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Biomedical subjects

G Kosaki

Publications and source records attributed to G Kosaki.

At least 37 records · Page 2Linked to original sources

A pregnancy-specific beta 1-glycoprotein, a CEA gene family member, expressed in a human promyelocytic leukemia cell line, HL-60: structures of protein, mRNA and gene.

Both genomic and cDNA clones encoding a precursor for a pregnancy-specific beta 1-glycoprotein (PS beta G) belonging to the CEA family, expressed in a human promyelocytic leukemia cell line, HL-60, have been isolated and the entire primary structure of the precursor is deduced. The 335-AA precursor has a 34-AA signal peptide followed by domains of N, IIA, IIB and C, which are encoded by separate exons. The genomic sequence contains extra exons IA and IB between exons N and IIA. Apparently, exon IA is excluded from the mRNA by alternative splicing while IB is a pseudo-exon having a stop codon formed by a deletion of dinucleotide in the middle of the sequence. This provides another mechanism to render exon IB abortive and is different from that we reported for another PS beta G (Biochem. Biophys. Res. Comm. (1988) 156, 68-77).

Amino Acid Sequence↗

Production of salivary type alpha-amylase in human lung cancer.

alpha-Amylase, which is produced by lung cancer tissue, was studied by cloning cDNAs from a cell line originating from lung cancer that produces amylase. Sequencing studies with this cDNA showed that the expressing gene is of the salivary type. The specific location of the start point of transcription, as revealed by S1 mapping, supported this conclusion.

Base Sequence↗

Involvement of platelet membrane glycoprotein Ib and glycoprotein IIb/IIIa complex in thrombin-dependent and -independent platelet aggregations induced by tumor cells.

Involvement of platelet membrane glycoproteins (GP) in interactions between platelets and tumor cells was studied by using two human tumor cell lines and two monoclonal antibodies against platelet membrane GP. HMV-I cells derived from vaginal melanoma induced platelet aggregation in heparinized plasma, which was not followed by coagulation. M7609 cells derived from colon adenocarcinoma also induced platelet aggregation in heparinized plasma, which, on the contrary, was followed by coagulation. Aggregating activities of the HMV-I cells were abolished by pretreatment with neuraminidase or trypsin, but M7609 activity was not labile to these enzymes. Aggregations induced by M7609 were inhibited by hirudin or MD805, while those by HMV-I were not. M7609 cells dose dependently shortened the recalcification time of normal as well as Factor IX-deficient plasmas, while they were not effective in shortening the time of Factor II- or Factor VII-deficient plasmas. The procoagulant activity of HMV-I cells was 1000 times less than M7609 on the basis of cell numbers. When human platelets were preincubated with monoclonal anti-GPIb or anti-GPIIb/IIIa complex antibodies, neither cell line could cause aggregations. These findings suggest that both GPIb and the GPIIb/IIIa complex on the platelet surface are involved in the thrombin-dependent and -independent platelet aggregations induced by tumor cells.

Adenocarcinoma↗

Influence of L-methionine-deprived total parenteral nutrition on the tumor tissue and plasma amino acids fraction and the host metabolism: experimental study with Sato lung carcinoma-bearing rats.

Creation of an amino acid imbalance, particularly curtailment of L-methionine, at the tumor cell level is thought to have a favorable effect on the inhibition of tumor growth. In the present study, we examined the influence of a specially-formulated amino acid mixture, avoid of sulfur-containing amino acids (L-methionine and L-cysteine), on the growth and amino acid fraction of Sato lung carcinoma (SLC) and the host metabolism in SLC-bearing rats. The rats were treated by total parenteral nutrition containing the above amino acid mixture, plus other nutrients (methionine-deprived TPN) for 10 days. Tumor growth began to decrease 4 days after the start of this treatment and the size was significantly less at the end of the treatment than in rats receiving conventional TPN with general purpose Vuj-N type amino acid solution as a protein source. The tumor-to-carcass weight ratio also showed a similar trend. In biochemistry, the albumin level and albumin-to-globulin ratio were significantly lower than in the rats receiving conventional TPN but other parameters such as total protein, glucose, GOT and GPT were not affected by the treatment. In the amino acid fraction of the tumor tissue extraction, both L-methionine and L-tyrosine were decreased and L-serine was increased significantly compared with the control group.

