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Biomedical subjects

T Toge

Publications and source records attributed to T Toge.

At least 37 records · Page 2Linked to original sources
PubMed2000

Overcoming of multidrug resistance by introducing the apoptosis gene, bcl-Xs, into MRP-overexpressing drug resistant cells.

Multidrug resistance associated protein (MRP) is one of drug transport membranes that confer multidrug resistance in cancer cells. Multidrug resistance has been known to be associated with resistance to apoptosis. In this study, using MRP overexpressing multidrug resistant nasopharyngeal cancer cells, we examined the expression of apoptosis related genes including p53, p21WAF1, bax and bcl-Xs between drug sensitive KB and its resistant KB/7D cells. We also examined whether the introduction of apoptosis related gene could increase the sensitivity to anticancer drugs in association with apoptotic cell death. The relative resistances to anticancer drugs in KB/7D cells evaluated by IC50 values were 3.6, 61.3, 10.4 and 10.5 to adriamycin (ADM), etoposide (VP-16), vincristine (VCR) and vindesine (VDS), respectively. The resistance to anticancer drugs in KB/7D cells was associated with the attenuation of internucleosomal DNA ladder formation in apoptosis. Of important, the mRNA expression of bcl-Xs gene in KB/7D cells was decreased in one-fourth as compared to that of KB cells among the apoptosis genes. The mRNA expression of bcl-Xs gene in a bcl-Xs transfected clone (KB/7Dbcl-Xs) was increased about 2-fold compared to that of KB/7Dneo cells, while the mRNA expression of MRP gene was not significantly different in KB/7bcl-Xs and KB/7Dneo cells. The sensitivities to anticancer drugs including ADM, VCR and VDS except VP-16 were increased in KB/7Dbcl-Xs cells, in turn, the relative resistance in KB/7Dbcl-Xs cells was decreased to 1.4, 4.0, and 3.0 in ADM, VCR and VDS, respectively, as compared to those of KB/7Dneo cells. Of interest, the studies on the accumulation of [3H]VCR showed that the decrease of [3H]VCR accumulation in KB/7Dbcl-Xs was not significantly different from that of KB/7Dneo cells. Collectively, these results indicated that the mechanism(s) of drug resistance in KB/7D cells could be explained at least by two factors: a) reduced drug accumulation mediated by MRP; b) resistance to apoptosis due to the decreased expression of the bcl-Xs gene. These results also indicated that the multidrug resistance mediated by MRP might be partially overcome by introducing apoptosis gene into drug resistant cells without modulation of MRP function in drug accumulation.

ATP-Binding Cassette Transporters↗
PubMed2000

[Interim report of JFMTC study no. 20 on the effectiveness of high dose CDDP plus 5-FU regimen as an adjuvant therapy for far-advanced cancer of the stomach].

This interim analysis of the JFMTC study as of May, 1998 covers 321 gastrectomized patients with far-advanced stomach cancer from 135 institutions between November, 1993 and March, 1996. The intensive therapy group (I-group) received CDDP i.p. administration on resective surgery with 70 mg/m2 followed by CDDP i.v. of 80 mg/m2 (day 1, i.v.), accompanying 5-FU of 350 mg/m2/day (day 1-5, c.v.i.) in the 4th, 8th and 12th weeks. The I-group was randomly compared with the standard therapy group (S-group) of MMC of 6 mg/m2 i.v. in the 4th, 8th and 12th weeks and UFT of 3-4 capsules daily for postoperative one year. The results obtained were that 1. adverse reactions were found more in the I-group than in the S-group, particularly notable in the decrease in blood cells, loss of appetite and nausea/vomiting, and incidence of grade 3 or more being 13% (neutrophile leukocytes), 26% and 21%, respectively; 2. there was no significant difference between I- and S-groups in terms of 3-year survival or disease-free survival rates. (JFMTC: Japanese Foundation of Multidisciplinary Treatment for Cancer).

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

[Current status of "low-dose cisplatin-5-FU therapy" for solid tumors (2nd report)--from a nationwide questionnaire on its adverse effects].

