Partial Least Squares Based Gene Expression Analysis in EBV-Positive and EBV-Negative Posttransplant Lymphoproliferative Disorders

Wu, Sa,Zhang, Xin,Li, Zhi-Ming,Shi, Yan-Xia,Huang, Jia-Jia,Xia, Yi,Yang, Hang,Jiang, Wen-Qi Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.11

Post-transplant lymphoproliferative disorder (PTLD) is a common complication of therapeutic immunosuppression after organ transplantation. Gene expression profile facilitates the identification of biological difference between Epstein-Barr virus (EBV) positive and negative PTLDs. Previous studies mainly implemented variance/regression analysis without considering unaccounted array specific factors. The aim of this study is to investigate the gene expression difference between EBV positive and negative PTLDs through partial least squares (PLS) based analysis. With a microarray data set from the Gene Expression Omnibus database, we performed PLS based analysis. We acquired 1188 differentially expressed genes. Pathway and Gene Ontology enrichment analysis identified significantly over-representation of dysregulated genes in immune response and cancer related biological processes. Network analysis identified three hub genes with degrees higher than 15, including CREBBP, ATXN1, and PML. Proteins encoded by CREBBP and PML have been reported to be interact with EBV before. Our findings shed light on expression distinction of EBV positive and negative PTLDs with the hope to offer theoretical support for future therapeutic study.

A Predictive Model for Evaluating Responsiveness to Pemetrexed Treatment in Patients with Advanced Colorectal Cancer

Wu, Xue-Yan,Huang, Xin-En,Cao, Jie,Shi, Lin,Xu, Xia,Qian, Zhi-Ying Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.14

Purpose: To highlight the potential factors that could predict the response rate of patients with metastatic colorectal cancer (mCRC) treated with pemetrexed combined chemotherapy after first- or second-line chemotherapy using the FOLFOX regimen. Materials and Methods: Between January 2007 and July 2014, 54 patients diagnosed and pathologically-confirmed with advanced colorectal cancer in Jiangsu Cancer Hospital and Research Institute, were enrolled. They received pemetrexed at a dose of $500mg/m^2$ by 10 minute infusion on day 1, repeated every 3 weeks. Doses were modified depending on nadir counts of blood cells. Combined chemotherapeutic agents included irinotecan, lobaplatin, carboplatin, oxaliplatin, gemcitabine, cis-platinum or bevacizumab. Multiple variables (age, sex, hemoglobin, platinum drugs combined, metastasis sites, LDH, ALP, CEA>40 ug/ml) reported earlier were selected. We used logistic regression analysis to evaluate relationships between these and tumor response. Results: On multivariable analysis, we found that age was significant in predicting the responsiveness to pemetrexed (p<0.05) combined with oxaliplatin. We did not find any other factors which were significantly associated with the response rate to chemotherapy with pemetrexed and irinotecan. Conclusions: By multivariate analysis, we found that age had significant impact on the responsiveness of pemetrexed when combined with oxaliplatin. Additional research based on genomic properties of host and tumors are needed to clarify markers for better selection of patients who could benefit from pemetrexed combined chemotherapy.

Fotemustine, Teniposide and Dexamethasone in Treating Patients with CNS Lymphoma

Wu, Jing-Jing,Wang, Xin-Hua,Li, Ling,Li, Xin,Zhang, Lei,Sun, Zhen-Chang,Fu, Xiao-Rui,Ma, Wang,Chang, Yu,Zhang, Xu-Dong,Han, Li-Juan,Zhang, Ming-Zhi Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.11

