crossing96/oncoscreening huggingface dataset:
Super-Enhancer-Driven Long Non-Coding RNA LINC01503, Regulated by TP63, Is Over-Expressed and Oncogenic in Squamous Cell Carcinoma.	BACKGROUND & AIMS: Long non-coding RNAs (lncRNAs) are expressed in tissue-specific pattern, but it is not clear how these are regulated. We aimed to identify squamous cell carcinoma (SCC)-specific lncRNAs and investigate mechanisms that control their expression and function. METHODS: We studied expression patterns and functions of 4 SCC-specific lncRNAs. We obtained 113 esophageal SCC (ESCC) and matched non-tumor esophageal tissues from a hospital in Shantou City, China, and performed quantitative reverse transcription polymerase chain reaction assays to measure expression levels of LINC01503. We collected clinical data from patients and compared expression levels with survival times. LINC01503 was knocked down using small interfering RNAs and oligonucleotides in TE7, TE5, and KYSE510 cell lines and overexpressed in KYSE30 cells. Cells were analyzed by chromatin immunoprecipitation sequencing, luciferase reporter assays, colony formation, migration and invasion, and mass spectrometry analyses. Cells were injected into nude mice and growth of xenograft tumors was measured. LINC01503 interaction with proteins was studied using fluorescence in situ hybridization, RNA pulldown, and RNA immunoprecipitation analyses. RESULTS: We identified a lncRNA, LINC01503, which is regulated by a super enhancer and is expressed at significantly higher levels in esophageal and head and neck SCCs than in non-tumor tissues. High levels in SCCs correlated with shorter survival times of patients. The transcription factor TP63 bound to the super enhancer at the LINC01503 locus and activated its transcription. Expression of LINC01503 in ESCC cell lines increased their proliferation, colony formation, migration, and invasion. Knockdown of LINC01503 in SCC cells reduced their proliferation, colony formation, migration, and invasion, and the growth of xenograft tumors in nude mice. Expression of LINC01503 in ESCC cell lines reduced ERK2 dephosphorylation by DUSP6, leading to activation of ERK signaling via MAPK. LINC01503 disrupted the interaction between EBP1 and the p85 subunit of PI3K, increasing AKT signaling. CONCLUSIONS: We identified an lncRNA, LINC01503, which is increased in SCC cells compared with non-tumor cells. Increased expression of LINC01503 promotes ESCC cell proliferation, migration, invasion, and growth of xenograft tumors. It might be developed as a biomarker of aggressive SCCs in patients.	esophagus
Coexistent Solid Malignancies in Pemphigus: A Population-Based Study.	IMPORTANCE: The association of pemphigus vulgaris and pemphigus foliaceus with comorbid malignancies is yet to be firmly established. OBJECTIVE: To estimate the association between pemphigus and a wide range of nonhematologic malignancies using one of the largest cohorts of patients with pemphigus to date. DESIGN, SETTING, AND PARTICIPANTS: For this cross-sectional study, we used the computerized database of Clalit Health Services, the largest public health care provider organization in Israel insuring 4.4 million individuals in the settings of general community clinics, primary care and referral centers, and ambulatory and hospitalized health care. The study included 1985 patients with pemphigus and 9874 control patients and was conducted from January 2004 to December 2014. MAIN OUTCOMES AND MEASURES: The prevalence of 17 different solid malignancies was compared between patients diagnosed with pemphigus and age-, sex-, and ethnicity-matched control patients; χ2 and t tests were used for univariate analysis, and a logistic regression model was used for multivariate analysis. The association was examined following a sensitivity analysis that included only cases treated with long-term pemphigus-specific medications (corticosteroids, immunosuppressants, or rituximab), and following the adjustment for several confounding factors. RESULTS: Overall, the total sample included 11 859 eligible patients, of whom 1985 were patients with pemphigus (mean [SD] age at presentation, 72.1 [18.5] years; 1188 women [59.8%]). In patients with pemphigus compared with control patients, there was a greater prevalence of esophageal cancers (0.4% vs 0.1%; odds ratio [OR], 2.9; 95% CI, 1.1-7.4) and laryngeal cancers (0.6% vs 0.3%; OR, 2.0; 95% CI, 1.0-4.1). No significant associations between pemphigus and other solid malignancies were observed. Estimates were not altered significantly after controlling for comorbidities, health care overutilization, immunosuppressive therapy, and other malignancy-specific risk factors (ie, smoking and alcohol abuse in laryngeal cancer, gastroesophageal reflux disease in esophageal cancer). CONCLUSIONS AND RELEVANCE: Significant associations were observed between pemphigus and solid malignancies of the larynx and the esophagus. Physicians treating patients with pemphigus should be aware of these findings. Further observational studies are warranted to establish this association in other cohorts.	esophagus