A nationwide questionnaire survey was carried out on low-dose cisplatin-5-FU therapy for solid malignant tumors (mostly stomach and colon cancer) regarding its antitumor as well as adverse effects. The regimen was defined as 4 weeks administration of cisplatin 2-5 mg/body, 5 days a week, which was used in 47% of 82 institutions studied. Cases were classified into an Ab regimen (86 cases) with cisplatin 3-5 mg/body, and a Bb regimen (122 cases) with cisplatin 6-30 mg (mostly 10 mg)/body, both of which were given 5-FU 300-500 mg/body daily. The antitumor effect (CR + PR) was shown to be slightly higher in the Bb regimen than in the Ab regimen, and was 35% overall. Very few adverse effects appeared with either regimen for mostly major digestive, hepatic and renal functions, except for myelodepressions (leucopenia and thrombocytopenia), which were more than grade 3 in only a few percent with the Ab regimen, and a little more than 10% with the Bb regimen. The advantages and disadvantages of the A/Bb regimens appeared to be counter-balanced in terms of their antitumor and adverse effects. Most institutions using the Ab regimen favored repeating the regimen cycle as much as possible. Those using more than 6 cycles accounted for about 20% of hospitals.

Antimetabolites, Antineoplastic↗
PubMed2000

Co-transduction of herpes simplex virus thymidine kinase gene and human interleukin-2 gene into mouse ovarian cancer cell line, OVHM.

We studied the thymidine kinase (TK) gene and the interleukin (IL)-2 gene co-transduction into tumor cells for a possible strategy of cancer gene therapy. A murine ovarian cancer cell line, OVHM, was retrovirally transduced with the TK (OVHM/TK) or the IL-2 gene (OVHM/IL-2). The TK or IL-2 expression was permanent in OVHM/TK or OVHM/IL-2. OVHM/TK cells were susceptible to gancyclovir (GCV) in vitro, and their intraperitoneal growth was completely regulated with GCV administration. The bystander effect was not observed in vitro and in vivo in this model, and only the marginal emergence of immune involvement was observed in the OVHM/TK-cured mice with GCV. OVHM/IL-2 cells produced IL-2 biologically active to be immunogenic, but still tumorigenic to kill the mice when inoculated intraperitoneally. Then, OVHM/TK cells were co-transduced with the IL-2 gene to establish OVHM/TK/IL-2 cells. OVHM/TK/IL-2 cells were also susceptible to GCV and transiently produced active IL-2. A significant resistance against the challenge of parental tumor cells was observed in the mice that were inoculated with OVHM/TK/IL-2 cells and cured with GCV administration. It is suggested that tumor cells transduced with both TK and IL-2 genes could be regressed with GCV administration with subsequent generation of immune activation in the host. Since the bystander effect may not always be a common phenomenon in gene therapy using the TK gene, this type of combination may be advantageous in the clinical application of gene therapy for human cancers.

Animals↗
PubMed2000

[The clinical effect of low-dose FP (5-FU + low-dose CDDP) in patients with far advanced gastric cancer, and their quality of life].

Low-dose FP therapy was carried out in 30 patients with far advanced gastric cancer and assessed according to anti-tumor effect and quality of life (QOL). This therapy consisted of CDDP (3.5-7 mg/m2/day infused on Days 1-5 every week) and continuous infusion of 5-FU (250 mg/m2/day for 28 days). A partial response was observed in 15 cases, so the overall response rate was 50%. The response rates with stomach and lymph node cancers were higher than those of other organs (64.3% and 55.6%). Patients without peritoneal dissemination, with good performance status (PS) (0, 1) and differentiated histologic type showed a significantly higher response rate than patients with peritoneal dissemination, poor PS (2, 3, 4) and undifferentiated histologic type (p = 0.0034, 0.0253, 0.0080). No side effects (> or = WHO grade 3) were observed. The QOL of patients was assessed according to the percentage of patients with an observed improvement of diet, who could be discharged from hospital, and the duration in hospitals in relation to survival time (hospital stay). The QOL of patients with low-dose FP therapy was better than that of patients with usual combination chemotherapy. Low-dose FP therapy is a promising regimen for patients with far advanced gastric cancer.

Adenocarcinoma↗
PubMed2000

A dose-escalation and pharmacokinetic study of subcutaneously administered recombinant human interleukin 12 and its biological effects in Japanese patients with advanced malignancies.

