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Biomedical subjects

M Kitajima

Publications and source records attributed to M Kitajima.

At least 271 records · Page 15Linked to original sources
PubMed1996

Further evidence for prognostic significance of epidermal growth factor receptor gene amplification in patients with esophageal squamous cell carcinoma.

To determine the value of epidermal growth factor receptor (EGFR) gene amplification as a biological prognostic indicator in patients with esophageal squamous cell carcinoma, the EGFR gene amplification was determined by slot-blot hybridization using DNA extracted from formalin-fixed and paraffin-embedded blocks of tissues from 107 patients with esophageal squamous cell carcinoma who had undergone curative surgery. Results were analyzed by both univariate and multivariate statistical analysis. EGFR gene amplification greater than 3-fold was detected in the primary tumors of 13 (12%) of the 107 cases. The cumulative survival rate for patients with EGFR gene amplification in the primary tumors was significantly lower than that for patients without amplification (P < 0.001). A significant correlation was observed between extensive lymph node involvement at the time of surgery and EGFR gene amplification (P < 0.05). In the multivariate analysis, EGFR gene amplification (P = 0.015) and vascular invasion (P = 0.003) proved to retain independent prognostic values. These results suggest that EGFR gene amplification may be a useful biological marker for the prediction of lymph node metastasis and a poorer prognosis of esophageal squamous cell carcinoma.

Adult↗
PubMed1996

Cyclin D1 amplification as a new predictive classification for squamous cell carcinoma of the esophagus, adding gene information.

The cyclin D1, referred to as PRAD-1, has been mapped to the 11q13 region, and its expression has been detected in squamous cell lines and several primary esophageal carcinomas. We assessed cyclin D1 amplification in 122 squamous cell carcinomas of the esophagus. Samples for DNA extraction were obtained from formalin-fixed paraffin-embedded specimens, and 10 microgram of each DNA sample were subjected to slot blot analysis. The presence of more than three gene copies was considered evidence of gene amplification. Amplification of cyclin D1 was detected in 28 (23%) of 122 cases of squamous cell carcinoma of the esophagus. There were no significant differences between the clinicopathological background factors in groups positive and negative for cyclin D1 amplification, but the survival rate of patients exhibiting amplification was significantly lower (P < 0.001). The groups were stratified according to the pN (pathological N category) factor and pT (pathological T category) factor in the TNM classification, and the cumulative survival rates in the amplification groups were always significantly lower. Amplification of cyclin D1 was correlated with distant organ metastasis after curative operations, but there was no significant difference in lymph node recurrence rates of patients with or without amplification. Cyclin D1 amplification had the second highest partial regression coefficient in the multivariate analysis, after the pN factor. Amplification of cyclin D1 was independent of the TNM classification as a prognostic factor, and was a useful marker for predicting outcome and distant organ metastasis in patients with squamous cell carcinoma of the esophagus. It appears that appropriate treatment can be selected by evaluating both TNM factors and cyclin D1 amplification.

Adult↗
PubMed1995

Liver colonization competence governs colon cancer metastasis.

Tumors that metastasize do so to preferred target organs. To explain this apparent specificity, Paget, > 100 years ago, formulated his seed and soil hypothesis; i.e., the cells from a given tumor would "seed'' only favorable "soil'' offered by certain groups. The hypothesis implies that cancer cells must find a suitable "soil'' in a target organ--i.e., one that supports colonization--for metastasis to occur. We demonstrate in this report that ability of human colon cancer cells to colonize liver tissue governs whether a particular colon cancer is metastatic. In the model used in this study, human colon tumors are transplanted into the nude mouse colon as intact tissue blocks by surgical orthotopic implantation. These implanted tumors closely simulate the metastatic behavior of the original human patient tumor and are clearly metastatic or nonmetastatic to the liver. Both classes of tumors were equally invasive locally into tissues and blood vessels. However, the cells from each class of tumor behave very differently when directly injected into nude mouse livers. Only cells from metastasizing tumors are competent to colonize after direct intrahepatic injection. Also, tissue blocks from metastatic tumors af fixed directly to the liver resulted in colonization, whereas no colonization resulted from nonmetastatic tumor tissue blocks even though some growth occurred within the tissue block itself. Thus, local invasion (injection) and even adhesion to the metastatic target organ (blocks) are not sufficient for metastasis. The results suggest that the ability to colonize the liver is the governing step in the metastasis of human colon cancer.

Adenocarcinoma↗
PubMed1995

Comparison of p53 gene abnormalities in bilateral and unilateral breast cancer.

