Progression-free Survival Outcome Is Independent of Objective Response in Patients With Estrogen Receptor-positive,Human Epidermal Growth Factor Receptor 2-negative Advanced Breast Cancer Treated With Palbociclib Plus Letrozole Compared With Letrozole: Analysis From PALOMA-2

BackgroundIn PALOMA-2, palbociclib + letrozole significantly prolonged progression-free survival (PFS) versus placebo + letrozole in patients with estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER⁺/HER2⁻) advanced breast cancer (ABC). We investigated clinical outcomes of patients who achieved or did not achieve a confirmed objective response (OR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (data cutoff: May 31, 2017).Patients and MethodsPostmenopausal patients untreated for ER⁺/HER2⁻ ABC were randomized 2:1 to palbociclib + letrozole or placebo + letrozole. Median PFS, median duration of OR, baseline characteristics, and palbociclib exposure were compared in patients with or without OR by treatment arm.ResultsIn the intent-to-treat population, OR was achieved by 194 (44%) of 444 and 77 (35%) of 222 patients in the palbociclib and placebo arms, respectively (odds ratio, 1.5; 95% confidence interval [CI], 1.0-2.1; P = .0156). Regardless of treatment, more OR than non-OR patients had de novo metastatic disease (47%-50% and 28%-31%, respectively) and no prior endocrine therapy (55% and 35%-37%, respectively). Rates of palbociclib dose reduction owing to adverse events were similar regardless of OR (41% and 38%, respectively). Among the patients with OR during the study, approximately 50% achieved OR within the first 3 months regardless of treatment. The median PFS was significantly prolonged with palbociclib + letrozole versus placebo + letrozole in patients with measurable disease in both OR (37.2 months; 95% CI, 28.1 months to not estimable vs. 27.4 months; 95% CI, 22.2-31.1 months; hazard ratio, 0.66; 95% CI, 0.47-0.94; P = .009) and non-OR groups (10.9 months; 95% CI, 8.2-11.2 months vs. 5.6 months; 95% CI, 5.3-8.3 months; hazard ratio, 0.72; 95% CI, 0.54-0.97; P = .016).ConclusionsPalbociclib + letrozole provided significant clinical benefit versus placebo + letrozole to patients with ER⁺/HER2⁻ ABC regardless of achieving RECIST-defined OR.Pfizer; ClinicalTrials.gov: NCT01740427     

Design,synthesis and pharmacological evaluation of 4-(3-chloro-4-(3-cyclopropylthioureido)-2-fluorophenoxy)-7-methoxyquinoline-6-carboxamide (WXFL-152): a novel triple angiokinase inhibitor for cancer therapy

Angiokinases, such as vascular endothelial-, fibroblast- and platelet-derived growth factor receptors (VEGFRs, FGFRs and PDGFRs) play crucial roles in tumor angiogenesis. Anti-angiogenesis therapy using multi-angiokinase inhibitor has achieved great success in recent years. In this study, we presented the design, synthesis, target identification, molecular mechanism, pharmacodynamics (PD) and pharmacokinetics (PK) research of a novel triple-angiokinase inhibitor WXFL-152. WXFL-152, identified from a series of 4-oxyquinoline derivatives based on a structure–activity relationship study, inhibited the proliferation of vascular endothelial cells (ECs) and pericytes by blocking the angiokinase signals VEGF/VEGFR2, FGF/FGFRs and PDGF/PDGFRβ simultaneously in vitro. Significant anticancer effects of WXFL-152 were confirmed in multiple preclinical tumor xenograft models, including a patient-derived tumor xenograft (PDX) model. Pharmacokinetic studies of WXFL-152 demonstrated high favourable bioavailability with single-dose and continuous multi-dose by oral administration in rats and beagles. In conclusion, WXFL-152, which is currently in phase Ib clinical trials, is a novel and effective triple-angiokinase inhibitor with clear PD and PK in tumor therapy.     

