Antitumour effect of fibrinogen microspheres containing doxorubicin on Ehrlich ascites carcinoma

The antitumour activity of fibrinogen microspheres containing doxorubicin has been evaluated against Ehrlich ascites carcinoma in mice in terms of changes in body weight and survival. Tumour cell injections were made on day 0 and microsphere injections on day 1, both intraperitoneally. The suppressive effect of the drug-containing microspheres on increase in body weight was higher than that of the free drug, and tumour-bearing mice given the microspheres lived longer than those given the free drug.     

蟾蜍毒素对小鼠移植艾氏腹水癌肿瘤细胞的抑制及毒副作用的实验研究

目的探讨醇溶性蟾蜍毒素在小鼠体内对艾氏腹水癌肿瘤细胞的抑制作用及其毒副作用。方法本研究用乙醇溶解蟾蜍分泌物原浆,采用减压蒸馏等方法进一步部分分离纯化,获得醇溶性的蟾蜍毒素混合物(EET),将其作用于艾氏腹水癌荷瘤小鼠模型,计算小鼠的生命延长率,同时通过血生化和病理等检测观察其对各脏器的毒副作用。结果5 mg/kg和0.5 mg/kg的EET对艾氏腹水癌荷瘤小鼠的生命延长率分别是42.6%(P<0.05)和33.7%(P<0.05);同时,0.5 mg/kg的EET可明显升高白细胞达(11.8±3.9)×109/L(P<0.05)。但EET在5 mg/kg时可引起总胆红素升高达(42.5±9.8)μmol/L(P<0.05)。结论0.5~5 mg/kg的EET可以明显抑制荷瘤小鼠体内艾氏腹水癌肿瘤细胞的生长,但EET的剂量达到5 mg/kg时可以损伤肝脏。     

Antitumor activity and antioxidant status of Caesalpinia bonducella against Ehrlich ascites carcinoma in Swiss albino mice

The methanol extract of Caesalpinia bonducella FLEMING (Caesalpiniaceae) leaves (MECB) were evaluated for antitumor activity against Ehrlich ascites carcinoma (EAC)-bearing Swiss albino mice. The extract was administered at the doses of 50, 100, and 200 mg/kg body weight per day for 14 days after 24 h of tumor inoculation. After the last dose and 18 h fasting, the mice were sacrificed. The present study deals with the effect of MECB on the growth of transplantable murine tumor, life span of EAC-bearing hosts, hematological profile, and biochemical parameters such as lipid peroxidation (LPO), glutathione content (GSH), superoxide dismutase (SOD), and catalase (CAT) activities. MECB caused significant (P<0.01) decrease in tumor volume, packed cell volume, and viable cell count; and it prolonged the life span of EAC-tumor bearing mice. Hematological profile converted to more or less normal levels in extract-treated mice. MECB significantly (P<0.05) decreased the levels of lipid peroxidation and significantly (P<0.05) increased the levels of GSH, SOD, and CAT. The MECB was found to be devoid of conspicuous short-term toxicity in the mice when administered daily (i.p.) for 14 days at the doses of 50, 100, 200, and 300 mg/kg. The treated mice showed conspicuous toxic symptoms only at 300 mg/kg. The results indicate that MECB exhibited significant antitumor and antioxidant activity in EAC-bearing mice.     

Effect of sulfhydryl-containing compounds on the antitumor effects of adriamycin

The lethality of single doses of adriamycin (ADR) in male mice has been reported to be antagonized by concurrent administration of the sulfhydryl compounds cysteamine (CYS) or N-acetylcysteine (NAC). The present investigation was undertaken to determine whether CYS and NAC also have an effect on the antitumor activity of ADR. The life span of male mice bearing a transplantable Ehrlich ascites carcinoma was significantly increased by ADR administered intraperitoneally for 4 successive days at sublethal dosages of 1.5 or 2.5 mg/kg/day. CYS or NAC (50 and 100 mg/kg ip, respectively) administered 1 hr before and 7 hr after ADR treatment did not inhibit the antitumor activity of ADR and further increased the life span of these tumorbearing animals. The uptake of ADR by Ehrlich ascites cells in vitro was not affected by CYS or NAC. ADR-induced inhibition of [³H]thymidine incorporation into DNA of Ehrlich ascites cells in vitro was also not affected by CYS or NAC. The mechanism of sulfhydryl-induced protection against the cardiotoxicity of ADR appears not to interfere with the antitumor activity of ADR.     

