1.Application of precision medicine in non-small cell lung cancer
International Journal of Biomedical Engineering 2015;38(4):247-252
Lung cancer, with growing morbidity and mortality worldwide, is one of the most malignant tumors, representing a significant threat to human health and life.The application of next-generation genomic technologies has offered a more comprehensive look at the mutational landscape across the different subtypes of nonsmall cell lung cancer (NSCLC).A number of recurrent mutations such as TP53, KRAS, and epidermal growth factor receptor (EGFR) have been identified in NSCLC.While targeted therapeutic successes have been demonstrated in the therapeutic targeting of EGFR and ALK, the majority of NSCLC tumors do not harbor these genomic events.This review looks at the current treatment paradigms for lung adenocarcinomas (LAC) and squamous cell carcinomas, examining genomic aberrations that dictate therapy selection, as well as novel therapeutic strategies for tumors harboring mutations in KRAS and TP53 which, to date, have been considered undruggable.A more thorough understanding of the molecular alterations that govern NSCLC tumorigenesis, aided by next-generation sequencing, will lead to targeted therapeutic options expected to dramatically reduce the high mortality observed in lung cancer.
2.Clinical characteristics of patients with primary pulmonary lymphoma
Lanfang LI ; Huaqing WANG ; Qian FAN ; Huilai ZHANG ; Xianming LIU
Chinese Journal of General Practitioners 2011;10(8):577-578
Clinical data of 13 patients with primary pulmonary lymphoma(PPL),treated in Tianjin Medical University Cancer Hospital from January 1999 to December 2009,were retrospectively reviewed.There were 8 patients with mucosa-associated lymphoid tissue(MALT)marginal zone lymphoma,2 patients with diffuse large B cell lymphoma,1 patient with NK/T cell lymphoma,1 patient with nodular sclerosis Hodgkin's lymphoma,and 1 patients with lymphocytic predominance Hodgkin's lymphoma.The main clinical symptoms were cough,fever,night sweat and weight loss.Two patients did not have any symptoms.Pulmonary consolidation shadows and multiple nodules were the main findings of CT scan.An air bronchogram was often seen in the consolidation imaging.The overall 5-year survival rate was 9/13 for all patients;while that was 7/8 for MALT marginal gone lymphoma.
3.Evaluation on case reports of inadvertent intrathecal vincristine administration
Huihui LIU ; Chang XU ; Huilai MA ; Guang ZENG
Chinese Journal of Disease Control & Prevention 2009;0(03):-
Objective To evaluate the reasons for intrathecal administration of vincristine,the characteristics of patients with nerve damage,and the effective rescue measures and outcome prognosis.Methods Electronic literature databases,English and Chinese Paper Documents databases,and Network Engine were searched for Case Reports of inadvertent intrathecal injection of vincristine.SPSS 15.0 was used for statistical analysis.Results Analysis of 32 cases report showed that the intrathecal injection of vincristine in patients had adverse outcome.Of these cases 25 led to death,and survival of cases was associated with lower limb paralysis or quadriplegia.Fatalities appeared due to a progressively ascending myeloencephalopathy.Early recognition and immediate treatment with CSF drainage appeared to be the only intervention that had improved patients' survival.The survival curves of different surgical treatments,whether or not to use folic acid treatment,whether or not to use glutamate treatment,whether or not to use pyridoxinetreatment,was a significant difference.Conclusions Timely ventriculo-lumbar washout,using folic acid treatment and glutamate treatment appear critical.It is difficult to obtain satisfactory clinical outcome,so the key lies in the implementation of effective preventive measures.
