HMVP、MVP和 HVP方案治疗晚期NSCLC的前瞻性随机研究

背景与目的非小细胞肺癌( non-small cell lung cancer,NSCLC)对常用的一、二线化疗方案敏感性较低,在化疗中联用喜树碱类衍生物已引起国内外的研究兴趣.本研究旨在观察羟基喜树碱( hydroxycamptothecin,HCPT)联合丝裂霉素( mitomycin,MMC)、长春花碱酰胺( vindesine,VDS)和顺铂( cisplatin,DDP)组成的 HMVP、 MVP和 HVP方案治疗晚期 NSCLC的近期、远期疗效和不良反应.方法 134例晚期 NSCLC患者随机分为 HMVP组( 46例)、 MVP组( 44例)和 HVP组( 44例),接受相应方案的化疗,观察各组的近期及远期疗效、不良反应和生存情况.结果 HMVP、 MVP和 HVP三组的有效率分别为 39.54%、 36.59%和 26.19%,三组之间无显著性差异( P >0.05);三组的中位缓解期、中位生存期、 1年及 2年生存率亦无明显差别.三组之间的Ⅲ～Ⅳ度白细胞减少、Ⅲ～Ⅳ度血小板减少、Ⅲ～Ⅳ度恶心 / 呕吐及Ⅲ～Ⅳ度便秘发生率均无显著性差异( P >0.05).结论 MVP方案治疗晚期 NSCLC的疗效略低于 HMVP方案,但后者未显示出明显的疗效优势,且可能增加白细胞抑制、恶心 /呕吐和便秘的发生率. MVP方案疗效略高于 HVP方案.     

鼻咽癌组织中P-gp、MRP和LRP的表达及其临床意义

目的探讨多药耐药基因蛋白(P-gp)、多药耐药相关蛋白(MRP)和肺耐药相关蛋白(LRP)在鼻咽癌组织中的表达情况及其临床意义。方法应用单克隆抗体多药耐药相关蛋白(P-gp),多药耐药基因蛋白(MRP),肺耐药相关蛋白(LRP),对54例鼻咽癌初诊患者的肿瘤组织进行免疫组化检测。结果3项多药耐药指标在54例患者中有不同程度表达。P-gp、MRP、LRP的表达与鼻咽癌病理类型、临床分期及有无淋巴结转移不相关;P-gp表达与MRP、LRP表达不相关,MRP与LRP表达间呈正相关。结论联合检测LP-gp、MRP、LRP在鼻咽癌组织中的表达,对鼻咽癌化疗药物的选择及预后的判断都有重要的参考价值。     

Study of CALR,MPL, and c-kit Gene Mutations in Thai Patients with JAK2 V617F Negative Myeloproliferative Neoplasms

Objective: The aim of this study to determine the prevalence of CALR, MPL and c-kit gene mutations in JAK2 V617F negative-MPN patients. Methods: The retrospective study of CALR, MPL and c-kit mutations were analyzed in 113 samples collected from March 2010 to May 2017 and identified as JAK2 V617F–negative MPN Thai patients. The samples were analysis by gel electrophoresis and direct sequencing. Results: 28.3% of JAK2 V617F–negative MPN patients showed CALR gene mutations. Within the MPN patients with CALR mutation, 46.9% were classified as essential thrombocythemia (ET) and 20.9% were classified as primary myelofibrosis (PMF). Previous studies classified CALR mutations into three types using negatively charged amino acid stretches at the C-terminal domain. Type 1-like mutations were observed in 12 of 49 (24.5%) ET patients and type 2-like mutations were observed in 10 of 49 (20.4%) patients. In addition, 8 of 43 (18.6%) PMF patients showed type 1-like mutations and 1 of 43 (2.3%) showed type 2-like CALR mutation. Interestingly, platelet counts were higher in patients with CALR gene mutation than in patients without CALR gene mutation. MPL mutations (W515K and W515L) were identified in 2 of 109 (1.8%) MPN patients; the MPL mutations were only found in ET patients, which was consistent with previous studies. We did not detect exon 17 c-kit mutation in JAK2-negative MPN patients but detected intronic single nucleotide polymorphisms at c.74,978 and c.75,255 in these samples. Approximately 66% of patients did not have mutations in CALR and MPL genes, in addition to lacking JAK2 gene mutation, and these cases are classified as triple-mutations. Conclusion: Our results showed that 66% of cases were triple-negative mutation MPN because they lacked mutations in JAK2, CALR and MPL genes. The frequencies of CALR and MPL mutation in this study are similar to other CALR and MPL patient data.     

