crossing96/oncoscreening huggingface dataset:
Bile salts differentially sensitize esophageal squamous cells to CD95 (Fas/Apo-1 receptor) mediated apoptosis.	BACKGROUND: The role of nonacidic reflux contents on the pathophysiology of Barrett's esophagus remains poorly understood. We hypothesized that esophageal squamous epithelium differs from Barrett's columnar epithelium in response to bile salts with respect to subsequent changes in the cell surface expression of CD95 (Fas/Apo-1) and sensitivity to CD95-mediated apoptosis. METHODS: Immortalized esophageal squamous cells (HET-1A) and Barrett's esophagus cells (BAR-T), and esophageal adenocarcinoma cells (Flo-1) were treated with toxic and nontoxic bile salts at concentrations observed in gastroesophageal refluxate. CD95 cell-surface expression and apoptotic response to activating anti-CD95 antibody treatment was determined by FACScan analysis. RESULTS: Bile salt exposure resulted in a dose-dependent increase in CD95 cell-surface expression in HET-1A cells, but not BAR-T or Flo-1 cells. This response occurred rapidly, within a time-frame inconsistent with de novo protein synthesis and was blocked by protein kinase C (PKC) inhibition. Surprisingly, PKC inhibition in Flo-1 cells resulted in an increase in CD95 cell surface expression. Following bile salt exposure, a corresponding increase in the induction of CD95-mediated apoptosis was observed in HET-1A cells; PKC inhibition sensitized Flo-1 cells to apoptosis. CONCLUSIONS: Our findings suggest that esophageal squamous cells are sensitized to CD95-mediated apoptosis following bile salt exposure. This differential response, compared with columnar epithelial cells, could exert a selection pressure that contributes to the pathophysiology of Barrett's esophagus.	esophagus
The relationship between p27(kip1) expression and the change of radiosensitivity of esophageal carcinoma cells.	OBJECTIVE: Radioresistance is considered the main reason for therapeutic failure in radiotherapy of esophageal carcinoma. However, the underlying mechanisms of radioresistance remain elusive. The purpose of this study was to investigate the relationship between p27(kip1) expression and the change of radiosensitivity of esophageal carcinoma cells. MATERIAL AND METHODS: Radioresistant cells were gradually isolated by means of repeated gamma-ray irradiation upon esophageal carcinoma cells. The radiosensitivity of established radioresistant cells and parental cells was measured by standard colony-forming assay. Cell cycle was detected by flow cytometry. Western blot method was performed to identify the expression of p27(kip1). RESULTS: Colony-forming assay showed that the radioresistant cells had obvious radioresistance. Percentage of the radioresistant cells at G(0)/G(1) and G(2)/M phase was significantly decreased, and the percentage of S phase cells was significantly increased compared with the parent cells (p < 0.05). Western blotting revealed that p27(kip1) expression of the radioresistant cells was lower than that of parent cells. CONCLUSIONS: Our results suggest that cell phase change due to the decrease of p27(kip1) expression is one of the mechanisms of radioresistance in esophageal carcinoma cells.	esophagus
Controversies in the diagnosis of Barrett esophagus and Barrett-related dysplasia: one pathologist's perspective.	CONTEXT: athologists frequently assess esophageal biopsy specimens to “rule out Barrett esophagus,” as well as to assess for the presence or absence of dysplasia. OBJECTIVE: To review some of the recent controversies in the diagnosis of Barrett esophagus and Barrett-related dysplasia. DATA SOURCES: Sources were the author's experience and review of the English literature from 1978 to 2009. CONCLUSIONS: Although goblet cells are required by the American College of Gastroenterology to confirm a diagnosis of Barrett esophagus, this definition might expand to include columnar-lined esophagus without goblet cells. The recognition of dysplasia in Barrett esophagus remains a difficult task for the surgical pathologist, with difficulties in distinguishing reactive epithelium from dysplasia, low-grade dysplasia from high-grade dysplasia, and even high-grade dysplasia from intramucosal adenocarcinoma.	esophagus
