Review: Pathogenesis of Helicobacter pylori infection

The original strategies developed by Helicobacter pylori to persistently colonise its host and to deregulate its cellular functions make this bacterium an outstanding model to study host‐pathogen interaction and the mechanisms responsible for bacterial‐induced carcinogenesis. During the last year, significant results were obtained on the role of bacterial factors essential for gastric colonisation such as spiral shape maintenance, orientation through chemotaxis and the formation of bacteria clonal population islands inside the gastric glands. Particularities of the H pylori cell surface, a structure important for immune escape, were demonstrated. New insights in the bacterial stress response revealed the importance of DNA methylation‐mediated regulation. Further findings were reported on H pylori components that mediate natural transformation and mechanisms of bacterial DNA horizontal transfer which maintain a high level of H pylori genetic variability. Within‐host evolution was found to be niche‐specific and probably associated with physiological differences between the antral and oxyntic gastric mucosa. In addition, with the progress of CryoEM, high‐resolution structures of the major virulence factors, VacA and CagT4SS, were obtained. The use of gastric organoid models fostered research revealing, preferential accumulation of bacteria at the site of injury during infection. Several studies further characterised the role of CagA in the oncogenic properties of H pylori, identifying the activation of novel CagA‐dependent pathways, leading to the promotion of genetic instabilities, epithelial‐to‐mesenchymal transition and finally carcinogenesis. Recent studies also highlight that microRNA‐mediated regulation and epigenetic modifications, through DNA methylation, are key events in the H pylori‐induced tumorigenesis process.     

An on-lattice agent-based Monte Carlo model simulating the growth kinetics of multicellular tumor spheroids

PurposeTo develop an on-lattice agent-based model describing the growth of multicellular tumor spheroids using simple Monte Carlo tools.MethodsCells are situated on the vertices of a cubic grid. Different cell states (proliferative, hypoxic or dead) and cell evolution rules, driven by 10 parameters, and the effects of the culture medium are included. About twenty spheroids of MCF-7 human breast cancer were cultivated and the experimental data were used for tuning the model parameters.ResultsSimulated spheroids showed adequate sizes of the necrotic nuclei and of the hypoxic and proliferative cell phases as a function of the growth time, mimicking the overall characteristics of the experimental spheroids. The relation between the radii of the necrotic nucleus and the whole spheroid obtained in the simulations was similar to the experimental one and the number of cells, as a function of the spheroid volume, was well reproduced. The statistical variability of the Monte Carlo model described the whole volume range observed for the experimental spheroids. Assuming that the model parameters vary within Gaussian distributions it was obtained a sample of spheroids that reproduced much better the experimental findings.ConclusionsThe model developed allows describing the growth of in vitro multicellular spheroids and the experimental variability can be well reproduced. Its flexibility permits to vary both the agents involved and the rules that govern the spheroid growth. More general situations, such as, e. g., tumor vascularization, radiotherapy effects on solid tumors, or the validity of the tumor growth mathematical models can be studied.     

Discovery of a novel selective water-soluble SMAD3 inhibitor as an antitumor agent

Targeting the SMAD3 protein is an attractive therapeutic strategy for treating cancer, as it avoids the potential toxicities due to targeting the TGF-β signaling pathway upstream. Compound SIS3 was the first selective SMAD3 inhibitor developed that had acceptable activity, but its poor water solubility limited its development. Here, a series of SIS3 analogs was created to investigate the structure–activity relationship for inhibiting the activation of SMAD3. On the basis of this SAR, further optimization generated a water-soluble compound, 16d, which was capable of effectively blocking SMAD3 activation in vitro and had similar NK cell-mediated anticancer effects in vivo to its parent SIS3. This study not only provided a preferable lead compound, 16d, for further drug discovery or a potential tool to study SMAD3 biology, but also proved the effectiveness of our strategy for water-solubility driven optimization.     

