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OBJECTIVE：To provide reference for further improving the establishment of drug registration applicant compliance management organizations in China. METHODS ：Through introducing and analyzing the establishment ，responsibility configuration and operation mechanism of drug registration applicant compliance management organizations in the United States ，the suggestions were put forward for improving the establishment of drug registration applicant compliance management institutions in China. RESULTS & CONCLUSIONS ：There were two levels of compliance management organizations for drug registration applicant in the United States ；at Office of the Commissioner of FDA level ，the Compliance Policy Council was responsible for ensuring consistency in the implementation of all compliance policies in the FDA regulated area ；at the level of Center for Drug Evalution and Research （CDER）and Office of Regulatory Affairs （ORA），the compliance management function was mainly undertaken by Office of New Drugs （OND），Office of Generic Drugs （OGD），Office of Compliance （OC） and Office of Communication （OCOMM）under CDER ，as well as Office of Policy and Risk Management （OPRM），OC，Office of Bioresearch Monitoring Operations（OBIMO）and Office of Pharmaceuticl Quality Operations （OPQO）under ORA ，which were responsible for developing compliance documents and procedures ，carrying out compliance education ，compliance guidance ，compliance inspection and punishment for violations. Before submission stage of drug registration application ，the compliance education function of OC and the compliance guidance function of OND/OGD played an important role ；in the application submission stage ，OND/OGD was responsible for the compliance review of application materials ；in the stage of reviewing the application materials ，OND/OGD and OC of CDER ensured drug compliance through collaboration with OC ，OBIMO and OPQO of ORA. The establishment of drug registration compliance management institutions in China was still in the preliminary exploration stage. It is suggested that China can learn from the relevant experience of the United States ，establish a multi-level or ganization structure ，set up an independent compliance education department ， and strengthen thecooperation between evaluation department and compliance inspection department ，and to improve the level of compliance management of drug registration applicants in China.
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Objective To examine the effects of genetic polymorphisms in GSTM1, GSTT1 and GSTP1 (rs1695) genes on hematologic toxicities of breast cancer patients receiving Anthracycline/Paclitaxel- based chemotherapy. Methods Multiply PCR technique and High Resolution Melting method were used to examine these 3 genes polymorphsim in female breast cancers (n=252). Results The GSTP1(rs1695) AG/GG genotype was a risk factor forⅢ-Ⅳdegree of neu-trophil toxicity when patients received Paclitaxel-based chemotherapy and Anthracycline-Paclitaxel-based chemotherapy (OR=6.111, 95%CI 1.526-24.469, P0.05);There was no statistic difference onⅢ-Ⅳdegree hematologic toxicities rates between GSTM1(+) and GSTM1(-), GSTT1(+) and GSTT1(-), GSTP1AA and GSTP1AG/GG patients after they receiced Anthracycline-based chemotherapy (P>0.05). Conclusion The genetic polymorphisms in GSTP1(rs1695) can be used as a gene marker for forecasting the chemotherapy, inducing neutrope-nia toxicities in breast cancer patients receiving Paclitaxel-based chemotherapy.
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Objective To study the role of expressions of vascular endothelial growth factor C (VEGF-C), vascular endothelial growth factor receptor-3 (VEGFR-3) and lymphatic vessel hyaluronan receptor-1(LYVE-1) on the lymphangio-genesis and prognosis in gastric cancer. Methods The tissue microarray technology was used to detect the expressions of VEGF-C, VEGFR-3 and LYVE-1 in 125 gastric cancer specimens, 96 adjacent normal tissues and 20 benign gastric lesion samples. The lymphatic vessel density (LVD) marked by Podoplanin was detected as well. Results The positive rates of VEGF-C, VEGFR-3 and LYVE-1 in gastric cancer tissues were 62.4%, 56.0%and 58.4%, which were significantly higher than those in adjacent normal tissues (10.4%,12.5%and 9.4%) and benign gastric lesion tissues (20%, 30%and 25%, P<0.05). The LVD score was significantly higher in gastric intra-tumoral and peri-tumoral samples (2.98±0.81 and 4.22±1.09) than that in adjacent normal tissues or benign gastric lesion samples (1.82±0.63 or 0.89±0.45, P<0.01). The LVD score was significantly higher in peri-tumoral samples than that of intra-tumoral samples (P<0.01). There was a positive relationship between expression levels of VEGF-C,VEGFR-3 and LYVE-1 with LVD (P<0.05). The positive expressions of the three indexes were the risk factors of lymph node metastasis and distant metastasis (P<0.05). There was a significantly longer 5-year survival rate in patients with negative expression of the three indexes (P<0.05). Conclusion VEGF-C, VEGFR-3 and LYVE-1 proteins were positively highly expressed in gastric cancer tissues, which were risk factors affecting the progno-sis of gastric cancer. The expression levels of the three indexes can be used to predict the prognosis and lymphangiogenesis of gastric cancer.
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<p><b>OBJECTIVE</b>To study the expression of angiotensin-2 (Ang-2), Tie-2 and vascular endothelial growth factor receptor-2 (VEGFR-2) in colorectal cancer and analyze their relationship with the occurrence, recurrence, metastasis, angiogenesis and prognosis of colorectal cancer.</p><p><b>METHODS</b>Immunohistochemistry with SP method was used to detect the expressions of Ang-2, Tie-2 and VEGFR-2 in 118 colorectal cancer, 40 adjacent normal tissue and 40 benign colorectal lesion specimens.</p><p><b>RESULTS</b>The positivity rates of Ang-2, Tie-2 and VEGFR-2 in colorectal cancer tissue were 74.58%, 69.49%, and 61.02%, respectively, significantly higher than those in the adjacent normal tissues (25.00%, 17.50%, and 17.50%, P<0.05) and benign colorectal lesion tissues (35.00%, 32.50%, and 32.50%, P<0.05). The rates of two or three coexpression were significantly higher than that of a single expression in the cancer tissues (61.02% vs 15.25%). The microvascular density (MVD) of colorectal cancer tissues was 31.43∓10.50, significantly higher than that of the adjacent normal tissues (10.61∓3.76) and benign colorectal lesions (16.89∓3.83) (P<0.05). The expressions of Ang-2, Tie-2, and VEGFR-2 were positively correlated with carcinoembryonic antigen (CEA) and MVD (P<0.05). The expression of Ang-2, but not Tie-2 and VEGFR-2, was positively correlated with CA199. Ang-2, Tie-2, and VEGFR-2 expressions showed significant differences between cases with tumor recurrence/metastasis and those without 5 years after radical mastectomy, and were all positively correlated with the 5-year survival rates (P<0.05).</p><p><b>CONCLUSION</b>Ang-2, Tie-2 and VEGFR-2 are involved in the development, invasion, metastasis, and prognosis of colorectal cancer, and play important roles in the angiogenesis of the tumors.</p>