4.Study of the expression of Ki-67,p53,bcl-2 related with prognosis of patients with malignant lymphoma after the autologous hematopoietic stem cell transplantation
Xianming LIU ; Huaqing WANG ; Huilai ZHANG ; Lanfang LI ; Zhengzi QIAN ; Xinghai LIU ; Yun HOU ; Xishan HAO
Journal of Leukemia & Lymphoma 2009;18(3):142-145
Objective To evaluate the expression of bcl-2, p53, Ki-67 in malignant lymphoma (ML)and the relationship between the expression of bcl-2, Ki-67, p53 and prognosis for the patients who were given autologous hematopoietic stem cell transplantation (AHSCT). Methods The expression of bcl-2,Ki-67, p53 were measured by immunohistochemistry (IHC) on paraffin-embedded slices in 33 cases of ML who received AHSCT. Survival analysis was done by the Kaplan-Meier method and Log-Rank test.Multivariate analysis was carried out using COX proportional hazard model. Results For patients with ML who received AHSCT, the 3-year disease free survival (DFS) of bcl-2(+) group was 35.71%, while that bcl-2(-) group was 88.89 %. There was significant difference of DFS between the two groups. Meanwhile, for these patients, the 3-year DFS of Ki-67(+) and Ki-67(-) were 43.75 % and 85.71%, respectively (P <0.05).Multivariate analysis showed that the expression of bcl-2 and Ki-67 were the independent prognostic factors.Conclusion The expression of bcl-2 and Ki-67 were closely related with relapse after AHSCT in patients with ML. They were useful molecular makers for predicting the prognosis of patients with ML after AHSCT.
5.Molecular mechanism of synergistic antitumor activity and induced apoptosis of zoledronic acid and paclitaxel
Xia LIU ; Huilai ZHANG ; Shiyong ZHOU ; Zhengzi QIAN ; Xianhuo WANG ; Huaqing WANG
Chinese Journal of Clinical Oncology 2014;(1):60-63
Objective:This study aimed to investigate the inhibitory effect of zoledronic acid (ZOL) alone or the combined treat-ment of ZOL and paclitaxel (PTX) on the cell growth of lung cancer cell line in vitro. Methods:The effects of different concentrations of ZOL alone, 2 nM PTX, and combined treatment of ZOL and PTX on the growth of A-549 cell line were determined using methyl thi-azolyl tetrazolium (MTT) method. The mechanism of the curative effect was analyzed by flow cytometry on the basis of apoptotic rate. AKT, phospho-AKT, ERK, phospho-ERK, and Bcl-2 expressions were determined by western blot analysis. AKT and ERK gene ex-pressions were determined by RT-PCR. Results:MTT results showed that ZOL alone could inhibit the growth of lung cancer cell line A-549 in a dose-dependent manner. The combined therapy of ZOL and PTX could inhibit cell growth. This combined treatment is more effective than the single treatment with either ZOL or PTX alone. The synergistic inhibition rate is dependent on drug sequencing. Fur-thermore, maximum inhibition was induced by sequence order, i.e., initial treatment with PTX and then with ZOL. RT-PCR results dem-onstrated that the mRNA of ERK and AKT of the group treated with PTX and then ZOL were lower than that in other treatment groups. Western blot analysis results demonstrated that the ERK and AKT levels of the treated groups were parallel in the cell line. However, the lowest phospho-ERK, phospho-AKT, and Bcl-2 levels were observed in the PTX then ZOL group. The cell lines treated with PTX alone and ZOL alone ranked second and third among the lowest results, respectively. The highest level was observed in the control group. Conclusion: The combined ZOL and PTX treatment induced the downregulation of phospho-ERK, phospho-AKT, and Bcl-2 protein expressions in RAF/MEK/ERK and PI3K/AKT signaling pathway. This pathway could be one of the synergistic antitumor mechanisms of the two drugs.
