[Father-son cases of arrythmogenic right ventricular dysplasia treated successfully by radiofrequency catheter ablation].
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Adult↗
Biomedical subjects
K Aizawa
Publications and source records attributed to K Aizawa.
Intramural metastases from thoracic esophageal cancer: local indicators of advanced disease.
The patterns of tumor spread and long-term survival of patients with (n = 54) and without (n = 270) intramural metastasis from esophageal cancer were investigated after either extended radical (n = 155) or less radical (n = 169) esophagectomy. The purpose was to evaluate whether extended radical esophagectomy has an impact on the long-term survival of patients with intramural metastases from the disease. The patients with intramural metastasis had significantly larger primary tumors (p < 0.01) and more frequent T4 tumors (p < 0.001), stage IV disease (p < 0.05), lymphatic invasion (p < 0.05), and lymph node metastasis (p < 0.01) than did those without intramural metastasis. The survival rates of patients with intramural metastases were significantly worse than those of patients without intramural metastases after resection (p < 0.001). No patient with intramural metastases survived more than 4 years after either extended or less radical esophagectomy, and there was no significant difference between the two survival curves. Therefore intramural metastases should be considered local indicators of advanced esophageal cancer, and radical esophagectomy may not be indicated for patients with intramural metastasis from the disease.
Aged↗
The relationship between quantitative changes in collagen and formation of wrinkles on hairless mouse skin after chronic UV irradiation.
Female albino hairless mice were irradiated chronically with sub-erythemal doses of UVB radiation. Collagen extracted from the irradiated or non-irradiated dorsal skin of mice was fractionated into neutral salt-soluble (NSC), acid-soluble (ASC) and insoluble fractions (ISC). An age-related exponential decrease in the content and proportion of acid-soluble collagen was found in each group. The contents and the proportions of ASC from irradiated mice were always significantly lower than those from age-matched control animals. Age-related slight decreases were observed in the contents (per fresh weight of tissues) of NSC, ISC and total collagen in the control group but decreases in these collagen contents after UVB irradiation were marked. A dramatic decrease in ASC occurred nearly concomitantly with wrinkle formation in the irradiated mice. The decrease of acid-soluble skin collagen in irradiated mice may play a role in the formation of wrinkles on hairless mouse dorsal skin.
Animals↗
Photodynamic therapy with a diode laser for implanted fibrosarcoma in mice employing mono-L-aspartyl chlorin E6.
The authors performed photodynamic therapy (PDT), avoiding any hyperthermic effects, using a newly developed diode laser and photosensitizer, mono-L-aspartyl chlorin e6 (NPe6), of Meth-A fibrosarcoma implanted in mice and achieved tumor therapeutic benefit. The photodynamic light treatment was performed 5 h following the photosensitizer administration. With 5.0 mg/kg NPe6 and light doses of 50, 100, 150 and 200 J/cm2, the tumor cure rates were 20, 50, 70 and 90%, respectively. With 100 J/cm2 laser exposure and NPe6 doses of 1.25, 2.5, 5.0, 7.5 and 10.0 mg/kg, the tumor cure rates were 0, 20, 50, 70 and 90%, respectively. A charge-coupled device (CCD) camera system was employed to measure the NPe6 fluorescence intensity correlating with the residual amount of the photosensitizer at deferent depth from the tumor surface. The ratios of the NPe6 fluorescence intensity at 3 mm from the tumor surface following 50, 100, 150 and 200 J/cm2 laser exposure to no laser exposure were 0.73, 0.36, 0.22 and 0.16, respectively. With samples sectioned at 1 mm depth, after 50 J/cm2 and the same photosensitizer dose (5 mg/kg) this ratio was 0.19. These results suggest that a certain increase in the tumor tissue level of NPe6 and a certain increase of laser light dose reaching deeper layer of tumor caused an increase in percent cure. In addition, the effectiveness of PDT depends on the total laser dose reaching deeper layers of tumors. Furthermore, the effectiveness of PDT tends to correlate with the amount of NPe6 photobleaching by PDT.
Animals↗
[Dynamics of photosensitizer in the cell].
