TNP-470/minocycline/cytotoxic therapy: a systems approach to cancer therapy.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
Y Kakeji
Publications and source records attributed to Y Kakeji.
Argyrophilic nucleolar organizer region in endoscopically obtained biopsy tissue: a useful predictor of nodal metastasis and prognosis in carcinoma of the stomach.
BACKGROUND: Argyrophilic nucleolar organizer region (AgNOR) staining is a simple and economical technique for investigating proliferative activity. We examined AgNOR measured in biopsy specimens of carcinoma of the stomach in humans. STUDY DESIGN: Argyrophilic nucleolar organizer region staining was done on 76 biopsy specimens and corresponding resected cancer tissues. All estimations were made at the invasive tumor margin. RESULTS: Of the 76 cases, intratumoral heterogeneity of AgNOR count (more than 1.0 difference) between superficial and deep layers was recognized in six (7.9 percent) cases, all of which were advanced. In biopsy specimens, the AgNOR count ranged from 1.68 to 7.74 (mean, 3.79). A significant correlation was found between AgNOR counts of biopsied materials and those of resected specimens, both in early and advanced cases. Tumors with a high AgNOR count (greater than or equal to 3.79) were more likely to be of a larger size (p < 0.01), to have metastasized to lymph nodes (p < 0.01), and to be associated with a lower survival rate (p < 0.05) compared to tumors with low AgNOR counts. CONCLUSIONS: Estimating the AgNOR count in endoscopically biopsied specimens at the margin of invasive gastric carcinoma is useful for assessing nodal metastasis and clinical prognosis. These preoperative estimates may aid in tailoring the operative procedure and administrating adjuvant therapy.
Adult↗
[Advances in the treatment of colorectal cancer].
Colorectal cancer is one of the most serious diseases of our time. Recent progress in its treatment is reviewed in this paper. There are many approaches for treating colorectal cancer; extended surgery to function-preserving surgery. The aim of surgical treatment is to excise the tumor completely, so extended surgery has been performed for curative resection of colorectal cancer. However, the quality of life (QOL) of the patients has been extremely impaired. In recent years, surgical treatments for avoiding colostomy, and urinary and sexual difficulties have been widely carried out, and QOL of the patients could be maintained in the postoperative period. Stage-oriented therapy is accepted as the concept of surgical treatment of colorectal cancer. For further improving the clinical results of colorectal cancer, we advocated "type-oriented therapy" which is based on the biological characteristics of colorectal cancer, by determining i.e., p53 abnormalities of cancer cells, serum p53 antibodies, micrometastasis in the bone marrow and/or sensitivity to anticancer drugs.
Antineoplastic Combined Chemotherapy Protocols↗
Influence of an anti-angiogenic treatment on 9L gliosarcoma: oxygenation and response to cytotoxic therapy.
Tissue oxygen tensions were measured in subcutaneously growing rat 9L gliosarcoma under normal air and carbogen breathing conditions prior to and after i.v. administration of a perflubron emulsion. When these animals were treated with the anti-angiogenic agents TNP-470 and minocycline for 5 days prior to oxygen measurement, tumor hypoxia was decreased compared with untreated tumors. Hypoxia, defined as the percent of pO2 readings < or = 5 mm Hg, was decreased from 71% in untreated air-breathing controls to 34% in animals treated with the anti-angiogenic agents, the perflubron emulsion and carbogen breathing. These effects were manifest in the increased response of the tumor to single-dose (10, 20 and 30 Gy) radiation therapy. Twenty-four hours after treatment with BCNU oxygenation of the tumors was not altered; however, 24 hr after administration of adriamycin oxygenation of the tumors was increased such that hypoxia in adriamycin-treated tumors in animals receiving the perflubron emulsion and carbogen was reduced to 21%. Tumor growth delay in the s.c. tumors was increased by the addition of treatment with the anti-angiogenic agents from day 4 through day 18 post-tumor cell implantation along with BCNU or adriamycin on days 7-11. Administration of the perflubron emulsion and carbogen breathing resulted in increased tumor growth delay with the chemotherapeutic agents alone and in combination with the anti-angiogenic agents. Life span in animals bearing intracranially implanted 9L gliosarcoma progressively increased with administration of the anti-angiogenic agents and then the anti-angiogenic agents and perflubron emulsion/carbogen compared to treatment with BCNU or adriamycin.
