The local inflammatory response in colorectal cancer – Type,location or density? A systematic review and meta-analysis

IntroductionThe host anti-tumour inflammatory response is a strong prognostic indicator, and tumour infiltrating lymphocytes (TILs) are believed to have a complimentary role alongside TNM assessment in dictating future management. However, there is wide disagreement regarding the most efficacious and cost-effective method of assessment.MethodsA comprehensive literature search was performed of EMBASE, MedLine and PubMed as well as an assessment of references to identify all relevant studies relating to the assessment of the peri-tumoural inflammatory response or TILs and prognosis in colorectal cancer (CRC). A meta-analysis was performed of 67 studies meeting the REMARK criteria using RevMan software.ResultsIntratumoural assessment of both CD3 and CD8 in CRC were significant for disease-free survival (DFS) (combined HRs 0.46; 95%CI: 0.39–0.54 and 0.54; 95%CI: 0.45–0.65), as well as overall survival (OS) and disease-specific survival (DSS). The same was true for assessment of CD3 and CD8 at the invasive margin (DFS: combined HRs 0.45; 95%CI: 0.33–0.61 and 0.51; 95%CI: 0.41–0.62). However, similar fixed effects summaries were also observed for H&E-based methods, like Klintrup-Makinen grade (DFS: HR 0.62; 95%CI: 0.43–0.88). Furthermore, inflammatory assessments were independent of MSI status.ConclusionThe evidence suggests that it is the density of a co-ordinated local inflammatory infiltrate that confers survival benefit, rather than any individual immune cell subtype. Furthermore, the location of individual cells within the tumour microenvironment does not appear to influence survival. The authors advocate a standardised assessment of the local inflammatory response, but caution against emphasizing the importance of any individual immune cell subtype.     

床旁肺部超声在儿童重度社区获得性肺炎中的应用价值

目的:探讨床旁肺部超声在儿童重度社区获得性肺炎(CAP)中的应用价值。方法:收集2016年12月至2018年8月在本院儿童重症监护病房住院并临床诊断为儿童重度CAP的患儿120例,这些患儿均在入院24 h内进行床旁肺部超声及床旁胸片检查。分析儿童重度CAP的床旁肺部超声特点,并与胸片进行比较。结果:儿童重度CAP的床旁肺部超声的特点是A线消失、B线增多、瀑布征、肺实变、支气管充气征、胸腔积液,床旁肺部超声诊断儿童重度CAP的敏感性为99%,特异性为100%,阳性预测值为100%,阴性预测值为50%,阳性似然比∞,阴性似然比为9%,约登指数0.99。结论:床旁肺部超声诊断儿童重度CAP准确可靠,敏感性高、特异性强,具有能随时检测、无辐射等优点,可作为一项儿童重度CAP的辅助诊断工具。     

Ursolic acid promotes apoptosis,autophagy, and chemosensitivity in gemcitabine‐resistant human pancreatic cancer cells

Gemcitabine (GEM) resistance in pancreatic adenocarcinoma mediated by the receptor for advanced glycation end products (RAGE) has been demonstrated. Therefore, investigating the safety and the potential of new auxiliary methods for pancreatic cancer treatment is urgent. Ursolic acid (UA), a natural pentacyclic triterpenoid found in apple peels, rosemary, and thyme, has been reported to have anticancer capacity. This study aimed to reveal the underlying mechanisms of UA in cell death and drug enhancement, especially in GEM‐resistant pancreatic cancer cells. First, GEM‐resistant cells (MIA Paca‐2^GEMR cells) were established by incrementally increasing GEM culture concentrations. UA treatment reduced cell viability through cell cycle arrest and endoplasmic reticulum (ER) stress, resulting in apoptosis and autophagy in a dose‐dependent manner in MIA Paca‐2 and MIA Paca‐2^GEMR cells. High RAGE expression in MIA Paca‐2^GEMR cells was suppressed by UA treatment. Interestingly, knocking down RAGE expression showed similar UA‐induced effects in both cell lines. Remarkably, UA had a drug‐enhancing effect by decreasing cell viability and increasing cell cytotoxicity when combined with GEM treatment. In conclusions, UA triggered ER stress, subsequently regulating apoptosis‐ and autophagy‐related pathways and increasing GEM chemosensitivity in pancreatic cancer cells by inhibiting the expression of RAGE.     

海莲叶提取物对胃癌细胞增殖的抑制作用及对小鼠急性毒性实验

目的:探究海莲叶提取物对胃癌细胞增殖的抑制作用及对小鼠急性毒性实验。方法:先通过实验证实海莲叶提取物可对患者的胃癌细胞SGC-7091、MGC80-3可起到促进作用,应对实验小鼠皮下建立移植瘤模型,随后对小鼠注射海莲叶提取物,观察对胃癌细胞增殖的抑制情况,随后对药物的毒性进行分析。结果:给药组与溶媒对照组急性毒性反应相比显著较高,差异具有统计学意义(P<0.05)。结论:海莲叶提取物可对胃癌细胞增殖的抑制作用,并均已经在实验中得到了证实,海莲叶提取物可明显降低小鼠的急性毒性反应。     

