Effect of 6-keto prostaglandin E1 on the ascitic hepatoma-130 in vivo. Comparison with chemotherapeutic agent

The effect of 6-keto-prostaglandin E1 which has a potential action for antiplatelet aggregation was investigated against AH-130 in vivo in comparison with mitomycin C. The experimental schemes were as follows: Group I: Control, Group II: Thromboxane B2 (0.5 mg/kg, X 8, iv), Group III: 6-keto-PG-E1 (0.5 mg/kg, X 10, iv), Group IV: MMC (1.5 mg/kg, X 1, ip), Group V: 6-keto-PGE1 + MMC (0.5 mg/kg, X 10, iv, + 1.5 mg/kg, X 1, ip). The mean survival days, median survival day, and ILS% for 60 days disclosed an inhibitory effect of 6-keto-PGE1, 6-keto-PGE1 + MMC on AH-130 tumor cell growth. By contrast, TXB2, had a promoting effect on AH-130 tumor cell growth. It is concluded that 6-keto-PGE1 which has a structure activity relationship with antitumor agents, such as MMC, Diketocoriolin B, etc., played an important inhibitory role in tumor cell growth in AH-130 in vivo, particularly in combination with the antitumor agents, MMC.     

Combined treatments with vitamin A and 5-fluorouracil and the growth of allotransplantable and syngeneic tumors in mice

The combined effect of retinol palmitate (RP) and 5-fluorouracil (FUra) was examined with the use of allotransplantable and syngeneic murine tumor systems. The ip combined administration of RP (5,000 IU/kg/day) and FUra (5 mg/kg/day, 20 mg/kg/day, or 20 mg/kg/every 3d day) suppressed the tumor growth in ICR/JCL mice given sc inoculations of 5 X 10(6) allotransplantable sarcoma 180 cells and prolonged the survival time of mice inoculated ip with 10(7) tumor cells, as compared with the survival time of mice given the single administration of either RP or FUra. Similar results were obtained when BALB/c mice were inoculated sc with a syngeneic BALB/c Meth A fibrosarcoma and treated with RP (5,000 IU/kg/day) and FUra (20 mg/kg/every 3d day). The growth of Meth A implanted on day 10, as a rechallenge, was significantly suppressed in the group pretreated with RP alone or both RP and FUra for 9 days from day 1. The growth of Meth 1, another syngeneic tumor of BALB/c origin, inoculated on day 10 as a rechallenge tumor was unaffected by the treatment with RP and/or FUra. An immune response to tumor-specific antigens seemed to be involved in the combined effects of these two drugs.     

Immunobiological studies of interferon-alpha A/D in comparison with a streptococcal preparation, OK-432

In order to clarify the characteristics of interferon-alpha A/D (IFN-alpha) as a biological response modifier (BRM), several immunobiological activities were compared with OK-432. 1) Both IFN-alpha and OK-432 inhibited the multiplication of Meth-A cells in vitro. 2) IFN-alpha (2 X 10(5) IU, ip) augmented the NK activity of peritoneal exudate cells (PEC) and spleen cells, and the peak of NK activity was observed 1 day after injection. OK-432 (1 KE, ip) augmented the NK activity of PEC, but not of spleen cells, and the peak was 3 days after. 3) Macrophage activating activity was more potent with OK-432 (1 KE) than IFN-alpha (2 X 10(5) IU). 4) Induction of CTL against alloantigens was augmented by IFN-alpha and OK-432. 5) By the combination of IFN-alpha with OK-432, a synergistic antitumor effect was obtained against Meth-A ascites tumor. Immunobiological effects of IFN-alpha seemed to be somewhat different from those of OK-432. Therefore, the combination of the two agents might cause a synergistic antitumor effect.     

