肿瘤分子靶向药物作用机制研究

目的:分子靶向治疗与传统化疗的作用机制和副反应不同,是针对肿瘤特殊的分子靶点而起到个体化治疗的作用,对正常组织的毒副反应轻微.由此应运而生的抗体药物独树一帜,对其研究和评价日趋活跃,本文总结其作用优势和临床评价.方法:查阅本院2009年7-12月份临床上分别应用过2种药物的病例,逐一核查分析患者的出院诊断与适应证的相符性.结果及结论:分子和抗体药物疗效确切、特异性强、不良反应和耐药性小,无疑是药学研究领域中的巨大突破,成为当今抗肿瘤药研发的重要方向.

AIM To study the relationship among typing of Traditional Chinese Medicine (TCM) and Helicobacterpylori infection, expression of oncogene and tumor suppresser genes in gastric cancer and precancerouslessions.METHODS According to TCM typing, 120 patients with chronic superficial gastritis, intestinal metaplasia,atypical hyperplasia and gastric cancer were divided into 4 groups: 21 patients with coexistence of cold andheat syndrome (group R), 22 patients with in coordination between the liver and the spleen (group U), 29patients with deficiency of the spleen-yin (group I) and 48 patients with insufficiency of the spleen-yang(group H). Protein expression of c-myc, p21 and p53 were detected immunohistochemically, and Hp wereconfirmed by modified Giemsa method.RESULTS The Hp infection of the group H was significantly higher (72.9%) than that of group R(38.1%, P<0.01) and group U (40.9%, P<0.01). Expression of c-myc, p21 and p53 were significantlyrelated to Hp infection and severity of gastric mucosa lesions (group H>group I>group U>group R).CONCLUSION Hp infection, expression of oncogene and tumor suppresser genes were related to TCMtyping. These parameters were helpful in identification of symptoms and signs and TCM differentiationdiagnosis.

AIM To study the effect of a wide range of concentration of arsenic trioxide on human hepatoma cell lineBEL-7402 and its mechanism.METHODS The BEL-7402 cells were treated with arsenic trioxide (a final concentration of 0.5, 1 and2 μmol/L, respectively) in various durations or for 4 successive days. The cell growth and proliferation wereobserved by cell counting and cell-growth curve. Morphologic changes were studied under electronmicroscopy. Flow cytometry was used to assay cell-DNA distribution and the protein expression of Bcl-2 andBax was detected by immunocytochemical method.RESULTS The cell growth was significantly inhibited by the different concentrations of arsenic trioxide asrevealed by cell counting and cell-growth curve. Arsenic trioxide treatment at 0.5, 1 and 2 μmol/L, resultedin a sub-G1 cell peak. The decreased G0/G1 phase cell and the increased percentage of S phase cell were observed by flow cytometer, suggesting that the inhibiting effect of arsernic trioxide on BEL-7402 cell lay inG0/G1 phase cell. Apoptotis-related morphology, such as intact cell membrane, nucleic condensation,apoptotic body formation, can be seen under the electron microscopy. High protein expression level of Bcl-2and Bax was detected in 1 and 2 μmol/L arsenic trioxide-treated cells, but that of Bax was more significant.Arsenic trioxide treatment at 0.5 μmol/L resulted in higher expression level of Bcl-2 and lower expressionlevel of Bax compared with control (P1<0.01, P2<0.01).CONCLUSION Arsenic trioxide not only inhibited the proliferation but also induced apoptosis of humanhepatoma cell line BEL-7402. The induced-apoptosis effect of 1 and 2 μmol/L arsenic trioxide was relative tothe expression level of Bcl-2 and Bax.

INTRODUCTION According to the therapeutic effect and strategy of antisense RNA for hepatocellular carcinoma (HCC), we have specifically synthesized partial cDNA of human insulin-like growth factor Ⅱ (IGFⅡ ) and constructed IGF-Ⅱ cDNA antisense eukaryotic expression vector. The constructed vector was introduced into hepatoma cell line SMMC-7721 to block the intrinsic IGF- Ⅱexpression. The biological behavior changes of hepatoma cells were observed. All these would provide scientific basis for IGF- Ⅱ antisense RNA in the treatment of HCC.

