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Biomedical subjects

Seiji Igarashi

Publications and source records attributed to Seiji Igarashi.

9 recordsLinked to original sources

Comparative characterization of pulmonary surfactant aggregates and alkaline phosphatase isozymes in human lung carcinoma tissue.

Alkaline phosphatase (AP) isozymes are surfactant-associated proteins (SPs). Since several different AP isozymes have been detected in the pneumocytes of lung cancer patients, we attempted to identify the relationship between pulmonary surfactant aggregate subtypes and AP isozymes. Pulmonary surfactant aggregates were isolated from carcinoma and non-carcinoma tissues of patients with non-small cell carcinoma of the lung. Upon analysis, ultraheavy, heavy, and light surfactant aggregates were detected in the non-carcinoma tissues, but no ultraheavy surfactant aggregates were found in the carcinoma tissues. Surfactant-associated protein A (SP-A) was detected as two bands (a 27-kDa band and a 54-kDa band) in the ultraheavy, heavy, and light surfactant aggregates found in the non-carcinoma tissues. Although both SP-A bands were detected in the heavy and light surfactant aggregates from adenocarcinoma tissues, the 54-kDa band was not detected in squamous cell carcinoma tissues. Liver AP (LAP) was detected in the heavy and light surfactant aggregates from both non-carcinoma and squamous carcinoma tissues, but not in heavy surfactant aggregates from adenocarcinoma tissues. A larger amount of bone type AP (BAP) was found in light surfactant aggregate fractions from squamous cell carcinomas than those from adenocarcinoma tissues or non-carcinoma tissues from patients with either type of cancer. LAP, BAP, and SP-A were identified immunohistochemically in type II pneumocytes from non-carcinoma tissues and adenocarcinoma cells, but no distinct SP-A staining was observed in squamous cell carcinoma tissues. The present study has thus revealed several differences in pulmonary surfactant aggregates and AP isozymes between adenocarcinoma tissue and squamous cell carcinoma tissue.

Alkaline Phosphatase↗

Methtrexate-associated lymphoproliferative disorders. A clinicopathological study of 13 Japanese cases.

We conducted clinicopathological and immunohistochemical analyses to investigate the prevalence of Epstein-Barr virus (EBV) among 13 cases with methotrexate (MTX)-associated lymphoproliferative disorder (LPD). The subjects of this study were four men and nine women ranging in age from 53 to 78 years (mean: 63 years). All 13 patients had received low dose MTX therapy for 1-13 years before the onset of LPD (mean: 5.8 years). LPDs were found at extranodal sites in six cases, and the disease stage was advanced in seven cases. The present study confirmed certain aspects of a previous observation made in the USA, including the following findings (i) the cases commonly showed diffuse large B-cell lymphomas (n=4) and Hodgkin lymphomas (HL) (n=3), (ii) EBV-encoded small RNA (EBER) + cells were identified in seven cases (60%), which is a much higher percentage than would be expected in lymphomas occurring in a general population, and (iii) three cases of polymorphous small lymphocytic or lymphoplasmacytic infiltrate achieved spontaneous remission of LPDs after MTX withdrawal. Of seven cases of EBER + in our series, three cases were PSLLPI, and two were HL. EBER + tumor cells were detected in only two (30%) of the seven cases with non-Hodgkin lymphomas. The present study suggests that EBV- associated non-Hodgkin lymphomas comprise only a portion of all non-Hodgkin lymphomas among MTX-associated LPDs.

Aged↗

Expression of Vicia villosa agglutinin (VVA)-binding glycoprotein in primary breast cancer cells in relation to lymphatic metastasis: is atypical MUC1 bearing Tn antigen a receptor of VVA?

