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T Mitsudomi

Publications and source records attributed to T Mitsudomi.

At least 55 records · Page 3Linked to original sources
PubMed1996

Correlations between intrinsic chemoresistance and HER-2/neu gene expression, p53 gene mutations, and cell proliferation characteristics in non-small cell lung cancer cell lines.

Using a panel of 20 non-small cell lung cancer (NSCLC) cell lines established from previously untreated patients, we investigated the relationships between intrinsic chemoresistance (to four agents used commonly in the therapy of NSCLC) and HER-2/neu gene expression (which encodes glycoprotein p185neu), p53 gene mutations, and cell proliferation characteristics. Our results demonstrated that high p185neu expression was correlated with chemoresistance, low S-phase fractions, and long doubling times. By contrast, cell lines expressing relatively low levels of p185neu were relatively chemosensitive and had higher S-phase fractions and shorter doubling times. Although mutation of the p53 gene was a common event in this panel of cell lines (present in 18 of 20 lines), there was no relationship between mutations at any specific codon and chemoresistance or cell proliferation characteristics. Multivariate analysis revealed that the level of p185neu was the only independent predictor for chemoresistance to doxorubicin, etoposide, and probably cisplatin. Although intrinsic chemoresistance almost certainly is a multifactorial process, overexpression of p185neu may be an important factor in the chemoresistance of NSCLC.

Carcinoma, Non-Small-Cell Lung↗
PubMed1996

Postoperative complications after pneumonectomy for treatment of lung cancer: multivariate analysis.

The charts of 62 patients with primary lung cancer who underwent a pneumonectomy at our department from 1979 through 1992 were reviewed for the evaluation of postoperative morbidity and mortality. The 30-day mortality was 3/62 or 4.8%. Postoperative complication occurred in 37 of 62 patients (60%). The most common complication was a supraventricular tachyarrythmia. A major complication, which was defined as one necessitating re-thoracotomy or one which caused death, occurred in 19 patients (31%). We analyzed 43 perioperative variables for their predictive value of postoperative morbidity and mortality. Univariate analysis indicated that an elevated serum LDH, low predicted forced vital capacity, low predicted forced expiratory volume in 1 sec (FEV1) were significantly associated with the occurrence of a major complication. A multivariate logistic regression model indicated that a high LDH level, a low predicted FEV1 and no extubation following surgery were associated independently with a postoperative major complication. Since only the complete removal of a tumor offers a chance for cure for the treatment of non-small cell lung cancer, it is sometimes necessary to perform a pneumonectomy for these high-risk patients. Patients identified as being at high risk of a major complication should be candidates for intensive preoperative evaluation and perioperative care.

Adult↗
PubMed1996

Kinetic analysis of recurrence and survival after potentially curative resection of nonsmall cell lung cancer.

BACKGROUND: About two-thirds of the patients with nonsmall cell lung cancer (NSCLC) who undergo a potentially curative resection eventually suffer from recurrent disease. However, it has yet to be elucidated as to how survival after recurrence is influenced by different variables, including timing, type of recurrence, or other clinicopathological features. There have been few studies concentrating on the kinetics of growth of occult micrometastatic tumor cells that eventually manifest as tumor recurrence. METHODS: We retrospectively reviewed the charts of 197 patients who developed recurrence after a potentially curative resection for NSCLC. RESULTS: The median disease-free interval was a little over 1 year (395 days), as was the median postrecurrence survival-383 days. We created a model for the kinetics of recurrence by assuming that: (1) a tumor of 10(9) cells is the usual limit of detection, (2) patients generally die before the tumor reaches 10(12) cells, and (3) it takes 1 year for average lung cancer cells to show a 10-fold increase. The model indicated that as much as 10(9) tumor cells should have been present immediately after the operation. Alternatively, the residual tumor cells should have an accelerated growth after the surgery. CONCLUSIONS: These models indicate the importance of developing a sensitive detection method for occult metastatic cells and to understand the tumor dormancy mechanism.

Adult↗
PubMed1996

Increased levels of serum intercellular adhesion molecule-1 (ICAM-1) in patients with non-small cell lung cancer.