Generalized cardiovascular disease on a preoperative CT scan is predictive for anastomotic leakage after esophagectomy.	BACKGROUND: Recent studies demonstrated that calcification of arteries supplying the gastric tube is associated with anastomotic leakage after esophagectomy. However, it remains unclear whether this association only derives from local flow limitations, or generalized vascular disease as well. The purpose of this study was to determine whether calcification throughout the entire cardiovascular system is associated with anastomotic leakage. METHODS: Consecutive patients who underwent an esophagectomy with gastric tube reconstruction and cervical anastomosis for esophageal cancer were analyzed. Diagnostic CT images were scored for the presence of arterial calcification on 10 locations based on a visual grading system. The association with anastomotic leakage was studied using logistic regression analysis. RESULTS: A total of 406 patients were included for analysis of whom 104 developed anastomotic leakage (25.6%). Presence of calcification in the coronary arteries (minor calcification: 36.5% leakage; no calcification: 18.1%, p = .001), supra-aortic arteries (minor calcification: 30.9% leakage; major calcification: 35.3%; no calcification: 16.1%, p = .007 and p < .001, respectively) and thoracic aorta (major calcification: 33.3% leakage; no calcification: 19.4%, p = .011) was associated with leakage. In multivariable analysis, minor calcification of the coronary arteries (OR 2.29, 95% CI: 1.28-4.12, p = .005) and calcification of the supra-aortic arteries (OR 2.48, 95% CI: 1.30-4.74, p = .006 for minor calcification and OR 2.72, 95% CI: 1.49-4.99, p = .001 for major calcification) remained independently associated with leakage. CONCLUSIONS: Calcification of the coronary and supra-aortic arteries on routine CT are predictive of cervical anastomotic leakage after esophagectomy. These results suggest that generalized cardiovascular disease is a strong indicator for the risk of leakage.	esophagus
Comparing cytotoxic backbones for first-line trastuzumab-containing regimens in human epidermal growth factor receptor 2-positive advanced oesophagogastric cancer: A meta-analysis.	According to the Trastuzumab for Gastric Cancer (ToGA) study, trastuzumab plus cisplatin and capecitabine/5-fluorouracil (5-FU) is standard first-line treatment for human epidermal growth factor receptor 2 (HER2)-positive advanced oesophagogastric cancer. We examined the relative efficacy and safety of alternative trastuzumab-based cytotoxic backbone regimens compared to the standard ToGA regimen using meta-analysis. We searched Medline, EMBASE, CENTRAL and ASCO and ESMO up to March 2017 for studies investigating alternative first-line trastuzumab-based regimens for HER2-positive oesophagogastric cancer, defined as high protein expression IHC3+ or IHC2+ and gene amplification by in situ hybridisation. We compared primary outcome overall survival (OS) of alternative trastuzumab-based regimens to the ToGA regimen. Hazard ratios (HRs) and 95% confidence intervals (95%CI) were calculated by extraction of the published Kaplan-Meier curves. Incidence counts and toxicity sample-sizes were extracted for adverse events and compared using single-arm proportion meta-analysis in R. Fifteen studies (N = 557 patients) were included. OS was significantly longer with regimen trastuzumab plus doublet oxaliplatin and capecitabine/5-FU (median OS = 20.7 months) versus ToGA (16.0 months, HR = 0.75, 95% CI = 0.59-0.99) and was less toxic. Trastuzumab plus doublet cisplatin and S-1 showed no OS difference versus ToGA, but showed a different toxicity profile, including less hand-foot syndrome. Trastuzumab plus cisplatin or capecitabine as singlet backbone showed significantly worse survival and more toxicity versus ToGA regimen. Trastuzumab with triplet cytotoxic backbones or with bevacizumab and doublet cytotoxic backbone showed no survival benefit and more toxicity. In conclusion, trastuzumab plus doublet cytotoxic backbone containing oxaliplatin is preferable over the ToGA regimen with cisplatin. S-1 can substitute capecitabine or 5-FU when specific toxicities are encountered.	esophagus
