Tatsuhei Kondo

Characteristics of three human gastric cancer cell lines, NU-GC-2, NU-GC-3 and NU-GC-4.

Three human gastric cancer cell lines, NU-GC-2, NU-GC-3 and NU-GC-4 were establishedin vitro from the cancer tissues obtained from 3 patients during surgery. The pathological findings of the gastric tumors of these cases revealed poorly differentiated adenocarcinoma (and partial signet-ring cell carcinoma in the case of NU-GC-4). NU-GC-2 and NU-GC-4 were originally obtained from metastatic paragastric lymph nodes and NU-GC-3 was obtained from a metastatic tumor in the brachial muscle. The cells of NU-GC-2 and NU-GC-3 are polygonal in shape and grow as a monolayer sheet. NU-GC-4 cells, however, are mainly spherical in shape with a few free floating cells. Electron microscopy revealed epithelial characteristics in all 3 cell lines. The average doubling time of NU-GC-2 was 36.1 hours, that of NU-GC-3 was 38.2 hours and that of NU-GC-4 was 29.9 hours. The modal chromosome number of NU-GC-2 was 62, that of NU-GC-3 was 58 and those of NU-GC-4 grown inin vitro andin vivo were 52–54 and 53, respectively.In vitro andin vivo lines of NU-GC-4 were established from the same tumor. These two cell lines are quite similar in morphology, but slightly different in karyotype. Thein vitro sensitivity to anticancer agents was highest in NU-GC-4 and lowest in NU-GC-2. Of the anticancer agents, mitomycin C and adriamycin were most effective on the cells of all 3 cell lines.

Clinical Efficacy of Lentinan on Neoplastic Diseases

Lentinan, a β-(1-3)-glucan with some β-(1-6)-gluco-pyranoside branchings, has been extracted and purified from Lentinus edodes a most popular edible mushroom in Japan. This substance has been shown to act as an immunostimulating agent through host defense mechanisms as reported by Chihara et al (1, 2). Lentinan exerts it’s antitumor activity on both syngeneic and spontaneous tumors. The cellular mechanisms of antitumor activity have been clarified by Hamuro et al (3), in that lentinan appears to stimulate host defense mechanisms to induce cytotoxic T cells, natural cytotoxicity and/or augmented macrophages against tumor cells. This suggests that lentinan may be effective for patients with malignant diseases. Based on the results of Phase I and II clinical trials conducted by Taguchi et al (4), the administration conditions for lentinan have been determined to be intravenous administration at doses of 0.5 to 1.0 mg/person/day once or twice a week in combination with chemotherapeutic agents for patients with advanced or recurrent cancer. In order to clarify the clinical efficacy of lentinan administration a Phase III randomized control trial has been conducted on patients with advanced or recurrent gastric or colorectal cancer.

Clinical evaluation of schizophyllan adjuvant immunochemotherapy for patients with resectable gastric cancer —A randomized controlled trial—

Adjuvant immunochemotherapy using schizophyllan (SPG), an extract from the culture broth ofSchizophyllum commune Fries, was prescribed at random for 326 Japanese patients with resectable gastric cancer. The overall survival rates for 3 years did not differ between the SPG and control groups. In 62 patients with stage I gastric cancer and 67 with stage II, there was little difference in the 3-year survival rates. The survival rates for 100 patients with stage III were enhanced at p=0.0811 in the SPG group, as compared to the controls. The survival rates in 97 patients with stage IV cancer were much the same. These results warrant further application of this immunopotentiating drug for treating patients with resectable gastric cancer.

Clinical outcome of postoperative adjuvant immunochemotherapy with sizofiran for patients with resectable gastric cancer: A randomised controlled study

Adjuvant immunochemotherapy using the antitumour polysaccharide sizofiran (SPG), an extract from the culture broth of Schizophyllum commune Fries, was prescribed randomly for 386 Japanese patients with resectable gastric cancer. Although the overall survival probability for 5 years did not differ between the SPG and control groups, in 264 patients with curatively resected cancer, the probability to 5 year survival and to recurrence in the sizofiran-administered patients was better than in the controls. In the multivariate analysis, four of six prognostic factors correlated with the prognosis of the 264 patients who underwent curative surgery, that is, nodal involvement (chi 2 = 21.426, P = less than 0.0001), age distribution (chi 2 = 9.262, P = 0.010), sizofiran administration (chi 2 = 6.507, P = 0.011), and primary tumour size (chi 2 = 9.345, P = 0.025). Thus, patients with a curatively resected gastric cancer had a better prognosis when sizofiran was prescribed in combination with antitumour drugs.

