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Biomedical subjects

S Imaoka

Publications and source records attributed to S Imaoka.

At least 91 records · Page 5Linked to original sources
PubMed1998

[Report of case who survived more than five years after repeated intraperitoneal chemotherapy with cisplatin and 5-fluorouracil for treatment of macroscopically negative but microscopically positive peritoneal dissemination of gastric cancer].

UNLABELLED: Prognosis of patients with macroscopically negative but microscopically positive peritoneal dissemination is so poor that the two-year survival rate after the surgery was 0% during 1975-1981. It improved to 38% during 1982-1988 but the five year survival rate was 0%. CASE REPORT: A 57-year-old male underwent distal gastrectomy and lymph node dissection on November 10, 1992 due to Borrmann type 3 gastric cancer measuring 5.4 cm in diameter and locating in the gastric antrum (H0 P0 t3 n3 stage IV a). Peritoneal lavage cytology revealed cancer cells, and, thus, this patient was treated with intraperitoneal chemotherapy using an intraperitoneal infuser port. Through the infuser port, cisplatin and 5-FU were given at a dose of 70 mg/m2 and 700 mg/m2, respectively. Because fluorouracil infusion caused abdominal pain after the second infusion, it was administered i.v. for 24 hours thereafter. The infuser port was removed after the four infusions because the patient developed appendicitis. Fluorouracil was given p.o. at a dose of 300 mg/day from one month after surgery (total dose of fluorouracil 54.6 g). Cytological examination of the ascites revealed no cancer cells after the second intraperitoneal chemotherapy, and the patient fared well five years and four months after the surgery. Therefore, it is suggested that intraperitoneal chemotherapy with cisplatin and fluorouracil is an effective treatment for microscopical peritoneal dissemination, though it may have an adverse effect such as chemical peritonitis.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Pancreatic invasion as the prognostic indicator of duodenal adenocarcinoma treated by pancreatoduodenectomy plus extended lymphadenectomy.

UNLABELLED: Pancreatoduodenectomy has become the standard procedure in resection of the duodenal adenocarcinoma, and some adjuvant therapies can be added to obtain further improvement in postoperative outcome. However, for patient selection, it is necessary to have a predictive indicator showing, if possible before laparotomy, which instances are noncurable by surgery alone or need adjuvant therapies. METHODS: A retrospective analysis was made for 24 consecutive patients whose duodenal adenocarcinoma were treated by pancreatoduodenectomy plus a wide range of lymphadenectomies without any adjuvant therapies at Osaka Medical Center for Cancer and Cardiovascular Diseases. Patient survival rates were related to macroscopic and microscopic findings and to findings obtained by preoperative imaging techniques. RESULTS: The overall survival rate was 69% at 3 years and 57% at 5 years; locoregional recurrence was the primary cause of death. Although the 5-year survival rate was 44% in patients with nodal involvement and 76% in those without, this difference did not reach statistical significance (P = .079). Instead, invasion into the pancreatic parenchyma at a macroscopic level was the most significant prognostic factor; the 5-year survival rate was 78% in the 16 patients without and 16% in the 8 patients with pancreatic invasion (P = .0047). Invasion into the pancreas correlated well with the angiographic findings; the 5-year survival rate was 25% in patients whose angiograms delineated the pancreatic invasion and 83% in patients whose angiograms did not (P = .0084). CONCLUSION: When duodenal adenocarcinoma was treated by pancreatoduodenectomy plus a wide range of lymphadenectomy, pancreatic invasion at a macroscopic level was most associated with patient survival. Pancreatic invasion was well delineated by the preoperative angiogram, which would be helpful in patient selection.

Adenocarcinoma↗
PubMed1997

Expression of four rat CYP2D isoforms in Saccharomyces cerevisiae and their catalytic specificity.