Animals↗
Immunohistochemical analysis of p53 in colorectal cancer regarding clinicopathological correlation and prognostic significance.
The overexpression of the tumor suppressor gene p53 was investigated immunohistochemically in 144 cases of primary colorectal cancer and in 8 cases with cancer in the corresponding metastatic lymph nodes. Abnormalities in p53 expression were found in 36 cases (25%) of the 144 primary cancer cases. In addition, p53-positive tumors were found to metastasize frequently to the lymph nodes, as compared to p53-negative tumors (61.1% vs. 41.7%, P = 0.0428). p53 staining was identical in 7 of 8 (87.5%) cases in primary and metastatic lesions. When the DNA content of the tumor was determined by flow cytometry, the DNA index (mean +/- SD) was significantly higher in p53-positive tumors than in p53-negative tumors (1.57 +/- 0.38 vs. 1.39 +/- 0.37, P = 0.012). Therefore, the immunohistochemical data of p53 in colorectal cancer may help in potentially predicting metastatic spread to the lymph nodes.
Colonic Neoplasms↗
Surgical treatment of patients with gastric carcinoma and duodenal invasion.
We retrospectively examined the extent of invasion of gastric cancer with duodenal involvement in order to design pertinent surgical procedures that may lead to a better prognosis. Examinations were made on excised tissues from 650 patients who underwent gastrectomy for adenocarcinoma in the gastric antrum. In 95 patients, the cancer cells extended to beyond the pyloric ring. Spread into the duodenum was limited to within 2 cm in 76% of the patients and to within 3 cm in 81%. In addition to high rates of metastasis in group 1 and 2 lymph nodes, some group 3 lymph nodes also were involved, and more frequently so in cases with duodenal invasion than in those without such invasion (P < 0.01). The 5-year survival rate for patients with duodenal invasion was 35.4% when a curative resection was done. For patients with advanced adenocarcinoma with duodenal invasion, gastrectomy with resection of 3-4 cm of the duodenum and dissection of group 1, 2, and 3 lymph nodes were recommended.
Adenocarcinoma↗
Absorption cytometric DNA analysis of sections of gastric carcinomas and a comparison with cytofluorometry of single-cell suspensions and flow cytometry.
Measurements were made of cellular deoxyribonucleic acid (DNA) content in paraffin-embedded materials from 44 gastric carcinomas, using three different methods; static cytometric light absorbance technique using tissue sections (SCM-abs), static cytometric fluorescence technique using single-cell suspensions (SCM-flu), and flow cytometry (FCM). The DNA ploidy determined by SCM-abs was grouped into low or high ploidy according to dispersion on the DNA histogram, and the DNA ploidy determined by SCM-flu and FCM was grouped into diploidy or aneuploidy, according to the peak DNA value. Accord between SCM-abs and SCM-flu or between SCM-abs and FCM was confirmed when low ploidy by SCM-abs showed diploidy by SCM-flu or FCM and high ploidy by SCM-abs showed aneuploidy by SCM-flu or FCM. An incomplete but good accord of DNA ploidy was obtained with these methods.
Absorption↗
Potentiation of cytotoxic therapies by TNP-470 and minocycline in mice bearing EMT-6 mammary carcinoma.