6.Clinical efficacy of pegaspargase plus GEMOX regimen for initial treatment of nasal NK/T-cell lymphoma
Shaoping LIANG ; Huaqing WANG ; Huilai ZHANG ; Zhengzi QIAN ; Shiyong ZHOU ; Jing ZHAO ; Xia LIU
Chinese Journal of Clinical Oncology 2014;(19):1225-1228
Objective:To evaluate the efficacy and safety of pegaspargase plus GEMOX (pegaspargase, gemcitabine, oxaliplatin) regimen in the initial treatment of nasal NK/T-cell lymphoma. Methods: Twelve preliminarily diagnosed nasal NK/T-cell lymphoma patients in Tianjin Medical University Cancer Institute and Hospital from June 2011 to March 2012 were analyzed. All patients took the pegaspargase plus GEMOX regimen (gemcitabine 800-1 000 mg/m2 on days 1 and 8, oxaliplatin 130 mg/m2 on day 1, and pegaspargase 2 500 IU/m2 on day 2), every three weeks for one cycle. The efficacy and toxicity of the regimen were evaluated in the follow-up treat-ment. Results:After two cycle treatments, 1 patient dropped out of treatment because of acute pancreatitis;the remaining 11 patients had response, in which 1 achieved complete response , 7 had partial response, 2 had stable disease, and 1 had progressive disease. The objective response rate was 72.7%, and the disease control rate was 90.9%. The 2-year overall survival rate was 90.9%. With median 6-cycle P-GEMOX regimen treatment, 81.8% of 11 patients presented side effects, primarily myelosuppression and hepatic dysfunc-tion. Conclusion:Pegaspargase plus GEMOX regimen showed high efficacy on the initial treatment of nasal NK/T-cell lymphoma pa-tients, but the incidence of adverse effect was still high.
7.Mir-520c-3p targeted GPC3 for hepatocellular carcinoma Huh-7cell proliferation, migration and invasion ability
Zhongkao LIU ; Changjiang LEI ; Zhidong QIU ; Mingyi LI ; Ran LI ; Shiting BAO ; Huilai MIAO
International Journal of Surgery 2013;(4):238-242,封3
Objective To research the effect of mir-520c-3p targeted GPC3 to the hepatocellular carcinoma Huh-7 cell proliferation,migration,and the influence of the attack ability and find new theoretical basis for liver hepatocellular carcinoma clinical treatment.Methods The cells were divided into three groups:not transfection of mir-520c-3p group (cell group),negative control group (Nc group),and transfection of mir-520c-3p group (treat ment group).Then used fluorescence quantitative PCR and Western Blot to detect GPC3mRNA gene and protein expression quantity.Cell proliferation of change was detected by the EDU.Made use of Transwell to detect cell invasion and migration ability of the change.Results Fluorescence quantitative PCR results showed that Cell group,NC group and treatment group were 1.13 ± 0.23,1.28 ± 0.15 and 1.05 ± 0.19 (P > 0.05),mir-520-3p could not reduce the GPC3mRNA; but Western Blot detection results showed that GPC3 protein expression level reduce significantly after transfection mir-520c-3p,Cell,NC and treatment group were 2.16 ± 0.08,1.99 ± 0.04 and 0.499 ± 0.05 (P < 0.01).The EDU detection results showed that hepatocellular carcinoma Huh-7 cell proliferation ability obviously inhibited after transfection mir-520c-3p,Cell group,NC group and treatment group were (90.12 ± 1.93) %,(91.02 ± 0.35) % and (77.73 ± 5.88) % (P < 0.05),and Transwell test found that hepatocellular carcinoma Huh-7cell invasion abilities were restrained,Cell group,NC group and treatment group were 0.071 ±0.008,0.105 ±0.001 and 0.048 ± 0.002 (P < 0.05),in the same the cells' migration abilities were reduced,Cell group,NC group and treatment group were 0.546 ± 0.010,0.328 ± 0.002 and 0.151 ± 0.002 (P <0.01).Conclusions Mir-520c-3p can target GPC3 so that affect hepatocellular carcinoma Huh-7 cell proliferation,invasion and migration abilities.
