Phase II Study on Javanica Oil Emulsion Injection (Yadanzi^®) Combined with Chemotherapy in Treating Patients with Advanced Lung Adenocarcinoma

Lu, Yan-Yan,Huang, Xin-En,Cao, Jie,Xu, Xia,Wu, Xue-Yan,Liu, Jin,Xiang, Jin,Xu, Lin Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.8

Purpose: To investigate the efficacy and safety of Javanica oil emulsion injection (Yadanzi$^{(R)}$) combined with pemetrexed and platinum (PP) for treating patients with advanced lung cancer. Patients and Methods: From June 2011 to June 2013, we recruited 58 patients with advanced lung cancer, and divided them into two groups. Twenty eight patients received Yadanzi$^{(R)}$ (from ZheJiang Jiuxu Pharmaceutical Co., Ltd.) together with PP chemotherapy (combined group), while the others were given only PP chemotherapy (control group). After two cycles of treatment, efficacy and safety of treatment were evaluated. Results: The overall respnse rate [(CR+PR+SD)/(CR+PR+SD+PD)] of the combined group was higher than that of control group (89.7% vs. 86.2%, p>0.05). Regarding rate of life improvement, it was 82.8% in combined group, and 51.7% in the control group (p<0.05). In terms of side effects, leukopenia in combined group was less frequent than that in control group (p<0.05). More patients in the control group were found to suffer liver toxicity. Conclusions: Javanica oil emulsion injection combined with chemotherapy could be considered as a safe and effective regimen in treating patients with advanced lung adenocarcinoma. It can improve the quality of life and reduce the possibility of leukopenia. Further clinical trials with a large sample size should be conducted to confirm whether addition of Yadanzi$^{(R)}$ to chemotherapy could increase the response rate, reduce toxicity, enhance tolerability and improve quality of life for patients with advanced lung cancer.

Potential Predictors of Sensitivity to Pemetrexed as First-line Chemotherapy for Patients with Advanced Non-Squamous NSCLCs

Lu, Yan-Yan,Huang, Xin-En,Xu, Lin,Liu, De-Gan,Cao, Jie,Wu, Xue-Yan,Liu, Jin,Xiang, Jin Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.3

Background: Pemetrexed (PEM) is effective in first-line treatment for patients with non-squamous non-small cell lung cancer (NSCLC). However there are currently no definitive determinants to certify which patients could benefit from PEM. To improve the efficacy of PEM combined with platinum as first-line therapy for advanced non-squamous NSCLC, we conducted this retrospective study to detect potential determinants of this regimen. Methods: We recruited 109 patients with advanced non-squamous NSCLC who received PEM with a platinum as first-line therapy from June 2006 to February 2013 in Jiangsu Cancer Hospital. Multiple variables (age, sex, smoking, degree of cell differentiation, hemoglobin, platinum drugs combined, positions of metastasis) were selected. Logistic regression analysis was used to analyse relationships between these variables and tumor response. Result: In univariate analysis, we found that age and platinum significantly influenced the results of PEM therapy (P<0.05). In multivariable analysis, no factors were independently significant. Conclusion: Our analysis did not suggest that the age, sex, metastasis of liver or other organs, hemoglobin, smoking history and pathological differentiation are associated with the response of PEM. We should conduct further analyses with larger sample size to reconfirm this issue.

Clinical Observations on Associations Between the UGT1A1 Genotype and Severe Toxicity of Irinotecan

Lu, Yan-Yan,Huang, Xin-En,Wu, Xue-Yan,Cao, Jie,Liu, Jin,Wang, Lin,Xiang, Jin Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.7

Background: Severe toxicity is commonly observed in cancer patients receiving irinotecan (CPT-11) UDPglucuronosyltransferase1A1 (UGT1A1) catalyzes the glucuronidation of the active metabolite SN-38 but the relationship between UGT1A1 and severe toxicity remains unclear. Our study aimed to assess this point to guide clinical use of CPT-11. Materials and Methods: 89 cancer patients with advanced disease received CPT-11-based chemotherapy for at least two cycles. Toxicity, including GI and hematologic toxicity was recorded in detail and UGT1A1 variants were genotyped. Regression analysis was used to analyse relationships between these variables and tumor response. Results: The prevalence of grade III-IV diarrhea was 10.1%, this being more common in patients with the TA 6/7 genotype (5 of 22 patients, 22.7%) (p<0.05). The prevalence of grade III-IV neutropenia was 13.4%and also highest in patients with the TA 6/7 genotype (4 of 22 patients; 18.2%) but without significance (p>0.05). The retreatment total bilirubin levels were significantly higher in TA6/7 patients (mean, $12.75{\mu}mol/L$) with compared to TA6/6 (mean, $9.92{\mu}mol/L$) with p<0.05. Conclusions: Our study support the conclusion that patients with a $UGT1A1^*28$ allele (s) will suffer an increased risk of severe irinotecan-induced diarrhea, whether with mid-or low-dosage. However, the $UGT1A1^*28$ allele (s) did not increase severe neutropenia. Higher serum total bilirubin is an indication that patients UGT1A1 genotype is not wild-type, with significance for clinic usage of CPT-11.

