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Biomedical subjects

S Baba

Publications and source records attributed to S Baba.

At least 199 records · Page 11Linked to original sources

Association of Ile462Val (Exon 7) polymorphism of cytochrome P450 IA1 with lung cancer in the Asian population: further evidence from a case-control study in Okinawa.

Okinawa, a group of islands that lie between the East China Sea and the Pacific Ocean, 2000 km south of the Japanese main islands, has a different profile of diseases, ethnicities, and cultures than does the rest of Japan. We examined an Ile462Val polymorphism (CYP1A1*2 allele) of cytochrome P450 IA1 in a hospital-based case-control study of lung cancer patients (247 cases and 185 controls) in Okinawa to ascertain the association of this variant with lung cancer. In addition, the distribution of this genotype was studied in populations from different areas of Japan, including Tokyo (n = 69) and Iwate (northern part of Japan; n = 81), as well as in a Chinese group from the Jiangsu province (n = 39) and in an Australian Caucasian group (n = 146). Genotype frequency in controls was not significantly different from area to area in Japan. In Okinawa, however, the genotype encoding Val/Val was associated with a significantly higher risk of lung cancer (odds ratio = 3.32, P = 0.013), especially of squamous cell carcinoma and small cell carcinoma (odds ratio = 4.85 and 9.35, respectively). The Val-encoding allele was less frequent in the Chinese population and was rare in Australian Caucasians. Thus, this study gives support to the value of the cytochrome P450 IA1 Ile462Val polymorphism as a practical high-risk marker of lung cancer in populations, especially those in southeast Asia, in which this variant is more common.

Adult↗

Association between tumor necrosis factor in serum and cachexia in patients with prostate cancer.

The present study was undertaken to evaluate the relationship between serum tumor necrosis factor (TNF) and cachexia in patients with prostate cancer. TNF levels were determined in 110 serum samples from prostate cancer patients by an enzyme immunoassay. Serum TNF activity was positive in 76% of the patients with relapsed disease, whereas only 11% of the untreated patients and 0% of the patients in remission as a result of endocrine therapy were positive. The serum total protein and albumin levels, hemoglobin levels, and body mass index of the patients with elevated serum TNF levels were significantly lower (P < 0.05) than the corresponding values in patients with undetectable serum TNF levels. The serum TNF levels of patients with serum albumin levels of <3.5 g/dl, serum total protein levels of <7.0 g/dl, hemoglobin levels of <11.0 g/dl, and a body mass index of <21 kg/m2 were significantly higher (P < 0.05) than the values in their respective counterparts. There was a significant correlation between the detectability of serum TNF and performance status (P < 0.05). Patients with elevated serum TNF levels had a significantly higher mortality rate (P < 0.05) than those with undetectable serum TNF levels. These findings suggest that TNF may be one of the factors contributing to the complex syndrome of cachexia in patients with prostate cancer.

Adenocarcinoma↗

[Molecular biological background of FAP and HNPCC, and treatment strategies of both diseases depend upon genetic information].

Recent advancement of molecular biology disclose responsible genes of FAP(familial adenomatous polyposis) and HNPCC(hereditary non polyposis colorectal cancer). Gardner Syndrome is now categorized as subtype of FAP. Turcot Syndrome is now known as a heterogeneous disease. Turcot Syndrome caused by APC gene develops medulloblastoma and Turcot Syndrome caused by mismatch repair gene develops glioblastoma. Because of the discovery of APC gene, the presymptomatic diagnosis of asymptomatic gene carriers are now available and preventive surgery can be planned. FAP patients with mutated APC gene between codon 1250 and 1464 shows severe phenotype. It is known that FAP patient whose APC gene mutation locates at codon 1309 develops cancer 10 years earlier in comparison to the rest of the cases. Consequently risky rectal mucosa should be removed in this group of patients. As for HNPCC, presymptomatic diagnosis is still not possible because the penetrance rate has not been estimated yet and some additional responsible genes are expected to be discovered. Replication error, mutator phenotype of mismatch repair gene is useful indicator to predict second primary cancers. When the patient in a HNPCC family develops adenoma with microsatellite mistability, preventive colectomy might be one of the surgical option with the informed consent of the patient.