A pilot dose-escalation study of recombinant human interleukin 12 (rhIL-12) was conducted in Japanese patients with advanced malignancies. Cohorts of three patients received escalating doses of rhIL-12 that increased from 50 to 300 ng/kg/day s.c. three times a week for 2 weeks followed by 1-week rest. The same dosage and schedule was repeated for two additional courses. Sixteen previously treated patients were registered, and 15 were evaluated. Common toxicities were fever and leukopenia; the abnormality of laboratory tests included elevations in aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, C-reactive protein, and beta2-microglobin. Dose-limiting toxicity was the grade 3 elevation of aminotransferases, and was observed in two of six patients at the 300-ng/kg dose level after the first course in one patient and after the third course in the other. Leukopenia was observed at all of the dose levels; two of six patients at 300 ng/kg experienced grade 3 leukopenia. Thus, 300 ng/kg was determined to be the maximum acceptable dose. Peak plasma levels of rhIL-12 decreased in the second courses, but the areas under the curve were almost the same in the first and second courses. Biological effects included increases of plasma levels of IFN-gamma, tumor necrosis factor-alpha, IL-6, IL-10, and neopterin. In two patients with renal cell carcinoma, complete response and partial response of metastatic tumors were observed with 50 and 300 ng/kg; the responses lasted for 5 and 3.5 months, respectively. Although immunological response to rhIL-12 varies depending on administration route and schedule and on patients' physiological conditions, the recommended dose for Phase II studies is 300 ng/kg s.c. three times a week for 2 weeks followed by 1-week rest.

Adult↗
PubMed2000

[A combined effect of fadrozole and tamoxifen in postmenopausal patients with recurrent breast cancer: a preliminary report: Japanese Cooperative Study Group of Fadrozole and Tamoxifen].

To elucidate the combined effects of fadrozole (nonsteroidal aromatase inhibitor) and tamoxifen, 11 postmenopausal patients with recurrent breast cancer were examined between October 1996 and June 1998. One patient, 49 years old, was ineligible due to the short period after castration. The patients were aged 53-71 years (mean 63.5). PS was 0-1. Six patients were pre-treated with tamoxifen and 6 with oral 5-FU derivatives. One had no previous treatment. The target lesions were soft tissues in 5, bone in 4, lungs in 6 and liver in 1. The response was CR in 2, PR in 2, SD (longer than 24 weeks) in 2, NC in 1 and PD in 3. Consequently, the response rate was 60% (6 out of 10 eligible cases). Hormonal concentration was measured before and after administration of two drugs in weeks 2, 4, 6, 8 and at the end of the treatment, and significant decreases in estrogens in peripheral blood were observed. Adverse effects (4 cases of low grade headache, dizziness and elevation of GOT, GPT, gamma-GTP) did not influence the continuous administration of the drugs. We conclude that combined administration of fadrozole (2nd generation aromatase inhibitor) and tamoxifen produces a good response in postmenopausal recurrent breast cancer patients, and can be a useful treatment for patients with breast cancer.

Aged↗
PubMed2000

[Locoregional immunotherapy of malignant effusions for colorectal cancer using OK-432 and its acting mechanisms--possibility of molecular diagnosis using TCRCDR 3 sequence].

Locoregional administration using OK-432 was evaluated in treating malignant effusion. Positive clinical responses were seen in 19 (52%) of 36 gastric cancer patients, and in 9 (90%) of 10 colon cancer patients (p < 0.05), indicating its clinical benefit in treating malignant effusion of colon cancer. Fever elevation was observed in 43 (93%) patients and local pain occurred with 9 (20%) of 46 administrations. Immunological analysis for responder patients with rectal cancer revealed that OK-432 induced autologous tumor-reactive CD 3+ CD 4+ TCRV beta 20+ killer lymphocytes. The TCR gene analysis permitted us to clone a V beta 20 CDR 3 sequence, by which positive bands were shown in 3 (75%) of 4 responders and negative bands in 3 (100%) of 3 non-responders. It is suggested that cross-antigenicity exists between OK-432 and colon cancer, and that genetic analysis using the TCRCDR 3 sequence makes it possible to predict responder patients to OK-432 immunotherapy.

ATP-Binding Cassette Transporters↗
PubMed1999

Effectiveness of immunochemotherapy for gastric cancer: a review of the current status.

