Abstract Lung cancer is the leading cause of death among all cancers. A persistent chronic inflammatory microenvironment is highly correlated with lung cancer. However, there are no anti‐inflammatory agents effective against lung cancer. Cytochrome P450 2E1 (CYP2E1) plays an important role in the inflammatory response. Here, it is found that CYP2E1 is significantly higher in the peritumoral tissue of non‐small cell lung cancer (NSCLC) patients and lung tumor growth is significantly impeded in Cyp2e1 −/− mice. The novel CYP2E1 inhibitor Q11, 1‐(4‐methyl‐5‐thialzolyl) ethenone, is effective in the treatment of lung cancer in mice, which can inhibit cancer cells by changing macrophage polarization rather than directly act on the cancer cells. It is also clarify that the benefit of Q11 may associated with the IL‐6/STAT3 and MAPK/ERK pathways. The data demonstrate that CYP2E1 may be a novel inflammatory target and that Q11 is effective on lung cancer by regulation of the inflammatory microenvironment. These findings provide a molecular basis for targeting CYP2E1 and illustrate the potential druggability of the CYP2E1 inhibitor Q11.
Objective: To investigate the clinical and pathologic features, diagnosis and differential diagnosis of hypertrophic port-wine stain (PWS). Methods: Cases of hypertrophic PWS, collected from Henan Provincial People's Hospital between 2012 and 2018, were retrospectively analyzed for their clinical and pathologic features, immunophenotype and histochemical data, and the relevant literature was reviewed. Results: Twenty-four cases of PWS were included in this cohort, located in the head and neck region (20 cases), limbs (2 cases), and trunk (2 cases). The clinical presentations were mainly red or purple-red plaques or slow growing, painless nodules, or thickened and raised above the skin surface. Microscopically, deformed blood vessels showed honeycomb-like, plexiform or cluster-like growth pattern, and diffusely involved the dermis, skin appendages, subcutaneous fat tissue, and deep skeletal muscles; The vascular lumen of the deformed vessels was dilated (≥100 μm in diameter), and in 18 cases the lumen was greater than 400 μm. The superficial dermis mainly contained few deformed capillaries. The deep wall showed thickening of blood vessel wall and fibrous tissue hyperplasia. Elastic fiber and Masson staining indicated abnormal venous vessel, which in some cases contained small amount of abnormal arterioid vessel,without vascular endothelial cell proliferation in all cases. In 24 cases, 19 cases had epidermal atrophy, 6 with vascular chronic inflammation or epidermal ulcer, 4 with capillary hemangioma, 4 with sebaceous gland hyperplasia, 2 with epidermal papillary hyperplasia and 2 with vascular keratomas. Conclusions: PWS is a common congenital capillary malformation. The number of histologically deformed capillaries is reduced and they usually locate in the superficial part. The deep vascular wall is increased with thick venous malformation, diffusely involving the dermis and deep skeletal muscle. Furthermore, PWS needs to be differentiated from infantile hemangioma, cavernous hemangioma and vascular keratomas.目的： 探讨增厚型葡萄酒色斑（port-wine stain，PWS）的临床及病理学特征、诊断及鉴别诊断。 方法： 收集并分析2012至2018年河南省人民医院确诊的增厚型PWS 24例，复查相关临床及病理学资料，同时采用免疫组织化学和组织化学染色方法检测相关组织成分，并复习文献。 结果： 24例增厚型PWS中，发病部位包括头颈部（20例）、四肢（2例）、躯干（2例）。临床表现主要为无痛性缓慢增长的红色或紫红色斑块、结节，隆起于表面皮肤，呈增厚结节状。镜下可见畸形血管呈蜂窝状、丛状或簇状生长方式，弥漫累及真皮、皮肤附属器、皮下脂肪组织，以及深部骨骼肌；畸形血管管腔扩张，且管腔直径均≥100 μm，其中>400 μm者18例，均为晚期病变；真皮浅层处以畸形毛细血管为主，数量多少不等，深部可见血管壁增厚、纤维组织增生，弹力纤维及Masson染色提示为畸形静脉样管腔，个别病例含有少量畸形动脉样管腔，且均未见血管内皮细胞增生；其中19例合并表皮萎缩，6例合并慢性脉管炎或表皮溃疡，4例合并毛细血管瘤，4例合并皮脂腺增生，2例合并表皮乳头状增生，2例合并血管角皮瘤。 结论： PWS是一种较常见的先天性毛细血管畸形，组织学上畸形毛细血管数量减少且位于浅表部位，深部血管管壁增厚以静脉畸形样特征为主，且弥漫累及真皮层及深部骨骼肌，需要与婴幼儿血管瘤、海绵状血管瘤、血管角皮瘤等进行鉴别诊断。.
