Impaired tumor necrosis factor receptor-1 (TNFR-1) signaling has been found in some malignant tumors with poor prognosis. However, the exact role of TNFR-1 signaling in fibrosarcoma remains unclear. Here, we explored the question by comparing the growth of TNFR-1 deficient (Tnfr1 (-)) and TNFR-1 competent (Tnfr1 (+)) fibrosarcoma FB61 cells (FB61-m and FB61-R1) in mice. TNFR-1 expression on fibrosarcoma cells delayed their growth in vivo but not in vitro. Moreover, reduced FB61-R1 tumor growth was also obtained in TNFR-1 knockout mice. The mechanism relies mainly on the TNFR-1-mediated downregulation of vascular endothelial growth factor (VEGF) production by tumor cells. Importantly, treatment of FB61-m tumors with melphalan resulted in a short delay of tumor growth, followed by a quick remission. However, when FB61-R1 tumors were treated with melphalan, tumor growth was similarly delayed at first and then completely rejected. Our results reveal evidence for TNFR-1 on tumor cells as a prerequisite in chemotherapy for fibrosarcoma, and provide novel insight into the therapeutic approach against some types of tumors using TNFR-1 angonist.
Animals ; Down-Regulation ; drug effects ; Fibrosarcoma ; drug therapy ; genetics ; pathology ; Gene Expression Regulation, Neoplastic ; drug effects ; Humans ; Melphalan ; administration & dosage ; Mice ; Molecular Targeted Therapy ; Receptors, Tumor Necrosis Factor, Type I ; genetics ; Signal Transduction ; drug effects ; Vascular Endothelial Growth Factor A ; biosynthesis

OBJECTIVETo investigate the anti-tumor effect of intraportal administration of Adv-p53 in the treatment of the liver metastasis in mice.

METHODS2 x 10(5) of MCA-205 cells were injected into the mouse portal vein to establish a murine liver metastasis model. The spleen was transpositioned subcutaneously to enable the administration of Adv-p53 continually into the portal system. Different doses of Adv-p53 were injected intraportally, while HBSS and Adv-CMV were injected intraportaly in the control group. Tumors in the liver were examined on day 21 after Adv-p53 administration.

RESULTSThe liver weight in the Adv-p53 treated mice on day 0 group (1.20 +/- 0.34 g) was significantly less than that in the Adv-CMV group (2.59 +/- 0.48 g, P < 0.05). The number of metastatic nodules in the Adv-p53 treated mice on day 0 group (9.0 +/- 9.9) was significantly less than that in the Adv-CMV group (57.1 +/- 11.3, P < 0.05), indicating that intraportal administration of Adv-p53 inhibited the formation of liver metastasis. This anti-tumor effect was in a dose-dependent manner. After the liver metastasis was formed, Adv-p53 was administered intraportally. The liver weight in the Adv-p53 treated mice on day 5 group (1.22 +/- 0.09 g) was significantly less than that in the Adv-CMV group (3.98 +/- 1.01 g , P < 0.05). The number of metastatic nodules in the Adv-p53 treaed mice on day 5 group (5.5 +/- 3.5) was significantly less than that in the Adv-CMV group (113.2 +/- 5.8, P < 0.05). Repeatedly intraportal administration of Adv-p53 could enhance this anti-tumor effect.

CONCLUSIONLocal administration of Adv-p53 into the portal system would be a useful strategy for the liver metastasis treatment.

Adenoviridae ; genetics ; Animals ; Cell Line, Tumor ; Dose-Response Relationship, Drug ; Female ; Fibrosarcoma ; pathology ; Genetic Therapy ; Liver Neoplasms, Experimental ; secondary ; therapy ; Mice ; Mice, Inbred C57BL ; Neoplasm Transplantation ; Recombinant Proteins ; genetics ; therapeutic use ; Tumor Suppressor Protein p53 ; administration & dosage ; genetics ; therapeutic use

Actins ; metabolism ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Back ; Desmin ; metabolism ; Diagnosis, Differential ; Fibrosarcoma ; pathology ; Humans ; Infant ; Male ; Neoplasm Recurrence, Local ; Reoperation ; Rhabdomyosarcoma ; drug therapy ; pathology ; surgery ; Vimentin ; metabolism

Actins ; metabolism ; Adult ; Diagnosis, Differential ; Female ; Fibroma ; pathology ; Fibrosarcoma ; pathology ; Follow-Up Studies ; Humans ; Hysterectomy ; Inflammation ; Keratins ; metabolism ; Leiomyoma ; pathology ; Neoplasm Recurrence, Local ; Neoplasms, Muscle Tissue ; drug therapy ; metabolism ; pathology ; surgery ; Receptor Protein-Tyrosine Kinases ; metabolism ; Uterine Neoplasms ; drug therapy ; metabolism ; pathology ; surgery ; Young Adult

OBJECTIVETo find out the anticancer effect of Indigofera aspalathoides (I. aspalathoides) on 20-methylcholanthrene induced fibrosarcoma in rats.

