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.Research progress into Castleman disease
Qingqing CHEN ; Huilai ZHANG ; Huaqing WANG
Chinese Journal of Clinical Oncology 2014;(17):1135-1139
Castleman disease (CD) is a rare polyclonal lymphoproliferative disorder characterized by enlarged hyperplastic lymph node(s). Unicentric Castleman disease (UCD) is an indolent condition often treated by local approaches. On the contrary, pa-tients with multicentric Castleman disease (MCD) have less favorable prognoses and require systemic treatments. Cytotoxic chemother-apy has been widely used to treat MCD with varying degrees of response because of the toxicity risk of the treatment. The pathogenesis remains unknown;however, most pieces of evidence to date point toward human herpes virus 8 (HHV-8) and deregulated overproduc-tion of interleukin (IL-6). Discovery of putative etiologic factors and targets in MCD, particularly HHV-8, CD20, and IL-6, has translat-ed to the use of rituximab, anti-IL-6-based, and antiviral therapy. Good results have been realized through targeting HHV-8 replication, CD20, and IL-6 pathways. In this article, we reviewed the classification, pathogenesis, and current treatments of CD and provided in-sights into future treatment strategies based on disease biology.
3.Mechanisms of histone deacetylase inhibitor in treating T-cell lymphoma and related clinical trials
Huilai ZHANG ; Huijuan LV ; Huaqing WANG
Chinese Journal of Clinical Oncology 2014;(19):1213-1216
Histone deacetylase inhibitors (HDACI) can improve the acetylation status of histone N-terminal, which will exert the effect on treatment. The N-terminal of histone modifications belongs to the category of epigenetics. Epigenetics mainly refers to the study of the heritable variation without change in DNA sequence. HDACI had been paid much attention as a new non-cytotoxic an-ti-cancer targeted drug. Thus, the application of this drug in clinical research is widespread. After the U.S. Food and Drug Administra-tion approved two HDACIs for the treatment of cutaneous T-cell lymphoma, the clinical applications of HDACI in other subtypes of T-cell lymphoma have obtained increasing attention. Studies on the mechanism of HDACI provide the theoretical basis for the applica-tion of HDACIs in other subtypes of T-cell lymphoma. In this article, we reviewed the mechanism and clinical trials of HDACIs on the treatment of T-cell lymphoma.
4.A long-term follow-up study on the treatment of small cell lung cancer using teniposide/carboplatin with etoposide/carboplatin as first-line therapy
Qingqing CHEN ; Huilai ZHANG ; Huaqing WANG
Tianjin Medical Journal 2015;(7):788-791
Objective To compare the efficacy and adverse reaction of teniposide (VM-26) plus carboplatin (TC regimen) and etoposide (VP-16) plus carboplatin (EC regimen) in treatment of newly diagnosed small cell lung cancer (SCLC), and the possible role of VM-26 on prevention of brain metastasis of SCLC. Methods A total of 102 previously untreated SCLC patients without brain metastasis were divided into VP-16 group received EC regimen (n=64) and VM-26 group received TC regimen(n=38). The carboplatin dosages in two groups were calculated by blood concentration-area under the curve(AUC)=5, and intravenous infusion of 1 h for the first day. In VM-26 group, VM-26 70 mg/m2+normal saline 500 mL was intravenously infused of 2 h for 1-3 days. VP-16 100 mg/m2+normal saline 500 mL was given to VP-16 group, 1 h for 1-3 days. Twenty-one day was for 1 treatment cycle. The curative effect, prognosis and adverse reaction were compared between two groups. Results The overall response rates (ORR) and disease control rates (DCR) were 78.9%(30/38) and 97.4%(37/38) in VM-26 group, respectively, and 76.6%(49/64) and 95.3%(61/64) in VP-16 group, respectively, with no significant differences between the two groups (χ2=0.078 and 0.283, P<0.05). The median progression-free survival (PFS) was 10 months (95%CI 7.4-12.6) in VM-26 group and 9 months (95%CI 6.4-11.6) in VP-16 group (χ2=0.029,P=0.866). The median overall survival (OS) was 18 months (95%CI 16.5-19.5) and 16 months (95%CI 9.9-22.1) in VM-26 group and VP-16 group (χ2=0.217,P=0.642), respectively. The survival rates for 1,2 and 3 years were 73.7%, 36.8%and 18.4%in VM-26 group, and 71.9%, 37.5%and 18.8%in VP-16 group, respectively, with no significant differences between the two groups (P>0.05). The brain metastasis rate was significantly higher in VP-16 group [43.8%(28/64)] than that of VP-26 group [21.1%(8/38),χ2=5.379,P=0.02). The adverse reactions were mainly grade 1/2 bone marrow suppression in two groups. Conclusion TC is a highly active regimen for treatment of SCLC. There is no difference in the ef?fectiveness and adverse reactions versus EC. Application of VM-26 can reduce the incidence of brain metastasis in SCLC patients.
