Three-year Follow-up on the Safety and Effectiveness of Rituximab Plus Chemotherapy as First-Line Treatment of Diffuse Large B-Cell Lymphoma and Follicular Lymphoma in Real-World Clinical Settings in China: A Prospective, Multicenter, Noninterventional Study / 中华医学杂志(英文版)

Background@#Prospective real-life data on the safety and effectiveness of rituximab in Chinese patients with diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL) are limited. This real-world study aimed to evaluate long-term safety and effectiveness outcomes of rituximab plus chemotherapy (R-chemo) as first-line treatment in Chinese patients with DLBCL or FL. Hepatitis B virus (HBV) reactivation management was also investigated.@*Methods@#A prospective, multicenter, single-arm, noninterventional study of previously untreated CD20-positive DLBCL or FL patients receiving first-line R-chemo treatment at 24 centers in China was conducted between January 17, 2011 and October 31, 2016. Enrolled patients underwent safety and effectiveness assessments after the last rituximab dose and were followed up for 3 years. Effectiveness endpoints included progression-free survival (PFS) and overall survival (OS). Safety endpoints were adverse events (AEs), serious AEs, drug-related AEs, and AEs of special interest. We also reported data on the incidence of HBV reactivation.@*Results@#In total, 283 previously untreated CD20-positive DLBCL and 31 FL patients from 24 centers were enrolled. Three-year PFS was 59% (95% confidence interval [CI]: 50-67%) for DLBCL patients and 46% (95% CI: 20-69%) for FL patients. For DLBCL patients, multivariate analyses showed that PFS was not associated with international prognostic index, tumor maximum diameter, HBV infection status, or number of rituximab treatment cycles, and OS was only associated with age >60 years (P < 0.05). R-chemo was well tolerated. The incidence of HBV reactivation in hepatitis B surface antigen (HBsAg)-positive and HBsAg-negative/hepatitis B core antibody-positive patients was 13% (3/24) and 4% (3/69), respectively.@*Conclusions@#R-chemo is effective and safe in real-world clinical practice as first-line treatment for DLBCL and FL in China, and that HBV reactivation during R-chemo is manageable with preventive measures and treatment.@*Trial Registration@#ClinicalTrials.gov, NCT01340443; https://clinicaltrials.gov/ct2/show/NCT01340443.

Expression and significance of HER-2/neu mRNA and RECK mRNA in breast carcinoma tissue / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To investigate the expression of HER-2/neu mRNA and RECK mRNA in breast carcinoma tissue and relationship with progression of breast carcinoma.</p><p><b>METHODS</b>92 cases of breast carcinoma tissue and homologous paraneoplastic breast tissue were selected, expressive level of HER-2/neu mRNA and RECK mRNA were detected with RT-PCR, expressive difference of HER-2/neu mRNA and RECK mRNA were contrasted between breast carcinoma tissue and homologous paraneoplastic breast tissue, along with different TNM stage breast carcinoma tissue and differentiate breast carcinoma.</p><p><b>RESULTS</b>The level of HER-2/neu mRNA was higher and RECK mRNA was lower in breast carcinoma tissue than homologous paraneoplastic breast tissue, the expressive level of HER-2/neu mRNA and RECK mRNA was remarkably different along with different TNM stage breast carcinoma tissue and differentiate breast carcinoma, there was a negative correlation between expressive level of HER-2/neu mRNA and RECK mRNA in breast carcinoma tissue.</p><p><b>CONCLUSIONS</b>Expression of HER-2/neu mRNA and RECK mRNA was abnormal in breast carcinoma tissue, HER-2/neu mRNA and RECK mRNA regulate each other and mutual participate occurrence and progression of breast carcinoma.</p>