Serum concentrations of soluble ICAM-1 were measured by an enzyme-linked immunosorbent assay in 80 patients with non-small cell lung cancer (NSCLC). The mean serum concentration of soluble ICAM-1 in 80 patients with NSCLC was 472.8 +/- 370.8 ng ml-1 (range 75.6-3177.4 ng ml-1), whereas it was 196.8 +/- 54.6 ng ml-1 (range 128.1-276.4 ng ml-1) in 10 healthy controls. Sixty of 80 patients with NSCLC (75.0%) showed elevated concentrations (more than 306 ng ml-1, mean+2 SD in controls). The differences in mean serum concentration and positive rate between control subjects and NSCLC patients were significant (P = 0.0001). Serum ICAM-1 concentrations showed a significantly positive correlation with primary tumour size (maximum diameter) (P = 0.0209). Although the difference was not significant, the overall survival of patients with low serum ICAM-1 concentrations (< 306 ng ml-1) tended to be longer than that of patients with high concentrations (> or = 306 ng ml-1). These results suggest that serum ICAM-1 may be useful for serological diagnosis, monitoring of tumour volume or quantity in patients with NSCLC.

Adult↗
PubMed1996

Combined resections of the diaphragm and the liver for a locally advanced non-small-cell lung cancer.

A 73-year-old man was admitted to our hospital to undergo treatment for right lung cancer (large cell carcinoma) which had directly invaded the liver through the diaphragm, and presented with T3N0M0, stage IIIa disease. A right lower lobectomy was performed with lymph node dissection, combined with a partial resection of the diaphragm and the liver, as well as a reconstruction of the diaphragm using the latissimus dorsi muscle. The patient had an uneventful postoperative course and was free of disease 1 year later at the time when this paper was written.

Aged↗
PubMed1996

[Genetic abnormalities in lung cancer and their prognostic implications].

Recent advances in molecular biology have revealed various genetic lesions in lung cancer. Mutations of the K-ras gene, amplification or overexpression of myc family genes, erbB2 gene, or bcl2 gene are frequent genetic changes of oncogenes in lung cancer. Inactivation of tumor suppressor genes such as Rb gene, p53 gene, or p16 gene are also seen rather frequently. Furthermore, loss of heterozygosity at certain chromosomal arms such as 3p, 5q, 18q and 22q suggesting inactivation of yet unidentified tumor suppressor genes, also occurs in a significant proportion of lung cancers. Most of these genetic lesions have been reported to be associated with a poor prognostic outcome of the patients. However, great controversy exists as to whether a certain genetic lesion is really a prognostic marker. For example, although about 20 studies have been published, the prognostic implications of the p53 gene for patients with lung cancer still remain unclear. Little is known about the mechanism through which a certain genetic change affects the patient's prognosis. To ultimately improve the prognosis of patients with this deadly disease, definitive studies on which subsequent clinical trials can rely are much awaited.

Genes, Retinoblastoma↗
PubMed1996

Prognostic value and clinicopathological correlation of thrombomodulin in squamous cell carcinoma of the human lung.

Aggregation of host platelets by circulating tumor cells is believed to play an important role in the metastatic process. Because thrombomodulin (TM) is one of the major mediators of the activation of the anticoagulant protein C by thrombin, we examined 136 primary tumor tissues and 45 metastatic lymph node tissues of lung squamous cell carcinomas for TM expression using immunohistochemical methods. The number of tumors with positive TM staining was less in metastatic tumors (44%) than in primary tumors (74%) (P < 0.01). Of various clinicopathological factors, better differentiation and lower N stage were significantly associated with TM expression. A loss of TM expression was associated with a shortened survival in 113 patients who underwent complete resection of the lung tumor (P < 0.01). In this group, TM expression and tumor-node-metastasis staging were independent significant determinants for survival, determined using Cox's multivariate survival analysis. Since TM is apparently associated with tumor progression and differentiation, this correlation may serve as a prognostic indicator in squamous cell carcinoma of the lung.

Aged↗
PubMed1996

Loss of heterozygosity at 3p in non-small cell lung cancer and its prognostic implication.