A clinical nomogram predicting pathologic lymph node involvement in esophageal cancer patients.	BACKGROUND: Esophageal cancer patients with pathologic lymph-node involvement (pN1) generally have a poor prognosis with surgery alone. We, therefore, constructed a nomogram to predict the risk of pN1 prior to surgical resection and externally validated the clinical utility of the model. METHODS: A total of 273 esophageal adenocarcinoma patients treated with surgery alone were reviewed from 2 different institutions (University of Texas M. D. Anderson Cancer Center = 164, training set; University of Rochester School of Medicine and Dentistry = 109, validation set). Pretreatment clinical parameters were used to construct a nomogram for predicting the risk of pN1. Internal and external validation of the nomogram was performed to assess clinical utility. RESULTS: Of the 164 patients in the training set, 56 patients (34%) had lymph-node involvement (pN1). Significant factors associated with pN1 on univariable logistic regression analysis (using a P < 0.05) included endoscopically determined clinical tumor depth (cT), clinical nodal (cN) status, and clinical tumor length (cL). Multivariable analysis suggested the significant independent factors were cT (odds ratio, 5.6; 95% confidence interval, 1.7-18.6; P < 0.01) and cL >2 cm (odds ratio, 7.0; 95% confidence interval, 2.7-18.1; P < 0.001). Regression tree analysis was used to determine the best cutoff for cL. A nomogram was created for pN1 using these clinical parameters and was internally validated by bootstrapping with a predicted accuracy of 85.1%. External validation performed on the validation set demonstrated an original C-index of 0.777 suggesting good clinical utility. CONCLUSIONS: Our analyses demonstrate that the risk of pathologic nodal involvement in esophageal adenocarcinoma patients can be estimated by this clinical nomogram, which will allow the identification of patients at high-risk of harboring positive lymph-nodes, who may be candidates for en bloc resection and/or neoadjuvant treatment.	esophagus
Psychological distress among family carers of oesophageal cancer survivors: the role of illness cognitions and coping.	OBJECTIVE: The research aimed to determine the extent to which illness cognitions and coping explain psychological distress (fear of cancer recurrence, anxiety and depression symptoms) among family carers of survivors of oesophageal cancer. METHODS: Carers of patients registered with the Oesophageal Patients' Association in the UK were mailed a questionnaire booklet containing questions about medical and demographic variables, the Illness Perception Questionnaire-Revised, the Cancer Coping Questionnaire, the Concerns about Recurrence Scale and the Hospital Anxiety and Depression Scale. RESULTS: Complete responses were received from 382 family carers (75% male; mean (SD) age=62 (10.91) years). Regression models indicated that the variables measured could explain between 35 and 49% of the variance in psychological distress among carers. Illness cognitions (particularly perceptions of the cause of, consequences of and personal control over oesophageal cancer and the carer's understanding of the condition) explained the majority of this variance. Positive focus coping strategies were also found to be important in explaining psychological distress. CONCLUSION: The results of this study are consistent with previous research demonstrating that illness cognitions are significant correlates of adaptive outcomes, thereby suggesting that cognition-based interventions could potentially be effective in minimizing emotional distress among family carers of oesophageal cancer survivors.	esophagus
Era of Barrett's surveillance: does equipment matter?	"Barrett's esophagus is a consequence of long standing gastro-esophageal reflux disease and predisposes to the development of esophageal adenocarcinoma. Regular surveillance endoscopies can detect curable early neoplasia in asymptomatic patients, which in turn could improve the prognosis compared to symptomatic cancer. Early neoplastic lesions, which are amenable for local therapy, could be treated endoscopically, avoiding a major surgery. However, in the absence of obvious mucosal lesions, random four quadrant biopsies are done, which is associated with significant sampling error. Newer imaging modalities, such as autofluorescence endoscopy, are helpful in detecting subtle lesions that could be examined in detail with narrow band imaging to characterize and target biopsies. This has the potential benefit of reducing the number of random biopsies with a better yield of dysplasia. Confocal endomicroscopy provides ""optical biopsies"" and is a valuable tool in targeting biopsies to improve dysplasia detection; however, this is technically challenging. Fuji intelligent chromoendoscopy and I-Scan are recent additions to the imaging armamentarium that have produced notable early results. While all these additional new imaging techniques are promising, a thorough examination by high resolution white light endoscopy after clearing the mucosa with mucolytics should be the minimum standard to improve dysplasia detection during Barrett's surveillance."	esophagus