Racial and Socioeconomic Differences in the Use of High-Volume Commission on Cancer-Accredited Hospitals for Cancer Surgery in the United States.	BACKGROUND: Although major cancer surgery at a high-volume hospital is associated with lower postoperative mortality, the use of such hospitals may not be equally distributed. OBJECTIVE: Our aim was to study socioeconomic and racial differences in cancer surgery at Commission on Cancer (CoC)-accredited high-volume hospitals. METHODS: The National Cancer Database (NCDB) was used to identify patients undergoing surgery for colon, esophageal, liver, and pancreatic cancer from 2003 to 2012. Annual hospital volume for each cancer was categorized using quartiles of patient volume. Patient-level predictors of surgery at a high-volume hospital, trends in the use of a high-volume hospital, and adjusted likelihood of surgery at a high-volume hospital in 2012 versus 2003 were analyzed. RESULTS: African American patients were less likely to undergo surgery at a high-volume hospital for esophageal (odds ratio [OR] 0.59, 95% confidence interval [CI] 0.49-0.73) and pancreatic cancer (OR 0.83, 95% CI 0.74-0.92), while uninsured patients and those residing in low educational attainment zip codes were less likely to undergo surgery at a high-volume hospital for esophageal, liver, and pancreatic cancer. In 2012, African Americans, uninsured patients, and those from low educational attainment zip codes were no more likely to undergo surgery at a high-volume hospital than in 2003 for any cancer type. These differences were not seen in colon cancer patients, for whom significant regionalization was not seen. CONCLUSIONS: Differences in the use of CoC-accredited high-volume hospitals for major cancer surgery were seen nationwide and persisted over the duration of the study. Strategies to increase referrals and/or access to high-volume hospitals for African American and socioeconomically disadvantaged patients should be explored.	esophagus
Surgical management of esophageal sarcoma: a multicenter European experience.	Esophageal sarcomas are rare and evidence in literature is scarce making their management difficult. The objective is to report surgical and oncological outcomes of esophageal sarcoma in a large multicenter European cohort. This is a retrospective multicenter study including all patients who underwent en-bloc esophagectomy for esophageal sarcoma in seven European tertiary referral centers between 1987 and 2016. The main outcomes and measures are pathological results, early and long-term outcomes. Among 10,936 esophageal resections for cancer, 21 (0.2%) patients with esophageal sarcoma were identified. The majority of tumors was located in the middle (n = 7) and distal (n = 9) third of the esophagus. Neoadjuvant chemoradiotherapy was performed in five patients. All the patients underwent en-bloc transthoracic esophagectomy (19 open, 2 minimally invasive). Postoperative mortality occurred in 1 patient (5%). One patient received adjuvant chemotherapy. Definitive pathological results were carcinosarcoma (n = 7), leiomyosarcoma (n = 5), and other types of sarcoma (n = 9). Microscopic R1 resection was present in one patient (5%) and seven patients (33%) had positive lymph nodes. Median follow-up was 16 (3-79) months in 20 of 21 patients (95%). One-, 3-, and 5-year overall survival rates were 74%, 43%, and 35%, respectively. One-, 3- and 5-years disease-free survival rates were 58%, 40%, and 33%, respectively. Median overall survival was 6 months in N+ patients vs. 37 months for N0 patients (p = 0.06). At the end of the follow-up period, nine patients had died from cancer recurrences (43%), three patients died from other reasons (14%), one patient was still alive with recurrence (5%) and the seven remaining patients were free of disease (33%). Recurrence was local (n = 3), metastatic (n = 3), or both (n = 4). In conclusion, carcinosarcoma and leiomyosarcoma were the most common esophageal sarcoma histological subtypes. Lymph node involvement was seen in one third of cases. A transthoracic en-bloc esophagectomy with radical lymphadenectomy should be the best surgical option to achieve complete resection. Long-term survival remained poor with a high local and distant recurrence rate.	esophagus
