Changes in cytokine production of breast cancer patients treated with interferons

A clinical randomized study was performed on advanced breast cancer patients who were treated by interferons (IFN) beta and gamma in combination with hormonotherapy (Megace or Tamoxifen). Cytokine levels (IL-1beta, IL-2, IL-6, TNF-alpha, IFN-gamma) and sIL-2R of individual patients before, during (3 months) and after (6 months) therapy were evaluated and correlated to clinical response according to UICC criteria (responder patients-partial or Complete Response versus non-responder patients-Stable/Progression). Decreases in IL-1beta, IL-6 and sIL-2R were associated with clinical response to therapy versus increases in their levels which corresponded to progression of disease. A significant and dramatic increase in IFN-gamma levels was associated with a favourable response to therapy in the IFNs-treated patients, mainly in the group of Tamoxifen. Baseline levels of sIL-2R and of IFN-gamma were prognostic of clinical response and were found to be the most sensitive cytokine parameters for defining the clinical utility of the combination of IFNs and hormonotherapy in breast cancer patients.     

肠道菌群特征与食管癌患者术后肺部感染的关系

探究食管癌患者术前肠道菌群特征与术后肺部感染的关系,为该类患者的治疗提供参考。

纳入我院2019年6月至2021年12月期间收治的272例食管癌手术患者为研究对象,根据术后是否并发肺部感染将其分为感染组（64例）和非感染组（208例）,记录患者年龄、高血压、吸烟史等一般资料。采用选择性培养基培养患者肠道大肠埃希菌、肠球菌属、葡萄球菌属、双歧杆菌属、酵母菌属、乳杆菌属、消化球菌属细菌并按照平板计数法计数,同时进行16S rRNA基因测序,进行菌群多样性分析。采用Logistic回归进行食管癌患者术后肺部感染的影响因素分析。

感染组与非感染组患者肠道菌群Chaol指数、Shannon指数、Simpson指数比较差异均无统计学意义（均P＞0.05）。与非感染组比较,感染组患者年龄≥60岁、吸烟史≥20年、术前FEV1/FVC＜70%、手术时间≥4 h患者比例及肠道大肠埃希菌、肠球菌属、葡萄球菌属数量显著升高,而肠道双歧杆菌属、酵母菌属、乳杆菌属、消化球菌属数量显著降低（均P＜0.05）。大肠埃希菌、肠球菌属是影响食管癌患者术后发生肺部感染的独立危险因素,而双歧杆菌属是影响食管癌患者术后发生肺部感染的保护因素（均P＜0.05）。

食管癌术后肺部感染患者与未发生肺部感染的其术前肠道菌群差异显著,大肠埃希菌、肠球菌属、双歧杆菌属是食管癌患者术后发生肺部感染的影响因素。

     

Percutaneous comprehensive cryoablation for metastatic esophageal cancer after failure of radical surgery

Esophageal cancer is common in China. There is a lack of treatment strategies for metastatic esophageal cancer (MEC) after radical surgery on the primary tumor. Cryoablation is an attractive option because tumor necrosis can be safely induced in a minimally invasive manner. This study assessed its therapeutic effect in MEC after failure of radical surgery. One hundred and forty patients met the inclusion criteria from May, 2003 to March, 2011. Comprehensive cryotherapy of multiple metastases was performed on 105 patients; 35 received chemotherapy. No severe complications occurred during or after cryoablation. Overall survival (OS) was assessed according to therapeutic protocol, pathologic type, treatment timing and number of procedures. The OS of patients who received comprehensive cryoablation (44 ± 20 months) was significantly longer than that of those who underwent chemotherapy (23 ± 24 months; P = 0.0006). In the cryotherapy group, the OS for squamous cell carcinoma (45 ± 19 months) was longer than that for adenocarcinoma (33 ± 18 months; P = 0.0435); the OS for timely cryoablation (46 ± 19 months) was longer than that for delayed cryoablation (33 ± 20 months; P = 0.0193); the OS for multiple cryoablation (50 ± 17 months) was longer than that for single cryoablation (37 ± 20 months; P = 0.0172); and the OS for cryo-immunotherapy (56 ± 17 months) was longer than that for cryoablation alone (39 ± 19 months; P = 0.0011). Thus, comprehensive cryotherapy may have advantages over chemotherapy in the treatment of MEC and, in patients with squamous cell carcinoma, supplementary immunotherapy and timely and multiple cryoablation may be associated with a better prognosis.     

