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A 60-year-old woman was diagnosed as having liver metastasis from gastric cancer 14 months after total gastrectomy and total pancreatectomy. The liver tumor was so huge and the complication, diabetes mellitus, was so severe that she was palliatively treated by hyperthermo-chemo-radiotherapy (HCR therapy) with 8-MHz capacitive heating system. Because hyperthermia for deep seated tumor is very difficult, irradiation (10 MV X-ray, 36 Gy) and systemic chemotherapy (CDDP, MMC) were combinedly used. After 10 session of hyperthermia, the tumor showed a remarkable regression in size, followed by S8 subsegmentectomy of the liver. Histologically, cancer cells were still viable in the midst of fibrosis around coagulation necrosis, while normal liver cells remained intact. Multidisciplinary HCR therapy is quite a useful modality for liver tumors and may serve to expand the indication for surgical operation.

Intrahepatic arterial infusion chemotherapy (HAI) was performed for 20 hepatocellular cancer (HCC) patients and 7 cholangiocellular cancer (CC) patients. HAI combined transcatheter arterial embolization (TAE) and/or hyperthermia were performed for 10 HCC and 3 CC patients. The effective responses were shown in 6 HCC and 1 CC patients who were treated with HAI-TAE-hyperthermia combination therapy, and 2 CC patients who were treated with HAI-hyperthermia combination therapy. The 1 and 2-year cumulative survival rate was 100% and 33.3%, respectively, for HCC patients treated with HAI-TAE-hyperthermia therapy. The 1 and 2-year survival rate for HCC patients treated with HAI therapy was 19.5%, and 7.3%, respectively. Generalized Wilcoxon test revealed that the survival was favorable for patients treated with HAI-TAE-hyperthermia therapy as compared with patients given with HAI therapy. Almost the same results were obtained in CC patients. These results suggest that the HAI-TAE-hyperthermia combination therapy was favorable for the treatment of advanced liver cancer.

For the investigation of the possibility of its being a marker enzyme for tumor cells, the activity of dipeptidyl peptidase (DPP) IV (EC 3.4.14.5), a membrane-bound enzyme, in cultured human carcinoma cells was examined. The homogenates of three carcinoma cell lines (HeLa, KB, and K-44) contained lower glycylprolyl methylcoumarinamide (Gly-Pro-MCA) hydrolase activities at pH 8.7 (assumed to be DPP IV) and higher activities of alkaline phosphatase and gamma-glutamyl transpeptidase, which are also membrane-bound enzymes, than those of normal human fibroblasts (HF). Examination of carcinoma cells for the subcellular localization and pH optimum of Gly-Pro-MCA hydrolase activity revealed that the activity of a lysosomal enzyme that hydrolyzes Gly-Pro-MCA at pH 6.4 was markedly increased in carcinoma cells, but not in normal cells. The separation and characterization of Gly-Pro-MCA hydrolases by gel filtration, affinity chromatography, and substrate specificity demonstrated that HF have three peaks indicating DPP IV, DPP II, and an unknown enzyme, whereas the three carcinoma cell lines gave a prominent peak indicating DPP II and a trace of DPP IV. The DPP II activity was 6- to 24-fold higher in carcinoma cell lines than in HF, and it also was 2.85- to 4.13-fold higher than the DPP IV activity in carcinoma cell lines but was 10-fold lower in HF. These clear enzymatic differences between carcinoma cells and normal HF may be useful as a marker of malignancy.