We cloned four cDNAs belonging to the CYP2D subfamily to express these enzymes in yeast cells and to compare their catalytic activities simultaneously. Three are believed to be alleles of CYP2D1, 2D2, and 2D3, respectively, based on high nucleotide sequence similarity, while CYP2D4 had both sequences of CYP2D4 and CYP2D18. Expression plasmids carrying CYP2D cDNAs were transformed into Saccharomyces cerevisiae. Typical P450 CO-difference spectra with absorbance maximum at 448 nm were recorded with microsomal preparations from the yeast cells expressing the four CYP2D forms. A catalytic study of these CYP2D forms was done with debrisoquine, bufuralol, and lidocaine. CYP2D2 had the highest debrisoquine 4-hydroxylation (2.2 nmol/min/nmol P450) activity, similar to that (2.2 nmol/min/nmol) of human CYP2D6 expressed in yeast cells. CYP2D3 had high lidocaine N-deethylation (43 nmol/min/nmol P450) activity, and both CYP2D3 and 2D2 exhibited high lidocaine 3-hydroxylation (2.4 and 1.6 nmol/min/nmol P450, respectively) activity. Bufuralol 1'-hydroxylation catalytic capabilities were comparable among the four isoforms. The activity of CYP2D1 was relatively low toward the three substrates (debrisoquine, 0.091; bufuralol, 1.5; lidocaine 3-hydroxylation, 0.019; lidocaine N-deethylation, 2.8 nmol/min/nmol P450). These findings indicate that debrisoquine, a typical substrate for CYP2D forms, was mainly metabolized by CYP2D2 but not CYP2D1 in rat liver and that the CYP2D forms have different substrate specificity.

Animals↗
PubMed1997

Mutagenic activation of urinary bladder carcinogens by CYP4B1 and the presence of CYP4B1 in bladder mucosa.

We investigated the mutagenic activation of 2-naphthylamine (2-NA), 3,2'-dimethyl-4-aminobiphenyl (DMAB), and 3,3'-dichlorobenzidine (DCB), bladder carcinogens, by renal and bladder microsomes and by purified P450s using the umu gene expression system, which detects DNA damage. Mouse renal microsomes had high mutagenic activation toward DCB and low activity toward 2-NA. Purified mouse Cyp4b1 also had high mutagenic activity toward DCB. Anti-Cyp4b1 antibody efficiently inhibited DCB bioactivation by mouse renal microsomes with a high Cyp4b1 content. Lauric acid, a substrate of Cyp4b1, efficiently inhibited DCB bioactivation by renal and bladder microsomes of the mouse and by purified Cyp4b1. To assess the contribution of CYP4B1 to bladder carcinoma, further investigation was done with the umu test and an immunochemical study. Ten forms of purified rat P450s including rat CYP4B1 were used in the umu test for 2-NA, DMAB, and DCB. CYP4B1 had the highest activity toward DMAB and DCB. Other P450s had activities of less than 20% that of CYP4B1. CYP4B1 also activated 2-NA, but its activity was about 10% of that toward DMAB or DCB. Rat bladder epithelium was stained specifically with anti-Cyp4b1 antibody, indicating the presence of CYP4B1 in the rat bladder mucosa. Also, CYP4B1 mRNA was detected by northern blotting and reverse transcription-polymerase chain reaction (RT-PCR). These findings suggested that CYP4B1 could contribute to the initiation of carcinogenesis in rat and mouse bladder by activation of aromatic amines.

Animals↗
PubMed1997

Detection of pancreatic and gastric cancer cells in peripheral and portal blood by amplification of keratin 19 mRNA with reverse transcriptase-polymerase chain reaction.