1) Mono-L-aspartyl chlorin e6 is a photosensitizer with a molecular weight of 799.7 in which the double bond porphyrin ring has been reduced and an aspartic acid is attached to the propionic group at the carbon of the tetrapyrole ring via a peptide linkage. 2) The absorption spectrum of mono-L-aspartyl chlorin e6 is characterized by a Soret band at 398 nm and four Q bands located at 502, 530, 620, and 654 nm in PBS solution at pH 7.4. However, when it bound to serum albumin at ratios of more than 1:1 absorption peaks showed a red shift at 6 nm in the PBS solution. 3) Erythrocytes in the blood containing serum albumin and the same concentration of mono-L-aspartyl chlorin e6 were not lysed with the diode laser irradiation. 4) The concentration of mono-L-aspartyl chlorin e6 in mitochondria fraction of normal tissue decreased from 2 hours after intravenous injection. However, the concentration of mono-L-aspartyl chlorin e6 in mitochondria fraction of tumor increased during 4 hours after injection and then gradually decreased.
Animals↗
Primary small cell carcinoma of the esophagus: report of a case.
A case of esophageal small cell carcinoma successfully treated with combination therapy consisting of both pre- and postoperative chemotherapy as well as surgical resection is presented. A 74-year-old man presented with a small cell carcinoma measuring 11 cm in diameter in the lower half of his thoracic esophagus. After undergoing preoperative chemotherapy with cisplatin (25 mg, iv, days 1 through 5), the gross tumor completely regressed. However, a microscopic focus of residual cancer showing squamous cell carcinoma was found in the resected esophageal specimen. The patient received an additional two courses of postoperative chemotherapy with cisplatin (75 mg, iv monthly). He has since survived more than 9 years with no evidence of recurrent disease. We herein report a rare case of a patient with esophageal small cell carcinoma who demonstrated a complete cure.
Aged↗
Chemotherapy of human small-cell gastrointestinal carcinoma xenografts in nude mice.
We established two xenografts of small-cell carcinoma (SCC) arising in the oesophagus or the stomach, designated TEG13 and TSG15, and investigated the responses to experimental chemotherapy on these strains. Both tumours were classified as the intermediate cell type of SCC composed of small cells having neuroendocrine features in terms of morphology, argyrophil property, and immunoreactivity for neuron-specific enolase. Mitomycin C, cisplatin, and cyclophosphamide were judged to be effective against both strains. Particularly, cisplatin produced almost complete regression of tumour growth of the TEG13 strain. Etoposide proved effective only against the TSG15 strain. Moreover, the combined treatment with etoposide and cisplatin produced the most pronounced antitumour effect against the TSG15 strain. These studies suggest that cisplatin may be a key drug for chemotherapy of oesophageal SCC, and etoposide plus cisplatin treatment may be especially recommended in the treatment of gastric SCC. Mitomycin C should be re-evaluated in gastrointestinal SCC.
Aged↗
Photofrin photosensitization. Correlation of Photofrin:erythrocyte binding processes with photolysis.
Unilamellar suspensions of dimyristoylphosphatidylcholine (DMPC) can be utilized to remove Photofrin from the erythrocyte. This enables correlation of the Photofrin membrane-binding processes with Photofrin-sensitized photolysis. The observed rates of erythrocyte biding as well as the observed rates of removal of PHotofrin from the erythrocyte membrane suggest the existence of two Photofrin species that differ in their rates of exchange between the erythrocyte and buffer phases. Selective depletion and readdition of these Photofrin species to the erythrocyte membrane permits evaluation of their separate and joint photolytic efficiencies. These rapidly and slowly exchanging membrane-bound Photofrin species are separately much less efficient photosensitizers than the two species together. The two Photofrin species exhibit essentially identical fluorescence emission spectra in the presence of DMPC. Nevertheless, models consistent with the results involve partitioning by chemically distinct Photofrin components or partitioning of chemically similar Photofrin components into distinct membrane environments, or a combination of these.
Dihematoporphyrin Ether↗
[Experimental cancer of the digestive tract--cultured cells of human gastric cancer and tumor transplanted into nude mice].
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Animals↗
Direct visualization of atherosclerosis in small coronary arteries using the epifluorescence stereoscope.