miR-186 Represses Proliferation,Migration, Invasion,and EMT of Hepatocellular Carcinoma via Directly Targeting CDK6

The present study aimed to investigate the effect of miR-186 on proliferation, migration, invasion, and epithelial–mesenchymal transition (EMT) of hepatocellular carcinoma (HCC). In this work, miR-186 was downregulated in HCC tissues and cells, and low miR-186 level helped predict the occurrence of vascular invasion and poor prognosis in patients with HCC. miR-186 overexpression inhibited cell proliferation and tumor growth in nude mice, repressed migration and invasion abilities, and enhanced apoptosis in HCC cells. miR-186 also retarded progression of EMT. miR-186 directly bound to the 3 -untranslated regions of cyclin-dependent kinase 6 (CDK6) to inhibit its expression. Overexpression of CDK6 markedly reversed inhibitory effects of miR-186 on proliferation, apoptosis, migration, and invasion of HCC cells. Conversely, inhibition of CDK6 exerted synergic effect on the biological functions of miR-186. In conclusion, miR-186 represses proliferation, migration, invasion, and EMT, and induces apoptosis through targeting CDK6 in HCC, which may provide a new therapeutic target for HCC.     

Development and validation of a Surveillance,Epidemiology, and End Results (SEER)-based prognostic nomogram for predicting survival in elderly patients with gastric cancer after surgery

BackgroundElderly gastric cancer (ELGC) remains one of the intensively investigated topics during the last decades. To establish a comprehensive nomogram for effective clinical practice and assessment is of significance. This study is designed to develop a prognostic nomogram for ELGC both in overall survival (OS) and cancer-specific survival (CSS).MethodsThe recruited cases were from the Surveillance, Epidemiology, and End Results (SEER) database and input for the construction of nomogram.ResultsA total of 4,414 individuals were recruited for this study, of which 2,208 were randomly in training group and 2,206 were in validation group. In univariate analysis of OS, significant variables (P<0.05) included age, marital status, grade, American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) stage, bone/brain/liver/lung metastasis and tumor size. In univariate analysis of CSS, significant variables (P<0.05) included age, grade, AJCC TNM stage, bone/brain/liver/lung metastasis and tumor size. In multivariate analysis of OS, sex, age, race, grade, TNM stage, lung metastasis and tumor size were considered as the significant variables and subjected to the establishment of nomogram. In multivariable analysis of CSS, age, grade, TNM, tumor size were considered as the significant variables and input to the establishment of nomogram. Sex, age, race, grade, TNM stage, lung metastasis and tumor size were included for the establishment of nomogram in OS while age, grade, TNM, tumor size were included to the establishment of nomogram in CSS. C-index, decision curve analysis (DCA) and the area under the curve (AUC) showed distinct value of newly established nomogram models. Both OS and CSS nomograms showed higher statistic power over the AJCC stage.ConclusionsThis study established and validated novel nomogram models of OS and CSS for ELGC based on population dataset.     

肿瘤坏死因子、干扰素和免疫活性肽对癌瘤患者骨髓粒－巨造血祖细胞的影响

应用ＣＦＵ－ＧＭ软琼脂培养技术，在体外观察了不同浓度的ｒｈ－ＴＮＦ，ｒｈ－ＩＦＮα－２和ＩＡＰ对９例恶性淋巴瘤和１例睾丸癌患者的骨髓粒－巨造血祖细胞生长的影响。结果表明，在培养体系中，加入ｒｈ－ＴＮＦ５０和１００ｕ／ｍｌ，其ＣＦＵ－ＧＭ较空白对照均明显增多（Ｐ＜０．０５）。ｒｈ－ＩＦＮα－２１０００ｕ／ｍｌ可使ＣＦＵ－ＧＭ减少（Ｐ＜０．０５）。ＩＡＰ似乎对ＣＦＵ－ＧＭ无影响（Ｐ＞０．０５）。集落形态学显示，ｒｈ－ＴＮＦ和ＩＡＰ均能增加巨噬细胞为主形成的集落（Ｐ＜０．０１）。我们认为，该实验为骨髓移植及肿瘤患者在选择应用这些细胞因子上提供了一定的佐证。     