5.CTLA-4 and PD-1:the potential immunotherapeutic targets for malignant lymphoma
Xiaohui JIA ; Xianhuo WANG ; Huilai ZHANG
Chinese Journal of Microbiology and Immunology 2016;36(10):783-789
The human immune system has the regulatory functions of eradicating pathogens and limiting excessive inflammation, which protect the surrounding tissue from being damaged. The immune bal-ance of self-limiting is mainly controlled by complex interactions between antigen-presenting cells ( APCs ) and T cells. However, the immune balance is destroyed in cancer, which results in immune evasion and tumor metastasis or promotes the development of drug resistance. Immune checkpoints play critical roles in the immune system. Therefore, blocking tumor immune evasion by targeting the immune checkpoints has be-come a research focus in the treatment of relapsed or refractory malignant tumors. Currently, in the studies of malignant lymphomas, some phaseⅠ/Ⅱclinical studies of immune checkpoint inhibitors have achieved sur-prising results. This review will discuss the regulation and immunotherapy of immune checkpoints in malig-nant lymphomas.
6.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.
7.New therapeutic strategy for peripheral T-cell lymphoma
Huaqing WANG ; Zhengzi QIAN ; Huilai ZHANG ; Zheng SONG
Journal of Leukemia & Lymphoma 2009;18(10):577-581
The incidence rate is high in Asia country, accounting for 15 %-20 % of Non-Hodgkin lymphoma. Every phynotype has different heterogeneity, therapeutic effect and prognosis are also different. There is no standard rigemen for T cell lymphoma at present. CHOP like regimen is commonly used. But therapeutic effect is not as good as we expected. Clinical research shows that dose and intensity regimen, such as m-BACOD,ProMACE-CytaBOM, MACOP-B, do not exhibit survival advantage compared with CHOP regimen. New treatment includes cytotoxic drug, such as gemcitabine. As first line therapy for T cell lymphoma or as salvage therapy for refractory or relapsed T cell lymphoma, the therapeutic effect is good. Gemcitabine based regimen is new for PTCL. Alemtuzumab is a humanized CD52 mono-clonal antibody and is expected as good effect on PTCL therapy. Zanolimumab is a humanized mono-clonal antibody which targets CD4 antigen on T cell. Phase Ⅱclinical research has also got good effect. Denileukin difiitox and Pralatrexate also have good effect on PTCL therapy in clinical researches. Autologous stem cell transplantation(ASCT) is also used in PTCL therapy.
8.A new subtype of lymphoma:double-hit lymphoma with bcl-2 and myc translocation
Huilai ZHANG ; Qin MA ; Kai FU ; Huaqing WANG
Journal of Leukemia & Lymphoma 2012;21(12):712-715
Double-hit lymphoma (DHL) is a kind of disease with features intermediated between diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma (BL),usually accompanied by myc gene breakpoint with other recurrent chromosomal breakpoint and mainly involving myc and bcl-2 translocation.The presentation of this disease is characterized by elevated serum lactate dehydrogenase levels,B symptoms,bone marrow involvement,advanced stage disease,extranodal involvement,and central nervous system involvement.Because its features are similar with DLBCL and BL,it's difficult to distinguish them by pathological diagnosis.At present,the differential diagnosis is mainly by chromosomal analysis (G-banding),FISH and immunohistochemistry.This subtype received a poor response to conventional chemotherapy for DLBCL,and has a poor prognosis.The median survival time is only 0.2-1.5 years.Currently,the main regimens include RCHOP,RICE,RCVD,methotrexate prophylaxis for central nervous system involvement,high-dose chemotherapy and bone marrow transplantation.