Amino Acids↗

[Clinico-pathological study of solid poorly differentiated carcinoma of the stomach].

We have studied the clinico-pathological features of 42 autopsied cases involving solid, poorly differentiated carcinomas that histologically revealed a medullary growth pattern but none showing a tubular formation. Ninety percent of these 42 cases were male, and the 42 carcinomas were of 5 histological types as listed below: 1) small cell carcinoma-atypical carcinoid type (15 cases); 2) AFP-producing type (so-called "hepatoid carcinoma") (4 cases); 3) acinar type (8 cases); 4) signet ring cell-medullary type (2 cases); and, 5) large cell type (13 cases) The small cell carcinoma-atypical carcinoid type, the AFP-producing type, and the large cell type showed a severe hematogenous metastasis. In contrast, the acinar type had a lymphogenous metastasis the signet ring cell-medullary type, showed a lymphogenous and peritoneal metastasis. Each histological type well corresponded to the typical biological characteristics of each of these carcinomas of the stomach.

Adenocarcinoma, Mucinous↗

[Arterial infusion chemotherapy in patients with gastric cancer in liver metastasis and long-term survival after treatment].

Fifty-five gastric cancer patients with liver metastasis received arterial infusion chemotherapy. In 14 patients who had lesions in the liver intra-hepatic artery infusion chemotherapy was performed, while in 41 patients who had lesions in the liver and other sites intra-aortic infusion chemotherapy was performed. Methods for inserting the catheter into the aorta or hepatic artery and treatment schedules were reported previously. Between 1975 to 1981, 33 gastric cancer patients with liver metastasis were treated with 5-FU only (4 cases). MMC.5-FU (18 cases) and ADM.5-FU (11 cases). No response was seen, but minor response was seen in two cases. Between 1982 to 1988, 22 gastric cancer patients with liver metastasis were treated using arterial MMC.5-FU therapy combined with angiotensin II (13 cases), arterial MMC therapy combined with degradable starch microsphere (6 cases) and sequential MTX.5-FU (3 cases). The response rate of MMC.5-FU therapy combined with angiotensin II was 5/13 (38%) including one complete response. The responders of MMC-combined DSM therapy were seen in 3 (50%) out of 6 patients. However, no response was seen in sequential MTX.5-FU therapy. In the present study, a 61-year-old patient treated with MMC.5-FU combined with angiotensin II therapy, survived for 49 months after treatment. In order to improve the prognosis of gastric cancer patients with liver metastasis, it is important to increase the delivery of anticancer drugs to the target tissues by using certain drugs like angiotensin II and DSM. In the future, further studies should be done to prolong the duration of remission by arterial chemotherapy.

Angiotensin II↗

[Radical operation for carcinoma of gastric cardia--lymph node dissection by laparosternophrenotomy approach].

The adequate esophago-gastric resection and lymph node dissection can be performed without the necessity of a thoracotomy, by using the laparosternophrenotomy approach. For tumors restricted to lower esophagus of 4cm in localized tumors or 3cm in invaded tumors above the EG junction, the sternotomy approach is utilized. However, if the tumor extends to more than the above criteria, the thoracoabdominal approach must be utilized. For 14 years, 85 cases with tumor of gastric cardia were performed by sternotomy approach and 76 cases were performed by thoracotomy approach. The lymph node metastatic rate in the lower thoracic cavity was 26% in total. The lymph node metastatic rate of No. 110 was 22.6%, No. 111 was 17.4% and No. 112 was 12.5%. These results show the lymph node dissection in the lower thoracic cavity is very important in tumors of gastric cardia. The five year survival rate was 41% in patients who undergone curative operation by the sternotomy approach, and 45% in patients performed by the thoracotomy approach. According to our study of the lymph fluid stream in gastric cardia tumors using carbon, the lymph node dissection around the renal vein is important. This approach has less respiratory disturbance than the thoracotomy. This procedure is one of the best approaches for carcinoma of gastric cardia according to our criteria.