INFLUENCES OF CHLOROPAZINE,NIMODIPINE AND THEIR COMBINATON ON THE TOXIC EFFECTS OF CADMIUM ON LIVERS AND KIDNEYS OF MICE

观察钙调素拮抗剂氯丙嗪（ Ｃ Ｐ Ｚ） 和钙离子通道阻断剂尼莫地平（ Ｎ Ｉ Ｍ Ｏ） 以及同时给予以上两药对镉（ Ｃｄ） 致小鼠肝、肾毒作用的保护作用。利用模拟镉中毒动物模型。实验组预先灌胃给予小鼠 Ｃ Ｐ Ｚ、 Ｎ Ｉ Ｍ Ｏ、 Ｃ Ｐ Ｚ＋ Ｎ Ｉ Ｍ Ｏ，１ 小时后以１／５ Ｌ Ｄ－ ５０ Ｃｄ Ｃｌ２ 腹腔注射，连续五天，第六天收集生物样本检测各项指标。结果表明， Ｃ Ｐ Ｚ 能明显降低血镉，降低尿中ｒ － Ｇ Ｔ 及 Ｎ Ａ Ｇ 活性。 Ｃ Ｐ Ｚ和 Ｎ Ｉ Ｍ Ｏ 对于镉引起的钙泵活性降低，均表现出明显的保护作用，两药合用作用增强。 Ｃ Ｐ Ｚ 和 Ｎ Ｉ Ｍ Ｏ 均能显著提高镉中毒小鼠肝、肾组织中镉金属硫蛋白（ Ｍ Ｔ） 含量。揭示这两种钙拮抗剂对小鼠镉中毒肝、肾毒效应均有防护作用。 Ｃ Ｐ Ｚ 比 Ｎ Ｉ Ｍ Ｏ 明显。这两种药物合用在某些方面起协同作用。该两药的防护作用可能与 Ｍ Ｔ 参与有关。     

Evolution of imaging in rectal cancer: multimodality imaging with MDCT,MRI, and PET

Magnetic resonance imaging (MRI), multidetector computed tomography (MDCT), and positron emission tomography (PET) are complementary imaging modalities in the preoperative staging of patients with rectal cancer, and each offers their own individual strengths and weaknesses. MRI is the best available radiologic modality for the local staging of rectal cancers, and can play an important role in accurately distinguishing which patients should receive preoperative chemoradiation prior to total mesorectal excision. Alternatively, both MDCT and PET are considered primary modalities when performing preoperative distant staging, but are limited in their ability to locally stage rectal malignancies. This review details the role of each of these three modalities in rectal cancer staging, and how the three imaging modalities can be used in conjunction.     

比较研究TPS、CEA、CYFRA21-1和STNFR四种肿瘤活性标志物在肺癌中的诊断价值

背景与目的近年来,肿瘤标志物的研究不断取得新的进展。其中,组织多肽特异性抗原(TPS)、细胞角蛋白19片段(CYFRA21-1)和可溶性肿瘤坏死因子受体(STNFR)是近几年逐步应用于临床的新的肿瘤标志物。本研究旨在比较四种肿瘤标志物TPS、癌胚抗原(CEA)、CYFRA21-1和STNFR对肺癌的临床诊断价值。方法用ELISA法对72例肺癌患者的血清TPS、CEA、CYFRA21-1和STNFR水平进行检测,并与54例肺部良性疾病患者及32例正常健康人比较。结果四种肿瘤标志物在肺癌组的水平均明显高于良性疾病组(P<0.005)和正常对照组(P<0.001)。在对肺癌的诊断中,相对而言,STNFR的敏感性(81.9%)最高,CYFRA21-1的特异性(91.5%)最高,TPS的诊断符合率(83.5%)最高。结论TPS、CYFRA21-1和STNFR均是用于肺癌诊断的较好的肿瘤标志物,优于传统标志物CEA,其中又以CYFRA21-1的综合临床应用价值最好。     

