[A preliminary exploration into the efficacy of personalized surgical schemes in the repair of maxillary sinus perforation and maxillary sinus fistula].

To explore the efficacy and value of personalized surgical schemes in the repair of maxillary sinus perforation and maxillary sinus fistula based on the size of the maxillary sinus perforation and maxillary sinus fistula. A total of 28 patients with maxillary sinus perforation and maxillary sinus fistula who were admitted to the Department of Oral and Maxillofacial Surgery, Stomatology Hospital of Kunming Medical University from July 2017 to May 2020 were included to conduct a prospective case clinical study. After the inflammation in the maxillary sinus was controlled, a proper surgical repair method was selected according to the size of the perforation and fistula based on the double-layer closure technique. The diameter of the perforation and fistula was measured with the assistance of cone-beam CT. After that, the platelet rich fibrin (PRF) repair was performed on the perforation and fistula with 3 mm≤diameter<7 mm in size in 14 patients. The PRF repair and buccal flap repair were performed on the perforation and fistula with 7 mm ≤diameter<15 mm in size in 7 patients. The adjacent buccal pad repair, palatine flap repair, and buccal flap repair were performed on the perforation and fistula with 15 mm≤ diameter<25 mm in size in 4 patients. The nasolabial axial flap repair and nasolabial free flap repair were performed on the perforation and fistula with a diameter ≥25 mm in size in 3 patients. The medical follow-up was conducted in all patients in the 1st, 2nd, and 4th week after surgery, with an overall success rate reaching 96.4% (27/28) after the initial intervention. The relapse of disease occurred in one patient (4.6%) with diabetes and a smoking history in the 2nd week after surgery. Identifying a proper surgical repair method according to the size of the oral and maxillary sinus perforation and maxillary sinus fistula based on the double-layer closure technique can improve the one-time cure rate in these patients under the premise that the inflammation in the maxillary sinus can be controlled.

[Clinical characteristics of 272 437 patients with different histopathological subtypes of primary esophageal malignant tumors].

Objective: To characterize the histopathological subtypes and their clinicopathological parameters of gender and onset age by common, rare and sparse primary esophageal malignant tumors (PEMT). Methods: A total of 272 437 patients with PEMT were enrolled in this study, and all of the patients were received radical surgery. The clinicopathological information of the patients was obtained from the database established by the State Key Laboratory of Esophageal Cancer Prevention & Treatment from September 1973 to December 2020, which included the clinical treatment, pathological diagnosis and follow-up information of esophagus and gastric cardia cancers. All patients were diagnosed and classified by the criteria of esophageal tumor histopathological diagnosis and classification (2019) of the World Health Organization (WHO). The esophageal tumors, which were not included in the WHO classification, were analyzed separately according to the postoperative pathological diagnosis. The χ2 test was performed by the SPSS 25.0 software on count data, and the test standard α=0.05. Results: A total of 32 histopathological types were identified in the enrolled PEMT patients, of which 10 subtypes were not included in the WHO classification. According to the frequency, PEMT were divided into common (esophageal squamous cell carcinoma, ESCC, accounting for 97.1%), rare (esophageal adenocarcinoma, EAC, accounting for 2.3%) and sparse (mainly esophageal small cell carcinoma, malignant melanoma, etc., accounting for 0.6%). All the common, rare, and sparse types occurred predominantly in male patients, and the gender difference of rare type was most significant (EAC, male∶ female, 2.67∶1), followed with common type (ESCC, male∶ female, 1.78∶1) and sparse type (male∶ female, 1.71∶1). The common type (ESCC) mainly occurred in the middle thoracic segment (65.2%), while the rare type (EAC) mainly occurred in the lower thoracic segment (56.8%). Among the sparse type, malignant melanoma and malignant fibrous histiocytoma were both predominantly located in the lower thoracic segment (51.7%, 66.7%), and the others were mainly in the middle thoracic segment. Conclusion: ESCC is the most common type among the 32 histopathological types of PEMT, followed by EAC as the rare type, and esophageal small cell carcinoma and malignant melanoma as the major sparse type, and all of which are mainly occur in male patients. The common type of ESCC mainly occur in the middle thoracic segment, while the rare type of EAC mainly in the lower thoracic segment. The mainly sparse type of malignant melanoma and malignant fibrous histiocytoma predominately occur in the lower thoracic segment, and the remaining sparse types mainly occur in the middle thoracic segment.

