近年来,转移性肾癌的治疗方式从细胞因子药物的治疗,到现在的针对血管生成、哺乳动物的雷帕霉素途径、免疫应答的药物的应用发生了巨大的变化.尽管耐药仍然是一个巨大的挑战,但通过对这些药物的应用及药物联合应用,转移性肾癌的治疗疗效得到大大的提高.目前新的治疗方法正在迅速发展,治疗前景一片大好.

[目的]研究c-Met抑制剂PHA665752联合5氟尿嘧啶(5-fluorouracil,5-Fu)对人结肠癌细胞SW620生长的抑制作用及机制.[方法]选取48只4周龄的雄性裸鼠皮下接种人结肠癌细胞SW620,建立裸鼠移植瘤模型,随机分为对照组(2.5％二甲亚砜稀释液隔日用药)、5-Fu组(40mg/kg 5-Fu每隔3日给药)、PHA组(25mg/kg PHA665752隔日给药)、5-Fu+PHA组(40mg/kg 5-Fu每隔3日给药+25mg/kg PHA665752隔日给药)各12只.免疫组织化学SP法检测瘤体组织内的E-cadherin和Ki-67蛋白表达情况,TUNEL法检测细胞凋亡情况.[结果]治疗结束时,5-Fu组、PHA组、5-Fu+PHA组3组裸鼠的体重和瘤体体积均明显低于对照组(P＜0.05),且5-Fu+PHA组裸鼠的瘤体体积显著低于5-Fu组、PHA组(P＜0.05).5-Fu组、PHA组、5-Fu+PHA组3组裸鼠的E-cadherin蛋白OD值显著高于对照组(P＜0.05);5-Fu+PHA组裸鼠的E-cadherin蛋白OD值显著高于5-Fu组、PHA组(P＜0.05);5-Fu组、PHA组、5-Fu+PHA组3组裸鼠的Ki-67蛋白OD值显著低于对照组(P＜0.05);5-Fu+PHA组裸鼠的Ki-67蛋白OD值显著低于5-Fu组、PHA组(P＜0.05);5-Fu组、PHA组、5-Fu+PHA组3组裸鼠的凋亡指数(apoptotic index,AI)显著高于对照组(P＜0.05);5-Fu+PHA组裸鼠的AI值显著高于5-Fu组、PHA组(P＜0.05).[结论]c-Met抑制剂PHA665752联合5-Fu对人结肠癌细胞SW620生长的抑制有协同作用,其机制可能与上调E-cadherin、下调Ki-67表达有关.

Objective To study the clinical efficacy and safety of icotinib in treating non-small cell lung cancer. Methods 62 cases of patients with stage Ⅲ or Ⅳ NSCLC were randomly divided into the treatment group and the control group, 31 cases in each group. The control group was given docetaxel or pemetrexed, the treatment group was given oral Icotinib. The medication stopped when patients de-veloped to PD or cannot tolerate. Results The total remission rate of the treatment group was 38. 71%, which had no significant differ-ence with 32. 26% of the control group ( P > 0. 05 ) . Compared with before treatment, the CEA, CA125 expression levels of the two groups reduced, and the treatment group reduced more obvious ( P < 0. 05 ); the incidence rate of nausea and vomiting, diarrhea of the treatment group had no statistically significant difference with the control group ( P > 0. 05 ) , while the significant decrease rate of the white blood cells was significantly lower than the control group ( P < 0. 05 ) . The two groups were followed up for 1 year and the sur-vival rate showed no difference ( P > 0. 05 );the overall survival rate of the treatmet group was higher than the control group ( P < 0. 05 ) . Conclusion Icotinib hydrochloride in treating advanced NSCLC has better efficacy, can prolong the patient's overall survival time, and reduce the expression of tumor markers CEA and CA125, with low toxicity, high safety and good tolerance, and provide a new choice for patients with advanced NSCLC provides.