Currently, the most effective treatment of gastric cancer is surgical resection of the tumor with lymphadenectomy, which is the standard treatment in Japan. It is important to determine whether chemotherapy or immunochemotherapy regimens may prolong the survival of patients with gastric cancer. Although gastric cancer cells, in general, have a low sensitivity to chemotherapy and a low immunogenicity related to stimulation of immune competent cells, a new method including biochemical modulation and nonspecific immunopotentiation with biological response modifiers (BRMs) has permitted us to augment the clinical efficacy of immunochemotherapy for gastric cancer. Further, promising new drugs are being developed and await testing for their possible benefit in an adjuvant setting, and recent advances in molecular biology may open a new avenue for tumor antigen-specific immunotherapy for gastric cancer. We will review the current status of immunochemotherapy for gastric cancer and examine its clinical benefit for survival.

Adjuvants, Immunologic↗
PubMed1999

Laparoscopic resection of submucosal gastric tumors.

In order to elucidate the efficacy in gastric surgery, we evaluated seven resected cases of a submucosal gastric tumor in which laparoscopic techniques were used. The patients consisted of 1 man and 6 women. The tumors were located in the upper, middle, and lower third of the stomach in 4, 1, and 2 cases, respectively. Three tumors were located mainly on the anterior gastric wall, 2 were on the posterior wall, and 2 were on the lesser curvature. The resected tumor size averaged 3.2 x 2.6 cm. The tumors were classified as intraluminal type (4 cases) and the extraluminal type (3 cases) according to the classification of growth type. A histopathological examination identified 4 leiomyomas, 1 leiomyosarcoma, and 4 smooth muscle tumors of indeterminate malignant potential. After a tumor resection, no recurrence of the lesions occurred during the postoperative follow-up. An extraluminal growing tumor was easily resected by the laparoscopic method without any additional procedures, and this therefore seemed to be a good indication for the laparoscopic method. In contrast, an intraluminal tumor was found to be more difficult to resect using the laparoscopic method without a companion method, e.g., intraoperative endoscopy, because of the difficulties in the detection and resection of the tumor from the serosal side. A more efficient technique must therefore be developed for this type of tumor.

Aged↗
PubMed1999

Finger bougie method compared with pyloroplasty in the gastric replacement of the esophagus.

To elucidate the necessity of pyloroplasty for the gastric tube through the posterior mediastinum in esophageal surgery, gastric emptying and duodenogastric reflux (DGR) were evaluated in 16 cases undergoing an anterior pylorectomy (group P) and in 16 cases treated by the finger bougie method (group F). First, the obstruction and reflux symptoms were examined based on a patient questionnaire using a brief scoring system. The median value of the symptom score showed the patients in P to have more symptoms than those in F; however, the difference was not significant (8.0 vs 6.0). Secondly, the swallowed Tc O4- (85MBq) was counted using a gamma camera at three sites on the sternal bone in the upright position based on a gastric transit scintigram. Both the descending time of the RI peak and the clearance rates were similar between the two groups. Thirdly, intragastric 24-h pH monitoring was carried out. Antimony pH sensors were anchored 5 and 15cm below the esophagogastrostomy. We could not find any difference between the two groups in both the %time pH > 4 and %time pH > 7. These findings thus revealed no big difference between groups P and F. The finger bougie method to drain the vagotomized posterior mediastinal stomach was found to achieve results similar to conventional pyloroplasty, while it was also simpler and safer.

Adult↗
PubMed1999

Postoperative chemo-endocrine treatment with mitomycin C, tamoxifen, and UFT is effective for patients with premenopausal estrogen receptor-positive stage II breast cancer. Nishinihon Cooperative Study Group of Adjuvant Therapy for Breast Cancer.

