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Biomedical subjects

Y Kakeji

Publications and source records attributed to Y Kakeji.

102 records · Page 6Linked to original sources

Gastric cancer with high telomerase activity shows rapid development and invasiveness.

Telomerase activity was reported to be activated in most immortal cells and cancers. As the clinical significance of telomerase activity in human gastric cancer is controversial, we investigated this activity using a telomeric repeat amplification protocol. The telomerase activity was tentatively defined by strength of activity as follows: 3+, observed with 0.06 microg of protein; 2+, observed with 0.6 microg of protein; 1+, observed with 6 microg of protein; 0, not observed under these three conditions. Telomerase activity was detected in 35 of 39 (89.7%) gastric cancer specimens. Tumors with high telomerase activities (2+/3+) tended to have a deeper invasion, lymphatic and vascular invasion, lymph node metastasis, liver metastasis, and peritoneal dissemination, as compared to findings in case of low telomerase activities (-/1+). Thus, telomerase activity of gastric cancer tissue may reflect the malignant potential of the tumor and intensive postoperative care might be required for such patients.

Adult↗

Infiltration of S-100 protein positive dendritic cells and peritoneal recurrence in advanced gastric cancer.

We investigated the influence of the infiltration of S-100 protein positive dendritic cells on peritoneal recurrence of carcinoma in 113 patients who had undergone curative resection for gastric carcinoma invading beyond the muscularis propria. The infiltration of dendritic cells was classified into marked and slight. In patients with marked infiltration, peritoneal recurrences were rare, the rate being 5.6%, with a statistical difference compared to the rate of 20.3% with slight infiltration (p < 0.05). When patients were classified into infiltrative and expanding types with regard to the mode of invasion, patients with a marked infiltration survived longer than did those with slight infiltration in the infiltrative type carcinoma (p < 0.01). Such relationship was also observed when width of the serosal invasion was less than 4 cm in diameter (p < 0.01). Analysis of the pattern of recurrence revealed that infiltration of dendritic cells may prevent peritoneal recurrences in patients with advanced gastric cancer which has infiltrative mode of invasion.

Dendritic Cells↗

Postoperative adjuvant immunochemotherapy and infiltration of dendritic cells for patients with advanced gastric cancer.

To determine the group of patients for whom a biological response modifier is useful, the efficacy of postoperative adjuvant immunotherapy was investigated with regard to infiltration of dendritic cells (DC) in patients with advanced gastric cancer who underwent absolute curative resection. The infiltration of DC was classified into marked and slight. The chemotherapy group was prescribed mitomycin C and tegafur, while for the immunochemotherapy group a biological response modifier, PSK, was also prescribed in survival between the chemotherapy and immunochemotherapy groups. In patients with slight infiltration, however, the 5 - year survival rates were 0% in the chemotherapy and 15% in the immunochemotherapy group. Patients given PSK survived longer than those given chemotherapy only (P less than 0.05). Therefore, adjuvant immunotherapy may be considered for patients with advanced gastric cancer with slight infiltration of DC.

Adjuvants, Immunologic↗

Successful treatment of Budd-Chiari syndrome with early gastric cancer.

In a patient with Budd-Chiari syndrome associated with early gastric cancer, the membranous obstruction of the inferior vena cava was removed by Percutaneus Transluminal Angioplasty (PTA) without any complication. Due to continuous poor clinical status and hepato-renal dysfunction, her early cancer stomach lesion was treated with Nd: YAG laser. In follow-up biopsies, malignant change became evident three months after laser therapy. By that time hepatorenal function gradually improved, and a partial gastrectomy was performed successfully. PTA is a safe and effective procedure for clinical management of Budd-Chiari syndrome, and when there is concomitant early stage malignancy, PTA followed by laser therapy paves the way for major surgery.

Adenocarcinoma, Mucinous↗

Increased efficacy of chemo- and radio-therapy by a hemoglobin solution in the 9L gliosarcoma.

