Yoshikazu Masai

Comparison of survival curves of gastric cancer patients after surgery according to the UICC stage classification and the General Rules for Gastric Cancer Study by the Japanese Research Society for gastric cancer.

ObjectiveThis study compared the UICC classification with the General Rules for Gastric Cancer Study (GRGCS) of the Japanese Research Society by analyzing recent results of gastric cancer surgery in Japan. Summary Background DataThe present UICC stage classification for gastric cancer was published in 1987 and the Japanese GRGCS were published in 1985. Both are based on the results of surveys conducted in the early 1970s. MethodsThe survival curves of 926 patients, who underwent gastric cancer surgery between 1982 and 1985 at Kyoto University Hospital and its 31 associated hospitals, were analyzed according to the UICC classification and the GRGCS using SAS computer software. ResultsThere was no difference in survival rate between UICC stages IA and IB. GRGCS stage III was found to include UICC stages II, IIIA, and IIIB, and GRGCS stage IV included UICC stages IIIA, IIIB, and IV, with significantly different survival rates. In contrast, each UICC stage included different GRGCS stages with no significant differences in survival rates. The survival rate of stage IV patients of both classifications who underwent gastrectomy was significantly higher than that of stage IV patients receiving bypass or exploratory surgeries.

Immunomodulation by orally administered protein-bound polysaccharide PSK in patients with gastrointestinal cancer

The present study was designed to assess the effects of the protein-bound polysaccharide PSK on the immunological status of patients with gastrointestinal cancer. Twenty-nine gastric and 18 colorectal cancer patients were randomly assigned to either the control or PSK group. Patients in the PSK group were given 3.0 g of PSK orally before surgery, either daily or every other day. Patients in the control group received no PSK. The data of peripheral blood lymphocytes (PBL) were compared before and after administration of PSK, and those of the regional node lymphocytes (RNL) were compared between the control and the PSK group. The results indicate that the effects of PSK were significantly influenced by the duration of administration, but not by the frequency of administration. In the patients belonging to the short term PSK group (administration <14 days), the response of the PBL to PSK and Con A become significantly stronger compared to before the administration of PSK, whereas the cytotoxicity against K562 and KATO-3, and the proportion of CD16+ cells increased significantly in those patients belonging to the long term PSK group (≧14 days). In addition, the proportion of CD9 + 11b + suppressor T cells decreased in the RNL of the short term PSK group, whereas the proportion of CD4 + Leu8 - helper T cells in the RNL increased in the long term PSK group.These results suggest that the oral administration of PSK leads to the suppression of suppressor cells in the RNL. Thus, increased numbers of cytotoxic effector cells appear to be activated in the PBL while helper T cells predominate in the RNL.

A phase II study of 5-fluorouracil, cisplatin, and 4'-epirubicin in the treatment of advanced solid cancers.

This phase II study was designed to assess the therapeutic potential of intensive course treatment with three anticancer agents: 50 mg of cisplatin on day 1, 40 mg/m2 of epirubicin on day 2, and 250 mg of 5-fluorouracil on days 2 through 5. Drug courses were repeated every 2 weeks and most patients received between 4 and 6 courses. Thirty-five patients with measurable advanced solid cancers entered the study. They consisted of 16 gastric, 5 colorectal, 4 gallbladder, 3 pancreatic, 3 lung, 2 esophageal, 1 uterine, and 1 ovarian cancers. Of the 35 patients, 29 were evaluated for therapeutic effect of the regimen, and the overall response rate was 31.0% (5 CR + 4 PR/29). A 33.3% rate of tumor regression, consisting of 2 complete responses (CR) and 3 partial responses (PR) out of 15 patients (2 CR + 3 PR/15), was seen for gastric cancers. For the other types of tumors the responses were achieved in 2 lung cancers (1 CR + 1 PR/3), 1 uterine cancer (1 CR/1), and 1 ovarian cancer (1 CR/1). The esophageal. colorectal, pancreatic, and gallbladder cancers were unresponsive to this regimen. Toxicities of the drug treatment were clinically tolerable and consisted of general malaise, nausea, vomiting, stomatitis, alopecia, and leucopenia. However, two patients died of uncontrollable metabolic acidosis after 1 and 2 courses, respectively. This intensive course treatment appears to promote the regression of gastric, lung, and gynecologic cancers.