Objective: To study clinical and pathologic characteristics of leiomyomas of the gastrointestinal tract, and to investigate the distribution characteristics of interstitial cells of Cajal ( ICCs ) in gastrointestinal leiomyomas. Methods: One hundred and forty-seven cases of leiomyomas of gastrointestinal tract were collected at the Second Affiliated Hospital of Zhengzhou University from June 2012 to June 2017. Clinical and pathologic findings were analyzed, combined with immunohistochemistry, Alcian blue-osafranin staining and molecular study. Results: The age of patients ranged from 13-82 years with mean age of 52 years. Male to female ratio was about 1∶2. Histologically, all tumors were composed of ovoid to spindle cells arranged in short intersecting fascicles. All tumors were diffusely and strongly positive for smooth muscle antibodies, desmin and h-caldesmon by immunohistochemical staining. A prominent interspersed subpopulation of elongated/dendritic-like cells with CD117 and DOG1 positivity (accounting for 1% to 30% of all tumor cells) and negative for Alcian blue-osafranin staining was identified in all esophageal leiomyomas, 16 of 20 (80%) gastric leiomyomas and 3 of 12 small bowel leiomyomas, but none in colonic/rectal leiomyomas. Mutational analysis in 16 cases showed absence of mutation in exons 9, 11, 13 or 17 of C-KIT and exons 12 or 18 of PDGFRA. Conclusions: ICCs are identified in esophageal and gastric leiomyomas, as well as in small percentage of intestinal leiomyomas. Such findings may bring significant diagnostic pitfalls for misdiagnosis as gastrointestinal stromal tumor. Careful attention to the distribution of CD117 and DOG1 positive cells and molecular mutation analysis of C-KIT and PDGFRA may be necessary to establish the correct diagnosis.目的： 探讨消化道平滑肌瘤的临床病理特征，以及Cajal间质细胞(interstitial cells of Cajal，ICC)在消化道平滑肌瘤中的分布特点。 方法： 收集郑州大学第二附属医院2012年6月至2017年6月147例消化道平滑肌瘤临床及病理资料，光镜下观察HE切片，免疫组织化学及奥辛蓝－沙红染色，Sanger测序检测C－KIT和PDGFRA基因突变状态。 结果： 患者年龄13～82岁，平均年龄52岁。男女比例接近1∶2。发生于食管100例，胃20例，小肠12例，结直肠15例。组织学上卵圆形或梭形肿瘤细胞呈条束状或编织状排列。肿瘤细胞弥漫阳性表达平滑肌肌动蛋白、结蛋白及h－caldesmon，CD117与DOG1阳性且奥辛蓝－沙红染色阴性的分支状细胞散在分布于肿瘤内，该类细胞见于100%(100/100)食管平滑肌瘤、80%(16/20)胃平滑肌瘤、3/12的小肠平滑肌瘤，所占比例1%～30%不等，而不存在于结直肠平滑肌瘤中。16例CD117与DOG1阳性且奥辛蓝－沙红染色阴性细胞比例≥20%的平滑肌瘤均未检测到C－KIT及PDGFRA基因突变。 结论： ICC普遍存在于食管、胃及小肠平滑肌瘤中，不能因为肿瘤细胞表达CD117与DOG1而误诊为胃肠道间质瘤，必要时可借助分子检测进行鉴别。.