Purpose: We developed and evaluated a regimen including fotemustine, teniposide and dexamethasone (FTD) for treating patients with central nervous system (CNS) lymphoma based on pharmacokinetic properties of individual agents and in combination. Patients and Methods: In a comparison study, 8 patients with primary CNS lymphoma (PCNSL) and 8 with secondary CNS lymphoma (SCNSL) were treated with FTD (comprising fotemustine 100 mg/m2, 1h infusion, day 1; teniposide 60 mg/m2, >0.5 h infusion, on day 2, 3, 4; dexamethasone 40 mg, 1h infusion, on day 1, 2, 3, 4 and 5; and methotrexate 12 mg, cytosine arabinoside 50 mg plus dexamethasone 5 mg intrathecally, on day 2 and 7). Cycles were repeated every 3 weeks. After response assessment, patients received whole brain radiotherapy. Results: Of the 8 PCNSL patients, 4 (50%) achieved CR and 3 (38%) PR, an overall response rate of 88%. Four patients (50%) were in continuing remission at the end of this study after a median follow-up of 30 months (range 10 to 56 months). Of the 8 SCNSL patients the overall response rate was 63% (CR+PR: 38%+25%). All responses were achievable with predictable toxicity mainly reflecting reversible myelosuppression. Conclusion: This study suggests that FTD could be an effective treatment for CNS lymphoma, and is worthy of further evaluation.

Clinical Application of Endoscopic Inguinal Lymph Node Resection after Lipolysis and Liposuction for Vulvar Cancer

Wu, Qiang,Zhao, Yi-Bing,Sun, Zhi-Hua,Ni, Jing,Wu, Yu-Zhong,Shao, Heng-Hua,Qu, Jun-Wei,Huang, Xin-En Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.12

Aim: To examine lymph nodes obtained after lipolysis and liposuction of subcutaneous fat of the inguinal region of female vulvar cancer patients to explore the feasibility of clinical application. Methods: The field of operation was on the basis of the range of the conventional resection of inguinal lymph nodes. We injected lipolysis liquid fanwise, started liposuction after 15-20 minutes; then the subcutaneous fatty tissue was sucked out clearly by suction tube. We selected the first puncture holes located on 2-3 cm part below anterior superior spine, the others respectively being located 3cm and 6cm below the first for puncturing into the skin, imbedding a trocar to intorduce $CO_2$ gas and the specular body, and excise the lymph nodes by ultrasonic scalpel. The surgical field chamber was set with negative pressure drainage and was pressured with a soft saline bag after surgery. Results: A lacuna emerged from subcutaneous of the inguinal region after lipolysis and liposuction, with a wide fascia easily exposed at the bottom where lymph nodes could be readily excised. The number of lymph nodes of ten patients excised within the inguinal region on each side was 4-18. The excised average number of lymph nodes was 11 when we had mature technology. Conclusion: Most of adipose tissue was removed after lipolysis and liposuction of subcutaneous tissue of inguinal region, so that the included lymph nodes were exposed and easy to excise by endoscope. This surgery avoided the large incision of regular surgery of inguinal region, the results indicating that this approach is feasible and safe for used as an alternative technology.

Leucogen Tablets at 60 mg Three Times per Day are Safe and Effective to Control Febrile Neutropenia

Huang, Xin-En,Cao, Jie,Qian, Zhi-Ying,Xu, Xia,Shi, Lin,Wu, Xue-Yan,Liu, Jin,Wang, Lin Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.19

Purpose: To investigate whether it is safe to use leucogen tablets 60 mg three times per day (180 mg for a day) and whether this regimen could reduce the incidence of febrile neutropenia caused by chemotherapy. Methods: This prospectively designed study focused on the safety and effectiveness of leucogen tablets 60mg three times per day for a group of cancer patients during chemotherapy for mainly lung or gastric cancers. The tablets were administered from 5 days before until the termination of chemotherapy. Neutropenia and other healthcare encounters were defined as events and occurrence was estimated for comparison. Results: We identified 39 patients receiving leucogen tablets 60mg three times per day, including 11 with gastric, 12 with lung and 16 with other sites of cancer. The mean age was 65 (29-75) years and there were 27 male and 12 female patients. The mean duration of leucogen tablets intake was 59 days. Eighteen patients were treated with taxane-based, 4 with irinotecan-based and 17 with other chemotherapy. The incidence of febrile neutropenia was 0%. Twelve patients were found severe neutropenia (grade III/IV), and the duration of severe neutropenia (grade III/IV) was 5 days. Treatment-emergent adverse events were attributable to complications of myelosuppressive chemotherapy or the primary disease (i.e., alopecia, nausea, asthenia, neutropenia, and severe hepatic renal dysfunction). No chemotherapy was delayed and no treatment related death was observed. Conclusions: This study suggested that leucogen tablets 60mg three times per day (180mg for a day) are safe and could be effective for preventing febrile neutropenia in patients with chemotherapy.

