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Biomedical subjects

M Mai

Publications and source records attributed to M Mai.

At least 37 records · Page 2Linked to original sources
PubMed2000

Altered expression of beta-catenin and c-erbB-2 in early gastric cancer.

To investigate the possible relationship between altered expression (loss of membranous staining or nuclear accumulation) of beta-catenin and invasion/metastasis in early gastric cancer (EGC), beta-catenin was detected immunohistochemically in 116 cases of EGC, including 86 differentiated and 30 undifferentiated carcinomas. In parallel, immunohistochemical expression of c-erbB-2 was analyzed in all EGC cases. Regardless of histological type, altered expression of beta-catenin was found in 47% of mucosal carcinomas and 89% of carcinomas with submucosal invasion (p<0.001). Of particular interest is that beta-catenin alteration was found in almost all EGCs with lymph node metastasis, even though no significant statistical comparison could be made. These results suggest that molecular changes resulting in abnormal beta-catenin expression participate in the process of submucosal invasion and metastasis. While loss of expression was preferentially observed in undifferentiated EGCs, nuclear accumulation was found exclusively in 24% of differentiated EGCs. c-erbB-2 was overexpressed in only 16% of differentiated EGCs but there was no correlation between this overexpression and invasion or metastasis. However, it is intriguing that 12 out of 14 cases with c-erbB-2 overexpression also showed altered beta-catenin expression, suggesting that both molecules are involved in the development of a certain set of differentiated EGCs.

Adenocarcinoma↗
PubMed1999

Overexpression of the wild type p73 gene in human bladder cancer.

p73, a first p53 relative, was recently identified and shown to be monoallelically expressed in a number of different human tissues. To determine the potential role of this gene in human bladder cancer, we investigated p73 expression levels, allelic expression patterns, and analysed p73 mutations in 23 unselected primary invasive bladder cancers with matched normal tissues and in seven bladder cancer cell lines. In a comparison between normal and tumor tissues using quantitative RT-PCR analysis, we found that p73 was overexpressed in 22/23 bladder cancers, sometimes as great as 20-fold. Allelic expression analysis using a C/T polymorphism in exon 2 and a newly identified T/C polymorphism in exon 5 revealed that p73 was biallelically expressed in both normal bladder and cancer tissues, suggesting that p73 is not imprinted in bladder tissue. Mutation screening of the p73 gene in bladder cancer DNAs using denaturing high-performance liquid chromatography analysis and DNA sequencing revealed no tumor-specific mutations in any coding exons of the p73 gene. These data suggest that the p73 is unlikely to be a tumor suppressor gene, but that overexpression of p73 may contribute to tumorigenesis in bladder cancer.

Alleles↗
PubMed1999

Cloning of the human homolog of conductin (AXIN2), a gene mapping to chromosome 17q23-q24.

Conductin or Axil, an Axin homolog, plays an important role in the regulation of beta-catenin stability in the Wnt signaling pathway. To facilitate the molecular analysis of the human gene, we isolated the human homolog, AXIN2. The cDNA contains a 2529-bp open reading frame and encodes a putative protein of 843 amino acids. Compared with rat and mouse homologs, AXIN2 shows an overall 89% amino acid identity. Several functional domains in this protein are highly conserved including the GRS (95.9%), GSK-3beta (96.3%), Dsh (98%), and beta-catenin (89.9%) domains. Radiation hybrid mapping localized the AXIN2 gene to human chromosome 17q23-q24, a region that shows frequent loss of heterozygosity in breast cancer, neuroblastoma, and other tumors. Human AXIN2 is thus a very strong candidate involved in multiple tumor types.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Mutation and expression analysis of the p73 gene in prostate cancer.

BACKGROUND: p53 is the most highly mutated tumor suppressor gene in human cancers. Recently, p73, a first homologue of p53, was identified and considered to be an imprinted tumor suppressor gene. Thus, we analyzed the possible role of p73 in human prostate cancers. METHODS: We investigated the expression levels and expressed allelotypes and searched for mutations in the p73 gene in 27 primary prostate cancers with matched normal tissues as well as in four prostate cell lines. RESULTS: Allelic expression analysis using polymorphisms in exons 2 and 5 revealed that p73 is biallelically expressed in both normal and tumor tissues, suggesting that p73 is not imprinted in prostate tissues. Quantitative PCR demonstrated that p73 expression is the same in both normal and tumor prostate tissues. Denaturing high-performance liquid chromatography and DNA sequencing revealed that there were no tumor-specific mutations in the p73 gene at the genomic level. CONCLUSIONS: These data indicate that alterations of p73, including mutations, changes in message abundance, and changes in allelic expression, are likely to be rare in early-stage prostate cancer, and that p73 could be a tissue-specific imprinting gene.