The preproghrelin (GHRL) Leu72Met polymorphism (rs 696217) is associated with obesity, reduced glucose-induced insulin secretion in healthy or diabetic subjects, and reduced serum creatinine (Scr) levels in type 2 diabetes. We evaluated the association of the Leu72Met polymorphism with measures of insulin sensitivity in non-diabetic control individuals and type 2 diabetics, and whether this variation contributes to the development of diabetic nephropathy (DN) in type 2 diabetes. A case–control study was performed of 291 non-diabetic control subjects and 466 patients with type 2 diabetes, of whom 238 had DN with overt albuminuria (DN group; albuminuric excretion rate [AER] ≥ 300 mg/24 h) and 228 did not have DN, but had diabetes for more than 10 years (non-DN group). Genotyping was performed using a TaqMan PCR assay. The Leu/Leu, Leu/Met, and Met/Met genotype frequencies were significantly different between the non-DN and DN groups (p = 0.011). The frequency of the variant genotypes (Leu/Met, Met/Met) was significantly lower in the DN group than the non-DN group (23.5 vs. 36.0 %, p = 0.003). Met/Met non-diabetic control subjects had lower BMI and Scr levels and higher eGFR level than Leu/Leu or Leu/Met individuals (p < 0.05). Leu/Met and Met/Met type 2 diabetics had significantly lower AER and Scr levels and higher eGFR level than Leu/Leu type 2 diabetics (all p < 0.001). The GHRL Leu72Met polymorphism may help to maintain normal renal function and may protect against the development of DN by reducing albuminuria and improving renal function in Chinese patients with type 2 diabetes.

近年，恶性肿瘤发病率上升迅速，发病人群具有年轻化的趋势，其主要治疗方法为放、化疗、靶向治疗，常伴有一些不良反应，影响患者的生存质量。因此，中药的开发利用在恶性肿瘤的治疗上受到越来越多的重视。目前，一些基础和临床研究发现，中药薏苡仁油可联合手术、放化疗和靶向治疗用于肺癌、肝癌和乳腺癌等的治疗，具有抗恶性肿瘤增殖、减轻患者不良反应和提高免疫力的作用。

目的 建立人乳腺癌裸鼠皮下移植瘤模型,探讨重组脂联素体内对人乳腺癌生长的抑制作用.方法 将乳腺癌MDA-MB-231细胞接种于nu/nu裸鼠右侧腋窝皮下建立乳腺癌裸鼠皮下移植瘤模型,随机将荷瘤裸鼠分为4组:环磷酰胺组、脂联素高浓度组、脂联素低浓度组、生理盐水组,并于接种后14天腹腔注射给药2周,隔日1次,每3天记录各组皮下移植瘤的体积变化,给药结束后24h麻醉拉颈处死裸鼠,剥离肿瘤组织,称取瘤质量并计算抑瘤率;HE染色观察细胞形态变化.结果 环磷酰胺组及脂联素组肿瘤体积及瘤质量均小于生理盐水组,差异有统计学意义(P＜0.05),而环磷酰胺组与脂联素组比较差异无统计学意义(P＞0.05),环磷酰胺组、脂联素高浓度组、脂联素低浓度组的抑瘤率分别为60.21％、58.72％和31.47％;HE染色病理组织学观察环磷酰胺组和脂联素组裸鼠的移植瘤组织出现明显坏死区和凋亡改变.结论 脂联素对人乳腺癌MDA-MB-231细胞移植瘤的生长具有明显的抑制作用.

Objective. To compare clinical characteristics, immunological markers, and β-cell functions of 4 subgroups (“Aβ” classification system) of ketosis-onset diabetes and ketosis prone diabetes patients without known diabetes, presenting with ketosis or diabetic ketoacidosis (DKA) and admitted to our department from March 2011 to December 2011 in China, with 50 healthy persons as control group. Results. β-cell functional reserve was preserved in 63.52% of patients. In almost each subgroup (except A− β− subgroup of ketosis prone group), male patients were more than female ones. The age of the majority of patients in ketosis prone group was older than that of ketosis-onset group, except A− β− subgroup of ketosis prone group. The durations from the patient first time ketosis or DKA onset to admitting to the hospital have significant difference, which were much longer for the ketosis prone group except the A+ β+ subgroup. BMI has no significant difference among subgroups. FPG of ketosis prone group was lower than that of A− β+ subgroup and A+ β+ subgroup in ketosis-onset group. A− β− subgroup and A+ β+ subgroup of ketosis prone group have lower HbA1c than ketosis-onset group. Conclusions. Ketosis-onset diabetes and ketosis prone diabetes do not absolutely have the same clinical characteristics. Each subgroup shows different specialty.