Comparison of Efficacy and Toxicity of First Line Chemotherapy with or without Epirubicin for Patients with Advanced Stage Soft Tissue Sarcoma

Cao, Jie,Huang, Xin-En,Liu, Jin,Wu, Xue-Yan,Lu, Yan-Yan Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.12

Purpose: To compare the safety and efficacy of first-line chemotherapy regimen with or without doxorubicin in treating patients with advanced soft tissue sarcoma (STS). Patients and Methods: We retrospectively analyzed a cohort of 56 patients histologically confirmed with STS who were treated at Jiangsu Cancer Hospital and Research Institute from July 2011 to June 2012.The basic element of first line chemotherapy contained epirubicin in group B and lacked epirubicin in group A. Response was assessed using RECIST criteria. The Kaplan-Meier method was used to estimate progress free survival (PFS). Results: According to RECIST criteria, patients in group treated by chemotherapy without epirubicin, the objective response (OR) ratio was 6.5 % (CR0%+PR6.5%). Disease control rate (DCR=CR+PR+SD) was 25.8% with a median follow-up of 14.6 months, including 2 patients achieving a partial response (PR 6.5%) and a stable response (SD 19.4%) in 6. In group B with epirubicin based regimens, no patient had complete response, PR (28 %) was observed in 7 and SD (24 %) in 6. DCR was observed in 13 patients (52%). By Fisher's exact test, the DCR difference between the two groups was statistically significant (p=0.046). In group A, median PFS was 3.0 months (95%CI:2.1-3.8), compared with 4.0 months (95% CI:3.03-4.97) in group B (p=0.0397 by log-rank test). Epirubicin based chemotherapy and ECOG performance status 0-1 were identified as favorable factors for progression in our cohort of patients. Differences of nonhematologic and hematologic toxicities were not statistically significant between the two groups, and the addition of epirobicin was not associated with cardiac toxicity (p=0.446). Conclusion: Our study demonstrates that epirubicin-based chemotherapy is effective and well tolerated, and is superior to chemotherapy without epirubicin regarding efficacy. Therefore it is recommended that epirubicin-based chemotherapy should be considered as first line for patients with advanced STS.

Phase II Study of Pemetrexed as Second or Third Line Combined Chemotherapy in Patients with Colorectal Cancer

Wu, Xue-Yan,Huang, Xin-En,You, Shan-Xi,Lu, Yan-Yan,Cao, Jie,Liu, Jin,Xiang, Jin Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.3

Purpose: To investigate the safety and efficacy of pemetrexed combined with chemotherapy as second or third line in patients with stage IV colorectal cancer (CRC). Patients and Methods: This trial was conducted to evaluate the effectiveness and safety of pemetrexed given to patients with recurrent or metastatic colorectal carcinoma who previously received 5-FU-based chemotherapy. All patients were required to have a histological diagnosis of colorectal adenocarcinoma with measurable metastatic disease and prior chemotherapy. Patients received pemetrexed at a dose of 500 $mg/m^2$ by 10 minute infusion on day 1, repeated every 21 days. Doses were modified depending on nadir counts. Combined chemotherapy included Oxaliplatin, Irinotecan and cis-platinum. Results: Thirty patients were enrolled and twenty-nine were evaluable for response. One patient did not have repeat radiological testing to determine response because he went off study after only one cycle of treatment for economic reasons. For 29 evaluable patients, 1 partial response, 6 stable disease and 22 progressive disease were recorded. Response rate was 3.45% (1/29). All responses occurred in patients receiving a starting dose of pemetrexed 500 $mg/m^2$. Median time to progression for all eligible patients was 2.5 months. The most common toxicities experienced were mild to moderate fever, hepatic damage, myelosuppression, nausea, vomiting, constipation, abdominal pain, diarrhea, and skin rash. Conclusion: Pemetrexed at 500 $mg/m^2$ given every three weeks combined with chemotherapy is associated with moderate response and good tolerability in patients with stage IV CRC.

