基于网络药理学和实验验证探讨香菇多糖抑制三阴乳腺癌的作用机制

目的 基于网络药理学研究香菇多糖抑制三阴乳腺癌（TNBC）的作用机制并采用细胞和动物实验进行验证。方法 通过GeneCards数据库和DisGeNET数据库筛选与TNBC相关基因靶点，利用TCMID、PubChem、SwissTargetPrediction和GeneCards数据库查询香菇多糖相关基因靶点。使用Sangerbox软件进行基因本体论（GO）富集和京都基因与基因组百科全书（KEGG）通路富集分析。结合STRING数据库与Cytoscape 3.7.0软件将共同靶点进行可视化处理，筛选核心靶点，构建"化合物-靶点-通路"网络。利用Metascape软件进行转录因子及相关调控基因特异富集。体外培养小鼠TNBC细胞4T1和人TNBC细胞MDA-MB-231，磺酰罗丹明B染色法观察香菇多糖（31.25、62.5、125、250、500、1 000μg·mL^-1）对细胞存活率的影响；健康雌性BABLC小鼠sc接种1×10⁶个4T1-Luc细胞构建TNBC模型，通过小动物活体成像系统观察香菇多糖（100、200 mg·kg^-1）对肿瘤生长的影响，实时荧光定量PCR （qRT-PCR）技术检测肿瘤组织信号转导和转录活化因子3（STAT3）和血管内皮生长因子A （VEGFA） mRNA表达。结果 数据库及软件分析得到香菇多糖治疗TNBC关键靶点52个，靶点主要涉及PI3K-Akt、AGE-RAGE、HIF-1、MAPK信号通路和肿瘤蛋白多糖相关通路，PPI分析得到VEGFA、STAT3、MAPK1、IL2、TNF、RELA、AKT1、MAPK3、BCL2L1和HSP90AA1 10个hub基因。与对照组比较，香菇多糖对4T1和MDA-MB-231细胞存活率均有显著抑制作用（P<0.05、0.01），且作用呈浓度相关性；在给药14、21d后，与模型组比较，香菇多糖能够剂量相关性地抑制小鼠TNBC肿瘤的生长，高剂量组差异显著（P<0.05、0.01），21 d抑制率达到（91.9±4.7）%；与对照组比较，香菇多糖给药后能够剂量相关性抑制STAT3和VEGFA的mRNA表达，高剂量组差异显著（P<0.05、0.01）。结论 香菇多糖可通过多靶点、多途径协同作用抑制TNBC的生长。     

Telehealth: An Effective Model of Care for Renal Cancer Surveillance

The coronavirus disease 2019 pandemic presented challenges for urology patients to receive care in the format of a traditional clinic visit. For renal cancer patients, active surveillance and postintervention surveillance are the standard components of management. Telehealth, which was defined as a televideo encounter via the BlueJeans (Verizon) platform (a telehealth platform), was used to ensure continuity of care. Telehealth using the televideo modality was shown to be an effective model of care delivery to provide an optimal patient experience with ease of use.     

Postoperative mortality and morbidity after D2 lymphadenectomy for gastric cancer:A retrospective cohort study

BACKGROUND Surgery for gastric cancer is a complex procedure and lymphadenectomy is often mandatory.Postoperative mortality and morbidity after curative gastric cancer surgery is not insignificant.AIM To evaluate the factors determining mortality and morbidity in a population of patients undergoing R0 resection and D2 lymphadenectomy for gastric cancer.METHODS A retrospective analysis of clinical data and pathological characteristics(age,sex,primary site of the tumor,Lauren histotype,number of positive lymph nodes resected,number of negative lymph nodes resected,and depth of invasion as defined by the standard nomenclature)was conducted in patients with gastric cancer.For each patient we calculated the Kattan’s score.We arbitrarily divided the study population of patients into two groups based on the nomogram score(<100 points or≥100 points).Prespecified subgroups in these analyses were defined according to age(≤65 years or>65 years),and number of lymph nodes retrieved(≤35 lymph nodes or>35 lymph nodes).Uni-and multivariate analysis of clinical and pathological findings were performed to identify the factors affecting postoperative mortality and morbidity.RESULTS One-hundred and eighty-six patients underwent a curative R0 resection with D2 lymphadenectomy.Perioperative mortality rate was 3.8%(7 patients);a higher mortality rate was observed in patients aged>65 years(P=0.002)and in N+patients(P=0.04).Following univariate analysis,mortality was related to a Kattan’s score≥100 points(P=0.04)and the presence of advanced gastric cancer(P=0.03).Morbidity rate was 21.0%(40 patients).Surgical complications were observed in 17 patients(9.1%).A higher incidence of morbidity was observed in patients where more than 35 lymph nodes were harvested(P=0.0005).CONCLUSION Mortality and morbidity rate are higher in N+and advanced gastric cancer patients.The removal of more than 35 lymph nodes does not lead to an increase in mortality.     

