crossing96/oncoscreening huggingface dataset:
Expression of SLP-2 was associated with invasion of esophageal squamous cell carcinoma.	INTRODUCTION: Stomatin-like protein 2 (SLP-2), a member of the Stomatin superfamily, has been identified as an oncogenic-related protein and found to be up-regulated in multi-cancers. Nonetheless, the expression pattern and regulation of SLP-2 in human esophageal squamous cell carcinoma (ESCC) remain unexplored. METHODS: Immunohistochemistry and immunofluorescence staining analysis were performed to show SLP-2 expression and location. RNAi method was used to inhibit specific protein expression. Transwell assay was done to investigate cells invasive capability. RT-PCR and Western blot analysis were used to detect mRNA and protein expression levels. RESULTS: Immunohistochemical analysis showed that up-regulation of SLP-2 was found in invasive front compared with cancer central tissue in ESCC. Inhibition of SLP-2 by SLP-2 siRNA can decrease ESCC cells invasive capability through MMP-2 dependent manner. Up-regulation of SLP-2 was effectively abrogated by the ERK1/2 inhibitors either PD98059 or U0126, but no effect was showed by the treatment of AKT inhibitors either LY294002 or MK-2206. So the regulation of SLP-2 was involved in activation of the MAPK/ERK pathway. CONCLUSIONS: We found that PMA/EGF could induce the up-regulated expression of SLP-2 probably through activating ERK signalling. The current study suggests that SLP-2 may represent an important molecular hallmark that is clinically relevant to the invasion of ESCC.	esophagus
Overexpression of PLCE1 in Kazakh esophageal squamous cell carcinoma: implications in cancer metastasis and aggressiveness.	Three recent large-scale genome-wide association studies (GWAS) in Chinese Han populations have identified an esophageal squamous cell carcinoma (ESCC) susceptibility locus within phospholipase C epsilon 1 (PLCE1) gene, which encodes a phospholipase involved in intracellular signaling. The expressed PLCE1 in ESCC, however, are inconsistent. This study examined PLCE1 expression by immunohistochemistry (IHC) from 110 ethnic Kazakh ESCC patients and 50 from adjacent normal esophageal tissues (NETs). The expressed PLCE1 was localized in cytoplasm, especially in the peripheral layers of cancer cell nests, which was significantly higher in tumors than in NETs (p < 0.001). Increased expression of PLCE1 was correlated with advanced tumor-node-metastasis (TNM) stages (p = 0.015) and lymph node metastasis (p = 0.003) in patients with ESCC. Of the 110 patients, we examined 50 paired ESCC tissues and corresponding NETs by quantitative RT-PCR (polymerase chain reaction) and the mean mRNA level of PLCE1 in ESCC was 1.85-fold higher compared with those in corresponding NETs (p = 0.0012). Meanwhile, 4 of 5 ESCC cell lines also showed elevated expression of PLCE1 mRNA. Furthermore, elevated expression of PLCE1 mRNA in Kazakh ESCC was associated with its immunoreactivity (ρ = 0.297, p = 0.040), lymph node metastasis (p < 0.001), and advanced TNM stages of ESCC (p = 0.013). To our knowledge, this study demonstrates for the first time that PLCE1 overexpression correlates with lymph node metastasis and advanced TNM stages of Kazakh ESCC, implicating a role of PLCE1 in cancer metastasis and aggressiveness in ethnic Kazakh patients with ESCC. Furthermore, the current findings may warrant investigations into whether inhibiting PLCE1 could be a strategy for targeted anticancer therapy particularly for Kazakh ESCC.	esophagus
Prognostic impact of postoperative radiation in patients undergoing radical esophagectomy for pathologic lymph node positive esophageal cancer.	PURPOSE: Though postoperative radiation for esophageal squamous cell carcinoma is offered in selected cases, there is conflicting evidence as to whether it improves overall survival (OS). A retrospective investigation was performed to analyze the prognostic impact of postoperative radiation therapy (PORT) in a large cohort of patients. METHODS: From 2001 to 2009, 725 patients underwent radical esophagectomy (R0) with or without PORT were eligible for retrospective analysis. Patients were grouped into surgery alone (n = 467) and surgery plus PORT (n = 258). Median irradiation doses were 50 Gy (range: 40-56 Gy). Radiation fields encompassed the bilateral supraclavicular fossa, mediastinum, subcarinal area, and the tumor bed for the upper/middle-third disease; the bilateral supraclavicular fossa, mediastinum, the tumor bed, subcarinal area, and lower thoracic paraesophageal area for the lower-third disease. Kaplan-Meier and Cox regression analysis were used to compare OS. RESULTS: After median follow-up of 53 months, the median OS was 29 months in the PORT group and 23 months in the surgery alone group. The addition of PORT improved OS at 3 years from 36.6 