Reverse transcriptase-polymerase chain reaction (RT-PCR) targeted at keratin 19 mRNA was applied to detect circulating cancer cells in the peripheral and portal blood of pancreatic and gastric cancer patients. Keratin 19 mRNA expression was studied by RT-PCR in cancer tissues (12 pancreatic and 15 gastric cancers) and in peripheral and/or portal blood samples from patients with pancreatic cancer (stage I, n = 5; stage II, n = 1; stage III, n = 15; stage IV, n = 19), gastric cancer (stage la,b, n = 28; stage II, n = 9; stage IIIa,b, n = 5; stage IVa,b, n = 7) and benign pancreatic diseases (n = 7). Peripheral blood samples from 50 healthy volunteers served as controls. RT-PCR was conducted in duplicate in each sample, and only samples showing keratin 19 transcript in both determinations were considered as being positive. All the pancreatic and gastric cancers, but none of the control blood samples, were found to be positive. Dilution study using pancreatic cancer cells serially mixed against peripheral blood showed that detection sensitivity was more than one cancer cell in 10(6) peripheral blood mononuclear cells. In pancreatic cancer patients, RT-PCR analysis of the portal blood samples gave positive results in one stage III and one stage IV patient, and that of peripheral blood samples gave positive results in 2 stage IV patients. No positive results were obtained in any of the blood samples from gastric cancer patients. Our results indicate that incidence of circulating cancer cells is unexpectedly very low even in advanced pancreatic and gastric cancer patients.

Humans↗
PubMed1997

Specific binding of 1-[2-(diphenylmethoxy)ethyl]-4-(3-phenyl propyl) piperazine (GBR-12935), an inhibitor of the dopamine transporter, to human CYP2D6.

The binding of [3H]1-[2-(diphenylmethoxy)ethyl]-4-(3-phenyl propyl) piperazine (GBR-12935), an antagonist of the dopamine transporter, to human P450s expressed in yeast cells was investigated. Among the ten forms of human P450 tested (CYP1A1, 1A2, 2A6, 2B6, 2C8, 2C9, 2C18, 2D6, 2E1, and 3A4), [3H]GBR-12935 bound most strongly to CYP2D6. The calculated Kd of [3H]GBR-12935 binding to CYP2D6 was 42.2 nM, indicating that GBR-12935 has a high affinity for CYP2D6. The characteristics of [3H]GBR-12935 binding to CYP2D6 were investigated by competitive studies using several chemicals. The binding of [3H]GBR-12935 to CYP2D6 was not changed by dopamine, suggesting that these binding sites are not dopamine-sensitive binding sites. The binding of [3H]GBR-12935 to CYP2D6 was decreased partially by substrates or inhibitors of CYP2D isoforms (quinine, quinidine, propranolol, bufuralol, imipramine, and desipramine). By means of binding studies using several forms of expressed human P450, we demonstrated that the CYP2D isoform is one GBR-12935 binding site that is insensitive to dopamine.

Carrier Proteins↗
PubMed1997

Isolation of murine and human homologues of the fission-yeast dis3+ gene encoding a mitotic-control protein and its overexpression in cancer cells with progressive phenotype.

To investigate genes involved in metastasis, we used a differential display method to compare the levels of gene expression in three cell lines derived from murine colon-adenocarcinoma 26 that show different metastatic potentials. The results, and subsequent Northern analyses, confirmed that one gene was expressed most strongly in NL17, the cell line with the highest experimentally metastatic potential to the lung; strongly in NL22, the line with moderately metastatic potential; and very weakly in NL4, which has no metastatic potential in recipient mice. Using this fragment as a probe, we isolated the murine cDNA as well as its human homologue and determined their DNA sequences. The cDNA sequences from both species contained open reading frames of 2874 nucleotides, encoding peptides of 958 amino acids with calculated molecular weights of approximately 109,000; the murine and human nucleotide sequences were 90% identical. The deduced amino acid sequences of these cDNAs revealed significant homology (45% identity) to the dis3+ gene product of Schizosaccharomyces pombe, a protein thought to be essential for mitotic control in the yeast. We therefore termed the murine and human genes hmc (homologue to the mitotic-control gene) and HMC, respectively. In 7 of 13 patients with colorectal cancers and liver metastases, expression of HMC was increased up to 38-fold in primary tumors and metastatic foci as compared to adjacent normal colorectal mucosa. An increase in expression of HMC, its novel product likely to belong to a structurally distinct family of mitotic-control proteins, may be associated with malignant phenotypes of some colorectal cancers.