DNA Mutational Analysis↗
PubMed1999

p73 mutations are not detected in sporadic and hereditary breast cancer.

Recently, a novel tumor suppressor gene, p73, was isolated and mapped to chromosome 1p36, a region commonly associated with loss of heterozygosity in neuroblastoma and other human malignancies, including breast cancer. The p73 gene shares considerable homology with the common tumor suppressor gene p53, both in composition and function. This study examines the potential participation of p73 in the pathogenesis of sporadic and hereditary breast cancers. Mutation analysis of 29 hereditary breast cancer cases revealed five independent silent mutations in the hereditary cases that are unlikely to play a role in tumor development. Mutation analysis of 48 sporadic breast tumors did not identify any unique variants. Eleven common polymorphisms scattered throughout the gene were also detected. Thus, mutations in the p73 gene appear to play little if any role in hereditary or sporadic breast cancer.

Breast Neoplasms↗
PubMed1999

Meningitis or madness: a delicate balance.

A child with meningitis who developed a psychosis 2 weeks after commencing treatment with antituberculous therapy is described here. The psychosis resolved with cessation of isoniazid, but the meningitis returned. The meningitis was treated by re-introduction of daily doses of isoniazid, but the psychosis recurred. Successful treatment of the meningitis, with minimal psychotic symptoms, eventually was achieved using isoniazid at 48 h dose intervals. The psychosis resolved completely after completion of therapy for tuberculous meningitis and cessation of isoniazid. This is the first case of isoniazid-associated psychosis reported in a child.

Antitubercular Agents↗
PubMed1999

Environmental factors as regulators and effectors of multistep carcinogenesis.

This review highlights current knowledge of environmental factors in carcinogenesis and their cellular targets. The hypothesis that environmental factors influence carcinogenesis is widely supported by both epidemiological and experimental studies. The fact that only a small fraction of cancers can be attributed to germline mutations in cancer-related genes further buttresses the importance of environmental factors in carcinogenesis. Furthermore, penetrance of germline mutations may be modified by either environmental or other genetic factors. Examples of environmental factors that have been associated with increased cancer risk in the human population include chemical and physical mutagens (e.g. cigarette smoke, heterocyclic amines, asbestos and UV irradiation), infection by certain viral or bacterial pathogens, and dietary non-genotoxic constituents (e.g. macro- and micronutrients). Among molecular targets of environmental influences on carcinogenesis are somatic mutation (genetic change) and aberrant DNA methylation (epigenetic change) at the genomic level and post-translational modifications at the protein level. At both levels, changes elicited affect either the stability or the activity of key regulatory proteins, including oncoproteins and tumor suppressor proteins. Together, via multiple genetic and epigenetic lesions, environmental factors modulate important changes in the pathway of cellular carcinogenesis.

Biomarkers↗
PubMed1999

[A late phase II clinical study of RP56976 (docetaxel) in patients with advanced or recurrent gastric cancer: a cooperative study group trial (group B)].

A late phase II clinical study of RP56976 (docetaxel) in patients with advanced or recurrent gastric cancer was performed to evaluate the anti-tumor activity and clinical toxicity as a multicenter cooperative trial. Docetaxel was administered intravenously at a dose of 60 mg/m2 every 3-4 weeks. Of 72 patients enrolled, 63 patients were eligible and 59 patients were evaluable for response. The anti-tumor effects obtained complete response (CR) in one patient partial response (PR) in 13, minor response (MR) in 3, no change (NC) in 20, and progressing disease (PD) in 22 patients. The overall response rate in 59 patients was 23.7% (14/59). For 14 CR or PR cases, a response appeared 10 to 107 days (median 33.5 days) and 1 to 8 (median 2) times of dosing after the initial administration. The response rate was 9.5% in the primary tumor, 31.3% livers, 50.0% abdominal tumor, and 24.1% lymph nodes, respectively. The major adverse reactions were gastrointestinal symptoms including nausea/vomiting, anorexia, fatigue, alopecia and fever. Leukocytopenia and neutrocytopenia were also observed with a high incidence, but they recovered after 8 days from the nadir. The results show that docetaxel is an effective anti-tumor agent for advanced or recurrent gastric cancer. It is necessary to conduct another clinical trial by concomitant administration with other anti-tumor agents.