to 43.6% compared with surgery alone. The use of PORT was associated with significantly improved OS (p = 0.018). For American Joint Committee on Cancer (AJCC) stage III esophageal cancer (T1-2N2M0, T3N1-2M0, T4N1-3M0), there was significant improvement in OS (p = 0.002) in the PORT group, not only for lymph-node metastatic ratio (LNMR) ≥0.25 (p = 0.001), but also for LNMR <0.25 (p = 0.043). However, for stage IIB disease (T1-2N1M0) there was no significant differences. The addition of POCT didn't prolong the OS significantly (Surgery alone group, p = 0.079; PORT group, p = 0.111). CONCLUSIONS: This large retrospective analysis supports the use of PORT for pathologic lymph node positive stage III esophageal squamous cell carcinoma. Given the retrospective nature of this study, the results should be confirmed by appropriately powered randomized trials. Further development of adjuvant therapy in EC is warranted.	esophagus
Primary tumor vascularity in esophagus cancer. CD34 and HIF1-α expression correlate with tumor progression.	OBJECTIVE: Hypoxia inducible factor α (HIF1-α) is a key protein regulating the response of a variety of genes and pathways, including angiogenesis, to hypoxic stimuli. High vascularity in various carcinomas correlates with invasion and metastasis. Assessment of primary tumor vascularity and HIF1-α expression in esophageal carcinomas was an objective of this study. METHODS: The vascularity in esophageal carcinomas (n=52) was quantified by Chalkley method on CD34 immunostained sections. HIF1-α expression was examined by immunohistochemistry. The relationships between CD34 Chalkley count, HIF1-α and various clinico-pathological characteristics with clinical outcome were evaluated. RESULTS: High HIF1-α expression in squamous cell carcinoma (SCC) was significantly associated with the T3-4 group (p=0.02). A higher percentage of SCC with high HIF1-α expression compared to its expression in adenocarcinoma (AC) (p=0.005) was observed. In the SCC group, high CD34 Chalkley count and high HIF1-α expression implied a significantly reduced survival (p=0.003 and p=0.001). No such significant association was found in the AC group. CONCLUSIONS: HIF1-α expression is different in two separate tumor microenvironments: SCCs and ACs of the esophagus. This suggests that different mechanisms may be involved in HIF1-α expression- and activity between the two histological types of esophageal carcinoma.	esophagus
Dietary flavonoid intake and esophageal cancer risk in the European prospective investigation into cancer and nutrition cohort.	We prospectively investigated dietary flavonoid intake and esophageal cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. The study included 477,312 adult subjects from 10 European countries. At baseline, country-specific validated dietary questionnaires were used. During a mean follow-up of 11 years (1992-2010), there were 341 incident esophageal cancer cases, of which 142 were esophageal adenocarcinoma (EAC), 176 were esophageal squamous cell carcinoma (ESCC), and 23 were other types of esophageal cancer. In crude models, a doubling in total dietary flavonoid intake was inversely associated with esophageal cancer risk (hazard ratio (HR) (log₂) = 0.87, 95% confidence interval (CI): 0.78, 0.98) but not in multivariable models (HR (log₂) = 0.97, 95% CI: 0.86, 1.10). After covariate adjustment, no statistically significant association was found between any flavonoid subclass and esophageal cancer, EAC, or ESCC. However, among current smokers, flavonols were statistically significantly associated with a reduced esophageal cancer risk (HR (log₂) = 0.72, 95% CI: 0.56, 0.94), whereas total flavonoids, flavanols, and flavan-3-ol monomers tended to be inversely associated with esophageal cancer risk. No associations were found in either never or former smokers. These findings suggest that dietary flavonoid intake was not associated with overall esophageal cancer, EAC, or ESCC risk, although total flavonoids and some flavonoid subclasses, particularly flavonols, may reduce the esophageal cancer risk among current smokers.	esophagus