Admission neopterin and interleukin 12 concentrations in identifying infections in adult cancer patients

Differential diagnosis between infections and neoplastic fever is a common diagnostic problem. The utility of admission serum concentrations of neopterin and interleukin 12 (IL-12) was prospectively evaluated in this respect. The infection group (n=56) had a higher median neopterin value (12.8 nmol/l vs 4.0 nmol/l, P<0.001) and neopterin-to-IL-12 ratio (1.74 vs 0.11, P<0.001) than the non-infection group (n=36); the median IL-12 values were higher in the latter group (10.6 pg/ml vs 71.6 pg/ml, P=0.007). According to the area under the operating characteristics curves (AUC), especially neopterin (0.90), but also the neopterin-to-IL-12 ratio (0.79), was good at identifying bacteremia. However, in differentiating infections in general from neoplastic fever (n=10), the neopterin-to-IL-12 ratio was less powerful (0.64), though still better than neopterin (0.58) and clearly better than IL-12 (0.42). The present results show that the neopterin-to-IL-12 ratio, which reflects simultaneously both the ongoing infection and the tumour load, may have promising clinical implications for differential diagnosis between infections and neoplastic fever.     

Intrafraction esophageal motion in patients with clinical T1N0 esophageal cancer

Aim

To investigate the intrafraction movement of the esophagus using fiducial markers.

结直肠癌患者血清GDF-15、G-CSF水平与临床病理特征及预后的关系

摘要 目的：探究结直肠癌血清生长分化因子-15（GDF-15）、粒细胞集落刺激因子（G-CSF）水平与患者临床病理参数、预后的关系,并分析其对结直肠癌的诊断价值。方法：采集结直肠癌患者、结直肠腺瘤患者及健康体检志愿者的血清样本,酶联免疫吸附测定（ELISA）实验检测血清GDF-15、G-CSF;分析结直肠癌患者血清GDF-15、G-CSF水平与患者临床病理参数的关系;Kaplan Meier生存曲线分析血清GDF-15、G-CSF水平与患者预后的关系;受试者工作特征曲线（ROC）分析血清GDF-15、G-CSF水平对结直肠癌的诊断价值。结果：结直肠癌患者血清GDF-15、G-CSF水平高于结直肠腺瘤患者及健康体检志愿者（均P<0.05）;血清GDF-15水平与肿瘤直径、分化程度、远处转移及TNM分期相关（均P<0.05）;血清G-CSF水平与肿瘤分化程度、远处转移及TNM分期相关（均P<0.05）;Kaplan Meier生存曲线结果显示,血清GDF-15低表达、G-CSF低表达患者的术后5年总生存率及中位生存时间均分别高于血清GDF-15高表达、G-CSF高表达患者（均P<0.05）;ROC分析结果表明,血清GDF-15、G-CSF有较好的诊断结直肠癌的价值,血清GDF-15、G-CSF联合应用的敏感度、特异度分别为0.876、0.863。结论：结直肠癌患者血清GDF-15、G-CSF水平升高,且均与患者病情恶性进展、不良预后相关;血清GDF-15、G-CSF是诊断结直肠癌的潜在指标。     

右旋美托咪啶用于食道癌手术麻醉的临床研究

目的：观察右旋美托咪啶用于食道癌手术麻醉的临床研究。方法：100例美国麻醉医师协会（ASA）Ⅰ-Ⅱ级择期行食道癌手术患者,随机分为生理盐水组（A组）和右旋美托咪啶组（B组）（n=50）,麻醉诱导前10min分别静脉注射右旋美托咪啶1μg／kg、生理盐水10ml后,两组麻醉诱导和维持相同。随后持续注射右旋美托咪啶0．4μg／kg·h直至手术结束前30min,观察与记录麻醉诱导前（T0）、插管即刻（T1）、拔管后1min（T2）、5min（T3）、10min（T4）平均动脉压（MAP）、心率（HR）、血氧饱和度（SaO2）、中心静脉压（CVP）、丙泊酚用量、芬太尼用量及不良反应。结果：T0、T1、T2,T3、T4A组与B组比较,MAP明显下降、HR明显减慢（P〈0．05）,丙泊酚和芬太尼用药量B组显著少于A组（P〈0．05）。B组术后咽喉疼痛、呛咳躁动发生率也明显低于A组（P〈0．05）。结论：右旋美托咪啶可减轻食道癌手术气管插管与拔管的心血管反应、减少麻醉药用量,减少胸科手术后咽喉疼痛、呛咳躁动的发生率。     

Association of perioperative allogeneic blood transfusion with postoperative survival of patients with gastric cancer after curative gastrectomy