OBJECTIVE: To visualize specifically at the beating heart surface atherosclerosis in small coronary arteries using the photosensitiser, mono-L-aspartyl chlorin e6 (NPe6). METHODS: Cholesterol-fed atherosclerotic rabbits were injected intravenously with 2.0 mg/kg of NPe6. Atherosclerosis was visualized by allowing NPe6 to accumulate in atheromatous plaques, and then used as a potent fluoroprobe to illuminate atherosclerotic coronary arteries upon excitation by light. An epifluorescence stereoscope system was used to visualize atherosclerosis in small coronary arteries. RESULTS: Although it was unable to specify the parts of the coronary arteries which had atherosclerotic changes under room light with the naked eye, several brightly illuminated branching small coronary arteries were observed clearly against the dark heart surface through the epifluorescence stereoscope, as an exciting mercury blue light beam was used to irradiate the beating heart. A fluorescence micrograph of the coronary artery, at which orange-red fluorescence was seen through the epifluorescence stereoscope, showed that the atheromatous plaques emitted orange-red fluorescence. CONCLUSIONS: The presence and extent of small coronary atherosclerosis were demonstrated in the beating heart. Such information may help assess the clinical significance of atherosclerosis in small coronary arteries.
Animals↗
Different characteristics of hepatoid and non-hepatoid alpha-fetoprotein-producing gastric carcinomas: an experimental study using xenografted tumors.
The characteristics, including metastatic potential, of 5 xenografts of alpha-fetoprotein (AFP)-producing gastric carcinomas in nude mice, designated TSG1, TSG3, TSG11, TSG17 and TSG20, were examined. Of these xenografts, TSG1, TSG11 and TSG20 were regarded as hepatoid adenocarcinomas based on their morphological resemblance to hepatocellular carcinoma, frequent immunoreactivity for liver-cell markers, and excessive production of AFP with a high concanavalin A (Con-A)-binding property of hepatic type. On the other hand, TSG3 and TSG17 tumors showed the features of poorly differentiated medullary adenocarcinoma with scattered AFP-positive cells consistent with low AFP levels in mouse sera, and negative immunoreactivity for other liver-cell markers. Ultrastructurally, these tumors were composed of undifferentiated cells with a little adenocarcinomatous differentiation. Moreover, the AFP produced by TSG3 and TSG17 tumors had an extremely high Con-A nonbound fraction (80% to 90%), which was different from that of the hepatic or yolk-sac types. Therefore, both TSG3 and TSG17 tumors were regarded as non-hepatoid, poorly differentiated adenocarcinomas which could be differentiated from any types of AFP-producing gastric carcinoma. Furthermore, cells from hepatoid adenocarcinoma strains (TSG1, TSG11 and TSG20) injected into the spleens of nude mice produced liver metastases in all the mice examined, whereas cells from non-hepatoid carcinoma strains (TSG3 and TSG17) produced few or no liver metastases. Our data show that some non-hepatoid AFP-producing gastric carcinomas have lower liver-metastasizing potential than hepatoid AFP-producing gastric carcinomas.
Adenocarcinoma↗
Patterns of lymphatic spread in thoracic esophageal cancer.
BACKGROUND: The cervical nodes have been excluded from the category of regional nodes in cases of thoracic esophageal cancer in the present TNM classifications. METHODS: One hundred and forty-one patients with thoracic esophageal cancer who had undergone extensive radical lymphadenectomy were included in the study. The patterns of early lymph node metastasis from the disease, in terms of lymph node metastases from the intramural tumors or those found in patients with a single metastatic node, were studied. Prognostic significance of the removal of the positive nodes also was examined in relation to the metastatic sites. RESULTS: Of the 47 patients with intramural cancer, only 21% had nodal metastases confined to the mediastinum, 11% had positive cervical nodes, and 23% had jumping metastases to the extramediastinal nodes. Of the 31 patients with a single metastatic node, 61% showed metastasis in a jumping fashion, and 19% had a positive node in the neck. Seventy-four (79.6%) of the 93 patients with vessel invasion also had lymph node metastases, whereas 20 (41.7%) of the 48 patients without vessel invasion had metastases to the lymph nodes (P < 0.001). The 5-year projected survival rate for patients with positive cervical nodes was 27%, with no significant difference in survival rate compared with that for patients with metastatic nodes in the mediastinum or the abdomen. The number of involved nodes was related significantly to outcome: The 5-year survival rates for the 45 patients with negative nodes the 66 patients with one to four positive nodes were 71.8 and 34.2%, respectively (P < 0.01), whereas none of the 27 patients with five or more positive nodes survived more than 3 years after the operation (P < 0.001). CONCLUSIONS: The cervical nodes should be included in the category of regional nodes in cases of thoracic esophageal cancer on the basis of the patterns of early lymph node metastases and the prognostic significance of a lymphadenectomy for metastases to these nodes.