MicroRNA profiling in locally advanced esophageal cancer indicates a high potential of miR-192 in prediction of multimodality therapy response.	To identify possible predictive markers, our study aimed to characterize microRNA (miRNA) profiles of responder and nonresponder in the multimodality therapy of locally advanced esophageal cancer. Initially, a microarray-based approach was performed including eight patients with esophageal cancer. Patients received neoadjuvant chemoradiation followed by surgical resection. Major histopathological response was defined if resected specimens contained less than 10% vital tumor cells (major/minor response: 4/4 patients). Intratumoral RNA was isolated from both, pretherapeutic tissue biopsies in addition to corresponding surgical specimens. The profile of 768 miRNAs was analyzed in 16 specimens (preneoadjuvant and postneoadjuvant therapy). Selected miRNAs were than analyzed on pretherapeutic and post-therapeutic biopsies of 80 patients with esophageal cancer, who underwent multimodality therapy (major/minor response: 30/50 patients). Comprehensive miRNA profiling identified miRNAs in pretherapeutic biopsies that were significantly different between major/minor responders. Based on the microarray results, miR-192, miR-194 and miR-622 were selected and the dysregulated miRNAs were studied on an extended series of esophageal cancer patients. The expression of miR-192, miR-194 and miR-622 was significantly reduced after neoadjuvant therapy confirming the array profiling data. Importantly, the pretherapeutic intratumoral expression of miR-192 and miR-194 was significantly associated with the histopathologic response of esophageal squamous cell carcinoma to multimodal therapeutic treatment. Therefore, in patients with locally advanced esophageal cancer undergoing neoadjuvant chemoradiation followed by esophagectomy, miR-192 and miR-194 in pretherapeutic biopsies are considered as indicators of major histopathologic regression.	esophagus
Soluble interleukin-6 receptor is a serum biomarker for the response of esophageal carcinoma to neoadjuvant chemoradiotherapy.	Preoperative chemoradiotherapy has been shown to improve the outcome of patients with esophageal cancer, but because response to this therapy varies, it is desirable to identify in advance individuals who would be unlikely to benefit, in order to avoid unnecessary adverse drug effects. The serum profiles of 84 cytokines and related proteins were determined in 37 patients with esophageal squamous cell carcinoma who received identical neoadjuvant preoperative chemoradiotherapy regimens and underwent surgical resection. Histological response to this therapy was assessed in surgically resected specimens. The serum soluble interleukin-6 receptor (sIL6R) level was significantly higher in 30 patients who failed to achieve a histological complete response (P = 0.005). Multivariate analysis revealed that the increased level of sIL6R was one of several significant independent predictors of an unfavorable outcome (hazard ratio, 2.87; P = 0.017). The increased level of this cytokine in patients who did not obtain a complete response was reproducibly observed in an independent cohort of 34 patients. Esophageal squamous cell carcinoma patients with an increased serum level of sIL6R are predicted to respond poorly to preoperative chemoradiotherapy, therefore, their exclusion from this treatment may be considered. Persistent systemic inflammation is implicated as a possible mechanism of resistance to this therapy.	esophagus
Palliative brachytherapy with or without primary stent placement in patients with oesophageal cancer, a randomised phase III trial.	PURPOSE: To investigate whether a combination of self-expanding metal stent (SEMS) and brachytherapy provided more rapid and prolonged effect on dysphagia without increased pain compared to brachytherapy alone in patients with incurable oesophageal cancer. METHODS: 41 Patients were randomised to SEMS followed by brachytherapy, 8 Gy×3 (n=21) or brachytherapy alone, 8 Gy×3 (n=20). Change in dysphagia and pain three and seven weeks after randomisation (FU1 and FU2) was assessed by patient-reported outcome. Dysphagia, other symptoms and health-related quality of life were assessed every four weeks thereafter. The study was closed before the estimated patient-number was reached due to slow recruitment. RESULTS: Patients receiving SEMS followed by brachytherapy had significantly improved dysphagia at FU1 compared to patients receiving brachytherapy alone (n=35). Difference in pain was not observed. At FU2, patients in both arms (n=21) had less dysphagia. Four patients in the combined treatment arm experienced manageable complications, no complications occurred after brachytherapy alone. CONCLUSION: For the relief of dysphagia, SEMS followed by brachytherapy is preferable and safe for patients in need of immediate alleviation, while brachytherapy with or without preceding SEMS provides relief within a few weeks after treatment.	esophagus