BACKGROUND: The results of recent studies have suggested that p53 gene abnormalities are associated with carcinogenesis in several neoplasms. It is believed that bilateral breast carcinomas develop as a result of a different carcinogenetic mechanism and genetic environment from those of unilateral lesions. METHODS: p53 Gene abnormalities in bilateral primary breast cancer were detected by polymerase chain reaction-single strand comformation polymorphism (PCR-SSCP) analysis. A total of 76 paraffin embedded tissue specimens from 38 patients with bilateral primary breast cancer were examined, and 62 patients with unilateral breast cancer were analyzed as control subjects. The bilateral tumors were defined as primary, based on clinical parameters and the presence of an intraductal component. There were 13 patients with synchronous bilateral breast cancer and 25 with metachronous bilateral breast cancer. RESULTS: p53 Gene abnormalities were detected in 50% of the bilateral and 25.8% of the unilateral cases, and the difference was significant (P < 0.01, chi-square test). Abnormalities were detected in 56% of the metachronous cases, representing a much higher incidence than that of the unilateral cases (P < 0.001, chi-square test). The incidence of p53 gene abnormalities in the first and second tumors of the metachronous cases was 44% and 68%, respectively. The percentage of patients with a p53 gene abnormality and positive family history was higher for those with bilateral than with unilateral breast cancer (P < 0.01, chi-square test). CONCLUSION: These findings indicate that the genetic changes and mechanism of carcinogenesis in bilateral and unilateral breast cancer are different.

Adult↗
PubMed1995

Isolation and sequence analysis of human cadherin-6 complementary DNA for the full coding sequence and its expression in human carcinoma cells.

The expression pattern of E- and P-cadherin in human carcinomas has been reported by many laboratories. However, little is known about the involvement of other cadherin types in human carcinomas. cDNA clones for a cadherin molecule were isolated from a cDNA library of human hepatocellular carcinoma cells which lacked E- and P-cadherin expression but exhibited cell aggregation activity mediated by an unknown cadherin, and they were subjected to sequence analysis. The overlapped clones covered 4315 nucleotides and were found to encode a typical cadherin molecule consisting of 790 amino acids. Since the deduced amino acid sequence was identical to a partially available human cadherin-6 sequence except for two amino acid residues, the clones were considered to be human cadherin-6 cDNAs encoding the entire open reading frame. The deduced amino acid sequence also showed extremely high homology with recently reported rat K-cadherin, 97% for the putative mature protein, suggesting that cadherin-6 is the human counterpart of rat K-cadherin. Expression of cadherin-6 in various human normal tissues and carcinoma cells was examined by Northern blot analysis using a specific probe corresponding to the signal and precursor sequence. Among normal tissues examined, brain, cerebellum, and kidney showed strong expression of cadherin-6, whereas lung, pancreas, and gastric mucosa showed weak expression. Transcripts of cadherin-6 were not detected in normal liver, whereas four of six hepatocellular carcinoma cell lines examined expressed cadherin-6 abundantly. As reported for rat K-cadherin, three renal carcinoma cell lines also expressed cadherin-6 strongly. The most interesting finding was obtained for small cell lung carcinoma lines. Among 15 of such cell lines examined, all of 11 cadherin-6-positive lines were classified into the classic type, whereas the negative cell lines were all of the variant type. The present results suggest that besides E- and P-cadherin, other cadherin molecules are expressed in human cancers and are responsible for additional biological properties of the carcinoma cells.

Base Sequence↗
PubMed1995

Alteration of expression in integrin beta 1-subunit correlates with invasion and metastasis in colorectal cancer.

We have investigated the expression of the integrin beta 1 subunit in 51 colorectal cancer tissues using immunoblotting and have determined the relationship between expression and clinical stage. In comparison with normal mucosa the pre-beta-subunit (the precursor of beta 1-subunit) was increased in 15 cases and decreased in two cases, and expression of the beta 1-subunit was decreased in two cases. These alterations of expression of the beta 1-subunit were significantly correlated with lymph node metastasis and depth of invasion (P < 0.01). These results suggest that integrin plays an important role in the invasion and metastasis of colorectal cancer.

Colorectal Neoplasms↗
PubMed1995

Expression of sialyl Lewis(a) as a new prognostic factor for patients with advanced colorectal carcinoma.