Liver metastasis of colon 26 cells implanted into the superior mesenteric vein in mice

The intraportal implantation of mouse transplantable colon adenocarcinoma 26 was investigated as an experimental liver metastasis model of colorectal cancer. CDF1 male mice (5 weeks old) were laparotomized under pentobarbital sodium anesthesia, and colon 26 tumor cells (1 X 10, 1 X 10(3), or 1 X 10(5) cells) were inoculated into the superior mesenteric vein. On day 21 after inoculation, mice inoculated with 1 X 10(3) tumor cells showed five to 12 colonies of liver metastasis (mean, 9.2 colonies; n = 6). The survival time was 27 to 36 days (median, 27 days; n = 5) in these mice. When mitomycin C (MMC) was administered into the superior mesenteric vein 15 min after the inoculation of tumor cells, the number of metastatic foci in the liver was strongly inhibited; 81.1% and 100% inhibitions were observed in the groups given 4 mg/kg and 6 mg/kg of MMC, respectively. The mouse colon 26 model seems to be one of the more useful experimental models for evaluating treatments for the prevention of liver metastases from colorectal cancer.     

Potentiation of the therapeutic effect of chemotherapy and hyperthermia on experimental tumor and reduction of immunotoxicity of mitomycin C by juzen-taiho-toh, a Chinese herbal medicine

Potentiation of the therapeutic effects of chemotherapy and local hyperthermia by the Chinese herbal medicine, Juzen-Taiho-Toh (JTX, TJ-48), was studied using murine tumours. Mouse sarcoma 180 tumor cells were inoculated s. c. into the footpads of ICR mice. TJ-48 was given (days 1-50) orally. On appropriate days (days 5, 8, 12, 15 and 19), mice were administered mitomycin C (MMC, 3 mg/kg/day) and treated with hyperthermia (43 degrees C, 30 min). TJ-48 markedly potentiated the effects of the combined use of MMC and hyperthermia. Similar results were observed against B16 melanoma inoculated into BDF1 mice. Tumor-bearing feet of mice treated with MMC (days 5, 8, 12, and 15) and TJ-48 (days 1-40) were amputated on day 14, the S180 tumor was reinoculated sc into the axillary region on day 19, and the subsequent tumor growth was observed. These results indicated that tumor growth and the incidence of tumors in the nontreated group were suppressed. However, a marked tumor growth was observed in the group administered MMC. In contrast, tumor growth and the incidence were suppressed in the group given MMC plus TJ-48 when compared with MMC alone. These results suggest that TJ-48 not only potentiates the combined effects of MMC and hyperthermia but also reduces and/or eliminates the immunotoxicity of MMC in the host.     

Transforming growth factor beta 1: lack of in vivo antitumor activity on A549 and Wehi 3BD+ tumors.

A large number of reports have described the potential of transforming growth factor beta 1 (TGF-beta 1) as an antitumor agent on the basis of its antiproliferative action on a wide variety of tumor types in culture. In this report we now extend the assessment of TGF-beta 1's antitumor potential by evaluation in vivo versus the mouse monomyelocytic leukemia, Wehi 3BD+, and the human lung adenocarcinoma, A549. In culture both Wehi 3BD+ and A549 cells, sampled from in vivo, were sensitive to inhibition (greater than or equal to 50%) by TGF-beta 1 (greater than or equal to 1 ng/ml) in a 6 day proliferation assay. Despite their sensitivity to TGF-beta 1 in culture, in vivo the growth of neither tumor was reproducibly altered following treatment with various doses, routes and schedules of TGF-beta 1. For example, the median lifespan of mice inoculated with Wehi 3BD+ cells (10(3) or 10(5) cells, ip) was not increased by TGF-beta 1, given as 9 daily ip injections or 7 days of continuous ip infusion. Dose levels in these studies ranged over greater than 2 logs and were escalated to include those frankly lethal (28 micrograms/mouse by injection or 7 micrograms/mouse/day by infusion). Furthermore, the growth of A549 tumors implanted sc in athymic mice was not inhibited by iv injection (every 3 days for 5 injections or 6 consecutive daily injections), sc treatment distal to the tumor (every 3 days for 5 injections or continuously infused for 14 days), or even sc injection adjacent to the tumor (every 3 days for 5 injections), although dose levels of TGF-beta 1 covered a wide range including those which produced lethalities. On the basis of cumulative dose, continuous infusion of TGF-beta 1 by both ip and sc routes was more toxic than frequent injections given by the same routes. These studies indicate lethality is reached without a meaningful tumor inhibition being produced following ip, sc, or iv injections, and sc or ip infusions of TGF-beta 1.     