Objective To detect the cell viability and the expressions of stem cell surface markers after chemotherapeutic drug treatment. Methods We observed the cytotoxic effects of three chemotherapeutic agents [ epirubicin ( Epi ) , fluorouracil ( 5-FU ) and cyclophosphamide ( Cyc ) ] in three cell lines, and the cell viabilities after removed these chemotherapeutic agents. Expressions of stem cell surface markers CD44, CD24, CD90, CD14 and aldehyde dehydrogenase1(ALDH1) in breast cancer cells were analyzed by real-time PCR. The post hoc analysis (Tukey’s tests) in conjunction with one-way ANOVA was used for statistical analysis. Results The initial cytotoxic efficacy was most notable. After the treatment of the same therapeutic agents, cell viability was decreased by 64. 8% 35. 14%, 32. 25% in BT-483 cells, 66. 4%, 22. 94% and 45. 88% in MDA-MB-231 cells, 97. 1%, 99. 5% and 76. 4% in MCF cells. The difference was significant compared with that before treatment ( P=0. 000 ) . However, the inhibitory effects were diminished after chemotherapeutic agent withdrawal. Cell viabilities were increased to 167. 9%, 212. 04% and 188. 66% in MDA-MB-231 cells at 48 h after withdrawal. At 72 h after withdrawal, cell viability was increased with a significant difference in three cell lines (all P values=0. 000). Expressions of CD44 and ALDH1 were most prevalent for MDA-MB-231, BT-483 and MCF-7 cells. ALDH1 mRNA level was significant higher in BT-483 ( HER-2 overexpression cell line) than MDA-MB-231 ( triple negative cell line ) ( P = 0. 012 ) . CD14 mRNA level in MCF-7 cells were significantly lower than that in MDA-MB-231 and BT-483 (P=0. 003, 0. 001). BT-483 showed significantly higher level of CD44 than MDA-MB-231 and MCF-7 cell line (P= 0.013, 0.020), and no significant difference was detected between MDA-MB-231 and MCF-7 breast cancer cells ( P=0. 955 ) . CD90 mRNA expressions were detected in MDA-MB-231 cells and MCF-7 cells, but not in BT-483 cells. Conclusion Some malignant cells could survive in vitro and begin to proliferate again between cycles of chemotherapy.

To investigate the effect of early rehabilitation on neurofunctional outcome after surgery in chil-dren with spinal tumors, this study reviewed the medical charts and radiographic records of 70 pediatric patients (1-17 years old) who received spinal tumor surgical removal. The peddiatric patients received rahabilitation treatment at 4 (range, 2-7) days after surgery for 10 (range, 7-23) days. Results from the Modiifed McCormick Scale, Functional Independence Measure for Chil-dren, American Spinal Injury Association Impairment Scale and Karnofsky Performance Status Scale demonstrated that the sensory function, motor function and activity of daily living of pedi-atric children who received early rehabilitation were signiifcantly improved. Results also showed that tumor setting and level localization as well as patients’s clinical symptoms have no inlfuences on neurofunctional outcomes.

重组人红细胞生成素在肿瘤相关贫血中的应用

Recombinant human erythropoietin(rhEPO) is safe and effective in treating cancer related anemia and solid tumors in children through promoting recovery of hematopoietic function of bone marrow and replacing renal endogenous EPO.rhEPO can significantly elevate serum Hb levle and reduce transfusion dependancy in anemiac patients.Some studies showed rhEPO is especially effective for lymphoma and myeloma patients with lower concentration of serum EPO.EPO levle after treatment and dissolubilitive transferrin receptor 2 weeks after treatment are indexes for effectiveness of rhEPO.