The ability of the antiangiogenic agents TNP-470 and minocycline, singly or in combination, to potentiate the antitumor effects of several cytotoxic therapies was assessed in the murine EMT-6 mammary carcinoma as well as in two drug resistant sublines of that tumor designated EMT-6/CTX and EMT-6/CDDP. The antiangiogenic agents alone or in combination did not alter the growth of the tumors. However, their administration along with cyclophosphamide, CDDP, or thiotepa substantially increased the tumor growth delay produced by these cytotoxic therapies in tumors responsive to the drugs--the increase was about 2-fold for TNP-470 and minocycline together. In drug resistant tumors, treatment with the antiangiogenic agents did not reverse drug resistance but did increase the effect of the cytotoxic drugs. Treatment with TNP-470/minocycline also increased the oxygenation of each of the three tumors. Thus, TNP-470/minocycline administration increased the efficacy of fractionated radiation therapy, especially when used along with a perflubron emulsion oxygen delivery agent/carbogen. These results indicate that treatment regimens including therapies directed toward the proliferating normal cells within a tumor mass as well as therapies directed toward the malignant cells can produce improved outcomes.
Animals↗
A tumour-associated cell-surface glycoprotein accompanying p53 overexpression and higher growth potential for gastric cancer.
Tumour-associated cell-surface glycoprotein is associated with tumour progression in gastric cancer. We investigated the biological significance of tumour-associated cell-surface glycoprotein, determined by the binding of Helix pomatia agglutinin (HPA), with regard to survival time and to the malignant potential of cancer cells in serosally invasive gastric cancer in 119 patients. HPA was positively stained in 75 of 119 patients (63.0%) with gastric cancer with serosal invasion. In patients with HPA-positive tissue, the tumour was larger than in HPA-negative cases and was frequently located in the middle third of the stomach. The incidence of lymph node metastasis was higher than in patients with HPA-negative tissue. There were no differences between the cases staining negatively and positively with HPA with respect to the other factors examined. Gastric cancer tissues with HPA-positive staining revealed a higher positive rate of abnormal p53 staining and a higher concentration of proliferating cell nuclear antigen (PCNA) labelling. The survival time of the patients with HPA positive staining was shorter than for those whose tissues were HPA negative. Thus, tumour-associated cell-surface glycoprotein is apparently closely related to the malignant potential of serosally invasive gastric cancer.
Aged↗
Correlation between sialyl Tn antigen and lymphatic metastasis in patients with Borrmann type IV gastric carcinoma.
The expression of sialyl Tn (STn) antigen in 180 patients with Borrmann type IV gastric carcinomas was examined immunohistochemically. The rate of positive STn staining was 32% (57/180) for the primary tumours, and this positive staining correlated well with tumour extension, lymph node metastasis (P < 0.05) and peritoneal dissemination (P < 0.01). One-third (5/15) of patients with positive STn-staining cancer cells had a high level of serum STn. Lesions with positive STn staining were related to a lower survival rate for the patients (P < 0.05). Proliferative activity of the tumour, as measured by proliferating nuclear antigen (PCNA) labelling percentage and argyrophilic nucleolar organiser region (AgNOR) count, was significantly higher (41.5 +/- 13.0%, 3.78 +/- 0.98) in the STn-positive group than in the STn-negative group (34.2 +/- 13.2%, 3.48 +/- 0.85) (P < 0.01, P < 0.05 respectively). Estimating STn antigen may be useful for predicting the likelihood of lymph node metastasis or peritoneal dissemination and the clinical prognosis for patients with Borrmann type IV gastric carcinoma.
Adult↗
Flow cytometric analysis of variations in the DNA content of superficial and deep layers in colorectal cancer.
We investigated variations in the DNA content of multiple samples from both superficial and deep layers of tumors from 81 colorectal cancer cases. The findings were only diploid in 21 cases (25.9%) and only aneuploid in 49 cases (60.5%). On the whole, the DNA ploidy agreed in 70 cases (86.4%) between both layers. In the 49 cases with only aneuploid tumors in both layers, the DNA index (mean +/- SD) was 1.58 +/- 0.25 in the superficial layer and 1.59 +/- 0.25 in the deep layer, with the values being almost identical. In contrast, a variation in the DNA ploidy of 11 cases (13.6%) was observed. These findings show that DNA ploidy remains stable during tumor progression from the superficial into the deep layers in most cases of colorectal cancer. However, the existence of heterogeneity in the DNA ploidy also shows that several specimens should be collected from both layers before making a determination of DNA ploidy.