METHODSFibrosarcoma was induced in Wistar strain male albino rats by 20-methylcholanthrene. Intraperitoneous (i.p.) administration of 250 mg/kg body weight/day of aqueous extract of I. aspalathoides for 30 d effectively suppressed chemically induced tumors. Parameters such as body weight, liver and kidney weight, tumor weight, mean survival time, behavioral changes, blood glucose, blood glycogen and marker enzymes such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), acid phosphatase (ACP) and 5'-nucleiotidase (5'-NT) in serum, liver and kidney and lipid profiles such as total cholesterol, phospholipids, free fatty acids in liver and kidney of control and experimental animals were studied.

RESULTSFibrosarcoma bearing animals were ferocious and anxious. The mean survival time was found to increase after the treatment. The body weights were significantly decreased (P<0.001) in group II fibrosarcoma animals which steadily increased after the treatment with I. aspalathoides. The liver and kidney weights were significantly increased whereas the tumor weights decreased as compared to the weights in untreated fibrosarcoma bearing rats. The blood glucose and the liver and kidney glycogen levels were found to decrease significantly (P<0.001) in group II animals. Elevated activities of marker enzymes were observed in serum, liver and kidney of fibrosarcoma bearing Group II animals which were normalize after I. aspalathoides treatment. In the liver and kidney of Group II animals the total cholesterol increased whereas the phospholipids and free fatty acid levels decreased (P<0.001) which were normalized after treatment.

CONCLUSIONSThe treatment by I. aspalathoides on fibrosarcoma bearing rats has improved the levels of various parameters indicating its antiproliferative and anticancer activity.

Animals ; Antineoplastic Agents ; pharmacology ; Chemoprevention ; Fibrosarcoma ; drug therapy ; pathology ; Indigofera ; chemistry ; Kidney ; drug effects ; pathology ; Liver ; drug effects ; pathology ; Liver Neoplasms, Experimental ; chemically induced ; pathology ; prevention & control ; Male ; Methylcholanthrene ; Phytotherapy ; methods ; Plant Extracts ; pharmacology ; Plant Leaves ; chemistry ; Plant Stems ; chemistry ; Rats ; Rats, Wistar ; Seeds ; chemistry

A novel combined treatment of conventional chemotherapy with an intratumoral injection of syngeneic dendritic cells (DCs) has emerged as a potent cancer treatment strategy. In this study, we evaluated the synergistic effect of an intraperitoneal (i.p.) injection of a chemotherapeutic drug, paclitaxel, and an intratumoral (i.t.) injection of syngeneic bone marrow- derived DCs for the treatment of pre-existing fibrosarcoma. Subcutaneous tumors were established using MCA102 fibrosarcoma cells in syngeneic C57BL/6 mice. The results demonstrated that the combined treatment of paclitaxel chemotherapy and the injection of DCs led to complete tumor regression, in contrast to only partial eradication of the tumors with chemotherapy or DCs alone. Furthermore, the tumor-free mice were able to resist a repeat challenge with the same type of tumor. These findings suggest that a combination therapy of systemic chemotherapy along with the intratumoral administration of DCs is a potent treatment strategy for fibrosarcoma.
Treatment Outcome ; Transplantation, Isogeneic ; Phenotype ; Paclitaxel/administration & dosage/*therapeutic use ; Mice ; Injections, Intraperitoneal ; Immunologic Memory ; Fibrosarcoma/drug therapy/pathology/*therapy ; Dendritic Cells/cytology/*transplantation ; Combined Modality Therapy ; Cells, Cultured ; Cell Line, Tumor ; Bone Marrow Cells/cytology ; Antineoplastic Agents, Phytogenic/administration & dosage/*therapeutic use ; Animals