钼靶、彩超及磁共振在乳腺导管原位癌中的诊断价值

目的 探讨如何合理选用钼靶(mammography, MG)、彩超(color Doppler ultrasonography, CDUS)、磁共振(magnetic resonance imaging,MRI)对乳腺导管原位癌（ductal carcinoma in situ,DCIS）进行诊断。方法 收集2009年7月-2014年9月贵阳医学院临床医学院收治的DCIS患者资料,对26例资料完整的患者术前影像学资料进行总结分析,并用Kruskal-Wallis方法进行检验。结果 DCIS在钼靶X线上的表现有钙化（73%, 19/26）、结构紊乱（36%, 8/26）、结节（30%, 7/26）,其中特征性的表现为密集细小钙化（70%, 18/26）;在彩超上的表现有结节（85%, 22/26）、导管扩张（11.5%,3/26）,其中典型的表现为无包膜、低回声结节（59%, 13/22）;在MRI增强上的特征表现为非肿块样强化病灶（73%, 19/26）,病灶时间-信号强度（TIC）曲线多呈Ⅱ、Ⅲ型（73%, 19/26）。钼靶、彩超、磁共振对DCIS诊断率分别为77%、50%、85%,钼靶联合彩超为85%,三者联合为96%,差异有统计学意义（P＜0.05)。结论 钼靶、彩超、磁共振均可发现DCIS,各具优势,不同影像学检查相应结合,可有效提高DCIS诊断率。     

P-糖蛋白与ER、PR在乳腺癌中的表达及意义

探讨耐药基因Ｐ－糖蛋白在乳腺癌的表达,以及与组织学类型,淋巴结转移,ＥＲ和ＰＲ之间的相互关系,为乳腺癌的优化疗,预测预后提供有用的指标。方法应用免疫组化检测３７例乳腺癌和１０例非癌病变的Ｐ－ｇＰ、ＥＲ、ＰＲ。     

Induction of the anticarcinogenic marker enzyme, quinone reductase, in murine hepatoma cells in vitro by flavonoids

Some flavonoids induce phase II enzymes both in vivo and in vitro. We have determined the structural requirements for this activity by examining the ability of naturally-occurring flavonoids to induce the phase II enzyme, quinone reductase (NAD(P)H:quinone oxidoreductase; EC 1.6.99.2), in murine Hepa1c1c7 cells. Hydroxylation of the B ring is not essential for induction, since galangin and kaempferol (with 0 and 1 hydroxyl in the B ring, respectively) are better inducers than quercetin (2 B ring hydroxyls). A 2,3 double bond in the C ring is essential for induction, since taxifolin, which has the same substitution pattern as quercetin but lacks the 2,3 double bond, is not an inducer. This is supported by catechin and epicatechin, which do not possess the 2,3 double bond and are also not inducers. A 3-hydroxyl group increases the activity but is not essential for induction, since apigenin is an inducer but kaempferol (which has the same structure as apigenin but possesses a 3-hydroxyl group) is more effective. The data show that, of the flavonoids, the flavonols are the most effective inducers of quinone reductase activity in Hepa1c1c7 cells (kaempferol˜galangin>quercetin>myricetin˜apigenin (a flavone)) and that flavanols and flavans are ineffective.     

Somatostatin Receptors 3, 4 and 5 Play Important Roles in Gallbladder Cancer

Expression changes of somatostatin receptor subtypes (SSTRs) including SSTR1, SSTR2, SSTR3, SSTR4and SSTR5 in the development of gallbladder cancer were assessed with attention to relationships with clinicalpathological characteristics. SSTRs in 29 gallbladder cancer and 25 normal gallbladder tissue specimens wereexamined by immunohistochemical staining. Differences between SSTRs expressions and clinical pathologicalparameters were analyzed by chi-square test. The five subtypes of SSTR were all expressed in gallbladder cancertissues and SSTR3 presented the highest expression. SSTR5 expression was increased significantly in gallbladdercancer (P<0.05) compared with that in normal gallbladder tissue. SSTR3 expression in highly and moderatelydifferentiated gallbladder cancer was significantly higher than that in poorly differentiated lesions (P<0.05).SSTR4 expression was lower in gallbladder cancer with lymph node metastasis than that in gallbladder cancerwithout lymph node metastasis (P<0.05). Therfore, these results indicated that SSRT5, SSTR3 and SSTR4 mayplay important roles in the formation and development of gallbladder cancer.     