Adult↗
Postoperative immunochemotherapy including streptococcal lysate OK-432 is effective for patients with gastric cancer and serosal invasion.
The effects of postoperative immunochemotherapy including the streptococcal preparation OK-432 on the rate of peritoneal recurrence and survival time after curative resection were studied in 36 patients with gastric cancer. Patients randomized to group B received 18 months of a therapy that is widely used in Japan for patients with gastric cancer: mitomycin C (MMC) and UFT, a combination of tegafur and uracil in a molar ratio of 1:4. Patients randomized to group A received the same drugs given to group B plus an intraperitoneal injection of OK-432 on postoperative day 0 and intradermal injections of OK-432 for 18 months at 2-week intervals. There were no differences between the two groups in any known prognostic factor or dose of any drug received, except for OK-432. There was no difference in the toxicity rates between the groups. The concomitant administration OK-432 and anticancer drugs significantly decreased the rates of peritoneal recurrence and lengthened survival time (P < 0.05).
Adjuvants, Immunologic↗
Proliferative activity as a prognostic factor in Borrmann type 4 gastric carcinoma.
Proliferative activities in 181 primary Borrmann type 4 gastric carcinomas were investigated using percentage labelling of proliferating cell nuclear antigen (PCNA) and an argyrophilic nucleolar organiser region (AgNOR) count. Tumours with a high proliferative activity often metastasised to lymph nodes (P < 0.01), and these patients had a lower survival rate (P < 0.05). A significant correlation was recognised between the PCNA labelling percentage and AgNOR count (r = 0.452, P < 0.001). Cox's regression analysis showed that PCNA labelling percentage is an independent prognostic factor. These results indicate that estimating proliferative activity may be useful in predicting lymph node metastasis and patients' prognosis in cases of Borrmann type 4 gastric carcinoma.
Adenocarcinoma↗
Combined evaluation of preoperative serum sialyl-Tn antigen and carcinoembryonic antigen levels is prognostic for gastric cancer patients.
We have found that elevation of preoperative serum sialyl-Tn antigen (STN) levels is associated with a poor prognosis for gastric cancer patients, and these high levels remain in the advanced stage of the disease. We have now examined findings with the combined assay of STN and carcinoembryonic antigen (CEA) levels with regard to prediction of the prognosis of gastric cancer patients. Serum CEA levels and STN levels were determined preoperatively in 349 Japanese patients with gastric cancer. The patients were divided into four groups: (A) the CEA (-) STN (-) group (CEA < or = 5 ng ml-1, STN < or = 45 U ml-1, n = 286); (B) the CEA (-) STN (+) group (CEA < or = 5 ng ml-1, STN > 45 U ml-1, n = 31); (C) the CEA (+) STN (-) group (CEA > 5 ng ml-1, STN < or = 45 U ml-1, n = 17); and (D) the CEA (+) STN (+) group (CEA > 5 ng ml-1, STN > 45 U ml-1, n = 15). Clinicopathological features and the prognosis of these groups were examined. The distribution of two markers showed no significant correlation. The patients in the CEA (+) STN (+) group (group D) had more advanced disease than the patients in CEA (-) STN (-) group (group A); tumour size was larger, serosal invasion was prominent, lymphatic and vascular involvement was frequent and the tumour was more infiltrative. Lymph node metastasis and hepatic metastasis were more common. Total gastrectomy was usually performed, and the non-curative rate was higher. The 5-year survival of patients in the CEA (+) STN (+) (group D) was 14.5 +/- 9.5%, that is lower than that of patients in any other group [CEA (+) STN (-) (group C) 44.1 +/- 12.7% (P < 0.05); CEA (-) STN (+) (group B) 60.1 +/- 9.5% (P > 0.05); CEA (-) STN (-) (group A) 77.6 +/- 9.5% (P < 0.05)]. This combined assay of these markers will aid in estimating the prognosis and selecting appropriate drugs and care for gastric cancer patients.
