F10蛋白及mRNA在部分正常组织及癌组织中的表达

目的:了解F10基因在部分正常组织及肿瘤组织中的表达情况。方法:利用原位杂交和免疫组化方法对F10在部分正常组织和肿瘤组织中的mRNA和蛋白表达情况进行分析。结果:F10基因不仅在腺癌组织中表达呈阳性,在鳞癌组织中表现出较腺癌更强的强阳性,并且在正常组织中也有一定的表达。结论:F10是一个在多种组织普遍表达的细胞内蛋白,其功能可能与物质转运相关。     

Esophageal squamous cell carcinoma and adenocarcinoma in Malaysia – Pooled data from upper gastrointestinal centers in a multiethnic Asian population

BackgroundEsophageal cancer is the sixth leading cause of cancer death worldwide with considerable geographical histological variation There is a paucity of data in esophageal cancer in demographics, histology, and survival among the multi-ethnic Malaysian population. This paper is a review of esophageal cancer epidemiology and survival among esophageal cancer patients from data collected by the Malaysian Upper Gastrointestinal Surgical Society.MethodsThis is a multicenter retrospective observational study of esophageal cancer patients from six upper gastrointestinal surgical centers in Malaysia between 2005 and 2019. Patient characteristics, histological type and stage were compared and survival analyzed.ResultsThere were 820 patients with esophageal cancer included, where 442 (53.9 %) cases had squamous cell carcinoma (SCC) and 378 (46.1 %) had adenocarcinomas (AC). Malays were the predominant ethnicity with AC (66.7 %) while Indians were the ethnic majority (74.6 %) with SCC. Majority of patients (56.8 %) presented as stage IV disease. Overall, the 1-, 3-, and 5-years’ survival were 35.8 %, 13.8 % and 11.0 %, respectively. Surgical resection with curative intent yielded the best 5-year survival (29.4 %). Intervention in stage IV AC yielded superior survival when compared to SCC (median survival, 7.9 months vs 4.8 months; p, 0.018) Our series demonstrated an increase in AC to SCC over the last 15 years.ConclusionsThere was an ethnic preponderance seen between different histology in this region, not previously discussed. An increase in AC was observed over the last 15 years. Late diagnosis seen in most patients imparts poor prognosis as curative surgery affords the best outcome.     

Recent advancement in the discovery and development of COX-2 inhibitors: Insight into biological activities and SAR studies (2008–2019)

Cyclooxygenase-2 is a very important physiological enzyme playing key roles in various biological functions especially in the mechanism of pain and inflammation, among other roles, making it a molecule of high interest to the pharmaceutical community as a target. COX 2 enzyme is induced only during inflammatory processes or cancer and reflects no role in the guarding stomach lining. Thus, selective COX-2 inhibition can significantly reduce the adverse effects including GI tract damage and hepatotoxic effects of traditional NSAIDs like aspirin, ibuprofen, etc. Recent developments on COX-2 inhibitors is primarily focused on improving the selectivity index of the drug towards COX-2 along with enhancing the potency of the drug by modifying the scaffolds of Coxibs currently in the market like Celecoxib, Indomethacin, Oxaprozin, etc. We have reported the progress on new COX-2 inhibitors in the last decade (2008–2019) focussing on five heterocyclic rings- Pyrazole, Indole, Oxazole, Pyridine and Pyrrole. The addition of various moieties to these core rings and their structure-activity relationship along with their molecular modelling data have been explored in the article. This review aims to aid medicinal chemists in the design and discovery of better COX-2 inhibitors constructed on these five heterocyclic pharmacophores.     

Characteristics of long-term survivors of brain metastases from lung cancer

Background and aim

Long-term survival of lung cancer patients with brain metastases (BM) is very rare. Our aim is to report the characteristics of patients who survived for at least three years after a BM diagnosis.

Materials and methods

Nineteen lung cancer patients who had survived ≥3 years after a BM diagnosis were identified in our database. Seven (37%) had undergone whole-brain radiotherapy (WBRT) only, five (26%) BM surgery + WBRT, three (16%) BM surgery + WBRT + BM radiosurgery, and four (21%) no WBRT (one, surgery; one, radiosurgery; two, BM surgery + radiosurgery). Their characteristics were compared with historical data for 322 lung cancer patients with BM (control group, CG), who had received WBRT between 1986 and 1997.

Results

Median survival from BM in long survivors group was 73 months (in CG – 4 months). Characteristics comparison: median age 55 vs. 58 (CG), p = 0.16; female sex 68% vs. 28% (CG), p = 0.003; RTOG/RPA class 1 – 75% vs. 13% (CG), p = 0.00001; adenocarcinoma histology 84% vs. 24% (CG), p < 0.00001; control of primary tumor 95% vs. 27% (CG), p < 0.00001; extracranial metastases 0 vs. 26% (CG), p = 0.01; single BM 63% vs. 9% (CG), p = 0.00001; surgery of BM 53% vs. 14% (CG), p = 0.00001.

Conclusions

Beside prognostic factors already recognized as favorable in patients with BM, the adenocarcinoma histology and female sex were prevalent in long-term survivors of BM from lung cancer.     