Association of polymorphisms of cytosine arabinoside-metabolizing enzyme gene with therapeutic efficacy for acute myeloid leukemia / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The cytosine arabinoside (Ara-C)-based chemotherapy is the major remedial measure for acute myeloid leukemia (AML). Deoxycytidine kinase (DCK) and cytidine deaminase (CDA) are the key enzymes in the metabolism of Ara-C. Many single nucleotide polymorphisms (SNPs) and haplotypes of DCK and CDA, which contribute to susceptibility to Ara-C, have been identified in Africans and Europeans. However, there has been no report about the relation among three SNPs in DCK (rs115543896, rs72552079, and rs111454937) and two SNPs in CDA (rs2072671 and rs60369023), and their clinical response to Ara-C for a Chinese population. In this study, we aimed to investigate whether these five SNPs are associated with the therapeutic outcomes of Ara-C-based chemotherapy regimens in patients with AML.</p><p><b>METHODS</b>A total of 151 Chinese patients with AML were enrolled in our study. SNPs genotyping were performed using the MassARRAY system by means of the matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF-MS) method.</p><p><b>RESULTS</b>The results illustrated that DCKrs111454937 AA genotype was more frequent in patients with higher platelet count, and A allele frequency was significantly higher in the group £40 years, lower white blood cell (WBC) count patients group and the group with platelet counts > 60'10(9)/L. Meanwhile, both DCKrs72552079 TC (OR = 1.225, 95%CI = 1.225 - 9.851, P = 0.0192) and CDArs60369023 GA (OR = 9.851, 95%CI = 1.31 - 77.93, P = 0.0263) significantly improved Ara-C-based chemotherapy response. While DCKrs11554389 AA (OR = 0.147, 95%CI = 0.027 - 0.801, P = 0.0267) was associated with the decrease of Ara-C-based chemotherapy response.</p><p><b>CONCLUSION</b>It is evident that the DCK and CDA polymorphisms might be the important markers for the AML patients' therapy outcomes in a Chinese population.</p>

Polymorphisms of dihydropyrimidine dehydrogenase gene and clinical outcomes of gastric cancer patients treated with fluorouracil-based adjuvant chemotherapy in Chinese population / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Dihydropyrimidine dehydrogenase (DPD), a key enzyme involved in the catabolism of 5-fluorouracil (5-FU), is the attractive candidate for pharmacogenetic research on efficacies and toxicities of 5-FU. The aim of this study is to explore the association between polymorphisms of dihydropyrimidine dehydrogenase gene (DPYD) and clinical outcomes of gastric cancer patients treated with fluorouracil-based adjuvant chemotherapy in the Chinese population.</p><p><b>METHODS</b>Three hundred and sixty-two patients with gastric cancer in the Chinese population were treated with fluorouracil-based adjuvant chemotherapy. The single nucleotide polymorphic genotypes of DPYD were determined by matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF-MS) using DNA samples isolated from peripheral blood collected before treatment.</p><p><b>RESULTS</b>The average response rate for chemotherapy was 46.7%. A significantly different distribution of the rs1801159 (c2=8.76, P=0.012) genotypes was observed. Homozygous genotype rs1801159A/A was over-represented in responsive patients. Conversely, carriers of the rs1801159A/G genotype were prevalent in non-responsive patients. In the haplotype association analysis, there was significant difference in global haplotype distribution between the groups (c2=3.96, P=0.0465).</p><p><b>CONCLUSIONS</b>These results suggest that polymorphisms of rs1801159 in DPYD may be used as valuable predictors of the response to fluorouracil-based chemotherapy for gastric cancer patients in the Chinese population. Well-designed, comprehensive, and prospective studies on determining these polymorphisms of DPYD as predictive markers for gastric cancer in response to fluorouracil-based therapies are warranted.</p>

Choledochal cysts with malignancy in adult: a retrospective study with an experience of twenty-two years

