Biomedical subjects

S Fujimura

Publications and source records attributed to S Fujimura.

477 records · Page 27Linked to original sources

PubMedDate not supplied

Expression of Bcl-2, Bax, and p53 proteins in carcinogenesis of squamous cell lung cancer.

BACKGROUND: Apoptosis is regulated by many genes, including bcl-2, p53, and bcl-2 family genes. The expression of Bcl-2, p53, and Bax in very early lung cancers or precancer lesions is not been fully understood. MATERIALS AND METHODS: The expression of these proteins was examined immunohistochemically in 11 normal bronchial epithelia, 23 dysplasias, and 40 roentgenographically occult squamous cell lung cancers (ROCs). RESULTS: The expression of the Bcl-2 and p53 protein increased along with the advance of the morphological atypia in bronchial epithelial cells, whereas no difference in the Bax expression. The patients with Bcl-2 positive ROCs had a better prognosis than those with Bcl-2 negative ROCs. CONCLUSIONS: Bcl-2 and p53 proteins play important roles in early steps of carcinogenesis in squamous cell lung cancer of central type. The Bcl-2 protein could be a prognostic marker in ROCs.

Bronchi↗

PubMedDate not supplied

Immunohistochemical study on tumor angiogenic factors in non-small cell lung cancer.

BACKGROUND: In order to elucidate the roles of tumor angiogenesis in lung carcinogenesis, the expressions of several angiogenic factors in lung carcinoma tissues were examined. MATERIALS AND METHODS: Tissue specimens from 112 cases of resected non-small cell lung cancer (NSCLC) were studied. The expressions of platelet-derived endothelial cell growth factor (PD-ECGF) and vascular endothelial growth factor (VEGF) were examined immunohistochemically. Microvessel density (MVD) was also evaluated. RESULTS: VEGF-positive cases were observed more frequently in advanced stage lung cancers than in early cancers, and VEGF-positive tumors had higher MVD than VEGF-negative tumors, while such differences were not observed for PD-ECGF. In squamous cell carcinoma, the patients with high-MVD tumor had significantly worse survival than those with low-MVD tumor. CONCLUSIONS: Our results suggest that VEGF plays an important role in angiogenesis of lung cancers, while the contribution of PD-ECGF may be limited.

Adenocarcinoma↗

PubMedDate not supplied

Immunohistochemical study of basaloid squamous cell carcinoma, adenoid cystic and mucoepidermoid carcinoma in the upper aerodigestive tract.

Non-squamous cell carcinoma is a rare but distinct neoplasm of the upper aerodigestive tract. Among these carcinomas, basaloid-squamous cell carcinoma (BSCC) has frequently been confused with adenoid cystic carcinoma (ACC) and mucoepidermoid carcinoma of the upper aerodigestive tract. In this study, we examined immunohistochemically the expression of differentiation-related substances, including cytokeratin (CK) subtypes, p53 and p27, and cell adhesion-related molecules E-cadherin and alpha-catenin to clarify the biological features of these neoplasms. We studied seven cases of BSCC of the oesophagus, five cases of ACC and seven cases of mucoepidermoid carcinoma. Squamous cell carcinoma and adenocarcinoma of the oesophagus and trachea were also studied for comparison. Among the cytokeratin subtypes examined, CK14, CK17 and CK19 immunoreactivity was detected in BSCC. ACC and mucoepidermoid carcinoma were immunopositive for CK8, CK14 and CK17 and for CK8, CK14, CK17 and CK19, respectively. These findings suggest that CK subtypes, especially CK8, CK14 and CK17, are useful in differentiating these malignancies. BSCC was more frequently associated with decreased E-cadherin and alpha-catenin immunoreactivity than ACC and mucoepidermoid carcinoma. Nuclear p53 immunoreactivity was detected more frequently in BSCC (5 out of 7) than in ACC (2 out of 5) and mucoepidermoid carcinoma (4 out of 7). There were no significant differences in p27 immunoreactivity among these carcinomas. Carcinoembryonic antigen (CEA) immunoreactivity was detected in mucoepidermoid carcinoma (2 out of 7), SCC (8 out of 11) and adenocarcinoma (9 out of 9), but it was not detected in BSCC (7) or ACC (5). Carbohydrate antigen 19-9 (CA19-9) immunoreactivity was detected only in mucoepidermoid carcinoma (4 out of 7) and adenocarcinoma, but not in BSCC, ACC, or SCC. These findings indicate that BSCC, ACC and mucoepidermoid carcinoma are distinct neoplasms arising in the upper aerodigestive tract. In addition, decreased expression of E-cadherin and alpha-catenin proteins and increased p53 expression in BSCC may be correlated with aggressive behaviour.

