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Biomedical subjects

K Sugio

Publications and source records attributed to K Sugio.

At least 55 records · Page 3Linked to original sources
PubMed1997

Micrometastatic P53-positive cells in the lymph nodes of non-small-cell lung cancer: prognostic significance.

OBJECTIVES: Approximately one fourth of all patients with stage I non-small-cell lung cancer die of tumor recurrence, despite radical removal of their tumors. We thus tried to detect micrometastasis in the regional lymph nodes indicated to be tumor free by conventional histopathologic methods in patients with non-small-cell lung cancer by using immunohistochemical staining for p53 protein. We also investigated the relation between micrometastatic p53-positive cells in the lymph nodes and the prognosis of the patients. METHODS: Samples from 480 regional lymph nodes were taken from 47 patients who underwent pulmonary resection for non-small-cell lung cancer and whose primary lesions were positive for p53 immunohistochemical staining. These samples were fixed in formalin and embedded in paraffin. We used p53 immunohistochemical staining to detect micrometastatic tumor cells in the lymph nodes. RESULTS: Cells positive for p53 protein were found in 14 of 31 (45%) patients with a negative pathologic lymph node status and in 26 of 315 (8.3%) lymph nodes in these patients. The proportion of patients with micrometastasis who survived was also significantly lower than the proportion of patients without micrometastasis who survived (p = 0.0001). CONCLUSIONS: Immunohistochemical staining for the p53 protein offers a rapid, sensitive, and useful way of detecting for micrometastasis to the regional lymph nodes in patients with non-small-cell lung cancer that is positive for p53 staining. The patients with such micrometastases have a poor prognosis and thus need to be carefully followed up after the initial pulmonary resection.

Carcinoma, Non-Small-Cell Lung↗
PubMed1997

K-ras and p53 mutations are an independent unfavourable prognostic indicator in patients with non-small-cell lung cancer.

We examined 159 consecutive cases of non-small-cell lung cancer (NSCLC) for a mutation at codon 12 of the K-ras gene and for a mutation of the p53 gene occurring in exons 5-8. Eleven (6.9%) had mutations of the K-ras (ras+) and 57 (35.8%) had mutations of the p53 (p53+). There were 95 cases (59.7%) with ras- p53-, seven cases (4.4%) with ras+/p53-, 53 cases (33.3%) with ras-/p53+ and four cases (2.5%) with ras+/p53+. The ras+ group had a worse prognosis than the ras group in all cases and in 107 early-stage cases (stage I-II, P<0.05). The p53+ group had a worse prognosis in 107 early-stage cases (P<0.01), but there was no statistically significant difference when 52 advanced-stage cases (stage III-IV) or all patients were considered. Both ras and p53 mutations were unfavourable prognostic factors in 94 cases with adenocarcinoma, but there was no statistical significance in 57 cases with squamous cell carcinoma. According to Cox's model, the pathological stage, ras mutation and p53 mutation were found to be independent prognostic factors. Our results suggest that ras and p53 mutations were independent unfavourable prognostic markers especially in the early stage of NSCLC or in adenocarcinoma.

Adult↗
PubMed1997

Aggressive pulmonary metastasectomies for synovial sarcoma.

A 51-year-old woman underwent a bilateral wedge resection of lung metastases through a median sternotomy 10 months after an initial operation for synovial sarcoma of the left lower extremity. Since then, five right and two left posterolateral thoracotomies have been performed over a 6-year period. The patient is presently doing well 7 years after the initial operation of the left lower extremity without any evidence of recurrence.

Adult↗
PubMed1997

Laparoscopic pylorus-preserving gastrectomy with intracorporeal hand-sewn anastomosis.

To prevent stapled stenosis after laparoscopic local gastric resection by using autosuturing devices, we developed a technique for laparoscopic pylorus-preserving gastrectomy with intracorporeal hand-sewn anastomosis. We describe this procedure and present two case reports. The intracorporeal hand-sewn anastomotic technique is an important advance in the field of minimally invasive laparoscopic surgery.

Aged↗
PubMed1996

The usefulness of FDG positron emission tomography for the detection of mediastinal lymph node metastases in patients with non-small cell lung cancer: a comparative study with X-ray computed tomography.