Adenomatous Polyposis Coli↗

[Microwave tissue coagulation therapy with mini-laparotomy for hepatocellular carcinoma].

Recently microwave tissue coagulation therapy (MCT) has been established as a therapeutic procedure for hepatocellular carcinoma (HCC). The route of approach to penetrate the tumor is two-fold: By the percutaneous route (PMCT) or by conventional laparotomy. PMCT has the advantage of less invasive therapy, however, it is not applicable to a tumor that cannot be detected by ultrasonography. Therefore, we tried MCT with mini-laparotomy. The patient was a 57-year old man with HCC located in the S6 subsegment. The operation was performed at the semi-right side up position, and laparotomy was done by skin incision of 12 cm in the right hypochondral area. MCT was performed about 30 times, with an output of 60 watts for 45 seconds at a time. Abdominal CT image showed a low-density area of 7 x 4 cm on the 18th postoperative day. Slight damage to the liver and no obvious complications were observed. We concluded that a much wider range-coagulation than PMCT was able to be obtained by MCT with mini-laparotomy, and postoperative quality of life was better than MCT with conventional laparotomy.

Carcinoma, Hepatocellular↗

[Dysfunction of E-cadherin-catenin system in invasion and metastasis of colorectal cancer].

The E-cadherin-mediated cell adhesion system is now considered to be an "invasion suppressor system" in cancer cells. Dysfunction of the E-cadherin system due to mutations of the genes of E-cadherin and catenins has not been reported in colorectal cancer. Histologically, well-differentiated colorectal cancer cells are found to be scattered at the invasive front in primary lesions and form glands again in metastatic sites. We have reported the association and presence of signal transduction between c-erbB-2/epidermal growth factor receptor (EGF-R) and beta-catenin in human cancer cells. This temporal dysfunction of the E-cadherin system observed in colon cancers may be caused by tyrosine phosphorylation of beta-catenin through activated receptor-type tyrosine kinases. Overexpression of EGF-R and tyrosine phosphorylation of beta-catenin are often observed in "focal dedifferentiated cells" at the invasive front of colorectal cancers. In addition, beta-catenin expression is regulated by the APC tumor suppressor gene product. Thus the E-cadherin-catenin system may play important roles not only in invasion and metastasis but also in the carcinogenesis of colorectal cancer.

Adenomatous Polyposis Coli Protein↗

[Therapeutic effect of angiogenesis inhibitors on liver metastases of human colorectal carcinoma].

Angiogenesis is essential for the growth of solid tumors. Antiangiogenic therapy has therefore attracted considerable interest as a novel therapy for various tumors including colorectal carcinoma. We experimentally investigated the therapeutic effect of TNP-470, a nonspecific inhibitor of angiogenic factors, and vascular endothelial growth factor (VEGF)-neutralizing antibody (VEGFAb), was a VEGF-specific inhibitor, on liver metastases of colon carcinoma using a murine orthotopic transplantation model. TK-4 and TK-13 are moderately differentiated adenocarcinoma strains established in our department which express VEGF mRNA and protein. Administration of TNP-470 30 mg/kg significantly inhibited the liver metastases of both strains, as did administration of VEGFAb 100 micrograms/mouse. The therapeutic effect on liver metastases was more dominant with antiangiogenic therapy than with chemotherapy (mitomycin C). Furthermore, the sustained effect of TNP-470 induced tumor dormancy and consequently improved the survival of the animals. These results suggest that antiangiogenic treatment will be a potent therapy for liver metastases of human colorectal carcinoma in the future.

Animals↗

[Studies on the conditions of blood sampling and storage for the liposome-based CH50 assay].

The CH50 values in the serum and plasma, especially those from chronic hepatitis caused by hepatitis C virus (HCV), are strongly affected and reduced through a process known as cold activation. We attempted to optimize the conditions of blood sampling and storage for the CH50 assay with a recently developed liposome-based assay kit. The bloods were obtained from HCV hepatitis patients as well as healthy donors. Regardless of the temperature (room temperature, 4 degrees C or 37 degrees C) at which samples were kept until the assay, higher values were always obtained in the serum than in the plasma. The plasma samples could either be heparinized or given any of the other anticoagulants, EDTA-2K and sodium citrate, at the time of sampling. We also attempted to optimize the temperature at which the fresh specimens were left during the period from sampling to assay and the temperatures to freeze them for storage and to thaw for assays. In the assays immediately after sampling, higher values were obtained when the specimens were left at 37 degrees C than at room temperature or 4 degrees C. To store at -80 degrees C rather than at -20 degrees C and to thaw rapidly at 37 degrees C rather than slowly at room temperature were found to be advantageous.

