Expressions of HIF-1α and CA9 in breast carcinoma and their relationships with basal-like subtype / 国际肿瘤学杂志

Objective To study the expressions of hypoxia inducible factor-1 α (HIF-1 α) and carbonic anhydrase 9 (CA9) in different molecular subtypes of breast carcinoma and their relationships with basallike subtype.Methods The expressions of HIF-1α and CA9 were detected by immunohistochemistry in five subtypes of breast carcinoma (n =803).The relationships of the expressions of HIF-1α and CA9 with the clinicopathologic parameters of basal-like subtype and with the prognosis of patients were analyzed.Results The positive expression rates of HIF-1α and CA9 protein in breast carcinoma were much higher than those in paratumor breast tissues (43.96％ vs.3.86％,x2 =354.858,P ＜ 0.001;19.80％ vs.4.61％,x2 =86.495,P ＜ 0.001).The positive expression rates of HIF-1α in Luminal A,Luminal B,epidermal growth factor receptor-2 (HER-2) over-expression,basal-like and normal breast-like subtypes were 31.97％,25.00％,56.06％,77.89％ and 55.76％ respectively,and the positive expression rates of CA9 were 7.48％,5.56％,60.61％,40.00％ and 27.88％ respectively,with significant differences (x2 =88.628,P ＜ 0.001;x2 =147.128,P ＜0.001).The positive expression rates of HIF-1α and CA9 in estrogen receptor (ER)-negative breast carcinomas(HER-2 over-expression,basal-like and normal breast-like) were significantly higher than those in ER-positive subtypes (Luminal A and Luminal B,all P ＜ 0.005).There was a significant positive correlation between HIF-1 α and CA9 (C =0.315,P =0.001),and both were correlated with the lymph node metastasis (x2 =4.542,P =0.033;x2 =7.025,P =0.008),pTNM stage (x2 =5.390,P =0.020;x2 =10.179,P =0.001) and poor prognosis (x2 =4.353,P =0.037;x2 =6.056,P =0.014) of basal-like subtype.Conclusion Over-expressions of HIF-1α and CA9 may be related to the ER-negative breast cancer more closely,and both may play important roles in the occurrence and development of basal-like subtype.Overexpressions of HIF-1α and CA9 may suggest the poorer prognosis of patients with basal-like breast carcinoma.

Advances in researches on β-carbonic anhydrases as anti-parasitic drug tar-gets / 中国血吸虫病防治杂志

β?carbonic anhydrases(β?CAs)are ubiquitous metalloenzymes which active site contains a zinc ion(Zn2+),and they could catalyze the hydration of carbon dioxide to bicarbonate and protons efficiently and are involved in many biological pro?cesses,such as respiration,pH and CO2 homeostasis,biosynthetic reactions,virulence regulation and so on,and may play a critical role in the life activity of many organisms which contain these enzymes. β?CAs are widely distributed in fungi,bacteria, algae,plants and a small number of protozoan and metazoan except vertebrates. Therefore,as potential drug targets for design?ing and developing antibacterial and anti?parasitic drugs,β?CAs promise a broad application prospect. This paper focuses on the distribution,physiological function and the progress of researches on β?CAs in parasites and their vectors.

Expression and clinical significance of carbonic anhydrase 1 in different clinical stages of colorectal cancers / 中国医师杂志

Objective To investigate the expression pattern of carbonic anhydrase 1 (CA1) in different clinical stages of color ectal cancers and the correlation between CA1 expression and pathologic characteristics of colorectal cancer.Methods The expression of CA1 in genetic level was detected by real-time quantitative polymerase chain reaction (PCR) and the expression of CA1 in protein level was detected by Western blot and immunohistochemical staining.Results The expression pattern of CA1 in the protein level was very similar to the genetic level.It had a very low expression level in carcinoma tissue,especially at stages Ⅲ and Ⅳ (P ＜0.01),CA1 had significantly lower expression level in the colorectal patients with metastasis (P ＜0.01).CA1 was gradually decreased from well-differentiation tissue to poorly-differentiation tissue with a significant difference between well-differentiated adenocarcinoma and poorly-differentiated adenocarcinoma (P ＜ 0.01).Kaplan-Meier survival analysis showed that the expression of CA1 was extremely related to colorectal carcinoma (CRC) prognosis.The 5-year survival rate was only 8％ in the CA1 negative expression group,and the 5-year survival rate of the patients with CA1 positive expression was 92.86％ (P ＜ 0.01).Conclusions CA1 had the similar expression patterns at genetic and protein levels.In the colorectal cancer tissue,the expression of CA1 was downregulated and even missing.CA1 had significantly lower expression level in the advanced colorectal cancers with metastasis and poorly differentiated colorectal cancer tissues.The patients with lower CA1 expression level had the worse prognosis.

