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Biomedical subjects

T Tsuchida

Publications and source records attributed to T Tsuchida.

408 records · Page 23Linked to original sources

Effects of quinolinone derivative, vesnarinone, in combination with irradiation on human lung cancer cell lines.

The quinolinone derivative, vesnarinone, is a novel inotropic agent used in the treatment of heart failure. It has also been found that vesnarinone has a potential anti-cancer activity. To evaluate the anti-cancer activity of vesnarinone in combination with irradiation, we investigated the cytostatic and cytotoxic effects on human lung cancer cell lines (PC-9 and Lu 134A) using MTT assay and isobologram analysis. We also analyzed the nuclear fragmentation of tumor cells by flow cytometric analysis. Our study demonstrated that combination of vesnarinone with irradiation had an additive inhibitory effect on both PC-9 and Lu 134A tumor cell growth. Vesnarinone could improve the sensitivity of tumor cells to irradiation and thus the dose of irradiation could be reduced to half without decreased inhibitory effect. Significant increase of the tumor cell nuclear fragmentation was observed with combination of vesnarinone and irradiation. These results indicate that vesnarinone not only directly inhibited tumor cell growth, but also improved the sensitivity to irradiation. Combination of vesnarinone with irradiation may be an efficacious protocol for lung cancer treatment. The inhibitory effect was ascribed to inducing tumor cell apoptosis.

Adenocarcinoma↗

Inhibition of liver metastasis of colon cancer by in vivo administration of anti-vascular endothelial growth factor antibody.

Cancer metastasis via blood vessels is a complicated process involving a number of stages. Vascularization in the cancer stroma is essential for the metastatic process. Vascular endothelial growth factor (VEGF) is an angiogenic factor, and has important roles in tumor progression or metastasis. In this study, we developed a polycolonal antibody to VEGF and examined whether the anti-VEGF antibody could inhibit the metastasis of human xenografts expressing VEGF in nude mice. The xenograft Col-23-JCK expressing VEGF formed metastatic lesions in the liver and/or pancreas when inoculated via the portal vein (splenic vein) into nude mice. The anti-VEGF polyclonal antibody inhibited metastasis to the liver and/or pancreas (4.75+/- 3.62, anti-VEGF-treated vs. 9.73 +/- 8.24, w/o anti-VEGF treatment; Student's t-test, p=0.035). Vascularity in the metastatic lesions was also decreased by anti-VEGF treatment. These results suggest that anti-VEGF antibody administration may be therapeutically useful for prevention of colon cancer metastasis.

Animals↗

Heterozygous ras mutations are preserved in serially passaged human tumor xenografts and established cell lines.

We examined c-K-ras gene point mutations in human tumor xenografts and established cell lines as markers of genetic stability. Our previous study demonstrated the stability of c-K-ras gene mutations in human primary neoplasms and their tumor xenografts through serial passages in mice. In this study, we established 27 human cell lines derived from various human tumor xenografts in nude mice. Point mutation of the c-K-ras gene at codon 12 was found in 29.6% (8/27) of the cell lines, as well as in 29.6% (8/27) of the xenografts. The eight ras-mutated cell lines were derived from corresponding tumor xenografts carrying the ras mutation. Heterozygous ras gene mutation was confirmed in seven of the eight ras-mutated cell lines, as well as their corresponding xenografts. The incidence, type and heterozygosity of the c-K-ras gene mutation showed no discrepancies between the original xenografts and the established cell lines. From these findings, we concluded that point mutation of the c-K-ras gene was very stable in human tumor xenografts and established cell lines derived from the xenografts.

Animals↗

Overexpression of human H-ras transgene is responsible for tumors induced by chemical carcinogens in mice.

Level of human prototype H-ras transgene expression in tumors induced by chemical carcinogens (N-ethyl-N-nitrosourea and N-methyl-N-nitrosourea) was analyzed in human H-ras transgenic mice (CB6F1-TgrasH2 Jic mice). All forestomach tumors examined revealed about 2-fold overexpression of the human H-ras transgene with or without point mutation at codon 12 or codon 61. However, endogenous mouse H- and K-ras genes exhibited neither point mutation nor overexpression. These results suggested that increased levels of ras gene products in the cell played an important role in facilitating chemical carcinogenesis in transgenic mice.