Blood Preservation↗

Human squamous-cell-carcinoma cell line (DJM-1) cells synthesize P-cadherin molecules via an elevation of extracellular calcium: calcium regulates P-cadherin-gene expression at the translational level via protein tyrosine phosphorylation.

Spatially-regulated P-cadherin expression is crucial for maintaining the normal epidermal architecture. P-cadherin expression in cutaneous squamous-cell carcinomas (SCC) is altered, and may participate in tumor progression. We therefore investigated how P-cadherin expression was regulated in a cultured cutaneous SCC cell line (DJM-1). At low calcium concentration (0.05 mM), DJM-1 cells expressed P-cadherin weakly in the cytoplasm. At a higher calcium concentration, P-cadherin was promptly translocated to the cell surface within 30 min, gradually increased on the cell surface for up to 48 hr, and was continuously expressed for at least 7 days. During this time course, the total amount of P-cadherin protein had increased, whereas the steady-state mRNA levels for P-cadherin had not changed. The inhibition of protein synthesis by cycloheximide, but not the inhibition of gene transcription by actinomycin-D, completely suppressed the expression of P-cadherin. The effect of calcium was inhibited by tyrphostins but not by H-7, cholera toxin, or dibutylic cyclic AMP. Increments in the extracellular calcium concentration did not mobilize the intracellular calcium pool, and were accompanied by the tyrosine phosphorylation of a 62-kDa protein. In addition, DJM-1 cells expressed mRNA for a calcium-sensing receptor originally demonstrated in the parathyroid gland. The results suggest an unique mechanism for regulating P-cadherin gene expression in DJM-1 cells by extracellular calcium, which stimulates the de novo synthesis of P-cadherin at the translational level through protein tyrosine phosphorylation.

Base Sequence↗

Alteration of reticuloendothelial phagocytic function and tumor necrosis factor-alpha production after total hepatic ischemia.

BACKGROUND: This study was conducted to determine whether the duration of total hepatic ischemia influences reticuloendothelial phagocytic activity and tumor necrosis factor (TNF)-alpha production after reperfusion. METHODS: Male rats pretreated with either normal saline (NS group) or gadolinium chloride (7 mg/kg) for 2 days to inhibit Kupffer cell function (GC group) were subjected to 30, 60, or 90 min of total hepatic ischemia. RESULTS: The animals tolerated hepatic ischemia well for 30 and 60 min. Although the 7-day survival rate of the NS group decreased to 28% after 90 min of hepatic ischemia, that of the GC group improved significantly to 68% (P<0.01). In the NS group, plasma alanine transaminase and TNF-alpha levels after reperfusion increased with the length of hepatic ischemia. The phagocytic index (PI) after 60 min of reperfusion following 90 min of hepatic ischemia showed significant depression compared with the preischemic level and the value after 30 or 60 min of ischemia. The GC group had significantly lower plasma alanine transaminase and TNF-alpha levels as well as significantly less polymorphonuclear leukocyte infiltration in the liver compared with the NS group. The preischemic PI was significantly inhibited in the GC group when compared with that in the NS group, but PI in the GC group did not change significantly after reperfusion, irrespective of the ischemic time. CONCLUSIONS: This study demonstrated that warm ischemia of up to 60 min is tolerable for normal rat liver without a detrimental effect on phagocytic activity. Modulation of Kupffer cell function may have the potential to prevent reperfusion injury after hepatic ischemia, which may allow safe prolongation of the ischemic time.

Alanine Transaminase↗

Development of flexible ventriculoscope (Yamadori-type VII) and its application to experimental animals.

We developed a new ventriculoscope (Yamadori-type VII), a 2.1 mm calibrated fiberscope with a monopolar coagulator, that can be inserted from the cisterna cerebellomedullaris into the third cerebral ventricle of experimental animals, like dogs. With the improved performance of the neuroendoscope compared to its prototype, Yamadori III, it was possible to inspect clearly and to produce electrocoagulative lesions accurately on any part of the intraventricular structures with minimal injury to nearby vital brain areas.