Latin dance and Qigong/Tai Chi effects on physical activity and body composition in breast cancer survivors: A pilot study

BackgroundBreast cancer survivors (BCS), particularly Latina BCS, experience weight gain and reduced physical activity (PA) post-treatment increasing the risk for recurrence. There is a lack of evidence on the intensity and type of PA needed to engage cultural subgroups and improve clinical outcomes. This study developed and piloted two non-traditional PA interventions among a diverse sample of BCS.MethodsTwenty BCS (65% Latina; age 25–75) participated in a 2-arm parallel group-randomized pilot study to test the effects of an 8-week Latin dance and Qigong/Tai Chi intervention on PA and body composition. A seven-day pedometer protocol was used to measure steps/week and a bioelectric impedence scale was used to assess BMI and %body fat. T-tests were used to examine preliminary outcomes across both interventions and within intervention arms.ResultsThere were no significant changes in steps/week, BMI, or %body fat across or in each separate intervention. A small effect size for increase in steps/day was found among participants in the Qigong/Tai Chi arm (0.10) and low-to-moderate effect sizes for reductions in % body fat overall (0.36), and separately for participants in Latin dance (0.26) and Qigong/Tai Chi (0.46).ConclusionLatin dance and Qigong/Tai Chi are engaging and acceptable PA modalities that are promising for improving PA and body fat among diverse, high-risk BCS. Our findings highlight the need to continue to reach and engage high-risk BCS, including Latina survivors, using novel, culturally-sensitive PA interventions. Future studies should extend and more rigorously test these novel approaches to improving outcomes associated with recurrence.     

Effectiveness,safety and quality of life of trifluridine/tipiracil in pretreated patients with metastatic colorectal cancer: Real-world data from the noninterventional TACTIC study in Germany

The prospective, multicenter, noninterventional TACTIC study assessed effectiveness and safety of trifluridine/tipiracil (FTD/TPI) in patients with metastatic colorectal cancer (mCRC) in a real-world setting in Germany, thus evaluating the external validity of the findings from the pivotal RECOURSE trial. Primary endpoint was overall survival (OS). Secondary objectives included progression-free survival (PFS), safety, and quality of life (QoL). Subgroups comprised patients with good (<3 metastatic sites at inclusion, ≥18 months from diagnosis of first metastasis to inclusion) or poor (remaining patients) prognostic characteristics (GPC/PPC). GPC without liver metastases was considered best prognostic characteristics (BPC). In total, 307 eligible patients (pretreated or not suitable for other available therapies) were treated with FTD/TPI. Overall, median [95%-CI] OS was 7.4 months [6.4-8.6], median PFS was 2.9 months [2.8-3.3]. In BPC (n = 65) and GPC (n = 176) compared to PPC (n = 124) subgroup, median OS (13.3 [9.1-17.6] vs 8.9 [7.6-9.8] vs 5.1 [4.4-7.0] months) and median PFS (4.0 [3.3-5.3] vs 3.4 [3.0-3.7] vs 2.6 [2.4-2.8] months) were longer. Patient-reported QoL, assessed by validated questionnaires (EQ-5D-5L, PRO-CTCAE), was stable throughout FTD/TPI treatment. Predominant FTD/TPI-related adverse events of grades 3 or 4 were neutropenia (13.0%), leukopenia (7.5%), and anemia (5.2%). Altogether, palliative FTD/TPI therapy in patients with pretreated mCRC was associated with prolonged survival, delayed progression, maintained health-related QoL, and manageable toxicity. Low metastatic burden and indolent disease were favorable prognostic factors for survival. TACTIC confirms the effectiveness and safety of FTD/TPI, highlighting its value in routine clinical practice.     

Cribado de cáncer de pulmón: Supervivencia en un amplio programa de detección precoz en España (I-ELCAP)

IntroductionLung cancer (LC) is usually diagnosed at advanced stages with only a 12% 5-year survival. Trials as NLST and NELSON show a mortality decrease, which justifies implementation of lung cancer screening in risk population. Our objective was to show survival results of the largest LC screening program in Spain with low dosage computed tomography (LDCT).MethodsClinical records from International Early Lung Cancer Detection Program (IELCAP) at Valencia, Spain were analysed. This program recruited volunteers, ever-smokers aged 40-80 years, since 2008. Results are compared to those from other similar sizeable programs.ResultsA total of 8278 participants were screened with at least two-rounds until November 2020. A mean of 6 annual screening rounds were performed. We detected 239 tumours along 12-year follow-up. Adenocarcinoma was the most common histology, being 61.3% at stage I. The lung cancer prevalence and incidence proportion was 1.5% and 1.4%, respectively with an annual detection rate of 0.17. One-year survival and 10-year survival were 90% and 80.1%, respectively. Adherence was 96.84%.ConclusionLargest lung cancer screening in Spain shows that survival is improved when is performed in multidisciplinary team experienced in management of LC, and is comparable to similar screening programs.