KIF20A对胶质瘤细胞增殖、迁移和侵袭、凋亡及细胞周期分布的影响

目的:研究KIF20A对胶质瘤U87细胞系增殖、侵袭、迁移、凋亡及细胞周期分布的影响。方法:利用 RNA干扰技术下调胶质瘤细胞系 U87中 KIF20A 的表达。RT-qPCR 和 Western blot 分别检测 KIF20A 在mRNA 和蛋白水平上的表达。CCK-8 实验检测 U87细胞增殖能力的变化，Transwell 实验检测U87细胞迁移及侵袭能力的变化，流式细胞术检测 U87细胞凋亡及细胞周期的变化。结果:RT-qPCR和Western blot 结果显示 siRNA-KIF20A显著下调 KIF20A 的表达，CCK-8和Transwell 实验显示下调 KIF20A 的表达显著抑制了U87细胞的增殖、迁移及侵袭能力，流式细胞术结果显示下调 KIF20A 的表达显著促进了U87细胞的凋亡，诱导细胞周期阻滞在G0/G1期。结论:下调KIF20A的表达抑制胶质母细胞瘤细胞的增殖、迁移及侵袭，促进胶质母细胞瘤细胞的凋亡并诱导细胞周期G0/G1期阻滞。     

基于单中心的恶性肿瘤患者合并心血管及代谢疾病的调查

目的:探讨恶性肿瘤、心血管病变和代谢疾病三者之间的关联。方法:搜索2018年9月1日至2018年10月31日期间在复旦大学附属中山医院心脏超声诊断科进行心脏超声心动图检查的患者，根据病史资料统计恶性肿瘤患者例数，并分析其合并心脏疾病和代谢疾病情况。结果:搜索行心脏超声心动图检查的患者共计26 698例，其中经病理检查或经影像学检查明确证实的恶性肿瘤患者1 992例，男性1 084例，女性908例，平均年龄（62.62±11.42）岁。左室射血分数平均值为（65.35±4.94）%。合并心脏疾病共220例，占11.04%。合并代谢疾病共1 052例，占52.81%。结论:恶性肿瘤患者在心脏超声心动图检查的患者中比例较高，合并心脏疾病、代谢疾病情况也不在少数；恶性肿瘤及相关治疗既能造成心脏疾病的发生又可导致代谢疾病的出现，故需对恶性肿瘤患者进行早期预防和干预治疗，以减少心脏疾病和代谢疾病的发生或加重。     

超声造影联合血清CEA、CA72-4对卵巢良恶性肿瘤鉴别诊断的价值

目的:探讨超声造影联合血清癌胚抗原（CEA）、糖类抗原72-4（CA72-4）对卵巢良恶性肿瘤鉴别诊断的价值。方法:选取2017年1月至2018年6月本院肿瘤科收治的128例卵巢肿瘤患者进行研究，进行超声造影和血清CEA、CA72-4水平检测，观察超声造影、CEA、CA72-4及联合检测对卵巢良恶性肿瘤鉴别诊断的价值。结果:在良性肿瘤组中超声造影符合率为72.92%，恶性肿瘤组中超声造影符合率为75.00%，两组比较差异无统计学意义（P>0.05）；恶性肿瘤组患者血清CEA、CA72-4水平高于良性肿瘤组，两组比较差异有统计学意义（P<0.05）；恶性肿瘤组超声造影、CA72-4检测阳性率均高于良性肿瘤组（P<0.05），两组血清CEA检测阳性率比较差异无统计学意义（P>0.05），三者联合检测阳性率高于单项指标检测（P<0.05）；通过ROC曲线分析显示，CEA的AUC为0.644，诊断灵敏度为31.25%，特异性为82.29%，CA72-4的AUC为0.702，诊断灵敏度为40.63%，特异性为79.17%，二者联合检测的AUC为0.785，诊断敏感性为56.25%，特异性为73.96%；三项指标单独检测，超声造影检测的灵敏度、阳性预测率、阴性预测率、诊断准确度及误诊率最高，CEA检测的特异性、漏诊率最高，三者联合检测的灵敏度、特异性、阳性预测率、阴性预测率、诊断准确度最高，漏诊率、误诊率最低。结论:超声造影联合血清CEA、CA72-4检测较单独检测诊断效能高，对卵巢良恶性肿瘤鉴别诊断有较高参考价值。     