Tissue oxygen tensions were measured in the rat 9L gliosarcoma under conditions of normal air breathing or carbogen breathing and after intravenous administration of a hemoglobin solution with air breathing or carbogen breathing. Administration of the hemoglobin decreased the level of hypoxia in the tumors. Treatment of the animals with the antiangiogenic combination of TNP-470 and minocycline also increased tumor oxygenation compared with untreated controls. Treatment with the antiangiogenic agents along with administration of the hemoglobin solution/carbogen breathing decreased the hypoxic fraction (% pO2 readings < or = 5 mmHg) from 71 % to 30%. Treatment of the tumor-bearing animals with BCNU or adriamycin modestly reduced hypoxia in the tumors, while treatment with fractionated radiation markedly increased hypoxia in the tumors. Tumor growth delay was used to assess the response of the subcutaneous tumor to the various treatment combinations. There was a strong correlation between increased therapeutic response and decreased tumor hypoxia. Tumor growth delay from BCNU increased from 5.3 days to 16.4 days with TNP-470/-minocycline/hemoglobin solution/carbogen. Similarly, the tumor growth delay from adriamycin increased from 3.9 days to 17.0 days with TNP-470/minocycline/hemoglobin solution/carbogen. Finally, the tumor growth delay from fractionated radiation increased from 4.8 days to 13.3 days with TNP-470/minocycline/hemoglobin solution/carbogen. When etanidazole was added to the complete radiation regimen, the tumor growth delay increased further to 20.5 days. These data show that the addition of non-toxic agents that increase tumor oxygenation to cytotoxic therapies can markedly increase therapeutic response.

Animals↗

Dendritic cells prevent lymph node metastasis in patients with gastric cancer.

Infiltration of S-100 protein positive dendritic cells into tumor tissues was investigated immunohistochemically. Although the survival time of patients with Stage I, II or IV gastric cancer did not relate to the density of dendritic cells, survival time in Stage III patients correlated with the density of dendritic cells. In patients with a marked infiltration, survival time was longer than in cases of only a slight infiltration (P < 0.001). The frequency in the marked infiltration group at the mucosal stage did not change in proportion to invasion into the deeper layers. There was a similar incidence of lymph node metastasis between the marked and slight infiltration groups in each grade of tumor invasion. However, marked infiltration of dendritic cells prevented widespread nodal involvement beyond the primary node in cases of advanced cancer (P < 0.05). This may be one of the reasons why the infiltration of dendritic cells is clinically effective in patients with Stage III gastric cancer.

Dendritic Cells↗

Margins of resection of the esophagus for gastric cancer with esophageal invasion.

BACKGROUND/AIMS: We retrospectively examined the rate of infiltration of proximal margins of resection in patients resected for gastric cancer with esophageal invasion. MATERIAL AND METHODS: In the 175 proximal margins examined, the incidence was related to the gross appearance, histologic type, size, depth of invasion, shape of the oral edge, length of grossly tumor-free edge and length of histologic esophageal invasion. RESULTS: Multivariate analysis indicated that undifferentiated adenocarcinoma and length of histologic esophageal invasion are significant risk factors for positive margin. Infiltration occurred in 13.7% (24 cases) of the oral margins of transection. Eight patients were potentially curative other than positive margin and 5 were caused by underestimation of the distance of oral margin. With reference to the length of margin of resection, no involvement was found when the cranial distance between the lesion and the line of transection exceeded 2 cm in patients with orally well-defined type esophageal invasion. In patients with the orally ill-defined type, transection with a distance greater than 4 cm commonly guarantee safety of the proximal margin, except for cases with lymphatic invasion. CONCLUSIONS: These data provide the surgeon with a rational basis for assessing the extent of resection when performing esophagectomy combined with gastrectomy for cancer.

Adenocarcinoma↗

c-erbB-2 expression is predictive for lymphatic spread of clinical gastric carcinoma.