To explore the association of perioperative allogeneic blood transfusion (PABT) and postoperative survival rates in patients with gastric cancer (GC). In total, 186 patients with gastric cancer accepted curative gastrectomy were divided into three groups, the PABT <2 U group, the PABT > 2 U group, and the no blood transfusion group. The relationships between PABT and clinical pathological parameters were analyzed and their effects on the postoperative survival of patients with GC were studied. Multivariable COX regression results showed that PABT and tumor size are the important factors influencing the postoperative survival of patients with GC (P<0.05). When comparing with the no blood transfusion group and the PABT < 2 U group, the patient’s risk of death in the PABT > 2 U group rises to 3.282 and 2.130 times (95%CI: 1.731-4.886 and 1.194-3.797) (P<0.05), respectively. This study suggests that PABT is significantly associated with postoperative survival after curative gastrectomy in patients with GC.     

MTP-PE in liposomes as a biological response modifier in the treatment of cancer: Current status

MTP-PE in liposomes is a BRM which can be given relatively safely to patients with cancer. The maximum tolerated dose appears to be higher than the optimal dose inducing immunomodulatory effects such as cytokine induction and monocyte/macrophage activation. The most consistently induced cytokines measured in the plasma of patients a few hours after MTP-PE are TNF and IL-6. Indirect evidence supports the assumption that increased levels of TNF and IL-6 are signs of macrophage activation occurringin situ in tissues taking up liposomal MTP-PE shortly after injection. These tissues are mainly lungs, liver and spleen, as shown in 4 patients injected with radiolabelled liposomes containing MTP-PE. Assuming that activated monocytes and macrophages cannot eliminate gross tumor load, the main targets for MTP-PE are micrometastases after removal of the primary tumor. Thus, adjuvant treatment using liposomal MTP-PE in combination with chemotherapy is a major goal for the future.     

Oridonin-induced mitochondria-dependent apoptosis in esophageal cancer cells by inhibiting PI3K/AKT/mTOR and Ras/Raf pathways

Oridonin, an active diterpenoid isolated from Rabdosia rubescens, has been reported for its antitumor activity on several cancers. However, its effect on human esophageal cancer remains unclear. In this study, we demonstrated that oridonin could inhibit the growth of human esophageal cancer cells both in vitro and in vivo. Oridonin not only suppressed the proliferation, but also induced cell cycle arrest and mitochondrial-mediated apoptosis in KYSE-30, KYSE-150, and EC9706 cells with dose-dependent manner. Further mechanism studies revealed that oridonin led cell cycle arrest in esophageal cancer cells via downregulating cell cycle-related proteins, such as cyclin B1 and CDK2, while upregulating p53 and p21. Oridonin also increased proapoptotic protein Bax and reduced antiapoptotic protein Bcl-2, as well as the increased expression of cleaved caspase-3, -8, and -9. In addition, oridonin treatment could significantly inhibit the PI3K/Akt/mTOR and Ras/Raf signaling pathway. In vivo results further demonstrated that oridonin treatment markedly inhibited tumor growth in the esophageal cancer xenograft mice model. Taken together, these results suggest that oridonin may be a potential anticancer agent for the treatment of esophageal cancer.     

Establishment of a human anaplastic thyroid cancer cell line secreting granulocyte colony-stimulating factor in response to cytokines

Summary A human anaplastic thyroid cancer cell line K-119, derived from a 77-yr-old woman who had developed marked neutrophilia and underwent surgery for anaplastic thyroid cancer, has been established. The spindlelike and polygonal cells in shape are stably proliferating since the beginning of its culture 2 yr ago. The cells grow rapidly and the population doubling time is 26 h. The chromosomes show many abnormalities and many marker chromosomes have been observed. Heterotransplantation of the cells into nude mice has resulted in the formation of tumors that are histologically interpreted as anaplastic cancer. The most noteworthy characteristics of the cell line are the many Ki-67-positive cells (86.3%) and that the cell line spontaneously secretes granulocyte colony-stimulating factor (G-CSF) and releases increased amounts of G-CSF in response to the stimulation of tumor necrosis factor, interleukin 1α, and interleukin 1β. The conditioned medium obtained from K-119 cells contains an autocrine factor stimulating the proliferation of themselves.     