Adenocarcinoma↗
PubMed1999

[Low-dose CPT-11 against a recurrent rectal cancer--a case report].

We attempted a new regimen of low-dose CPT-11 on a 5-FU resistant recurrent rectal cancer patient with multiple lung metastases and a paraaortic lymph node metastasis. CPT-11 was administered at 25 mg/m2/day x 3/week by intravenous infusion. Serum CEA level decreased gradually with a half time of approximately 4 weeks. The lung metastases almost disappeared and the paraaortic lymph node was also reduced more than 50%. There were no adverse effects except slight alopetia. This treatment could be continued on an outpatient basis. These results suggest that low-dose CPT-11 may be more effective and tolerable than the conventional, CPT-11 therapy.

Antineoplastic Agents, Phytogenic↗
PubMed1999

Significance of head-shaking nystagmus in the evaluation of the dizzy patient.

In a series of studies, the phenomenon of head-shaking nystagmus (HSN) was assessed in 50 control subjects and 1364 consecutive dizzy patients who underwent formal electronystagmography (ENG) at the Toronto Hospital Center for Advanced Hearing and Balance Testing. HSN was compared in a series of 30 patients who underwent conventional electro-oculography (EOG) vs magnetic (scleral) coil eye movement recordings. Clinical correlation of HSN to other parameters of the ENG test battery was performed in another sub-series of 300 patients with known diagnoses. HSN was identified in 31.7% of dizzy patients vs 24% of control subjects. No significant difference in its manifestation was noted between active vs passive head-shaking tests or on EOG vs magnetic (scleral) coil eye movement recordings. When compared to other aspects of the ENG test battery, HSN was neither specific nor sensitive for vestibular dysfunction. It nevertheless correlated well with the presence of a caloric reduction and with increasing R/L excitability differences on ENG testing. When present, HSN was characteristically monophasic in 76.8%, biphasic in 22.7% and triphasic in 0.5% of subjects. The initial direction of HSN generally obeyed Ewald's second law, but the reverse was noted in 27% with monophasic and 17.6% of patients with biphasic HSN. In the subseries of 300 patients with known diagnoses, the presence of HSN was statistically significant (p < 0.05) in patients with peripheral vestibular dysfunction vs psychogenic dizziness. Its presence was also significant in well-documented peripheral vestibular disorders such as Meniere's disease (p < 0.01), vestibular neuronitis (p < 0.05) and acoustic neuroma (p < 0.05). Localization of the disease involvement based on the initial direction of HSN was especially unpredictable in patients with Meniere's disease. The significance and usefulness of the head-shake test in the otoneurological evaluation of the dizzy patient is further commented on.

Dizziness↗
PubMed1998

Loss of imprinting and allele switching of p73 in renal cell carcinoma.

p73, a protein that has substantial structural and functional similarity to p53, has recently been identified. It was found to be monoallelically expressed in all cell lines and normal individuals tested. To elucidate its role in cancer development and as a potential imprinted tumor suppressor, we investigated the allele-specific expression of the human p73 gene in 28 cases of renal cell carcinoma and its imprinting status in fetal pancreatic and thymic tissues. Of 12 informative pairs of renal cell carcinoma and matched normal tissues identified by StyI restriction fragment length polymorphism (RFLP) in exon 2, p73 showed monoallelic expression in 11 out of 12 normal tissues but biallelic expression in 8/12 and switched allele expression in 2/12 of the matched corresponding cancers. An imprinting study of the p73 gene in two families using a newly identified exonic BanI RFLP indicated that expression of p73 was limited to the maternal allele in RNA from fetal pancreas and thymus, demonstrating that p73 is imprinted in at least these two tissues. These findings strongly suggest that loss of imprinting or switching of allelic expression of the p73 gene is associated with the development of renal cell carcinoma.

