Biomedical subjects

T Toge

Publications and source records attributed to T Toge.

At least 55 records · Page 3Linked to original sources

PubMed1998

Poor prognosis in esophageal cancer patients with postoperative complications.

We investigated the relationship between postoperative complications and prognosis in esophageal cancer patients. Two hundred five patients with esophageal cancer were divided into three case groups. Group A (n = 100) consisted of cases without postoperative complications. Groups B (n = 58) and C (n = 47) consisted of cases with minor and major postoperative complications. The 5-year survival rates were 41.8%, 21.3%, and 20.2% in groups A, B, and C, respectively. There was a significant difference in the prognosis between groups A and B, and also between groups A and C. Any patients who died within 5 years without a relapse their cases were excluded from the study; the 5-year survival rates were 46.7%, 32.3%, and 22.5% in groups A, B, and C, respectively, with a significant difference between groups A and B. There were no significant differences between the three groups regarding the patient characteristics. These results therefore indicate that postoperative complications might contribute to a poor prognosis in cancer patients.

Esophageal Neoplasms↗

PubMed1998

Clinical results of transhiatal esophagectomy for carcinoma of the lower thoracic esophagus according to biological markers.

We generally choose transhiatal esophagectomy (THE) for patients with high risk for postoperative complications and for carcinoma of the lower thoracic esophagus, even if the tumor is in the advanced stage. In order to define indications for THE in esophageal cancer patients, we investigated 40 THE cancer patients according to the expressions of EGF/EGFR, p53 and p21. In patients with stage I, II, III and IV tumors, 5-year survival rates were 66.7%, 28.6%, 30.0% and 11.4%, respectively. The sites of first recurrence were the lymph nodes (n = 10) and single organs (n = 10). Dissemination (n = 3) and local recurrence (n = 2) were also seen as a first recurrence. According to EGF/EGFR, 5-year survival rate was 69% and 14% in the low and high EGF/EGFR groups, respectively. According to p53 expression, 5-year survival was 60% and 30% in the negative and positive groups, respectively; according to p21 expression, 5-year survival was 71% and 0% in the negative and positive groups, respectively. Significant difference was seen in EGF/EGFR and p21 groups. These data support less invasive surgery for some patients even for esophageal cancer patients. THE is a less invasive surgery, that also implies fewer curative procedure. Our results also showed that THE alone will be the only curative procedure necessary for some patients. We can determine therapeutic procedures using these new factors, and thus avoid unnecessary excess surgical stress in esophageal cancer patients.

Adult↗

PubMed1998

[An early phase II clinical study of S-1 in patients with breast cancer. S-1 Cooperative Study Group (Breast Cancer Working Group)].

An early phase II clinical study of S-1 in patients with advanced or recurrent breast cancer was undertaken by a cooperative study group (Breast Cancer Working Group) of 14 institutes in Japan. S-1 was administered twice daily at 75 or 50 mg (dose FT)/body for 28 consecutive days with 14 days rest (one course). Twenty-eight patients were enrolled, 27 were eligible for the study, and 25 were evaluable for efficacy. Four complete responses and seven partial responses were obtained, and the response rate was 40.7% (11/27) [ninety percent confidence interval for this response was 26.7-56.4%]. The major adverse reactions observed were myelosuppression represented by leukopenia 44.4% (12/27), neutropenia 40.7% (11/27), RBC decreased 37.0% (10/27), hemoglobin decreased 29.6% (8/27), anorexia 55.6% (15/27), nausea/vomiting 48.1% (13/27), and fatigue 33.3% (13/27). The results suggested that the efficacy and safety of S-1 were effective against advanced or recurrent breast cancer. The objective of study judged should be investigated in a late phase II clinical study.

Adult↗

PubMed1998

[Usefulness of percutaneous low output microwave tissue coagulation therapy for solitary liver cancer].

The possible use of percutaneous transhepatic low output microwave tissue coagulation therapy (PMCT) using ultra-sonography under local anesthesia for solitary liver cancer was studied. The subjects were 13 patients having primary or metastatic liver cancer with solitary liver tumor less than 3 cm in diameter, including 7 hepatocellular carcinomas and 6 metastatic liver cancers. PMCT was performed continuously 3 times at an output of 30 watts for 30 seconds at a time. Tumors less than 3 cm in diameter were completely coagulated by irradiation from 2 to 6 times, judging by enhanced CT. No tumor recurrence was recognized in the coagulation area. However, in two cases of metastasis from pancreatic carcinoma, multiple metastases were found at another site in the liver by 2 months after PMCT. Thus, the results suggest that PMCT is a useful therapy for small liver tumor as a local control.

