Treatment Of Bone Metastatic Cancer Research Articles

A multi-targeted approach to treating bone metastases

The treatment of bone-metastatic cancer now takes advantage of the unique biology of this clinical state. The complex interplay between the cancer cells and the bone microenvironment leads to a host of therapeutic targets, with agents in various stages of clinical use or study. Targets include interactions between the cancer cells and osteoclasts, osteoblasts, endothelial cells, stromal cells, hematopoietic progenitor cells, cells of the immune system, and the bone matrix. Efforts at understanding specific mechanisms of drug resistance in the bone are also ongoing. Successful clinical outcomes will be the result of co-targeting and interrupting the various tumor-supportive elements and cooperating pathways at the level of the tumor cell, the primary and metastatic microenvironments, and systemic cancer effects, leading to a "scaled network disruption" to undermine the disease state.

Therapeutic effect of pamidronate combined with chemotherapy on bone metastases cancer

Objective To study the curative effect and adverse drug reactions of pamidronate combination with chemotherapy in treatment of bone metastatic cancer. Methods 42 cases of cancer patients with bone metastasis are divided into two groups,20 patients in one group are treated with pamidronate only( pamidronate group) ,22 pa-tients in the other group are treated with pamldrunate combination with chemotherapy( combination group). Combined chemotherapy regiments in combination group are:NP regiment in non-small cell lung cancer,CAF regiment in mam-mary carcinoma,FAM regiment in prostate cancer. Results The effective rate of analgesia in pamidronate group is 65% ,combination group is 90.9%. There is statistically significant difference between two groups(X2=4.17 ,P 0.05). Conclusion Pamidronate combination with chemotherapy is an effective curative method for bone metastasis of advanced malignant tumor. Pamidronate only is a satisfactory curative method for advanced malignant tumor patients that can not endure chemotherapy. Key words: Bone neoplasms; Drug therapy, combination; Pamidronate

Efficient delivery of small interfering RNA to bone-metastatic tumors by using atelocollagen in vivo

Silencing of gene expression by small interfering RNAs (siRNAs) is rapidly becoming a powerful tool for genetic analysis and represents a potential strategy for therapeutic product development. However, there are no reports of systemic delivery for siRNAs toward treatment of bone-metastatic cancer. Accordingly, we report here that i.v. injection of GL3 luciferase siRNA complexed with atelocollagen showed effective reduction of luciferase expression from bone-metastatic prostate tumor cells developed in mouse thorax, jaws, and/or legs. We also show that the siRNA/atelocollagen complex can be efficiently delivered to tumors 24 h after injection and can exist intact at least for 3 days. Furthermore, atelocollagen-mediated systemic administration of siRNAs such as enhancer of zeste homolog 2 and phosphoinositide 3'-hydroxykinase p110-alpha-subunit, which were selected as candidate targets for inhibition of bone metastasis, resulted in an efficient inhibition of metastatic tumor growth in bone tissues. In addition, upregulation of serum IL-12 and IFN-alpha levels was not associated with the in vivo administration of the siRNA/atelocollagen complex. Thus, for treatment of bone metastasis of prostate cancer, an atelocollagen-mediated systemic delivery method could be a reliable and safe approach to the achievement of maximal function of siRNA.

199. Efficient Inhibition of Bone Metastasis Via Systemic Delivery of siRNA Using Atelocollagen-Mediated Delivery System

Top of pageAbstract RNA interference has been one of the most powerful tool for genetic analysis, and much research on the development of siRNA for therapeutic use has progressed. Since siRNA shows a very low efficiency in gene silencing in vivo, various delivery methods have been investigated. However, there are no reports of efficient treatment of bone metastatic cancer by a systemic delivery of siRNA. We have demonstrated the excellent properties of an atelocollagen-mediated delivery system for nucleic acid medicines such as plasmids, antisense DNA and siRNA. Atelocollagen has been widely used because of its high biocompatibility and biodegradability. Last year, we reported that atelocollagen forms a complex with siRNA, and intratumor injection of the complex containing siRNA against FGF 4 mRNA inhibits growth of an orthotropically xenografted human nonseminomatous germ cell tumor. In this study, we demonstrated that the delivery system markedly enhanced the efficiency of siRNA in inhibiting bone metastasis through systemic administration. The siRNA/atelocollagen complex was formed by mixing siRNA with atelocollagen. The formation of the complex was confirmed by gel electrophoresis, and the complex can be administrated by conventional methods. To facilitate the detection of metastatic lesions and tumor regression as the effect of the caused by the complex, noninvasive optical imaging technologies and the bioluminescent human prostate carcinoma cell line PC-3M-luc-C6 were employed. An intracardiac injection of PC-3M-luc-C6 induced metastasis to the thorax, jaws and/or legs of mice. Prior to a metastasis inhibition study, we tested whether a systemic administration of the complex induces a gene silencing effect on metastatic sites. When the complex containing siRNA against luciferase mRNA was administered via the tail vein, bioluminescence was inhibited by 80|[ndash]|90% in the entire body including bone metastatic sites. In contrast, treatment with siRNA alone did not changed or slightly suppressed photon emission from tumor cells. The findings indicate that the complex delivered siRNA with high integrity and inhibited gene expression in metastatic sites including the bone. To inhibit bone metastasis, siRNAs against mRNAs related to cell growth were complexed with atelocollagen, and the complexes administered via the tail vein. When atelocollagen alone, siRNA alone or a non specific siRNA/atelocollagen complex was administered, a high metastasis was observed. On the other hand, bioluminescence intensity in mice administered the complexes of siRNA that inhibits cell growth was inhibited by 40|[ndash]|50% in the entire body including the bone. These findings indicate that the atelocollagen-mediated systemic delivery of siRNA could be a novel strategy for the inhibition of bone-metastatic prostate tumor growth. Furthermore, we confirmed that thecomplex did not induce an interferon response. In summary, an atelocollagen-mediated delivery system has great potential in significantly advancing the practical therapeutic applications of gene suppression using siRNAs.