To study the diagnosis, therapy, precaution, and prognosis after surgical treatments of malignant changes that occurred in adult choledochal cysts. We analysed retrospectively the clinicopathologic data, the ways of operative treatment and the survival time of patients with malignancy in 74 cases of adult choledochal cysts in our hospital from 1986 to 2008. Among the 74 patients, 9 cases [3 males and 6 females] had carcinomas arising from choledochal cysts at the mean age of 51.6 +/- 16.4 years [range: 22 to 72 years] with the prevalence of 12.2% [9/74], which was significant difference comparing with no malignant change groups [P=0.0037]. The prevalence of malignancy for different groups were closely related to the age increased [r=0.363, p=0.011]: 3.4% for 16-30 group [1/29], 8.7% for 31-45 group [2/23], 15.4% for 46-60 group [2/13], and 44.4% for 61-75 group [4/9], respectively. Surgical treatments included cysts excision with Roux-en-Y hepaticojejunostomy in three patients, cysts excision with cholangiojejunostomy in two patients, partial cyst excision with left lobectomy and Roux-en-Y hepaticojejunostomy, pancreatoduodenectomy, chemotherapy with implantable drug delivery system via hepatic artery and portal vein, and choledochotomy with T-tube drainage and metastatic lymph node biopsy in one patient, respectively. The survival time was from three months to 66 months with the mean survival of 19.1 +/- 18.6 months. Choledochal cyst is a premalignant lesion and the incidence of malignancy increases remarkably with the increase in age. Patients require close monitoring so that recurrent carcinoma of the remnant bile duct can be identified as early as possible

Expression of MT1-MMP and RECK protein in human gastric carcinoma / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To examine the expression of membrane-type-1 matrix metalloproteinase (MT1-MMP) and reversion-inducing cysteine-rich protein with Kazal motifs (RECK) in gastric carcinoma, and investigate its clinical significance, at the same time analyze the correlation between MT1-MMP and RECK expression.</p><p><b>METHODS</b>MT1-MMP and RECK expression in surgically resected tissue samples of gastric carcinoma was examined by immunohistochemical method (two-step method) , and its correlation with clinicopathological factors was analyzed.</p><p><b>RESULTS</b>Among the 44 gastric carcinoma samples, 37 (84.1%) were stained positive for MT1-MMP, and 31 (70.5%) for RECK. The expression of MT1-MMP was much higher in poorly differentiated gastric carcinoma samples than moderately and well-differentiated samples (P = 0.015). The expression level of MT1-MMP was associated with invasive depth of tumor cells (P = 0.007), but no difference between sex and lymph node metastasis. On the contrary, the well-differentiated samples showed higher expression of RECK than poorly and moderately differentiated gastric carcinoma samples (P = 0.006). The expression level of RECK did not correlate with sex, lymph node metastasis and invasive depth of tumor cells. RECK expression showed no relation to MT1-MMP expression in the gastric carcinoma.</p><p><b>CONCLUSION</b>Overexpression of MT1-MMP in gastric carcinoma may play an important role during tumor differentiation and metastasis, the RECK protein may have positive effects on the tumor differentiation.</p>

XPC Lys939Gln polymorphism is associated with the decreased response to platinum based chemotherapy in advanced non-small-cell lung cancer / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Platinum-based chemotherapeutics are the most common regimens for advanced non-small-cell lung cancer (NSCLC) patients, and genetic factors are thought to represent important determinants of drug efficacy. We prospectively assessed the status of the XPC Ala499Val and Lys939Gln gene polymorphisms and investigated whether these SNPs can predict the response to cisplatin/carboplatin-based regimens in advanced NSCLC patients in a Chinese population.</p><p><b>METHODS</b>The treatment outcomes of 96 advanced NSCLC patients who were treated with platinum-based chemotherapy were evaluated. The polymorphic status of xeroderma pigmentosum group C (XPC) gene was genotyped by the 3-D polyacrylamide gel-based DNA microarray method.</p><p><b>RESULTS</b>The distributions of XPC Lys939Gln genotypes differed significantly between the response group (complete + partial responses) and the non-response group (stable + progressive disease; P = 0.022). The heterozygous A/C genotype carriers had a poorer response rate than the wild A/A genotype carriers in stage III (OR, 0.074; 95%CI, 0.008 - 0.704; P = 0.023). The XPC Ala499Val polymorphisms were not associated with response to platinum-based chemotherapy.</p><p><b>CONCLUSION</b>Polymorphisms of the XPC gene, Lys939Gln, may be a predictive marker of treatment response for advanced NSCLC patients in stage III.</p>