Aged↗

PubMed1998

[Results of clinical study with epirubicin hydrochloride injectable solution and cyclophosphamide in breast cancer].

A 10-center cooperative clinical study with a new formulation of epirubicin hydrochloride injectable solution (Epirubicin-RTU) was conducted in patients with breast cancer. One course of treatment consisted of one intravenous administration of Epirubicin-RTU at the dose of 60 mg/m2 followed by a 3-week drug-free interval and concomitant daily administration of oral cyclophosphamide at 100 mg/day during the period between Days 1 through 14. At least, two courses of treatment were given. Among 20 registered cases, all 20 cases were eligible and 16 cases completed the whole course of the study. In 16 completers, PR was observed in 5 cases, indicating the efficacy rate of 31.3% (5/16).. No local irritation was observed at the injection sites. Adverse reactions frequently observed were leukopenia, neutropenia, anorexia, alopecia, and nausea/vomiting, which were all reversible and tolerable. From the above results, Adverse reactions both locally and systemically were tolerable. Intravenous administration of Epirubicin-RTU was considered to be useful for the treatment of breast cancer.

Administration, Oral↗

PubMed1998

[New molecular prognostic markers in gastric carcinoma].

Many molecular events have been reported as prognostic factors in gastric cancer. Amplifications of K-sam and c-met genes are often associated with poorly differentiated adenocarcinoma, while ERBB2 genes are amplified in well--differentiated adenocarcinomas of the stomach. Alterations of tumor suppressor regulators confer progression of gastric cancer. On the other hand, multi autocrine loops of growth factors/receptors in gastric cancer cells play a key role in the progression and metastasis of cancer cells. The overexpression of K-sam gene, occurs in 31.9% of gastric cancers, and the prognosis of patients with overexpression of K-sam gene is poorer than those without it. Multivariate analysis reveals that the overexpression of K-sam gene is an important factor for prognosis, lymphnode metastasis and the depth of tumor invasion of gastric carcinomas.

Female↗

PubMed1997

Molecular targeting of mitomycin C chemotherapy.

In 10 human cancer cell lines, the activity of mitomycin C (MMC) was found to be determined by an interplay between activation by DT-diaphorase (DTD) and inactivation by glutathione S-transferase (GST). NADPH/cytochrome P-450 reductase was not responsible for MMC activation and expression of MDRI (Mr 170,000 P-glycoprotein), and MRP (multidrug resistance-associated protein) genes did not relate to MMC resistance. Gene expression analysis for NQO1 (DTD gene) and GSTpi predicted which enzyme activity predominated in a cell line, except K562 and K562/DOX. For tumors with DTD activity only, MMC given by itself was most active. In cell lines in which DTD action was predominant, tumor selectivity was achieved by enhancing DTD-mediated activation with m-iodobenzylguanidine and hyperglycemia, which reduced the intra-tumoral pH. KW2149, a novel MMC analogue activated by glutathione, was most active against tumors in which GSTpi predominated. These various enzyme-specific effects could be observed even in cell lines derived from tumors with multidrug resistance. Such MMC treatment based on cell enzymology may enhance significantly MMC efficacy, helping to overcome multidrug resistance.

Animals↗

PubMed1997

A Combination Therapy with Mitomycin C, Etoposide, Doxifluridine and Medroxyprogesterone Acetate as Second Line Therapy for Advanced Breast Cancer Refractory to Combination Chemotherapy of Cyclo-phoshamide, Doxorubicin and 5-Fluorouracil.

Thirty-two patients with advanced breast cancer refractory to combination chemotherapy with cyclophosphamide (CPA), doxorubicin (ADR) and 5-fluorouracil (5-EU) (CAF) were treated with the combination of mitomycin C, etoposide, doxifluridine and medroxyprogesterone acetate as second line therapy. Observed responses included 6 patients (18.7%) with complete response (CR) and 7 (21.9%) with partial response (PR). Two (50%) out of 4 patients who had bone pain due to bone metastasis noted pain relief. CR or PR were obtained in 4 out of 12 patients who had not responded to the previous CAF therapy. While grade III myelosuppression was observed in 3 patients, other adverse effects were minimal. It is suggested that this combination therapy may be recommended for advanced breast cancer patients as a second therapy.