[Introduction and implications of WHO position paper: vaccines against influenza, May 2022].

On May 13, 2022, World Health Organization(WHO) Position Paper on Influenza Vaccine (2022 edition) was published. This position paper updates information on influenza epidemiology, high risk population, the impact of immunization on disease, influenza vaccines and effectiveness and safety, and propose WHO's position and recommendation that all countries should consider implementing seasonal influenza vaccine immunization programmes to prepare for an influenza pandemic. In addition, it proposes that the influenza surveillance platform can be integrated with the surveillance of other respiratory viruses, such as SARS-CoV-2 and Respiratory Syncytial Virus. This position paper has some implications for the prevention and control of influenza and other respiratory infectious diseases in China: (1) Optimize influenza vaccine policies to facilitate the implementation of immunization services; (2) Influenza prevention and control should from the perspective of Population Medicine focus on the individual and community to integrate with "Promotion, Prevention, Diagnosis, Control, Treatment, Rehabilitation"; (3) Incorporate prevention and control of other respiratory infectious diseases such as influenza, COVID-19, respiratory syncytial virus and adenovirus, and intelligently monitor by integrating multi-channel data to achieve the goal of co-prevention and control of multiple diseases.

[Clinical pathological features of 180 cases with primary esophageal malignant melanoma].

Objective: To investigate the clinical pathological and epidemiological characteristics of primary esophageal malignant melanoma (PMME). Methods: The clinical pathology data of 180 PMME patients in the esophageal cancer database of the key laboratory of esophageal cancer research in Henan Province from 1973 to 2016 were collected, of which 136 were male, aged (58.5±9.0) years, 44 were female, aged (56.7±12.2) years. Kaplan-Meier and Log rank test were used for survival analysis, Cox regression scale model was used for risk factor analysis. Results: The incidence of PMME is 0.036% (180/500, 000), mostly were male (about 3∶1 for men: female). The common sites of PMME were the lower part of the esophagus (48.9%, 85/174), followed by the middle section of the esophagus (46.0%, 80/174) and the upper part of the esophagus (5.2%, 9/174). No black particles were seen in the PMME cells of 3 patients under microscope, and strong positive expressions of Melan-A and HMB453 were observed in these 3 patients by immunohistochemical results. Of the 129 patients who had a routine preoperative esophageal biopsy, 69 were undiagnosed with PMME (53.5%). The medium survival time of the whole group was 7.9 months, and the survival rates of 1, 2, 3, 5 years were 25.0%, 7.9%, 6.6% and 1.3%, respectively. The univariate analysis showed that N, M, TNM phase and radiotherapy were related to the overall survival of patients (P<0.05). Multivariate analysis showed that TNM phase and radiotherapy were the independent risk factors for overall survival of patients (P<0.05). Conclusions: PMME is more common in men, the common site of the disease is the lower part of the esophagus. The preoperatively missed diagnosis rate of Chinese PMME is high. TNM phase and radiotherapy are the independent risk factors for overall survival of patients.

Chimeric antigen receptor signaling: Functional consequences and design implications.

Chimeric antigen receptor (CAR) T cell therapy has transformed the care of refractory B cell malignancies and holds tremendous promise for many aggressive tumors. Despite overwhelming scientific, clinical, and public interest in this rapidly expanding field, fundamental inquiries into CAR T cell mechanistic functioning are still in their infancy. Because CAR T cells are manufactured from donor T lymphocytes, and because CARs incorporate well-characterized T cell signaling components, it has largely been assumed that CARs signal analogously to canonical T cell receptors (TCRs). However, recent studies demonstrate that many aspects of CAR signaling are unique, distinct from endogenous TCR signaling, and potentially even distinct among various CAR constructs. Thus, rigorous and comprehensive proteomic investigations are required for rational engineering of improved CARs. Here, we review what is known about proximal CAR signaling in T cells, compare it to conventional TCR signaling, and outline unmet challenges to improving CAR T cell therapy.

[The association between the whole blood riboflavin level and the occurrence, development and prognosis of esophageal squamous cell carcinoma].