Antitumor effect of the seashell protein Haishengsu on Ehrlich ascites tumor: an experimental study

The aim of the study was to investigate the in vivo effect of the seashell protein Haishengsu (HSS) on Ehrlich ascites tumor. Mice were inoculated with Ehrlich ascites tumor cells and randomly divided into three HSS groups and a control group. The survival times in the three HSS-treated groups was longer than in the control (P < 0.01) and the increased life span in the high-dose HSS group was greater than in the lower-dose groups (P < 0.05). In comparison with control group, the mice receiving pretreatment of HSS had longer survival times and greater life spans following inoculation of the ascites tumor (P < 0.05). HSS therefore prolongs survival times and increases the life spans of mice bearing Ehrlich ascites tumor. Pretreatment with HSS also diminishes the detrimental effect of Ehrlich ascites tumor on the prognosis of these animals.     

Antitumor efficacy and amelioration of oxidative stress by Trichosanthes dioica root against Ehrlich ascites carcinoma in mice

Context: Trichosanthes dioica Roxb. (Cucurbitaceae) is a dioecious climber, traditionally used in India for several medicinal purposes.

Objective: The present study assessed the hydroalcoholic extract of T. dioica root (TDA) for antitumor effect and antioxidant influence against Ehrlich ascites carcinoma (EAC) in Swiss albino mice.

Methods: Twenty four hours after intraperitoneal inoculation of tumor (EAC) cells in mice, TDA was administered at 5 and 10?mg/kg body weight daily for 9 consecutive days. On the 10th day, half of the mice were sacrificed for estimation of tumor proliferation, hematological, and liver antioxidant parameters viz. lipid peroxidation, reduced glutathione (GSH), glutathione S-transferase (GST), superoxide dismutase (SOD) and catalase (CAT); and the rest were kept alive for assessment of increase in life span. The antitumor effect of TDA was assessed by evaluating tumor weight, tumor volume, packed cell volume, viable and non-viable tumor cell counts, median survival time and percentage increase in life span of EAC bearing mice.

Results and discussion: TDA exhibited dose dependent and significant (p?<?0.001) decrease in tumor weight, tumor volume, packed cell volume and viable cell count and extended the life span of EAC bearing hosts. Hematological profiles were significantly (p?<?0.001) restored near to normal in TDA treated mice as compared to EAC control. TDA treatment significantly (p?<?0.001) modulated the aforesaid liver antioxidant parameters as compared to EAC control.

Conclusion: The present study demonstrated that TDA possessed promising antitumor efficacy in mice, plausibly mediated by amelioration of oxidative stress by multiple mechanisms.     

Evaluation of intraperitoneal vincristine in malignant peritoneal effusion

The efficacy and safety of intraperitoneal administration of vincristine sulphate was determined in mice bearing Ehrlich ascitic carcinoma. The tumor bearing animals were administered with 0.5 mg/kg body weight (b.wt) of freshly prepared vincristine sulphate intraperitoneally on day 6 after tumor transplantation followed by drug administration once daily 5 days a week consecutively. The observations regarding the survival, alteration in the volume of peritoneal fluid, increase in life span and pathological changes in the liver, kidney, gastrointestinal tract and bone tissues were made. The vincristine sulphate treatment reduced the malignant cell population significantly and there were no significant changes in the histological picture of liver, kidney, bone, except the intestine, where atropy of villi demonstrating nests and cords of uniform small round cells were observed. Our experimental data suggests that intraperitoneal administration of vincristine is beneficial in malignant peritoneal effusion.     