Adenocarcinoma↗
PubMed1997

Genetic detection of colorectal cancer cells in circulation and lymph nodes.

PURPOSE: This study was undertaken to investigate the clinical implications of detection of genetic alterations in blood and lymph nodes in colorectal cancer patients. METHODS: The reverse transcriptase polymerase chain reaction product of the cytokeratin gene in blood was examined as a cancer cell-specific expression in 35 colorectal cancer patients. The K-ras or p53 gene mutations in the lymph nodes histopathologically negative for metastasis were studied by the mutant-allele-specific amplification method in 26 colorectal cancer patients. RESULTS: The reverse transcriptase polymerase chain reaction assay was able to detect a cytokeratin reverse transcriptase polymerase chain reaction product at a concentration from a single to ten colon cancer cells per 10(6) normal peripheral blood mononuclear cells. Cytokeratin reverse transcriptase polymerase chain reaction products were detected in nine patients' blood samples, although none of the samples were cytologically detectable. The blood's cytokeratin positivity correlated with the invasive mode of the tumor (P < 0.05) and the presence of distant metastasis (P < 0.01). Two (50 percent) of four patients whose blood was positive for cytokeratin had recurrences. Of 17 patients with the K-ras or p53 gene mutation in primary tumors, 9 (53 percent) had the corresponding mutations in lymph nodes. Mutation positivity in lymph nodes correlated with the presence of lymphatic invasion of the primary tumor (P < 0.05). All patients with mutation-negative lymph nodes remained disease-free for more than two years after surgery. CONCLUSION: Detection of cytokeratin reverse transcriptase polymerase chain reaction products in the blood and K-ras or p53 gene mutations in the lymph nodes histologically negative for metastasis may be applicable for clinical use, despite some limitations, and may serve as a useful clinical factor for stratifying patients who are at high or low risk for recurrence after surgery.

Biomarkers, Tumor↗
PubMed1997

Involvement of carbohydrate antigen sialyl Lewis(x) in colorectal cancer metastasis.

PURPOSE: Recognition of metastatic tumor cells with distinct biochemical phenotypes predominant in the primary tumors should be useful not only for establishment of new therapeutic approaches but also for identification of high-risk or low-risk patients for relapse. We examined whether carbohydrate antigens, sialyl Lewis(x) (sLe(x)) and sialyl Lewis(a) (sLe(a)) are involved in colorectal cancer metastasis. METHODS: Metastatic abilities of human colon cancer cell variants that were selected for their high or low cell surface levels of sLe(x) (KM12-HX and KM12-LX, respectively) were analyzed. Also, immunohistochemical expressions of sLe(x) and sLe(a) in 159 primary colorectal cancers were examined to determine the clinical significance of increased expression of these antigens. RESULTS: KM12-HX cells adhered more readily to tumor necrosis factor-alpha activated endothelial cells than did KM12-LX cells. Increased adhesion of KM12-HX cells to activated endothelial cells was inhibited by antibodies against E-selectin and sLe(x) and by modification of cell surface carbohydrates. KM12-HX cells showed more invasive ability in vitro and more metastatic potential in the liver of nude mice than KM12-LX cells. Although no difference was seen in the expression of six messenger ribonucleic acids corresponding to progression or metastasis of colorectal cancer, expression of fucosyltransferase was found to be responsible for the higher expression of sLe(x) in KM12-HX cells. Clinical records of patients showed that disease-free survival rate of patients with sLe(x)-positive tumors was significantly poorer than that of those with sLe(x)-negative tumors. Cox's multivariate analysis revealed that the sLe(x) status was an independent predictive factor for disease recurrence (P = 0.004), depth of invasion (P = 0.0005), and histologic type (P = 0.037), but sLe(a) status, age, gender, tumor location, N stage, and vessel invasion were not. CONCLUSION: Increased expression of sLe(x) could be involved in establishment of colorectal cancer metastasis. It appears that examining sLe(x) expression may serve as a potent marker of the recurrence in patients with colorectal cancer.