Journal Article↗

PubMed1997

Overcoming CPT-11 resistance by using a biscoclaurine alkaloid, cepharanthine, to modulate plasma trans-membrane potential.

Irinotecan, 7-ethyl-10-[4-(1-piperidino)-1-piperidino] carbonyloxycamptothecin, (CPT-11) resistance was overcome by using a biscoclaurine alkaloid, cepharanthine, in CPT-11- and multidrug-resistant 50MT-1 cells. 50MT-1 cells were established from a mouse breast-cancer cell line, FM3A, by subjecting the cells to a low dose of CPT-11 continuously. 50MT-1 cells exhibited resistance to CPT-11 (40-fold in colony-formation assay) and to other drugs such as doxorubicin (11.7-fold) and etoposide (VP-16) (16.8-fold). The plasma trans-membrane potential was lower in 50MT-1 cells than in FM3A cells, although there were no differences in expressions of P-glycoprotein and of DNA topoisomerase-I and -II proteins. The lower membrane potential in 50MT-1 cells was augmented by co-treatment with a non-toxic dose of cepharanthine. CPT-11 resistance in 50MT-1 cells was overcome (5.0- to 1.4-fold, 6-hr exposure) by the co-treatment with cepharanthine through increasing intracellular accumulation of CPT-11. Resistance to doxorubicin and VP-16 was also overcome by cepharanthine treatment (2.5- to 0.69-fold and 4.2- to 1.4-fold respectively). We conclude that the modification of plasma trans-membrane potential by cepharanthine should be effective in overcoming CPT-11 and multidrug resistance in 50MT-1 cells.

Alkaloids↗

PubMed1997

Enhancing effect of thoraco-laparotomy on liver metastasis and the role played by active oxygens in its mechanism.

The enhancing effect on liver metastasis produced by the excessive surgical stress of thoraco-laparotomy (TL), and its regulation with a radical scavenger, were studied in 10-week-old Donryu rats. The rats were divided into three groups: those given thoraco-laparotomy for 1 h (the TL group); those given laparotomy alone for 1 h (the L group); those given a short laparotomy (the C group). The effects of treatment with 5 mg/kg of EPC-K1 was assessed in the TL group. A rat hepatocellular carcinoma cell line AH 60C (5 x 10(5) cells) was administered into the portal vein under general anesthesia. The number of metastatic liver nodules was counted 3 weeks later, and the lipid peroxide (LPO) levels of the liver and serum were measured by the TBA method on postoperative days (PODs) 1, 2, and 3. The number of metastatic liver nodules was 40.6 +/- 29.7, 15.0 +/- 15.8, and 13.7 +/- 9.4 in the TL, L, and C groups, respectively. When EPC-K1 was administered to the TL group, the LPO level on POD 1 decreased from 49.8 +/- 25.8 to 18.9 +/- 7.9 nM/g, and the number of metastatic liver nodules decreased from 27.2 +/- 30.0 to 8.9 +/- 12.7 in parallel. The findings of this study suggested that the excessive surgical stress produced by thoraco-laparotomy enhanced liver metastasis in parallel with an increase in LPO levels; however, the radical scavenger EPC-K1 could aid in reversing this effect.

Animals↗

PubMed1997

Detection of telomerase activity in exfoliated cancer cells in colonic luminal washings and its related clinical implications.

Telomerase is a ribonucleoprotein capable of replacing telomeric DNA sequences that are lost at each cell division. Under normal circumstances, it is active in rapidly dividing embryonic cells and in stem cell populations but not in terminally differentiated somatic cells. Much attention has recently focused on the hypothesis that activity of this enzyme is necessary for cells to become immortal. This predicts that telomerase activity should be detectable in malignant cells and tissues but not in their normal counterparts, which slowly senesce and die. In accordance with this notion, telomerase activity has been reported in a wide range of malignancies, including those of the gastrointestinal tract, breast and lung. In the present study, we used a polymerase chain reaction (PCR)-based assay for telomerase activity, designated the "telomeric repeat amplification protocol (TRAP)', to examine initially 35 colonic carcinomas, their corresponding normal tissues and 12 inflammatory bowel disease (IBD) lesions. We detected strong enzyme activity in 32 (92%) of the 35 colon carcinomas while there was no activity in 30 (86%) of 35 matched normal colonic tissue specimens and only very weak activity in the remainder. Four of seven specimens of ulcerative colitis and two of five Crohn's disease lesions were negative, and the rest were only weakly positive. These results led us to examine whether telomerase could be detected in carcinoma cells exfoliated into the colonic lumen. We assayed lysates of exfoliated cells in luminal washings from colectomy specimens of 15 patients with colon carcinoma and nine with IBD. Telomerase activity was detected in washings from 9 (60%) of the 15 colon carcinoma cases but not in any from cases with IBD, suggesting that it can be a good marker for the detection of colon carcinoma, possibly even in non-invasively obtained samples.