Aberrant carbohydrate expression frequently occurs in breast cancer and may endow cells with metastatic potential. Here we first studied the relationship between expression of Vicia villosa agglutinin (lectin) (VVA)-binding carbohydrates and aggressive breast cancer. We then investigated the molecular characteristics of these glycoproteins and compared them with those of glycoproteins recognized by the mouse anti-Tn monoclonal antibody (MAb) HB-Tn1. Histochemical studies of samples from 322 cases of invasive ductal carcinoma demonstrated that VVA-binding carbohydrate expression correlated with tumor stage, lymphatic invasion, and lymph node metastasis (p=0.0385, p=0.0019, and p=0.0430. respectively). Western blotting analysis of frozen materials from 39 cases, under denaturing and reducing conditions, revealed that the major cancer cell-specific VVA-binding proteins were molecules of about 30, 33, and >200 kDa. Cases expressing the approximately 33 kDa molecule had significant lymphatic invasion more frequently than did cases not expressing this molecule (p=0.0076). Binding of VVA to the approximately 30 and approximately 33 kDa molecules was completely lost by preincubation of VVA with 1 mM Tn antigen (N-acetylgalactosamine alpha1-O-serine). The VVA-binding molecules appeared to react with VU-3C6 anti-MUC1 MAb. Expression of HB-Tn1 in breast cancer cells showed significant correlation with expression of VVA-binding carbohydrate(s) (p<0.0001) but HB-Tn1 reactivity was not clearly related to breast cancer aggressiveness. Because anti-Tn MAbs bound to Tn antigen clusters, we concluded that atypical MUC1 bearing the noncluster form of Tn antigen is implicated in aggressive growth of primary breast cancer cells, particularly in lymphatic metastasis.

Adult↗

Patterns of recurrence after curative resection of pancreatic cancer, based on autopsy findings.

The autopsy findings of patients who died of recurrence after curative resection of pancreatic cancer may afford a reliable guide to increase long-term survival after surgery. Recurrence patterns were analyzed for 27 autopsied patients who had undergone potentially curative resection of pancreatic cancer. The pattern of recurrence was classified as follows: (1) local recurrence, (2) hepatic metastasis, (3) peritoneal dissemination, (4) para-aortic lymph node metastasis, and (5) distant metastasis not including hepatic metastasis, peritoneal dissemination, and para-aortic lymph node metastasis. Of the 27 autopsied patients, recurrence was confirmed for 22 of 24 patients, except for three who died of early postoperative complications. Eighteen (75%) of the 24 patients had local recurrence, 12 (50%) had hepatic metastasis, and 11 (46%) had both. For four patients, local recurrence confirmed by autopsy was undetectable by computed tomography, because the recurrent lesions had infiltrated without forming a tumor mass. Peritoneal dissemination, para-aortic lymph node metastasis, and distant metastasis were found for eight (33%), five (21%), and 18 (75%) of the cases, respectively. Twenty patients died of cancer, but local recurrence was judged to be the direct cause of death of only four. Local recurrence frequently occurs, but is rarely a direct cause of death, and most patients died of metastatic disease. Therefore, treatment that focuses on local control cannot improve the survival of patients with resectable pancreatic cancer, and thus, treatment regimens that are effective against systemic metastasis are needed.

Adult↗

Correlated expression of human beta defensin-1, -2 and -3 mRNAs in gingival tissues of young children.

OBJECTIVE: Human beta-defensins (hBDs) are a group of antimicrobial peptides, expressed by the epithelial cells of many organs including gingival epithelium. The present study examined correlation between the gene expressions of hBD-1, -2, -3 mRNAs and the inflammatory cytokines in human gingival tissues. STUDY DESIGN: The gingival tissues were obtained from surgical discards from 20 different patients (age range, 5-13 years). The expression levels of mRNAs were evaluated by quantitative RT-PCR with LightCycler. The mRNA expression levels were normalized with those of keratin 10 mRNA. The data were statistically analysed using Person's correlation coefficient. RESULTS: The expression levels of hBD-1,-2 and -3 were significantly correlated with each other and also correlated with that of TNF-alpha. CONCLUSIONS: The results indicate that the expression levels of hBDs vary from one individual to another.

Adolescent↗

Dysfunction of p53 pathway in human colorectal cancer: analysis of p53 gene mutation and the expression of the p53-associated factors p14ARF, p33ING1, p21WAF1 and MDM2.