The effectiveness of combining mitomycin C (MMC), tamoxifen (TAM), and 1-(2-tetrahydrofuryl)-5-fluorouracil (tegafur) was evident in patients with estrogen receptor-positive (ER+) breast cancers. UFT, an oral preparation of tegafur and uracil at a molar ratio of 1:4, was reported to have higher antitumor effects than tegafur alone for patients with breast cancer. Therefore, the combined chemotherapy of MMC, TAM and UFT may possibly be effective for breast cancer. From 1988 to 1991. we studied the effects of postoperative adjuvant therapy for Japanese women with stage 11 breast cancer, all seen at 71 institutions in western areas of Japan. Five hundred and ninety four patients with stage II primary breast cancer who had undergone curative surgery, including total mastectomy and axillary lymph node dissection, were enrolled. On the day of surgery, each patient was given 13 mg/m2 of MMC intravenously. Patients with ER+ tumors were then assigned to group A or group B. Group A received 30 mg/day of TAM given orally from postoperative 2 weeks, for 2 years. Group B was additionally given an oral dose of 300 mg/day of UFT for 2 years, given concomitantly with 30 mg/day of TAM. Patients with ER- tumors were assigned to group C or group D. Group C were prescribed 300 mg/day of UFT, orally, from postoperative 2 weeks for 2 years, and group D were additionally given an oral dose of 30 mg/day of TAM together with 300 mg/day of UFT. There were no differences among the groups regarding prognostic factors or doses of MMC and TAM in ER+ patients and MMC and UFT in ER- patients. Toxicity rates for leukopenia, anorexia, and nausea/vomiting were higher in group B than in group A patients. There were no statistical differences in the overall survival and disease-free survival times between groups A and B, or groups C and D, for all eligible cases. In a retrospective subgroup analysis using Bonferroni's adjustments, the additional effect of UFT on the combined treatment of MMC and TAM lengthened the disease-free survival time for patients with premenopausal ER+ cancers (corrected P value by Bonferroni's adjustments <0.05). Multivariate analysis showed that effects of the combined treatment of MMC, TAM, and UFT was significantly related to the menopausal status (P<0.01). Our findings show that postoperative ingestion of MMC, TAM, and UFT was effective for patients with premenopausal ER+ stage II breast cancer.

Adult↗
PubMed1999

p53, p21(Waf1/Cip1) and cyclin D1 protein expression and prognosis in esophageal cancer.

Recently, various cell cycle regulators have been investigated as biological markers of malignant potential. These regulators might influence the survival rate and the effect of adjuvant therapies. In this study, we analyzed p53, p21(Waf1/Cip1) and cyclin D1 expression in 64 esophageal cancer patients and the relationship between clinicopathologic parameters and patient survival. The positive expression rate was 48.4%, 42.2% and 43.8% in the p53, p21 and cyclin D1 groups respectively. Multivariant analysis revealed that tumor depth, chemotherapy, p53, p21 and cyclin D1 expression showed significant values. p53- and cyclin D1-negative patients had a worse prognosis. p21-positive patients had a better prognosis. In stage 0, I and II patients, there was a significant difference between p53-positive and -negative, p21-positive and -negative, and cyclin D1-positive and -negative groups. In stage III and IV patients, there was no significant difference between any two groups. However, a significant difference was seen in the p21 group: among patients who received adjuvant chemotherapy, the p21-positive group had a 5-year survival rate of 50% compared with 13.4% in the p21-negative group (not significant).

Cyclin D1↗
PubMed1999

Dihydropyrimidine dehydrogenase, multidrug resistance-associated protein, and thymidylate synthase gene expression levels can predict 5-fluorouracil resistance in human gastrointestinal cancer cells.

Gene expression of dihydropyrimidine dehydrogenase (DPD) and newly multidrug resistance-associated protein (MRP) was found to correlate well with primary 5-FU resistance in 7 human gastrointestinal cancer cell lines. Although mRNA and protein levels of thymidylate synthase (TS) did not relate to the resistance, 5-FU treatment revealed a remarkable increase of TS expression. Such enhanced TS expression was more significant than DPD and MRP, and observed less in 5-FU sensitive cells. DPD and MRP expression levels can predict primary 5-FU resistance, and TS may be a potent predictor of cellular 5-FU resistance after 5-FU treatment.

ATP-Binding Cassette Transporters↗
PubMed1999

Activation and the interaction of proapoptotic genes in modulating sensitivity to anticancer drugs in gastric cancer cells.