The histologic squamo-oxyntic gap: an accurate and reproducible diagnostic marker of gastroesophageal reflux disease.	The present definition of gastroesophageal reflux disease (GERD) is based on clinical criteria that are difficult to reproduce accurately. This study provides a method to develop a histologic definition of GERD based on biopsies obtained from the affected esophagus. Pathology reports from 1655 patients who had upper gastrointestinal endoscopy and biopsy according to a systematic protocol were reviewed. Biopsies were obtained from the esophagus, around the gastroesophageal junction and the stomach: proximal, body, and antrum. Patients who had oxyntocardiac±cardiac±intestinal epithelia between the squamous epithelium proximally and the proximal limit of gastric oxyntic mucosa distally were defined as having a squamo-oxyntic gap. The length of the squamo-oxyntic gap varied from less than 1 cm in 1399 (84.5%) patients to greater than 5 cm in 80 (4.8%) of the patients. Only oxyntocardiac epithelium was seen in 190 (11.5%) of the patients, oxyntocardiac and cardiac epithelia in 898 (54.3%), and intestinal metaplasia in addition to the other 2 epithelial types in 567 (34.2%). The prevalence of intestinal metaplasia was directly proportional to length of the squamo-oxyntic gap, being 24.3% (340/1399) when the length was <1 cm, and 83.5% (147/176) with length 1 to 5 cm. All patients with a length more than 5 cm had intestinal metaplasia. The distribution of the 3 epithelia was constant irrespective of the length of the squamocolumnar gap; intestinal metaplasia, when present, was seen maximally in the proximal region of the gap, cardiac epithelium intermediate and oxyntocardiac epithelium in the most distal segment of the gap. The squamo-oxyntic gap started in a dilated region distal to the end of the tubular esophagus and distal to the proximal limit of the rugal folds and extended into the tubular esophagus. Distal gastric biopsies showed no evidence of significant inflammation, intestinal metaplasia or Helicobacter pylori infection in 1543 (93.2%) of the patients, indicating that the squamo-oxyntic gap was largely independent of gastric pathology. We provide evidence that the squamo-oxyntic gap is equivalent to the columnar-lined esophagus. Its presence is a specific and sensitive indicator of reflux and can be used as a cellular criterion to define GERD. The length of the squamo-oxyntic gap provides an accurate assessment of the severity of chronic GERD. The distal limit of the squamo-oxyntic gap, which is the junction between oxyntocardiac and gastric oxyntic epithelium is the true gastroesophageal junction. The presence of intestinal metaplasia within the squamo-oxyntic gap is the most accurate risk indicator for esophageal adenocarcinoma and defines Barrett esophagus.	esophagus
Relationship between NRAGE and the radioresistance of esophageal carcinoma cell line TE13R120.	BACKGROUND AND OBJECTIVE: The mRNA levels of 59 genes, detected by cDNA microarray, were up-regulated in the radioresistant human esophageal cacinoma cell line TE13R120 as compared with its parental cell line TE13 before and after radiation, and the expression of NRAGE gene showed a gradually up-regulating tendency. This study aimed to further detect the differences of NRAGE gene and protein expression and apoptosis between TE13R120 and TE13 cells, and to investigate the relationship between the NRAGE and the radioresistance of TE13R120 cells and its mechanism. METHODS: The two cell lines were irradiated by ⁶⁰Co γ-ray at different conditions. Reverse transcription-polymerase chain reaction (RT-PCR), Western blot, and immunocytochemistry were used to detect the expression of NRAGE. Flow cytometry (FCM) was used to detect the cell apoptosis before and after irradiation. RESULTS: The mRNA level of NRAGE was higher in TE13R120 cells than in TE13 cells before and after irradiation (before radiation: 0.25 ± 0.03 vs. 0.49 ± 0.03; 4 Gy 4 h: 0.31 ± 0.03 vs. 0.53 ± 0.02; 4 Gy 16 h: 0.32 ± 0.04 vs. 0.59 ± 0.04; 4 Gy 24 h: 0.36 ± 0.05 vs. 0.72 ± 0.04; 2 Gy 12 h: 0.32 ± 0.02 vs. 0.64 ± 0.04; 6 Gy 12 h: 0.36 ± 0.02 vs. 0.79 ± 0.05; 10 Gy 12 h: 0.46 ± 0.04 vs. 0.85 ± 0.01; P < 0.01), and the mRNA level of NRAGE was increased gradually with the increase of radiation dose and time in the two cell lines (P < 0.05 and P < 0.01). Western blot results showed no difference of NRAGE protein level in cytoplasm between TE13R120 cells and TE13 cells before and after irradiation, but its level in nuclei was higher in TE13R120 cells than in TE13 cells at different radiation time and dosages. Immunocytochemistry showed similar results as Western blot. FCM showed no significant difference in apoptosis rate between TE13R120 and TE13 cells before and after radiation. CONCLUSION: NRAGE may play an important role in the radiation responses of the two cell lines, and may participate in the formation of radioresistance of TE13R120 cells by changing its subcellular localization, but its relationship with cell apoptosis has not been confirmed.	esophagus