We examined 110 patients with non-small cell lung cancer who underwent consecutive pulmonary resection for loss of heterozygosity (LOH) at the short arm of chromosome 3 (3p). We performed a PCR-based microsatellite polymorphism analysis for detection of LOH. The microsatellite markers used were D3S966 (3p21.3), D3S1007 (3p21. 3-22), and D3S1228 (3p14.1-14.3). Of 98 informative cases, 3p LOH was found in 45 (46%). 3p LOH was more prevalent in squamous cell carcinoma (24/35, 69%) than in adenocarcinoma (18/52, 35%; P = 0.0019). There was no significant association between 3p LOH and sex, disease stage, or grade of differentiation. However, patients with 3p LOH tended to survive for a shorter period of time (P = 0.0631, log rank test). There was no such tendency in squamous cell carcinoma (P = 0.7513), but in adenocarcinoma, the difference of survival was significant (P = 0.0015). Cox's proportional hazards model also predicted that 3p LOH was an independent poor prognostic marker in adenocarcinoma (P = 0.0502) but not in squamous cell carcinoma or in the entire cohort (P = 0.7866 and 0.1371, respectively). LOH at 3p may help to identify non-small cell lung cancer patients with a poor prognosis, who thus need an intensive postoperative follow-up protocol or who are suitable for novel investigational therapeutic approaches. It is also suggested that the putative tumor suppressor gene at 3p may have a different role in squamous cell carcinoma and adenocarcinoma of the lung.

Adult↗
PubMed1995

[A case of postoperative hyponatremia caused by Sheehan syndrome associated with lung carcinoma].

A 54-year-old woman underwent a left upper lobectomy for lung carcinoma after which hyponatremia developed within 5 days. Her serum concentration of ADH was within normal range disapproving the presence of SIADH frequently associated with lung carcinoma. An endocrinological examination showed panhypopituitarism. From her anamnesis it was seen that there was much perinatal bleeding and amenorrhea. She was diagnosed as suffering from Sheehan syndrome. She was treated with glucocorticoid and beneficial results were obtained. Her serum concentration of natrium returned to normal and she discharged on the 74th postoperative day. We present this paper because we had difficulty in determining that she had Sheehan syndrome, and think that a careful search for a diagnosis before operation is important for the management of the patient during the perioperative and postoperative period.

Adenocarcinoma↗
PubMed1995

Characteristics of non-small cell lung cancer 3 cm or less in diameter.

We retrospectively investigated 308 cases of non-small cell lung cancer of < or = 3 cm diameter. There were 204 adenocarcinomas, 78 squamous cell carcinomas, 15 large cell carcinomas, and 11 other carcinomas. According to TNM staging, there were one case stage 0, 208 stage I, 22 stage II, 49 stage IIIA, 15 stage IIIB, and 13 cases stage IV. T1 disease was seen in 262 cases, T2 in 19, T3 in 10, T4 in 16, and Tis in 1. N0 disease was seen in 217 cases, N1 in 30, N2 in 60, and N3 in 1. The 5-year survival rate of all cases was 63%. There were statistically significant differences among T status (T1 vs. T3, T4), N status (N0 vs. N1, N2), and M status (M0 vs. M1) (P < 0.01). The 5-year survival rates of cases with adenocarcinoma and squamous cell carcinoma were 60% and 64%, respectively. In 204 cases of adenocarcinoma, T3 disease was found in one case, T4 disease in 15 (7%), and nodal involvement (N1 + N2) was present in 69 (34%). In 78 cases of squamous cell carcinoma T3 was seen in 6 (8%), T4 in 1, and nodal involvement in 14 (18%). The incidence of T3 disease, T4, and N(+) varied significantly according to histology (P < 0.05). Our investigation suggested that cases of small-sized lung cancer were often at an advanced stage at detection, and that the spread of disease differed according to histology. The patient with small-sized lung cancer should be offered a standard operation regardless of histology.

Adenocarcinoma↗
PubMed1995

Detection of CYP1A1 gene polymorphism using designed RFLP and distributions of CYP1A1 genotypes in Japanese.