Adult↗
PubMed1997

Increased endothelial cell retraction and tumor cell invasion by soluble factors derived from pancreatic cancer cells.

BACKGROUND: Tumor cells induce endothelial cell retraction before invasion. In pancreatic cancer cells, the factors affecting endothelial cell retraction are not well-understood. METHODS: The activities of the endothelial cell retraction in conditioned media (CM) derived from three human pancreatic cancer cell lines, PSN-1, MiaPaca-2, and Capan-1, were measured for the amount of intercellular junctional transport of FITC dextran through an endothelial cell monolayer in a transwell cell culture system. RESULTS: The CM derived from the three pancreatic cancer cells induced endothelial cell retraction. The endothelial cell retraction activity in the CM from PSN-1 cells was significantly higher than those from MiaPaca-2 and Capan-1 cells. The CM from PSN-1 cells enhanced both the adhesion and the invasion of MiaPaca-2 and Capan-1 cells. The factors with endothelial cell retraction activity in the CM from PSN-1 cells were characterized as heat-stable, trypsin-sensitive glycoproteins ranging from 10,000 to 50,000 in molecular weight, and were found both in heparin-bound and unbound fractions. CONCLUSIONS: PSN-1 cells produced and secreted at least two factors inducing the endothelial cell retraction. The factors could play an important role in the establishment of invasion and metastasis of PSN-1 cells.

Cell Adhesion↗
PubMed1997

Effects of ischemia-reperfusion on individual cytochrome P450 isoforms in the rat kidney.

Ischemia-reperfusion of organs such as the kidney produces reactive oxygen and free radical species in tissues and leads to injury of intracellular molecules critical to cell homeostasis. Ischemia-reperfusion affects the NADPH-dependent monooxygenase system including P450 system, which is also a source of reactive oxygen species. In this study, the effects of ischemia-reperfusion on monooxygenase activity and levels of individual P450 isoforms including CYP2C23, 4A2, and 4A8 in the rat kidney were investigated. Ischemia of the rat kidney for 30 min had little effect on lauric acid hydroxylation activity and levels of P450 isoforms but ischemia for 60 min significantly decreased lauric acid omega- and (omega-1)-hydroxylation activities and also decreased the levels of CYP2C23, 4A2, and 4A8. Reperfusion for 60 min after 30-min ischemia decreased the levels of CYP2C23 and 4A2 in the rat kidney although 30-min ischemia did not. Reperfusion for 240 min after 30-min or 60-min ischemia recovered the decreased levels of lauric acid hydroxylation activity and the levels of CYP2C23 and 4A2. Changes in the levels of monooxygenase activity and the levels of P450 isoforms in kidneys by ischemia-reperfusion are faster than those in the liver; it takes several hours for ischemia-reperfusion to affect the levels of monooxygenase activity and the levels of P450 in the rat liver. Our findings suggest that damage of P450 isoforms in the kidney by ischemia-reperfusion occurs by a mechanism different from that in the liver and that active oxygen or free radical species directly attack proteins.

Animals↗
PubMed1997

Expression of cytochrome P450 isoforms in rat hepatic stellate cells.

The current study evaluated the expression and the inducibility of cytochrome P450 isoforms in rat hepatic stellate cells (HSCs). Immunoblotting study revealed that HSCs expressed several P450s and CYP2C11, 3A2, and 2D1 were major isoforms. The levels of CYP2B1, 2C11, 2D1, 2E1, and 3A2 in HSCs were 14 - 38% of those in hepatocytes. CYP1A2 content was similar in each cell type. These P450 levels in HSCs gradually decreased during culture as seen in hepatocytes; the level of CYP3A2 rapidly, whereas that of CYP2D1 slowly decreased. Phenobarbital, a typical inducer of CYP3A2 and 2B1 increased CYP3A2 level as well, but had less potency in the induction of CYP2B1 in HSCs. These results indicate that multiple P450 isoforms were present in HSCs, but their content and inducibility were different between HSCs and hepatocytes.