Four kinds of cultured human tumor cell lines sensitive or resistant to bleomycin (BLM) were examined for the effect of filipin, a polyene antibiotic, on peplomycin (PEP)-induced cell killing. Although PEP was more effective than BLM against BLM-resistant HeLa cells (HeLa-BLMr), neoplastic cells derived from salivary gland (HSG) and melanoma cells (MEC), these three cell lines were still at least ten times more resistant to PEP than epidermoid carcinoma cell lines including HeLa cells by comparison of IC50, and showed lower cellular accumulation of 3H-PEP as compared with HeLa cells. When these lines were pretreated with filipin, 3H-PEP accumulation by the cells was increased 1.33-, 2.34-, 1.91- and 1.14-fold in HeLa, HeLa-BLMr, HSG and MEC cells, respectively. Combination use of PEP and filipin resulted in a remarkable enhancement of cytocidal effect in HeLa-BLMr and HSG cells (100- and 25-fold decrease of IC50, respectively), and a slight enhancement in HeLa cells, but not in MEC cells. It is therefore suggested that there are differences among cell types in the potentiation of PEP-induced cell killing by filipin.

A 58-year-old woman who had undergone subtotal gastrectomy for advanced gastric cancer yielded massive ascites after 6 months. The cytology of ascites showing Class V indicated recurrence of peritoneal dissemination in the gastric cancer. Since laparotomy disclosed diffusely small tubercular seedings in all areas of the peritoneal cavity, she received continuous hyperthermic peritoneal perfusion (CHPP) with 300 mg Cisplatin and 30 mg Mitomycin C. After CHPP ascites disappeared for 4 months. Macroscopically and microscopically, there was no cancerous lesion in the peritoneal cavity by following second-look operation. This result encouraged us to try therapeutic CHPP for overt peritoneal dissemination.

A case of metastatic choriocarcinoma involving the mandible is reported. This case is analyzed for the potentiality of immunologic defense by utilizing tuberculin test and scoring the rate of blast formation of peripheral blood lymphocytes by phytohemagglutinin, resulting in a greatly decreased ability of cellular immunity.

Rubella virus is very sensitive to photodynamic action. When tested with 1.2 X 10(-5) M toluidine blue and 8 W fluorescent lamp at a fluence of 11 W/m2, inactivation kinetics showed a linear single hit curve with a k value of 1.48 min-1. Photodynamic inactivation of rubella virus greatly enhanced recombination with a latent virus (R-virus) of baby hamster kidney BHK21 cells. In contrast, no hybrids were detected in lysates of the cells infected with either UV-treated or untreated rubella virus. Therefore, hybrid viruses were readily detected only in lysates of BHK21 cells infected with photodynamically treated rubella virus. Photodynamic damage of rubella virus genomes generated a new hybrid type (hybrid type 3) in addition to a previously described type 2 hybrid (formerly designated as HPV-RV variant). Although both of these hybrid types carry the CF antigens of rubella virus, plaque forming ability of type 3 hybrid is neutralized neither by anti-rubella serum nor by anti-latent virus serum while type 2 hybrid is neutralized by anti-latent virus serum.

Dipeptidyl peptidase (DPP) IV activities in normal human sera and in the sera of patients with malignant tumors of the oral region were assayed. Patients with oral squamous cell carcinoma had significantly lower enzyme activity than that of normal controls (p less than 0.001). Patients with advanced carcinoma showed a more significant reduction of serum enzyme activity. On the other hand, in oral squamous cell carcinoma patients with hepatic dysfunction, the serum enzyme activity was significantly increased (p less than 0.02).

A case of multiple myeloma detected by the first symptom of severe postextraction bleeding was presented. Although laboratory data showed severe anemia, rouleaux formation of erythrocytes, abnormal hemostatic parameters, elevated erythrocyte sedimentation rate and hyperglobulinemia, no involvement of bones such as the jaws, skull, ribs or sternum was demonstrated roentgenologically. Final diagnosis obtained by immunoelectrophoresis was Ig A . K type myeloma. During a therapeutic period with melphalan and predonine, bleeding from the extracted wound was repeated. 2 months after the onset of the first symptoms, the patient died of systemic bleeding. Autopsy findings revealed many hemorrhagic sites in the lungs, stomach, kidney and bladder and the existence of plasma cell-like tumor cells in the bone marrow of lumber vertebra and sternum.