REG1A expression status suggests chemosensitivity among advanced thoracic esophageal squamous cell carcinoma patients treated with esophagectomy followed by adjuvant chemotherapy.	BACKGROUND: Regenerating gene 1A (REG1A) plays an important role in tissue regeneration and in cell proliferation in the mucous membrane of the gastrointestinal tract. We previously reported that the positive expression status of REG1A was predictive of chemoradiosensitivity in patients treated with preoperative chemoradiotherapy before esophagectomy or with definitive chemoradiotherapy. To further confirm the utility of REG1A as a chemosensitivity marker, we carried out an additional retrospective clinical study aimed at determining whether REG1A is a reliable chemosensitivity marker in patients treated with esophagectomy followed by adjuvant chemotherapy. METHOD: A total of 177 patients with T2-4 thoracic esophageal squamous cell carcinoma received curative surgery without preoperative treatment at Akita University Hospital between 2001 and 2011. A tissue microarray was constructed, and REG1A expression status was analyzed immunohistochemically. We then statistically analyzed the relationships between REG1A expression status and 5-year overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS). RESULTS: In the adjuvant group (n=105), REG1A-positive patients showed significantly better prognoses than REG1A-negative patients. (5-year OS, p=.0022; DSS, p=.0004; and DFS, p=.0040). However, there were no significant differences between REG1A-positive and REG1A-negative patients in the surgery group (n=72). Univariate and multivariate analyses showed REG1A expression status to be a significant prognostic factor affecting 5-year DSS, comparable to lymph node metastatic status. CONCLUSION: The present study suggests REG1A expression status has the potential to be a highly reliable and clinically useful chemosensitivity marker in patients treated with advanced thoracic esophageal squamous cell carcinoma. REG1A expression status will provide a good indication of treatment strategy and enable more individualized treatment for patients.	esophagus
Accuracy of multidetector-row CT for restaging after neoadjuvant treatment in patients with oesophageal cancer.	OBJECTIVES: To assess the diagnostic accuracy of 64-multidetector CT (MDCT) for restaging of patients with oesophageal cancer undergoing neoadjuvant therapy. METHODS: Results of pathological staging were correlated with those from 64-MDCT before and after neoadjuvant treatment in 35 patients using the American Joint Committee on Cancer/TNM classification (7th edition). CT response was determined using the Response Evaluation Criteria in Solid Tumours (RECIST) method, modified for one-dimensional tumour diameter measurement. RESULTS: 64-MDCT predicted T stage correctly in 34 % (12/35), overstaged in 49 % (17/35) and understaged in 17 % (6/35). Sensitivity/specificity values were as follows: T0, 20 %/92 %; T1-T2, 31 %/59 %; T3, 60 %/64 %; T4, 100 %/4 %. Negative predictive values for T3/T4 were 80 %/100 %. MDCT accurately predicted complete histopathological response in 20 % (accuracy 74 %) and overstaged in 80 %. Tumour regression grade was predicted correctly in only 8 % (2/25) and underestimated in 68 % (17/25). Accurate N stage was noted in 69 % (24/35). CONCLUSION: Although MDCT tends to be able to exclude advanced tumour stages (T3, T4) with a higher likelihood, the diagnostic accuracy of high resolution MDCT for restaging oesophageal cancer and assessing the response to neoadjuvant therapy has not improved in comparison to older-generation CT. Therefore, the future assessment of oesophageal tumour response should focus on combined morphologic and metabolic imaging. KEY POINTS: • Multidetector CT (MDCT) has been beneficial for the evaluation of many tumours. • However diagnostic accuracy for restaging oesophageal cancer has not improved with MDCT. • MDCT tends to be able to exclude advanced tumour stages (T3/T4). • MDCT has a low accuracy for determining lymph node metastasis. • Oesophageal tumour response should be assessed by combined morphological and metabolic imaging.	esophagus
A strategy for supraclavicular lymph node dissection using recurrent laryngeal nerve lymph node status in thoracic esophageal squamous cell carcinoma.	BACKGROUND: The desirability of supraclavicular lymph node (LN) dissection, which is the cervical part of three-field LN dissection, has been discussed for a long time. In this study, we examine the pattern of supraclavicular LN metastasis in esophageal cancer, with a particular focus on the correlation between recurrent laryngeal nerve (RLN) LN and supraclavicular LN metastasis. METHODS: In all, 220 cases of R0 resected T1 to T3 squamous cell carcinomas were retrospectively examined. All of these patients underwent bilateral RLN LNs dissection; none received cancer treatment before surgery. RESULTS: Of 21 upper esophageal cancer cases, 33.3% of the patients had metastasis in the supraclavicular LN. Every patient in whom supraclavicular LN metastasis developed had metastasis in the RLN LN. Of 141 cases of middle esophageal cancer, 19.1% had metastasis in the supraclavicular LN. Among the patients whose RLN LN metastasized, 38.3% had metastasis in the supraclavicular LN. A similar correlation between RLN LN and supraclavicular LN metastasis was observed in lower esophageal cancer cases, especially in T3 cases. When considering cancers of the esophagus and patients who had metastasis in the supraclavicular LN, our data demonstrated that RLN LN metastasis did not always lead to metastasis on the same side of the supraclavicular LN. CONCLUSIONS: The status of the RLN LN can be an indicator of supraclavicular LN dissection in upper esophageal cancer patients and advanced cases of middle and lower esophageal cancer patients. Bilateral supraclavicular LN dissection should be recommended even when only unilateral RLN LN metastasis occurs.	esophagus