A20 ameliorates disc degeneration by suppressing mTOR/BNIP3 axis-mediated mitophagy

Peng Xin,Zhang Cong,Gao Jia-Wei,Wang Feng,Bao Jun-Ping,Zhou Zhi-Min,Sun Rui,Ji Hang-Yu,VLF Cabral,Wu Xiao-Tao 한국유전학회 2023 Genes & Genomics Vol.45 No.5

Background The pathological mechanism of intervertebral disc degeneration (IDD) is an unanswered question that we are committed to exploring. A20 is an anti-inflammatory protein of nucleus pulposus (NP) cells and plays a protective role in intervertebral disc degeneration. Objective This study aims to investigate the molecular mechanism by which A20 attenuates disc degeneration. Methods The proteins of interest were measured by immunoblotting, immunofluorescence, ELISA assay, and immunohistochemical technique to conduct related experiments. Immunofluorescence assays and mitochondrial membrane potential (JC-1) were used to assess mitophagy and mitochondrial fitness, respectively. Results Here, we demonstrated that A20 promoted mitophagy, attenuated pyroptosis, and inhibited the degradation of the extracellular matrix, consequently significantly ameliorating disc degeneration. Mechanistically, A20 reduces pyroptosis and further suppresses cellular mTOR activity. On the one hand, A20-induced mTOR inhibition triggers BNIP3-mediated mitophagy to ensure mitochondrial fitness under LPS stimulation, as a result of mitigating mitochondrial dysfunction induced by LPS. On the other hand, A20-induced mTOR inhibition reduces the loss of mitochondrial membrane potential and the generation of Mitochondrial ROS. Conclusion The study revealed that A20 promotes BNIP3-mediated mitophagy by suppressing mTOR pathway activation against LPS-induced pyroptosis.

SCYL1BP1 has Tumor-suppressive Functions in Human Lung Squamous Carcinoma Cells by Regulating Degradation of MDM2

Yang, Zhi-Ping,Xie, Yong-Hong,Ling, Dan-Yan,Li, Jin-Rui,Jiang, Jin,Fan, Yao-Hua,Zheng, Jia-Lian,Wu, Wan-Xin Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.17

SCY1-like 1-binding protein 1 (SCYL1BP1) is a newly identified transcriptional activator domain containing protein with many unknown biological functions. Recently emerging evidence has revealed that it is a novel regulator of the p53 pathway, which is very important for the development of human cancer. However, the effects of SCYL1BP1 on human lung squamous carcinoma cell biological behavior remain poorly understood. In this study, we present evidence that SCYL1BP1 can promote the degradation of MDM2 protein and further inhibit the G1/S transition of lung squamous carcinoma cell lines. Functional assays found that reintroduction of SCYL1BP1 into lung squamous carcinoma cell lines significantly inhibited cell proliferation, migration, invasion and tumor formation in nude mice, suggesting strong tumor suppressive function of SCYL1BP1 in lung squamous carcinoma. Taken together, our data suggest that the interaction of SCYL1BP1/MDM2 could accelerate MDM2 degradation, and may function as an important tumor suppressor in lung squamous carcinomas.

In Vitro and in Vivo Antitumor Evaluation of Berbamine for Lung Cancer Treatment

Hou, Zhi-Bo,Lu, Kai-Jin,Wu, Xiao-Li,Chen, Cong,Huang, Xin-En,Yin, Hai-Tao Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.4

Purpose: Lung cancer, one of the most frequently diagnosed cancers in the world, is characterized by relatively high morbidity and mortality. Berbamine (BER) has been initially reported to exert anti-proliferative effects against a series of cancers. Methods: In this study the in vitro cytotoxicity of BER was measured by MTT assay. In vivo anti-cancer efficacy of BER was assessed in A549 xenografts. Results: Cytotoxicity tests showed dose-dependent cell growth inhibition effects of BER against A549 cells. Moreover, BER significantly reduced the growth of lung cancer in a dose-dependent manner in nude mice with prolonged survival time. Conclusion: Therefore, BER might be in herbal medicine for cancer therapy and further efforts are needed to explore therapeutic strategies.