A cell line from a human salivary gland mixed tumor

A cell line called Nagoya‐78 has been established from a human salivary gland mixed tumor. The cytoplasm of the cells contain much glycogen but little acid polysaccharide and mucin. The ultrastructure of the cells exhibit epithelial characteristics with desmosomes, and no virus particles are present. The doubling time is around 24 hours. The cell line can be cultured as a suspension, but the growth rate is lower than that of stationary cultures. The chromosome constitution approximates trisomy with 5 marker chromosomes. The cells grow slowly in the cheek pouch of unconditioned hamsters.

Liver regeneration and tumor growth in the rat after partial hepatectomy

Tumor growth of Yoshida sarcoma implanted in the remnant liver was studied in rats subjected to a hepatectomy. After 70 percent hepatectomy, the liver progressively regenerated and the total liver weight was reverted to be 10 days after the operation. Concomitantly with liver regeneration, tumor growth in the remnant liver was stimulated significantly, compared with that in the sham-operated liver. Incorporation of tritiated thymidine into tumor cells in the remnant liver was strikingly high and progressive, while that in the sham-operated liver was low and retained. Mitomycin C given to the hepatectomized rats was more effective against the tumor in the remnant liver than in the sham-operated liver. We conclude from this study that cancer cell proliferation in the remnant liver can be accelerated by the process of liver regeneration.

Application of Radioactive Precursors for the Evaluation of Sensitivity of Cancer Cells to Anticancer Drugs

An in vitro drug sensitivity test was developed to estimate the lethal effects of drugs on cancer cells. Cancer cells were incubated in the presence of radioactive precursors and anticancer drugs. The drug effects were estimated from the changes in rates of incorporation of precursors into DNA, RNA, and protein. A microtiter plate and a multiple automatic cell harvester made feasible handling of a large number of samples. Incorporation of radioactive precursors was well correlated with drug-induced cell lethality. The results of this test were also correlated with in vivo regression of tumors of mice. This test appeared to be more reliable than other similar tests of cell lethality in vitro. For utilization in clinical studies, a test plate was simplified and 25 human cancers were tested. The in vitro results demonstrated a positive correlation with clinical results in 80% of the observations.

Postoperative adjuvant immunochemotherapy with mitomycin C, tegafur, PSK and/or OK-432 for gastric cancer, with special reference to the change in stimulation index after gastrectomy

In order to evaluate the efficacy of combined immunochemotherapy with mitomycin-C, tegafur, PSK and/or OK-432 as an adjunct for curatively resected gastric cancer, a prospective randomized controlled study using the envelope method was performed, in which 266 institutions from around Japan participated. The 3 year survival rates for all cases, and for ps(+)·n(+) cases, were insignificantly higher in the immunochemotherapy groups receiving PSK and/or OK-432 than in the control group. However, because 28.2 per cent of the cases were excluded from the final statistical analyses, the results of this study may have questionable statistical credibility. Changes in the stimulation index (SI) suggest that the administration of PSK may result in an inhibition of the immunosuppressive activity of cancer patients. The high SI group showed a significantly higher 4 year survival rate than the low SI group.

Esophageal cyst, a case report and a review of the literature.

The esophageal cyst is a rare disease only 20 cases of which have been reported in the literature in Japan. We recently treated such a patient and at thoracotomy, we found the cyst to be located the submucosal layer of the esophagus. The cyst could be easily extirpated and the patient made an uneventful recovery. Gross findings revealed thick, yellow and mucus-like contents inside the cyst. Microscopically, the cyst was lined with ciliated columnar epithelium and there was no evidence of cartilage. The 21st such occurrence in Japan is reported herein and a discussion is made of related literature.

Alternating immunochemotherapy of advanced gastric carcinoma: A randomized comparison of carbazilquinone and PSK to carbazilquinone in patients with curative gastric resection

A total of 103 patients with advanced gastric carcinoma were randomized after curative surgery to receive an alternate administration of carbazilquinone (CQ and PSK (Krestin) or carbazilquinone alone. Each course of therapies started 1 week after the surgical operation and therapy schedules consisted of 9 courses. In each course of 6 weeks, CQ (2 mg/m2/week) was administered on day 0, 8, and 15. In combined immunochemotherapy group, PSK was given orally in 3-divided doses of 2 g/m2/day from the day of the third CQ administration for consecutive 4 weeks. Estimated survival rate and cumulative survival curve were compared utilizing the data up to 7 years after the operation. There was no overall significant difference in survival rates between the CQ plus PSK group and the CQ alone group, but a group of patients whose disease was classified as S1 + S2(N1–2) survived significantly longer when treated with the combination of CQ and PSK. Neither in more advanced cases (> S3 or > N3) nor in cancers of early stages, the addition of PSK provided an additive effect. The favorable result obtained in one subgroup treated with PSK, suggests that the use of this agent in treating gastric cancers should be carefully evaluated in terms of serosal infiltration and nodal metastasis.