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Biomedical subjects

A Kondo

Publications and source records attributed to A Kondo.

588 records · Page 33Linked to original sources

Combined analysis of tumour neoangiogenesis and local immune response in advanced gastric carcinoma.

Neovascularization and host immune response are important in the growth and metastasis of solid tumours. Thus, microvessel density, and dendritic cell (DC) infiltration, which was thought to be an indicator of local immune function, were examined by immunohistochemistry and their prognostic significance was determined in patients with advanced gastric carcinoma. The 5-year survival rates in patients with both low microvessel counts and marked DC infiltration, in patients with either low microvessel counts or marked DC infiltration, and in patients with both high microvessel counts and slight DC infiltration were 82.6%, 68.6%, and 30.2%, respectively, the differences were statistically significant. Moreover, the multivariate analysis showed that combined analysis of microvessel counts and DC density was an independent prognostic indicator. Our findings indicate that combined analysis of tumour neoangiogenesis and local immune response might be useful for predicting prognoses of patients with advanced gastric carcinoma.

Adenocarcinoma↗

Mutated p53 protein expression and proliferative activity in advanced gastric cancer.

BACKGROUND/AIMS: When the DNA of cells is damaged, wild-type p53 protein induces the expression of p21 (Waf1/Cip1/Sdi1), and regulates the progression of the cell cycle by inducing G1 arrest. Thus, wild type p53 or p21 protein negatively regulates cancer cell proliferation. However, in tumor with loss of expression of functional wild-type p53 protein by mutation or allelic deletion of the gene for p53, whether the proliferative activity of cancer cells might be accelerated or not is unclear. In this study, we investigated the correlation between the level of expression of mutated p53 protein and the proliferative activity of cancer cells in advanced gastric cancer. METHODOLOGY: Ninety-seven samples from patients with gastric cancer that had invaded the serosa without lymph node metastasis (t3, n0, stage II) were investigated by immunohistochemical staining with a monoclonal antibody against p53 and against p21, and with the monoclonal antibody Ki-67. DNA ploidy patterns were analyzed by flow cytometry. The immunoreactivity against p53 and the proliferative activity of cancer cells were scored in terms of a labeling index (LI; percentage of immunostained cells) in each case. Moreover, the prognostic values for 93 surviving patients were evaluated by univariate and multivariate analysis. RESULTS: The mean p53 LI was 24% (range: 0-82.4%) and the mean Ki-67 LI was 23.1% (range: 0-70.7%) in 97 tumors. The expression of p21 protein was detected in 30 of 97 tumors (30.9%) and DNA aneuploidy was detected in 36 of 97 tumors (37.1%). There was significant correlation between the p53 LI and the Ki-67 LI (r = 0.61, t = 7.456, p < 0.001) in 97 tumors. Although, no significant difference was detected, the mean p53 LI (18.3%) of 30 tumors with expression of p21 protein was lower than that of 67 tumors without expression of p21 protein (26.6%, p = 0.096). However, no significant correlation between expression of p21 protein and Ki-67 LI was observed. The p53 LI was not an independent prognostic factor in 93 surviving patients by multivariate survival analysis (p = 0.069). However, the 5-year survival rate of 50 patients with a low level of p53 LI (p53 LI (< or = 10%, 78.3%) was significantly better than that of 43 patients with a high level of p53 LI (p53 LI > 10%, 62.1%, p = 0.045). CONCLUSIONS: Accumulation of mutated p53 protein might suppress the expression of p21 protein in gastric adenocarcinoma, and cancer cells with overexpression of mutated p53 protein might have a high proliferative activity.

Adenocarcinoma↗

The expression of thymidine phosphorylase and its correlation with angiogenesis in gastric adenocarcinoma.