Isoleucine (Ile)-valine (Val) polymorphism, which is caused by a point mutation from A to G in exon 7, is reported to be associated with an elevated risk of lung cancer among Japanese. Because CYP1A1 catalyzes bioactivation of environmental procarcinogens, such as benzo[a]pyrene, it is very important to study the clinical meaning of Ile-Val polymorphism using an epidemiological study. In an epidemiological study, easy, economical, rapid and reliable identification of the CYP1A1 genotype is necessary. The present study shows that the new method, designed restriction fragment length polymorphism (designed RFLP), can detect Ile-Val polymorphism of CYP1A1. The Ile-Val polymorphism detected using this new method was consistent with that found by the allele-specific PCR amplifications (ASA) method in six cases tested. This new method detected Ile-Val polymorphism of CYP1A1 using 240 healthy Japanese who lived in the northern Kyusyu region. The frequency of the genotypes was as follows: Ile/Ile 159 (66.2%); Ile/Val, 65 (27.1%); Val/Val, 16 (6.7%). The frequency of the Ile gene was 0.798 and that of the Val gene, 0.202. There was no difference in Ile-Val polymorphism based on sex or age. Racial differences influenced the distribution of this polymorphism, but Japanese regional differences did not. Since this new method, designed RFLP, is rapid, reliable and suitable for large-scale screening of polymorphisms, it may be used routinely to detect Ile-Val polymorphism of CYP1A1. Furthermore, it will help to evaluate the relationship between CYP1A1 polymorphism and individual sensitivity to xenobiotics that may affect the incidence of lung cancer.

Adult↗
PubMed1995

Frequent loss of the short arm of chromosome 9 in resected non-small-cell lung cancers from Japanese patients and its association with squamous cell carcinoma.

We analyzed 87 Japanese non-small-cell lung carcinomas (NSCLC) including 30 squamous cell, 51 adenocarcinomas and 6 large-cell carcinomas for loss of heterozygosity (LOH) on the short arm of chromosome 9, and we correlated our findings with clinicopathological features. We used four polymorphic microsatellite markers on 9p (interferon A gene, D9S171, D9S126, and D9S169), which flank the critical region (9p21-22) involved in lung cancer. We observed alterations of DNA sequences at 9p in NSCLC (27 of 82 informative cases or 33%). Concordance among the four markers was high (87%), indicating that the deletions often were relatively large. The 27 genetic alterations observed on 9p include 26 examples of LOH, 1 homozygous deletion, and 1 case with LOH and evidence of microsatellite alteration characterized by shift in band mobility. We noted a high frequency of LOH at 9p especially in squamous cell carcinoma (17 of 29 informative cases or 59%), and in poorly differentiated NSCLC (12 of 23 informative cases or 52%). There was no correlation between LOH at 9p and the other clinical parameters, including survival, gender, tumor size and the presence of regional or distant metastases. In contrast to other reports, we found only rare instances of homozygous deletions (1%) and microsatellite alteration showed as a mobility shift (1%). Our findings demonstrate that LOH at the short arm of chromosome 9 is correlated with squamous cell and poorly differentiated carcinomas in Japanese patients with NSCLC.

Base Sequence↗
PubMed1995

The close relationship between growth factors and the nucleolar organizer regions in adenocarcinoma of the lung.

We examined immunohistochemically 111 cases of primary adenocarcinoma of the lung, for transforming growth factor alpha (TGF alpha) or epidermal growth factor (EGF), and argyrophilic nucleolar organizer regions (AgNORs). The presence of more than 75% positive cells for both growth factors was designated as a high-GF, while all others were considered to be a low-GF. If AgNORs counts were more than 5.00, it was considered to be a high-AgNORs group, while less than 5.00 was designated as a low-AgNORs group. In our 111 examined specimens, there were 51 (46%) cases of high-GF, and 64 (58%) with high AgNORs. The 5-year survival rates of the patients with a high-GF and low-GF were 34% and 57% (P < 0.05) respectively, while those with high-AgNORs and low-AgNORs were 21% and 81% (P < 0.001), respectively. In the cases of high-AgNORs, the 5-year survival rates of the patients with high-GF and low-GF were 0% and 36% (P < 0.05), respectively. However, in the cases of low-AgNORs, the 5-year survival rates of the patients with high-GF and low-GF were 83% and 79%, respectively. These data suggest that growth factors might be related to the biological malignancy of tumours with a high cell proliferation.

Adenocarcinoma↗
PubMed1995

Proliferating cell nuclear antigen may be superior to argyrophilic nucleolar organizer regions in predicting shortened survival of patients with non-small cell lung cancer.

