1.
Roles and Mechanisms of Human Cathelicidin LL-37 in Cancer.
Chen, X, Zou, X, Qi, G, Tang, Y, Guo, Y, Si, J, Liang, L
Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology. 2018;(3):1060-1073
Abstract
LL-37, the C-terminal peptide of human cathelicidin antimicrobial peptide (CAMP, hCAP18), reportedly increases resistance to microbial invasion and exerts important physiological functions in chemotaxis, promotion of wound closure, and angiogenesis. Accumulating evidence indicates that LL-37 also plays a significant role in human cancer. LL-37 induces tumorigenic effects in cancers of the ovary, lung, breast, prostate, pancreas, as well as in malignant melanoma and skin squamous cell carcinoma. In contrast, LL-37 displays an anti-cancer effect in colon cancer, gastric cancer, hematologic malignancy and oral squamous cell carcinoma. Mechanistically, LL-37-induced activation of membrane receptors and subsequent signaling pathways lead to alteration of cellular functions. Different membrane receptors on various cancer cells appear to be responsible for the tissue-specific effects of LL-37. Meanwhile, the findings that vitamin D-dependent induction of cathelicidin in human macrophages activates the anti-cancer activity of tumor-associated macrophages (TAMs) and enhances antibody-dependent cellular cytotoxicity (ADCC) support critical roles of vitamin D-dependent induction of cathelicidin in cancer progression. This review describes novel advances involving the roles and mechanisms of human cathelicidin LL-37 in cancer.
2.
Diagnostic value of S100P for pancreatic cancer: a meta-analysis.
Hu, H, Zhang, Q, Huang, C, Shen, Y, Chen, X, Shi, X, Tang, W
Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine. 2014;(10):9479-85
Abstract
Pancreatic cancer (PC) is a fatal disease with a high mortality and poor prognosis. PC is the fourth leading cause of cancer death in America, and 80 % of PCs are diagnosed at an unresectable stage. Effective early detection assays are crucial since a successful operation at early stage is the best strategy for this disease. S100 calcium-binding protein P (S100P) has been reported as a predictive diagnostic index for PC and involves in the development of PC. However, the diagnostic accuracy of S100P in detecting PC has never been systematically assessed. The aim of the present study was to evaluate the diagnostic performance of S100P for PC. All relevant original articles about S100P in the diagnosis of PC published up to December 2013 were retrieved. The methodological quality of each study was assessed by QUADAS. The overall diagnostic sensitivity, specificity, diagnostic odds ratio (DOR), with 95 % confidence interval (CI), and area under the receiver operating characteristic curve (AUC) were pooled to evaluate the diagnostic value of S100P for PC using the Meta-DiSc1.4 statistical software. Eight studies met our criteria in the present meta-analysis. The pooled sensitivity, specificity, and DOR calculated by the bivariate random effects model were 0.87 (95 % CI 0.83-0.90), 0.88 (95 % CI 0.82-0.93), and 38.32 (95 % CI 11.22-130.87), respectively. The summary receiver operating characteristic (SROC) curve was located near the desirable left corner and the AUC was 0.9272. The current evidence suggests that S100P plays an important role in the diagnosis of PC with a high sensitivity and specificity. S100P may be regarded as a promising diagnostic marker to PC screening.
3.
The effects of CYP3A4, CYP3A5, ABCB1, ABCC2, ABCG2 and SLCO1B3 single nucleotide polymorphisms on the pharmacokinetics and pharmacodynamics of docetaxel in nasopharyngeal carcinoma patients.
Chew, SC, Singh, O, Chen, X, Ramasamy, RD, Kulkarni, T, Lee, EJ, Tan, EH, Lim, WT, Chowbay, B
Cancer chemotherapy and pharmacology. 2011;(6):1471-8
Abstract
PURPOSE This exploratory study aimed to explain the interindividual variabilities of docetaxel pharmacokinetics and pharmacodynamics in Asian nasopharyngeal carcinoma patients (n = 54) through the genotyping of CYP3A4, CYP3A5, ABCB1, ABCC2, ABCG2 and SLCO1B3 genes. METHODS Docetaxel was administered over 1 h on days 1, 8, and 15 every 28 days at 30 mg/m(2)/dose. Genomic DNA was isolated from peripheral blood and genotyped for the selected polymorphisms in the candidate genes. Docetaxel pharmacokinetic parameters were estimated by non-compartmental modelling. RESULTS Patients homozygous for the variant allele (GG) of SLCO1B3 rs11045585 (IVS12-5676A > G) had significantly higher area under the plasma concentration-time curve of docetaxel (P = 0.026) and lower clearance (P = 0.036) compared to patients with AA/AG genotypes. Patients harbouring the heterozygous genotype (GA + GT + TA) for ABCB1 rs2032582 (2677G > T/A) had the highest percentage decrease in nadir haemoglobin from cycle 1 baseline compared to those with GG/TT genotypes (P = 0.006). Similar trend was observed for ABCB1 rs1045642 (3435C > T) with heterozygotes (CT) having the highest percentage decrease in nadir haemoglobin from cycle 1 baseline compared to those with CC/TT genotypes (P = 0.066). CONCLUSIONS This study suggests that the cooperative influence of functional polymorphisms in SLCO1B3 and ABCB1 genes may be responsible for the interindividual variability in docetaxel disposition in Asian nasopharyngeal cancer patients.