Comparison of Serum Tumor Associated Material (TAM) with Conventional Biomarkers in Cancer Patients

Shu, Jian,Li, Cheng-Guang,Liu, Yang-Chen,Yan, Xiao-Chun,Xu, Xu,Huang, Xin-En,Cao, Jie,Li, Ying,Lu, Yan-Yan,Wu, Xue-Yan,Liu, Jin,Xiang, Jin Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.5

Objective: To compare expression level of serum tumor associated materials (TAM) with several conventional serum tumor biomarkers, eg., carcinoembryonic antigen (CEA), carbohydrate antigen19-9 (CA19-9), carbohydrate antigen 15-3 (CA15-3), alpha-fetoprotein(AFP), in selected solid tumors. Methods: Patients diagnosed histologically or cytologically with liver, breast, esophageal, gastric, colorectal or pancreatic cancers were enrolled into this study. After diagnosis, the level of TAM was determined by chemical colorimetry, and levels of conventional tumor markers was measured by chemiluminescence methods. Results: A total of 560 patients were enrolled into this study. No statistically significant difference was detected in TAM and the above mentioned tumor biomarkers in terms of their positivity and negativity ( P>0. 05). Conclusions: Detection of TAM in liver, breast, esophageal, gastric, colorectal, and pancreatic cancer patients demonstrates a good accordance with CEA, CA199, CA153, and AFP, thus suggesting that further study is warranted to verify whether TAM could be a surrogate for these conventional biomarkers.

A NEW CORE – SHELL HYBRID NANOSTRUCTURES OF GOLD NANOROD FOR ENHANCING FLUORESCENCE AND APPLICATION IN DUAL-COLOR IMAGING

LU ZHANG,Peihui Yang,YAN-JIE GUO,JIAN-JUN LUO,GUI-MIN SUN,ZHI-HONG LIANG,YAN-JUAN TANG 성균관대학교(자연과학캠퍼스) 성균나노과학기술원 2014 NANO Vol.9 No.3

A novel core – shell hybrid nanostructure was constructed by employing gold nanorod (AuNR)combined with rhodamine B (RB) as a core and silica as a shell. The poly(sodium 4-styr-enesulfonate) (PSS), a negatively charged polyelectrolyte, played the role of linker to electro-statically trap RB on AuNRs. Due to the °uorescence spectral overlap between RB and AuNRs at560 nm, the red °uorescence and enhanced green °uorescence of the hybrid nanostructures wereobserved obviously, which is capable for dual-color labeling. To reduce toxic side e®ects ofAuNRs, silica was coated on AuNRs as a shell to fabricate the novel core – shell hybrid nano-structure function as a dual-color labeling for cancer-cell imaging. The fabricated compositestructures were characterized by transmission electron microscopy (TEM), absorption spectrum,°uorescence spectrum, zeta potential measurements and laser scanning confocal microscope(LSCM). The experiment results con¯rmed that the obtained hybrid nanostructures providedexcellent photostability, biocompatibility and active surface for further biological functionali-zation. The novel composite structures may have great potential application in cell multicolorlabeling and imaging instead of traditional °uorescent dyes.

Weight Loss Correlates with Macrophage Inhibitory Cytokine-1 Expression and Might Influence Outcome in Patients with Advanced Esophageal Squamous Cell Carcinoma

Lu, Zhi-Hao,Yang, Li,Yu, Jing-Wei,Lu, Ming,Li, Jian,Zhou, Jun,Wang, Xi-Cheng,Gong, Ji-Fang,Gao, Jing,Zhang, Xiao-Tian,Li, Jie,Li, Yan,Shen, Lin Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.15