Adenocarcinoma↗

PubMedDate not supplied

Targeting of LAK activity to CEA-expressing tumor cells with an anti-CEA scFv/IL-2 fusion protein.

BACKGROUND: Fusion of tumor-specific monoclonal antibody (MAb) and cytokines has proved to be an efficient way to target cytokines to tumor cells and hence focuses the killing activity of effector cells to the target cells. We previously produced a high affinity MAb, F11-39, against carcinoembryonic antigen (CEA), which is often overexpressed on the surface of various tumor cells. MATERIALS AND METHODS: To target the cytotoxicity of effector cells to CEA-expressing tumor cells, we employed recombinant DNA techniques to fuse recombinant human interleukin-2 (rhIL-2) to a single chain variable fragment (scFv) antibody derived from F11-39. The resulting fusion protein, designated F39scFv/IL-2, was expressed in the Sp2/0-Ag14 mouse hybridoma cells, purified by CEA-affinity chromatography and characterized for the CEA-binding specificity and the IL-2 biological activity. RESULTS: F39scFv/IL-2 protein effectively targeted rhIL-2 onto the surface of CEA-expressing tumor cells and consequently introduced a specific cytotoxicity of lymphokine-activated killer cells to the tumor cells. CONCLUSIONS: This approach may be used for in vivo administration to localize IL-2 to tumor tissues, maximizing the immune response to CEA-expressing tumors while keeping systemic side effects to a minimum.

Animals↗

PubMedDate not supplied

Inflammatory pseudotumor of the lung diagnosed as granulomatous lesion by preoperative brushing cytology. A case report.

The clinical and cytologic features of a case of inflammatory pseudotumor of the lung are presented. Chest roentgenograms revealed a solitary circumscribed round mass in a nine-year-old boy. The mass was diagnosed as a granulomatous lesion by bronchoscopic brushing cytology. Although smears and cultures of sputum and brushing specimens were negative for tuberculosis, a tuberculin reaction was positive and antitubercular therapy was instituted. Since the mass had grown further after six months of therapy, an open lung biopsy was performed to resect the lesion and establish the diagnosis. Imprint smears of the cut surface of the lesion showed cytologic features similar to those of the brushings: short, spindle-shaped cells with a tendency to be arranged in stori-form patterns against a background of minimal necrotic debris. Histopathology established the final diagnosis of inflammatory pseudotumor, a rare granulomatous lesion radiologically resembling a true tumor. Since this lesion usually occurs in younger patients, inflammatory pseudotumor should be considered in pediatric cases with an intrapulmonary lesion that shows histiocytic spindle-shaped cells in stori-form patterns, but whose smears and cultures test negative for tuberculosis.

Biopsy↗

PubMedDate not supplied

Localization of double, roentgenographically occult lung cancer. Cytologic findings from selective brushing of all segmental and subsegmental bronchi.

Using selective brushing of all segmental and subsegmental bronchi, six patients were diagnosed as having synchronous, double, roentgenographically occult lung cancers. Experienced bronchoscopists failed to detect four "second cancer" lesions in six patients. The appearance of atypical cells as shown by cytologic examination indicated the probability of the presence of cancer in the examined bronchus. Single cancer cells or tiny clusters of cells with orangeophilic cytoplasm can appear in specimens obtained from all bronchi, and such cells should not be considered to have originated in the bronchi under examination. Medium-sized or large clusters of cancer cells without degeneration and with basophilic cytoplasm appear only in specimens obtained from bronchi in which a cancer lesion exists, and thus they should be considered to have originated in the bronchi under examination. Cancer cells with orangeophilic cytoplasm in clusters should be considered to have originated in unknown locations. To determine the origin of such cells, one must compare the specimens with those obtained from other segmental and subsegmental bronchi. Our findings suggest that selective brushing of all segmental and subsegmental bronchi is a useful method of detecting unrecognizable second cancers and that the method should be employed for all patients with positive sputum cytology.