Animals↗
PubMed1997

A comparison of hepatic cytochrome P450 protein expression between infancy and postinfancy.

We immunochemically measured the contents of 9 different cytochrome P450 (CYP) isoenzymes expressed in the liver and compared them between two groups: one group of 6 infant and 4 perinatal patients and one group of 10 patients after infancy (over 1 year old). CYP protein expressed in human liver can be divided into three groups on the basis of expression pattern: (a) CYP2A6, 2C9, 2D6, 2E1, and 3A were present in all samples and no difference was observed between the two groups; (b) CYP1A2, 2B6, and 2C8 were expressed more after infancy than during infancy; and (c) CYP3A7, which has been considered a major CYP enzyme in fetal liver microsomes, was expressed in all infants as well as the four perinatal patients, whereas it was detected in only 2 patients after infancy. These results implied that CYP2A6, 2C9, 2D6, 2E1, and 3A are already expressed during perinatal and infant period, while CYP1A2, 2B6, and 2C8 are expressed highly in subjects over 1 year old, and CYP3A7 disappeared after infancy.

Adolescent↗
PubMed1997

Practical grouping of positive lymph nodes in pancreatic head cancer treated by an extended pancreatectomy.

BACKGROUND: Until recently long-term survival has not been expected when at least one positive node was detected at any site in pancreatic head cancer treated by conventional pancreatectomy. However, even when nodal involvement is seen, there has been an increasing number of long-term survivors after extended pancreatectomy in which a wide range of lymphatic and connective tissues were cleared. Thus the purpose of the present study was to establish a practical rational grouping of positive lymph nodes in pancreatic head cancer treated by extended pancreatectomy. METHODS: In 81 patients who tolerated extended pancreatectomy for cancer of the pancreatic head, a mean of 56 +/- 23 (range, 28 to 89) lymph nodes in each patient were examined under a microscope to determine the presence or absence of cancer. They were classified anatomically into 14 lymph node groups, and the incidence, distribution, and number of positive nodes were examined. A simplified grouping was made on the basis of the histologic findings and was checked against long-term survival rates. RESULTS: Nodal involvement was detected in 59 (73%) of 81 patients, and positive nodes were more commonly observed in the posterior pancreaticoduodenal (PPD), superior mesenteric (SM), and anterior pancreaticoduodenal (APD) groups than in the 11 other groups (p < 0.05). The PPD, APD, and SM groups offered the sole sites of nodal involvement with incidence levels of 23%, 17%, and 6%, respectively, whereas none of the 11 other groups did. Thus patients were classified into four groups: (a), negative in all 14 lymph node groups (n = 22); (b), positive but limited to the PPD/APD groups (n = 14); (c), also positive in the SM group, but negative in the 11 other groups (n = 13); and (d), also positive in at least one of the 11 other groups (n = 32). This classification was associated well with the 5-year survival rate: 59% in group (a), 53% in group (b), 15% in group (c), and 0% in group (d) [p < 0.05; group (b) versus group (c)]. Also this grouping associated well with the total number of positive nodes (p < 0.05). The 5-year survival rate in patients with one to three positive nodes was 47% and was more than 6% in patients with four to seven positive nodes (p < 0.05). CONCLUSIONS: In the clinicopathologic staging of the lymphatic spread from carcinoma of the pancreatic head, the PPD and APD groups were considered the first stations of lymphatic metastasis, whereas the 12 other groups-including the SM group-were categorized as second or more distant stations.

Humans↗
PubMed1997

Association of cumulative allelic losses with tumor aggressiveness in hepatocellular carcinoma.