Objective: To investigate the association between the whole blood riboflavin level and the occurrence, development and prognosis of esophageal squamous cell carcinoma (ESCC) in China. Methods: From March 2014 to September 2018, ESCC patients from three hospitals (the Affiliated Hospital of Medical College of Shantou University, Shantou Central Hospital in Southern Chaoshan area and First Affiliated Hospital of Zhengzhou University in Northern Taihang Mountain) were selected as a case group; non-esophageal patients who had a physical examination were selected as a control group. The case and control group were paired by age (±5 years) and a 1:1 ration. A total of 1 528 subjects were enrolled including 764 patients in the case group and 764 patients in the control group. About 3-5 ml venous blood samples were collected, and the erythrocyte glutathione reductase activity coefficient (GRAC) was measured to assess the whole blood riboflavin level. A multivariate conditional logistic regression model was used to analyze the association between the GRAC and the risk of ESCC. The association between the GRAC and the prognosis of ESCC was analyzed by using Cox proportional risk regression model based on 288 patients with complete survival data. They were divided into two groups, the high GRAC group (GRAC≥7.87) group and the low GRAC group (GRAC<7.87) according to the strongest correlation between the total survival time, survival outcome and GRAC (GRAC=7.87). Results: Among the 1 528 patients, 958 patients were from Southern Chaoshan area, including 479 patients in the case group with an average age about (59.90±9.34) years and 479 patients in the control group with an average age about (59.55±8.77) years. Other 570 patients were from Northern Taihang Mountain area, including 285 patients in the case group with an average age (58.39±5.19) years and 285 patients in the control group with an average age about (58.74±4.57) years. The multivariate conditional logistic regression showed that the OR (95%CI) of the GRAC and the risk of ESCC was 1.009 (0.998-1.019). The Cox proportional hazard regression model analysis showed that the HR (95%CI) of the high GRAC group was 1.712 (1.034-2.824) compared with the low GRAC group in the 50-70 years group. Conclusion: The whole blood riboflavin level might not be associated with the occurrence of ESCC. The high whole blood riboflavin level would be more beneficial to the prognosis of ESCC patients aged 50-70 years.

[Gender-specific factors of ischemic stroke among atrial fibrillation patients].

Objective: To explore gender-specific factors and their contributions to ischemic stroke among atrial fibrillation (AF) patients. Methods: A case-control study was conducted. The relevant data were obtained from the database of China National Stroke Screening Survey. The cases were first-ever ischemic stroke cases diagnosed from September 2013 to September 2015. Frequency-matched for the age and distribution of city and country, controls were randomly selected by 1∶3 ratio from individuals with AF but without stroke in the program. Altogether, there were 85 male cases (320 controls) and 147 female cases (484 controls). Unconditional logistic regression model was applied for the analysis of relevant factors of the onset of ischemic stroke, and their population-attributable risk proportion [PARP, (95%CI)] was calculated. Results: The age of male subjects in the case group and control group were (65.26±11.20) and (64.83±11.08) years old, and that of females in two groups were (63.63±10.40) and (63.93±10.35) years old. According to the PARP (95%CI), relevant factors of the onset of ischemic stroke in a descending sequence were hypertension history [35.63 (18.64-47.73)], family history of stroke [28.70 (23.63-32.30)]and physical inactivity [15.73 [5.62-23.06)] among male AF patients, and family history of stroke (29.39 (24.21-33.08)), dyslipidemia (22.17 (2.26-36.45)) and smoking [2.09 (0.76-3.24)] among female AF patients. Conclusion: The relevant factors of ischemic stroke were different between male and female AF patients.

[The association of health-related behavior and the risk of stroke in people with hypertension].

Objective: To investigate the association between the combination of different health-related behaviors and the risk of stroke in people with hypertension. Methods: The data in this study were obtained from the China National Stroke Screening Survey (CNSSS). The case group was the people with hypertension who were also diagnosed as the first-ever stroke cases (total stroke and ischemic stroke) during 2013-2014 screening period. Their corresponding controls (1∶3 frequency-matched for age group and urban/rural ratio) were randomly selected from individuals with hypertension without stroke. The information on demographic data, stroke history, influence factors and health-related behaviors (non-smoking, normal body mass index maintenance and physical activity) was obtained using standardized face-to-face questionnaires. Univariate analysis included t-test and Chi-square test. Multivariate analysis included unconditional logistic regression. Results: There were 603 total stroke cases (1 909 controls) and 536 ischemic stroke cases (1 608 controls) in men with hypertension, and 600 total stroke cases (1 800 controls) and 534 ischemic stroke cases (1 602 controls) in women with hypertension. We found that women with three health-related behaviors had lower risk of total stroke (OR=0.29, 95%CI: 0.11-0.79) and ischemic stroke (OR=0.28, 95%CI: 0.10-0.77). Only the combination of non-smoking and physical activity was significantly associated with the decreased risk of total stroke (OR=0.30, 95%CI: 0.11-0.78) and ischemic stroke (OR=0.32, 95%CI: 0.12-0.87). We had not found significant association between the combination of different health-related behaviors and risk of total stroke and ischemic stroke (P>0.05) in men. Conclusion: This study indicated that health-related behavior intervention might be more effectively to prevent stroke in women with hypertension, especially the smoking control and physical activity.

