Angiogenesis as a Target for Breast Cancer Therapy

Angiogenesis, the development of new bloodvessels, is crucial for the growth of both primarytumors and metastases beyond a minimal size and thevasculature of tumors facilitates their metastaticspread. Inhibition of angiogenesis is thus seen as apotentially useful approach to anti-metastasis therapy,and is an area of active research and development. Herewe discuss this therapeutic approach in the context of breast cancer. An overview of thecontribution of angiogenesis to tumor development isprovided and current treatment options for breast cancerare briefly summarized. Assessment of angiogenesis inprimary breast tumors has been shown to provideindependent prognostic information. There areopportunities for the application of anti-angiogenesistherapeutic strategies in the treatment of breastcancer. Clinical trial design must take into account the uniqueproperties of anti-angiogenic agents to fully assesstheir potential clinical benefit.     

Amphiregulin as a Novel Target for Breast Cancer Therapy

Amphiregulin, an EGF family growth factor, binds and activates the epidermal growth factor receptor (EGFR or ErbB1). Activation of the EGFR by amphiregulin can occur through autocrine, paracrine and juxtacrine mechanisms. Amphiregulin plays a role in several biological processes including nerve regeneration, blastocyst implantation, and bone formation. Amphiregulin also plays an important role in mammary duct formation as well as the outgrowth and branching of several other human tissues such as the lung, kidney and prostate. This effect is most likely due to the induction of genes involved in invasion and migration such as cytokines and matrix metalloproteases. Clinical studies have suggested that amphiregulin also plays a role in human breast cancer progression and its expression has been associated with aggressive disease. Therefore, amphiregulin may be a novel and effective target for the treatment of breast cancer and could represent an alternative to targeting the EGFR.     

The ErbB2 Signaling Network as a Target for Breast Cancer Therapy

Overexpression of the ErbB2/Her2 receptor tyrosine kinase in breast cancers is associated with the most aggressive tumors. Experimental studies have revealed that ErbB2 shows many features of a therapeutic target: ErbB2 is able to confer many of the characteristics of a cancerous cell, including uncontrolled proliferation, resistance to apoptosis and increased motility; ErbB2 overexpression is specific to tumor cells; as a cell surface-associated protein, it is easily accessible to drugs and as a kinase it is amenable to targeted inhibition by small molecules. Recent clinical results demonstrate the efficacy of ErbB2-targeting therapy and promise an expanding use of ErbB2-targeting drugs for breast cancer treatment. However, as only a fraction of patients responds successfully to therapy and risks of recurrence are still high, further investigation is required for an improved understanding of the complex network of signaling pathways underlying ErbB2-driven cancer progression.     

The Potential of Osteopontin as a Therapeutic Target for Human Colorectal Cancer

Objective  

Osteopontin (OPN), a phosphorylated glycoprotein, is involved in tumor progression and metastasis. Previously, we have reported that high OPN mRNA expression level possessed clinicopathological or prognostic significance in human colorectal cancer (CRC). The aim of this study is to investigate whether OPN can serve as a novel molecular target for CRC therapy.     

Mammary Gland Involution as an Immunotherapeutic Target for Postpartum Breast Cancer

Postpartum mammary gland involution has been identified as tumor-promotional and is proposed to contribute to the increased rates of metastasis and poor survival observed in postpartum breast cancer patients. In rodent models, the involuting mammary gland microenvironment is sufficient to induce enhanced tumor cell growth, local invasion, and metastasis. Postpartum involution shares many attributes with wound healing, including upregulation of genes involved in immune responsiveness and infiltration of tissue by immune cells. In rodent models, treatment with non-steroidal anti-inflammatory drugs (NSAIDs) ameliorates the tumor-promotional effects of involution, consistent with the immune milieu of the involuting gland contributing to tumor promotion. Currently, immunotherapy is being investigated as a means of breast cancer treatment with the purpose of identifying ways to enhance anti-tumor immune responses. Here we review evidence for postpartum mammary gland involution being a uniquely defined ‘hot-spot’ of pro-tumorigenic immune cell infiltration, and propose that immunotherapy should be explored for prevention and treatment of breast cancers that arise in this environment.     

乳腺癌临床治疗策略的研究进展

一个多世纪以来 ,随着医学科学的进步 ,临床医生对乳腺癌的认识经历了几次转变 ,相应的治疗策略亦发生了重大变化。乳腺癌的每一项重大治疗策略的改变都体现了肿瘤基础和临床研究的重大成果 ,不但改变了人们对肿瘤生物学行为的认识 ,而且明显改善了乳腺癌的治疗效果。了解乳腺癌临床治疗策略的发展过程 ,有助于对乳腺癌治疗方法的正确、合理选择 ,减少盲目性 ,提高治疗水平。早期 ,对乳腺癌临床治疗以手术为主 ,效果不佳 ,术后复发率高达 80 %以上 ,而 3年生存率仅为5 %。现代乳腺癌临床治疗策略的第一次重大改变是 19世纪后期基于病理解剖…     

LFA-1 (CD11a) as a Therapeutic Target

Leukocyte function associated antigen-1 (LFA-1) was one of the earliest of cell-surface molecules identified by monoclonal antibodies generated against leukocyte immunogens. This integrin heterodimer is perhaps best known as a classic adhesion molecule facilitating the interaction between T cells and antigen-presenting cells. However, varied studies indicate that LFA-1 has multi-faceted roles in the immune response including adhesion, activation and trafficking of leukocyte populations. While there has been long-standing interest in LFA-1 as a therapeutic target for regulating immunity, anti-LFA-1 therapy is still not a first-line indication for any clinical condition. Antagonism of LFA-1 with monoclonal antibodies, either alone or in combination with other agents, can result in regulatory tolerance in vivo. Furthermore, new generation humanized anti-LFA-1 monoclonal antibodies (Efalizumab) show at least modest promise for continued application in clinical trials. Thus, anti-LFA-1 forms a potential, but still largely unexploited, immunotherapy which may find its greatest application as an agent which augments other therapies.     

Msi-1 is a Predictor of Survival and a Novel Therapeutic Target in Colon Cancer

Background  

Musashi1 (Msi-1), a neural RNA-binding protein, plays an important role in regulating cell differentiation in precursor cells. Recently, aberrant expression of Msi-1 has been detected in several malignancies. However, its role in the progression of colon cancer is largely unknown.     

早期乳腺癌保乳手术疗效分析

目的探讨早期乳腺癌保乳综合治疗的疗效。方法行保留乳房的肿瘤切除及腋窝淋巴结清扫术52例,术后给予放化疗和内分泌治疗。结果平均随访56个月,无局部复发病例,3年和5年生存率分别为96.2%和92.3%,远隔脏器转移率为3.8%。结论早期乳腺癌采用保乳综合疗法,可以达到与根治术相似的治疗效果,且提高了患者生存质量,可作为首选治疗方法。