Animals↗

Expression of cathepsin B and cystatin C in the human adenohypophysis and in pituitary adenomas.

The localization of cathepsin B, a potential promoter of prolactin (PRL) release via extra renal renin-angiotensin system in the adenohypophysis, and its inhibitor cystatin C in the human adenohypophysis and in pituitary adenomas were examined using single and dual immunohistochemical staining. In the adenohypophysis, cathepsin B was expressed in about 50% of the ACTH-producing cells, and in 5% or less of the GH- and PRL-producing cells. In contrast, cystatin C was expressed in about 70% of the GH- and PRL-producing cells, but in only 5% or less of the ACTH-producing cells. PRL-producing adenomas strongly expressed cathepsin B, but only weakly expressed cystatin C, a pattern of staining contrary to the expression in normal PRL-producing cells. The above results suggest that cathepsin B may play a role in promoting PRL release especially in PRL-producing adenomas.

Adenoma↗

Stromal thrombospondin-1 expression is correlated with progression of esophageal squamous cell carcinomas.

Thrombospondin-1 (TSP1) is an extracellular matrix glycoproteins that affecting cell adhesion, motility and growth. Based on its effects on tumors, TSP1 is thought to be a potential regulator of tumor growth and metastasis. In this study, we clarified TSP1 immunoreactivity in human esophageal squamous cell carcinoma and its clinicopathological significance. TSP1 immunoreactivity was detected mainly in the cancer stroma and was observed infrequently in cancer cells. According to the TNM classification, 70.6% (12/17) of the T3 esophageal cancers were TSP1-positive, while only 26.9% (7/26) of the Tis and T1 cancers showed TSP1 expression. Lymph node metastasis and venous involvement was frequently found in the TSP1-positive cases (71.4% and 80.0%, respectively) of esophageal squamous cell carcinoma (p < 0.001). This observation suggested that TSP1 expression plays an important role in cancer cell growth and metastasis of human esophageal squamous cell carcinomas, and that stromal TSP1 immunoreactivity is a good predictor of venous involvement and lymph node metastasis.

Aged↗

A case of pulmonary adenocarcinoma with overexpression of multidrug resistance-associated protein and p53 aberration.

A 66-year-old female patient underwent left upper lobectomy and dissection of the mediastinal lymph nodes. The pathological diagnosis was well-differentiated papillary adenocarcinoma of the lung with metastasis to the mediastinal lymph nodes, p-T2N2MO, stage IIIA. After the operation, she was treated by chemotherapy including lipophilic anticancer compounds (carboplatin and VP-16). The patient unexpectedly showed long survival for 6 years and 2 months without obvious recurrence or metastasis of the cancer. The anticancer compounds were not effective on the recurrent lesions and then she died due to respiratory failure 8 months after recurrence. The autopsy revealed pleural dissemination and intrapulmonary metastasis. Immunohistochemical analysis showed increased multidrug resistance-associated protein (MRP)-positive tumor cells in the recurrent and metastatic lesions, while few MRP-positive cells were apparent in the primary lesion. The MRP-positive cells were accompanied by p53 nuclear accumulation in the carcinoma. This was a case of pulmonary adenocarcinoma with acquired multidrug resistance caused by MRP overexpression and aberrant p53 after chemotherapy.

Adenocarcinoma, Papillary↗

Clinicopathological studies of esophageal carcinoma in achalasia: analyses of carcinogenesis using histological and immunohistochemical procedures.

Achalasia of the esophagus is a benign disease caused by dyskinesia of the lower esophagus and cardia and is presumed to be a premalignant lesion leading to an increased risk of squamous cell carcinoma. We analyzed six surgically or endoscopically resected carcinomas among 54 cases of esophageal achalasia using histological and immunohistochemical procedures. The mean interval between the diagnosis of achalasia and carcinoma was 21.5 years. Four of the six cases were superficial early-stage cancers whilst the other two were advanced cancers invading the adventitia. Histological mapping of the resected esophageal specimens demonstrated marked hyperplastic changes of stratified squamous epithelium and multiple foci of dysplastic changes. The squamous cell carcinomas showed well-differentiated type with low-grade atypia, closely associated with dysplastic foci. Immunohistochemical staining for p53, p21, p16 and epidermal growth factor receptor suggested that the dysplastic epithelium was a borderline lesion between hyperplasia and in situ carcinoma. Our observations suggested that esophageal food stasis induces chronic hyperplastic esophagitis and eventually malignant transformation of esophageal epithelial cells, associated with dysplasia-carcinoma sequence.