Antitumor effects of polyribonucleotides for mouse transitional cell carcinoma enhanced by cyclophosphamide

Mouse bladder tumor (MBT-2), derived from a carcinogen-induced transitional cell carcinoma of the bladder, has proven a useful model for study of pathogenesis and prediction of cytotoxic drug sensitivity of human bladder carcinoma. To define optimal conditions for activity of the potent interferon inducer polyriboinosinic-polyribocytidylic acid [poly(I) X poly(C)] in this model, studies of dose, timing, and combinations with a cytotoxic drug were initiated. Poly(I) X poly(C) inhibited MBT-2 growth when 10(5) or 10(6) tumor cells were implanted. Tumor growth reduction was relatively more pronounced in mice inoculated with higher numbers of MBT-2 cells (10(6] than in mice inoculated with an intermediate dose (10(5] or small dose (10(4]. In mice inoculated with 10(5) MBT-2 tumor cells, poly(I) X poly(C) (2.5 or 10 mg/kg i.p.) on Days 5 to 19 every other day reduced tumor size markedly. It had no effect, however, on tumor incidence or the time of their first detection. Treatment for a shorter period (alternate days from Days 11 to 19) resulted in less inhibition of tumor growth. Once treatment was discontinued, tumors grew progressively. Polyriboadenylic:polyribouridylic acid [poly(A) X poly(U)] (10 mg/kg) which inhibited tumor growth but to a lesser degree than poly(I) X poly(C) induced lower, less sustained levels of serum interferon. Cyclophosphamide, injected i.p. on Day 1, resulted in inhibition of tumor incidence and growth in direct proportion to the dose administered (25 to 200 mg/kg), but it was curative only at greater than or equal to 30% lethal doses. When combined with poly(I) X poly(C) (2.5 or 10 mg/kg), cyclophosphamide (50 mg/kg) had an additive antitumor effect. Optimal inhibition of MBT-2 tumor growth occurred by combining cyclophosphamide (100 mg/kg) with poly(I) X poly(C) (2.5 mg/kg); eight of 14 mice were tumor free on Day 60.     

Mechanism of the antitumor activity of 5,5′-bis(2′-tetrahydropyranyl) secalonic acid D against Meth-A

The mechanism of the antitumor activity of 5,5'-bis(2'-tetrahydropyranyl) secalonic acid D (PSA) was examined in Balb/c mice bearing Meth-A fibrosarcoma. IP-injected PSA showed remarkable antitumor activity against IP-implanted Meth-A tumor. Antitumor activity of PSA was not abolished by treatment with silica as an antimacrophage agent or anti-asialo GM1 antiserum that selectively eliminates natural killer cells. Although it was significantly suppressed by treatment with antithymocyte globulin in Balb/c mice, PSA was effective against Meth-A tumors implanted in athymic Balb/c mice. PSA inhibited in vitro Meth-A proliferation as effectively as mitomycin C and was not effective against Meth-A tumor implanted SC at a site where direct contact of PSA and Meth-A cells was unlikely. These results suggest that the antitumor activity of PSA was mainly achieved by inhibiting Meth-A cell proliferation, although the host T cell-mediated immunity was partly involved in the eventual therapeutic efficacy of PSA.     