Meta-analysis of late course accelerated hyperfractionated radiotherapy combined with FP chemotherapy for esophageal carcinoma.	BACKGROUND AND OBJECTIVE: Although there are many randomized clinical trials of late course accelerated hyperfractionated radiotherapy (LCAHFR) combined with FP chemotherapy for esophageal cancer, the efficacy and toxicity are controversial. This study was to evaluate the efficacy and toxicity of LCAHFR combined with FP chemotherapy in treating esophageal cancer. METHODS: Reports of randomized clinical trials on LCAHFR combined with FP chemotherapy for esophageal cancer published between January 1999 and January 2009 were researched through Wanfang, CNKI, and PubMed databases. RevMan4.2 software was used for Meta-analysis. RESULTS: Twenty-one reports, including 2030 patients, were included in the meta-analysis. Of the 2030 patients, 1006 underwent LCAHFR (LCAHFR group), and 1024 underwent LCAHFR combined with FP chemotherapy (combination group). Compared with those of the LCAHFR group, the 1-, 2-, 3-, 5-years survival rates and 1-, 2-, 3-year local control rates of the combination group were significant increased, and the acute toxicity was also increased, but chronic toxicity showed no significant difference. CONCLUSIONS: LCAHFR combined with FP chemotherapy can improve the survival rate and the local control rate of the patients with esophageal cancer. The increased acute toxicity need to be concerned, whereas the chronic toxicity needs a long-term observation.	esophagus
Literature analysis of radiotherapy for esophageal cancer in China.	BACKGROUND AND OBJECTIVE: Many patterns of treatment have been used to treat esophageal carcinoma in the past years, however, an optimal treatment is still the key issue to be explored. Therefore, we analyzed the published literature about radiotherapy for esophageal cancer in recent 15 years in China, and observed the survival rate, local control rate, adverse events, and so on. METHODS: A total of 56 eligible papers about radiotherapy for esophageal squamous cell carcinoma published in Chinese core periodicals between 1994 and 2009 were selected. The survival rates, local control rates, and adverse events were analyzed. RESULTS: The 1-, 2-, 3-, and 5-year overall survival rates of the patients reported in the 56 papers were (67.99 ± 12.55)%, (49.59 ± 11.79)%, (34.50 ± 11.49)%, and (23.31 ± 10.21)%, respectively. The 1-, 2-, 3-, and 5-year local control rates were (73.04 ± 13.37)%, (61.60 ± 15.50)%, (51.77 ± 15.00)%, and (50.15 ± 21.36)%, respectively. The acute esophageal toxicity rate was (44.84 ± 25.71)% in 32 papers reported in recent 15 years, and the acute esophageal toxicity over grade II accounted for (35.93 ± 22.90)%. The rates of acute esophageal toxicity were (26.84 ± 13.12)% for conventional radiation, (53.72 ± 21.82)% for late course accelerated hyperfractionation radiation, (61.33 ± 28.69)% for concurrent chemoradiotherapy, and (40.31 ± 27.22)% for other ways of radiation. The late toxicity rate described in 23 papers was (5.13 ± 4.07)% in recent 15 years. The late toxicity rates were (5.66 ± 3.42)% for conventional radiation, (4.53± 4.07)% for late course accelerated hyperfractionation radiation, (2.24±1.31)% for concurrent chemoradiotherapy, and (7.34 ± 5.06)% for other ways of radiation. The Meta analysis indicated that concurrent chemoradiotherapy was better than late course accelerated hyperfractionation radiation and conventional radiation. CONCLUSIONS: The long-term survival of patients with esophageal cancer is still disappointed in recent years. Concurrent chemoradiotherapy shows advantages in treating esophageal cancer and, currently, is the best non-surgical treatment of esophageal cancer.	esophagus
