Anti-KDR monoclonal antibody

Introduction: Shoulder pain and disability are well-documented sequelae of breast cancer treatment. Angiogenesis signaling may have a role in the development of shoulder pain or shoulder disability in breast cancer survivors. The aim of this study was to determine if polymorphisms in angiogenesis-related genes are associated with shoulder pain or disability following breast cancer treatment. Participants and methods: A cross-sectional study was conducted on 220 South African breast cancer survivors. The study aimed to evaluate associations between shoulder pain/disability and seven single nucleotide polymorphisms (SNPs) within five angiogenesis-associated genes: KDR (rs2305948 C> T; rs7667298 C> T), NOS3 (rs1549758 C> T), MMP2 (rs708269 A> T), THBS2 (rs9766678 A> G) and TIMP3 (rs5754312 T> A; rs715572 G> A). In addition, associations between shoulder pain/disability and inferred haplotypes for KDR and TIMP3 SNPs were evaluated. Participants were grouped into no-low and moderate-high shoulder pain/disability based on total pain/disability scores: <= 30 and > 30, respectively using the shoulder pain and disability index (SPADI). Results: No independent associations with shoulder pain/disability categories were found for all SNPs. However, 1 inferred haplotype (KDR "TT") differed significantly (P=0.014) between the shoulder disability categories. After adjusting for participants' age, the differences in KDR inferred haplotype frequencies between shoulder disability categories became non-significant (P=0.052). Conclusion: Our findings provide a preliminary suggestion of a possible association between polymorphisms in genes involved in angiogenesis and the presence of moderate-high shoulder disability among South African breast cancer survivors. A larger prospective cohort study is currently being conducted by our group.

The aim of this study was to investigate the role of kinase-insert domain-containing receptor (KDR) in intrauterine adhesions (IUA) and its mechanism. The Case group consisted of 92 patients diagnosed with IUA, and the Control group included 86 patients with uterine septum who had normal endometrium verified with an uteroscope. In addition, 50 rats were randomly assigned into Control, Sham, Model, NC-siRNA, and KDR-siRNA groups. Rats in the Model, NC-siRNA, and KDR-siRNA groups were induced by uterine curettage and lipopolysaccharide (LPS) treatment to establish the IUA model. Then, immunohistochemistry was applied for detection of VEGF and KDR expression, HE staining was used for observation of the endometrial morphology and gland counting, Masson staining for measurement of the degree of endometrial fibrosis, and qRT-PCR and western blot for the expression of KDR, VEGF, MMP-9, as well as TGF-beta 1/Smads pathway-related proteins. Compared with the Control group, the mRNA and protein expressions of KDR were significantly higher in IUA endometrial tissues, and the expression of KDR was positively correlated to the severity of IUA. In addition, the injection of si-KDR increased the number of endometrial glands, reduced the area of fibrosis, inhibited mRNA and protein expression of KDR and VEGF, up-regulated the expression of MMP-9 and Smad7, and decreased the expression level of TGF-beta 1, p-Smad2, p-Smad3, and Smad4 in rats with IUA. Highly-expressed KDR was related to patients' severity of IUA, and silencing KDR may prevent the occurrence and development of IUA via TGF-beta 1/Smads signaling pathway and up-regulating the expression of MMP-9.