PDCA循环在提高肿瘤患者输液港护理依从性的应用

目的探讨PDCA循环在提高肿瘤患者输液港护理依从性的应用效果。方法选取2018年2~8月我院收治的504例输液港置管的肿瘤患者按随机分配原则分为对照组240例和观察组264例,对照组给予一般治疗和常规管理,观察组在对照组基础上实施PDCA循环管理,观察两组患者的并发症发生情况、输液港护理依从性,并进行统计分析。结果观察组的并发症发生率明显低于对照组,差异有统计学意义(P<0.05);观察组的输液港护理依从性明显高于对照组,差异有统计学意义(P<0.05)。结论运用PDCA循环能优化维护流程,降低并发症,提高患者输液港护理依从性,值得临床应用。     

消癌平注射液联合表柔比星新辅助化疗对三阴性乳腺癌患者免疫功能、生活质量及血清肿瘤标志物的影响

摘要 目的：探讨消癌平注射液联合表柔比星新辅助化疗对三阴性乳腺癌（TNBC）患者免疫功能、生活质量及血清肿瘤标志物的影响。方法：选取TNBC患者89例,按照随机数字表法分为对照组和研究组,对照组（n=44）患者给予表柔比星新辅助化疗治疗,研究组（n=45）患者给予消癌平注射液联合表柔比星新辅助化疗。对比两组疗效、免疫功能、生活质量、血清肿瘤标志物及不良反应。结果：研究组治疗12周后的临床总有效率为91.11%（41/45）,高于对照组的63.64%（28/44）（P<0.05）。两组治疗12周后健康调查简表（SF-36）量表各维度评分升高,且研究组较对照组高（P<0.05）。两组治疗12周后CD4+CD25+Treg、Th17/ Treg均降低,且研究组较对照组低（P<0.05）,Th17升高,且研究组较对照组高（P<0.05）。两组治疗12周后癌胚抗原（CEA）、糖类抗原199（CA199）、糖类抗原125（CA125）均降低,且研究组较对照组低（P<0.05）。两组不良反应发生率对比未见差异（P>0.05）。结论：消癌平注射液联合表柔比星新辅助化疗治疗TNBC,具有确切的治疗效果,可降低血清肿瘤标志物水平,改善患者免疫功能和生活质量。     

肺癌住院患者营养不良风险调查及其影响因素分析

摘要 目的：肺癌住院患者营养不良风险调查及其影响因素分析。方法：选择2015年2月至2020年1月期间我院诊治的125例肺癌住院患者的临床资料进行回顾性分析。根据患者的营养状态评估结果将其分为81例营养不良组和44例营养良好组。比较两组患者的人口学资料和临床资料,采用多因素Logistic回归分析营养不良发生的影响因素。结果：营养不良患者占比64.80%（81/125）。与营养良好组相比,营养不良组年收入≥50000元患者比例明显下降（P<0.05）,营养不良组体质量指数（BMI）≤22 kg/m²患者比例、肿瘤分期III~Ⅳ期+广泛期患者比例以及肿瘤低分化患者比例明显升高,血清白蛋白水平和淋巴细胞绝对值（LYM）明显下降（P<0.05）。经多因素Logistic回归分析显示肿瘤分期III~Ⅳ期+广泛期以及肿瘤低分化是肺癌住院患者营养不良的危险因素（OR=1.743、1.812,P<0.05）,年收入≥50000元、BMI>22kg/m²、白蛋白水平≥29.55 g/L和LYM≥2.47×10⁹/L是肺癌住院患者营养不良的保护因素（OR=0.487、0.502、0.453、0.731,P<0.05）。结论：肺癌住院患者营养不良风险较高,年收入情况、BMI、肿瘤分期、分化程度、白蛋白水平以及LYM均是肺癌住院患者营养不良风险的影响因素,对上述指标进行监测有利于提前预测营养不良的发生,从而为预防肺癌住院患者营养不良的发生提供指导。     