长链非编码RNA在结直肠癌中的研究进展

长链非编码RNA（LncRNA）是近十年来肿瘤领域分子机制研究的热点之一，被证实在生物体内对基因的表达具有调控作用，与肿瘤的发生与发展密切相关。结直肠癌是一种严重危害人类健康的恶性肿瘤，研究发现许多LncRNA在结直肠癌中表达失调。异常表达的LncRNA作为关键的调控因子，参与了多种生物学过程，影响肿瘤细胞的增殖和凋亡、侵袭转移及调节肿瘤耐药。研究LncRNA在肠癌中的作用机制可以为结直肠癌临床治疗提供一些新思路。此外，LncRNA还可作为一种潜在的生物标志物用于结直肠癌早期诊断及预后评估。     

六西格玛在肿瘤标志物质量目标选择上的应用

目的应用6σ理论对肿瘤标志物项目的分析性能进行评价，并初步确定各项目的质量目标。 方法收集本实验室2018年1至12月室内质控数据和国家卫生健康委临床检验中心室间质量评价结果，以生物学变异导出的质量规范和国家室间质量评价标准作为允许总误差(TEa)计算6项肿瘤标志物的σ水平，并依据质量目标选择流程图和肿瘤标志物分析性能验证图评价肿瘤标志物的分析性能，进而为肿瘤标志物选择合适的质量目标。 结果应用不同层级的生物学变异导出的质量规范和国家室间质量评价标准，肿瘤标志物项目的σ水平存在显著差异；依据质量目标选择流程图：选择生物学变异导出的"适当的"质量规范作为CA125项目的质量目标，选择生物学变异导出的"最低的"质量规范作为t-PSA、CEA、AFP、CA199和CA153项目的质量目标。 结论6σ能够客观评价肿瘤标志物的分析性能，并为实验室质量目标的选择提供重要的参考价值。     

Análisis de supervivencia en pacientes con micosis fungoide foliculotropa de un centro latinoamericano

IntroductionFolliculotropic mycosis fungoides is a variant that has poor prognosis and a variable clinical presentation. Concerns have been expressed that the current TNMB staging of this tumor may not be useful. A recently developed classification system based on clinical and histologic variables classifies this tumor as early or advanced, a distinction found to correlate with prognosis. The aim of this study was to compare survival in FMF in Colombia between patients with early versus advanced tumors.Material and methodsRetrospective, observational study of clinical course and outcomes in patients with FMF treated at the National Cancer Institute of Colombia between 2008 and 2020. Survival was compared between early and advanced disease.ResultsTwenty-one patients (11 with early FMF and 10 with advanced FMF) were studied. Seven patients, all with advanced disease, died. Survival at 5 years was 62% overall and 40% for patients with advanced FMF. No differences were observed when survival was analyzed according to TNMB stage.ConclusionsTNMB staging is not useful in FMF. The new classification system based on clinicopathologic features appears to provide reliable information for assessing prognosis and guiding treatment decisions.     

隔药灸神阙八阵穴对术后粘连性肠梗阻患者疗效及炎性反应因子的影响

目的：探讨隔药灸神阙八阵穴对术后粘连性肠梗阻（AIO）患者疗效及血清白细胞介素-6（IL-6）、肿瘤坏死因子（TNF-α）水平的影响。方法：选取2013年1月至2017年4月唐山市人民医院收治的行腹腔手术患者280例作为研究对象，按照随机数字表法随机分为对照组和观察组，每组140例，对照组采用常规治疗；观察组在对照组基础上给予隔药灸神阙八阵穴，均治疗1周。比较2组患者临床疗效、治疗后肠功能评分、治疗前后胃动素（MOT）水平、IL-6、TNF-α水平。结果：观察组总有效率为91.43%，显著高于对照组77.14%（P<0.05）；治疗后，观察组恢复排气时间、腹部症状缓解时间、肠鸣音恢复时间均短于对照组（P<0.05）、2组患者MOT水平均低于治疗前，且观察组的MOT水平低于对照组（P<0.05）、2组患者的血清IL-6、TNF-α水平均显著低于治疗前，且观察组的血清IL-6、TNF-α水平均低于对照组（P<0.05）。结论：隔药灸神阙八阵穴治疗AIO疗效显著，能改善患者胃肠功能，降低MOT水平，有效调节血清IL-6、TNF-α水平。     

肝细胞癌肝移植供肝选择策略

供肝数量不足是制约肝移植发展的主要因素,更是制约肝细胞癌肝移植治疗的突出因素。既往对肝细胞癌肝移植的研究多集中在受者选择标准、降期治疗、免疫抑制方案等方面,近年来研究发现供肝的选择对肝细胞癌肝移植术后肿瘤复发也有显著影响。笔者从临床供肝的主要类型、肝细胞癌肝移植适应证的把握、适应证内肝细胞癌肝移植和超适应证肝细胞癌肝移植的供肝选择以及供肝选择对肝细胞癌肝移植预后的影响进行深入探讨。