Animals↗

Effects of endocrine therapy on the primary lesion in patients with prostate carcinoma as evaluated by endorectal magnetic resonance imaging.

BACKGROUND: Little effort has been made at the quantitative and qualitative evaluation of patients with prostate carcinoma, including downsizing and downstaging of the primary lesion, after conservative therapy. The current study was undertaken to investigate the qualitative and quantitative effects of endocrine therapy on the primary prostate carcinoma using magnetic resonance imaging (MRI). METHODS: The primary prostate carcinoma was evaluated by endorectal MRI approximately 4 months after the initiation of endocrine therapy in 48 patients with histologically confirmed prostate carcinoma detected by endorectal MRI before therapy. RESULTS: The volumes of the prostate gland, the carcinoma, and the noncarcinomatous components were reduced to 60.2 +/- 2.7%, 25.5 +/- 2.9%, and 83.2 +/- 6.3% of their pretreatment volumes respectively after endocrine therapy, indicating that the tumors are more susceptible to endocrine therapy than the nontumorous components. The number of prostate carcinomas that demonstrated low signal intensity compared with the normal peripheral zone on T2-weighted images decreased after endocrine therapy and the number of carcinomas with enhancement of T1-weighted contrast-enhanced images increased after therapy. Seven of the 48 patients underwent downstaging after endocrine therapy, based on the endorectal MRI evaluation. CONCLUSIONS: The results of the current study suggest that downsizing and occasionally downstaging of the carcinoma may occur after endocrine therapy in patients with prostate carcinoma. In addition, the androgen sensitivity of the prostate carcinoma tissue is relatively high compared with the residual noncancerous prostate gland.

Antineoplastic Agents, Hormonal↗

Effect of angiogenesis inhibitor TNP-470 on the progression of human gastric cancer xenotransplanted into nude mice.

The effect of an angiogenesis inhibitor, TNP-470, on primary tumor growth, liver metastasis and peritoneal dissemination of gastric cancer was investigated by means of an orthotopic xenotransplanted model of 2 human gastric cancers, MT-2 and MT-5. TNP-470 showed a significant inhibitory effect on the growth of primary tumors after orthotopic transplantation of both xenografts when given at a dose of 30 mg/kg on alternate days from day 7 after transplantation (early treatment). However, growth of the MT-2 primary tumor was not inhibited by administration from day 14 after transplantation (late treatment). Liver metastasis was prevented significantly by early treatment of TNP-470. In particular, early treatment of MT-2 completely inhibited the development of macroscopic foci in the liver and was significantly more effective than late treatment. Peritoneal dissemination also was inhibited. Thus, TNP-470 was revealed to have strong inhibitory activity not only on primary tumors and liver metastases but also against peritoneal dissemination. These results suggest that this agent may provide a new approach to the treatment of gastric cancer.

Adenocarcinoma↗

Expression of alpha and beta genes of human chorionic gonadotropin in lung cancer.

To confirm the ectopic production of human chorionic gonadotropin (hCG) in lung cancer, we attempted to detect the presence of mRNA transcripts of the alpha and beta genes for hCG in lung cancer tissues obtained from surgical operations. Although we were able to show the presence of hCG beta mRNA transcripts in lung cancer tissue by Northern blot, the sensitivity of the assay was too low for a precise analysis of hCG beta mRNA transcripts in most lung cancers. Using reverse transcription PCR (RT-PCR) and Southern blot analysis, however, various amounts of mRNA transcripts of hCG beta genes 3, 5, 7 and 8 were demonstrated in 9 of the 14 lung cancer tissues examined, while no mRNA transcripts were detectable in 12 normal lung tissues from the same patients. Our results are consistent with a clear difference in serum and urinary hCG beta levels observed between normal subjects and lung cancer patients. The expression of the hCG alpha gene, however, was detected in normal lung tissues more frequently than in lung cancer tissues using RT-PCR Southern blot. Our results strongly suggest the production of hCG beta as being part of the phenotype of malignantly transformed lung cells and further strengthen its superior specificity over intact hCG or hCG alpha as a tumor marker for lung cancers.

Aged↗