The FAS-FASL system plays crucial role in counterattack of cancer cell against immune system. This study examined the effects of FAS (-1377G/A and -670A/G) and FASL (-844T/C and 7896G/C) polymorphisms on breast cancer risk and apoptosis of T lymphocytes. The effect on breast cancer risk was determined by case-control analysis of 840 patients and 840 controls. The effects on T-lymphocyte apoptosis were determined by activation-induced cell death (AICD) of T cells ex vivo and by analyzing apoptotic tumor-infiltrating lymphocytes (TILs) in breast cancer tissue. We found moderately increased risk associated with FAS -1377AG [odds ratio (OR), 1.29; 95% confidence interval (CI), 1.05-1.59] and -1377AA (OR, 1.36; 95% CI, 1.01-1.82) genotypes compared with the -1377GG genotype and decreased risk associated with FASL -844CT (OR, 0.76; 95% CI, 0.62-0.94) and -844TT (OR, 0.66; 95% CI, 0.43-1.00) genotypes compared with the -844CC genotype. T lymphocytes with the FASL -844CC genotype had heightened FASL expression that is associated with increased AICD of the T cells stimulated by MCF-7 cells or phytohemagglutinin compared with the FASL -844TT genotype (10.38 +/- 4.09% and 24.29 +/- 1.50% versus 6.03 +/- 0.41% and 17.96 +/- 3.66%; P < 0.05 and 0.001). Breast cancer patients with the FASL -844CC genotype had higher apoptotic TILs in their cancer tissues than those with the FASL -844TT genotype (33.7 +/- 1.2% versus 19.1 +/- 2.0%; P = 0.007). These findings indicate that functional polymorphisms in FAS and FASL contribute to increased apoptosis of tumor infiltration lymphocytes and risk of breast cancer.

To investigate the clinicopathological characteristics and optimal treatment modalities of primary non-Hodgkin lymphoma (NHL) in the small and large intestine. Forty patients with primary NHL in the small and large intestine were studied retrospectively. All cases were reclassified according to the World Health Organization (WHO) classification of lymphoma in 2001. Fourteen patients had primary disease in the small intestine, which were all of B-cell origin with diffuse large B-cell lymphoma (DLBCL) diagnosed in 5 of 14 (35.7%) patients and mucosa-associated lymphoid tissue (MALT) lymphoma in 8 of 14 (57.1%) patients. Ileum was the most commonly involved site (8 of 14 patients, 57.1%), followed by jejunum (2 of 14 patients, 14.3%) and duodenum (1 of 14 patients, 7.1%). Twenty-five patients had primary colorectal lymphoma, with B-cell origin accounting for 92.0% and T-cell origin for 8.0% of these patients. The ileocaecal region has the highest involved rate (13 of 25 patients, 52.0%), followed by colon (7 of 25 patients, 28.0%) and rectum (3 of 25 patients, 12.0%). Compared with surgery alone, post-operation chemotherapy or chemoradiotherapy can significantly improve DLBCL patients' event-free survival (EFS). However, no post-operation treatment modality can improve OS or EFS for patients with MALT lymphoma. B-cell lymphoma is the most common pathological type of intestinal lymphomas. Chemotherapy-containing treatment modality is an effective way to improve intestinal lymphoma patients' EFS, especially for those with DLBCL subtype.

SUMMARY Humans with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), a T cell–driven autoimmune disease caused by impaired central tolerance, are susceptible to developing chronic fungal infection and esophageal squamous cell carcinoma (ESCC). However, the relationship between autoreactive T cells and chronic fungal infection in ESCC development remains unclear. We find that kinase-dead Ikkα knockin mice develop phenotypes reminiscent of APECED, including impaired central tolerance, autoreactive T cells, chronic fungal infection, and ESCCs expressing specific human ESCC markers. Using this model, we investigated the potential link between ESCC and fungal infection. Autoreactive CD4 T cells permit fungal infection and incite tissue injury and inflammation. Antifungal treatment or depletion of autoreactive CD4 T cells rescues, whereas oral fungal administration promotes, ESCC development. Inhibition of inflammation or EGFR activity decreases fungal burden. Importantly, fungal infection is highly associated with ESCCs in non-autoimmune human patients. Therefore, autoreactive T cells and chronic fungal infection, fostered by inflammation and epithelial injury, promote ESCC development.