BACKGROUND: Sialyl Lewis(a) antigen (SLA) is considered to be a cancer-associated carbohydrate antigen. METHODS: A total of 309 surgically resected primary colorectal cancer specimens and 501 associated metastases to regional lymph nodes were analyzed immunohistochemically using a monoclonal antibody (NS19-9) recognizing SLA. The specimens were obtained from 1981 to 1988 at the Department of Surgery, Keio University School of Medicine (Tokyo, Japan). RESULTS: Sialyl Lewis(a) antigen expression was detected in 75.4% (233/309) of the primary tumors and in 78.5% (99/126) of the metastases to regional lymph nodes. Significantly stronger expression was noted in the regional lymph node metastases than in the primary lesions (P = 4.5E-7). Sialyl Lewis(a) antigen expression in the primary tumors correlated significantly with regional lymph node metastasis (P < 0.005), recurrence (P < 0.005), and postoperative survival (P < 0.001) as determined by univariate analysis. Sialyl Lewis(a) antigen expression in the regional lymph node metastases also correlated strongly with recurrence (P < 0.005) and survival (P < 0.01). As determined by multivariate analysis, SLA expression in the primary tumor correlated strongly with recurrence (P = 3.0E-6) and survival (P = 6.9E-3). CONCLUSIONS: Sialyl Lewis(a) antigen expression in primary tumors and metastases to regional lymph nodes is a useful marker for evaluating tumor aggressiveness and prognosis in patients with advanced colorectal cancer.

Aged↗
PubMed1995

K-ras gene mutations in early colorectal cancer ... flat elevated vs polyp-forming cancer....

K-ras gene mutations in early colorectal cancer were detected by two-step sensitive polymerase chain reaction (PCR) and enzyme digestion method. Early colorectal cancer was classified into flat elevated cancer or polyp-forming cancer according to morphology and presence of adenomatous components. A total of 60 paraffin-embedded tissue specimens from patients with early colorectal cancer were analysed. K-ras codon 12 mutations were detected in 23.3% (7/30) of flat elevated cancer and 63.3% (19/30) of polyp-forming cancer. The incidence of K-ras codon 12 mutations in flat elevated cancer was significantly lower than in polyp-forming cancer (P < 0.01). These data suggested that K-ras gene mutations may be correlated with morphology or clinical features in flat elevated cancer, and that flat elevated cancer may originate from a pathway different from adenoma-carcinoma sequence.

Base Sequence↗
PubMed1995

Diverse incidences of individual oligopeptides (dipeptidic to hexapeptidic) in proteins of human, bakers' yeast, and Escherichia coli origin registered in the Swiss-Prot data base.

Oligopeptidic permutations of the 20 amino acid residues give rise to proteins of diverse functions. Our long-term goal is to produce a lexicon of oligopeptides, classifying them into at least five categories: (i) ubiquitous, (ii) function specific, (iii) group specific, (iv) species specific, and (v) nonexistent. To begin with, we report on the varying frequencies of individual oligopeptides (dipeptidic to hexapeptidic in length) found among 2862 human proteins, 1942 Saccharomyces cerevisiae proteins, and 2672 Escherichia coli proteins registered in the Swiss-Prot data base (version 29.0, released in June 1994). At all lengths (dipeptides to hexapeptides), homooligopeptides were very prominent among the most frequently occurring varieties in proteins of human and bakers' yeast origins. However, this was not the case with E. coli. While all of the expected 20(3) varieties of tripeptides were found among human proteins, three tripeptides (Cys-Cys-Trp, Trp-Trp-Cys, and Trp-Trp-His) were missing from the bakers' yeast proteins. Three tripeptides (Cys-Ile-Trp, Cys-Met-Tyr, and Cys-Trp-Trp) were also absent from E. coli proteins. Inasmuch as the Swiss-Prot data base already contained 67% of the expected total of 4000 E. coli proteins, it is virtually certain that 96,000 varieties of hexapeptides containing at least one or another of the three missing tripeptides noted above shall be nonexistent in E. coli. Furthermore, the observation of missing tripeptides in the bakers' yeast proteins suggests that nonexistent hexapeptides shall be highly phylum specific. Because of the sample size, only a small fraction of the 20(6) varieties of hexapeptides were expected to be encountered in the present survey. Indeed, only 1.2-1.5% of the possible hexapeptides were found, and the average copy number of observed hexapeptides varied between 1.06 and 1.25. Nevertheless, 33 varieties of hexapeptides occurred in 102-169 copies among human proteins. Furthermore, 15 of the 33 varieties contained such rarely used residues as Tyr, His, Cys, and Trp.

Amino Acid Sequence↗
PubMed1995

p53 gene mutations in early colorectal carcinoma. De novo vs. adenoma-carcinoma sequence.

p53 gene mutations in early and advanced colorectal cancer were detected by PCR-SSCP analysis. Early colorectal cancer was classified into de novo cancer and polyp-forming cancer, respectively, according to morphology and presence of adenomatous components. A total of 94 paraffin-embedded tissue specimens from patients with colorectal cancer were analysed. p53 gene mutations were detected in 40.0% (12/30) of de novo cancer, 36.7% (11/30) of polyp-forming cancer, and 44% (15/34) of advanced cancer. p53 mutations were detected at a high frequency in both types of early colorectal cancer as well as in advanced cancer. No correlations were found between p53 mutations and clinicopathological data. Our data suggest that the p53 gene mutations occurred in the early colorectal cancer stage of carcinogenesis regardless of the pathway.