8.The Relativity Between the Expression of Bcl-2,Ki-67, C-myc and Prognosis of Patients with Malignant Lymphoma
Yanling MA ; Huaqing WANG ; Xianming LIU ; Huilai ZHANG ; Lanfang LI ; Zhengzi QIAN
Tianjin Medical Journal 2009;37(10):832-834,后插1
Objective: To study the relationship between the expressions of Bel -2, Ki -67, C -myc and prognosis in patients given chemotherapy for malignant lymphoma (ML). Methods: The expressions of Bel-2, Ki-67 and C-myc were measured by immunohistochemistry (IHC) in paraffin-embedded samples of 65 ML cases who received chemotherapy. The survival analysis was done by the Kaplan -Meier method and Log -rank test. Results: For patients with non -Hodgkin lymphoma (NHL) who received chemotherapy, the 3-year disease free survival (DFS) was 22.22% in Bcl-2(+) group compared with that of 55.56% in Bcl-2 (-) group. The difference of DFS was significant between the two groups. Meanwhile, for ML patients, the 3-year DFS was 37.50% in Ki-67(+) group, and 61.54% in Ki-67(-) group respectively(P < 0.05). Conclusion: The expressions of Bcl-2 and Ki-67 were closely related with relapse after chemotherapy in patients with ML. They were useful molecular makers for predicting the prognosis in patients with ML after chemotherapy.
9.Survey of different types of field epidemiology training programs in China
Huihui LIU ; Lijie ZHANG ; Guoqing SHI ; Yingxin PEI ; Huilai MA ; Guang ZENG
Chinese Journal of Medical Education Research 2014;13(5):490-493
Objective To understand the current status,type,and effect of training programs conducted by Health Bureau and CDC in China.Methods One person of each province was selected from China field epidemiology training network and designated as contact person who was responsible for collecting information of field practical training lasting for at least 6 months for staff of public health emergency and infectious disease control in each province from October 2001 to October 2010.Questionnaire including basic condition,organization and management,training design,faculty condition,trainee condition and training outputs was designed and filled in by contact person.Results There were 35 training programs covering over 9 provinces in China.The first province and city FETP started in 2004,including Guangdong FETP,Zhejiang FETP,Hangzhou FETP,Ningbo FETP and Guizhou FETP.Thirty-five training programs had 355 mentors,22(6%)were CFETP graduates and 57 (16%)were local FETP graduates.All program funds were paid by local governments.The training programs included two parts,theoretical lectures and field practice,which occupying 10%-20% and 80%-90% of the whole training time,respectively.Among 6 evaluative items including emergency investigation,surveillance analysis,surveillance evaluation,planned investigation,investigation report and paper publication,most programs(50%-94%) had less than average one person per time.Conclusions Field epidemiology training program after several years of development in china achieves the certain scale.Some provincial programs are successful,but the effect and quality of training programs in different areas are uneven.We suggest optimizing of field epidemiology training resources and further expanding China field epidemiology training network.
10.Clinical characteristics and prognostic analysis of primary testicular lymphoma
Cuicui ZHAO ; Huaqing WANG ; Kai FU ; Zhengzi QIAN ; Xianming LIU ; Huilai ZHANG ; Xishan HAO
Chinese Journal of Urology 2010;31(11):777-781
Objective To discuss the clinical features and prognostic factors of primary testicular lymphoma (PTL). Methods A retrospective review was performed based on the clinical records of 33 PTL cases treated at Tianjin Medical University Cancer Hospital from June 1977 to May 2009.Drawing survival curves by Kaplan-Meier method, using Log-rank test to the univariate analysis, and multivariate analysis by COX regression model to evaluate independent prognostic factors. Results The median age of patients was 62 years at presentation(range 33-81 years). Painless testicular swelling was the initial symptom. The majority of histological subtype was B cell lymphoma, 48% of which was diffuse large B-cell non-Hodgkin's lymphoma. By postoperative chemotherapy and/or radiotherapy, 23 patients achieved complete remission and 7 achieved partial remission, with a median follow-up of 23 months (4-231 months). The 5 years and 10 years of overall survival was 39.1% and 19.5%. The effect of patients who received chemotherapy≥4 cycles and B cell lymphoma patients combination with Rituximab were better. In multivariate analysis, Ann Arbor stage, B symptoms, age of patient and number of extranode site were independent prognostic factors of survival. Conclusions Primary non-Hodgkin lymphoma should be treated with multi-modality strategies. Treatment with doxorubicin-based chemotherapy after orchiectomy should be recommended. Ann Arbor stage, B symptoms, age of patient and number of extranode site were independent prognostic factors of survival in PTL.