Local antitumor activity of a primary and an anamnestic response to a syngeneic guinea pig hepatoma.

After intradermal (id) injection, the line-10 hepatoma grew progressively in nonimmune guinea pigs, whereas the line-1 hepatoma grew for approximately 2 weeks, developed central necrosis, ulcerated, and regressed. Growth of the line-10 hepatoma was suppressed when line-10 hepatoma cells were mixed with antigenically distinct line-1 hepatoma cells before id injection into syngeneic strain-2 guinea pigs. Mixture of line-10 with irradiated line-1 or viable strain-2 embryo cells did not inhibit tumor growth. Preimmunization of recipients to line-1 cells abrogated the suppression of tumor growth from mixtures of line-1 and line-10.     

猪松果体提取物抗肿瘤实验研究

作者应用猪松果体提取物，松乐素Ａ、Ｂ、Ｃ三种制剂在小鼠肉瘤１８０（Ｓ＿（１８０）），肉瘤３７（Ｓ＿（３７））和Ｂ＿（１６）黑色素瘤研究了其抗瘤活性。松乐素Ａ、Ｂ、Ｃ对Ｓ＿（１８０）抑制率分别为１４～２２％，１７～５２．５％和１９～２１．４％（剂量为０．０５～０．２ｍｌ／天）；对Ｓ＿（３７）抑制率分别为３１～３４．６％（Ｐ＞０．０５），４．５～２２．９％和２２～２２．９％；对黑色素瘤抑制率分别为２２．７～３４．７％，３１～４５％（Ｐ＜０．０１）；２８～３１％（Ｐ＜０．０５）。因此，本实验表明，猪松果体提取物松乐素有一定的抗肿瘤作用。     

Biological activity of Pityrosporum. II. Antitumor and immune stimulating effect of Pityrosporum in mice

The antitumor activity of Pityrosporum (P. orbiculare, P. ovale, P. pachydermatis, and Pityrosporum sp.) on Ehrlich ascites carcinomas (EACs) implanted into outbred ICR mice was studied. Pityrosporum significantly prolonged the survival of mice, regardless of the administration mode. In the case of P. orbiculare, the maximum survival time was 32.3 days on the mean and was obtained by injection ip of 1 mg (dry weight) P. orbiculare for 7 consecutive days following inoculation of the tumor cells. In contrast, the mean survival time of the nontreated mice was 14.9 days. For the investigation of the mechanisms of this antitumor activity, an examination was done on the ability of intracellular killing of Salmonella typhimurium and oxygen intermediate release by Pityrosporum, as elicited by mouse peritoneal exudate cells (PEC) or mouse peritoneal macrophages (PM). With about 40-minute incubation, 60-80% of S. typhimurium phagocytized by Pityrosporum elicited PEC or PM or were killed. The amounts of superoxide released from Pityrosporum-elicited cells were 1.5 times higher than those of P. acnes-elicited ones. Furthermore, three serum proteins (LA, LB, and LC), which closely related to the anti-tumor activity of immunomodulators, increased in the mice given Pityrosporum. These results indicated that the better survival rate seen in the case of Pityrosporum administration to mice with an implanted EAC may relate to the potent activation of phagocytes and to the increase in serum proteins LA, LB, and LC.     

Antitumor activity of cis-dichlorodiammineplatinum(II) and its effect on cell cycle progression

Antitumor activity of cis-dichlorodiammineplatinum(II) (cisplatin) on various mouse transplantable tumors was investigated. Cisplatin was active against a wide variety of the following tumor systems: L1210 leukemia, P388 leukemia, B16 melanoma, colon tumor 38, Ehrlich ascites and solid carcinoma, WHT squamous cell carcinoma, and human stomach cancer G/S heterotransplanted in nude mice. From the comparison of growth inhibitory effect by cisplatin with various other antitumor agents in cultured Ehrlich ascites carcinoma cells, cisplatin was found to be mainly a concentration depending drug, but also time depending, so that it was identified as a type Ib class drug proposed by Shimoyama. Effect of cisplatin on the cell cycle progression of Ehrlich ascites carcinoma cells in mice was studied by flow cytometry of DNA. At an early stage after administration of cisplatin, cell cycle progression was delayed in S phase and blocked in G2 phase. With the elapse of time block in G1 phase or G1-S boundary was observed and the cell population, partially synchronized in G1 phase or G1-S boundary, progressed slowly through S phase to be blocked in G2 phase finally.     

Immunotherapy of a guinea pig hepatoma with living BCG: a frozen liquid and a lyophilized preparation are equally active.

A freeze dried preparation of BCG with a low ratio of living to dead organisms (LV) was compared to a frozen liquid preparation with high viability (HV) for its ability to eradicate established dermal tumors and microscopic lymph node metastases in guinea pigs. The cure rate achieved by the intralesional injection of LV-BCG did not differ significantly from that of HV-bcg when similar numbers of viable organisms were injected.     