Cardia↗

Exon-intron organization of a gene for pregnancy-specific beta 1-glycoprotein, a subfamily member of CEA family: implications for its characteristic repetitive domains and C-terminal sequences.

A fragment of human gene for pregnancy-specific beta 1-glycoprotein(s), recently identified CEA family member(s), has been cloned. Analyses of nucleotide and deduced amino acid sequences revealed that it carried, from 5' to 3' direction, exons IA, IB, IIA, IIB, C3, C1 and C2, the first four encoding peptides distinct from but highly similar to domains of PS beta Gs. The lack of consensus 3' splice site sequence ahead of IB indicated that it was an abortive exon, which would explain the peculiar domain construction of PS beta Gs, i.e. N-IA-IIA-IIB-C1, 2 or 3. Apparently, the multiple C-terminal sequences for a PS beta G were generated by alternative splicing among C1, C2 and C3 exons. Furthermore, sequences which overlapped partly with Cexons, were found to be similar to parts of 3'-UTR of CEA and NCA, indicating further the close relationship of CEA/NCA and PS beta G subfamily genes.

Amino Acid Sequence↗

Primary structure of nonspecific crossreacting antigen (NCA), a member of carcinoembryonic antigen (CEA) gene family, deduced from cDNA sequence.

A cDNA containing the entire coding region for a member of carcinoembryonic antigen (CEA) gene family has been cloned from cDNA library of HLC-1 cells by immunochemical screening with the antibody specific to nonspecific crossreacting antigen (NCA). The cDNA encodes a precursor form of a polypeptide consisting of a 34-residue signal sequence, a 108-residue N-terminal (N-) domain, a 178-residue domain (NCA-I domain) and a 24-residue domain rich in hydrophobic amino acids (M-domain). Each domain has a distinct but homologous amino acid sequence to that of the corresponding domain of CEA. Unlike the coding sequences, the 3'-untranslated sequences differ markedly in the NCA and CEA cDNAs facilitating the preparation of probes that will discriminate between nucleotide sequences for CEA and NCA.

Amino Acid Sequence↗

Differential expression of carcinoembryonic antigen and nonspecific crossreacting antigen genes in human colon adenocarcinomas and normal colon mucosa.

The level of mRNA for carcinoembryonic antigen (CEA) and nonspecific crossreacting antigen (NCA) in human colon adenocarcinomas and normal colon mucosa was analyzed by Northern blot hybridization using as probes 32P-labeled CEA cDNA and synthetic oligodeoxyribonucleotides specific to CEA and NCA mRNA sequences. The major 3.5-kb mRNA and a minor 4.2-kb mRNA are shown to be CEA-specific and expressed in both tissues, albeit at slightly different degrees, suggesting that the expression of CEA is regulated posttranscriptionally. Another minor mRNA of 2.9 kb is NCA-specific and expressed predominantly in cancerous tissues, suggesting its usefulness as a marker for colon cancer.

Adenocarcinoma↗

Molecular cloning of a gene for a member of carcinoembryonic antigen (CEA) gene family; signal peptide and N-terminal domain sequences of nonspecific crossreacting antigen (NCA).

A 2073-base pair DNA fragment containing a part of gene for a member of carcinoembryonic antigen (CEA) gene family, has been isolated from human DNA library after screening with 32P-labeled 53-mer oligodeoxyribonucleotide corresponding to N-terminal 18 amino acids of CEA gene family and cDNA encoding CEA (1,2). The fragment contains two exons; the one encodes the first 60% of signal peptide and the other the rest of it in addition to 107 amino acids which correspond to the N-terminal domain of CEA (1,2). Apparently, the second intron is inserted between the first and the second nucleotides of the codon for 108th amino acid. The presence of Ala instead of Val as the 21st amino acid of the N-terminal domain indicates that the exon encodes nonspecific crossreacting antigen (NCA).