We evaluated the usefulness of fluorine-18-fluoro-2-deoxy-d-glucose positron emission tomography (FDG PET) in the detection of mediastinal lymph node metastases in patients with non-small cell lung cancer and then compared the findings with the results of X-ray CT by region based on the histological diagnoses. We examined 29 patients with non-small cell lung cancer. One hundred and thirty-two mediastinal lymph nodes were surgically removed and the histological diagnoses were confirmed. FDG PET images, including 146 mediastinal regions, were visually analysed and the mediastinal lymph nodes were scored as positive when the FDG uptake was higher than that in the other mediastinal structures. On the X-ray CT scans, any mediastinal lymph nodes with a diameter of 10 mm or larger were scored as positive. All three examinations were successfully performed on 71 regions. For FDG PET, we found a sensitivity of 76%, a specificity of 98% and an accuracy of 93%. On the other hand, for X-ray CT a sensitivity of 65%, a specificity of 87% and an accuracy of 82% were observed. A significant difference was observed in respect of both specificity and accuracy (P<0.05). Based on the above findings, FDG PET is suggested to be superior to X-ray CT when used for the detection of mediastinal lymph node metastases in patients with non-small cell lung cancer.

Aged↗
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

High yields of K-ras mutations in intraductal papillary mucinous tumors and invasive adenocarcinomas induced by N-nitroso(2-hydroxypropyl)(2-oxopropyl)amine in the pancreas of female Syrian hamsters.

Ductal adenocarcinoma, the most common form of pancreatic cancer in humans, is associated with activation of the K-ras oncogene in approximately 90% of cases. In contrast, K-ras mutations are found in < 50% of the relatively rare intraductal papillary mucinous tumor (IPMT), which arises in the main pancreatic ducts. Since both adenocarcinomas and IPMTs are believed to arise from ductal cells and progress through similar sequences of morphological changes (i.e. flat hyperplasia, papillary hyperplasia, atypia and carcinoma in situ), it is clear that such progression may not always necessitate activation of the ras oncogene. Experimentally ductal adenocarcinomas of the pancreas can be induced in the hamster model by a brief treatment with N-nitroso(2-hydroxypropyl)(2-oxopropyl)amine (HPOP), while IPMTs can be induced by a combined treatment with HPOP and orotic acid (OA) in an initiation/promotion schedule. Since animals are exposed to the carcinogen only once, initiated normal epithelium is expected to give rise to a wide spectrum of neoplastic and preneoplastic lesions, progression of which will depend on the extent of mutagenesis induced at initiation in the targeted cells. In order to investigate the role of K-ras in progression of IPMTs as compared with adenocarcinomas we have examined the presence of K-ras mutations in the above two types of experimentally induced pancreatic cancers, as well as in associated and preneoplastic lesions. K-ras mutations at codons 12, 13 and 61 were determined by a designed restriction fragment length polymorphism method using mismatched nested primers in 77 neoplastic and preneoplastic foci microdissected from 20 pancreases. Mutations were found in all foci of atypical hyperplasia, in carcinomas in situ and invasive cancer, whether such lesions originated in lobular tissue or in the main pancreatic duct. Mutations were also found in papillary hyperplasia and flat hyperplasia in small ducts and also in the main duct at high frequency. With one exception, all ras mutations were G-->A transitions at the second base of codon 12. Mutations were occasionally accompanied by excessive presence of the mutant ras allele or loss of the wild-type ras allele, events that were more frequent in atypical hyperplasia (5/17), carcinomas in situ (5/14), IPMTs (2/5) and invasive adenocarcinomas (2/5) than in flat hyperplasia (0/6) or papillary hyperplasia (2/18). Our results demonstrate that: (i) K-ras mutations, predominantly G-->A transitions, are present in all experimentally induced hamster tumors; (ii) the incidence of K-ras mutations in IPMTs is lower in humans than in the hamster model; (iii) advanced lesions in both adenocarcinomas and IPMTs were frequently associated with an excess of the mutant over the wild-type K-ras allele. It is likely that both adenocarcinomas and IPMTs induced chemically in the hamster model arise by mechanisms which involve early activation of K-ras. Such a mechanism seems to be applicable only in a fraction of human IPMTs.

Adenocarcinoma, Mucinous↗
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

Allele-specific loss in chromosome 9p loci in preneoplastic lesions accompanying non-small-cell lung cancers.