BACKGROUND/AIMS: In patients with gastric carcinoma, the prognostic significance of c-erbB-2 oncogene expression was elucidated, but its role in the aggressive behavior of tumors is not clear. PATIENTS AND METHODS: We asked whether or not cerbB-2 gene expression may have predictability with regard to the metastatic potential in 160 patients with gastric carcinoma using a immunohistochemical staining and a multivariate analysis. RESULTS: c-erbB-2 immunoreactivity was observed in 11% (17/160) of tumors. Patients with c-erbB-2 product positive tumors had a significant shorter prognosis (p < 0.05), and were characterized by a high incidence of peritoneal dissemination (41%), liver metastasis (18%) and lymph node involvement (94%). In the multivariate logistic analysis revealed that c-erbB-2 expression was a significant risk factor related to lymph node involvement (p < 0.01). CONCLUSIONS: Our multivariate analysis revealed that c-erbB-2 expression is linked to the metastatic potential in patients with gastric carcinoma.

Female↗

Significance of routine annual esophagram for early detection of carcinoma of the esophagus.

BACKGROUND/AIMS: In order to achieve increased survival rates for patients with carcinoma of the esophagus, early detection of the disease is vital. Serial esophagrams were evaluated to clarify which interval would be effective for early detection of carcinoma of the esophagus during routine examination. MATERIALS AND METHODS: One hundred eighty-nine patients with carcinoma of the esophagus were grouped into three, according to the experience and the time of the previous roentgenograms before the definite diagnosis. RESULTS: Five patients were in Group 1, in which roentgenographic examination had been done within 12 months prior to the diagnosis. Retrospective observation revealed a slight but certain abnormal shadow at the same location as the esophageal tumor seen on the second films. In Group 2, seven had received an esophagram between 12 and 24 months before the diagnosis. In contrast to Group 1, neither abnormality nor findings indicating esophageal tumors were detected on the former x-ray films, in all seven cases. Group 2 was characterized by relatively small tumors and low stage of the disease. Mean tumor length was 4.1 +/- 2.9 cm, and three of seven were classified as Stage I and two as Stage IIA. On the other hand, most of the 177 patients in Group 3, with no previous examination of the esophagus within 24 months before the diagnosis, had far advanced disease. Mean tumor length was 6.3 +/- 2.6 cm. Only nine (5.1%) were classified as Stage I, whereas 115 (65.0%) were classified as Stage III or IV. CONCLUSION: In light of these data, for populations in which esophageal cancer frequently occurs, esophageal examination every 12 months will no doubt contribute towards the early detection of lesions.

Adult↗

Clinicopathological characteristics of stage 1 gastric cancer: comparison of macroscopic and microscopic findings.

BACKGROUND/AIMS: Laparoscopic surgery or endoscopic mucosal resection for early stages of gastric cancer have been introduced recently in many regions. In such cases, a precise diagnosis is needed prior to treatment, since understaging of gastric cancer may lead to treatment failure and impairment of curability and prognosis. The clinicopathological features of understaged cases in macroscopic Stage 1 gastric cancer have not been clarified yet. MATERIAL AND METHODS: We examined 435 patients with intra-operative findings of macroscopic Stage 1 gastric cancer and compared clinicopathological features of 354 patients (Group A) with both macroscopic and histological stage 1 cancer and 81 patients (Group B) with macroscopic Stage 1 but histologically proven to be more advanced cancer. RESULTS: Among 435 patients with macroscopic Stage 1, there were 81 (18.6%) with histologically more advanced stages (44 of stage 2, 34 of stage 3, and 3 of stage 4). There were no statistical differences in age, sex, operative procedure, and extend of lymph node dissection between the groups. Carcinomas in the 81 Group B patients tended to have larger tumors (> 4 cm), located in the middle third and along the lesser curvature of the stomach, appeared to be Borrmann V type (unclassified type) and were histologically more often associated with undifferentiated type, INF-gamma, lymphovascular invasion, lymph node metastasis, and invasion into a layer deeper than submucosa, all of which resulted in significantly poorer prognosis. CONCLUSIONS: Pre-operative and intra-operative assessment of the stage for gastric cancer was not always accurate enough and about one fifth cases with macroscopic Stage 1 gastric cancer were understaged. Thus, we recommend gastrectomy plus radical lymphadenectomy (at least D2) for the treatment of choice, from the points of view of curability and prognosis when gastric carcinoma is associated with the above mentioned characteristics.