BACKGROUND/AIMS: Loss of heterozygosity on various chromosomal arms has been reported in hepatocellular carcinoma and a multistep accumulation of genetic alteration has become accepted as the mechanism underlying progression of the disease. Although cumulative genetic alterations may imply more malignant tumors with poorer prognosis, the assumption requires further investigation. METHODS: Presence of loss of heterozygosity was analyzed by microsatellite markers at 13 loci on six chromosomal arms in 56 hepatocellular carcinomas. Association with cumulative allelic losses and prognosis of the patient following curative resection was studied. RESULTS: Frequency of allelic losses at each chromosomal arm was 31% on 1p, 20.6% on 4q, 17.5% on 8p, 17.5% on 13q, 25.5% on 16q and 17.4% on 17p. Thirty-three tumors (59%) presented loss of heterozygosity. Tumors with more allelic losses were significantly more likely to be un-infected by hepatitis C virus, and to be histologically poorly differentiated, to have higher alpha-feto protein value, to be advanced in T classification and in tumor stage. Patients with more than one loss of heterozygosity revealed poorer 3-year disease-free survival than those with one or no (p=0.0004). A multivariate Cox model analysis revealed cumulative loss of heterozygosity as an independent and influential factor for disease recurrence (relative risk, 2.66; 95% confidence interval, 1.23-5.75; p=0.013), followed by tumor stage. CONCLUSIONS: Cumulative loss of heterozygosity reflects the multistep genetic mechanism of progression of hepatocellular carcinoma. The study confirms the potential significance of genetic analysis in the management of the disease.

Adult↗
PubMed1997

Isozyme selective alterations of the expression of cytochrome P450 during regeneration of male rat liver following partial hepatectomy.

1. During liver regeneration in the male rat, the metabolic activities of imipramine were differentially affected depending on the specific metabolic pathways. Imipramine N-demethylation was markedly reduced whereas 2-hydroxylation showed only a moderate reduction following partial hepatectomy. 2. A slight decline was observed in the hepatic microsomal content of CYP2D apoprotein, whereas a substantial decrease occurred in CYP2C11 content during liver regeneration. Since imipramine 2-hydroxylation and N-demethylation are mediated by CYP2D and 2C11 respectively, metabolic pathway-specific alterations in the activities of imipramine metabolism are explained by the isozyme selective alteration in the levels of CYPs in regenerating liver. 3. No significant effect of regeneration was observed on expression of CYP2B1 and 2E1 apoproteins. CYP3A2 apoprotein, one of the male-specific CYP isoforms, was significantly suppressed in regenerating liver showing a similar pattern of alteration to the levels of CYP2C11. The alteration pattern of the CYP1A1 level was different to the above with a moderate decline at the first day post-operation and a marked rebound thereafter. 4. In the partially hepatectomized male rate, no significant increase in androstenedione 5-alpha reductase activity, an activity predominant in the female rat, was detected. It is concluded that the pattern of alterations of hepatic oxidative metabolism during liver regeneration was not related to the functional feminization of the liver.

Androstenedione↗
PubMed1997

Isolation of a novel gene showing reduced expression in metastatic colorectal carcinoma cell lines and carcinomas.

To investigate genes involved in metastatic stages of cancer, we analyzed expression of mRNAs in three cell lines derived from murine colon adenocarcinoma 26 by means of a differential display method. Each of these lines exhibits distinct metastatic characteristics. Among many bands representing different expression patterns in the display, we confirmed by northern analysis that a gene corresponding to one amplified fragment, termed grm2 (gene related to metastasis 2), was expressed more abundantly in NL4, the derivative with the lowest metastatic potential, than in cell lines NL17, an experimentally metastatic derivative, and in NL22, a spontaneously metastatic derivative. Using the grm2 fragment as a probe, we isolated murine cDNA clones and subsequently human cDNA clones corresponding to the GRM2 gene. The human and mouse homologues both encode proteins of 600 amino-acid residues, which show weak homologies to proteins belonging to the myosin family. When we examined the expression levels of this novel gene in human colon cancers and in corresponding metastatic foci, we found that in more than half of these tissues, expression was significantly reduced in association with malignant potential. Our results imply that in humans the GRM2 gene product may regulate the metastatic phenotype of some colorectal cancers.

Adenocarcinoma↗