食管癌患者化疗联合细胞免疫治疗前后外周血淋巴细胞亚群变化的分析

目的:探讨肿瘤分期和治疗对食管癌患者外周血淋巴细胞亚群的影响及其相应的临床意义。方法:选取在我院治疗的113例食管癌患者，其中45例中晚期患者接受了化疗联合细胞免疫治疗。对113例患者进行了治疗前外周血淋巴细胞亚群检测，对45例患者进行了联合治疗前后外周血淋巴细胞亚群、肿瘤标志物检测。分析细胞免疫治疗周期、疗效与外周血淋巴细胞亚群的相关性以及治疗前肿瘤血清学标志物与疗效的相关性。结果:早期食管癌患者CD8+/CD28+T细胞(Tc)比例高于中晚期患者，CD4+/CD25+T细胞(Treg)比例低于中晚期患者（P=0.011、P=0.015）。45例患者治疗后CD3+T细胞(TT)、Tc、髓系树突状细胞(mDCs)比例明显升高（P=0.003、P=0.039、P=0.007）。细胞免疫治疗1个周期14例（A组），2个周期16例（B组），3个周期及以上15例（C组）。A组患者治疗后TT比例明显升高，Treg比例明显下降；B组患者治疗后TT、Tc比例明显升高；C组患者发现了三组淋巴细胞亚群的变化，其中TT、Treg比例变化较A、B两组更为显著（P=0.003 7、P=0.002）。30例获得客观缓解的患者治疗后TT、Tc、自然杀伤T细胞(NKT)和mDCs比例较治疗前明显升高，而Treg比例则较前明显下降。治疗前鳞状上皮细胞癌相关抗原（SCC）正常的患者客观缓解率要好于升高的患者（P=0.029）。结论:中晚期食管癌患者较早期患者免疫失衡更为明显，细胞免疫治疗联合化疗可以改善食管癌患者的免疫状态，治疗效果与患者的免疫功能改善程度有关，SCC升高可能影响食管癌患者的近期疗效。     

CyclinA1 Promoter Methylation in Self-Sampling Test

Background: Self sampled HPV testing is a cervical cancer screening method . However, cytology in self-sampled specimen cannot be used as a triage test.  Therefore, other methods for triage should be considered. CyclinA1 (CCNA1) promoter methylation has strong association with cervical precancerous and cancerous lesion. The objective of this study was to compare the diagnostic value of CCNA1 and self-sampled specimen for detecting high-grade cervical intraepithelial lesions or worse (CIN2+). Materials and Methods: A cross sectional study was conducted. Women with abnormal cytology or positive for high risk HPV (hrHPV) indicated for colposcopic examination were enrolled.  Self-collected sampling for hrHPV DNA (SS-HPV) and CCNA1 were performed. hrHPV DNA testing was done by Cobas 4800 method. CCNA1 promoter methylation was detected by CCNA1 duplex methylation specific PCR. Histopathologic result as CIN2+ obtaining from colposcopic directed biopsy or excisional procedure  was considered as positive a gold standard. The results of hrHPV and CCNA1 were reported as positive or negative. Sensitivity specificity, positive predictive value, and negative predictive value of SS-HPV and CCNA1 were calculated by comparing the results with the gold standard. Results: Two hundreds and eighty women were recruited. High-grade cervical lesions and cervical cancer (CIN2+) were diagnosed in 21.8% (61 cases) of the patients. The most common type of hrHPV was non 16, 18 subtype, followed by HPV16 and 18. CCNA1 was positive in 13 patients out of whom, twelve were CIN2+. Sensitivity of CCNA1 was 19.7 % and its  specificity and accuracy were 99.5% and 82.14%, respectively.  The sensitivity of SS-HPV was 70.5%, and its  specificity and accuracy were 39.2% and 43.3%, respectively. Conclusion:  Due to high specificity and positive predictive value of CCNA1, it can be used as alarming sign of having high-grade cervical intraepithelial lesions, especially in patient who has positive hrHPV DNA test based on self-collected sampling.     

Anti-Cancer Effects of Traditional Medicinal Herbs on Oral Squamous Cell Carcinoma

Backgrounds: Oral squamous cell carcinoma (OSCC) is among the most frequent oral cancers in individuals under 40. Documents have endorsed that a diet enriched with fruit and vegetables can banish the risk of developing major cancers. This study aimed to evaluate the effects of different concentrations of four medicinal herbs including saffron, ginger, cinnamon and curcumin on OSCC cell line. Methods: Having obtained the aqueous extract of the four herbs, they were administered on OSCC cell lines per se and in dual, triple, and quadruple combinations. Their effects were measured in different concentrations and in 24 and 48 hours by using MTT assay. Results: The minimum and maximum effective concentrations were respectively 108 and 217 mg/ml for curcumin with IC30 of 77mg/ml, 108 and 270 mg/ml for ginger with IC30 of 58 mg/ml, 2 and 10 mg/ml for saffron with IC30 of 1.9 mg/ml, and 5 and 40 mg/ml for cinnamon with IC30 of 3.3 mg/ml. The best effect of the combinations was seen for cinnamon-saffron after both 24 and 48 hours and the four herbs combination after 48 hours. Conclusion: Although all the four herbs were effective on OSCC cell line, the strongest extract was saffron, followed by cinnamon. Combination of cinnamon-saffron and combination of the four herbs showed maximum effects. These findings suggest that traditional medicinal herbs may potentially contribute to oral cancer treatment; providing new windows for the development of new therapeutic strategies for OSCC.