Age Factors↗

Elevated levels of serum and plasma metalloproteinases in patients with gastric cancer.

BACKGROUND: Levels of serum and plasma metalloproteinases, especially type IV collagenases are important factors related to metastasis and invasion in various human cancer. The clinical significance of serum matrix metalloproteinase 2 (MMP-2, 72 kDa type IV collagenase) and plasma matrix metalloproteinase 9 (MMP-9, 92 kDa type IV collagenase) was evaluated as possible tumor markers in gastric cancer. MATERIALS AND METHODS: The precursor form of MMP-2 (proMMP-2) in serum and the precursor form of MMP-9 (proMMP-9) in plasma were examined prior to surgery on 70 patients with gastric cancer, one-step sandwich immunoassay (EIA) was used and serum carcinoembryonic antigen (CEA) levels were also examined in the same patients. Normal sera and plasma samples obtained from healthy individuals without cancer were used as controls. RESULTS: ProMMP-2 levels in patients (mean +/- standard deviation) with gastric cancer (602 +/- 200 micrograms/l) were significantly higher than levels (542 +/- 80 micrograms/l) in sera from 70 healthy individuals (P < 0.02). Plasma proMMP-9 levels (119 +/- 232 micrograms/l) in patients with cancer were also significantly higher than those (37 +/- 13 micrograms/l) in plasma (P < 0.004). On the other hand, there was no significant correlation between CEA and proMMP-2 levels, and between CEA and proMMP-9 levels. Neither proMMP-2 levels nor proMMP-9 levels significantly related to clinicopathologic features. CONCLUSIONS: Serum proMMP-2 levels and plasma proMMP-9 levels may serve as tumor markers, independent from known factors and CEA.

Adenocarcinoma↗

Prostate carcinoma response to cytotoxic therapy: in vivo resistance.

Androgen independent prostate cancer is recognized as a chemotherapy resistant disease. Human prostate carcinoma DU-145, LNCaP and PC-3 cells in monolayer in exponential growth were exposed to various concentrations of melphalan, 4-hydroperoxycyclophosphamide or adriamycin for 1 hour. These cells were all responsive to the drugs, with DU-145 cells being the least sensitive and PC-3 cells the most sensitive. When the three human prostate carcinoma cell lines were grown as xenografts in nude or SCID mice and the animals treated with single doses of melphalan, cyclophosphamide or adriamycin, the tumors were not very responsive to the drugs. The DU-145 tumors were highly resistant to each drug. The PC-3 tumors were more sensitive; however, even the PC-3 tumors were less drug responsive than several murine tumors. All three prostate cell lines secreted transforming growth factor-beta (TGF-beta) into the cell culture medium, and when grown as xenograft tumors increased the plasma levels of TGF-beta in the animals. DU-145 cells produced the most TGF-beta and LNCaP cells produced the least. After administration of single doses of each of the chemotherapeutic agents to animals bearing the prostate carcinoma xenografts, there was a time dependent increase in plasma TGF-beta that was greatest in animals bearing the DU-145 tumor and least in animals bearing the LNCaP tumor. Immunohistochemical staining, showed that PC-3 tumors tended to have the most intense staining for TGF-beta and LNCaP tumors the least. In situ hybridization for TGF-beta mRNA showed an increase in TGF-beta mRNA that was time independent after chemotherapy administration in all three tumors. These results support the hypothesis that the drug resistance of prostate carcinoma is manifest in vivo, and that in vivo high levels of TGF-beta may protect these tumors from cytotoxic cancer therapies.

Animals↗