Glutathione reduces the toxicity associated with antitumor therapy of ascites fluid adsorbed over Staphylococcus aureus Cowan I in tumor bearing mice.

It has been well documented in the literature that the removal of circulatory immune complexes (CICs) from the host circulation leads to the immunopotentiation as well as generation of antitumor responses in a variety of tumors in rats, cats, dogs and human patients. CICs are the major immunosuppressive factors in tumor bearing host. Protein A (PA) has been extensively used for the removal of these CICs from the sera/plasma of tumor bearers, because PA has the ability to bind with the Fc portion of mammalian immunoglobulins. Previously, we reported for the first time a potent antitumor response by the inoculation of cell free Ehrlich's ascites fluid adsorbed in vitro over PA containing Staphylococcus aureus Cowan I (SAC) in Ehrlich's ascites tumor model. However, there was toxicity associated with this form of therapy in terms of early death of treated animals and the depletion of hepatic glutathione pool as well as phase I biotransformation enzyme and increase in glutathione-S-transferase (GST) activities. In the present investigation, tumor bearing animals were treated intraperitoneally (i.p.) on alternate days for 15 days with adsorbed ascites fluid (ad-ASF) (0.1 ml) and glutathione (GSH) (250 mg/kg body weight) separately. We found that GSH supplementation increases mean survival time of GSH and ad-ASF treated mice up to 37.2 days in comparison with 19.9 days for only ad-ASF treated animals, while percent increase in body weight was found to be not affected by the GSH substitution, which remains significantly lower (P < 0.01) in comparison to the tumor control animals. GSH supplementation causes a significant decrease (P < 0.05) of glutathione-S-transferase and restoration of aniline hydroxylase activity (P < 0.05) and aminopyrine-N-demethylase activity. We have also observed that GSH supplementation does not alter the tumor cell viability and tumor cell counts in ad-ASF treated animals in comparison to only ad-ASF treated animals, which indicates that GSH supplementation does not alter the antitumor effect of the therapy. Treatment of Ehrlich's ascites tumor bearing mice with ad-ASF and glutathione increased their survival, but did not reduce the mortality of animals because of tumor.     

Antitumour Activity of Mitoxantrone-loaded Chitosan Microspheres Against Ehrlich Ascites Carcinoma

Glutaraldehyde cross-linked chitosan microspheres containing the antineoplastic agent mitoxantrone were prepared and the antitumour activity was evaluated against Ehrlich ascites carcinoma in mice by intraperitoneal injections. The tumour inhibitory effect was followed by monitoring animal survival time and change in body weight for a period of 60 days. While the mean survival time of animals which received 2 mg and 1 mg of free mitoxantrone intraperi-toneally was 2.1 and 4.6 days, respectively, animals which received 2 mg mitoxantrone via microspheres showed a mean survival time of 50 days. Five out of 8 animals treated using microspheres lived beyond 60 days. The percentage ratio mean survival time of the treated group divided by the mean survival time of the untreated group for animals treated using mitoxantrone-loaded chitosan microspheres containing 2 mg of the drug was 290 compared with 12.2 for those which received 2 mg of the free drug. The antitumour effect of mitoxantrone-loaded microspheres against Ehrlich ascites carcinoma was much higher than that of doxorubicin-loaded microspheres reported by previous workers. Our data demonstrate the potential of mitoxantrone-loaded chitosan microspheres for sustained drug delivery to minimize drug toxicity and maximize therapeutic efficacy.     

Evaluation of Antitumor and Antioxidant Activity of Melothria heterophylla (Lour.) Cogn