特罗凯靶向治疗联合培美曲塞和顺铂对非小细胞肺癌患者血清肿瘤标志物、免疫球蛋白和T淋巴细胞亚群的影响

摘要 目的：探讨特罗凯靶向治疗联合培美曲塞和顺铂对非小细胞肺癌（NSCLC）患者血清肿瘤标志物、免疫球蛋白和T淋巴细胞亚群的影响。方法：选取2018年2月~2020年2月期间我院接收的NSCLC患者80例,采用抽签法分为对照组、观察组两组,各40例。对照组给予培美曲塞和顺铂化疗方案治疗,观察组在对照组基础上联合特罗凯靶向治疗,对比两组总有效率、血清肿瘤标志物、免疫球蛋白、T淋巴细胞亚群及不良反应发生率。结果：对比两组不良反应无差异（P>0.05）。治疗3个疗程后,对照组、观察组的临床总有效率分别为37.50%、60.00%,观察组的总有效率高于对照组（P<0.05）。治疗3个疗程,观察组CD3⁺、CD4⁺、CD4⁺/CD8⁺高于对照组,CD8⁺低于对照组（P<0.05）。治疗3个疗程,观察组免疫球蛋白G（IgG）、免疫球蛋白A（IgA）、免疫球蛋白M（IgM）高于对照组（P<0.05）。治疗3个疗程,观察组细胞角蛋白19片段（CYFRA21-1）、糖类抗原50（CA50）、癌胚抗原（CEA）低于对照组（P<0.05）。结论：特罗凯靶向治疗联合培美曲塞和顺铂治疗NSCLC患者,疗效较好,可能与该方案可降低患者血清肿瘤标志物含量、调节免疫应答等因素有关。     

肿瘤坏死因子α刺激基因/诱导蛋白-6的抗炎作用研究进展

炎症损伤是众多临床疾病的病理学基础,常可引起严重并发症甚至导致死亡。然而传统临床治疗不仅方法有限,且效果不佳。近年研究报道,肿瘤坏死因子α刺激基因/诱导蛋白-6(tumor necrosis factor alpha stimulated gene/inducible protein 6, TSG-6)可通过与体内相应的配体结合参与炎症反应的多个过程,并发挥抗炎和促进细胞外基质重塑等重要作用。本文就TSG-6的生物学特性、作用机制及其在病理性瘢痕、神经炎症、动脉粥样硬化和关节炎等多种疾病中发挥的抗炎作用作一综述。     

Clinical and pathological significance of programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) expression in high grade serous ovarian cancer

We investigated programmed cell death 1 (PD-1) / programmed cell death ligand 1 (PD-L1) expression in high grade serous ovarian cancer (HGSOC) and its relationship to tumor infiltrating lymphocytes (TIL) and prognosis. Formalin fixed paraffin embedded (FFPE) samples of 94 HGSOC cases were included in the study. Immunohistochemical analysis (CD3, CD4, CD8, PD-1 and PD-L1) was performed. Samples were analyzed for expression of immune proteins in the peritumoral stromal and intratumoral areas, scored, and expression was correlated with overall survival, stage, and age. PD-L1 staining ratio with a score greater than 0 was found to have lower survival. There were two positive staining patterns, patchy/diffuse and patchy/focal patterns, in 24 (25.5%) cases. Considering the threshold value ≥5%, we demonstrated that the PD-L1 positive cancer cell membrane immunoreactivity rate and patchy/diffuse PD-L1 expression were 9.6% (n = 9). There was statistically significant relationship between high PD-1 scores and PD-L1 cases of ≥ 5%. A statistically significant difference was found between PD-L1 staining and survival in patients with a threshold ≥ 5%. However an appropriate rate for treatment was determined in 9.6% cases. There was a statistically significant correlation between PD-1 positive TIL score and intratumoral CD3, peritumoral stromal CD3, intratumoral CD4 and intratumoral CD8 positive cells. Survival was lower in cases with higher PD-L1 positive stromal TIL score.     

Understanding the function of the tumor microenvironment,and compounds from marine organisms for breast cancer therapy

The pathology and physiology of breast cancer(BC),including metastasis,and drug resistance,is driven by multiple signaling pathways in the tumor microenvironment(TME),which hamper antitumor immunity.Recently,long non-coding RNAs have been reported to mediate pathophysiological developments such as metastasis as well as immune suppression within the TME.Given the complex biology of BC,novel personalized therapeutic strategies that address its diverse pathophysiologies are needed to improve clinical outcomes.In this review,we describe the advances in the biology of breast neoplasia,including cellular and molecular biology,heterogeneity,and TME.We review the role of novel molecules such as long non-coding RNAs in the pathophysiology of BC.Finally,we provide an up-to-date overview of anticancer compounds extracted from marine microorganisms,crustaceans,and fishes and their synergistic effects in combination with other anticancer drugs.Marine compounds are a new discipline of research in BC and offer a wide range of anti-cancer effects that could be harnessed to target the various pathways involved in BC development,thus assisting current therapeutic regimens.