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Biomedical subjects

K Emoto

Publications and source records attributed to K Emoto.

53 records · Page 3Linked to original sources

Mesangial bridges. A mode of progression in diabetic glomerulosclerosis.

Electron microscopic examination of the renal biopsy material obtained from a 35-year-old diabetic patient revealed subdivisions of glomerular capillaries into several branches by dendritic mesangial projections built between the mesangium and peripheral loop, a similar process which was described as mesangial bridges in a chronic phase of masugi nephritis. In comparison with those in experimental animals, mesangial bridges in the present case appeared rather solid with matrix formation, most presumably depending on long duration of the disease state in the diabetic patient. This process may represent a more complicated type of lesion invariably accompanying the nodule formation and is assumed to be an irreversible lesion ultimately undergoing segmental obliteration of glomerular capillaries.

Adult↗

Heterotransplantation of human urinary bladder cancers in nude mice.

Thirty-one human urinary bladder cancers were transplanted subcutaneously into congenitally athymic nude mice. Subcutaneous growth was obtained in eight at the initial transplantation. Only one of these eight successful transplants, which was derived from squamous cell carcinoma, has been serially transplanted successfully and was characterized by high thromboplastic and low fibrinolytic activities which were virtually constant throughout the serial passages. This strain will provide a useful model system for studying anticancer therapies.

Animals↗

Heterotransplantation of human upper urinary tract tumors in nude mice.

Eight human upper urinary tract tumors were transplanted subcutaneously into congenitally athymic nude mice. Subcutaneous growth was obtained in three (NKPP 1, NKPP 2, and NKPU 1) at initial transplantation and they were all serially passaged up to 29, 28, and 5 passages, respectively. Their histologic appearances were similar to those of the originals. These established strains with high transplantability and differing degrees of thromboplastic and fibrinolytic activities will provide a useful model system for studying anticancer therapies and biological characteristics of upper urinary tract tumors.

Adult↗

Antisense epidermal growth factor receptor delivered by adenoviral vector blocks tumor growth in human gastric cancer.

Epidermal growth factor receptor (EGFR) protein overexpression is commonly found in human gastric cancer, and its gene amplification is known to correlate with poor prognosis in gastric cancer patients. With regard to therapy trials targeting EGFR, it has been reported that stable transfection of EGFR antisense or treatment with antibody against EGFR results in growth suppression of human cancer cells that express high levels of EGFR. We have designed an adenovirus-expressing antisense EGFR and have investigated its effect on the growth of gastric cancer in vitro and in vivo. Following infection with EGFR antisense RNA-expressing adenovirus (Ad-EAS), the cell surface EGFR protein levels of infected cancer cells were markedly reduced, and the in vitro growth of Ad-EAS-infected cells was significantly inhibited relative to control-infected cells in all three gastric cancer cell lines (AGS, KKLS, and MKN28) studied here (P < .0002). In a nude mouse subcutaneous tumor system, in vivo tumor growth of MKN28 was significantly inhibited after Ad-EAS treatment, and inhibition on day 48 was 93% by volume compared with that of untreated controls. These results suggest that an adenoviral vector system targeting the down-regulation of EGFR could be a good candidate for the therapy of gastric cancers that overexpress EGFR.

Adenoviridae↗

Intracellular binding sites of acridine orange in living osteosarcoma cells.

There have been many reports concerning the intracellular binding sites of acridine orange (AO), although the actual localization of AO in living cells remains controversial. This study was undertaken to clarify the intracellular localization of AO in living mouse osteosarcoma cells by cytochemical staining. A mouse osteosarcoma cell line (MOS) was cultured and continuously exposed to 0.5 microgram/ml of AO. The intracellular localization and stainability of AO the living tumor cells was morphologically detected by a high resolution fluorescence microscope. To detect the intracellular microstructure, cytochemical staining with rhodamin 123 for mitochondria, acid phosphatase for lysosome, Sudan-black for fat vesicle and toluidine blue for glucosaminoglycan were performed using fixed cells. The results showed that both the nucleus and cytoplasm of tumor cells at 10 minutes after exposure to 0.5 microgram/ml of AO emitted green fluorescence, which was especially intense in the nucleolus, but not brilliant in the nucleus and was granular orange to red fluorescence in the perinuclear particles. This stainability of AO was different from that of rhodamin 123, Sudan-black or toluidine blue, but similar to that of acid phosphatase. Based on these results, we conclude that the green fluorescence may have derived from AO binding to double stranded RNA, not to DNA, and that orange fluorescence may have derived from aggregated AO binding to lysosome.

Acid Phosphatase↗

Relationship between binuclear and multinuclear cells in giant cell tumor of bone.