Background: Weight loss during chemotherapy has not been exclusively investigated. Macrophage inhibitory cytokine-1 (MIC-1) might play a role in its etiology. Here, we investigated the prognostic value of weight loss before chemotherapy and its relationship with MIC-1 concentration and its occurrence during chemotherapy in patients with advanced esophageal squamous cell carcinoma (ESCC). Materials and Methods: We analyzed 157 inoperable locally advanced or metastatic ESCC patients receiving first-line chemotherapy. Serum MIC-1 concentrations were assessed before chemotherapy. Patients were assigned into two groups according to their weight loss before or during chemotherapy:>5% weight loss group and ${\leq}5%$ weight loss group. Results: Patients with weight loss>5% before chemotherapy had shorter progression-free survival period (5.8 months vs. 8.7 months; p=0.027) and overall survival (10.8 months vs. 20.0 months; p=0.010). Patients with weight loss >5% during chemotherapy tended to have shorter progression-free survival (6.0 months vs. 8.1 months; p=0.062) and overall survival (8.6 months vs. 18.0 months; p=0.022), and if weight loss was reversed during chemotherapy, survival rates improved. Furthermore, serum MIC-1 concentration was closely related to weight loss before chemotherapy (p=0.001) Conclusions: Weight loss both before and during chemotherapy predicted poor outcome in advanced ESCC patients, and MIC-1 might be involved in the development of weight loss in such patients.

Lack of Association Between CYP1A1 Polymorphisms and Risk of Bladder Cancer: a Meta-analysis

Lu, Yu,Zhang, Xiao-Lian,Xie, Li,Li, Tai-Jie,He, Yu,Peng, Qi-Liu,Deng, Yan,Wang, Jian,Qin, Xue,Li, Shan Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.9

Background: The effects of CYP1A1 gene polymorphisms on the risk of bladder cancer (BC) remain controversial. We carried out a meta-analysis to clarify the role of CYP1A1 gene polymorphisms in BC. Material and Methods: A comprehensive literature search was conducted up to November 20, 2013. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to estimate the strength of the association. Meta-regression, subgroup analysis, sensitivity analysis and publication bias were also performed. Results: Eight studies involving 1,059 BC cases and 1,061 controls were included. The meta-analysis showed that there was no significant association between the two common mutations of CYP1A1 and BC risk. For the I1e462Val A/G polymorphism with GG vs. AA the OR was 1.47 (95 % CI= 0.70-3.07, P =0.308). For the MspI T/C polymorphism, though a slight trend was found this was not statistically nonsignificant (CC vs.TT, OR = 1.24, 95 % CI= 0.98-1.58, P =0.078). Subgroup analyses by ethnicity also found no obvious association between CYP1A1 and BC risk. Conclusion: The present meta-analysis suggests that CYP1A1 polymorphism is not associated with bladder cancer risk.

Correlation of Adventitial Vasa Vasorum with Intracranial Atherosclerosis: A Postmortem Study

Lu Zheng,Wen Jie Yang,Chun Bo Niu,Hai Lu Zhao,Ka Sing Wong,Thomas Wai Hong Leung,Xiang Yan Chen 대한뇌졸중학회 2018 Journal of stroke Vol.20 No.3

Background and Purpose Vasa vasorum (VV) have been believed to be rare or non-existent in small-caliber intracranial arteries. In a series of human cerebral artery specimens, we identified and examined the distribution of VV in association with co-existing intracranial atherosclerosis. Methods We obtained cerebral artery specimens from 32 consecutive autopsies of subjects aged 45 years or above. We scrutinized middle cerebral artery (MCA), vertebral artery (VA), and basilar artery (BA) for the presence of adventitial VV. We described the distribution of VV, and the characteristics of co-existing atherosclerotic lesions. Results Among 157 intracranial arteries, adventitial VV were present in 74 of the 157 specimens (47%), involving MCA (n=13, 18%), BA (n=14, 19%), and VA (n=47, 64%). Although qualitatively these 74 adventitial VV distributed similarly in arteries with or without atherosclerotic lesions (disease-free arteries n=4/8; arteries of pre-atherosclerosis n=17/42; and arteries of progressive atherosclerosis n=53/107), the presence of adventitial VV in intracranial VA was associated with a heavier plaque load (1.72±1.66 mm2 vs. 0.40±0.32 mm2, P<0.001), severer luminal stenosis (25%±21% vs. 12%±9%, P=0.002), higher rate of concentric lesions (79% vs. 36%, P=0.002), and denser intraplaque calcification (44% vs. 0%, P=0.003). Histologically, intracranial VA with VV had a larger diameter (3.40±0.79 mm vs. 2.34±0.58 mm, P<0.001), thicker arterial wall (0.31±0.13 mm vs. 0.23±0.06 mm, P=0.002), and a larger intima-media (0.19±0.09 mm vs. 0.13± 0.04 mm, P=0.003) than VA without VV. Conclusions Our study demonstrated the distribution of adventitial VV within brain vasculature and association between vertebral VV and progressive atherosclerotic lesions with a heavier plaque load and denser intraplaque calcification.