Alleles↗
PubMed1998

Genomic organization and mutation analysis of p73 in oligodendrogliomas with chromosome 1 p-arm deletions.

p73, a protein having substantial structural and functional similarity to p53, has recently been identified and demonstrated to be a potential tumor suppressor. Its location on human chromosome 1p36.33 implicates p73 as a candidate for neuroblastoma. Like neuroblastoma, oligodendrogliomas also show a high frequency of deletions in chromosome 1p36.3. To determine whether p73 is a potential tumor suppressor gene involved in the development of oligodendrogliomas, we performed mutation analysis of p73 in oligodendrogliomas with chromosome 1 p-arm deletions. We first determined the genomic organization and the intron-exon boundary sequences of the p73 gene by long PCR, vectorette PCR, and Southern hybridization. This gene spans about 65 kb with a large first intron. Primer pairs for the amplification of each of the 13 p73 encoding exons were designed in corresponding introns. The amplicons were then analyzed using the denaturing high-performance liquid chromatography system for mutations in the p73 gene. Twenty oligodendroglioma samples with 1p36.3 deletions were screened, but no mutations were detected except for several polymorphisms. It is thus clear that p73 is not a candidate gene for oligodendroglioma despite its location in the frequently deleted 1p36.3 region.

Chromosomes, Human, Pair 1↗
PubMed1998

Activation of p73 silent allele in lung cancer.

p73, a first p53 relative, has recently been identified and demonstrated to be monoallelically expressed. This protein shows significant amino acid sequence and functional similarities to p53. However, it is unclear whether this protein functions as a tumor suppressor. To elucidate the role of p73 in tumor development, we investigated the expression of the p73 gene in lung cancer. In a comparison between normal lung and tumor tissues, p73 was more highly expressed in tumors. Moreover, using a C/T polymorphism in exon 2 for allele-specific expression analysis in 21 pairs of lung tumors and matched normal tissues, we found that five heterozygous samples exclusively expressed both alleles in tumors while showing monoallelic expression in matched normal tissues. This result was confirmed by single-nucleotide primer extension analysis. Mutation analysis of all 13 coding exons of the gene in 21 lung tumor DNAs revealed several polymorphisms, but no tumor-specific mutations were detected. These findings strongly suggest that p73 may play an important role in lung tumorigenesis through activation of a silent allele and overexpression of wild-type p73 rather than as a tumor suppressor.

Alleles↗
PubMed1998

Expression and tissue localization of matrix metalloproteinase 7 (matrilysin) in human gastric carcinomas. Implications for vessel invasion and metastasis.

We examined the production and tissue localization of matrix metalloproteinase-7 (MMP-7 = matrilysin) in human gastric carcinomas and analyzed the data in connection with the clinicopathological factors. Sandwich-enzyme immunoassay for the zymogen of MMP-7 (proMMP-7) showed enhanced production of MMP-7 in carcinoma tissues compared with control normal gastric mucosa. Immunohistochemical studies demonstrated that MMP-7 is localized predominantly to the carcinoma cells in 71% of the carcinoma samples (30/42 cases). The percentage of immunoreactive carcinoma cells to total carcinoma cells (positive ratio) was significantly higher in intestinal-type carcinomas (26%, median) than in diffuse-type carcinomas (3%, median) (p < 0.05). The positive ratio was markedly higher in carcinoma groups with vascular invasion (28%) or lymphatic permeation (12%) than in those without invasion (6%) or permeation (0%) (p < 0.05). It was also significantly higher in carcinoma groups with liver (49%) or lymph-node metastases (15%) than in those without metastases (6 and 2% respectively) (p < 0.05). Both proMMP-7 of 28 kDa and active MMP-7 of 19 kDa were detected in the carcinoma tissues by immunoblotting. Reverse-transcription-PCR showed specific amplification in 50% of the carcinoma cases (6/12 cases) and 8% of the normal control specimens (1/12 cases). In situ hybridization demonstrated that the carcinoma cells almost selectively express MMP-7 mRNA. These data suggest that enhanced production of proMMP-7 and its activation are implicated in invasion and metastasis of human gastric carcinomas.