Carbonic Anhydrase IX is Not a Predictor of Outcomes in Non-Metastatic Clear Cell Renal Cell Carcinoma - A Digital Analysis of Tissue Microarray

Introduction The knowledge about the molecular biology of clear cell renal cell carcinoma (ccRCC) is evolving, and Carbonic Anhydrase type IX (CA-IX) has emerged as a potential prognostic marker in this challenging disease. However, most of the literature about CA-IX on ccRCC comes from series on metastatic cancer, with a lack of series on non-metastatic cancer. The objective is to evaluate the expression of CA-IX in a cohort of non-metastatic ccRCC, correlating with 1) overall survival, and 2) with established prognostic parameters (T stage, tumor size, Fuhrman nuclear grade, microvascular invasion and peri-renal fat invasion). Materials and Methods This is a retrospective cohort study. We evaluated 95 patients with non-metastatic clear cell renal cell carcinoma, as to the expression of CA-IX. The analyzed parameters where: overall survival (OS), TNM stage, tumor size (TS), Fuhrman nuclear grade (FNG), microvascular invasion (MVI), peri-renal fat invasion (PFI). We utilized a custom built tissue microarray, and the immunoexpression was digitally quantified using the Photoshop® software. Results: Th e mean follow-up time was 7.9 years (range 1.9 to 19.5 years). The analysis of CA-IX expression against the selected prognostic parameters showed no correlation. The results are as follows: Overall survival (p = 0.790); T stage (p = 0.179); tumor size (p = 0.143); grouped Fuhrman nuclear grade (p = 0.598); microvascular invasion (p = 0.685), and peri-renal fat invasion (p = 0.104). Conclusion Carbonic anhydrase type IX expression does not correlate with overall survival and conventional prognostic parameters in non-metastatic clear cell renal cell carcinoma. .

The expression and clinical significance of Paxillin and CA Ⅸ in the benign and malignant lesions of gallbladder / 中华消化杂志

Objective To study the expression and clinicopathological significance of Paxillin and CAⅨ in the benign and malignant lesions of gallbladder.Methods The surgical resected specimens of 108 cases of gallbladder adenocarcinoma, 46 cases of peritumoral tissue, 15 cases of adenomatous polyp and 35 cases of chronic cholecystitis were routinely made paraffin embedded sections.The expressions of Paxillin and CAⅨ were stained with Envision immunohistochemistry.Results The positive rates of Paxillin and CAⅨ expression was significantly higher in gallbladder adenocarcinoma (60.2% and 49.1%) than those in peritumoral tissues (26.1%, x2 =15.00, P ＜0.01 and 23.9%,x2=8.41,P ＜0.01), adenomatous polyp (20.0%,x2=8.60,P＜0.01 and 20.0%,x2 =4.49,P＜0.05) and chronic cholecystitis(14.3% ,x2 =22.89, P＜0.01 and 11.4%,x2 =15.63,P ＜0.01).All the gallbladder epithelia of the benign cases with Paxillin and CA Ⅸ positive expression showed moderate to severe atypical hyperplasia.The positive expression rates of Paxillin and CA Ⅸ were significanctly lower in the cases of well-differentiated, maximal diameter of mass less than 2 cm, no lymph nodes metastasis and no surrounding tissues invasion than those of the cases with poorly differentiated, maximal diameter of mass over 2 cm, lymph nodes metastasis and surrounding tissues invasion.With Kaplan-Meier analysis, it suggested that the survival period after the surgery in Paxillin and CAⅨ positive expression cases was shorter than that of negative expression cases (x2 = 5.65,P＜0.05,5.65=5.92, P＜0.01).With multivariate Cox regression analysis, it indicated that both Paxillin and CAⅨ positive expression was an important indicator of the poor prognosis in gallbladder adenocarcinoma.Conclusion The expression of Paxillin and CA Ⅸ may be closely related to the carcinogenesis, tumor biological behaviors, and prognosis of gallbladder adenocarcinoma.The positive expression of Paxillin and/or CAⅨ is associated with poor prognosis.