We examined proliferating cell nuclear antigen (PCNA) in 102 patients with surgically treated non-small cell lung cancer (NSCLC). PCNA labelling index (LI) tended to be higher in tumours of higher stages than those of early stages, in squamous cell carcinomas than adenocarcinomas, or in poorly differentiated adenocarcinoma than in well-differentiated. A positive correlation was observed between the PCNA LI and argyrophilic nucleolar organizer regions (Ag-NOR) count which we previously examined (r = 0.31, P = 0.002). In survival analysis of 79 patients who died of lung cancer, only age, stage and PCNA LI were found to be significant prognostic factors on multivariate analysis among seven potential prognostic factors including sex, age, year of operation, histological type, stage, Ag-NOR count, and PCNA LI. We conclude that PCNA may be superior to Ag-NOR in predicting shortened survival of patients with non-small cell lung cancer. PCNA staining can be performed with ease and it may be applied in a clinical laboratory on a routine basis to help predict prognosis of NSCLC.

Adult↗
PubMed1995

p53 nuclear immunostaining and gene mutations in non-small-cell lung cancer and their effects on patient survival.

BACKGROUND: p53 gene mutations are known to occur in about half of all non-small-cell lung cancer (NSCLC) cases. Mutations of the p53 gene usually but not always lead to an increased half life of the p53 protein, and result in a nuclear accumulation of protein which can be detected by immunohistochemistry (IHC). Controversy still exists as to whether the presence of an aberration of the p53 gene or protein is a poor prognostic indicator in patients with NSCLC. PATIENTS AND METHODS: DNA samples and paraffin blocks were obtained from 129 patients of 143 consecutive patients who underwent a pulmonary resection during a 22-month period from July 1991 to April 1993. Mutations of the p53 gene occurring at exons 5-8 were detected by a polymerase chain reaction (PCR)/single strand conformation polymorphism (SSCP) assay, while the nuclear accumulation of the p53 protein was detected by immunohistochemistry. RESULTS: Of the patients studied, 35% had mutations and 54% showed overexpression, when we defined a positive case as being one in which more than 10% of the tumor cell nuclei were stained. There was a 59.5% concordance between the p53 gene mutations and p53 immunopositivity. p53 immunopositivity in adenocarcinoma and any p53 abnormality (i.e. p53 immunopositivity and/or mutation) in adenocarcinoma were a poor prognostic indicator. However, Cox's proportional hazards model indicated that the stage was the only significant prognostic factor. CONCLUSIONS: p53 immunopositivity and mutations of the p53 gene are frequently seen in NSCLC. They are considered to be mutually related but may sometimes represent a different aspect of p53 abnormality. p53 alteration may be a poor prognostic indicator only in a subset of patients with NSCLC, especially for adenocarcinoma.

Carcinoma, Non-Small-Cell Lung↗
PubMed1995

Serum level and tissue expression of c-erbB-2 protein in lung adenocarcinoma.

Serum levels of c-erbB-2 protein were measured by an enzyme immunoassay in 64 patients with lung adenocarcinoma. Immunohistochemical staining was performed in 40 of these tumors. The mean serum concentration was 16.5 +/- 8.5 U/mL (range: 3.4 to 49.0) in patients with lung adenocarcinoma, whereas it was 14.0 +/- 3.7 U/mL (range: 6.9 to 20.9) in 15 controls (1 U/mL = 0.61 ng/mL). Elevated concentrations (> or = 22.0 U/mL, control mean + 2 SD) were observed in 17/64 lung adenocarcinoma patients (26.6%), as compared with none of the control subjects (p < 0.05). Patients with stage IIIB or T4 disease had increased serum levels. The serum concentration was decreased significantly by surgical tumor ablation. Tissue overexpression was obtained in 17/40 cases (42.5%), and serum levels in patients with tissue overexpression were higher than in patients without overexpression. Serum c-erbB-2 protein may be a useful indicator of tumor burden in patients with lung adenocarcinoma.

Adenocarcinoma↗
PubMed1995

[Expression of CD44 alternative splicing variants in lung cancer].

Expression of isoforms of the CD44 is generated by alternative splicing of CD44 gene; CD44H: lacks all 10 alternative exons, CD44R: the alternative exons v8 to v10, CD44V: other group of variants which contains the alternative exon v6. In some tumors such as colorectal cancer, breast cancer, non-Hodgkin lymphoma, and melanoma, over-expressed CD44 isoform which contains such alternative-spliced variant exons may play a causative role in tumor metastasis. In lung cancer, however, the role of CD44 variants in tumor progression and metastasis is uncertain. In our study and reported literature, no definite correlation was observed between the expression of specific CD44 isoform and tumor progression or metastasis of lung cancer.

Alternative Splicing↗