Sclerosing angiomatoid nodular transformation (SANT) of spleen is a benign lesion with a distinct morphological and immunohisochemical characteristics. Only Weinred I et al (Virchow Arch 451: 73-9, 2007) reported 6 cases of SANT expressing CD30, of which positive for EBV by in situ hybridization (EBER). 4 cases of SANT were added to investigate the clinicopathological features and focused on the expression of CD30 and EBER combined with the previously published literature. Histologically, individual angiomatoid nodules were sharply delineated by fibrocollagenous stroma with numerous vascular lumens and surrounded by a different population of spindle and ovoid cells. Angiomatoid nodules of all of the 4 cases heterogeneously expressed CD34, CD8, CD68 and diffusely demonstrated CD31 and CD30, but none were positive for EBER. We added these cases with reviewed literature to emphasize and verify the fact that upregulated expression of CD30 in SANT is quite common, which should be taken into consideration when making differential diagnosis.
Background The role of p16 INK4a as a surrogate marker for screening human papillomavirus (HPV) in esophageal squamous cell carcinoma (ESCC) remains controversial. Methods A comprehensive search of EMBASE, PubMed, China National Knowledge Infrastructure and China Biology Medicine was performed from inception to December 27, 2015. A random-effects model was applied to the pooled odds ratios (ORs) with 95% confidence intervals (CIs). Results Ten studies were identified (985 cases). The pooled results showed no significant relationship between p16 INK4a expression and HPV infection in ESCC based on overall HPV types (OR: 1.79, 95% CI: 0.69-4.66, p = 0.235). Subgroup analysis by HPV detection method showed no statistical significance in either the polymerase chain reaction (PCR) (OR: 1.65, 95% CI: 0.83-3.30, p = 0.154) or in situ hybridization (ISH) group (OR: 2.58, 95% CI: 0.03-268.14, p = 0.689). The pooled OR of the sensitivity analysis ranged from 1.27 (95% CI: 0.58-2.84) to 2.32 (95% CI: 0.95-5.64). Of these studies, 6 involved only high-risk human papillomavirus types (HR-HPV), HPV16 or HPV18. However, similar observations were made for HR-HPV (OR = 1.31, 95% CI: 0.26-6.59, p = 0.741). Subgroup analysis again showed no statistical significance in the PCR group (OR: 0.95, 95% CI: 0.25-3.64, p = 0.940) and ISH group (OR: 2.58, 95% CI: 0.03-268.14, p = 0.689). Sensitivity analysis showed that the pooled OR ranged from 0.69 (95% CI: 0.21-2.22) to 1.89 (95% CI: 0.33-10.86). Conclusions p16 INK4a is not a reliable screening marker of HPV infection in ESCC. Further multicenter, large-sample and well-matched prospective studies are still required to illuminate the possible etiological roles of HPV in ESCC.
BACKGROUND:H2A histone family member Z (H2AFZ) is a special subtype in the H2A histone family, which participates in the regulation of gene transcription. Nevertheless, little is known about the role of H2AFZ in the tumor microenvironment and genetic factors associated with lung cancer. MATERIAL AND METHODS:The expression of H2AFZ in LUAD was analyzed via Tumor Immune Estimation Resource (TIMER), the Cancer Genome Atlas (TCGA), and Gene Expression Omnibus (GEO) databases at the mRNA level. To detect the protein expression level of H2AFZ, immunohistochemistry (IHC) was performed using LUAD tissues and non-tumor lung tissues. Kaplan-Meier survival analysis and Cox regression analysis were conducted to identify the effect of H2AFZ expression on overall survival (OS) based on TCGA-LUAD and the GEO dataset GSE68465 cohorts, and our LUAD patient cohort was used for validation. Identification of signaling pathways associated with the expression of H2AFZ was performed using Gene Set Enrichment Analysis (GSEA). The influences of expression of H2AFZ on tumor immune-infiltrating cell (TIICs) were assessed via TIMER and CIBERSORT. RESULTS:The expression of H2AFZ was increased in LUAD tissues at both mRNA and protein levels. In addition, high expression of H2AFZ predicted poor OS and might be an independent prognostic predictor in LUAD patients. Moreover, H2AFZ affected the relative proportion of TIICs and was positively associated with Myeloid-derived suppressor cells (MDSC) infiltration level in LUAD. CONCLUSIONS:H2AFZ was upregulated in LUAD and related to poor prognosis of LUAD patients; thus, it could be an underlying prognostic biomarker correlated with immune infiltration in LUAD.