Characterization of tissue chromogranin A (CgA) immunostaining and clinicohistopathological changes for the 125 Chinese patients with primary small cell carcinoma of the esophagus.

The rarity of primary small cell carcinoma of the esophagus (PSCE) has limited the clinical feature and survival analysis with large sample size. Tissue chromogranin A (CgA) protein expression has been reported to be a useful biomarker for diagnosing PSCE. Interestingly, recent studies have indicated tissue CgA as a significant prognostic marker in multiple human cancers, but without PSCE. The present study, thus, was undertaken to characterize the clinicopathological changes and to evaluate the associations of tissue CgA expression with clinical response on Chinese PSCE patients. All the 125 PSCE patients were enrolled from our 500,000 esophageal and gastric cardia carcinoma databases (1973-2015), constructed by the cooperative team from more than 700 hospitals in China and established by Henan Key Laboratory for Esophageal Cancer Research in Henan, China. Immunostaining for CgA showed that CgA was mainly located in cytoplasm of tumor cells with a positive detection rate of 44.6%. The CgA positive expression rate in PSCE at lower segment of the esophagus (72.2%) was higher than that at middle segment (41.5%) (P = 0.001). However, CgA protein expression did not correlated with lymph node metastasis (P = 0.767), TNM staging (P = 0.740), tumor invasion (P = 0.253), gender (P = 0.262), and age (P = 0.250). Multivariate survival analysis showed that the patients with higher CgA protein expression had a superior long survival than those without CgA expression (P = 0.037). The clinicopathological analysis showed that PSCE occurred predominantly in male (M:F = 1.9:1) at the middle segment (68%) of the esophagus. Histologically, 89.6% were pure PSCE and 10.4% were mixed type with either squamous cell carcinoma (8%) or adenocarcinoma (2.4%). It was noteworthy that, with the in-depth invasion from T1 to T2 and T3, the positive lymph node metastasis rate increased dramatically from 38%, 56% to 74%, respectively. The survival rates of 1-, 2-, 3-, and 5-year were 64%, 35%, 18%, and 7%, respectively. The Kaplan-Meier survival analysis showed that the young patients (≤60 years) had longer survival than the elderly (P = 0.011). Interestingly, multivariate survival analysis revealed that the patients with mixed PSCE had a significantly better survival than those with pure PSCE (P = 0.015). Furthermore, the median survival time for the patients with and without lymph node metastasis was 1.16 and 2.03 years, respectively. But, the difference was not significant (P = 0.143). Univariate analysis did not show any survival influence by gender, tumor location, tumor invasion depth, and TNM staging. It was noteworthy that, of the 13 early PSCE patients (T1N0M0), only one patient had more than 5 year survival, the others died with less than one or two year (65%). The present study indicates that the PSCE is of badly worsen prognosis, even in the pathological early stage. Tissue CgA protein expression is a promising maker not only for diagnosis and also for prognosis. Further assessment is needed to establish specific PSCE pathological staging system and to clarify the mechanisms of CgA protein in PSCE progression and prognosis.

Integrative analyses of transcriptome sequencing identify novel functional lncRNAs in esophageal squamous cell carcinoma.