Actins ; metabolism ; Adult ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Breast Neoplasms ; drug therapy ; metabolism ; pathology ; surgery ; Calcium-Binding Proteins ; metabolism ; Carcinoma ; metabolism ; pathology ; Cyclophosphamide ; therapeutic use ; Desmin ; metabolism ; Diagnosis, Differential ; Female ; Fibrosarcoma ; metabolism ; pathology ; Fluorouracil ; therapeutic use ; Follow-Up Studies ; Humans ; Leiomyosarcoma ; drug therapy ; metabolism ; pathology ; surgery ; Mastectomy, Segmental ; Methotrexate ; therapeutic use ; Microfilament Proteins ; metabolism ; Neurilemmoma ; metabolism ; pathology ; Phyllodes Tumor ; metabolism ; pathology ; Postoperative Period ; Vimentin ; metabolism

This study is to investigate the inhibitory effect of lidamycin (LDM) and its combination with methotrexate (MTX) on lung metastasis of fibrosarcoma by bioluminescence imaging in athymic mice. A stable luciferase transfected HT-1080 cell line was constructed and the capability to establish experimental lung metastasis in athymic mice was confirmed. The optical imaging system was applied to evaluate the formation of lung metastasis in vivo. In addition, metastatic nodules were counted for the evaluation of inhibition rates. As shown, the fluorescent intensity of luciferase-transfected HT-1080 cells was colinear with the cell population and the minimal detected cell population was 100 cells/well. Optical imaging showed that the fluorescent intensity of treated group was apparently lower than that of the control. The inhibition rates of lung metastasis by LDM alone at 0.025 mg x kg(-1) and 0.05 mg x kg(-1) were 53.9% and 75.9%, respectively, while that of MTX alone at 0.5 mg x kg(-1) was 70.2%. The combination of LDM at 0.025 mg x kg(-1) and MTX at 0.5 mg x kg(-1) showed an inhibition rate of 88.7%. The coefficient of drug interaction (CDI) was 0.82. The results herein demonstrated that LDM alone had strong anti-metastasis effect on human fibrosarcoma HT-1080 and the inhibition efficacy is strengthened when combined with MTX.
Aminoglycosides ; administration & dosage ; Animals ; Antibiotics, Antineoplastic ; administration & dosage ; Antimetabolites, Antineoplastic ; administration & dosage ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Cell Line, Tumor ; Drug Synergism ; Enediynes ; administration & dosage ; Female ; Fibrosarcoma ; pathology ; Humans ; Luminescent Measurements ; Lung ; pathology ; Lung Neoplasms ; drug therapy ; pathology ; secondary ; Methotrexate ; administration & dosage ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Random Allocation ; Transfection ; Xenograft Model Antitumor Assays

This study is to investigate the antitumor activities of the immunoconjugates composed of anti-type IV collagenase monoclonal antibody 3G11 and lidamycin (LDM) prepared by different methods. The immunoconjugates were prepared by linking 2-iminothiolane modified 3G11 to lysine-69 of LDM apoprotein by SPDP and SMBS as the intermediate drug linker. Immunoreactivity of the conjugates was determined by ELISA. The cytotoxicity of the conjugates was examined by clonogenic assay. Antitumor effects of the conjugates in vivo were evaluated in nude mice bearing subcutaneously implanted HT-1080 tumor. ELISA assay showed that the immunoconjugates retained the immunoreactivity of 3G11 against type IV collagenase. The cytotoxicity of the 3G11-SMBS-LDM to HT-1080 cells was significantly more potent than that of free LDM and 3G11-SPDP-LDM. In animal model at the same condition, free LDM inhibited the growth of HT-1080 tumor by 71.2%, while 3G11-SPDP-LDM and 3Gl1-SMBS-LDM reached 77.1% and 86.1%, respectively. The median survival time of the mice treated with free LDM was prolonged by 71.9% compared with that of untreated group. Whereas, the median survival time of 3G11-SPDP-LDM and 3G11-SMBS-LDM was prolonged by 125.3% and 163.7%, respectively, indicating that 3G11-SMBS-LDM was more effective than 3G11-SPDP-LDM in tumor suppression and life span prolongation. 3Gll-SMBS-LDM has more selective antitumor efficacy and lower toxicity, and might be a novel candidate for cancer therapy. LDM was more effective than 3G11-SPDP-LDM in tumor suppression and life span prolongation. 3Gll-SMBS-LDM has more selective antitumor efficacy and lower toxicity, and might be a novel candidate for cancer therapy.
Aminoglycosides ; therapeutic use ; Animals ; Antibiotics, Antineoplastic ; therapeutic use ; Antibodies, Monoclonal ; immunology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Collagenases ; immunology ; Enediynes ; therapeutic use ; Fibrosarcoma ; pathology ; therapy ; Humans ; Immunoconjugates ; therapeutic use ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Transplantation ; Tumor Burden ; drug effects