ILK在肺鳞状细胞癌和肺腺癌的表达及其与临床病理特征和预后的关系

目的 探讨ILK在肺鳞状细胞癌和肺腺癌组织中的表达情况,及其与病理分型、肿瘤分化、分期、淋巴结转移及预后的关系。方法采用S-P免疫组织化学方法和Western Blot法,检测肺鳞状细胞癌和肺腺癌组织及相应癌旁肺组织中整合连接激酶（integrin-linkedkinase,ILK）的表达情况,并结合临床和病理资料进行分析。结果免疫组化结果显示：ILK在53／76（70％）的肺癌组织中阳性表达。其中鳞状细胞癌阳性率75％（33／44）,腺癌阳性率62．5％（20／32）,其表达与肺鳞状细胞癌的分化呈负相关（P〈0．01）,与临床分期（P〈0．01）、淋巴结转移（P〈0．01）呈正相关;与肺腺癌的临床分期（P〈0．01）和淋巴结转移（P〈0．01）正相关,与分化程度无相关性（P〉0．05）。同时,其表达与患者的生存时间呈负相关（P〈0．01）,与年龄、性别、肿瘤大小和组织类型等因素无关。Western Blot法进一步证实ILK在肺癌组织中的表达显著高于癌旁正常肺组织（P〈0．01）,其表达与肺癌的分化（P〈0．01）显著负相关。结论肺鳞状细胞癌和肺腺癌中,ILK与肺癌的侵袭和转移有关。ILK可作为判断肺鳞状细胞癌和肺腺癌预后的参考指标。     

Adenocarcinoma of the gallbladder in an owl monkey (<Emphasis Type="Italic">Aotus trivirgatus</Emphasis>)

This paper describes an adenocarcinoma of the gallbladder in a 12-year-old male owl monkey. Whereas the histological appearance in the gallbladder itself was relatively benign, well-differentiated cystic structures were found in the pancreatic lymph node. In addition, paradox metastazing behavior revealed a few cystic structures in the lymph nodes of the gut.     

Glucocorticoids inhibit the induction of nitric oxide synthase and the related cell damage in adenocarcinoma cells

Lipopolysaccharide (LPS) induced a time-dependent synthesis of nitric oxide (NO) in EMT6 adenocarcinoma cells, assayed by accumulation of NO-derived nitrite in the medium. The induction NO synthesis was inhibited in a concentration-dependent manner by the glucocorticoids dexamethasone (IC₅₀ = 5 nM) and hydrocortisone (IC₅₀ = 20 nM) and this effect was partially antagonized by progesterone and cortexolone. If addition of dexamethasone was delayed 6 h or more, inhibition of nitrite accumulation over 24 h was substantially reduced, indicating a lack of direct effect of glucocorticoids on the NO synthase. Nitrite accumulation was accompanied by cell damage, which was increased by L-arginine and inhibited by $\text{N}{}^{\mathrm{<mtext>G</mtext>}}\text{-}\text{monomethyl-}\text{L}\text{-arginine}$ (L-NMMA) and dexamethasone. These data show that NO is a primary cytotoxic mediator and that suppression of its formation by glucocorticoids explains some of their anti-inflammatory and cytoprotective effects.     

Inhibition of pancreatic adenocarcinoma cellular invasiveness by blebbistatin: a novel myosin II inhibitor

Blebbistatin is a novel 1-phenyl-2-pyrrolidinone derivative capable of inhibiting non-muscle myosin II activity with a high degree of specificity. We examined the effects of blebbistatin on pancreatic adenocarcinoma cellular migration, invasion, adhesion, and spreading. Blebbistatin dose-dependently inhibited cellular migration and invasiveness, quantified by modified Boyden chamber assay. Matrix metalloproteinase 2 and 9 activities were unaffected by blebbistatin and cellular proliferation was inhibited only by concentrations of blebbistatin exceeding those required to inhibit myosin II activity and to interfere with migration and invasion. While blebbistatin treatment did not affect cell adhesion to the extracellular matrix component fibronectin, it markedly impaired cell spreading on this substrate. Cell surface expression of the archetypal fibronectin receptor (alpha(5)beta(1) integrin) was unaffected by blebbistatin. Our observations illustrate the critical role of non-muscle myosin II in pancreatic adenocarcinoma cellular invasiveness and extracellular matrix interaction and suggest that therapeutic strategies targeting myosin II warrant further investigation.     

Proteomic signature of human cancer cells

We assessed proteomic profiles as biomarkers for monitoring cell phenotypes. Protein expression profiles were obtained by fluorescence two-dimensional difference gel electrophoresis (2-D-DIGE), in which quantitative ability is improved by labeling proteins with fluorescent dyes prior to electrophoresis. Integrated protein spot intensities were analyzed by a statistical approach. The proteomic data of two groups of cell lines: (1) adenocarcinoma (AC) cell lines derived from lung, pancreas and colon tissues and (2) lung cancer cell lines with different histological backgrounds, including AC, squamous cell carcinoma and small cell carcinoma, were assessed on the basis of prior biological information. Hierarchical clustering analysis and principal component analysis were used to divide the cell lines into subgroups on the basis of similarities between their protein expression profiles. The majority of cell lines were grouped according to their organ of origin or histological background. A machine-learning algorithm selected 32 protein spots that were responsible for the classification. The results indicate that proteomic data generated by 2-D-DIGE can provide a signature of essential cell phenotypes, suggesting that it might be possible to apply this technique to developing tumor markers that could identify the organ of origin of metastatic tumors and contribute to the differential diagnosis of lung cancer.