Long non-coding RNAs (lncRNAs) have a critical role in cancer initiation and progression, and thus may mediate oncogenic or tumor suppressing effects, as well as be a new class of cancer therapeutic targets. We performed high-throughput sequencing of RNA (RNA-seq) to investigate the expression level of lncRNAs and protein-coding genes in 30 esophageal samples, comprised of 15 esophageal squamous cell carcinoma (ESCC) samples and their 15 paired non-tumor tissues. We further developed an integrative bioinformatics method, denoted URW-LPE, to identify key functional lncRNAs that regulate expression of downstream protein-coding genes in ESCC. A number of known onco-lncRNA and many putative novel ones were effectively identified by URW-LPE. Importantly, we identified lncRNA625 as a novel regulator of ESCC cell proliferation, invasion and migration. ESCC patients with high lncRNA625 expression had significantly shorter survival time than those with low expression. LncRNA625 also showed specific prognostic value for patients with metastatic ESCC. Finally, we identified E1A-binding protein p300 (EP300) as a downstream executor of lncRNA625-induced transcriptional responses. These findings establish a catalog of novel cancer-associated functional lncRNAs, which will promote our understanding of lncRNA-mediated regulation in this malignancy.

The role of Lin28b in myeloid and mast cell differentiation and mast cell malignancy.

Mast cells (MCs) are critical components of the innate immune system and important for host defense, allergy, autoimmunity, tissue regeneration and tumor progression. Dysregulated MC development leads to systemic mastocytosis (SM), a clinically variable but often devastating family of hematologic disorders. Here we report that induced expression of Lin28, a heterochronic gene and pluripotency factor implicated in driving a fetal hematopoietic program, caused MC accumulation in adult mice in target organs such as the skin and peritoneal cavity. In vitro assays revealed a skewing of myeloid commitment in LIN28B-expressing hematopoietic progenitors, with increased levels of LIN28B in common myeloid and basophil-MC progenitors altering gene expression patterns to favor cell fate choices that enhanced MC specification. In addition, LIN28B-induced MCs appeared phenotypically and functionally immature, and in vitro assays suggested a slowing of MC terminal differentiation in the context of LIN28B upregulation. Finally, interrogation of human MC leukemia samples revealed upregulation of LIN28B in abnormal MCs from patients with SM. This work identifies Lin28 as a novel regulator of innate immune function and a new protein of interest in MC disease.

Detection of autoantibodies to a panel of tumor-associated antigens for the diagnosis values of gastric cardia adenocarcinoma.

To evaluate the diagnostic values of using autoantibodies in sera to a panel of eight tumor-associated antigens (TAAs) of P53, Koc, P62, C-myc, IMP1, Survivn, P16 and Cyclin B1 full-length recombinant proteins for early detection of patients with gastric cardia adenocarcinoma (GCA) and high-risk subjects screening. Enzyme-linked immunosorbent assay was used to detect autoantibodies against the eight selected TAAs in 383 sera samples from four groups, including 140 subjects with normal gastric cardia epithelia (NOR), 76 patients with chronic atrophic gastritis (CAG), 79 patients with gastric cardia dysplasia (DYS) and 88 patients with GCA. In addition, the expression of the eight antigens was analyzed in gastric cardia tissues by immunohistochemical method. The individual autoantibodies to six TAAs (P53, P62, IMP1, Survivn P16 and Cyclin B1) were significantly higher in sera from patients with GCA than that in normal subjects (P < 0.05). When autoantibody assay successively accumulated to seven TAAs (P53, Koc, P62, C-myc, IMP1, Survivn and P16), a stepwise increased detection frequency of autoantibodies was found in the four sera groups (13% in NOR, 39% in CAG, 46% in DYS, and 64% in GCA, respectively), the risks to CAG, DYS and GCA steadily increased about 4.4-, 5.7- and 12.0-fold. The sensitivity and the specificity for autoantibodies against the seven TAAs in diagnosing GCA reached up to 64% and 87%, respectively. The area under the receiver operating characteristic curve for the seven anti-TAA autoantibodies was 0.73 (95%CI: 0.68-0.78) No more increase in sensitivity was found with the addition of new anti-TAA autoantibodies. A combination detection of autoantibodies to TAAs might be helpful to distinguish GCA patients from normal subjects and the patients with gastric cardia precancerous lesions. In addition, further studies in patients with GCA and precancerous lesions using enlarged TAA panels might improve the sensitivity and specificity of cancer detection and high-risk subjects screening.

Autoantibody detection to tumor-associated antigens of P53, IMP1, P16, cyclin B1, P62, C-myc, Survivn, and Koc for the screening of high-risk subjects and early detection of esophageal squamous cell carcinoma.