BACKGROUND: It has been recently reported that thymidine phosphorylase (dThdPase) is identical to platelet-derived endothelial cell growth factor (PD-ECGF). dThdPase is known to be one of the angiogenic factors. Expression of dThdPase has been detected both in cancer cells and in stroma cells. However, the role of dThdPase, in cancer cells and in stroma cells regarding, neovascularization in gastric adenocarcinoma is still unclear. In this study, we analyzed the correlation between dThdPase activity and neovascularization in gastric cancer. MATERIALS AND METHODS: We obtained fresh samples (tumors and adjacent normal mucosas) from 67 patients with gastric cancer who underwent gastrectomy between 1993 and 1994. The dThdPase activity was analyzed by the ELISA (enzyme-linked immunosorbent assay) method and by the immunohistochemical staining. Microvessel density (MVD) and vascular endothelial growth factor expression of tumors were analyzed by immunohistochemical staining. RESULTS: The dThdPase activity of tumors (117 +/- 98 U/mg protein) was significantly higher than that of normal mucosas (46 +/- 36 U/mg protein, P < 0.0001). The expression of dThdPase was detected by immunostaining in stroma cells but not in mucosal cells in normal tissues. Based on the immunostaining results, 16 tumors expressed dThdPase both in cancer cells and stroma cells. The mean dThdPase activity and the mean MVD of these 16 tumors were significantly higher than those of 15 tumors with expression of dThdPase only in the stroma cells, and than those of 36 tumors with expression of dThdPase in neither the cancer cells or the stroma cells. The MVD of tumors strongly correlated with the dThdPase activity of tumors detected by the ELISA method (P < 0.0001). CONCLUSIONS: The total amount of dThdPase produced by cancer cells and stroma cells may influence tumor angiogenesis in gastric cancer.

Adenocarcinoma↗

Pharmacokinetics of hypotonic cisplatin chemotherapy administered into the peritoneal and the pleural cavities in experimental model.

The pharmacokinetics of intraperitoneal (i.p.) and intrapleural (i.pl.) hypotonic cisplatin (CDDP) were compared under the same experimental conditions. The same dose of CDDP was administered in hypotonic (62 mOsm/L) and isotonic (308 mOsm/L) solutions to the peritoneal and pleural cavities of Ehrlich carcinoma cell bearing mice. The intracellular amount of platinum increased for more than 60 minutes after an i.pl. injection of the hypotonic solution of CDDP, whereas it increased for up to 30 minutes after an i.p. injection. Although hypotonic conditions augmented the amount of platinum taken-up by Ehrlich cells, the amount was significantly greater in the pleural cavity than in the peritoneal cavity. In Donryu rats, the levels of platinum in the i.p. and i.pl. fluids decreased rapidly after injection of hypotonic solution as compared with isotonic solution. The extent of this decrease was greater in the peritoneal cavity than in the pleural cavity. In the hypotonic condition, the area under the curve of concentration versus time (AUC) for platinum of i.pl. fluid was greater than that of i.p. fluid. When i.p. and i.pl. hypotonic CDDP were administered, the osmolarity of the fluid returned rapidly to the isotonic level, with equilibration in 30 or 180 minutes respectively. The lower osmolarity continued for a longer duration in the pleural cavity than in the peritoneal cavity. These results indicate that the pleural cavity may require a smaller amount of CDDP to achieve the same effect on intracellular uptake of platinum than the peritoneal cavity.

Animals↗

An elevated serum level of transforming growth factor-beta 1 (TGF-beta 1) significantly correlated with lymph node metastasis and poor prognosis in patients with gastric carcinoma.

BACKGROUND: Overexpression of transforming growth factor beta s (TGF-beta s), multifunctional polypeptides, have been reported in the tissue of various types of carcinomas, including gastric carcinoma. To our knowledge, serum levels of TGF-beta 1 have not previously been examined in patients with gastric carcinoma as a possible indicator of prognosis. METHODS: Preoperative serum levels of TGF-beta 1 were measured in 111 patients with gastric carcinoma by an enzyme-linked immunosorbent assay. RESULTS: An elevated level of TGF-beta 1 was significantly correlated with lymph node metastasis and poor prognosis. Moreover, the preoperative serum levels of TGF-beta 1 in patients with peritoneal recurrence were significantly higher than those in patients both with lymph node recurrence and without recurrence. CONCLUSION: The serum level of TGF-beta 1 might be useful for predicting recurrence patterns and prognosis in patients with gastric carcinoma.