Detection of single nucleotide polymorphisms of Jak2 gene in multiple myeloma by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry / 中国实验血液学杂志

This study was purposed to investigate the practicality of matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) for detection of single nucleotide polymorphisms (SNP) on jak2 gene in multiple myeloma (MM) cells. The DNA fragment containing 2 SNPs of jak2 (C428T and C643T) was amplified using PCR and was purified. The purified product was used as the template for primer extension (PEX). The small products of allele-specific reaction were purified, the SNPs on jak2 gene of 5 patients with MM and 5 healthy persons were detected by MALDI-TOF MS. The results showed that the distribution of genotype C428T and C643T was not different between MM patients and healthy persons, both of which are homozygous T/T. In conclusion, the method based on MALDI-TOF MS and PEX technique for detecting SNP in jak2 gene is rapid, accurate and reliable method, and can be used in clinical practice.

Phase III clinical study of zoledronic acid in the treatment of pain induced by bone metastasis from solid tumor or multiple myeloma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of zoledronic acid in the treatment of bone pain in patients with bone metastasis from solid tumor or multiple myeloma.</p><p><b>METHODS</b>A randomized, double-blind, double-simulated and multi-center phase III clinical trail with pamidronate as control was conducted. Patients with moderate to severe bone pain (VAS > 50 mm) induced by solid tumor or multiple myeloma were randomized to receive intravenous zoledronic acid 4 mg or pamidronate 90 mg. Then the change of VAS and urinary NTX/Cr and CTX/Cr were observed in two groups.</p><p><b>RESULTS</b>From July 2005 to September 2006, 228 patients with bone pain induced by bone metastasis from 15 cancer centers were randomize into two groups: 116 patients in zoledronic acid group and 112 patients in pamidronate group. The VAS value was decreased gradually after treatment in these two groups. Significant improvement in bone pain after treatment were observed both in zoledronic acid group and the control group when compared with baseline VAS on D8 (-11.77% vs. -10.87%), D15 (-24.60% vs. -21.06%) and D28 (-32.37% vs. -31.26%) (P< or =0.0001), but no significant difference existed between two groups (P =0.6587). Compared with baseline, urine NTX/Cr and CTX/Cr level were decreased rapidly after treatment in both groups, the nadir was on D8, the median decreased on D28, which was -36.9% vs. -32.1% for NTX/Cr (P = 0.7922) and -63.2% vs. -47.9% for CTX/Cr (P =0.834). The frequently observed adverse events were pyrexia (19.0% vs. 31.3%), vomiting (6.0% vs. 8.9%), nausea (4.3% vs. 4.5%), fatigue (3.4% vs. 2.7%) and constipation (2.6% vs. 1.8%) in the two groups. Compared with baseline, the serum creatinine level was not significantly increased throughout the study.</p><p><b>CONCLUSION</b>Intravenous injection of 4 mg zoledronic acid can significantly reduce bone pain and bone resorption marker in urine in the Chinese patients with bone metastasis from solid tumor or multiple myeloma, which is tolerable and also comparable to pamidronate in the efficacy and safety.</p>