Background Radiofrequency ablation (RFA) is safe and effective for eradicating neoplasia in Barrett’s esophagus. Objective Evaluate RFA for eradicating early esophageal squamous cell neoplasia (ESCN) defined as moderate- and high-grade squamous intraepithelial neoplasia (MGIN, HGIN) and early flat-type esophageal squamous cell carcinoma (ESCC). Design Prospective cohort study. Setting Tertiary referral center. Patients Esophageal unstained lesions (USLs) were identified using Lugol’s chromoendoscopy. Inclusion: at least 1 flat (type 0-IIb) USL ≥3cm, USL-bearing esophagus ≤12 cm, and a consensus diagnosis of MGIN, HGIN, or ESCC by two expert GI pathologists. Exclusion: prior endoscopic resection or ablation, stricture, or any non-flat mucosa. Interventions Circumferential RFA creating a continuous treatment area (TA) including all USLs. At 3-month intervals thereafter, chromoendoscopy with biopsies, followed by focal RFA of USLs, if present. Main outcome measures Complete response (CR) at 12 months, defined as absence of MGIN, HGIN or ESCC in TA; CR after one RFA session; neoplastic progression from baseline; and adverse events. Results 29 patients (14 male, mean age 60.3 years) with MGIN (18), HGIN (10), or ESCC (1) participated. Mean USL length was 6.2 cm (TA 8.2 cm). At 3-months, after one RFA session, 86% of patients (25/29) were CR. At 12-months, 97% (28/29) of patients were CR. There was no neoplastic progression. There were 4 strictures, all dilated to resolution. Limitations Single center study with limited number of patients. Conclusions In patients with early ESCN (MGIN, HGIN, flat-type ESCC), RFA was associated with a high rate of histological complete response (97% of patients), no neoplastic progression, and an acceptable adverse event profile.

Esophageal squamous cell carcinoma (ESCC) has a multifactorial etiology involving environmental and/or genetic factors. End-binding protein 1 (EB1), which was cloned as an interacting partner of the adenomatous polyposis coli (APC) tumor suppressor protein, was previously found overexpressed in ESCC. However, the precise role of EB1 in the development of this malignancy has not yet been elucidated. In this study, we analysed freshly resected ESCC specimens and demonstrated that EB1 was overexpressed in approximately 63% of tumor samples compared to matched normal tissue. We report that overexpression of EB1 in the ESCC line EC9706 significantly promotes cell growth, whereas suppression of EB1 protein level by RNA interference significantly inhibited growth of esophageal tumor cells. In addition, EB1 overexpression induced nuclear accumulation of b-catenin and promoted the transcriptional activity of b-catenin/T-cell factor (TCF). These effects were partially or completely abolished by coexpression of APC or DN TCF4, respectively. Also, we found that EB1 affected the interaction between b-catenin and APC. Furthermore, EB1 overexpression was correlated with cytoplasmic/ nuclear accumulation of b-catenin in primary human ESCC. Taken together, these results support the novel hypothesis that EB1 overexpression may play a role in the development of ESCC by affecting APC function and activating the b-catenin/TCF pathway. Oncogene (2005) 24, 6637-6645.