Giant cell tumor of bone (GCT) consists of stromal and multinuclear type tumor cells. Although most people believe that the stromal cells are mononuclear, we recently found the existence of many binuclear cells among stromal cells using DNA cytofluorometric examination. This study, using 18 tumors of GCT was conducted to elucidate the cell biological significance of the binuclear cell, especially its relationship to multinuclear cell formation or tumor cell proliferation. The investigation was carried out by means of DNA-RNA cytofluorometry with acridine orange (AO) and histological method. Using fluorescence microscopic observation, we counted the numbers of both mononuclear and binuclear cells and calculated the index of % BNC, which expresses the frequency (percentage) of binuclear cells in a population of mononuclear and binuclear cells. The index of % S-G2 obtained by DNA-RNA cytofluorometry showed the frequency (percentage) of mononuclear cells in the S and G2 phases of the cell cycle. In the histological study, we counted the numbers of multinuclear giant cells with more than 3 nuclei in the cytoplasm and stromal cells including mononuclear and binuclear cells and calculated MNS/SC, which showed the percentage of multinuclear cells in the stromal cells in the microscopic field. Eight tumors showed a value of % BNC greater than 10% and 2 had a value of 40%. The index of % BNC significantly correlated with the average value of MNC/SC in all tumors. There was no significant correlation between % BNC and the average value of % S-G2, in 18 tumors although 4 tumors having a % BNC value greater than 20% showed a % S-G2 value greater than 12% in 18 tumors. These results revealed the presence of many binuclear cells among stromal cells of GCT and suggested that these binuclear cells might be formed in association with the active proliferation of mononuclear cells and closely relate to the formation of multinuclear giant cells.

Adolescent↗

Binuclear cells induced by acridine orange in giant cell tumor of bone.

We have recently found the presence of many binuclear cells among isolated and smeared cells in giant cell tumor of the bone (GCT). These binuclear cells are possibly associated with the formation of multinuclear cells. Therefore, this study was undertaken to clarify the mechanism of binucleation in GCT, using primary culture cells exposed to acridine orange (AO) which is a fluorescent vital staining dye for the cytoplasm and nucleus and which inhibits mitosis. The cells were isolated from explants of fresh tumor materials obtained from two GCT patients (GCT1 and GCT2). These cells were cultured in Dulbecco's modified Eagle medium (DMEM) with 10% Fetal calf serum (FCS). After exposure to 0.5 microgram/ml AO, for 0, 6, 24, 48, 96 and 144 hours the following parameters were investigated: 1) cell growth rate (GR); 2) frequency of hyperdiploid cells (%HDC) by DNA cytofluorometry; 3) mitotic index (MI); 4) BrdU labeling index (LI); 5) frequency of binuclear cells (%BNC). Compared to the control cells which were cultured in AO-free medium, the GR of both GCT cells exposed to AO was remarkably inhibited. The MI was 0 from 24 to 144 hours. The %HDC was increased at 24 hours and was maintained high until 144 hours. The LI was temporarily increased at 6 hours, but was decreased at 48 hours. The %BNC was gradually increased. AO inhibited DNA synthesis and cell mitotic activity in cultured GCT cells and it finally caused inhibition of cell growth. However, the frequencies of G2 arrest cells and binuclear cells were increased. These results suggested that the binuclear cells in GCT may be formed from G2 arrest cells by amitotic nuclear division, but not by mitosis without cytoplasmic division, or by cell fusion.

Acid Phosphatase↗

Nerve contact with muscle component in neuromuscular hamartoma.

Neuromuscular hamartoma is a very rare soft tissue tumor, of which only 20 cases have been reported previously. None of these reports has described the relation between hamartomatous skeletal muscle and nerve fibers in the tumor. We experienced a patient with neuromuscular hamartoma arising at the brachial plexus. In this tumor, the localization of synaptophysin (SYP), S-100 protein (SP), neuron-specific enolase (NSE) neurofilament protein (NFP) and myoglobin (MG) was immunohistochemically detected. The results showed that SYP and MG were diffusely localized in the hamartomatous muscle fibers, SP in the schwann cells, and NSE and NFP in the axons of the hamartomatous nerve. Therefore, it is suggested that in the neuromuscular hamartoma, the structure of the neuromuscular junction may be similar to that in the motor end-plate of the normal muscle, but it may not be functional, because the hamartomatous muscles could not contract by nerve stimulation.

Hamartoma↗

Relationship between doxorubicin binding ability and tumor volume decrease after chemotherapy in adult malignant soft tissue tumors in the extremities.

We have previously reported that the doxorubicin (DOX) binding ability detected by the DOX (or adriamycin) binding assay closely correlated with the chemosensitivity of human osteosarcomas (1). We performed the present study to clarify the relationship between the DOX binding ability (%DB) and the histologic response, rate of decrease in tumor volume of malignant soft tissue tumors after preoperative chemotherapy and prognosis. Nine malignant soft tissue tumors (4 liposarcomas, 3 synovial sarcomas, one malignant fibrous histiocytoma (MFH) and one extraskeletal osteosarcoma (EOS)) which arose at the extremities of adult patients were analyzed by the DOX binding assay using freshly biopsied specimens. After preoperative chemotherapy including DOX or pirarubicin (THP), the rate of decrease in tumor volume was measured using magnetic resonance imaging, and the histologic response expressed as tumor necrosis to chemotherapy was also investigated. All the patients, apart for one, were continuously disease-free after treatment. One patient with EOS died of metastatic disease before surgery. The histologic response in 8 tumors without EOS was poor. The %DB of 5 tumors was greater than 80% (average: 95.90%), whereas that of 4 tumors was less than 80% (average: 38.33%). Although there was no correlation between the %DB and the histologic response, or prognosis, a significantly positive correlation was found between the %DB and the rate of decrease in tumor volume (r = 0.7455, p < 0.05). These results suggest that in malignant soft tissue tumors, the rate of decrease in tumor volume after chemotherapy might be a better indicator for chemosensitivity than the histologic response and also that the DOX binding ability might be a good predictor for chemosensitivity before chemotherapy.