Minimally invasive esophagectomy may contribute to long-term respiratory function after esophagectomy for esophageal cancer.	Evidence suggests that minimally invasive esophagectomy has several advantages with regard to short-term outcomes, compared to open esophagectomy in esophageal cancer patients. However, the impact of minimally invasive esophagectomy on long-term respiratory function remains unknown. The objective of this study is to assess the association between use of the minimally invasive esophagectomy and long-term respiratory dysfunction in esophageal cancer patients after esophagectomy. This retrospective single institution study using prospectively collected data included 87 consecutive esophageal cancer patients who had undergone esophagectomy. All patients underwent a respiratory function test before, and one year after esophagectomy. Logistic regression analysis was used to compute the hazard ratio for long-term respiratory dysfunction. Minimally invasive esophagectomies were performed in 53 patients, and open esophagectomies in 34 patients. The two groups showed no significant differences in terms of postoperative complications and postoperative course. Nor were any differences observed between the two groups in terms of volume capacity (L) and forced expiratory volume 1.0 (L) before esophagectomy (P > 0.34). However, one year after esophagectomy, the decreases in volume capacity and forced expiratory volume 1.0 were significantly less in the minimally invasive esophagectomy group than in the open esophagectomy group (P = 0.04 and P = 0.007, respectively). Multivariate analyses revealed that minimally invasive esophagectomy was an independent favorable factor for maintenance of forced expiratory volume 1.0 (hazard ratio = 0.17, 95% confidence interval 0.04-0.71; P = 0.01). Minimally invasive esophagectomy may be an independent favorable factor for maintenance of long-term respiratory function in esophageal cancer patients after esophagectomy.	esophagus
Neoadjuvant treatments for locally advanced, resectable esophageal cancer: A network meta-analysis.	The relative survival benefits and postoperative mortality among the different types of neoadjuvant treatments (such as chemotherapy only, radiotherapy only or chemoradiotherapy) for esophageal cancer patients are not well established. To evaluate the relative efficacy and safety of neoadjuvant therapies in resectable esophageal cancer, a Bayesian network meta-analysis was performed. MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials were searched for publications up to May 2016. ASCO and ASTRO annual meeting abstracts were also searched up to the 2015 conferences. Randomized controlled trials that compared at least two of the following treatments for resectable esophageal cancer were included: surgery alone, surgery preceded by neoadjuvant chemotherapy, neoadjuvant radiotherapy or neoadjuvant chemoradiotherapy. The primary outcome assessed from the trials was overall survival. Thirty-one randomized controlled trials involving 5496 patients were included in the quantitative analysis. The network meta-analysis showed that neoadjuvant chemoradiotherapy improved overall survival when compared to all other treatments including surgery alone (HR 0.75, 95% CR 0.67-0.85), neoadjuvant chemotherapy (HR 0.83. 95% CR 0.70-0.96) and neoadjuvant radiotherapy (HR 0.82, 95% CR 0.67-0.99). However, the risk of postoperative mortality increased when comparing neoadjuvant chemoradiotherapy to either surgery alone (RR 1.46, 95% CR 1.00-2.14) or to neoadjuvant chemotherapy (RR 1.58, 95% CR 1.00-2.49). In conclusion, neoadjuvant chemoradiotherapy improves overall survival but may also increase the risk of postoperative mortality in patients locally advanced resectable esophageal carcinoma.	esophagus
Detection of HPV16 in Esophageal Cancer in a High-Incidence Region of Malawi.	"This study was designed to explore the role of human papillomavirus (HPV) in esophageal squamous cell carcinoma (ESCC). Fifty-five patients receiving diagnostic upper gastrointestinal endoscopy at Zomba Central Hospital or Queen Elizabeth Hospital in Blantyre (Malawi) in 2010, were included in our study. Formalin-fixed paraffin-embedded biopsies were collected for histopathological diagnosis. HPV DNA was detected using multiplex Quantitative PCR (qPCR) and in situ hybridization (ISH). p16(INK4a) staining served as a surrogate marker for HPV oncogene activity. Cell proliferation was determined by Ki-67 staining. Human immunodeficiency virus (HIV) status was evaluated by serology. Data on the consumption of alcohol and tobacco, and history of tuberculosis (TBC), oral thrush, and Herpes zoster, were