Treatment guideline of radiotherapy for Chinese esophageal carcinoma (draft).	Esophageal carcinoma is one of the most common human cancers in China. Radiotherapy plays an important role in combination therapy of esophageal carcinoma. With regret, there is still no unified standard for the treatment of esophageal carcinoma in China, and there are many controversies in the treatment regimens, indications, methods and efficacy. Clinically, the clinical practice guidelines of the National Comprehensive Cancer Network (NCCN) of the United States were often consulted, but the data of them were mainly from the patients from Europe and America, and they might not be applicable for Chinese patients. In order to standardize clinical process of radiotherapy for esophageal carcinoma in China, the Esophageal Carcinoma Cooperative Group of Radiation Oncology Society of Chinese Medical Association wrote a consensus and controversies on the radiotherapy for esophageal carcinoma (draft) after years of research and discussion. We hope it be tried out and discussed with advice and valuable suggestions, in order to accelerate the process of standardization of esophageal carcinoma treatment in China.	esophagus
Esophageal cancer in the elderly: an analysis of the factors associated with treatment decisions and outcomes.	BACKGROUND: Only limited data has been reported so far regarding oesophageal cancer (EC) in elderly patients. The aim of the study is to identify the baseline parameters that influenced therapeutic decision. METHODS: All consecutive patients 70 years or older being treated for EC were retrospectively analyzed. Patients without visceral metastasis were divided into two groups: treatment with curative intent (chemoradiotherapy, surgery, radiotherapy, mucosectomy or photodynamic therapy) or best supportive care (BSC). Patients with metastasis were divided into two groups: palliative treatment (chemotherapy, chemoradiotherapy or radiotherapy) or BSC. RESULTS: Two hundred and eighty-two patients were studied. Mean age was 76.5 ± 5.5 years and 22.4% of patients had visceral metastasis. In patients without visceral metastasis (n = 220) the majority had treatment with curative intent (n = 151) whereas in patients with metastasis (n = 62) the majority had BSC (n = 32). Severe adverse events (≥ grade 3) were observed in only 17% of the patients. Patients without specific carcinologic treatment were older, had more weight loss, worse WHO performance status and Charlson score in multivariate analysis. DISCUSSION: Our results suggest that elderly patients with an EC could benefit from cancer treatment without major toxicities. Weight loss, WHO performance status and the Charlson score could be used to select the appropriate treatment in an elderly patient.	esophagus
Trastuzumab mediated T-cell response against HER-2/neu overexpressing esophageal adenocarcinoma depends on intact antigen processing machinery.	BACKGROUND: Esophageal adenocarcinoma (EAC) is a highly aggressive disease with poor prognosis, which frequently exhibits HER-2 gene amplification. Trastuzumab, the humanized antibody against HER-2, has potent growth inhibitory effects on HER-2 overexpressing cancers. One effect of trastuzumab is that it causes HER-2 receptor internalization and degradation, enhancing presentation of HER-2 epitopes on MHC-Class I molecules. This enhances the ability of HER-2 specific cytotoxic T lymphocytes (CTLs) to recognize and kill cancer cells. Novel strategies targeting the HER-2 receptor either directly by trastuzumab and/or indirectly by inducing a CTL response against HER-2 epitopes with, for instance, DC immunotherapy and consequently combining these strategies might prove to be very effective. METHODOLOGY/PRINCIPAL FINDINGS: In this study we report that trastuzumab has potent growth inhibitory effects on two HER-2 overexpressing EAC cell lines OE33 and OE19. However, we found that trastuzumab and HER-2 specific CTLs act synergistically in inducing tumor lysis in OE33 but not in OE19. We discovered that in OE19 this deficient response is due to a down-regulation of the Transporter Associated with Antigen Processing-2 (TAP-2). TAP-2 is an important member of the Antigen Processing Machinery (APM), and is one of the essential elements for loading antigens on MHC class I molecules. Importantly, we demonstrated that by inducing re-expression of TAP-2 in OE19 with INF-γ treatment or by incubating the cells with INF-γ producing CTLs, the specific anti HER-2 CTL tumor lysis response and synergistic effect with trastuzumab can be restored. CONCLUSION: An inefficient response of HER-2 overexpressing EAC to trastuzumab and/or DC immunotherapy can be due to a down-regulated TAP-2 expression and thus a deficient APM. Future studies combining trastuzumab with IFN-γ and/or immune-therapies inducing potent anti HER-2 CTL responses could lead to an effective combinatorial strategy for successful treatment of HER-2 overexpressing but APM defective cancers.	esophagus