Adult↗

Assessment of chemosensitivity in patients with malignant bone and soft tissue tumors using thallium-201 scintigraphy and doxorubicin binding assay.

This study was performed to compare the accumulation of thallium (Tl)-201 which is correlated with malignancy and the doxorubicin binding ability, which is correlated with chemosensitivity, in nine patients who received preoperative chemotherapy with doxorubicin and cisplatin. Tl-201 scintigraphy was performed at 15 minutes (early image) and 3 hours (delayed image) after injection of 111 MBq of Tl-201. The change of degree of the radionuclide uptake between the early and delayed images was evaluated before and after preoperative chemotherapy. The doxorubicin binding ability (%DB) to nuclear DNA in living tumor cells isolated from biopsy materials was assessed by doxorubicin binding assay. The histologic response to preoperative chemotherapy was evaluated by the percentage of tumor necrosis. Before preoperative chemotherapy no changes of Tl-201 uptake between the early and delayed images was detected in any tumors. Five patients, who had no change of Tl-201 uptake after preoperative chemotherapy, showed a poor histologic response and had a %DB ranging from 10% to 70% (mean: 36.0%). The other four patients, who had a %DB greater than 90%, showed a good histologic response. All of these four patients had decreased Tl-201 uptake after preoperative chemotherapy. This study demonstrated that doxorubicin binding assay and midcourse Tl-201 scintigraphy are useful methods to assess the response to chemotherapy early in malignant bone and soft tissue tumors.

Adolescent↗

Indication of splenectomy for gastric carcinoma involving the proximal part of the stomach.

BACKGROUND/AIMS: The role of splenectomy in the surgical management of gastric carcinoma is controversial and there is no consensus of opinion regarding the therapeutic value of splenectomy. The aim of this study was to search for possible metastasis to lymph nodes in the splenic hilum or along the splenic artery to avoid unnecessary splenectomy and to determine its indication. METHODOLOGY: The clinical records of 204 patients who underwent total gastrectomy combined with splenectomy for gastric carcinomas involving the proximal part of the stomach were analyzed. RESULTS: The incidence of nodal involvement to the splenic hilum and/or along the splenic artery was 49 (24.0%) of 204 gastric carcinomas involving the proximal part of the stomach that underwent combined gastrectomy and splenectomy. The characteristics of gastric carcinoma with metastasis to these nodes included a larger tumor, deeper penetration (T3, 4 tumors), a number of lymph node metastasis, and infiltrative type. In T2 cases, all the tumors with cancerous involvement to these nodes showed intraoperative gross serosal change). When the tumor size was less than 40 mm, nodal metastatic rate to the splenic hilum and/or along the splenic artery was very low. CONCLUSIONS: In conclusion, splenectomy should be conducted in T2 cases with gross serosal change and T3, 4 cases. With regard to tumor size, in the cases with a tumor whose size was less than 40 mm, it is possible to preserve the spleen in most cases. In the near future, splenectomy should be clarified precisely by randomized trials in advanced gastric carcinoma.

Adenocarcinoma, Papillary↗

Annexin II overexpression is correlated with poor prognosis in human gastric carcinoma.

Annexins belong to a family of the calcium-dependent phospholipid binding proteins. They are also substrates of receptor tyrosine kinases. Overexpression of Annexin II, which has been reported in various carcinomas, is thought to be associated with cell proliferation, differentiation and cell-cell adhesion in the pathogenesis of carcinoma, but the functions of Annexins have not been fully elucidated. In this study, we investigated the role of Annexin II (p36) and its relationship with c-erbB-2 overexpression in gastric carcinoma. We studied Annexin II expression using Western blot analysis in 8 human gastric carcinoma cell lines and expression of Annexin II and c-erbB-2 using, immunohistochemistry in 153 primary gastric carcinomas. Western blot revealed that Annexin II was expressed in 8 human gastric carcinoma cell lines. It was more strongly expressed in the cell membrane than in the cytoplasm of tumor cells in primary gastric carcinoma tissues. Thirty-three percent of all cases were immunopositive for Annexin II, overexpression of which was more frequent in differentiated type (p = 0.0009), lymph node, metastasis (p = 0.0147) and venous invasion (p = 0.0092). Annexin II and c-erbB-2 overexpression were significantly correlated p = 0.0002) and patients with Annexin II had poorer prognoses (p = 0.0066). Multivariate analysis showed that immunopositivity of both Annexin II and c-erbB-2 was an independent and poor prognostic factor (p = 0.0037). In conclusion, Annexin II was overexpressed in advanced gastric carcinomas and it could contribute to the progression of gastric carcinoma.

Annexin A2↗