微血管密度、p53蛋白和PCNA与肝细胞癌的关系

目的研究肝细胞癌(HCC)内微血管密度(MVD)、p53蛋白与增殖细胞核抗原(PCNA)表达之间的关系.方法采用免疫组化SABC法检测47例人HCC组织的MVD值、PCNA指数和p53蛋白表达情况.结果生存期≥5年者的MVD值(41.19±15.31)明显低于生存期＜5年者的MVD值(54.73±24.72).MVD值与患者的年龄、性别、肿瘤的大小、Edemondson分级无关,也与PCNA指数和p53蛋白表达无直接相关性(P＞0.05).p53蛋白在生存期≥5年及＜5年的2组患者中的异常表达率分别为10.5%和50.0%,有非常显著性差异(P＜0.01),但其与MVD值无关(P＞0.05).低分化HCC的PCNA指数(54.14±14.26)高于高分化HCC的PCNA指数(34.62±6.16),有显著性差异(P＜0.05),但与MVD值无关(相关系数γ=0.082,P＞0.05).结论MVD值和p53基因异常表达均与HCC的5年生存率直接相关,但MVD值、PCNA指数和p53蛋白异常表达相互之间无直接相关性.     

组织多肽抗原联合ProGRP、CEA、NSE、SCC、CYFRA21-1在肺癌诊治中的价值

目的 评估组织多肽抗原（TPA）联合ProGRP、CEA、NSE、SCC、CYFRA21-1在肺癌诊断与疗效监测中的应用价值。方法 用化学发光法和电化学发光法检测238例肺癌患者、25例肺部良性疾病患者及65名健康对照者血清中的TPA、ProGRP、NSE、SCC、CYFRA21-1和CEA水平,并对33例肺癌患者进行随访检测。同时用SPSS19.0统计软件及接受器工作性能曲线（ROC）分析,评价肿瘤标志物的临床应用价值。结果 肺癌患者血清TPA水平（中位数为130.45 U/L）明显高于肺部良性疾病患者（中位数为82.21 U/L）和健康对照组（中位数为70.96 U/L）（P=0.000, 0.002）。根据ROC曲线分析,TPA检测肺癌的临界值为130 U/L,敏感度为50%,特异性为88.9%,相比于其他肺癌标志物( ProGRP、NSE、SCC、CYFRA21-1、CEA）,敏感度较高,特异性稍低。肺癌患者血清TPA水平及阳性率随着肿瘤分期的升高而升高（P均<0.05）。TPA水平与疗效也密切相关,临床治疗有效时TPA下降,而病情恶化或出现转移时则升高。各种组合检测中,以六项组合诊断肺癌的敏感度和有效性最高。结论 TPA联合ProGRP、CEA、NSE、SCC、CYFRA21-1测定在肺癌的诊断、疗效及监测复发转移中,具有一定的临床价值。     

外周血NLR、MLR、SII在甲状腺髓样癌中的应用价值

目的:探讨外周血中性粒细胞与淋巴细胞比值（NLR）、单核细胞与淋巴细胞比值（MLR）、系统免疫炎症指数（SII）在甲状腺髓样癌（MTC）中的应用价值。方法:以我院2012年2月至2020年7月收治的MTC患者50例（MTC组）、甲状腺乳头状癌患者50例（PTC组）、健康体检者50例（健康对照组）为研究对象,比较三组患者外周血NLR、MLR、SII水平的差异,并采用受试者工作特征曲线（ROC）分析上述三个指标及其联合检测在MTC中的诊断效能,进一步根据上述三个指标在诊断MTC中的最佳诊断界值分析其与MTC临床病理特征的相关性。结果:比较各组间外周血NLR、MLR、SII水平示:MTC组NLR显著高于PTC组,差异有统计学意义（P＜0.05）;MTC组MLR、SII水平显著高于PTC组与HC组,差异有统计学意义（P＜0.05）。通过ROC曲线分析发现, NLR、MLR、SII单独诊断MTC患者的ROC曲线下面积分别为0.620、0.681、0.634,NLR、MLR、SII三者联合检测ROC曲线下面积为0.726。MLR单独检测及联合检测对MTC的诊断效能高于NLR、SII单独检测（P＜0.05)。MTC患者MLR与淋巴结转移及TNM分期有关,比较差异有统计学意义（P＜0.05）。结论:NLR、MLR、SII对MTC具有诊断价值,MLR单独检测及联合检测对MTC的诊断效能高于NLR、SII单独检测。MLR与MTC患者淋巴结转移及TNM分期有关。     