Adenoma↗
PubMed1995

Antitumor activity of cis-diamminedichloroplatinum (II) depends on its time x concentration product against human gastric cancer cell lines in vitro.

A pharmacodynamic study of cisplatin (DDP) was conducted using the gastric cancer cell lines MKN-45 and MKN-74 in vitro. Ten thousand tumor cells were incubated with 0.4-500 micrograms/ml DDP for 1-25 h, followed by recovery culture for a further 48 h. At the end of incubation, cell viability was detected by the MTT end-point, and the inhibition rate was compared in relation to the incubation time, DDP concentration, and the time X concentration product (area under the curve in vitro: AUC vitro). In both of the cell lines, the IC50 and IC90 values decreased as the exposure time increased, going a linear curve with a slope of almost -1, and showing a typical log-log AUC vitro-dependent curve. These results indicate that the antitumor activity of DDP is dependent on its AUC vitro, suggesting the clinical usefulness of this drug when administered daily in small divided doses.

Antineoplastic Agents↗
PubMed1995

Molecular evolution of group II phospholipases A2.

The nucleotide sequences of 13 cDNAs encoding group II phospholipases A2 (PLA2s), which are from viperidae snake venoms and from mammalian sources, were aligned and analyzed by phylogenetic trees constructed using various components of the sequences. The evolutionary trees derived from the combined sequences of the untranslated (5' and 3') region and the signal peptide region of cDNAs were in accord with the consequences from taxonomy. In contrast, the evolutionary trees from the mature protein-coding region sequences of cDNAs and from the amino acid sequences showed random patterns. These observations indicated that the mature protein-coding region has evolved through a process differently from the untranslated and signal peptide regions. The trees built from the nucleotide differences at each of three positions of codons in the mature protein-coding region suggested that snake-venom-gland PLA2 genes have evolved via a process different from mammalian PLA2 genes. The occurrence of accelerated evolution has been recently discovered in Trimeresurus flavoviridis venom-gland group II PLA2 isozyme genes (Nakashima et al. 1993, Proc Natl Acad Sci USA 90:5964-5968), so the present phylogenetic analysis together with the estimation of nucleotide divergence of cDNAs provides further evidence that snake-venom-group II PLA2 isozyme genes have evolved by accelerated evolution to gain diverse physiological activities.

Amino Acid Sequence↗
PubMed1995

Conversion of the rabbit gracilis muscle for transposition as a neoanal sphincter by electrical stimulation.

To re-establish anal function in fecally incontinent patients it may be feasible to transpose the gracilis muscle around the anal canal, using electrical stimulation to trigger contraction. However, because the fast-twitching gracilis muscle is incapable of prolonged contraction without fatigue, it is necessary to convert it to a slow-twitching, fatigue-resistant muscle. We demonstrated this conversion by longterm electrical stimulation at low frequencies using a rabbit model. The nerve to the gracilis muscle was continuously stimulated at 2 Hz, 5 Hz, and 10 Hz for 2, 4, or 6 weeks. In the 6-week conditioning group, the percentage of type I fibers, identified by ATPase staining, increased as the conditioning frequency became higher, but the twitch contraction speed reduced with conditioning at a frequency of more than 5 Hz. The fatigue resistance improved by conditioning at 10 Hz, and conversion occurred in 6 weeks. Thus, we concluded that conditioning at 10 Hz for 6 weeks can convert rabbit gracilis muscle to a slow-twitching, fatigue-resistant muscle suitable for use as a neoanal sphincter.

Anal Canal↗
PubMed1995

Plasticity of myofibroblasts appearing in granulation tissues after acetic acid treatment. Effect of bFGF.

To clarify the origin of the myofibroblasts appearing in the healing process of the acetic acid-induced ulcer and effect of basic fibroblast growth factor (bFGF) on these myofibroblasts, we conducted an immunohistochemical study using antibody to intermediate filaments, desmin and vimentin. The binding sites of bFGF on the regenerative tissues were also studied by the radioautographic study of soluble compounds. As a result, the binding sites of bFGF were accumulated on the fibroblasts and myofibroblasts as well as on endothelial cells. The effect of CS23, acid-stable human recombinant bFGF was shown on distribution of myofibroblasts and regeneration of the microvascular system in the mucosal and submucosal layers.

Acetates↗