七氟醚对宫颈癌患者围术期炎性应激反应的影响

目的 研究七氟醚麻醉对宫颈癌患者围术期血清相关细胞因子的影响.方法 将组织学诊断为宫颈癌的患者90例,按手术时采用的麻醉药物的不同随机分为三组:第Ⅰ组患者为异丙酚组(Ⅰ组,n=30);第Ⅱ组患者为七氟醚组(Ⅱ组,n=30);第Ⅲ组患者为异丙酚+七氟醚组(Ⅲ组,n=30);观察麻醉前30 min,手术开始后1、2h,手术结束后1、24和48 h六个时点患者血清肿瘤坏死因子-α(TNF-α)、白细胞介素-8(IL-8)和白细胞介素-10(IL-10)水平的变化.结果 三组患者术后血清TNF-α、IL-8和IL-10水平与麻醉前值比较均升高(P＜0.01),一般在术后24 h达峰值.比较血清TNF-α、IL-8和IL-10浓度变化,Ⅰ组和Ⅱ组之间差异无统计学意义,Ⅲ组抑制这三种细胞因子释放的能力明显强于Ⅰ组和Ⅱ组(P＜0.05).结论 应用七氟醚或异丙酚进行麻醉维持在官颈癌手术中,两者控制炎性应激反应的作用类似;七氟醚联合异丙酚进行麻醉维持可更有效地降低术后炎性应激反应.     

Co-drug development of gallic acid and metformin targeting the pro-inflammatory cytokines for the treatment of breast cancer

It is well-documented that pro-inflammatory cytokines and inflammation play a significant role in the expansion of cancer disease. Gallic acid (GA), a natural compound, and metformin (Met), a synthetic drug exhibit potent anticancer potential via the distinct molecular mechanism. However, whether both these compounds can act synergistically to preclude and treat cancer is still unknown. This prompted us to scrutinize, the synergism between GA and Met, and that of a new co-drug synthesizing of GA and Met (GA-Met) and investigated the chemo-protective effect against breast cancer with possible intervention of cytokines. In vivo studies were based on chemical carcinogenesis, challenging breast tissue by dimethylbenz[α]anthracene (DMBA). Tumour incidence, tumour burden, pro-inflammatory cytokines in serum, breast, hepatic tissue, macroscopically and histological analysis of mammary tumours were carried out and estimated. GA, Met and GA-Met co-drug exhibited the inhibition of cell proliferation; higher reduction of cell proliferation was observed by GA-Met. The inhibitory effect of GA-Met was linked to cell cycle arrest at G0/G1 phase, along with induction of apoptosis and accumulation in the sub-G1 phase. GA-Met significantly inhibited the cytokines production along with protection against DMBA-induced hyperplasia. Taken altogether, the current result suggests that GA-Met co-drug endows a safe and protective effect against cancer metastasis and can possibly use for the treatment of human breast cancer.     

Prevalence of esophageal squamous dysplasia in relatives of patients with esophageal cancer in Southwestern Kenya

BackgroundEsophageal squamous cell carcinoma (ESCC) and its asymptomatic precursor lesion, esophageal squamous dysplasia (ESD), are common in East Africa. It is unknown whether family history of esophageal cancer is a risk factor for both ESD and ESCC in Africa, and whether family members of affected persons should be screened.MethodsWe recruited 296 asymptomatic adult first-degree relatives of ESCC patients residing in southwestern Kenya. Participants completed questionnaires and underwent endoscopy with Lugol’s iodine staining and biopsy to determine the prevalence of ESD. Prevalence comparisons were made with a prior population-based cohort from the same catchment area who also underwent Lugol’s chromoendoscopy.ResultsMean age was 40.7 years, compared to 62.7 years in the prior population study. The overall prevalence of ESD/ESCC among first-degree relatives was 14.7%, comparable to the background population prevalence of 14.4%, and this comparability remained even after adjusting for the different age distributions of the studies. Post-primary education was the only measured variable that was associated with a decreased risk of ESD/ESCC (adjusted OR=0.31, 95% CI: 0.11, 0.83). There was heterogeneity in the ESD prevalence across families, even after adjustments for varying age and other measured factors.ConclusionsThe prevalence of esophageal squamous dysplasia among first-degree relatives of persons with ESCC was similar to that of the background population of southwestern Kenya; however, there was heterogeneity in ESD prevalence between families, suggesting other genetic or environmental factors may influence family prevalence. Further study of families with a high prevalence of ESD or ESCC is justified.     