BACKGROUND: Carcinogenesis is a multistep process, which may begin as a consequence of chromosomal changes. Deletions in the short arm of chromosome 9 (9p) have been observed in lung carcinomas. In addition, morphologically recognizable preneoplastic lesions, frequently multiple in number, precede onset of invasive carcinomas. PURPOSE: We tested for deletions and loss of heterozygosity (LOH) at 9p loci in preneoplastic and neoplastic foci in lungs of patients with non-small-cell lung carcinomas (NSCLCs). METHODS: Seven archival, paraffin-embedded, surgically resected NSCLC specimens were selected. They were predominantly from patients with adenocarcinomas and contained multiple preneoplastic lesions, including hyperplasia, metaplasia, dysplasia, and carcinoma in situ (CIS). Fifty-three histologically identified preneoplastic and malignant lesions present in bronchi, bronchioles, and alveoli were precisely microdissected from stained tissue sections with a micromanipulator. Stromal lymphocytes were used to determine constitutional heterozygosity. The specimens were analyzed for LOH using polymerase chain reaction-based assays for polymorphism in dinucleotide repeats (microsatellite markers) in interferon alfa (IFNA) and D9S171 loci on 9p. RESULTS: All seven cases were constitutionally heterozygous for one or both microsatellite markers. Five of seven cases had LOH at one or both 9p loci in the invasive primary cancers (doubly informative cases). Four of these five cases also revealed LOH in preneoplastic foci. In the doubly informative cases, LOH was detected in five (38%) of 13 foci of hyperplasia, four (80%) of five foci of dysplasia, and three (100%) of three CIS lesions. LOH was detected in preneoplastic lesions from all regions of the respiratory tract, including bronchi, bronchioles, and alveoli, and involved five different cell types. The identical allele was lost from both the preneoplastic lesions and the corresponding tumors (12 of 12 lesions, 17 of 17 comparisons), a phenomenon we have referred to as "allele-specific mutation." Statistical analyses employing a cumulative binomial test demonstrated that the probabilities of such findings occurring by chance are 2.4 x 10(-4) and 7.6 x 10(-6), respectively. From comparisons with the previously published data on other chromosomal abnormalities in the same tissue specimens, it appears that LOH at 3p and 9p loci occurred early in the hyperplasia stage, but the ras gene point mutations were relatively late, at the CIS stage. CONCLUSIONS: LOH at 9p loci occurs at the earliest stage in the pathogenesis of lung cancer and involves all regions of the respiratory tract. LOH in NSCLC is not random but targets a specific allele in individuals. Studying preneoplastic lesions may help identify intermediate markers for risk assessment and chemoprevention.

Adenocarcinoma↗
PubMed1995

Allele-specific mutations involved in the pathogenesis of endemic gallbladder carcinoma in Chile.

Although gallbladder carcinoma is one of the most frequent neoplasms in Chile, there is limited information about the molecular changes involved in its pathogenesis. We investigated the incidence of ras gene mutations and loss of heterozygosity (LOH) at the following genes/loci: p53, DCC, rb, 5q 3p, 8p, and 9p. We precisely microdissected 194 relevant areas from paraffin-embedded microslides from 25 gallbladder carcinomas and their accompanying nonneoplastic lesions (which were present in 15 cases) from patients in Chile. The specimens were analyzed by PCR-based assays for LOH, and we designed a RFLP method for ras mutations and immunohistochemistry for p53 protein overexpression. We determined that LOH at p53 (91%), 9p (50%), 8p (44%) and DCC (31%) are frequent events and that LOH at p53, 9p, and DCC are early events, while ras mutations and LOH at 3p, rb, and 5q occurred occasionally. LOH at p53 occurred more frequently and earlier than protein overexpression. The mean number of mutations present in invasive carcinomas was 2.1, and in six cases, LOH at the p53 gene was the sole mutation detected. The same allele was lost in 61 (93%) of 71 nonneoplastic foci as in the corresponding invasive carcinomas for all four mutations studied. The odds of this occurring by chance are approximately 4 x 10(-15). Although clonality cannot be excluded, allelic loss appears to be highly directed, but the mechanism for allele-specific mutations remains to be determined.

Adenocarcinoma↗
PubMed1995

Allele-specific chromosome 3p deletions occur at an early stage in the pathogenesis of lung carcinoma.

