected in three tumors: a missense mutation, a nonsense mutation, and a 5-base pair deletion resulting in a frame shift which causes truncation of the gene product. These results suggest that the mutation of the APC gene also plays an important role during the carcinogenesis of at least some gastric cancers.

Adenocarcinoma↗
PubMed1992

Somatic mutations of the APC gene in colorectal tumors: mutation cluster region in the APC gene.

We examined somatic mutations of the adenomatous polyposis coli (APC) gene in 63 colorectal tumors (16 adenomas and 47 carcinomas) developed in familial adenomatous polyposis (FAP) and non-FAP patients. In addition to loss of heterozygosity (LOH) at the APC locus in 30 tumors, 43 other somatic mutations were detected. Twenty-one of them were point mutations; 16 nonsense and two missense mutations, and three occurred in introns at the splicing site. Twenty-two tumors had frameshift mutations due to deletion or insertion; nineteen of them were deletions of one to 31 bp and three were a 1-bp insertion. One tumor had a 1-bp deletion in an intron near the splicing site. Hence, 41 (95%) of 43 mutations resulted in truncation of the APC protein. Over 60% of the somatic mutations in the APC gene were clustered within a small region of exon 15, designated as MCR (mutation cluster region), which accounted for less than 10% of the coding region. Combining these data and the results of LOH, more than 80% of tumors (14 adenomas and 39 carcinomas) had at least one mutation in the APC gene, of which more than 60% (9 adenomas and 23 carcinomas) had two mutations. These results strongly suggest that somatic mutations of the APC gene are associated with development of a great majority of colorectal tumors.

Adenoma↗
PubMed1992

Inactivation of both APC alleles in an early stage of colon adenomas in a patient with familial adenomatous polyposis (FAP).

To examine whether the dosage effect of germ-line mutations in patients with familial adenomatous polyposis (FAP) is sufficient to cause colorectal adenomas, or an additional somatic mutation of the normal allele is required as well, we have investigated somatic mutations of the APC gene in multiple adenomas developed in one FAP patient. In addition to a 5-bp deletion of one allele present constitutionally in this patient, the normal APC allele had been lost in five of seven DNA samples extracted from small adenomas (< 3 mm in diameter) with mild or moderate atypia. This result indicates that the inactivation of both alleles of the APC gene is probably essential for the development of an early-stage adenoma, in agreement with the two-hit mutational model underlying the concept of tumor suppressor genes.

Adenoma↗
PubMed1992

Somatic mutation of the APC gene in gastric cancer: frequent mutations in very well differentiated adenocarcinoma and signet-ring cell carcinoma.

We searched for somatic mutations of the adenomatous polyposis coli (APC) gene in DNA samples isolated from 57 sporadic gastric cancers, by means of a ribonuclease (RNase) protection analysis coupled with DNA amplification by the polymerase chain reaction (PCR). Examining 30% of the APC coding region, including a region where somatic mutations in colorectal tumors are known to be clustered, we detected somatic mutations in 12 tumors; seven in 17 very well differentiated adenocarcinomas, two in 19 well or moderately differentiated adenocarcinomas, and three in ten signet-ring cell carcinomas. So far, no somatic mutations have been identified in 11 poorly differentiated adenocarcinomas. Eight of the 17 somatic mutations found in 12 tumors caused truncation of the gene product due to a nonsense mutation and a 1-, 2- or 5-bp deletion; nine others were point mutations that altered amino acids. Our results suggest that inactivation of APC plays a role in development of some gastric cancers, particularly very well differentiated adenocarcinomas and signet-ring cell carcinomas.

Adenocarcinoma↗
PubMed1991

Atypical depressive symptoms possibly predict responsiveness to phototherapy in seasonal affective disorder.

Phototherapy was administered to 24 depressed patients with seasonal affective disorder (SAD), of which 62%, 24%, and 14%, respectively, showed improvements of greater than or equal to 50%, 25-50%, and less than 25% based on the Hamilton rating scale for depression for SAD (HAMSAD). No patients showed aggravation or side effects. Although the improvement rate in HAMSAD correlated significantly with the pretreatment severity of atypical symptoms of depression, it did not correlate with that of typical symptoms. This suggests that phototherapy is a useful treatment in SAD and that responsiveness to phototherapy in SAD can possibly be predicted by the atypical depressive symptoms before treatment.

Adolescent↗
PubMed1991

Re-investigation of ontogenesis of epidermal growth factor receptor mRNA in the liver of rats: quantitative evaluation of northern blot analysis.

Changes in the expression rate of epidermal growth factor receptor (EGFR) mRNA with age in the liver of rats were examined to assess the contribution of EGF to the proliferation of hepatocytes in younger animals. Northern blot analyses with a 32P-labeled probe derived from the extracellular domain of EGFR cDNA were evaluated quantitatively by normalizing the densitometric scanning data with the relative amounts of poly(A)+ RNA in the samples. The expression of EGFR mRNA was low during the early period and increased towards the adult level after 21 days of birth. In contrast, the rate of beta-actin mRNA expression was significantly higher immediately after birth and showed a tendency to decrease with time.

Actins↗