Aged↗

PubMedDate not supplied

Diagnostic value of differential brushing of all branches of the bronchi in patients with sputum positive or suspected positive for lung cancer.

In roentgenographically occult lung cancer, it is often difficult to determine the location of the tumor despite the existence of cancer. This complicates diagnosis and points to a need for a more systematic method of examination. Differential brushing was performed on all the respective segmental bronchi in both lungs of 196 patients with positive or suspected positive indications of lung cancer as revealed by sputum cytology. Fifty-nine borderline lesions in 43 cases and 107 lung cancer lesions in 95 cases were diagnosed. Localization was possible in 70.4% of the cases. The diagnosis of borderline lesions was also possible. At the first examination, the rate of localization, as compared with that in the historical control group, improved from 64.1% to 95.8%, and, in particular, an improvement from 0% to 86.2% was noted in those cases in which abnormal bronchoscopic findings were not observed. Concurrent multiple primary cancer was also diagnosed in 12.6% of lung cancer cases before treatment. With this method, cytologic findings in sputum and in specimens obtained by brushing and histologic findings of resected lung can be compared in an integrated manner, and henceforth more accurate diagnostic criteria can be established.

Biopsy↗

PubMedDate not supplied

Inhibition of experimental lung metastasis of murine colon carcinoma cells depends on the amount of interleukin-2 secreted from the transduced cells.

We examined the antitumor effect of low and high interleukin-2 (IL-2) producers of murine colon carcinoma cells (Colon 26) which were generated by transduction with IL-2 gene in an experimental lung metastasis model using syngeneic mice. Intravenous injection of the low IL-2 producer cells formed multiple lung metastatic foci and the survival of the mice was not different from that of the mice injected with wild-type cells. However, the mice administrated with the high producer cells survived significantly longer. Subcutaneous inoculation of the low producers, although it caused the development of local tumors at the inoculation sites in some of the mice tested, inhibited lung metastasis of wild-type cells subsequently inoculated and prolonged the survival of the mice rechallenged with Meth A cells, syngeneic fibrosarcoma cells. In contrast, inoculation of the high producers did not cause the development of subcutaneous tumors and inhibited the experimental metastasis of parental but not Meth A cells inoculated thereafter. Thus, the amount of secreted IL-2 from tumor cells differentially influences antitumor effects by inducing tumor specific and nonspecific immunity.

Animals↗

PubMedDate not supplied

Specific primer design and exonuclease III treatment for the reduction of nonspecific staining in direct in situ PCR.

Although direct in situ PCR is more rapid than indirect method for the in situ identification of low copy number genes, several reports indicate serious nonspecific signals with this method. Some procedures have been reported in an effort to eliminate the nonspecific signals, but the results have not been satisfactory. Exonuclease III can progressively digest blunt or recessed 3' termini of double-stranded DNA whereas DNA with 3' overhanging end is resistant to digestion. DNA fragments amplified by PCR with primers incorporating the recognition site for Sph I generate 3' four bases extensions at both end after digestion. These fragments are expected to be resistant to exonuclease III digestion. It is also expected that nonspecifically incorporated digoxigenin would be released by treatment with exonuclease III thereby reducing background. We succeeded in digesting selectively with the samples after standard PCR by Sph I and exonuclease III treatment. However, we failed to eliminate the nonspecific signals of direct in situ PCR. Southern blotting revealed that the amount of nonspecific incorporation was so huge that exonuclease III was unable to release all of nonspecifically incorporated digoxigenin and maintain specific incorporated digoxigenin simultaneously. Direct in situ PCR is a sensitive method. However, its specificity has a significant problem.

Base Sequence↗