Elective lymph node irradiation late course accelerated hyper-fractionated radiotherapy plus concurrent cisplatin-based chemotherapy for esophageal squamous cell carcinoma: a phase II study.	BACKGROUND: In this phase II study, we evaluated the efficacy, toxicity, and patterns of failure of elective lymph node irradiation (ENI) late course accelerated hyper-fractionated radiotherapy (LCAHRT) concurrently with cisplatin-based chemotherapy (CHT) for esophageal squamous cell carcinoma (ESCC). METHODS: Patients with clinical stage II-IVa (T1-4N0-1M0 or M1a) ESCC were enrolled between 2004 and 2011. Radiation therapy (RT) comprised two courses: The first course of radiation covered the primary and metastatic regional tumors and high risk lymph nodal regions, given at 2 Gy per fraction for a dose of 40 Gy. In the second course, LCAHRT was delivered to the boost volume twice a day for an additional 19.6 Gy in 7 treatment days, using 1.4 Gy per fraction. Two cycles of CHT were given at the beginning of RT. RESULTS: The median age and Karnofsky performance status were 63 years and 80, respectively. The American Joint Committee on Cancer stage was II in 14 (20.6%) patients, III in 32 (47.1%), and IVa in 22 (32.3%). With a median follow-up of 18.5 months, the overall survival at 1-, 3-, 5-year were 75.5%, 46.5%, 22.7% for whole group patients, versus 78.6%, 49.4%, 39.9% for patients with stage II-III. The patterns of first failure from local recurrence, regional failure, and distant metastasis were seen in 20.6%, 17.6%, and 19.1%, respectively. The most frequent acute high-grade (≥ 3) toxicities were esophagitis and leucopenia, occurred in 26.4% and 32.4%. CONCLUSIONS: ENI LCAHRT concurrently with CHT was appeared to be an effective regimen for ESCC patient with a favorable and tolerated profile. Further observation with longer time and randomized phase III trial is currently underway. TRIAL REGISTRATION: ChiCTR-TRC-09000568.	esophagus
Barrett's adenocarcinoma in long-segment Barrett's esophagus successfully detected by narrow-band imaging with magnifying endoscopy.	Conventionally, long-segment Barrett's esophagus (LSBE) has been considered a high-risk background for the occurrence of Barrett's adenocarcinoma in Western countries, and random biopsy has been proposed for surveillance, aiming to detect early cancer. However, accurate detection of a lesion and diagnosis of the expansion are difficult by this blind method. Herein, we report a case of early Barrett's adenocarcinoma derived from LSBE that was successfully detected by narrow-band imaging with magnifying endoscopy.	esophagus
Magnifying endoscopy with narrow-band imaging findings in the diagnosis of Barrett's esophageal adenocarcinoma spreading below squamous epithelium.	It has been described that most cases of Barrett's esophageal adenocarcinoma in Japan are cases of Barrett's esophageal adenocarcinoma on a background of short-segment Barrett's esophagus, frequently occurring rostrad to Barrett's epithelium, adjacent to the squamous epithelium of the right wall of the esophagogastric junction. Barrett's esophageal adenocarcinoma may spread below the squamous epithelium when the tumor is situated adjacent to the squamocolumnar junction, so that it is usually difficult to diagnose its presence and extent by conventional endoscopy alone. We have noted that the spread of Barrett's esophageal adenocarcinoma below the squamous epithelium is recognizable as annular vascular formations (AVF) by magnifying endoscopy with narrow-band imaging (ME-NBI), and have verified it by 3-D stereo-reconstruction using serial sections from a specimen of the same lesion. When horizontal cross-sections of the tissue were viewed from the surface, AVF emerged at a depth of approximately 100 μm from the surface and disappeared at a depth of approximately 300 μm. Therefore, it would be presumed to be difficult to visualize the characteristic structural features by ME-NBI if the carcinomatous glandular ducts were situated deeper than approximately 300 μm underneath a thick layer of squamous epithelium. Thickness of the overlying squamous epithelium may be a limiting factor for whether or not the characteristic structural features can be detected.	esophagus