新型肝癌组织的体外三维培养模型

目的:利用肝癌组织进行体外的三维（three-dimension，3D）组织块培养，通过添加PD98059和霍乱毒素（cholera toxin，CT）优化培养条件，建立一种高活性的肝癌组织体外培养模型。方法:收集中山大学肿瘤防治中心肝胆科的肝癌组织标本，经清洗、冻存、复苏等处理后分为对照组、PD组、CT组、PD+CT组，同时进行体外的二维（two-dimension，2D）和三维培养。各组组织采用DNA断裂的原位末端标记法（TUNEL）检测组织细胞凋亡情况，qRT-PCR检测BCL-2、BID、Caspase 3、Cyclin D1、CDK2、ELK-1、C-FOS、C-MYC、C-JUN等相关基因的mRNA表达水平，免疫荧光染色检测BCL-2和cleaved caspase-3蛋白表达情况，筛选并确定最优的体外培养方法。结果:3D培养组的组织细胞凋亡均少于2D培养组；PD98059通过上调BCL-2蛋白的表达，下调cleaved caspase-3蛋白的表达，激活MEK/ERK下游基因，从而减少体外培养的组织细胞凋亡，增强其抗凋亡能力；霍乱毒素通过上调Cyclin D1、CDK2的基因表达，促进其增殖。结论:我们开发了一种新型肝癌组织的体外三维培养模型，它可以作为进一步的药物试验和人源性异种移植(PDX)模型的工具。     

Grading Gliomas Capability: Comparison between Visual Assessment and Apparent Diffusion Coefficient (ADC) Value Measurement on Diffusion-Weighted Imaging (DWI)

Background: To compare diagnostic accuracy between DWI visual scale assessment and ADC value measurement of solid portion of the tumor in grading gliomas. Methods: This retrospective study included 38 patients who had pathologically proven gliomas between January 2013 and August 2018 with 18 low grade and 20 high grade tumors. All patients underwent MRI and biopsy. Two readers reviewed DWI visual scale independently. Disagreement was resolved by consensus. One reviewer measured ADC value of entire solid part of the tumor in single axial slice with greatest dimension of tumor which was chosen by consensus. Two data sets of visual scale and ADC value were analyzed and comparison of diagnostic accuracy in glioma grading was done by using area under the curve (AUC) of receiver operating characteristic curve (ROC). Results: Visual scale and ADC value could be used to distinguish between low and high grade gliomas with a statistically significant difference. (P-value 0.002 and <0.001). Almost all high grade gliomas had visual scale 5. The sensitivity, specificity, PPV NPV and accuracy were 50%, 100%, 100% , 64.3%,73.68% respectively. The cutoff level for the ADC value was determined to be 1119.48 x10-6 mm2/s in differentiation between low and high grade gliomas with the sensitivity, specificity, PPV, NPV, accuracy of 90%, 88.89% , 90%, 88.9% and 89.47% respectively. There was no statistically significant difference(P-value = 0.163). Conclusion: Both Visual scale and ADC value were capable of differentiating between low and high grade gliomas. Although visual scale may not replace ADC measurement, larger scale prospective study is needed for validate this initial result.     

Methylene Blue Absorption in Sentinel Lymph Node Biopsy for Early Breast Cancer after Neoadjuvant Chemotherapy

Introduction: Chemotherapy is claimed to cause lymphatic drainage damage because of the tumor cell’s apoptosis process. This event might cause decreased marker (radioactive solution and/or blue dye) absorption on sentinel lymph nodes (SLN). In this study, the researchers used methylene blue only and wished to evaluate the methylene blue absorption of the SLNB procedure on early-stage breast-cancer patients after neoadjuvant chemotherapy (NAC). Materials and methods: The method used was the historical cohort study conducted from 2016-2019 in Indonesia. Samples were collected from 117 patients of stage I and II breast cancer with clinically negative axillary lymph nodes, who were then grouped into post-NAC and no-NAC (control group), in which SLNB procedures were conducted on the two groups by using single-method methylene blue. The results of methylene blue absorption were then analyzed by the Chi-square hypothesis test. Results: From the total of 564 early-stage patients who were referred to surgical oncologists, 117 patients were found to meet criteria of inclusion, consisting of the control group (52 patients) and the post-NAC group (65 patents). Of 65 patients who had undergone NAC treatment and SLNB procedure, it was found that 40 patients (61.5%) showed positive blue SLN. Of 52 pre-NAC breast-cancer patients, it was found that 47 patients (90.4%) showed methylene blue absorption on SLN with the p-value of 0.000 (P<0.05, significant). The relative risk value amounted to 0.522. Post-NAC patients had a tendency of decreased absorption of methylene blue. Conclusion: Neoadjuvant chemotherapy can cause the decrease of methylene blue absorption on SLNB procedure.     