obtained by questionnaire. Forty patients displayed ESCC, three displayed dysplastic epithelium, and 12 displayed normal epithelium. HPV16 was detected in six ESCC specimens and in one dysplastic lesion. Among HPV-positive patients, viral load varied from 0.001 to 2.5 copies per tumor cell. HPV DNA presence could not be confirmed by ISH. p16(INK4a) positivity correlated with the presence of HPV DNA (p = 0.03). Of particular note is that the Ki-67 proliferation index, in areas with diffuse nuclear or cytoplasmatic p16(INK4a) staining ≥50%, was significantly higher in HPV-positive tumors compared to the corresponding p16(INK4a) stained areas of HPV-negative tumors (p = 0.004). HPV infection in ESCC was not associated with the consumption of tobacco or alcohol, but there were significantly more patients drinking locally brewed alcohol among HPV-positive tumor patients compared to non-tumor patients (p = 0.02) and compared to HPV-negative tumor patients (p = 0.047). There was no association between HIV infection, history of TBC, Herpes zoster, oral thrush, or HPV infection, in ESCC patients. Our indirect evidence for viral oncogene activity is restricted to single tumor cell areas, indicative of the role of HPV16 in the development of ESCC. The inhomogeneous presence of the virus within the tumor is reminiscent of the ""hit and run"" mechanism discussed for β-HPV types, such as HPV38."	esophagus
Synthesis and pharmacological evaluation of 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline derivatives as sigma-2 receptor ligands.	Increasing evidences have implicated that sigma-2 receptor is a biomarker and significantly over-expressed in many proliferative cancer cells with no or low expression in normal cells. Sigma-2 receptor selective ligands have been successfully used as valuable tools to study its pharmacological functions, tumor imaging, and cancer therapeutics or adjuvants. 6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinolinylalkyl benzamides are among a few categories of structures that have demonstrated high affinities and selectivities for sigma-2 receptor and been used extensively as study tools in various tumor imaging and therapy. As a continuous effort, we have synthesized a new series of 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline derivatives and evaluated their affinities for both sigma-1 and sigma-2 receptors. Most of these newly developed analogs showed good to excellent binding affinities for sigma-2 receptor with no or low affinities for sigma-1 receptor. In particular, compounds 3b, 3e, 4b, and 4e demonstrated K(i) values of 5-6 nM affinities and excellent selectivities for sigma-2 receptor. In addition, these analogs also demonstrated moderate anticancer activities against human liver Huh-7 tumor cells and human esophagus KYSE-140 cancer cells. But their cytotoxicities seem not to be correlated with their sigma-2 receptor affinities.	esophagus
Thoracoscopic total esophagogastrectomy with supercharged colon interposition for the treatment of esophageal adenocarcinoma in situs inversus.	Background: Esophagectomy in situs inversus is challenging. With long-segment supercharged reconstruction, it becomes more perplexing and multidisciplinary surgical skills are needed. Challenges met and the surgical technique used is presented in this case report. Methods: The case of a 49-year old patient with situs inversus abdominus and a locally advanced distal esophageal adenocarcinoma extending to the stomach is presented. Results: Following neoadjuvant chemotherapy and due to inability to use the stomach as a conduit, a thoracoscopic total esophagogastrectomy with long-segment reconstruction was performed. The conduit used was the left colon and was supercharged with venous and arterial anastomoses in the neck. Conduit perfusion, as assessed by the Spy system revealed marked improvement post supercharging. No anastomotic leak was noted and oral diet was started on day 4. On day 26 the patient developed pneumonia necessitating intubation that was declined. Organ support was withheld with patient death at day 29. Conclusion: In long-segment esophageal reconstruction with supercharged colon, although thoracoscopy is feasible, laparoscopy is found unsafe. Careful preoperative planning and colon assessment via computed tomography(CT) colonography/angiography and a multidisciplinary team approach is recommended. Adjuncts to assess conduit perfusion like the Spy system are helpful. Supercharging the long colonic conduit is a way of minimizing ischemia-related complications.	esophagus