Comparison of the inhibitory effect of the angiogenesis inhibitor, TNP‐470, and mitomycin c on the growth and liver metastasis of human colon cancer

Konno, Hiroyuki; Tanaka, Tatsuo; Matsuda, Iwao; Kanai, Toshikazu; Maruo, Yuji; Nishino, Norikazu; Baba, Shigeaki

doi:10.1002/ijc.2910610221

Cited by 65 publications

(34 citation statements)

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“…Antiangiogenic therapy offers a number of potential benefits including lack of resistance to some agents, synergistic interaction to other modalities, lack of significant toxicity compared with conventional agents, and a potent antitumor effect. However, the anti-neoplastic actions and side effects of angiogenitic inhibitors and cytotoxic agents were clearly different [6,7,14] . Administration of angiogenesis inhibitors such as TNP-470 might keep the tumor and its metastases dormant (rather than killing it), and co-administration of cytotoxic drugs might kill it [5,8,21,22] .…”

Section: Discussionmentioning

confidence: 99%

“…Kato et al [23] reported significant effects of TNP-470 in combination with mitomycin-C, adriamycin, CDDP, and 5-FU in mouse models. The anti-tumor effect of TNP-470 was enhanced by combination chemotherapeutic agents [7,8,14,25,26] . Shishido et al [6] further showed that the effect of TNP-470 in combination with CDDP against pancreatic carcinomas was enhanced.…”

Section: Discussionmentioning

confidence: 99%

“…The anti-neoplastic actions of angiogenic inhibitors and cytotoxic agents are clearly different. Treatment with antiangiogenic agents could interact in a positive way with a variety of anti-cancer therapies, and the anti-metastatic and anti-tumor effects of combination therapy were stronger than those of angiogenic inhibitors alone and cytotoxic agents alone [5][6][7][8] . Therefore, Satoh et al [9] (1998) first proposed the concept of angiocytotoxic therapy.…”

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Antiangiogenic therapy for human pancreatic carcinoma xenografts in nude mice

Jia¹

2004

WJG

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AIM:To investigate the anti-tumor effects of antiangiogenic therapy (a combination of TNP-470, an antiangiogenic compound, with gemcitabine, an antimetabolite) on human pancreatic carcinoma xenografts and its mechanism. METHODS:A surgical orthotopic implantation (SOI) model was established by suturing small pieces of SW1990 pancreatic carcinoma into the tail of pancreas in nude male mice. Mice then received either single therapy (n = 24) or combined therapy (n = 32). Mice receiving single therapy were randomly divided into control group, G100 group receiving 100 mg/kg gemcitabine IP on d 0, 3, 6 and 9 after transplantation, and T30 group receiving 30 mg/kg TNP-470 s.c on alternate days for 8 wk. Mice receiving combined therapy were randomly divided into control group, T15 group, G50 group and combination group (TNP-470 30 mg/kg and gemcitabine 50 mg/kg). Animals were killed 8 wk after transplantation. Transplanted tumors, liver, lymph node and peritoneum were removed. Weight of transplanted tumors, the T/C rate (the rate of mean treated tumor weight to mean control tumor weight), change of body weight, metastasis rate, and 9-wk survival rate were investigated. Tumor samples were taken from the control group, T30 group, G100 group and combination group. PCNA index (PI) and microvessel density (MVD) were investigated by immunohistochemical staining for PCNA and factor VIII, respectively. RESULTS:There was a significant inhibitory effect on primary tumor growth of pancreatic carcinoma in G100 group, compared to T30 group, whereas tumor metastasis was significantly inhibited in T30 group compared to G100 group. There was no significant improvement in survival rate in these two groups. No significant inhibitory effect on tumor growth and metastasis in T15 group and G50 group. However, significant anti-tumor and anti-metastatic effects were observed in the combination group with a significant improvement in survival rate. The inhibitory effect on tumor growth in combination group enhanced 2 times in comparison with G50 group and 5 times in comparison with T15 group. Moreover, 25% of the animals bearing tumors were cured by the combination therapy. The levels of MVD and PI were 14.50±5.93 and 0.41±0.02, 12.38±1.60 and 0.30±0.07, 7.13±2.99 and 0.37±0.03, and 5.21±1.23 and 0.23±0.02 respectively in the control group, G100 group, T30 group and combination group. A significant inhibitory effect on PI level and MVD level was observed in G100 group and T30 group respectively whereas both MVD and PI levels were significantly inhibited in the combination group (P<0.05). CONCLUSION:Antiangiogenic therapy shows significant anti-tumor and anti-metastatic effects, and is helpful to reduce the dosage of cytotoxic drugs and the side effects. These effects are related to the antiangiogenic effect of TNP-470 and cytotoxic effect of gemcitabine. INTRODUCTIONExocrine pancreatic carcinoma is now the fifth leading cause of cancer in the United States, Japan and Europe, with an overall 5-year survival rate of less than 5% [1] . O...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Antiangiogenic therapy for human pancreatic carcinoma xenografts in nude mice

Jia¹

2004

WJG

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“…Experimental protocol The tumor transplantation and evaluation methods have already been reported. 17) Briefly, small pieces of TK-13 tumor tissue (5 mm in diameter and about 100 mg in weight) were resected from subcutaneous tumors in the exponential growth phase, and the pieces were sutured to the wall of the cecum of nude mice with 6-0 Dexon (Davis-Geck, Manati, PR) after removal of the serosa. The mice were divided into 3 groups: a control group (n=17), a UFT group (n=18) and an S-1 group (n=17).…”

Section: Methodsmentioning

confidence: 99%

Therapeutic Effect of 1 M Tegafur‐0.4 M 5‐Chloro‐2,4‐dihydroxypyridine‐1 M Potassium Oxonate (S‐1) on Liver Metastasis of Xenotransplanted Human Colon Carcinoma

Konno

Tanaka

Baba

et al. 1999

Japanese Journal of Cancer Research

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administered orally at an equitoxic dose (S-1, 7.5 mg/kg; UFT, 17.5 mg/kg as FT) for 37 consecutive days beginning 10 days after the transplantation. S-1 showed higher tumor growth inhibition than UFT (P< < < <0.05) and also showed a significant anti-metastatic effect on liver metastasis, while UFT did not. Liver metastasis developed in only 2 of the 17 mice (12%) in the S-1 group, whereas it developed in 9 of the 17 (53%) and 7 of the 18 (39%) in the control and UFT group, respectively. Analysis of AUC (area under the curve) revealed that S-1 yielded higher 5-FU levels in both tumor tissue (1.6 times) and plasma (2.5 times) than UFT. These results suggest that S-1 will show a higher clinical therapeutic effect against human colorectal cancer than UFT.

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“…It is known that tumor expansion with formation of new blood vessels are related to metastasis (Weidner et al, 1991;Weidner et al, 1993;Holash et al, 1999;Hood et al, 2002). Therefore, the use of angiogenic inhibitors in order to reduce tumor metastasis is a promising method for treating tumors (O'Reilly et al, 1994;Konno et al, 1995;Zetter, 1998;Ebos et al, 2009;Pàez-Ribes et al, 2009). Prostate cancer is related to angiogenesis and vascular invasion and thus inhibition of angiogenesis can be used as a method to treat prostate cancers (Weidner et al, 1993;Bagley et al, 2011;Gyftopoulos et al, 2011;Assadian et al, 2012;Lynch et al, 2012;Pande et al, 2012;Pinto et al, 2012).…”

Section: Introductionmentioning

confidence: 99%