OBJECTIVE:To determine the tumoricidal ability of combined immunotherapy of natural killer (NK) cells and dendritic cells (DCs) in a melanoma mouse model and the functions of tumor-associated effector cells.MATERIALS AND METHODS:A C57BL/6 mouse model of subcutaneous melanoma and lung metastasis was established. NK cells and DCs were cultured and labeled in vitro. Varying frequencies of both NK cells and DCs were adoptively transferred into tumor-bearing mice. Tumor, liver, spleen, and lung were studied for the number and distribution of effector cells. Additionally, CD8+T cell numbers in the lung and numbers of metastatic lung nodules were determined.RESULTS:Co-culture of NK cells and DCs might maintain and promote NK cell activity without exogenous cytokines. Both NK cells and DCs were distributed in the tumor microcirculation and parenchyma. We found significant time-dependent differences in the numbers of infiltrating NK cells and DCs (P < 0.01), which stimulated the highest frequencies of effector cells 4 h after transfer and the lowest at 12 h. Low NK cell numbers were found in the spleen, and fewer numbers were found in liver and lung. Infiltration of tumors with effector cells was greatest following mixed cell transfers as compared to single transfers, and markedly increased CD8+T cells were associated with significant decreases in lung metastases.CONCLUSION:NK cells and DCs adoptive immunotherapy targeted the tumor and exhibited improved therapeutic efficacy as compared to that of the cells given alone. This strategy could induce tumorigenic immunological memory and suggests that mixed NK cells and DCs adoptive immunotherapy offers therapeutic options against cancer.

Adiponectin is a kind of adipocyte-specific protein which is only inversely related with obesity by now. It is involved in enhancing insulin sensitivity,anti-atherogenic and antiinflammatory activities.Recent studies have reported that adiponectin is closely correlated with the genesis and development of a variety of obesity related malignant tumors,especially postmenopausal breast cancer.Obesity is an independent risk factor for the development of breast cancer.Recently researches about the correlation between adiponectin and breast cancer relations and the action mechanisms,signaling pathways have made a progress.

目的 分析雌激素受体(ER)β在乳腺癌中表达的意义.方法 采用免疫组化的方法检测2002年7月至2004年3月我院收治乳腺癌患者癌组织中ERβ、孕激素受体(PR)、人类癌基因(CerbB-2)的表达.结果 ERβ的表达与患者的年龄、月经、病理类型、临床分期无相关性,与腋窝淋巴结转移具有相关性(P＜0.05).ERβ的表达与与PR的表达无相关性(P＞0.05),与CerbB-2表达有相关性(P＜0.05).结论 ERβ可作为判断乳腺癌预后的一个指标.CerbB-2与ERβ联合将有利于乳腺癌判断预后.

To investigate the efficacy of dendritic cells and natural killer cells in the inhibition of lung metastasis, we injected dendritic cells and natural killer cells intravascularly into mice bearing B16F10 tumour melanoma cells. This efficiently inhibited tumor growth and prolonged survival. In addition, surviving mice developed a long-lasting memory response against the original tumor when re-challenged with live tumor cells. Intravenous administration of dendritic cells and natural killer cells may be a potential way to treat lung metastasis in patients.