Taxotere (Docetaxel) is a novel microtubulin inhibitor which is currently in phase II/III clinical trial. We found that the sensitivity to taxotere was correlated with apoptotic cell death determined by the internucleosomal DNA ladders in gastric cancer cell lines. The treatment of taxotere activated proapoptotic genes such as bcl-Xs and bax genes. The relationship between the mRNA induction of bcl-Xs and bax genes and the internucleosomal DNA ladders by taxotere was significant, respectively (p<0.05). The introduction of bcl-Xs gene into MKN45 gastric cancer cells increased the sensitivity to VP-16 and taxotere 2-3-fold in the IC50 values, whereas the introduction of bax gene increased the sensitivity to CDDP, VP-16 and taxotere 2-5-fold in the IC50 values, as compared to that of the Neo-transfected MKN45 cells. The mRNA overexpression of bax gene was found in the bcl-Xs-transfected cells. Likewise, the mRNA overexpression of bcl-Xs gene was also found in the bax-transfected cells. These results indicate that the activation of bcl-2 family genes such as bcl-Xs and bax plays a crucial role in modulating apoptotic cell death in the sensitivity to anticancer drugs, and suggest that these proapoptotic genes might interact in the up-regulation for activating downstream signals leading to apoptosis in gastric cancer cells.

Antineoplastic Agents↗
PubMed1999

A phase II trial of low dose administration of 5-fluorouracil and cisplatin in patients with advanced and recurrent gastric cancer.

The clinical efficacy of chemotherapy for patients with advanced gastric cancer has not been established. We investigated in a phase II study the combination chemotherapy of low dose 5-fluorouracil (5-FU) and cisplatin (low dose FP) to evaluate its clinical efficacy in terms of response, quality of life and survival in 43 gastric cancer patients including 29 advanced and 14 recurrent cases. The administration of 5-FU was done by continuous intravenous infusion for 28 consecutive days with a dose of 250 mg/m2, while the administration of cisplatin was done by 1-h intravenous drip-infusion for 5 consecutive days and 2-day intervals per week with a dose of 3.5 mg/m2, that was repeated for 4 weeks in one cycle. The response rate in advanced cases was 48.3%, evaluated in 14 cases of partial response (PR), whereas its response rate in recurrent cases was 35.7%, evaluated in 5 cases of PR. The most effective lesions for low dose FP chemotherapy were primary lesion and lymph node metastasis. The quality of life assessed by performance status and oral intake was improved in 13.8% and 37.9% of advanced cases, and 21.4% and 28.6% of recurrent cases, respectively, as compared to those of pretreatment. The median survival time and 1-year survival rate were 6 months, 21.6% in advanced cases and 10 months, 28.8% in recurrent cases, respectively. The major adverse effect was observed in gastrointestinal toxicity and leukopenia, and the all toxicities were less than grade 2, that were controllable during the treatment. These results indicated that the combination chemotherapy of low dose administration of 5-FU and cisplatin might have therapeutic efficacy in tumor response and offer improvement in quality of life in patients with advanced and recurrent gastric cancer.

Adult↗
PubMed1998

Clinical evaluation of adjuvant chemoradiotherapy with CDDP, 5-FU, and VP-16 for advanced esophageal cancer.

OBJECTIVES: The aim of this study was to evaluate the efficacy of adjuvant chemoradiotherapy following surgery in patients with advanced esophageal cancer. SUBJECTS AND METHODS: We followed the cases of 57 such patients treated at our hospital, involving 19 who received adjuvant chemoradiotherapy (CR group), 19 who received radiotherapy alone (R group), and 19 who did received neither (N group). In the CR group, chemotherapy, consisting of cis-diaminodichloroplatinum (CDDP), 5-fluorouracil (5-FU), and etoposide (VP-16), was combined with radiotherapy was administered from 4 weeks after surgery. Concurrent radiotherapy was started at 3 weeks after esophagectomy. CDDP at 50 mg/m2 was administered on days 1 and 7.5-FU at 500 mg/m2 and VP-16 at 60 mg/m2 were administered on days 3, 4, and 5. Thirteen patients (68.4%) were treated with more than 2 cycles of chemotherapy combined with radiation. RESULTS: Side-effects of severe anorexia (grade 3) and leukocytopenia (< 1900/microliter) were observed in 47% and 39% of the patients, respectively. However no treatment-related death was observed. The 5-year-survival rate was 25.2%, 18.9%, and 15.8%, in the CR group, R group, and N group, respectively. The recurrence rate was 66.7% in the CR group, which was higher than in the matched control groups (46.2% in the N group and 54.5% in the R group), but with no a significant difference. CONCLUSION: These results suggested that adjuvant chemoradiotherapy did not contribute to improvement in prognosis for these patients with advanced esophageal cancer.

Adult↗