Mutations of p53 tumor suppressor gene increase with tumor progression in colorectal cancers. In this study, we examined the expressions of p33ING1, p14ARF, MDM2 and p21WAF1 mRNA in 25 advanced colorectal cancers by quantitative RT-PCR method, and compared the expression levels of p33ING1, p14ARF, p21WAF1 and MDM2 in relation to p53 status in the tumors. Fifteen of 25 colorectal cancers (60%) showed abnormal accumulation of p53 protein in the nucleus, and the remaining 10 colorectal cancers (40%) were negative for p53 immunostaining. We found a G --> T transition (nonsense mutation) at the first nucleotide of codon 298 (exon 8) in one p53-negative case, and a frame shift mutation on exon 7 in another p53-negative case. In remaining eight p53-negative cases, there was no mutation in the entire open reading frame of p53 cDNA. Interestingly, in eight cases with p53 wild-type gene, 6 cases (75%) showed a marked down-regulation of p14ARF mRNA, and three cases (37.5%) over-expressed MDM2 mRNA. Only one case with wild-type p53 gene showed normal level expression of p53 regulatory-factors (p33ING1, p14ARF, and MDM2). Thus, p53 tumor suppressor pathway was disrupted in 24 of 25 colorectal cancers (96%).

Aged↗

Methylation profile of the MLH1 promoter region and their relationship to colorectal carcinogenesis.

Methylation of the MLH1 promoter region has been suggested to be a principal mechanism of gene inactivation in sporadic microsatellite instability (MSI)-positive colorectal carcinoma. Recently, we have shown a novel methylation profile of the MLH1 promoter region (i.e., full, partial, and no methylation), among which full methylation was strongly associated with MSI. In this study, to confirm whether methylation requires the involvement of both alleles, we studied the MLH1 promoter region concerning the methylation profile and allelic loss. Furthermore, we studied correlations of methylation profiles with genetic alternations such as loss of heterozygosity (LOH) of the TP53 locus and KRAS mutation. Eighty-eight tumors were classified as full (n = 14), partial (n = 26), and no methylation (n = 48). Full methylation was observed in 78% (14/18) of high-frequency MSI, in which all CpG sites in the promoter region were methylated. Full methylation differed significantly from partial methylation regarding absence of TP53 LOH (0/12) and KRAS mutation (0/14). In cases with full methylation, we could show biallelic methylation by use of a single-base nucleotide polymorphism in the promoter. However, this did not accompany LOH of the MLH1 locus. In contrast, there were no significant differences in molecular features between partial and no methylation, except for low frequencies of LOH of the MLH1 locus (P = 0.02). In conclusion, biallelic extensive methylation of the MLH1 promoter region plays a significant role in gene inactivation and is independent of KRAS mutation and TP53 LOH.

Adaptor Proteins, Signal Transducing↗

[Hepatic metastases from alpha-fetoprotein producing colorectal cancer that responded remarkably to transcatheter arterial chemo-embolization].

Although alpha-fetoprotein (AFP)-producing colorectal cancer is extremely rare, its potential for liver metastasis is high and the prognosis of the patient is very poor. We report a case of metastatic liver tumor from an AFP producing sigmoid colon cancer that was successfully treated with transcatheter arterial chemo-embolization (TACE). A 48-year-old female was admitted to our hospital complaining of anal bleeding, and was diagnosed as harboring a type 2 advanced tumor with two metastatic lesions in the lateral segment of the liver. Serum AFP measured 948.2 ng/ml before surgery. We performed sigmoidectomy and lateral segmentectomy of the liver. Pathological examination revealed moderately differentiated adenocarcinoma both in the primary and the metastatic lesions, and AFP-stain positive nests were seen on immunohistochemical staining. The serum AFP value returned to normal soon after the surgery. Five months later, a recurrent lesion was discovered in the right lobe of liver, and it was surgically removed. Another 4 months later, multiple liver metastases were recognized and the patient's serum AFP level was found to be 593.3 ng/ml. For the re-recurrent hepatic lesions of 5.5 cm in diameter, she underwent two courses of TACE using Lipiodol and epirubicin hydrochloride. Following the treatment, the tumor shrank rapidly and almost disappeared. The patient has been in good health for 24 months since the last TACE, and the serum AFP level has been within the normal range.

Antibiotics, Antineoplastic↗