Analysis of Variance↗

Prediction of survival period for patients with postoperative recurrence after curative resection for advanced gastric carcinoma.

BACKGROUND/AIMS: Although many studies have attempted to clarify the prognostic indicators for gastric carcinoma, there have been few studies regarding the factors that correlate with the survival period of patients with postoperative recurrence. METHODOLOGY: Among 504 advanced gastric adenocarcinoma patients who had undergone curative gastrectomy, 188 patients who had died of recurrence were used in this study. RESULTS: Univariate analysis indicated that age, the presence of lymph node metastasis and blood vessel invasion, the number of positive lymph nodes, and gastrectomy significantly correlated with the survival period. Multivariate analysis indicated that the length of the survival period was independently influenced by the number of positive lymph nodes and blood vessel invasion. The survival time of patients with less than 3 positive lymph nodes and no accompanying blood vessel invasion was significantly longer than that of other patients. CONCLUSIONS: The number of positive lymph nodes and the presence of blood vessel invasion are the most important factors predicting the survival period of patients with postoperative recurrence after curative resection for advanced gastric carcinoma.

Adenocarcinoma↗

Prognostic factors in patients with advanced gastric cancer treated by noncurative resection: a multivariate analysis.

BACKGROUND/AIMS: The relationship between prognostic factors and survival time after noncurative gastric resection in patients with advanced gastric cancer was examined by a retrospective review of data on 364 patients. METHODOLOGY: There were 168 patients without metastasis to the liver or peritoneum (group A), 127 with peritoneal metastasis and no liver metastasis (group B), 50 with liver metastasis and no peritoneal metastasis (group C) and 19 with synchronous liver and peritoneal metastases (group D). Patients were primarily treated with the following 3 drugs: the fluorinated pyrimidines, cisplatin, and mitomycin C. RESULTS: Patients in group D had a very poor prognosis as compared with the other groups. Multivariate analysis using the Cox's proportional hazard model adjusted for sex, age, and other covariants indicated that lymph node metastasis, lymph node dissection, and fluorinated pyrimidines for group A, cisplatin for group B, and lymph node dissection for group C were independent prognostic factors. An analysis of patients excluding cases who died within 30 days after surgery revealed that lymph node dissection for group A, lymph node dissection and cisplatin for group B, and lymph node dissection for group C were independent prognostic factors. CONCLUSIONS: Treatment protocol specific for the residual disease may improve the survival of patients with advanced gastric cancer treated by noncurative resection.

Aged↗

A morphometric study of myelinated fibers in the fifth lumbar ventral roots in patients with cerebrovascular diseases.

In order to evaluate the effects of lesions in the upper motor neuron on the lower one, a morphometric study of the 5th lumbar ventral roots was performed in 16 patients with cerebrovascular diseases (CVD) and 8 age-matched controls plus 7 patients with muscular disorders as pathological controls. As a lesion of the upper motor neuron, the degree of lateral corticospinal tract degeneration in the spinal cord were classified into 4 groups. Total fascicular area (TFA), total myelinated fibers (TF) and large fibers (LF) of the ventral roots were significantly (p less than 0.001) decreased in CVD patients who revealed severe degeneration in the lateral corticospinal tracts in affected sides compared with those of controls. The apparent unilateral fiber loss in the ventral root was also observed in some cases whose lateral corticospinal tracts were degenerated with ipsilateral predominance. Therefore, the degree of degeneration of the lateral corticospinal tracts seemed to parallel that of fiber loss of the ventral roots. On the other hand, there were no significant decreases of TFA and TF in the patients with muscular disorders, which makes less likely the possibility that fiber loss in the ventral roots of CVD cases is attributed to long-term bed rest or lack of muscle movements in extremities. These findings suggest a trans-synaptic effect of the degenerated upper motor neuron (lateral corticospinal tract) in CVD patients facilitating fiber loss in the ventral roots.

Adult↗

A morphometric study of myelinated fibers in lumbar ventral roots and hypoglossal nerves in motor neuron diseases.