9.Changes and significance of serum tumor markers in patients with esophageal squamous cell carcinoma re-section
Huilai LV ; Li ZHANG ; Yong LI ; Shiwang WEN ; Yuefeng ZHANG ; Ziqiang TIAN
The Journal of Practical Medicine 2015;31(23):3900-3903
Objective To explore the dynamic changes of serum HMGB1, CEA and SCC as well as the value in the evaluation of prognosis of patients with esophageal squamous cell carcinoma resection. Methods The dynamic changes in serum levels of HMGB1, CEA and SCC were measured respectively in 100 patients preopera-tively as well as a month after esophagectomy. The relationships between the changes of serum tumor markers and the clinical efficacy were analyzed. Results The 5-years survival rate of the CEA, SCC and HMGB1 negative peo-ple before operation was significantly higher than that of the positive patients (P < 0.05). The 5-years survival rate of those patients with all three markers negative before operation was significantly higher than that of those patients with the three markers positive (P < 0.01). The Median Survive Time of the patients with the levels of all three markers decreased after operation was longer than those with the levels of all the three markers increased (χ2 =6.584, P=0.01). The Median Survive Time of the patients with levels of the three markers decreased by more than 50%was longer than those with the levels decreased by less than 50% (χ2=5.418, P = 0.02). Conclusions The dynamic and combined detections of serum HMGB1, CEA, SCC in patients with esophageal squamous cell carcino-ma resection can effectively evaluate the therapeutic effect and prognosis.
10.Clinical Observation of Taxol Combined with Cisplatin Neoadjuvant Chemotherapy in the Treatment of Esophageal Cancer
Huilai LYU ; Li ZHANG ; Shiwang WEN ; Yuefeng ZHANG ; Yong LI ; Ziqiang TIAN
China Pharmacy 2016;27(18):2500-2502
OBJECTIVE:To observe the clinical efficacy of taxol combined with cisplatin neoadjuvant chemotherapy in the treatment of esophageal cancer and effects on serum tumor markers in patients with esophageal cancer. METHODS:100 patients with esophageal cancer were randomly divided into control group(50 cases) and observation group(50 cases). Observation group was given taxol+Cisplatin injection(TP)neoadjuvant chemotherapy,given 175 mg/m2 taxol by intravenous infusion,d1-5. And ev-ery 5 d was a treatment course,the regimen was adjusted based on patients’efficacy;control group was given conventional sur-gery and TP after surgery,the same usage and dosage as observation group,it lasted for 4 courses. Clinical efficacy,high mobility protein B1(HMGB1),carcinoembryonic antigen (CEA) and squamous cell carcinoma antigen (SCC-Ag) level in 2 groups before and after treatment were observed,objective response rate,disease control rate,the incidence of toxicity and severe toxicity,inci-dence of postoperative complications and survival rate of postoperative 1,3 and 5 years were recorded. RESULTS:After treatment, objective response rate in observation group was significantly higher than control group,HMGB1,CEA and SCC-Ag levels were significantly lower than before and control group,HMGB1 and CEA levels in control group were significantly lower than before, the differences were statistically significant(P<0.05);there were no significant differences in the disease control rate,chemothera-py-related toxicity,severe toxicity,incidence of postoperative complications,survival rate of postoperative 1,3 and 5 years and the median survival time between 2 groups(P>0.05). CONCLUSIONS:Taxol combined with cisplatin neoadjuvant chemotherapy can significantly improve the efficacy of patients with esophageal cancer and reduce the levels of cancer-related indicators,with good safety.