Effect of intraperitoneal chemotherapy on experimental peritoneal dissemination of gastric cancer

In vitro chemosensitivity test using a collagen-gel method was done on 165 primary gastric cancers. All of 5-FU, CBDCA, CDDP and docetaxel showed a high sensitivity. The effects of per oral (po) administration of TS-1, a combination of po TS-1 and intraperitoneal (ip) administration of CDDP, ip 5-FU and ip docetaxel, were evaluated in athymic mice bearing peritoneal dissemination of a gastric cancer cell line (MKN-45-P that shows a high rate of metastasis to the peritoneal cavity of nude mice). Nude mice were inoculated by ip with 10(7) MKN-45-P cells. No survival benefit was obtained after po administration of TS-1 (12 mg/kg) alone or ip CDDP alone. However, a combination of po TS-1 (8 mg/kg x 10 days, from day 3) and ip CDDP (3.5 mg/kg, day 6 and 13) showed a significant survival improvement than that of po TS-1 or ip CDDP treatment alone. ip administration of 30 mg/kg (3 times/week x 3 weeks) or 15 mg/kg (6 times/week x 3 weeks) of 5-FU significantly improved the survival of mice bearing MKN-45-P. 5-FU concentration of ascites after ip administration of 30 mg/kg of 5-FU was 600-fold higher than po administration of 12 mg/kg of TS-1 at peak level. ip injections of docetaxel of 8 mg/kg, and 2 mg/kg improved the survival of 4 and 1 mice, respectively, and they were tumor-free on day 90. Survival of mice treated with ip injection of CBDCA (100 mg/kg, on day 3, or 50 mg/ kg on day 3 and 10) was significantly better than the control group. These results suggest the potential of po TS-1 + ip CDDP, ip 5-FU, ip docetaxel and ip CBDCA administration for the treatment of peritoneal dissemination of gastric cancer.     

Enhanced Antitumor Effect of Recombinant Human Tumor Necrosis Factor in Combination with Recombinant Human Granulocyte Colony-stimulating Factor in BALB/c Mice

The synergistic antitumor effect of tumor necrosis factor (TNF) and granulocyte colony-stimulating factor (G-CSF) was investigated. G-CSF was administered subcutaneously to BALB/c mice inoculated with Meth-A cells at a dose of 2.5 μ g/day for 5 consecutive days. When TNF (1 × 10³ U) was administered intravenously to mice which had been pretreated with G-CSF, tumor growth showed a 74.1% inhibition 17 days after the tumor cell inoculation, compared to that of untreated mice. In this experiment, G-CSF significantly ( P <0.025) enhanced the antitumor effect of TNF. The in vitro cytotoxicity of TNF (10 U/ml) towards Meth-A cells was increased about 5.2-fold in the presence of neutrophils (E/T=50) as compared to the cytotoxicity obtained with TNF alone. A combination of TNF and G-CSF (50 ng/ml) in the presence of neutrophils, resulted in a 2.1 times greater cytotoxicity against Meth-A cells as compared to that obtained without G-CSF. Significant augmenting effects of G-CSF on superoxide (O₂⁻) production by TNF-stimulated neutrophils were observed. These observation suggest that the neutrophil plays an important role in the antitumor action of TNF on Meth-A cells, and that the antitumor effect of TNF is enhanced by combination with G-CSF.     

Antitumor activity of an extract neurotropin isolated from the inflamed skin of rabbits inoculated with vaccinia virus

The antitumor activity of extracts (Neurotropin (NSP)) isolated from the inflamed skin of rabbits inoculated was studied in syngeneic mice-tumor system, C57BL/6-with mammary adenocarcinoma 755. NSP at a dose of 2 mg/kg of body weight was administrated for seven days. Intravenous administration of NSP was more effective than intraperitoneal and subcutaneous administration. NSP exhibited antitumor activity against primary inoculated tumor growths with a cell dose of less than 1 x 10(5) viable cells. Antitumor activity was observed when NSP administration was started one day after tumor inoculation. NSP also enhanced antitumor activity against secondary tumor growths inoculated after excision of the primary tumor. The antitumor activity of Neurotropin seemed to be exerted through a host-mediated tumor immunity.     