Background & Aims High-resolution microendoscopy is an optical imaging technique with the potential to improve the accuracy of endoscopic screening for esophageal squamous neoplasia. Although these microscopic images can readily be interpreted by trained personnel, quantitative image analysis software could facilitate the use of this technology in low-resource settings. In this study we developed and evaluated quantitative image analysis criteria for the evaluation of neoplastic and non-neoplastic squamous esophageal mucosa. Methods We performed image analysis of 177 patients undergoing standard upper endoscopy for screening or surveillance of esophageal squamous neoplasia, using high-resolution microendoscopy, at 2 hospitals in China and 1 in the United States from May 2010 to October 2012. Biopsies were collected from imaged sites (n=375); a consensus diagnosis was provided by 2 expert gastrointestinal pathologists and used as the standard. Results Quantitative information from the high-resolution images was used to develop an algorithm to identify high-grade squamous dysplasia or invasive squamous cell cancer, based on histopathology findings. Optimal performance was obtained using mean nuclear area as the basis for classification, resulting in sensitivities and specificities of 93% and 92% in the training set, 87% and 97% in the test set, and 84% and 95% in an independent validation set, respectively. Conclusions High-resolution microendoscopy with quantitative image analysis can aid in the identification of esophageal squamous neoplasia. Use of software-based image guides may overcome issues of training and expertise in low-resource settings, allowing for widespread use of these optical biopsy technologies.

Disruption of mitotic events contributes greatly to genomic instability and results in mutator phenotypes. Indeed, abnormalities of mitotic components are closely associated with malignant transformation and tumorigenesis. Here we show that ninein-like protein (Nlp), a recently identified BRCA1-associated centrosomal protein involved in microtubule nucleation and spindle formation, is an oncogenic protein. Nlp was found to be overexpressed in approximately 80% of human breast and lung carcinomas analyzed. In human lung cancers, this deregulated expression was associated with NLP gene amplification. Further analysis revealed that Nlp exhibited strong oncogenic properties; for example, it conferred to NIH3T3 rodent fibroblasts the capacity for anchorage-independent growth in vitro and tumor formation in nude mice. Consistent with these data, transgenic mice overexpressing Nlp displayed spontaneous tumorigenesis in the breast, ovary, and testicle within 60 weeks. In addition, Nlp overexpression induced more rapid onset of radiation-induced lymphoma. Furthermore, mouse embryonic fibroblasts (MEFs) derived from Nlp transgenic mice showed centrosome amplification, suggesting that Nlp overexpression mimics BRCA1 loss. These findings demonstrate that Nlp abnormalities may contribute to genomic instability and tumorigenesis and suggest that Nlp might serve as a potential biomarker for clinical diagnosis and therapeutic target.

BackgroundOral squamous cell carcinoma (OSCC) is becoming more common across the globe. The prognosis of OSCC is largely dependent on the early detection. But the routine oral cavity examination may delay the diagnosis because the early oral malignant lesions may be clinically indistinguishable from benign or inflammatory diseases. In this study, the new diagnostic method is developed by using the surface enhanced Raman spectroscopy (SERS) to detect the serum samples from the cancer patients.MethodThe blood serum samples were collected from the OSCC patients, MEC patients and the volunteers without OSCC or MEC. Gold nanoparticles(NPs) were then mixed in the serum samples to obtain the high quality SERS spectra. There were totally 135 spectra of OSCC, 90 spectra of mucoepidermoid carcinoma (MEC) and 145 spectra of normal control group, which were captured by SERS successfully. Compared with the normal control group, the Raman spectral differences exhibited in the spectra of OSCC and MEC groups, which were assigned to the nucleic acids, proteins and lipids. Based on these spectral differences and features, the algorithms of principal component analysis(PCA) and linear discriminant analysis (LDA) were employed to analyze and classify the Raman spectra of different groups.ResultsCompared with the normal groups, the major increased peaks in the OSCC and MEC groups were assigned to the molecular structures of the nucleic acids and proteins. And these different major peaks between the OSCC and MEC groups were assigned to the special molecular structures of the carotenoids and lipids. The PCA-LDA results demonstrated that OSCC could be discriminated successfully from the normal control groups with a sensitivity of 80.7% and a specificity of 84.1%. The process of the cross validation proved the results analyzed by PCA-LDA were reliable.ConclusionThe gold NPs were appropriate substances to capture the high-quality SERS spectra of the OSCC, MEC and normal serum samples. The results of this study confirm that SERS combined PCA-LDA had a giant capability to detect and diagnosis OSCC through the serum sample successfully.