Antitumor activity of a sulfated polysaccharide from Enteromorpha intestinalis targeted against hepatoma through mitochondrial pathway

A sulfated polysaccharide (EI-SP), extracted from Enteromorpha intestinalis that is a kind of algae, is found to have anticancer activity. This study was designed to investigate the anti-tumor effect of EI-SP on human hepatoma HepG2 cell line and its possible mechanisms. An MTT assay showed that EI-SP could specifically inhibit the growth of human hepatoma HepG2 cells in a dose-dependent manner. Analysis by flow cytometry indicated that the apoptosis of tumor cells increased after treatment with EI-SP in range of 100–400 μg/ml. Furthermore, Western blot analysis showed that EI-SP treatment led to decreased protein expression of Bcl-2 and an increase in Bax, cleaved caspase-3, cleaved caspase-9 and cleaved poly(ADP-ribose) polymerase (PARP). Moreover, it was found that EI-SP caused a loss of mitochondrial membrane potential (Δψ _m) and the release of cytochrome c to the cytosol. Collectively, our results showed that the EI-SP induces apoptosis in HepG2 cells involving a caspases-mediated mitochondrial signalling pathway.     

Multiple in vitro mechanisms of tumor cytotoxicity demonstrated in the line-1 guinea pig hepatoma model.

The line-1 guinea pig hepatoma was used to study in vitro tumor cytotoxicity. Cytotoxicity was determined by measurement of the loss of tritiated thymidine-labeled target cells from culture vessels. With this technique, we demonstrated that significant tumor cytotoxicity was caused by lymphoid cells from tumor-immune guinea pigs, by cells from guinea pigs immunized against an antigen urelated to the tumor target, and by cell-free supernatants rich in lymphocyte mediators. Addition of normal peritoneal exudate cells enhanced the cytotoxic potential of a small number of highly purified immune lymphocytes, which suggested that recruitment of normal cells is an additional mechanism of tumor cell death in this system.     

Efficacy of chemotherapeutic treatment of guinea pig hepatoma reflected in host's serum lipid composition

A correlation was found between the highly polar phospholipid (HPPL) content of serum lipids and the growth and metastasis of the line-10 hepatoma in strain 2 guinea pigs. Animals whose tumors were treated by intralesional injection of decarbazine (DTIC) or saline showed progressive tumor growth and metastasis resulting in death within 120 days of tumor implantation. The percent HPPl in the serum lipids of these animals rose to 40% by 80 days and remained elevated above 20-25% until death. Animals whose tumors were treated by intralesional injection of adriamycin were either cured of their tumors (67%) or showed little or no tumor growth. The percent HPPL in the serum lipids of these animals remained between 3 and 12% at all times. Adriamycin or DTIC injected into non-tumor-bearing animals resulted in an HPPL content of serum lipids that was not significantly different from that of control, saline-inoculated animals.     

Antitumor effect of IL-2 entrapped in liposomes on rat hepatoma, AH-66

The human recombinant interleukin 2 (IL-2) was entrapped in liposomes, and the therapeutic effects of the liposomes containing IL-2 (Lip-IL-2) were experimentally studied using the rat hepatoma strain, AH-66, maintained in donryu rats and challenged subcutaneously in the inguinal region. The peri-tumor injections of Lip-IL-2 (15 X 10(4)/kg units for the IL-2 dose) significantly inhibited the tumor growth as determined from the relative mean tumor weight, although no therapeutic effects were observed when the unentrapped IL-2 or liposomes containing saline was administered rats in the same way as the injections of Lip-IL-2. They also prolonged the survival time of rats. The studies of serum IL-2 values after i.v. or s.c. injections of Lip-IL-2 revealed that IL-2 was released gradually from the liposomes containing IL-2 into the circulation. As the result of the tumor tissue staining of the immunoperoxidase 18 hrs after the peri-tumor injection of IL-2, it was shown that a number of macrophages infiltrated into the tumor tissue and degenerated tumor cells were observed adjacent to those macrophages. It is suggested that Lip-IL-2 is useful as an antineoplastic agent in the immunotherapy and that the therapeutic effects of Lip-IL-2 would be related to both the slow release of IL-2 and the cytotoxicity on the tumor cells mediated by the macrophages.     

生长抑制因子-4抗肿瘤作用

 生长抑制因子(ING) 4是抑癌因子家族的重要成员,在多种人恶性肿瘤中呈显著低表达,参与调节肿瘤发生、细胞周期、细胞凋亡、DNA修复、血管生成等多个过程,对肿瘤的进程和预后产生重要影响。ING4有望成为评估肿瘤预后的指标及肿瘤治疗的新靶点。     

Antitumor quinolones with mammalian topoisomerase II mediated DNA cleavage activity.

Ninety quinolones were evaluated to determine whether their ability to induce mammalian topoisomerase II mediated DNA cleavage in vitro correlated with their antitumor activity in vivo. Ten quinolones generated linear DNA at a yield of more than 10% of substrate supercoiled DNA in the mammalian topoisomerase II mediated DNA cleavage assay. All of these compounds showed a significant increase in life span (greater than 20%) in the murine leukemia P388 model. These antitumor quinolones have closely related structures: two halogens at C-6 and C-8; and cyclopropyl at N-1 of quinolone skeleton. In contrast, many analogues of the above quinolones, as well as new quinolones used clinically as an antibacterial drug, did not induce the cleavable complex in vitro or show antitumor activity in vivo. These findings indicate that quinolone derivatives can be a promising new class of antitumor agent targeting mammalian topoisomerase II.     

Antitumor spectrum of TUT-7 on rat ascitic hepatoma

The antitumor activity of TUT-7, a new anthracycline compound, was compared to that of adriamycin in the screening system with rat ascites hepatomas. A marked antitumor effect was observed in most tumor lines, and the activity was assumed to be better than adriamycin.