Melothria heterophylla (Lour.) Cogn., (family-Cucurbitaceae) popularly known as kundari, has been shown to exhibit antioxidant effects. The main objective was to isolate active constituents of the plant extract. In this study, the ability of M. heterophylla to induce apoptosis was studied in Ehrlich ascites carcinoma cells. Treatment of the Ehrlich ascites carcinoma cells with a variety of concentrations of the ethanol extracts of M. heterophylla and gallic acid (100-1000 μM), to determine the sequences of events marked by apoptosis, assayed by the spectrofluorometric method. Gallic acid and rutin were isolated from plant extract which were quantified by high-performance liquid chromatography. Our results indicate that ethanol extracts of M. heterophylla and gallic acid-induced apoptotic cell death in a dose dependent manner could be due to the generation of reactive oxygen species, especially H₂O₂, which is confirmed by caspase 3 activation. Treatment of Ehrlich ascites carcinoma bearing Swiss albino mice with varied doses (200 and 400 mg/kg, b.w.) of plant extract significantly reduced tumor volume and viable tumor cell count and improved hemoglobin content, RBC count, mean survival time, tumor inhibition, and percentage life span. The enhanced antioxidant status in extract-treated animals were evident from the decline in the levels of lipid peroxidation and increased levels of glutathione, catalase, and superoxide dismutase. The data suggest that M. heterophylla exerts anticancer activity, valuable for application in food and drug products.     

Antitumor effects of royal jelly (RJ)

Antitumor effects of Royal Jelly (RJ) were investigated employing the transplantable tumors of mouse advance leukemia L1210 and P388 strains and Ehrlich, Sarcoma-180 ascites and solid tumor strains. RJ was administered orally in a prophylactic-therapeutic (30 days before and 30 days after the transplantations of tumor cells) or a therapeutic (30 days after the transplantations of tumor cells) manner. Tumor cells were transplanted i.p. (ascites tumor) or s.c. (solid tumor). The daily dose of RJ was 0 (control), 10, 100, or 1000 mg/kg. In the case of the therapeutic experiments employing advance leukemia L1210 and P388 strains, which gave quite a short survival period of 8 approximately 9 days, RJ did not show any antitumor effect. In the case of the therapeutic RJ application employing the Sarcoma-180 ascites tumor, which gave a moderate survival period of 16 days, the increased life span was 9.3 approximately 19.3%; and with the Ehrlich ascites tumor (survival period of 22.1 days), the increased life span was 20.4% (RJ 10 mg/kg . day) and 17.6% (RJ 1,000 mg/kg . day), but no antitumor effect was observed at the dose of 100 mg/kg . day. In the case of the therapeutic experiment employing Ehrlich solid tumor, tumor growth inhibition was 25.3 approximately 54.8%, where as the use of the prophylactic-therapeutic regimen gave a tumor growth inhibition of 38.3 approximately 45.7%. In the case of the therapeutic RJ application employing Sarcoma-180 solid tumor, tumor growth inhibition was 45.1 approximately 59.7%, where as the prophylactic-therapeutic regimen gave a tumor growth inhibition of 49.1 approximately 56.1%.(ABSTRACT TRUNCATED AT 250 WORDS)     

Plumbagin,A Plant Naphthoquinone with Antitumor and Radiomodifying Properties

The tumor inhibitory and radiomodifying effects of plumbagin (Pl), a naphthoquinone isolated from Plumbago rosea, on mouse Ehrlich ascites carcinoma was studied. Tumor response was assessed by increase in life span (% ILS) and animal survival at 120 days. The acute LD 50 of plumbagin in normal mice was 9.4 mg/kg body weight. Single doses from 2 to 6 mg/kg Pl, given intraperitoneally (i.p.), produced inhibition of exponentially growing tumors. However, increases in dose above 3 mg/kg did not increase 120 day survival significantly over that produced by 3 mg/kg. Multiple dose treatment, starting from 24 h after tumor cell inoculation, showed that a total dose of 9 mg/kg, administered in three fractions of 3 mg/kg, once daily, gave the maximum %ILS and tumor free survival. Combination of radiation (RT, 7.5 Gy to the abdomen) after the first Pl dose (1-3mg/kg/fraction) synergistically increased mouse survival at 120 days. The tumor inhibitory effect was less pronounced when treatment was started at more advanced tumor stages, but combination of low dose fractions (2.5 or 3 mg/kg/fraction) with RT enhanced the %ILS and animal survival. Higher dose fractions in combination with radiation were not tolerated by the mice. DNA appears to be the likely target of Pl cytotoxicity; the mechanism of interaction of Pl + RT in enhancing tumor response is not clear.     