Aged↗

PubMed1997

Gastrointestinal hormone in dumping syndrome and reflux esophagitis after gastric surgery.

Several problems are associated with gastric resection, including the dumping syndrome, reflux esophagitis, and malabsorption. A better understanding of the pathophysiological changes will shed light on new and improved therapy. Serum levels of seven circulating gastrointestinal hormones following a standardized solid meal and a brief score of symptoms were evaluated in 10 patients after partial distal gastrectomy and 12 patients after total gastrectomy, both groups reconstructed by Billroth II anastomosis, and 9 age-matched healthy controls. Patients underwent resection for gastric cancer and were studied 45 +/- 10 months after surgery. At the time of study, the patients had adapted well to surgery and no longer exhibited the severe symptoms of dumping seen immediately post-operatively. In contrast, the total gastrectomy patients exhibited the symptoms of reflux esophagitis. The gastrointestinal hormone changes could be divided into three patterns; obtunded responses (gastrin, PP), normal release (motilin, GIP) and increased secretion (CCK, neurotensin, PYY). In these, the early reaction of neurotensin correlated with the scores of late dumping syndrome and reflux esophagitis. In the literature, many gastrointestinal hormones have been shown to respond as an enhancement rather than adaptation. In other gastrointestinal hormones, secretin belonged to the obtunded type and enteroglucagon were classified in the increased type. However, pathophysiological significance of these hormonal changes remained uncertain. The late adaptive changes in gastrointestinal hormone secretion may help to compensate for loss of gastric motor function which accompanies gastric resection. On the other hand, these hormonal changes may exacerbate the esophageal reflux following gastrectomy.

Adaptation, Physiological↗

PubMed1997

Selection of adjuvant chemotherapy for gastric cancer using objective criteria.

Precise prediction of recurrence risks is of importance in the selection of adjuvant chemotherapy. A proportional hazards regression analysis was performed to seek objective criteria for 234 gastric cancer patients. The analysis showed that a high level of carcinoembryonic antigen (CEA) in peritoneal washing (100 ng/g protein) was an independent risk factor for peritoneal recurrence, and a high MMP9 (92 KD type IV collagenase) level in serum was a powerful indicator of hematogenous recurrence. In addition, the PHREG analysis in 1453 gastric cancer patients showed that MF therapy (mitomycin C i.v. + fluoropyrimidine derivatives) and PF therapy (Cisplatin i.p. + fluoropyrimidine derivatives) might be effective in the prevention of hematogenous and peritoneal recurrence after a curative operation, respectively. Based on these findings, a recurrence type-oriented adjuvant chemotherapy, i.e., PF therapy for high CEA group and MF therapy for high MMP9 group, was designed. The retrospective analysis showed significant survival benefit in stage III gastric cancer patients who underwent a curative operation. The 5-year survival rate was 67%, while that of the historical control was 46%. Prediction of recurrence type using CEA levels in peritoneal washings and MMP9 levels in sera may be of value in the selection of a proper population of patients for PE or MF therapy after gastrectomy. The selection system of adjuvant chemotherapy using such objective criteria may improve the prognosis of gastric cancer patients and keep their good quality of life through the selection of proper candidates and by eliminating patients in no need of therapy.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1997

Tumor-specific synergistic therapy of mitomycin C: modulation of bioreductive activation.

The bioreductive activation of mitomycin C (MMC) has been investigated using 10 human cancer cell lines. Except for 2 lines (COLO201 and COLO320DM), the cellular NAD(P)H: quinone oxidoreductase (DTD) activities correlated well with MMC-induced DNA damage and cytotoxicity. In addition, when the DTD activity was inhibited with 50 mM dicoumarol, the MMC activity decreased significantly. On the other hand, no correlation between the NADPH cytochrome P450 reductase (P450) activity and MMC efficacy was observed. We postulate that two electron reduction by DTD may be more important in MMC activation than one electron reduction by P450. The DTD-mediated metabolism was pH-dependent. In a nude mouse experimental model, the pH in the tumor decreased under hyperglycemic conditions due to unique glycolysis. The administration of m-iodobenzyl-guanidine (MIBG) enhanced the decrease in the pH of the tumor without affecting the pH of normal tissue (liver). It also significantly increased the antitumor activity of MMC. However, this biochemical modulation had no effect in the COLO201 and COLO320DM cells. Other mechanisms may be involved in the regulation of MMC activity in these cells. In conclusion, DTD may be an important target of MMC. Biochemical modulation using MIBG and glucose may selectively enhance the activity of MMC within cancer cells.