Biomarkers, Tumor↗

Collecting duct carcinoma mixed with common renal cell carcinoma: analysis of morphological characteristics using lectin histochemistry.

Recently, cases of collecting duct carcinoma have been reported which were thought to have arisen from the renal collecting ducts or distal tubuli. We present here a rare case of collecting duct carcinoma mixed with common (conventional) renal cell carcinoma. A 51-year-old man underwent right nephrectomy under the diagnosis of renal tumor. Histochemically, markers for the collecting ducts/distal tubuli, such as peanut agglutinin (PNA) and soybean agglutinin (SBA), were identified in the collecting duct carcinoma as well as on several luminar surfaces of the common renal cell carcinoma. Based on the results of histological, histochemical and chromosomal examinations, we speculated on the histogenesis of this collecting duct carcinoma.

3,3'-Diaminobenzidine↗

Glioependymal cyst in the posterior fossa.

A large cyst filled with clear fluid was resected from the cerebellum of a 29-year-old man. By light microscopy the cyst was lined by flat epithelial cells. These epithelial cells abutted on a glial layer and immunohistochemical staining revealed that some of them expressed glial fibrillary acidic protein. Corpora amylacea were noted within the glial layer. Ultrastructurally, 2 types of cells lining the cyst were identified. One was characterized by electron-dense cytoplasm, cytoplasmic vacuoles, microvilli without surface-coated material, cilia, and basal bodies. The other was a cell with a smooth cytoplasmic membrane, round nucleus, and clear cytoplasm. Zonulae adherentes was observed between cyst lining cells and the cyst lining cells were shown to rest directly on the glial layer. Surprisingly, myelinated axons were identified in the glial layer, although nerve cells were not identified. These findings are compatible with those of a glioependymal cyst. The origin of glioependymal cysts of the posterior fossa is not understood, but possibilities include neuroglial heterotopia, persistent Blake's pouch (diverticulum of the roof of fourth ventricle), and remnants of a tela chorioidea. The location of the cyst and the presence of myelinated axons in the cyst wall may be best explained by an origin from neuroglial heterotopia.

Adult↗

Disappearance of Ewing's sarcoma following bacterial infection: a case report.

We report a patient with multiple metastases of Ewing's sarcoma in whom the tumor vanished after a bacterial infection. To the best of our knowledge, no comparable case with Ewing's sarcoma has been reported in the literature. The patient was a 17-year-old male who had an irregular destructive lesion of the left pelvis on radiologic examination. Pathologic examination of a biopsy specimen revealed Ewing's sarcoma. After the operation, a roentgenogram showed multiple spinal metastases with paraplegia. Despite initiation of chemotherapy, a subsequent bone scan showed several areas of increased uptake indicating multiple metastatic lesions. A fistula with purulent discharge opened at the operative site. While being treated with antibiotics and fistula irrigation, the fistula narrowed and his high fever subsided. During this period, radiologic examinations indicated that the multiple bone metastases had nearly disappeared. Nine years after the operation, the patient is alive without any evidence of tumor. We postulate that the antitumor activity in this patient resulted from the bacterial infection, and believe that this case supports continued consideration of immunotherapy for cancer.

Adolescent↗

Small cell lung cancer can express CD34 antigen.

In humans CD34 is a valid and reliable marker for hematopoletic stem and progenitor cells. In general, solid tumors, with the exception of endothelial cancers, do not express CD34. Accordingly, immunological selection of CD34+ hematopoietic stem/progenitor cells can be used to remove CD34- malignant cells in the setting of autotransplantation. To rule out CD34 expression on tumor cells from small cell lung cancer (SCLC), eleven SCLC cell lines were analyzed by flow cytometry. Interestingly, two of these were positive for CD34 and their expression of full-length CD34 was further confirmed by reverse transcriptase and polymerase chain reaction (RT-PCR). This finding indicates that prior to subjecting SCLC patients to the above treatment modality, preparing CD34+ hematopoietic stem/progenitor cells from SCLC patients for autotransplantation, CD34 expression on their tumor cells should be screened using immunohistochemistry and/or flow cytometry.

Antigens, CD34↗