目的 观察顺铂分次应用联合多西他赛治疗非小细胞肺癌的疗效及毒副反应.方法 对经病理证实的56例非小细胞肺癌患者给予顺铂分次应用+多西他赛联合化疗.结果 全组部分缓解24例,稳定20例,进展12例,总有效率为42.9%.初治组有效率为46.9%,复治组有效率为37.5%.最常见的毒副反应为骨髓抑制,毒副反应均可耐受.结论 顺铂分次应用联合多西他赛治疗非小细胞肺癌具有较好的疗效,毒性反应小,可以耐受,具有较好应用价值.

Objective: To study magnetic nanoparticles biological behaviour on human liver cancer line HepG—2 and human normal liver cell line L02 in vitro. Methods: Magnetite nanoparticles whose diameter is about 10nm were prepared with chemical precipitation methods. Then their exosyndrome were observed. Both human liver cancer cell line HepG? and human normal liver cell line L02 were cultured respectively in culture medium contained Fe3O4 nanoparticles, then we observed transient changing and their differences. Result: The magnetite nanoparticles had favourable biocompatibility and were distributed in cytolysosome and phagocytotic vesicle. They could stay stably in HepG—2 for more than 72h. Under the same conditions, human liver cancer line HepG—2 take up a lot of nanoparticles within 1 hour, while human normal liver cancer cell line L02 take up only little nanoparticles after 3 hours. Conclusion: The results offer valuable data for the effect of magnetic nanoparticles on microstructure of tumor cell. They probably also offer valuable evidence for the application of magnetic nanoparticles on malignant tumor therapy.

Objective To compare the infiltration in melanoma models and cytotoxicity of natural killer cells activated by dendritic cells,IL-2 and IL-15.Methods Inoculating B16 Melanoma cells in C57BL/6 mice's back to establish subcutaneous models.NK cells labled by DAPI were injected via the lateral tail vein.DC,IL-2 and IL-15 were given respectively.Tumor tissues were removed at different times after injection and processed for electron microscope and fluorescence microscope.Cytotoxicity was detected by MTT assay.Results Cytotoxicity of NK cells cultured with DCs was enhanced.NK cells had higher cytotoxicity when NK/DC ratio was 1∶1 than when it was 10∶1(P0.05).NK cells and DCs were identified through electron microscope and necrosis of target cells was observed.Infiltration of NK cells was dose and time-dependent.More NK cells accumulated in tumors but not significantly when DCs were given compared to IL-2 or IL-15.Conclusion NK cells can be activated by DCs without exogenous cytotines.The activation between NK cells and DCs were related to their dose ratio.

Objective: To study the localization of effector adoptively transferred natural killer (NK) cells and dendritic cells (DCs) in murine subcutaneously tumor. Methods: B16-F10 melanoma cell line was implanted subcutaneously into C57BL/6 mice. NK cells and DCs were prepared and labeled with Brdu and DAPI. The mice received labeled NK cells and DCs via the vein or located injection. Tumor and other organs were removed at different time points after the adoptive transfer and processed. The histopathological change of tumors were observed by HE staining. The labeled NK cells and DCs were obsevered and numbered by use of fluorescense microscope. Results: NK cells and DCs adopted by the vein injection accumulated mostly in tumors and microcirculation of tumor, and the number of effector cells was significantly different(P<0.01). By four hours after injection, significantly more cells were seen in the tumor compared with other time points, and by 12 hours after injection, that was the least. As in the cases of adoptived by localized injection, infiltrative NK cells and DCs localized in the tumors. And the number of the effective cells in different time points was significantly different (P<0.01). It was the highest in one hour and the lowest in twelve hours after injection. There was a significantly difference (P<0.01) as adopting different cells, and the number of received NK cells combined with DCs was higher than injection of single kind of cells. Conclusions: NK cells and DCs are accumulated in tumor and those lead to the necrosis or apoptosis of the tumors. NK cells combined with DC are effective immunotherapy in tumor of mouse.