3-Iodobenzylguanidine↗

PubMed1997

[Current status of low-dose CDDP. 5-FU therapy for solid malignant tumors--nationwide questionnaire survey].

A nation-wide questionnaire survey was undertaken concerning low-dose anticancer therapy of CDDP plus 5-FU, which involves (5-10 mg CDDP/body/day + 300-500 mg/body/day) for 4-6 weeks. Out of 1,525 cases from 130 institutions, 847 cases with evaluable lesions were collected from 79 institutions. The response rate was 56.4% in esophageal cancer, 34.3% in gastric cancer, 35.3% in colorectal cancer, 47.2% in liver cancer and 35.9% in lung cancer, respectively. Adverse effects were found to be fewer and compliance was much better than the conventional therapy. Such figures suggest that the present regimen may be more effective than any so far. Problems for medical administration such as unlicensed CDDP for colorectal cancer were pointed out, which hinder the forthcoming third phase study.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1997

[Usefulness of percutaneous microwave tissue coagulation therapy for solitary liver cancer].

The possible use of percutaneous transhepatic microwave tissue coagulation therapy (PMCT) using ultra-sonography under local anesthesia for solitary liver cancer was studied. The subjects were 8 patients having primary or metastatic liver cancer with solitary liver tumor less than 4 cm in size, consisting of 2 hepatocellular carcinomas, and 6 metastatic carcinomas. PMCT was performed continuously 3 times at the output of 30 watts for 30 seconds at a time. Tumors less than 3 cm in size were completely coagulated by irradiation from 2 to 5 times judged by enhanced CT. No recurrence of tumor was recognized in the coagulation area. But in some cases, multiple metastases were found at another site in the liver by 3 months after PMCT. Thus, the results suggest that PMCT is a useful therapy for small liver tumor as a local control.

Aged↗

PubMed1997

[A case of advanced hepatocellular carcinoma with portal invasion effectively treated by continuous intra-arterial chemotherapy with 5-fluorouracil].

A 79-year-old male diagnosed as advanced hepatocellular carcinoma with portal invasion was treated by continuous intra-arterial chemotherapy of 5-FU, which was continuously administered for 72 hours at a dose of 333 mg/mm/day every 2 weeks and repeated 12 times. Total dose of 5-FU was 14.4 g. Toxicity of this therapy was not recognized. Levels of AFP were reduced from 4385.6 ng/ml to 11.9 for 6 months. No tumor was recognized on CT scan at 6 months after starting this therapy, after 15 months of this therapy, the patient is alive and disease-free. Given the above results, continuous intra-arterial administration of this 5-FU therapy may be effective for patients with hepatocellular carcinoma.

Aged↗

PubMed1997

[Phase I study of S-1. S-1 Study Group].

We have conducted Phase I study of a novel oral antitumor agent of fluorinated pyrimidines, S-1, in which tegafur (FT) is combined with two classes of modulator, 5-chloro-2,4-dihydroxypyridine (CDHP) and potassium oxonate (Oxo) at a molar ratio of FT:CDHP:Oxo = 1:0.4:1 as a multi-center study with 16 institutions nationwide. Two administration methods, once and twice daily administrations, were evaluated. As a result, MAD was determined as 150 mg/body/day approximately 200 mg/body/day and 75 mg/body x2/day approximately 100 mg/body x2/day, respectively. DLF was myelosuppression, mainly consisting of leukopenia in the two administrations. Most adverse reactions observed, including myelosuppression, disappeared by discontinuation of administration, and recovery was in about 2 weeks. Adverse reactions other than myelosuppression which induced the discontinuation were rash and vomiting. Other adverse reactions observed were anorexia, malaise, diarrhea and stomatitis. Diarrhea and stomatitis were mild (Grade 1), except those observed at a dose of 200 mg/body/day, and did not induce discontinuation of administration. Based on these findings and pharmacokinetic evaluation, the recommended dose and administration for Early Phase II studies were determined as twice daily administration of 75 mg/body for 28 consecutive days with 14 days rest (1 course).

Administration, Oral↗