Lack of Associations of the COMT Val158Met Polymorphism with Risk of Endometrial and Ovarian Cancer: a Pooled Analysis of Case-control Studies

Liu, Jin-Xin,Luo, Rong-Cheng,Li, Rong,Li, Xia,Guo, Yu-Wu,Ding, Da-Peng,Chen, Yi-Zhi Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.15

This meta-analysis was conducted to examine whether the genotype status of Val158Met polymorphism in catechol-O-methyltransferase (COMT) is associated with endometrial and ovarian cancer risk. Eligible studies were identified by searching several databases for relevant reports published before January 1, 2014. Pooled odds ratios (ORs) were appropriately derived from fixed-effects or random-effects models. In total, 15 studies (1,293 cases and 2,647 controls for ovarian cancer and 2,174 cases and 2,699 controls for endometrial cancer) were included in the present meta-analysis. When all studies were pooled into the meta-analysis, there was no evidence for significant association between COMT Val158Met polymorphism and ovarian cancer risk (Val/Met versus Val/Val: OR=0.91, 95% CI=0.76-1.08; Met/Met versus Val/Val: OR=0.90, 95% CI=0.73-1.10; dominant model: OR=0.90, 95% CI=0.77-1.06; recessive model: OR=0.95, 95% CI=0.80-1.13). Similarly, no associations were found in all comparisons for endometrial cancer (Val/Met versus Val/Val: OR 0.97, 95% CI=0.77-1.21; Met/Met versus Val/Val: OR=1.02, 95% CI=0.73-1.42; dominant model: OR=0.98, 95% CI=0.77-1.25; recessive model: OR=1.02, 95% CI=0.87-1.20). In the subgroup analyses by source of control and ethnicity, no significant associations were found in any subgroup of population. This meta-analysis strongly suggests that COMT Val158Met polymorphism is not associated with increased endometrial and ovarian cancer risk.

Increased brain uptake of venlafaxine loaded solid lipid nanoparticles by overcoming the efflux function and expression of P-gp

Yan Zhou,Xin’an Wu,Guo-Qiang Zhang,Zhi Rao,Yang Yang,Qian Zhou,Hongyan Qin,Yuhui Wei 대한약학회 2015 Archives of Pharmacal Research Vol.38 No.7

Venlafaxine (VLX) could be pumped out of the brain by P-glycoprotein (P-gp). Moreover, the expression of P-gp distributed in blood–brain barrier could be significantly induced by VLX. Thus, P-gp could be considered as the nature barrier for delivering of VLX to the brain. The aim of this study was to investigate whether the efflux function and increased expression of P-gp could be reversed by utilizing solid lipid nanoparticles (SLN). VLX solid lipid nanoparticles (VLX - SLN) were prepared and evaluated. Pharmacokinetics and brain distribution of VLX in different formulations were conducted after oral or intravenous administration. P-gp efflux function to VLX was evaluated by the brain uptake amount of VLX, while P-gp expression was investigated by Western blotting. Results indicated that the entrapment, mean size and zata potential of VLX - SLN was 74.9 ± 3.0 %, 186.3 ± 69.26 nm and -22.8 ± 7.78 mv, respectively. After vein injection of VLX formulations, the brain uptake amount of VLX from VLX - SLN was significantly higher than that of VLX solution, VLX solution with empty SLN (VLX? empty SLN) and VLX solution with Verapamil (VLX ? Ver), respectively. Furthermore, the protein mass of P-gp in VLX - SLN treated group was the lowest among all the investigated groups. These results indicated that SLN could overcome P-gp and achieve brain target by intravenous administration.