Aged↗
[Reexamination of multimodal treatment in patient with cancer].
Explore the source record for details and available documents.
Antineoplastic Combined Chemotherapy Protocols↗
[Effect of adjuvant chemotherapy for patients with early gastric cancer].
Effects of adjuvant chemotherapy following curative resection were evaluated in patients with early gastric cancer. According to postoperative chemotherapy, seven hundred and thirty-one patients were divided into four groups as follows. MMC+FT group: those who received mitomycin C and tegafur; MMC group: those receiving MMC; FT group: those given tegafur or 5-FU; NC group: those who never received chemotherapy. Postoperative recurrence was observed in 25(3.4%) of the 731 patients. Relationships between rates of recurrence or survival with clinicopathological findings were assessed among the four groups. In cases with cancer cell invasion of the intralesional veins, recurrence tended to occur less in the groups given postoperative chemotherapy, compared to the NC group. When a positive venous invasion was determined, rates of recurrence in the MMC+FT, MMC, FT and NC groups, were 7.4, 0, 0 and 35.7%, respectively. On the other hand, in relation to other clinicopathological findings, no differences were observed in rates of recurrence among those groups. As for the survival rate, no differences were observed in the clinicopathological findings among the four groups. These findings indicate that adjuvant chemotherapy may contribute to prevention of postoperative recurrence in patients with early gastric cancer, especially in cases with positive venous invasion.
Adult↗
Predictive value of preoperative serum sialyl Tn antigen levels in prognosis of patients with gastric cancer.
BACKGROUND: Expression of sialyl Tn antigen (STN) or serum STN levels were reported to be the independent prognostic factors of colon and ovarian cancers, respectively. The clinical significance of serum STN was evaluated as a tumor marker in gastric cancer. METHODS: Preoperative STN levels were examined in 350 patients with gastric cancer, surgically treated in the Department of Surgery II, Kyushu University Hospital, and in the National Kyushu Cancer Center, between April, 1981 and April, 1986. The patients were divided into two groups: a high STN group (n = 304), with over 45 U/ml of STN, and a low STN group (n = 46), with less than or equal to 45 U/ml. RESULTS: In the high STN group, the patients were older and the tumors were larger, compared to the low STN group. Histologically, tumors in the high STN group were deeply penetrating and the rates of lymphatic involvement, vascular involvement, and lymph node and hepatic metastases were higher. Infiltrative growth patterns dominated. Thus, the tumors were in an advanced stage. The 5-year survival rate for patients in the high STN group was significantly less than that of patients in the low STN group (44.8% +/- 7.9% versus 75.1% +/- 2.6%, P < 0.05). CONCLUSIONS: Because a high STN level correlates with an advanced tumor stage and a poorer prognosis, close follow-up and aggressive therapy are recommended.
Aged↗
Prognostic significance of tumor-host interaction in clinical gastric cancer: relationship between DNA ploidy and dendritic cell infiltration.
DNA ploidy of tumor cells and the degree of infiltration of dendritic cells were determined in 93 gastric cancer tissue specimens, and the mechanisms of tumor-host interaction on the prognosis were investigated. DNA ploidy patterns were grouped into low and high ploidy, and the degree of infiltration of dendritic cells (DC) was graded into marked and slight infiltration. In the low ploidy group, the 5-year survival rates in patients with marked and slight DC infiltration were 80.7% and 61.5%, respectively (P < 0.05). In the high ploidy group, however, there were no significant differences. In cases of low ploidy, the incidence of lymph node metastasis was significantly lower in the marked DC infiltration group compared with findings in the slight DC group. Thus, markedly infiltrating dendritic cells in gastric cancer tissue may lead to prolongation of survival time for patients with a carcinoma of the low ploidy profile, by preventing widespread nodal involvement.
Dendrites↗