Effect of cisplatin (CDDP) against peritonitis carcinomatosa in nude mice inoculated intraperitoneally with human gastric cancer

Development of effective chemotherapy for patients with peritonitis carcinomatosa is considered to be very important in cancer management. In this study, intraperitoneal injection (ip) of cisdichlorodiammineplatinum (II) (CDDP, cisplatin) together with subcutaneous injection (sc) of sodium thiosulfate (STS), abbreviated as 2-channel chemotherapy, were discussed with regard to its safety and efficacy on peritonitis carcinomatosa using nude mice inoculated intraperitoneally with SCK-8 tumor cells derived from human gastric cancer. A single ip lethal dose (16 mg/kg) of CDDP reproducibly caused weight loss in nude mice and killed 100% of the nude mice by day 5 after injection. However, sc of STS (1,200 mg/kg) protected nude mice against a lethal dose of CDDP, and reduced CDDP-induced weight loss. Two-channel chemotherapy (CDDP 16 mg/kg ip + STS 1200 mg/kg sc) using nude mice with advanced peritonitis carcinomatosa produced a 45% increase of life span with a survival of 74.6 +/- 6.2 days (n = 8), compared with control nude mice with peritonitis carcinomatosa surviving 51.5 +/- 13.3 days (n = 11). Therefore, it is conceivable that 2-channel chemotherapy can be applied to the management of cancer patients with peritonitis carcinomatosa.     

Enhanced anticancer efficacy by use of mitomycin C adsorbed on small activated carbon particles in mice

A new dosage form of mitomycin C (MMC-CH) was tested for toxicity and therapeutic efficacy against intraperitoneally inoculated cancer cells in mice. MMC-CH is a suspension comprising 7.16 mg/ml of activated carbon particles, 1 mg/ml of mitomycin C (MMC) and 20 mg/ml of polyvinylpyrrolidone in saline. The LD50 value determined by means of the Litchfield-Wilcoxon method after intraperitoneal administration was 2.29 times higher for MMC-CH than for MMC aqueous solution. Mice were inoculated intraperitoneally with 2 X 10(5) P388 leukemia cells and given an intraperitoneal injection of 10 to 1.25 mg/kg of MMC in the form of MMC-CH or MMC aqueous solution 24 hr after the inoculation. The median survival time was prolonged to 270.5%, 223.0% or 168.3% by MMC-CH at the dose equivalent to 10, 5 or 2.5 mg/kg of MMC, respectively, while it was prolonged to 182.7%, 139.6% or 155.4% by MMC aqueous solution at the dose of 5, 2.5 or 1.25 mg/kg of MMC, respectively, as compared with the median survival time in the non-treated group. MMC-CH prolonged the survival time to more than 120% as compared with the same dose of MMC given as MMC aqueous solution, and was less toxic.     

重组人白细胞介素-6抑制BTT_(739)小鼠膀胱癌生长和转移的实验研究

 目的　探讨重组人白细胞介素 6对小鼠膀胱癌BTT739生长和转移的抑制作用。方法将BTT739肿瘤细胞接种于T739近交系小鼠皮下 ( 2 6× 10 5/小鼠 ) ,2 4只小鼠随机分成 3组 ,第 3天始分别给予对照组溶剂 ( 0 9NS) 0 3mL ,治疗组重组人白细胞介素 6( 4× 10 6IU kg) ,日 2次 ,腹腔注射 ,共 2 0天 ,阳性对照组MMC ( 1mg kg)日 1次 ,腹腔注射计 14天。第 2 5天测对照组和治疗组的皮下瘤重及肺转移率 ,分别进行t检验和 χ2 检验。结果　两组皮下瘤重分别为 11 4± 1 9g和 7 4± 0 8g ,重组人白细胞介素 6有明显抑制BTT739肿瘤生长作用 ,抑瘤率 35 1% (P<0 0 5) ,而对肺转移灶数目及转移灶大小的抑制率分别为 61 3%和 2 6 2 % (P值均 <0 0 5) ,有显著性差异。结论　重组人白细胞介素 6可明显抑制BTT739小鼠膀胱癌生长和转移。     