The aim of this study was to evaluate the diagnostic values by detecting sera autoantibodies to eight tumor-associated antigens (TAAs) of P53, IMP1, P16, cyclin B1, P62, C-myc, Survivn and Koc full-length recombinant proteins for the screening of high-risk subjects and early detection of esophageal squamous cell carcinoma (ESCC). Enzyme-linked immunosorbent assay was used to detect autoantibodies against the eight selected TAAs in 567 sera samples from four groups, including 200 individuals with normal esophageal epithelia (NOR), 214 patients with esophageal basal cell hyperplasia (BCH), 65 patients with esophageal dysplasia (DYS), and 88 patients with ESCC. In addition, the expression of the eight antigens in esophageal tissues was analyzed by immunohistochemistry. Statistically significant distribution differences were identified among the four groups for each of the individual autoantibodies to six TAAs (P53, IMP1, P16, cyclin B1, P62, and C-myc); the detection rates of antoantibodies were positively correlated with the progression of ESCC. When autoantibody assay successively accumulated to six TAAs (P53, IMP1, P16, cyclin B1, P62, and C-myc), a stepwise increased detection frequency of autoantibodies was found in the four sera groups (6% in NOR, 18% in BCH, 38% in DYS, and 64% in ESCC, respectively), the risks to BHC, DYS, and ESCC steadily increased about 3-, 9-, and 27-folds. The sensitivity and the specificity for autoantibodies against the six TAAs in diagnosing ESCC reached up to 64% and 94%, respectively. The area under the receiver operating characteristic curve for the six anti-TAA autoantibodies was 0.78 (95% confidence interval 0.74-0.83). No more increasing in sensitivity was found with the addition of new anti-TAA autoantibodies. A combination detection of autoantibodies to TAAs might distinguish ESCC patients from normal individuals and the patients with esophageal precancerous lesions.

Functional single nucleotide polymorphism in C20orf54 modifies susceptibility to esophageal squamous cell carcinoma.

The aim of this study was to explore the association of C20orf54 functional single nucleotide polymorphism (SNP) with the susceptibility to esophageal squamous cell carcinoma (ESCC) in a northern China population. The C20orf54 SNP was genotyped by direct sequencing in 240 cancer patients and 198 controls in northern China. The results showed that drinking status, family history of ESCC, and body mass index have great influence on the risk of developing ESCC. The overall genotype frequencies of C20orf54 in ESCC patients have a significant difference with healthy controls (χ(2) = 8.06, P = 0.018). By using C/C genotype as the reference, the C/T genotype showed a significantly decreased risk to the development of ESCC. Thus, compared with the C/C genotype, smokers, drinkers with C/T genotype significantly decreased the risk of developing ESCC. A positive family history of ESCC with C/T and T/T genotype both increased the risk of developing ESCC. Body mass index between 18.5 and 24 with C/T genotype significantly decreased the risk of developing ESCC. The present study suggests that the C20orf54 functional SNP might be associated with a risk of development in ESCC.

Gefitinib compared with systemic chemotherapy as first-line treatment for chemotherapy-naive patients with advanced non-small cell lung cancer: a meta-analysis of randomised controlled trials.

To define the efficacy of gefitinib in chemotherapy-naive patients with advanced non-small cell lung cancer, we carried out a meta-analysis of randomised controlled trials. Medline, Embase, the Cochrane controlled trials register and the Science Citation Index were searched. Seven trials were identified, covering a total of 4656 subjects. As compared with chemotherapy, gefitinib was effective in the selected patients: the corresponding summary hazard ratios (gefitinib versus chemotherapy) for progression-free survival were 0.43 (0.32, 0.58) (P < 0.001) for the subgroup of patients with epidermal growth factor receptor (EGFR) mutant treated with gefitinib monotherapy, 0.71 (0.60, 0.83) (P < 0.001) for the subgroup of patients with lung adenocarcinoma; but was detrimental for the patients without EGFR mutant treated by gefitinib monotherapy [hazard ratio = 2.16 (1.17, 3.99), P = 0.01]. Significantly improved survival was found in the gefitinib group compared with the control in the subgroup of patients with lung adenocarcinoma [hazard ratio = 0.89 (0.81, 0.99); P = 0.03], but not found in the subgroup of patients with EGFR mutant [hazard ratio = 0.87 (0.68, 1.12); P = 0.28]. In conclusion, first-line treatment with gefitinib conferred prolonged progression-free survival than treatment with systemic chemotherapy in a molecularly or histologically defined population of patients with non-small cell lung cancer, and improved survival in the subgroup of patients with lung adenocarcinoma.