In vivo effects of human recombinant tumor necrosis factor alone and in combination with other biological response modifiers on human digestive organ cancer xenografts transplanted in nude mice

The present study was designed to evaluate the effect of rTNF alone or in combination with other BRMs on human digestive organ cancers. Six kinds of human digestive organ cancer xenografts (esophageal, stomach, colonic, pancreatic, bile duct, and liver cancers: EC-YO, GC-YN, CC-KK, PC-HN, BDC-SN and Li-7, respectively) were transplanted in nude mice, and rTNF was administered at 103, 5 × 103, or 104U/head directly into the tumor 3 times a week for 2 weeks. EC-YO was the most sensitive to rTNF, and intratumoral administration of rTNF at 103 U/head caused tumor regression. PC-HN, CC-KK and GC-YN were relatively sensitive to rTNF, and their growth was significantly inhibited by rTNF at 5 × 103 U/head, however, the tumors regrew after treatment. Li-7 and BDC-SN were resistant to rTNF. The effects of rTNF in combination with recombinant interferon-γ (rIFN-γ), recombinant interleukin-2 (rIL-2), or streptococcal preparation OK-432 were assessed in mice transplanted with GC-YN. All combinations of rTNF at 5 × 103 U/head and other BRMs were more effective than rTNF alone, and GC-YN tumors were completely regressed after treatment with a combination of rTNF and rIFN-γ or rTNF and OK-432. However in all cases, the combination of rTNF at 103 U/head and any other BRM did not improve the effect. Furthermore, the adverse effects of the combinations were more serious than those of rTNF alone.TNF may still be a useful cytokine, because it can induce the regression of tumors. However, for its clinical application, a method should be developed to reduce its side effects.

Anticancer chemosensitivity changes between the original and recurrent tumors after successful chemotherapy selected according to the sensitivity assay

ObjectiveThe authors compare and characterize the changes in chemosensitivity between the original tumors before chemotherapy and recurrent tumors after responses. Summary Background DataThe drug resistance in clinical chemotherapy appears to be different from that in experimental chemotherapy, and the profile and mechanisms of clinical drug resistance in recurrent tumors, especially after successful chemotherapy has scarcely been studied. MethodsApplied chemotherapies were selected out of four agents, cisplatin (CDDP), adriamycin (ADR), mitomycin-C (MMC) and 5-fluorouracil (5-FU), singly or in combinations by a DNA synthesis inhibition assay, by which the sensitivity of recurrent tumors was assessed. Responses were defined according to the standard criteria, and successful chemotherapy indicates complete response (CR) or partial response (PR) for solid tumors and complete disappearance for malignant effusion. ResultsIn 37 patients, the effectiveness of four agents were compared between before chemotherapy and after recurrence, and the response lasted between 2 and 26 months (mean ± SD, 7.7 ± 5.5). The results suggest that locally recurred tumors may become resistant to the agents previously administered; by contrast, distantly recurred tumors may not necessarily become resistant to the agents administered. The recurrent tumors are suggested to be sensitive to the agents as follows: locally recurrent solid tumors, 5-FU; distantly recurrent solid tumors, 5-FU and CDDP; locally recurrent effusion, CDDP; distantly recurrent effusion, ADR. Twenty-three of 37 recurrent tumors were re-treated with chemotherapies selected according to the sensitivity assay, singly or in combination with a biologic response modifier (BRM)–a streptococcal preparation, OK-432, or interferon-alpha. Responses were seen in 1 of 13 solid recurrent tumors and in 6 of 10 recurrent

Comparative effects of a recombinant and a mutein type of granulocyte colony stimulating factor on the growth of Meth-A fibrosarcoma with 5-fluorouracil chemotherapy

The present study was designed to evaluate the effects of a recombinant human G-CSF (rhG-CSF) and a mutein G-CSF(KW-2228) on leucopenia and tumor growth in mice treated with 5-fluorouracil (5-FU). In normal mice, the number of leucocytes (white blood cell, WBC) reached the peak 12 hours after a single injection of either type of G-CSF and decreased to the normal level after 24 hours. Daily administration induced a continuous increase in the WBC count, however, administrations at intervals did not. Meth-A fibrosarcoma was subcutaneously inoculated into the backs of syngeneic BALB/c mice. The mice were treated with 5-FU alone or with G-CSFs. Chemotherapy with 5-FU alone resulted in leucopenia and an insignificant inhibition of tumor growth. The conjunctive administration of G-CSFs with 5-FU resulted in a significantly augmented inhibition of tumor growth, and leukopenia was not seen. This augmenting effect was more prominent with KW-2228.These results suggest that in 5-FU chemotherapy G-CSFs may be beneficial in restoring the number of leucocytes from leucopenic state and in augmenting the tumor inhibitory effect. Furthermore, KW-2228 may be more beneficial than the natural type rhG-CSF.