Amino Acid Sequence↗

The carcinoembryonic antigen (CEA) contains multiple immunoglobulin-like domains.

The amino acid sequences of human carcinoembryonic antigen deduced from the cDNA sequences have been analysed. This antigen contains seven extracellular domains (previously recognized three highly repetitive domains are further divided into A and B subdomains each) which are strikingly homologous to each other and to immunoglobulin variable regions, poly-Ig receptor and Thy 1.1. The N-terminal domain lacks immunoglobulin-like fold but the other six domains have, suggesting that the CEA belongs to immunoglobulin superfamily.

Amino Acid Sequence↗

Primary structure of human carcinoembryonic antigen (CEA) deduced from cDNA sequence.

The cDNAs corresponding to the mRNA encoding a polypeptide which is immunoreactive with the antisera specific to carcinoembryonic antigen (CEA) (1) are cloned. The amino acid sequences deduced from the nucleotide sequences of the cDNAs show that it is synthesized as a precursor with a signal peptide followed by 668 amino acids of the putative mature CEA peptide, whose N-terminal 24 amino acids and amino acids 286 to 295 exactly coincide with those known for N-terminal sequences of CEA (2) and NFA-1 (3), respectively. The first 108 N-terminal residues are followed by three very homologous repetitive domains of 178 residues each and then by 26 mostly hydrophobic residues which probably comprise a membrane anchor. Each repetitive domains contains 4 cysteines at precisely the same positions and as many as 28 possible N-glycosylation sites are found in the CEA peptide region agreeing with high carbohydrate content of purified CEA.

Amino Acid Sequence↗

Inhibitory effect of L-methionine-deprived amino acid imbalance using total parenteral nutrition on growth of ascites hepatoma in rats.

The antitumor effect of an amino acid imbalance characterized by the absence of L-methionine was investigated in AH-109A ascites hepatoma-bearing rats with the technique of total parenteral nutrition (TPN). A central venous catheter was placed at the superior vena cava of the rat and hypertonic glucose solution plus an amino acid mixture, an ordinary amino acid compound but lacking L-methionine and L-cysteine, was administered as protein source for seven days. Increases in the volume of ascites and the number of tumor cells were significantly inhibited in the rats receiving glucose plus L-methionine-free amino acid mixture compared to the control rats given glucose only, glucose plus ordinary amino acid mixture and laboratory rations. Unfavorable side effects of TPN with amino acid compound lacking L-methionine and L-cysteine were loss of body weight and development of hypoproteinemia. No evidence of hepatic injury and bone marrow suppression due to this treatment were obtained from the results of biochemical and hematological studies. In liver cells and ascites tumor cells, morphologically, prominent enlargement of the nucleoli was observed in the rats treated with the amino acid mixture lacking of L-methionine and L-cysteine.

Amino Acids↗

Liver metastasis of colon 26 cells implanted into the superior mesenteric vein in mice.

The intraportal implantation of mouse transplantable colon adenocarcinoma 26 was investigated as an experimental liver metastasis model of colorectal cancer. CDF1 male mice (5 weeks old) were laparotomized under pentobarbital sodium anesthesia, and colon 26 tumor cells (1 X 10, 1 X 10(3), or 1 X 10(5) cells) were inoculated into the superior mesenteric vein. On day 21 after inoculation, mice inoculated with 1 X 10(3) tumor cells showed five to 12 colonies of liver metastasis (mean, 9.2 colonies; n = 6). The survival time was 27 to 36 days (median, 27 days; n = 5) in these mice. When mitomycin C (MMC) was administered into the superior mesenteric vein 15 min after the inoculation of tumor cells, the number of metastatic foci in the liver was strongly inhibited; 81.1% and 100% inhibitions were observed in the groups given 4 mg/kg and 6 mg/kg of MMC, respectively. The mouse colon 26 model seems to be one of the more useful experimental models for evaluating treatments for the prevention of liver metastases from colorectal cancer.

Adenocarcinoma↗