Morphometric studies of the 5th lumbar ventral spinal roots and hypoglossal nerves were made in twenty-one patients with motor neuron diseases and 12 age-matched controls. To evaluate the correlation between the numbers of the myelinated fibers and the patterns of white matter degeneration in spinal cords, the latter were classified into three groups: group A with selectively demarcated degeneration of lateral and anterior corticospinal tracts, group B with diffuse degeneration of antero-lateral spinal columns and group C with no degeneration of the spinal white matter. Although the numbers of large myelinated fibers of the 5th lumbar ventral roots were decreased in all three groups, the numbers in group C were significantly better preserved than those in group A. Even in the hypoglossal nerve, the numbers of total and large myelinated fibers were decreased and in addition, the longer the duration of bulbar signs and the more severe the pathological changes found in the hypoglossal nuclei, the fewer the number of myelinated fibers. Especially group A showed a significantly more severe decrease in the numbers of total and large myelinated fibers of the 5th lumbar ventral roots and hypoglossal nerves than group C. These findings suggest that the degeneration of the upper motor neuron accelerates that of the lower motor neuron system in motor neuron diseases.

Adult↗

The blood brain barrier in human leukodystrophies and allied diseases. Ultrastructural and morphometric studies on the capillaries in brain biopsies.

Capillaries in brain biopsies obtained from patients with globoid cell leukodystrophy (GLD), adreno-leukodystrophy (ALD), Canavan's disease (spongy degeneration) and Alexander's disease were examined ultrastructurally and morphometrically. The numbers of pinocytotic vesicles were significantly increased in capillaries in the white matter of all these patients except for a patient with GLD, in comparison with those in the gray matter of each patient. Enlargement of the perivascular space (PVS) was also observed in the white matter more frequently, together with collagen fibers and cytoplasm of infiltrating cells in the patients with ALD, Canavan's disease and Alexander's disease. In a case of GLD, the enlargement of PVS was less although demyelination was as advanced as in a case of ALD. These pathological findings were correlated with the positive contrast enhancement of computerized tomography (CT) images which have been reported in these white matter disorders. It is postulated that the increase of pinocytotic vesicles and the enlargement of PVS are closely related with the disruption of blood-brain barrier BBB) in these conditions.

Adolescent↗

Familial multiple system degeneration associated with iron deposition: determination of subcellular localization of elementary iron by energy-dispersive X-ray analysis.

We report an autopsy case characterized by iron deposition associated with multiple system degeneration. Although iron deposition was distributed as in Hallervorden Spatz syndrome, no spheroid was detectable. On the other hand, multiple system degeneration was observed mainly in the pallido-nigral and dentato-rubral systems which resembled pallido-nigro-luysian degeneration. However, the clinical course and manifestations, and the neuropathology of this case were not completely consistent with any previous report. Differential diagnosis and classification of the case are discussed, and the genetic diagnostic procedures are presented. We also investigated the subcellular localization of elemental iron in glial cells using energy-dispersive X-ray spectral analysis. A small amount of elementary iron was clearly demonstrated in some regions of membrane-bound electron-dense material presumably derived from lysosomes. Further accumulation of clinical and neuropathological data in such cases will provide some clues to discover the etiology and classification of multiple system degeneration that occurs in association with iron deposition.

Cytoplasm↗

Possibility of different cancer development between the proximal and distal colon: comparison of the distribution between adenomatous polyps and cancer.

BACKGROUND/AIM: The aim of this study was to compare the distribution of adenomatous polyps with that of cancer in the colon by using adenomatous polyps removed by colonoscopy. METHODOLOGY: 1223 adenomatous polyps removed by an endoscopic polypectomy were compared with 226 colon cancers with regard to their distribution, size and age. RESULTS: With patients over 65 years of age, the incidence of adenomatous polyps was lower in the proximal colon than in the distal colon, however, the incidence of cancer was higher in the proximal colon than in the distal colon (p<0.05). The distribution of adenomatous polyps according to size was also significantly different between the proximal and distal colon (p<0.05). CONCLUSION: These results thus suggest that some difference may exist in cancer development between the proximal and distal colon.

Adenocarcinoma↗