Epidermal growth factor receptor-mediated selective cytotoxicity of antitumor agents toward human xenografts and murine syngeneic solid tumors

Severe toxic side effects of antiproliferative agents limit their clinical usefulness as antitumor drugs. Recently we observed that the antitumor efficacy of various antitumor agents (5-fluorouracil, tegafur, adriamycin, mitomycin C, cyclophosphamide, and cisplatin) against experimental solid tumors was enhanced by prior or simultaneous administration of human epidermal growth factor (EGF). However, coadministration of EGF did not enhance the toxicity of antitumor agents as measured by LD50 and body weight loss. The above selective potentiation of efficacy of the antitumor agents by human EGF can be characterized as follows. In a dose-dependent manner, human EGF enhanced the efficacy of an antitumor agent (5-FU) treatment against human epidermoid carcinoma A431 transplanted sc in athymic nude mice [ED50 = 2.9 (0.2-49.7, 95% confidence interval) microgram/kg, sc]. Various degrees of enhancement were also observed against other experimental tumors transplanted sc. The degrees of enhancement were directly proportional to the numbers of human EGF binding sites present on tumor cell plasma membrane (threshold of binding site density = 1.5 X 10(3) sites/cell) using 5-FU or cisplatin as an antitumor agent, thus suggesting that the binding of EGF to the receptors on tumor cells is an essential process in enhancing the susceptibility of tumor cells to antitumor agents. Normal cells including intestinal epithelial and bone marrow cells are endowed with fewer EGF binding sites (less than 10(3) sites/cell). This may explain partially the absence of EGF-enhanced cytotoxicity by antitumor agents toward normal cells.     

明日叶查尔酮对小鼠肝癌细胞Caspase-3和Bax蛋白表达的影响

目的：研究明日叶查尔酮（Ashitabe chalcone,AC）对小鼠H22肝癌细胞Caspase-3和Bax蛋白表达的影响。方法：将50只荷H22肝癌小鼠随机分为AC不同剂量实验组（5、20、40 mg/kg）,阴性对照组和环磷酰胺（cytoxan,CTX）阳性对照组,共5组,每组10只。AC实验组小鼠每天分别按不同的剂量灌胃,阴性对照组小鼠给予生理盐水灌胃,CTX组隔天腹腔注射CTX 20 mg/kg,10d后处死小鼠,取瘤组织测定瘤质量、抑瘤率,并采用免疫组化法检测各组小鼠肿瘤细胞Caspase-3和Bax蛋白的表达,用MTT法检测各组小鼠肿瘤细胞增殖活性。结果：阴性对照组小鼠肿瘤细胞Caspase-3和Bax阳性细胞表达率分别为5.00%和4.68%,AC 40mg/kg剂量组分别为38.52%和35.76%,均高于阴性对照组（P〈0.05）;阴性对照组肝癌细胞增殖活性为1.135±0.032,AC 40 mg/kg剂量组为0.716±0.018,低于阴性对照组（P〈0.05）。AC 20、40 mg/kg剂量组平均瘤质量均明显低于阴性对照组（P〈0.05）。结论：明日叶查尔酮可上调Caspase-3和Bax蛋白的表达且具有抑制肿瘤细胞增殖作用。     

Influence of methylprednisolone on antitumor effect of cis-diamminedichloroplatinum (II)

To elucidate the influence of methylprednisolone (MPL) on the antitumor effect of cis-diamminedichloroplatinum (II) (CDDP), experimental chemotherapy of CDDP with or without MPL was performed. A human breast carcinoma, MX-1 serially transplanted into nude mice was treated with CDDP in doses of 1.5 and 3.0 mg/kg in schedule of q4d X 3 ip. KKN-1, a syngeneic fibrosarcoma of BALB/c transplanted into BALB/c +/+ or BALB/c nu/nu mice, was treated with CDDP in doses of 3 or 6 mg/kg in schedule of qd X 1 ip. In the combination of MPL, 20 mg of MPL per kg was administered ip three hours before CDDP treatment. Although some decrease of antitumor effect of CDDP was observed by combination with MPL, no statistically significant difference was noted between group given CDDP alone and those given CDDP plus MPL. It was concluded that the use of MPL is reasonable to prevent the severe emesis caused by CDDP when this adverse effect is resistant to other antiemetic agents.     