With the aim of improving the prognosis of patients with lung adenocarcinoma (LUAD), we identified the biomarker related to the sensitivity of patients to chemotherapy drugs and explored the potential mechanisms. As a cell cycle-related protein, CKS2 has an essential role to play in tumor progression and prognosis. CKS2 expression was measured using TCGA RNA-sequencing data and immunohistochemistry. The sensitivity data of tumor cells to chemotherapeutic drugs for lung cancer was acquired from the Cancer Therapeutics Response Portal (CTRP) database. A range of bioinformatics methods was used to explore the mechanisms of CKS2 upregulation. The biological functions of CKS2 were predicted using GO and KEGG enrichment analysis, as well as GSEA. CKS2 expression was up-regulated in stages I–III invasive non-mucinous lung adenocarcinoma and varied significantly between various histological subtypes. High CKS2 expression worsened the prognosis of patients. The CKS2 expression level was linked to the sensitivity of LUAD cells to carboplatin and paclitaxel. CKS2 upregulation was associated with the immune microenvironment, mRNA methylation, and competing endogenous RNAs (ceRNAs). CKS2 can serve as a diagnostic and prognostic biomarker for stages I–III invasive non-mucinous lung adenocarcinoma and modulate the effect of paclitaxel and carboplatin by regulating microtubule binding and influencing carboplatin binding to DNA.
According to the WHO, the cribriform pattern is a subtype of acinar (Aci) predominance in invasive adenocarcinoma (ADC) of the lung. Recently, several studies have demonstrated poor prognosis in patients with cribriform predominance. This study was performed to examine the correlations of cribriform pattern with the clinicopathology, molecular features and prognosis in patients with invasive ADC.Histological subtypes were evaluated in 279 patients who underwent complete resection for invasive ADC. Patients of the Aci-predominant subtype were divided into two subgroups according to the percentage of cribriform cancer (≥5% vs <5%). Clinicopathological characteristics, overall survival (OS), disease-free survival (DFS) and molecular changes were compared. In addition, both OS and DFS were compared between patients with cribriform-predominant (n=33) and pure Aci-predominant (n=88) ADCs.A cribriform pattern was found in 111 (39.8%) cases and ranged from 5 % to 100 % of the total tumour volume (mean±SEM, 30%±2%). Of 117 patients with Aci predominance, 79 showed the cribriform pattern, while the remaining 38 did not. The cribriform pattern was associated with aggressive pathological behaviour, including advanced stages of cancer, nuclear atypia, mitoses, lymph node invasion, metastasis and larger tumour size. The subgroup with cribriform cancer (≥5%) had significantly poorer OS and DFS compared with the cribriform-negative (<5%) group. In addition, Cox multivariate analyses revealed that the cribriform pattern was an independent predictor of OS but not DFS. Moreover, OS was significantly lower in the cribriform-predominant group than in the Aci-predominant group.The cribriform pattern is associated with aggressive pathological behaviour and is an independent poor prognostic indicator in patients with Aci-predominant ADC of the lung.
Zinc finger protein 267 (ZNF267) is a member of the Kruppel-like transcription factor family, which regulates various biological processes such as cell proliferation and differentiation. However, the biological significance of ZNF267 and its potential role in diffuse large B-cell lymphoma (DLBCL) remain to be documented. Experiments were herein conducted to study the role of ZNF267 in DLBCL. real-time quantitative reverse transcription PCR and Western blotting assays were conducted to detect the expression of ZNF267 in tissues and cells. Tissue microarray and bioinformatics analyses of public data were also done to detect the expression status and clinical significance of ZNF267. Functional cell experiments including CCK8 assay, colony formation assay, 5-ethynyl-2'-deoxyuridine (EDU) assay, terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) assay, transwell assay, and wound healing assay were conducted to study the effects of ZNF267 knockdown and overexpression on cell proliferation and mobility. Xenograft assay was also conducted to confirm the effects of ZNF267 knockdown
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