高压氧疗法对创伤性脑损伤大鼠氧化应激指标及促／抗炎细胞因子水平的影响

目的：研究高压氧（HBO）疗法对创伤性脑损伤（TBI）大鼠氧化应激指标及促／抗炎细胞因子水平的影响方法：SD雄性大鼠18只,随机分为3组（n=6）：假手术组、损伤对照组和HBO治疗组采用Feency法建立大鼠TBI模型,假手术组只开放骨面,不予打击HBO治疗组大鼠于脑损伤后6h采用动物高压舱,以3ATA压力纯氧治疗60min。所有动物于手术后24h处死,分离脑组织,取伤侧脑半球行组织匀浆,分别测定匀浆上清液中超氧化物歧化酶（SOD）、丙二醛（MDA）、NO的含量以及促炎细胞因子TNF-α、IL-6、IL-1β及抗炎细胞因子IL-10的水平,结果：与损伤对照组相比,HBO治疗使SOD、NO以及IL-10水平升高,同时降低脑内MDA及TNF-α、IL-6、IL-1β的含量结论：HBO治疗可抑制TBI后自由基的生成,从而减轻脂质过氧化反应;同时,HBO治疗可减少促炎细胞因子的生成,促进抗炎细胞因子的产生,从而可减轻损伤脑组织的炎症反应,有助于减轻TBI后脑组织的继发性损伤.     

先兆流产患者阴道微生态与Th1及Th2细胞因子的关系探讨

目的 探讨先兆流产患者阴道微生态与Th1及Th2类细胞因子的关系。 方法 回顾性分析2019年2月-2020年2月医院收治的98例先兆流产患者的资料,记为A组,另回顾性分析同期在该院体检的92例健康孕妇的资料,记为B组。对比A组和B组阴道微生物菌群组成,对比A组和B组血清Th1及Th2类细胞因子水平,采用Pearson相关性分析,分析先兆流产患者阴道微生物菌群相对丰度与血清Th1及Th2类细胞因子水平的相关性。 结果 A组阴道微生物群Chao1指数、Shannon指数均低于B组(P结论 先兆流产患者阴道微生物菌群分布与血清Th1及Th2细胞因子水平相关。     

A randomized clinical trial on the antitumoral effects of low molecular weight heparin in the treatment of esophageal cancer

The current treatment approaches for esophageal cancer are associated with poor survival, and there are ongoing efforts to find new and more effective therapeutic strategies. There are several reports on the antitumoral effects of low-molecular-weight heparins (LMWHs). We have assessed the possible survival benefit of LMWHs in esophageal malignancies. This was a randomized, single-blind, multicenter, Phase II clinical trial on nonmetastatic esophageal cancer candidate for neoadjuvant chemoradiotherapy. Patients were randomly assigned to the chemoradiotherapy-only arm or chemoradiotherapy plus enoxaparin arm using 1:1 allocation. Radiotherapy was delivered in 1.8-Gy daily fractions to a dose of 50.4 Gy in both groups. Paclitaxel 50 mg/m² and carboplatin (AUC 2) were administered weekly, concurrent with radiotherapy. In the intervention group, patients received enoxaparin (40 mg) and chemoradiation daily. 4–6 weeks after treatment, all patients underwent esophagectomy. After a median follow up of 7 months, estimated 1 year disease-free survival (DFS) in the intervention group was 78.9% and was 70% in the control groups ( p = 0.5). Toxicity from the experimental treatment was minimal, and there were no treatment-related deaths. A pathologically complete response in intervention and control group was 64.8% and 62.5%, respectively ( p = 0.9). There was a nonsignificant trend toward improved survival by the addition of enoxaparin to the concurrent chemoradiotherapy regimen. However, 1 y DFS of both groups were high as expected. A longer follow-up and a larger sample size are required.     

The role of pretreatment prognostic nutritional index in esophageal cancer: A meta-analysis

Clinicopathological characteristics and prognosis of esophageal cancer (EC) patients with decreased prognostic nutritional index (PNI) have not been well investigated. So, we conducted this meta-analysis. We performed comprehensive research in PubMed, Embase, and Cochrane databases. The effect size was hazard ratio (HR) with 95% confidence interval (CI) for overall survival (OS) and cancer-specific survival (CSS). The pooled odds ratio (OR) with 95% CI were used to assess the association between PNI and clinicopathological features. A total of 3,425 EC patients were included in the present meta-analysis. Male patients, advanced age, higher tumor stage, and lymph node metastases were associated with reduced PNI level (OR = 1.40, 95% CI: 1.10-1.79; OR = 1.35, 95% CI: 1.10-1.66; OR = 2.37, 95% CI: 1.91-2.94; OR = 1.63, 95% CI: 1.04-2.56). And, the EC patients with decreased PNI held a worse OS and CSS compared with those who carried a higher PNI (HR = 1.29, 95% CI: 1.10-1.50; HR = 2.53, 95% CI: 1.15-5.57). This meta-analysis demonstrated PNI level was associated with tumor stage and lymph nodes metastases and was an independent prognostic factor in EC.