Abrogated expression of DEC1 during oesophageal squamous cell carcinoma progression is age- and family history-related and significantly associated with lymph node metastasis.

BACKGROUND: Oesophageal squamous cell carcinoma (SCC) causes the highest number of cancer deaths in some regions of Northern China. Previously, we narrowed down a critical region at 9q33-34, identified to be associated with tumour-suppressive function of deleted in oesophageal cancer 1 (DEC1) in oesophageal SCC. METHODS: We generated DEC1 antibody and constructed tissue microarrays (TMAs) utilising tissue specimens from Henan, a high-risk region for oesophageal SCC, to investigate the importance of DEC1 expression in this cancer. RESULTS: Tissue microarray immunohistochemical staining reveals significant loss of DEC1 from hyperplasia, to tumour, and to lymph node metastasis. In addition, the loss of DEC1 in tumour is age-dependent. Interestingly, there is significant abrogation of DEC1 expression in patients with a family history of oesophageal SCC. Deleted in oesophageal cancer 1 localises to both the cytoplasm and nucleus. The vesicular pattern of DEC1 in the cytoplasm appears to localise at the Golgi and Golgi-endoplasmic reticulum intermediate compartment. CONCLUSION: This is the first TMA study to suggest a clinical association of DEC1 in lymph node metastatic oesophageal SCC, early onset oesophageal SCC and familial oesophageal SCC development. Subcellular localisation of DEC1 and its expression in oesophageal SCC tissues provide important insight for further deciphering the molecular mechanism of DEC1 in oesophageal SCC development.

Decreased expression of annexin A1 during the progression of cervical neoplasia.

The aim of this study was to evaluate whether the expression of annexin A1 (ANXA1) is associated with the progression of cervical neoplasia. ANXA1 expression was examined by immunohistochemistry in paraffin-embedded cervical tissue samples (n = 234), comprising 52 samples of normal cervical epithelia, 30 of cervical intraepithelial neoplasia (CIN) I, 27 of CIN II, 32 of CIN III, and 93 of invasive squamous cell carcinoma (ISCC). ANXA1 expression was strong in normal cervical squamous epithelium and significantly reduced with increasing progression of cervical neoplasia. Moreover, a close association was observed between ANXA1 expression and tumour cell differentiation in ISCC. These preliminary results indicate that ANXA1 may be an effective candidate for detecting CIN lesions and for evaluating tumour cell differentiation in squamous cell carcinoma of the cervix.

Epigenetic disruption of interferon-gamma response through silencing the tumor suppressor interferon regulatory factor 8 in nasopharyngeal, esophageal and multiple other carcinomas.

16q24 is frequently deleted in multiple tumors including cancers of nasopharynx, esophagus, breast, prostate and liver. By array comparative genomic hybridization (aCGH), we refined a 16q24 hemizygous deletion in nasopharyngeal carcinoma (NPC) cell lines. Semi-quantitative RT-PCR analysis revealed interferon regulatory factor 8 (IRF8) as the only downregulated gene within this deletion. IRF8 belongs to a family of interferon (IFN) regulatory factors that modulate various important physiologic processes including host defense, cell growth and differentiation and immune regulation. In contrast to the broad expression of IRF8 in normal adult and fetal tissues, transcriptional silencing and promoter methylation of IRF8 were frequently detected in multiple carcinoma (except for hepatocellular) cell lines (100% in NPC, 88% in esophageal and 18-78% in other carcinoma cell lines) and in a large collection of primary carcinomas (78% in NPC, 36-71% in other carcinomas). Methylation of the IRF8 promoter led to the disruption of its response to IFN-gamma stimulation. Pharmacological and genetic demethylation could restore IRF8 expression, indicating a direct epigenetic mechanism. Ectopic expression of IRF8 in tumor cells lacking its expression strongly inhibited their clonogenicity, confirming its tumor suppressor function. Thus, IRF8 was identified as a functional tumor suppressor, which is frequently silenced by epigenetic mechanism in multiple carcinomas.