The in vivo behavior and antitumor activity of doxorubicin-loaded poly(γ-benzyl l-glutamate)-block-hyaluronan polymersomes in Ehrlich ascites tumor-bearing BalB/c mice

The in vivo efficacy of doxorubicin (DOX)-loaded poly(γ-benzyl l-glutamate)-block-hyaluronan (PBLG(23)-b-HYA(10))-based polymersomes (PolyDOX) was evaluated. Samples were efficiently labeled with technetium-99m radionuclide with good stability for in vivo studies. PolyDOX enhanced circulation time compared to free DOX. Biodistribution studies revealed selective accumulation of PolyDOX in the Ehrlich ascites tumor (EAT) as a result of passive accumulation and active targeting (CD44-mediated endocytosis) in EAT-bearing mice. Toxicity studies demonstrated PolyDOX is a safe drug carrier, and no hemolysis was observed with PolyDOX equivalent to 200 μg/mL of free DOX. PolyDOX dominantly controlled tumor growth by delaying doubling time of EATs compared to free DOX over 30 days after treatment. PolyDOX also increased life span six times more than free DOX. Hence, it is reasonable to expect that higher DOX levels attributable to PolyDOX improve the therapeutic index and reduce side effects due to site-specific drug accumulation. FROM THE CLINICAL EDITOR: In this preclinical project, doxorubicin loaded polymersomes enhanced intracellular uptake of doxorubicin in a murine model of Ehrlich Ascites Tumor (EAT) through CD44 receptor mediated endocytosis, resulting in prolonged Tumor Doubling Time and increase in life span of mice.     

长春花生物碱部分之一 AC-875的抗肿瘤作用及毒性

木文对长春花(Catharanthus roseus Linn.G.Don)中分离提出的生物碱AC-875进行了毒性及抗癌作用的实验研究.试验结果表明AC-875在20-42毫克/公斤时,对小鼠Ehrlich腹水癌及腹水型肝癌均有明显的抑制作用.当剂量为10毫克/公斤时,对大鼠腹水型吉田肉瘤也有较好的疗效.在实体瘤的治疗中,注射35毫克/公斤,对小鼠S-180仅有轻度抑制作用,且不太稳定.对小鼠网织细胞瘤、Ehrlich腹水癌实体瘤、大鼠Jensen肉瘤及Walker癌等则无抑制作用.给小鼠腹腔注射AC-875的急性LD₅₀为170毫克/公斤,亚急性LD₅₀为61毫克/公斤.给大白鼠腹腔注射AC-875的意性及亚急性LD₅₀分别为122毫克/公斤及18毫克/公斤.给家兔静脉注射8毫克/公斤AC-875时,心电图无明显变化.静脉注射AC-875 1毫克/公斤、2.5毫克/公斤或皮下注射5毫克/公斤,对狗的肝、肾功能、尿常规、红血细胞、血红蛋白及体重均无明显影响,但2.5和5毫克/公斤组,狗的白细胞有下降现象.     

Mitomycin C-dextran conjugate: a novel high molecular weight pro-drug of mitomycin C

A high molecular weight derivative of mitomycin C (MMC), mitomycin C-dextran conjugate (MMC-D) has been synthesized and its biological and pharmacological properties investigated. MMC is released from MMC-D in vitro with a half-life of 24 h. After intraperitoneal injection of MMC-D, free MMC could be detected in plasma and urine of mouse for 5--8 h, while MMC administered as a free form was eliminated rapidly. After MMC-D, given to mice bearing Ehrlich ascites carcinoma or B16 melanoma there was a reduction in toxicitst that the high molecular weight MMC-dextran derivative is a kind of pro-drug which persists in the body giving a sustained release of free MMC thus significantly increasing the antitumour activity of the parent drug.     