Clinical Implication of Toll-Like Receptors (TLR2 and TLR4) in Acute Myeloid Leukemia Patients

Backgrounds: Toll-like receptors 2; 4 (TLR2;4) are an essential component of the innate immunity and play an important role in immune-surveillance and immune response to various microorganisms. This study aimed to investigate the association between TLR2 and TLR4 polymorphism and the risk of acquiring severe infections, and impact on AML patient’s outcome. Subjects and methods: Using polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP); we analyzed three SNPs in the TLR2 (Arg753Gln) and TLR4 (Asp299Gly and Thr399Ile) in 120 AML patients and 100 healthy control subjects. Results: No significant differences in genotype or alleles frequency between healthy controls and AML patients regarding TLR2 Arg753Gln, TLR4 Asp299Gly and TLR4 Thr399Ile polymorphisms (P>0.05 for all). Neutropenic fever was detected in 110 out of 120 (91.7%) of the studied AML patients. The sepsis and pneumonia were identified in 20 out of 120 patients (16.7%). The incidence of sepsis was associated with TLR2 Arg753Gln: AG genotypes, A allele and TLR4 Asp299Gly: CT genotype and C allele as compared to other genotypes and alleles. Moreover; TLR2 (Arg753Gln) GG polymorphisms significantly associated with shortest overall survival (OS) and shortest disease-free survival (DFS); while TLR4 polymorphisms affect the DSF only but not OS. In AML patients TLR2 Arg753Gln gene polymorphism is associated with high susceptibility to sepsis and TLR4 (Asp299Gly and Thr399Ile) gene polymorphism is associated with high susceptibility for both pneumonia; and sepsis. Conclusion: TLR2 Arg753Gln (AG; GG genotype) polymorphisms are associated with shortest OS and DFS. Moreover; significant association between TLR2 polymorphisms, TLR4 Arg753Gln polymorphisms and risk of severe infections in AML patients was documented.     

Clinical Utility of BRAF,NRAS, and TERT Promoter Mutation in Preoperative Thyroid Fine-Needle Aspiration Biopsy: A Diagnostic Study From Dharmais Cancer Hospital

Objective: Molecular testing of thyroid nodules becomes important for improving the accuracy of fine-needle aspiration biopsy (FNAB). This study aimed to investigate the diagnostic utility of BRAF, NRAS, and TERT promoter mutation in thyroid nodules at Dharmais Cancer Hospital.Methods: We performed a prospective diagnostic study involving 50 patients with thyroid nodules who needed surgery between September 2013 and August 2014. Mutational hotspots in BRAF exon 15, NRAS exon 3, and TERT promoter region were analyzed by Sanger sequencing from FNAB specimens. Cytology and molecular data were compared to histopathology results.Result: Of the 50 cases included in the analysis, 39 cases (78%) were thyroid malignancies. Mutations of BRAF, NRAS, and TERT promoter were detected in 31% (12/39), 18% (7/39), and 13% (5/39) cases, respectively. BRAF and NRAS mutations were found mutually exclusive, while all of TERT promoter mutation was found coexistent either with BRAF (40%) or NRAS (60%). The combination of FNAB cytology and molecular testing resulted in 69% sensitivity, 100% specificity, 100% positive predictive value, 48% negative predictive value, and 76% accuracy.Conclusion: Molecular testing of BRAF, NRAS, and TERT mutations improve the sensitivity of thyroid FNAB and is beneficial for more definitive treatment in selective cases. However, the NPV is relatively low to avoid the need for diagnostic surgery. Therefore, further studies to identify more sensitive methods and more comprehensive molecular markers in the diagnosis of thyroid nodules are needed.     

FMNL3在乳腺癌组织中的表达及其与临床预后的相关性

目的:比较formin like-3（FMNL3）蛋白在乳腺正常组织、癌旁组织和肿瘤组织中的表达差异及与患者临床预后的相关性。方法:回顾性分析我院乳腺外科在2014年6月到2016年6月期间收治的86例乳腺癌患者的临床和病理资料，比较乳腺癌组织、癌旁组织和正常乳腺组织中FMNL3蛋白的表达情况。分析乳腺癌组织中FMNL3蛋白表达与患者3年生存状况的关系。结果:乳腺癌组织、癌旁组织和正常组织中FMNL3表达阳性率比较，差异显著（P＜0.05）。乳腺癌组织中FMNL3表达阳性率显著高于癌旁组织和正常组织（P＜0.05），癌旁组织FMNL3表达阳性率显著高于正常组织（P＜0.05）。低度分化、病理分期Ⅲ-Ⅳ期及发生淋巴结转移的患者乳腺癌组织中FMNL3蛋白表达阳性率显著高于中度/高度分化、病理分期Ⅰ期/Ⅱ期及未发生淋巴结转移的患者（P＜0.05）。FMNL3表达阳性患者中位无进展生存期为58.182（95%CI:52.806~63.194）个月，表达阴性患者中位无进展生存期为63.621（95%CI:58.261~66.701）个月，两组比较，差异有统计学意义（P＜0.05）。结论:FMNL3蛋白在乳腺癌发生、进展和转移过程中可能具有重要作用，能够影响患者预后。