BACKGROUND: Deletions in the short arm of chromosome 3 (3p) are present in most lung carcinomas. OBJECTIVE: To investigate the role of these chromosome 3p deletions in the pathogenesis of non-small cell lung carcinomas. DESIGN: Seven archival, paraffin-embedded, surgically resected lung cancer specimens were studied. Fifty precisely identified malignant and preneoplastic lesions present in bronchi, bronchioles, and alveoli were microdissected from stained slides and analyzed for allele loss using polymerase chain reaction-based assays for dinucleotide repeat polymorphisms at three chromosome 3p loci (3p14, 3p21.3, and 3p25). SETTING: University-based medical center and affiliated hospitals. SUBJECTS: Samples were analyzed from seven patients who underwent surgical resection with curative intent for non-small cell lung cancer and whose specimens included extensive multifocal areas of preneoplastic lesions (hyperplasia, metaplasia, dysplasia, or noninvasive cancer). RESULTS: Lymphocytes from all seven cases were heterozygous (ie, informative) for all three microsatellites analyzed. Six (86%) of seven invasive cancers had loss of heterozygosity at one or more chromosome 3p sites. In the accompanying preneoplastic lesions, loss of heterozygosity was detected in none of two normal bronchioles, 13 (76%) of 17 hyperplasias, six (86%) of seven dysplasias, and four (100%) of four noninvasive cancers. Loss of heterozygosity was detected throughout the respiratory tract, in bronchi, bronchioles, and alveoli. In 18 (78%) of 23 preneoplastic lesions, the specific alleles lost were identical to those lost in the corresponding carcinomas. The probability of this happening by chance is 5.3 x 10(-3). CONCLUSIONS: Deletions in the short arm of chromosome 3 occur at the earliest stage (hyperplasia) in the pathogenesis of lung cancer and involve all regions of the respiratory tract. Allele loss is highly specific, but its mechanism remains unknown. Our findings may be of considerable biologic, prognostic, and clinical significance.

Aged↗
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

Neurogenic tumors of the mediastinum originated from the vagus nerve.

Thirty-nine patients with neurogenic tumors observed between 1974 to 1992 were reviewed. There were 32 patients with neurilemoma, one with neurofibroma, five with ganglioneuroma, and one with malignant neurilemoma. Two cases of neurilemoma originated from the vagus nerve, which is very rare. Surgical resection is recommended, not only to confirm the nature of the lesion, but also to prevent further growth and compression on adjacent structures. For benign encapsulated neurogenic tumors, resection is curative.

Ganglioneuroma↗
PubMed1995

The relationship between the immunodetection of transforming growth factor-beta in lung adenocarcinoma and longer survival rates.

We immunohistochemically examined the expression of transforming growth factor-beta (TGF-beta) on tissue specimens from primary 124 human lung adenocarcinoma, using a polyclonal antibody. The overall mean immunoreactivity of TGF-beta was 25.7 +/- 22.9, therefore we separated patients into two groups according to their mean immunoreactivity. There were 59 (48%) with a high TGF-beta and 65 (52%) with a low TGF-beta. No correlation was observed between the expression of TGF-beta and clinicopathological factors except for degree of differentiation. The 5-year survival rates of patients with high and low TGF-beta were 71% and 37%, respectively (P < 0.05). A multivariate analysis using the Cox life table regression model showed TGF-beta to be a significantly independent factor. We thus concluded, based on our findings, that the expression of TGF-beta was found to be related to a better prognosis. Therefore, estimating the negative cell proliferation activity induced by TGF-beta on immunohistochemical technique is considered to be useful for determining the patients' prognosis in cases of lung adenocarcinoma.

Adenocarcinoma↗
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

Glutathione S transferase Pi is a powerful indicator in chemotherapy of human lung squamous-cell carcinoma.

We immunohistochemically investigated the expression of glutathione S transferase pi (GST- pi) and clarified the correlation between GST-pi and the results of chemosensitivity testing on the tissue of primary human squamous-cell carcinoma of the lung. The expression of GST-pi was evaluated in 105 cases and their level of chemosensitivity was estimated by the in vitro succinate dehydrogenase inhibition test for cisplatin, Adriamycin, cyclophosphamide, mitomycin C, vindesine and fluorouracil. Tumors in which 25% and more of the cells stained for GST-pi were classified as having a high GST-pi expression, while those tumors demonstrating less than 25% of the cells staining for GST-pi were considered to have a low expression GST-pi. The percentage of high GST-pi was 52% (53 of 105) while that of low GST-pi was 48% (52 of 105). No significant correlation between the expression of GST-pi and clinicopathologic factors was observed, while no significant difference in the survival of the two groups was found either. An increase in succinate dehydrogenase activity was recognized in the high-GST-pi group compared with the low-GST-pi group for each anticancer drug; however, no statistical significance was seen except for cisplatin. In the cases with adjuvant combination chemotherapy using cisplatin after a complete resection, all cases demonstrating a relapse were associated with a high GST-pi. These findings thus indicate that an overexpression of GST-pi is related to the resistance to cisplatin in human lung squamous-cell carcinoma. It is therefore important to select carefully the optimal anticancer drug for high-GST-pi cases.

Aged↗