Myrocin C, a new diterpene antitumor antibiotic from Myrothecium verrucaria. I. Taxonomy of the producing strain, fermentation, isolation and biological properties

A new diterpene antitumor antibiotic, myrocin C, has been isolated from the culture filtrate of a soil fungus, Myrothecium verrucaria strain No. 55. The antibiotic was effective against Gram-positive bacteria, fungi and yeasts, and prolonged the life span of mice bearing Ehrlich ascites carcinoma.     

Trichosanthes dioica root extract induces tumor proliferation and attenuation of antioxidant system in albino mice bearing Ehrlich ascites carcinoma

Trichosanthes dioica Roxb. (Cucurbitaceae), called pointed gourd in English, is a dioecious climber grown widely in the Indian subcontinent. The present study assessed the influence of treatment of hydroalcoholic extract of Trichosanthes dioica root (TDA) on Ehrlich ascites carcinoma (EAC) in Swiss albino mice with effects on antioxidant systems. Twenty-four hours after intraperitoneal inoculation of tumor (EAC) cells in mice, TDA was administered at 25 and 50 mg/kg for 8 consecutive days. On the 9(th) day, half of the mice were sacrificed for estimation of tumor proliferation, hematological, and hepatic antioxidative parameters. The rest were kept for assessment of survival parameters. TDA exhibited dose dependent and significant increase in tumor weight, tumor volume, packed cell volume and viable cells and reduced non-viable cells and life span of EAC bearing animals. Hematological parameters were significantly worsened in TDA-treated mice. TDA treatment significantly aggravated the hepatic antioxidative parameters. The present study demonstrated that T. dioica root possessed tumor promoting activity in EAC bearing albino mice, plausibly mediated by attenuation of endogenous antioxidant systems.     

Studies of methyl 2-nitroimidazole-1-acetohydroxamate (KIN-804) 2: effect on certain antioxidant enzyme systems in mice bearing Ehrlich ascites carcinoma

In order to decrease toxicity and/or increase radiosensitizing activity, a new 2-nitroimidazole derivative, methyl 2-nitroimidazole-1-acetohydroxamate (KIN-804), was synthesized to solve the problem of tumor hypoxia. Evaluation of the efficiency of KIN-804 was carried out through studying the antioxidant enzyme system: The superoxide dismutase (SOD), catalase and lipid peroxide levels provide a rough index of the balance between free radical generation and scavenging. Female albino mice were inoculated with Ehrlich ascites carcinoma (EAC) in the thigh. The administration of KIN-804 (i.p. 80 mg/kg body weight) was carried out 20 min before localized irradiation of 10 Gy. In general, the data revealed that KIN-804 administration, followed or not by gamma irradiation, exerted significant inhibition of SOD and catalase activities accompanied by a significant increase in lipid peroxide level in tumor-bearing mice.     

抗肿瘤药物的研究——Ⅵ.对-双(2-氯乙基)氨基-隣甲氧基-苯丙氨酸的实验治疗及毒性

肿瘤化学治疗中氮芥类药物占有重要的地位,临床上已证明这类药对某些造血系统肿瘤有一定的疗效.近年来,很多学者都沿着这条路线,继续寻找更理想的药物.自溶肉瘤素(sarcolysin)发现以来,氨基酸类的氮芥更引起了大家的注意.我们茌这方面也进行了较系统的工作,在筛选中发现对-双(2-氯乙基)氨基-邻甲氧基-苯丙氨酸(药物编     

Antioxidant and hepatoprotective activity of the methanol extract of <Emphasis Type="Italic">Careya arborea</Emphasis> bark in Ehrlich ascites carcinoma-bearing mice

The methanol extract of Careya arborea bark (MECA) was tested for antioxidant and hepatoprotective activity in Ehrlich ascites carcinoma (EAC) tumor-bearing mice. Tumor control animals inoculated with EAC showed a significant alteration in the levels of antioxidant and hepatoprotective parameters. The extract treatment at 50, 100 and 200 mg/kg body weight doses given orally caused a significant reversal of these biochemical changes towards the normal in serum, liver and kidney when compared to tumor control animals indicating the potent antioxidant and hepatoprotective nature of the standardized extract.