This paper presents treatment of carcinoma of the maxillary sinus with an attenuated mumps virus. The mumps virus was inoculated into two cases of very advanced carcinoma of the maxillary sinus by local and general injection. Shortly after injection, relief from severe cancer pain and growth inhibition or necrosis of tumor were observed in both cases. In this communication, we discuss a possible mechanism of antitumor effect of mumps virus by utilizing immunologic tests and interferon assay.

A 70-year-old male had erythematous and vesiculous lesions in the area of the right maxillary branch of the trigeminus nerve and was clinically diagnosed as having herpes zoster; virological and serological investigations of this case were carried out. Consequently, an electron microscopic observation revealed a great number of virus particles of herpes type in the vesiculous lesion and in baby hamster kidney BHK21/WI-21 cells, cultured after inoculating the fluid from the vesicle formed on the patient's upper lip or from serum harvested during the viremia. When BHK21/WI-21 cells infected with this virus were tested for antigenicity by an indirect immunofluorescent staining technique, they showed a positive staining to antivaricella-zoster virus. When serum of this patient was assayed fof the antibody level against varicella-zoster virus by the complement fixation test at various time intervals during the therapeutic period, this antibody titer on recovery period showed a threefold increase in comparison to that at onset. From these findings, this infectious disease was precisely diagnosed as herpes zoster.

Human melanoma cells (MEC) continuously grown in protein-free RPMI-1640 medium were established. These cultured cells, designated "sf-MEC," grow well in suspension and have been successfully subcultured more than 100 passages for 30 months with complete loss of serum requirement for their growth. Although sf-MEC as well as MEC had a moderate number of mature melanosomes in the cytoplasm, the tumorigenicity in nude mice was lower in sf-MEC than in MEC. In the tumor tissue formed by sf-MEC but not by MEC, a few immature melanosomes and an increased C-type-like virus production were detected. Furthermore, conditioned medium of sf-MEC stimulated DNA synthesis in both normal and transformed cells, including MEC and sf-MEC. Addition of the conditioned medium of sf-MEC in its cell growth assay caused a twofold to eighteenfold increase in cell number as compared to that for the control.

Poly(ADP-ribose) polymerase activity was measured in bleomycin (BLM)-resistant HeLa (HeLa-BLMr) and the parental HeLa cells after BLM treatment. HeLa-BLMr cells, which had been subcultured in growth medium containing 1 micrograms/ml of BLM, showed a 3.75-fold higher enzyme activity than did HeLa cells, but this activity was decreased to the same level as that of HeLa cells after 48 h of BLM-free cultivation. When HeLa and HeLa-BLMr cells after a 48-h cultivation in BLM-free growth medium were treated with BLM, the enzyme activity was induced at a higher level (2.5-3.8 times) in HeLa-BLMr than in HeLa cells and was inhibited markedly in HeLa-BLMr and slightly in HeLa cells by nicotinamide, an inhibitor of this enzyme. The BLM-induced cell killing by nicotinamide was highly potentiated (about 18 times) in HeLa-BLMr as compared to HeLa cells.