骶骨肿瘤切除后腰骶关节稳定性重建中 USS钉棒系统的应用

Objective To introduce one operation method applied with USS (universal spine system) screw rods system for the reconstruction of the stability of the lumbar sacrum after resection of sacrum tumor and discuss indications and feasibility of the operation method.Methods 5 patients with sacrum tumor had accepted the clinical treatment of USS.Resect the sacrum tumor,insert pedicle screw into the normal pedicles (L3 or L4 or L5)above the region of laminectomy routinely,fix lower screw in the iliac plane,put metal rods,plant bone and put transverse links. Results There was no recurrence of sacrum tumor by MRI examination after 1～ 12 months follow up.The preoperative pain of lumbar- sacrum joint and roots of the spinal nerves relieved significantly.The patients turned to normal weight loading and movement.There were no fractures of the screw and rods and motion of the screw.X- ray examination hasn't found increase of screw passage,pelvic decrease, and L5 sinking.Conclusion The operation method applied with USS screw- rods system for the reconstruction of the stability of the lumbar- sacrum can reduce postoperative pain,promote early postoperative activity,and prevent pathologic fracture and paraplegia.

低功率毫米波对肿瘤患者红细胞、淋巴细胞免疫粘附功能的影响及相互作用

Objective To study the effects of low intensity millimeter wave(MMW) irradiation on the immune adhesion function of erythrocytes and lymphocytes in tumor patients.Methods MMW(36 GHz,0.73- 1.46 mW/cm2) was used to irradiate the vein blood from tumor patients in irradiation group for 30 minutes.Control group received false irradiation using the same method.Then test tumor RBC C3b receptor rosettes rate(RCR),tumor RBC rosette rate(TRR) and tumor lmphocyte rosette rate(TLR).Result In irradiation group,the RBC C3b TRR and TLR were higher than control group's(P< 0.01).Conclusion Low intensity MMW irradiation can improve the immune adhesion function of erythrocytes and lymphocytes in tumor patients.

Background:Despite numerous previous studies, the consideration of tumor location as a prognostic factor in resectable non–small cell lung cancer (NSCLC) remains controversial. The present study analyzed the association between tumor location and clinical outcome in patients with resectable NSCLC who had undergone lobectomy with systematic lymphadenectomy and who had presented with varying nodal statuses.
Methods:The data from a cohort of 627 eligible patients treated in Sun Yat?sen University Cancer Center between January 2000 and December 2008 were retrospectively collected, and the nodal statuses of patients with different tumor locations were compared. Cox proportional hazards regression model was used to determine the independent factors related to cancer?speciifc survival (CSS).
Results:Multivariate analysis demonstrated that left lower lobe (LLL) tumors [hazard ratio (HR): 1.465, 95% conif?dence interval (CI) 1.090–1.969,P= 0.011], lymph node metastasis (HR: 2.742, 95% CI 2.145–3.507,P < 0.001), and a tumor size of >4cm (HR: 1.474, 95% CI 1.151–1.888,P= 0.002) were three independent prognosticators in patients with resectable NSCLC. However, LLL tumors were associated only with CSS in node?positive patients (HR: 1.528, 95%CI 1.015–2.301,P= 0.042), and a tumor size of >4cm was the only independent risk predictor in the node?negative subgroup (HR: 1.889, 95% CI 1.324–2.696,P < 0.001).
Conclusions:Tumor location is related to the long?term CSS of NSCLC patients with lymph node metastasis. LLL tumors may be upstaged in node?positive patients to facilitate an optimal treatment strategy.

氯离子通道蝎毒素在肿瘤影像诊断及靶向治疗中的应用研究进展

Precisely locating tumors always proves to be difficult. To find a molecule that can specifically bind to tumor cells is the key. Recently, chlorotoxin (CTX) has been proved to be able to bind to many kinds of tumor cells. The CTX receptor on the cell surface has been demonstrated to be matrix metalloproteinase-2 (MMP-2). Many researchers have combined CTX with other molecules, including 131I, Cy5.5, iron oxide nanoparticles coated by polyethylene glycol (NP-PEG), and so on, and thus synthesized various types of probes that can be detected by y-camera, single photon emission computed tomography (SPECT) or magnetic resonance imaging (MRI). With these methods, the binding degree of CTX could be assessed. These studies demonstrated that CTX has a highly specific binding ability, high stability, and security. CTX could also inhibit or kill the tumor cells. A nonviral nanovector has been developed for gene therapy. As a result, it gradually develops into a new method of diagnosis and targeted therapy of tumors. This article reviews the current progress on CTX including the origin, chemical construction, the mechanism of binding with tumor cells, and the application to tumor imaging diagnosis and therapy.