Antitumor effect of PSK: role of regional lymph nodes and enhancement of concomitant and sinecomitant immunity in the mouse

PSK, a Coriolus preparation, inhibited the growth of not only the right but also the left, non-treated tumor in a double grafted tumor system. In order to examine the role of lymph nodes and the spleen in the antitumor activity of PSK, regional (axillary and inguinal) lymph nodes and spleen were resected. Since in resected mice the antitumor activity of PSK against the right and left tumors was weakened, the regional lymph nodes and the spleen probably have a very important role in the antimetastatic effect of intratumoral administration of PSK. TIL (tumor-infiltrating lymphocytes) obtained from left and right side tumors treated with PSK were examined by Winn assay for their antitumor activity against Meth-A sarcoma in BALB/c mice. TIL from both sides clearly inhibited the growth of admixed Meth-A cells, but control TIL did not. A primary growth of Meth-A sarcoma inoculated into the right flank resulted in the generation of concomitant immunity to the growth of a second graft of the same tumor cells in the left flank. A significant inhibitory effect on the proliferation of the tumor cells inoculated secondarily was shown in mice bearing a primary right tumor that had previously been inoculated with PSK 3 times. After surgical excision of the primary tumor on day 6, daily oral administration of PSK significantly inhibited the growth of the secondary tumor inoculated on day 21, that is, PSK treatment also enhanced sinecomitant immunity. These observations suggest that presurgical intratumoral injection and postoperative oral administration of PSK are highly effective in eradicating metastatic tumors.     

Antitumor Effect of PSK: Role of Regional Lymph Nodes and Enhancement of Concomitant and Sinecomitant Immunity in the Mouse

PSK, a Coriolus preparation, inhibited the growth of not only the right but also the left, non-treated tumor in a double grafted tumor system. In order to examine the role of lymph nodes and the spleen in the antitumor activity of PSK, regional (axillary and inguinal) lymph nodes and spleen were resected. Since in resected mice the antitumor activity of PSK against the right and left tumors was weakened, the regional lymph nodes and the spleen probably have a very important role in the antimetastatic effect of intratumoral administration of PSK. TIL (tumor-infiltrating lymphocytes) obtained from left and right side tumors treated with PSK were examined by Winn assay for their antitumor activity against Meth-A sarcoma in BALB/c mice. TIL from both sides clearly inhibited the growth of admixed Meth-A cells, but control TIL did not. A primary growth of Meth-A sarcoma inoculated into the right flank resulted in the generation of concomitant immunity to the growth of a second graft of the same tumor cells in the left flank. A significant inhibitory effect on the proliferation of the tumor cells inoculated secondarily was shown in mice bearing a primary right tumor that had previously been inoculated with PSK 3 times. After surgical excision of the primary tumor on day 6, daily oral administration of PSK significantly inhibited the growth of the secondary tumor inoculated on day 21, that is, PSK treatment also enhanced sinecomitant immunity. These observations suggest that presurgical intratumoral injection and postoperative oral administration of PSK are highly effective in eradicating metastatic tumors.     

明日叶查尔酮对小鼠肝癌细胞凋亡相关蛋白表达的影响

Objective: The aim of our study was to investigate the effect of Angelica keiskei chalcone (AC) on the expression of Caspase-3 and Bax in mice hepatocarcinoma cells. Methods: Fifty mice inoculated hepatocarcinoma 22 cells were divided into five groups, 10 mice per group. Mice were given 5, 20, 40 mg/kg AC daily by mouth in low, middle and high dose groups respectively. Saline were given to the tumor control group by mouth. Twenty mg/kg cytoxan (CTX) by injection every other day were given to the positive co...