Abdomen↗
Augmentation of 5-fluorouracil cytotoxicity by epidermal growth factor in a newly established human signet-ring cell carcinoma of the stomach in culture.
A cell line designated TSG6 was established from a signet-ring cell gastric carcinoma developed in a 57-year-old female patient. The TSG6 cells had well preserved the features of signet-ring cell carcinoma based on morphology. The cells exhibited both epidermal growth factor (EGF) and epidermal growth factor receptor (EGFR) immunoreactivities, and also secreted EGF. Moreover, the growth of TSG6 cells was stimulated in the presence of exogenous EGF. These results suggest that the possible presence of an EGF/EGFR autocrine growth mechanism is expressed in the TSG6 cells. The simultaneous treatment with EGF and 5-fluorouracil (5-FU) produced a nearly 2.4-fold enhancement of 5-FU cytotoxicity against TSG6 cells. A bromodeoxyuridine/DNA flow cytometry analysis revealed that EGF augmented 5-FU cytotoxicity by inducing the accumulation of S phase cells which might be more susceptible to 5-FU. Moreover, we found that the incorporation of 5-FU into the TSG6 cells was increased with the addition of EGF. These data indicate that EGF may be a potent agent as a biological response modifier for 5-FU against the tumors which express the EGF/EGFR autocrine mechanism, and that the TSG6 cell line is useful in furthering our understanding of the interaction between anticancer drugs and EGF.
Carcinoma, Signet Ring Cell↗
Clinical implications of cervical lymph node metastasis patterns in thoracic esophageal cancer.
OBJECTIVE: The authors attempt to clarify the clinical implications of cervical lymph node metastases from thoracic esophageal cancers. SUMMARY BACKGROUND DATA: Cervical lymph node metastases from thoracic esophageal cancer have been considered to be incompatible with curative resection. However, recent studies have demonstrated that cure is achievable in patients with such metastases. METHODS: Patterns of esophageal cancer metastasis to the cervical nodes and long-term results after tumor resection were investigated in 23 patients undergoing bilateral cervical lymphadenectomy for treatment of thoracic esophageal cancer. RESULTS: The number of positive nodes per patient was significantly greater (p < 0.05) in lower esophageal cancers (median: 15) than in upper or mid esophageal cancers (median: 2.5). Simultaneous metastases to three nodal regions (the neck, mediastinum, and abdomen) were significantly more common (p < 0.001) in lower esophageal tumors (88.9%) than in upper and mid esophageal lesions (7.1%). Although the overall 5-year survival rate was 16.5%, long-term survival was achieved only in patients with upper or mid esophageal cancer.
Adult↗
Flow cytometric analysis of early steps in development of adriamycin resistance in a human gastric cancer cell line.
We have established a low-level adriamycin (ADM)-resistant human gastric cancer cell line (MKN45R) from the parental cell line (MKN45) by exposure to stepwise increases of ADM concentration (final concentration, 0.026 microgram/ml). The purpose of this study was to identify the early steps in the development of ADM resistance in MKN45R by flow cytometric (FCM) analysis. Comparison of the concentration required for 50% growth inhibition, determined by a tetrazolium-based colorimetric assay, showed that MKN45R was about 2.6-fold more resistant to ADM than MKN45. However, the inhibition index values were 89.5% for MKN45 and 86.4% for MKN45R, respectively, showing that ADM was judged to be "effective" against both cell lines. On the other hand, cell kinetic analysis by FCM revealed that the increase of the ratio of G2M accumulation induced by ADM treatment was significantly lower (P < 0.01) in MKN45R. Moreover, the efflux of ADM estimated by FCM analysis was significantly increased (P < 0.05) in MKN45R even though there was no significant increase of P-glycoprotein expression. These results suggest that although ADM was still effective based on a standard drug sensitivity test, the cancer cells were already acquiring resistance to ADM as judged from FCM analysis. Moreover, the mechanism of this ADM resistance is considered to be independent of P-glycoprotein expression. Thus, FCM analysis is useful for detecting the early steps in the development of drug resistance of cancer cells.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Photodynamic therapy using a diode laser with mono-L-aspartyl chlorin e6 for implanted fibrosarcoma in mice.