Thirty-four patients with advanced gastric cancers had received continuous hyperthermic peritoneal perfusion (CHPP) for prevention or treatment of peritoneal dissemination (PD). These patients received intra-abdominal perfusion 30-40 minutes by about 10-liter saline heated to 50-52 degrees C dissolving 200-300 mg cisplatin (CDDP) and 20-30 mg mitomycin C (MMC). The perfusate was infused in the peritoneal cavity through the peritoneal cavity expander (PCE Nihon Kayaku Co. Ltd.) newly developed for sufficient irrigation in our clinic. Eleven patients with macroscopic serosal invasion without PD (P0) or with mild PD (P1) underwent prophylactic CHPP for prevention of peritoneal recurrence. (Pn means degree of PD according to The General Rules for the Gastric Cancer Study.) Twenty-three patients with moderate PD (P2) or severe PD (P3) underwent therapeutic CHPP. The prognosis of patients having undergone prophylactic or therapeutic CHPP (CHPP (+) group) was compared with those not having done CHPP (CHPP (-) group) in the historical control study. In the prophylactic study two-year-survival rates of CHPP (+) group was 90% significantly higher than 63% in CHPP (-) group. There was no significant difference between two-year-survival rates of CHPP (+) (11%) and CHPP (-) (0%) in the therapeutic CHPP. But ascites was observed to disappear in five of twelve (41.7%). Surprisingly second look operation disclosed macroscopic and microscopic disappearance of PD in three of nine (33.3%). The side-effects in those patients had consisted of leakage, bone marrow suppression, perforation of small bowel and so on. But there was no mortality after introduction of PCE. About laboratory data, rises in WBC, BUN, creatinine and LDH and drops in total lymphocytes counts and platelets were all normalized within four weeks. The maximal concentrations of total and free, which emerged at five minutes after CHPP, were 2.19 and 1.29 micrograms/ml. These results suggested that CHPP with CDDP and MMC was well tolerated and effective for prevention of peritoneal recurrence and treatment of peritoneal dissemination in the gastric cancer.

Several types of human cultured tumor cells were tested for the sensitivity to BLM, an effective antitumor antibiotic for epidermoid (squamous cell) carcinomas. Three cell lines (HeLa, KB, Hepd) derived from epidermoid carcinomas were very sensitive to BLM under concentrations tested, whereas BLM-resistant HeLa cells (HeLa-BLMr), neoplastic cells derived from salivary glands (HPA, HSG), malignant fibrous histiocytoma (MFH) and melanoma (MEC) were much less sensitive to BLM than epidermoid carcinoma cell lines under the same conditions. To investigate the possible mechanism of BLM resistance, these cell lines, namely HeLa, HeLa-BLMr, HSG and MEC, were examined for i) BLM permeability into cells by using 3H-PEP which was a new derivative of BLM, ii) BLM-inactivating activity in cell extracts by bioassay for antibacterial activity with B. subtilis PCI 219 strain, and iii) DNA repair activity after UV irradiation. Consequently, as compared with BLM-sensitive HeLa cells, BLM less sensitive HeLa-BLMr, HSG and MEC cells showed 34%, 50% and 39% reduction per 10(6) cells in BLM permeability, 1.6-, 5.6- and 4.7-fold increase per mg protein in BLM inactivating activity, and 24.5-, one and 8-fold enhancement in DNA repair activity, respectively. Therefore, it was indicated that above three factors at least were involved in the BLM sensitivity of human tumor cells.

We carried out a combination preoperative therapy involving radiofrequency hyperthermia (8 MHz or 13.56 MHz) with radiation (10-MV X-ray) or chemotherapy (Mitomycin C, CDDP or UFT) for 24 advanced gastric cancers with the aim of preventing local recurrence and improving resectability. The tumor and histological effects were evaluated in each case. Furthermore, an agar phantom possessing a cavity, for simulating the stomach, was employed in an experiment to evaluate temperature distribution upon RF-heating. In the experiment using the agar phantom, the rising temperature around the cavity at 3 o'clock was higher than at 5' and 6 o'clock. This suggested that gastric juice and air must be aspirated when treating a patient by RF-heating. Of the 24 tumors, 4 (17%) showed partial response. Histological effects were observed in 67% of 21 primary tumors. The rate of histological effects in metastases of lymph nodes, liver and peritoneum were 29% (4/14), 100% (2/2) and 0% (0/4), respectively. Tumor response was closely correlated with irradiation and the temperature in the stomach cavity (over 42.5 degrees C). Almost all patients showed good tolerance of this combined therapy. These results show that combined treatment involving radiation, chemotherapy and hyperthermia appears to be a potentially useful from of preoperative therapy for patients with advanced gastric cancer.