Chronomodulated chemotherapy of oxaliplatin, 5-fluorouracil and folinic acid for advanced gastric cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>The combination of oxaliplatin (L-OHP), 5-fluorouracil (5-Fu) and folinic acid (FA), being one of the effective regimens for advanced gastric cancer, is used in form of chronomodulated chemotherapy for advanced gastric cancer to investigate its efficacy and safety.</p><p><b>METHODS</b>Twenty-six patients received a 4-day chronomodulated infusion of L-OHP, 5-Fu and FA. L-OHP (25 mg.m(-2).d(-1)) infused from 10:00 am to 22:00 pm, and followed by 5-Fu (600 mg.m(-2).d(-1)) and FA (300 mg.m(-2).d(-1)) from 22:00 pm to 10:00 am for 4 days using a multichannel programmable pump, every 2 weeks as an cycle for at least 2 cycles.</p><p><b>RESULTS</b>Twenty-six patients with previously untreated advanced gastric cancer were eligible. Two complete and 13 partial remissions were observed with an overall response rate of 57.7%. Stable disease was observed in 6 patients (23.1%) and progressive disease in five (19.2%). Four of these patients underwent surgery. The median remission time was 3.5 months and time to tumor progression (TTP) was 4.5 months. The median overall survival time was 8 months. A total of 80 cycles were given without any grade 4 toxicity observed, but grade 3 thrombocytopenia (1.3%) and mucositis (1.3%) in one patient, two grade 3 neutropenia (2.5%) and nausea/vomiting (2.5%) in 2.</p><p><b>CONCLUSION</b>Chronomodulated intravenous chemotherapy of oxaliplatin, 5-fluorouracil and folinic acid is effective and safe in the treatment of advanced gastric cancer.</p>

Polymorphism of methylenetetrahydrofolate reductase and sensitivity of stomach cancer to fluoropyrimidine-based chemotherapy / 中华流行病学杂志

<p><b>OBJECTIVE</b>To investigate the relationship between polymorphisms of the methylenetetrahydrofolate reductase (MTHFR) C677T or A1298C and the response to fluoropyrimidine (5-FU)-based chemotherapy in advanced stomach cancer (SC).</p><p><b>METHODS</b>75 cases with advanced SC were analyzed. All patients were treated with 5-FU-based chemotherapy and DNA of peripheral blood leukocytes was obtained before therapy. MTHFR genotypes were detected by PCR-RFLP method.</p><p><b>RESULTS</b>(1) Of all the cases, the frequencies of MTHFR C677T C/C, C/T and T/T genotype were 32.0%, 44.0% and 24.0%, while the frequencies of MTHFR A1298C A/A, A/C and C/C genotype were 69.3%, 29.3% and 1.3%, respectively. The overal response rate to 5-FU-based chemotherapy was 29.3%. (2) The response rate to therapy among MTHFR C677T T/T genotype patients (83.3%) was significantly higher than the C677T C/T genotype (15.2%, chi(2) = 22.27, P = 0.000) or the C677T C/C genotype (8.3%, chi(2) = 23.44, P = 0.000). As compared with patients with C677T C allele, patients with C677T T/T genotype had a 7.64-fold sensitivity to 5-FU-based chemotherapy (adjusted for sex, age, prior adjuvant therapy and chemotherapy program, 95% CI: 3.14 - 18.62). The response rate to therapy among patients with MTHFR A1298C A/A genotype (36.5%) was significantly higher than patients with A1298C C allele (13.0%, chi(2) = 4.19, P = 0.041, adjusted OR = 3.75, 95% CI: 0.94 - 14.87). The response rate to therapy among patients with MTHFR C677T T/T and A1298C A/A genotypes (86.7%) was significantly higher than other groups of C677T and A1298C genotypes (15.0%, Fisher exact: P = 0.000, adjusted OR = 6.57, 95% CI: 2.8 - 15.6). (3) The incidence rates of nausea/vomiting in MTHFR C677T T/T, C/T or A1298C A/A genotypes were significantly higher than other genotypes, but the incidence rates of other treatment-related adverse reaction in MTHFR C677T or A1298C genotypes were not significantly different.</p><p><b>CONCLUSION</b>These results in the present study suggested that the polymorphisms of MTHFR were associated with clinical response to 5-FU-based chemotherapy, suggesting that MTHFR genotypes could identify advanced SC patients that would be responsive to 5-FU-based chemotherapy.</p>