We have developed a new high-power red (664 nm) laser diode system for photodynamic therapy (PDT) with mono-L-aspartyl chlorin e6 (NPe6). Meth-A fibrosarcoma cells (1 x 10(6)) were implanted subcutaneously in the right hind leg of 4-week-old BALB/c female mice. One week later, diode laser irradiation was applied 5 h after the intravenous administration of NPe6 to each tumor-bearing mouse. In the first study, the time course of intratumor temperature increase during PDT was measured by using a 23-guage thermocouple hypodermic needle at a depth of 2 mm from the tumor surface. In the second study, 6 groups of 10 to 17 tumor-bearing mice were treated with the diode laser 5 h after intravenous administration of NPe6 at the dose of 1.25, 2.5, 5.0 or 7.5 mg/kg i.v. per mouse. Total photoirradiation ranged from 0 to 150 J/cm2 and the dose rate was adjusted to 100 mW/cm2. Percentages of cures were determined from numbers of mice apparently disease-free 50 days after treatment. The results showed that this diode laser is effective in PDT of implanted fibrosarcoma after NPe6 administration. It also confirmed that the therapeutic effects of PDT were not due to hyperthermia. Moreover, the diode laser beam was demonstrated by CCD technology to be uniform in intensity throughout the photoirradiated field.
Animals↗
Characterization of a functional null cell line derived from NZB x NZW)F1 mice.
We attempted to establish a null cell line from NZB x NZW(B/W)F1 mice in order to investigate a regulatory role of null cells during polyclonal B cell activation in autoimmune diseases. NB2.2, a representative subclone of resulting null cell lines, was maintained in long-term tissue culture with 10% mouse ConA supernatant (MCAS). Interestingly, the cell free supernatant of the NB2.2 cells (NB-CFS) showed marked synergistic effects on IgM secretion by B cells induced by IL-5. In addition, NB-CFS had the ability to augment the production of autoantibodies against bromelain-treated mouse red blood cells (BrMRBC) and single-stranded DNA (ssDNA) by B cells induced by IL-5. To determine whether NB2.2 cells induce polyclonal B cell activation and autoantibody generation in vivo, BALB/c mice were injected with NB2.2 cells. The results showed that the level of anti-ssDNA antibodies in sera of BALB/c mice injected with NB2.2 cells was significantly higher than that of control BALB/c mice injected with FDC-P2 cells. In addition, splenic B cells from mice injected with NB2.2 cells significantly proliferated in vitro in response to IL-4 and IL-5, and produced anti-ssDNA antibodies in the presence of IL-5. These results suggest that NB2.2, a null cell line established from B/WF1 mice, produces mediators capable of promoting polyclonal B cell activation and inducing autoantibody secretion, and that this kind of null cell may play an important role in the pathogenesis of autoimmune diseases.
Animals↗
Coexistence of choriocarcinoma and hepatoid adenocarcinoma in the stomach.
The case is presented of a 46 year old woman who had a gastric tumor with components of choriocarcinoma, hepatoid adenocarcinoma and common types of adenocarcinoma. Although two histologic types of tumor producing carcinoplacental or carcinofetal proteins were contained within the tumor, immunohistochemical analyses, especially of placental alkaline phosphatase, clearly showed that each component was present separately within the same tumor. It was only hepatoid adenocarcinoma cells that permeated the lymph and blood vessels. After the recurrence, the serum level of alpha-fetoprotein (AFP) markedly elevated, but that of human chorionic gonadotropic beta-subunit (hCG-beta) was always within normal range. These findings indicate that in the present case the hepatoid adenocarcinoma component was more aggressive in growth than the choriocarcinoma component.
Adenocarcinoma↗