Adult↗
PubMed1998

Relationship between serum ELAM-1 and metastasis among patients with colon cancer.

PURPOSE: We studied serum ELAM-1 levels in colon cancer patients. METHODS AND RESULTS: Serum ELAM-1 levels were significantly higher in 52 patients with colon cancer (mean +/- standard deviation, 69.3 +/- 28.6 U/ml) compared with 32 healthy volunteers (36.5 +/- 11.9 U/ml; P < 0.001). The mean serum ELAM-1 level in patients with metastatic tumors was significantly greater than that of patients with nonmetastatic tumors. Sensitivity and specificity of serum ELAM-1 elevation in detecting metastasis was 75 and 87.5 percent, respectively. Those of carcinoembryonic antigen and carbohydrate antigen 19-9 elevations were 71.4 and 62.5 percent and 35.7 and 91.7 percent, respectively. Twenty-five (89.3 percent) of 28 metastatic tumors showed either serum ELAM-1 or carcinoembryonic antigen elevation. There were weak but significant correlations found between serum ELAM-1 and carcinoembryonic antigen or carbohydrate antigen 19-9 levels. Moreover, serum ELAM-1 increased before detecting the recurrence by imaging in five of seven recurrent colon cancer patients. CONCLUSION: These findings suggest that serum ELAM-1 could be a useful tumor marker for colon cancer, especially in synchronous and metaclonous metastasis.

Adult↗
PubMed1998

Angiogenesis in poorly differentiated medullary carcinoma of the stomach.

We studied the role of angiogenesis in patients with medullary type poorly differentiated adenocarcinoma (MTPDA) of the stomach. Immunohistochemical analyses were conducted using antibodies against factor VIII (endothelial cells), vascular endothelial growth factor (VEGF) and its receptors (KDR andflt-1), and basic fibroblast growth factor (bFGF) and its receptors (bek andflg). Archival specimens of MTPDA (n=22) and non-MTPDA (n=47) were studied. The expression of VEGF and bFGF, the vessel count, and positivity of KDR on endothelium were all significantly higher in MTPDA than in non-MTPDA. The vessel count correlated with the VEGF expression in MTPDA. The vessel count and VEGF expression increased with the increasing stage of disease in MTPDA but not in non-MTPDA. The expression of bFGF and its receptors did not correlate with the vessel count and stage of disease in either type. These findings thus suggest that the biological behavior of medullary type poorly differentiated adenocarcinoma of the stomach is angiogenesis-dependent. The correlation of the VEGF expression and its endothelial receptors with the vessel count and the stage of disease thus suggests that VEGF is a factor responsible for the induction of angiogenesis in this type.

Adult↗
PubMed1998

[Levels of endothelin and beta-human chorionic gonadotropin and their relationship in patients with pregnancy induced hypertention].

OBJECTIVE: To measure levels of endothelin (ET) and beta-human chorionic gonodotropin (beta-hCG) and analyse the correlation between them in patients with pregnancy induced hypertension (PIH), as well as to investigate their role in the pathogenesis of PIH. METHODS: 32 patients with PIH were matched with 17 normal term singleton pregnant women. ET and beta-hCG levels of above patients and 14 nonpregnant health reproductive age women were determined by radioimmunoassay. RESULTS: ET and beta-hCG levels were significantly higher in patients with PIH (30.35 +/- 14.52 ng/L and 7.35 +/- 4.86 nmol/L) than that of two control groups (P < 0.05), especially in middle and severe PIH (P < 0.05), but no significant different in mild PIH (P > 0.05), compared with normal pregnant group (20.79 +/- 7.08 ng/L and 4.13 +/- 1.91 nmol/L) and nonpregnant group (19.78 +/- 6.66 ng/L and 0 nmol/L). There was no significant difference of plasma ET levels between normal pregnant and nonpregnant women (P > 0.05). beta-hCG in nonpregnant woman hadn't been determined. We did not find any association between the levels of ET and beta-hCG in normal pregnancy (r = +0.2216, P > 0.05), but significant positive correlation in the patients with PIH (r = +0.5418, P < 0.01). CONCLUSION: The increased levels of ET and beta-hCG, as well as their positive correlation, suggested that the dysfunction of the placental cells may be associated with the endothelial cell damage in PIH patients.

Adult↗