Objective To study the induction and proliferation of murine natural killer cells and dendritic cells,and to learn the intercellular labeling and tracking methods.Methods B16-F10 melanoma cell line was implanted subcutaneously into C57BL/6 mouse.NK cells and DCs were prepared and labeled with Brdu and DAPI.The mouse received labeled NK cells and DCs via the vein.Labeled NK cells and DCs were observed and identified by use of eletron microscope and fluorescense microscope.Results NK cells and DCs were proliferated duplicately in vitro.Typical NK cells and DCs were observed with eletron microscope.Labelling rate of Brdu was about 65%,while that of DAPI was 100%.NK cells and DCs adoptived by the vein injection accumulated most in tumors and microcirculation of tumor.Conclusion NK cells and DCs proliferated duplicately in vitro with cytokine stimulating.Brdu and DAPI can label cells in vitro while track in vivo.

原发性肝癌是我国常见的恶性肿瘤之一,确诊时多为中晚期,进展快,预后差,治疗效果不佳,对放化疗均不敏感,生存期多为3～6个月.近年来发现,在原发性肝癌治疗中,亚砷酸也有一定的疗效.现将我科应用亚砷酸治疗原发性肝癌的临床观察报告如下.

目的:对比分析含奈达铂联合化疗方案和含顺铂联合化疗方案治疗中晚期非小细胞肺癌的疗效和不良反应.方法:70例中晚期非小细胞肺癌患者,其中奈达铂治疗组(A组)34例,顺铂治疗组(B组)36例.结果:A组有效率(32.35%)和B组有效率(34.28%)无显著差异(P＞0.05);A组胃肠道反应(23.53%)发生率明显低于B组(69.44%)(P＜0.01);两组肾脏毒性无明显差异;两组白细胞下降发生率分别为26.47%和25.00%,无显著差异;血小板下降A组(52.94%)较B组(27.78%)显著(P＜0.05).结论:奈达铂治疗中晚期非小细胞肺癌的有效率不低于顺铂,胃肠道毒性显著减轻,且从临床的实用性和便利性上考虑,奈达铂更容易为临床医生和患者所接受.

Purpose:To study the efficiency and safety on vinorelbine combined with capecitabine in the treatment of metastatic breast cancer. Methods:Twenty-eight patients with measurable lesions of metestetic breast cancer received vinorelbine 6 mg/m 2 d 1-5 civ,cycles were repeated every 21 days. Patients received capecitabine for 2-4 cycles at the same time. All patients received more than one course of chemotherapy regimens and 19 patients had adriamycin and (or) paclitaxel treatment. Results:Thirteen patients received two cycles treatment and fifteen patients received four cycles of treatment. Complete response in one patient,partial response in six patients,minor response in seven patients,stable response in seven patients and progressive disease in seven patients were observed. Overall responsed rate was 50%.The common side effects were neutronpenia,hand-foot syndrome,skin pigmentation,fatigue. Conclusions:The combination of vinorelbine and capecitabine in the treatment of metastatic breast cancer was effective and the toxicities were tolerable. It is possible that this regimen is an ideal second line chemotherapy for metastatic breast cancer.

Objective: The relationship between the expression of inducible nitric oxide synthase (iNOS) mRNA and acute cardiac allograft rejection was studied in this paper. The purpose was to investigate whether the expression of iNOS mRNA could be regarded as the monitor of cardiac allograft rejection or not. Methods: The model of heterotopic abdominal heart - transplantation was used as allogeneic group. The transcription levels of iNOS mRNA in myocardium were measured with RT- PCR assay. Results:The transcript levels of iNOS mRNA in the myocardium of allogeneic group at days 3, 5, 7, 9 and 11 after transplantation were (0.44 ±0.19) ,(0.97 ±0.25) ,(1.20 ±0.45 ), (0.89 ± 0.27 ) and ( 0.77 ± 0.22 ), respectively ( referred to β - action mRNA). The expression of iNOS mRNA was not observed in control group. Conclusions: The expression of iNOS mRNA was early and the transcript levels of iNOS mRNA increased significantly during cardiac allograft rejection. These results suggested that the expression of INOS mRNA could be regarded as an early and sensitive marker of cardiac allograft rejection.