甲状腺乳头状癌VEGF、MMP-9及COX-2蛋白表达与淋巴道转移和血管生成的相关性

 目的 通过检测血管内皮细胞生长因子(VEGF)、基质金属蛋白酶-9(MMP -9)、环氧化酶-2(COX-2)在 甲状腺乳头状癌（PTC）细胞中的表达情况,探讨它们与PTC颈淋巴结转移的关系。 方法 采用免疫组织化学SP法检测74例PTC(有淋巴结转移者39例,无淋巴结转移者35例)中VEGF、 MMP-9、COX-2的表达,并对CD34表达阳性血管进行MVD计数。 结果 VEGF、MMP-9、COX-2的表达与MVD值在淋巴结转移组与无转移组之间的差异均具有统计学意义 (P<0.05),与PTC淋巴结转移呈正相关;VEGF、MMP-9、COX-2的表达与MVD值正相关 (P<0.05) ,VGEF、MMP-9阳性表达率与肿瘤大小密切相关（P<0.05）。 结论 甲状腺乳头状癌VEGF、MMP-9、COX-2蛋白表达与其淋巴道转移和MVD有关,检测这几种蛋白表 达将有助于判断甲状腺乳头状癌的转移潜能、血管生成能力及预后。     

血清AFP-L3、GP73检测联合CT扫描在肝细胞癌诊断中的价值

目的:检测肝病患者血清中甲胎蛋白异质体(AFP-L3)和高尔基体蛋白73(GP73)浓度,分析肝病患者病灶CT平扫加增强扫描后经处理技术得到二维及三维重建图像,探讨联合运用AFP-L3、GP73浓度检测与CT扫描两种技术在肝细胞癌(hepatocellular carcinoma,HCC)诊断中的价值。方法:采用酶联免疫吸附法检测肝病患者血清AFP-L3、GP73浓度,运用受试者工作特征曲线(recover operation characteristic,ROC)确定AFP-L3、GP73浓度诊断HCC的cut-off值。分析141例肝病患者总共164个病灶的CT扫描后经处理技术得到二维及三维重建图像而诊断HCC,探讨采用AFP-L3、GP73浓度测定与CT增强扫描及这两种方法联合应用在HCC的检出与定性诊断方面的价值。结果:HCC组AFP-L3浓度(113.58±63.62)ng/ml明显高于良性肝病组[(23.19±34.54)ng/ml,P<0.001],绘制AFP-L3浓度诊断HCC的ROC曲线,AFP-L3浓度38.47ng/ml为诊断HCC的cut-off值,诊断敏感性为81.08%,特异性为88.06%,诊断正确率为87.23%;HCC组GP73浓度(126.55±49.56)ng/ml明显高于良性肝病组[(56.97±26.48)ng/ml,P<0.001],绘制GP73浓度诊断HCC的ROC曲线,GP73浓度69.44ng/ml为诊断HCC的cut-off值,诊断敏感性为75.68%,特异性为91.04%,诊断正确率为88.65%。CT扫描诊断HCC的灵敏度为82.43%,特异度为91.04%,诊断正确率为90.07%。联合AFP-L3、GP73浓度检测与CT扫描诊断HCC的灵敏度为85.14%,特异度为92.53%,诊断正确率为92.19%。结论:联合运用血清AFP-L3、GP73浓度检测及CT扫描两种技术对HCC诊断灵敏度、特异度、诊断正确率较运用单一技术均有所提高,联合运用两种技术对HCC的准确早期诊断具有积极的意义。