crossing96/oncoscreening huggingface dataset:
Tonglian Decoction () arrests the cell cycle in S-phase by targeting the nuclear factor-kappa B signal pathway in esophageal carcinoma Eca109 cells.	OBJECTIVE: To investigate the anti-tumor activity and molecular mechanism of Tonglian Decoction (, TLD) on esophageal carcinoma Eca109 cells. METHODS: Eca109 cells were treated with TLD and its separated formulae, including the clearing-heat and detoxification formula (Q), activating-blood and promoting-qi formula (H) and nourishing-yin and blood formula (Z). Cell proliferation was measured using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay, cell morphology was observed using a microscope, the cell cycle was measured using flow cytometry and the activity of the nuclear factor-kappa B (NF-κB) signal pathway was detected by Western blot. RESULTS: The half maximal inhibitory concentrations of TLD, Q and H were 386, 771 and 729 mg/L, respectively. TLD, Q and H significantly inhibited cell proliferation, with 69.43%, 60.84% and 61.90% of treated cells in the G phase of the cell cycle. The percentage of cells in S phase increased significantly after treatment with TLD, Q, and H compared with the control group (P<0.05), and TLD showed the strongest effect. Z had no influence on the cell cycle compared with the control group (P>0.05). Western blot detection indicated slight differences in the inhibition of the NF-κB pathway by the different formulae. TLD formula strongly inhibited IKKβ, NF-κB, interleukin-6 and tumor necrosis factor-α expression compared with the control group. CONCLUSIONS: TLD inhibited Eca109 cell proliferation by arresting cells in S phase. The possible mechanism might be related to inhibiting the NF-κB transduction cascade. The combination of the herbs found in the three separate formulae, H, Q and Z, work synergistically in TLD to produce the inhibitory effects of TLD treatment on Eca109 proliferation.	esophagus
Healthcare Cost of Over-Diagnosis of Low-Grade Dysplasia in Barrett's Esophagus.	INTRODUCTION: Published reports have demonstrated that many Barrett's esophagus patients are over-diagnosed as low-grade dysplasia (BE-LGD). We performed an analysis of the surveillance and treatment costs associated with the over-diagnosis of BE-LGD. METHODS: As the principal cost variables, we used endoscopic and histologic procedures performed during the recommended surveillance intervals for patients with BE-LGD, the national average Medicare reimbursement for the Current Procedural Terminology codes of the procedures performed, and a spreadsheet-based tool we created to determine the overall healthcare cost associated with the over-diagnosis of BE-LGD in the US population. RESULTS: The average excess cost (range) for every patient in the US who is over-diagnosed with BE-LGD is estimated to be $5557 ($3115 to $8072). The principal contributors to the excess cost of over-diagnosis of BE-LGD in these patients are: endoscopy ($2626 to $4639), pathologist biopsy review ($275 to $2185), and esophagogastroduodenoscopy-guided endoscopic ablation ($214 to $1249). CONCLUSIONS: The healthcare cost of over-diagnosis of BE-LGD is significant. To reduce the overall healthcare cost impact of over-diagnosis of BE-LGD, strict adherence to the recommendations of the American Gastroenterological Association, American College of Gastroenterology, and American Society for Gastrointestinal Endoscopy that pathology review of all BE biopsy specimens be performed by a gastrointestinal pathologist is warranted.	esophagus
Oral Bisphosphonates and Upper Gastrointestinal Cancer Risks in Asians with Osteoporosis: A Nested Case-Control Study Using National Retrospective Cohort Sample Data from Korea.	BACKGROUND: Bisphosphonate can irritate the gastrointestinal mucosa and increase the risk of esophageal or gastric cancer. The relatively high prevalence of upper gastrointestinal cancers and the widespread use of bisphosphonate in Korea call for further investigation. We conducted a case-control study to evaluate the risk of esophageal or gastric cancer after exposure to oral bisphosphonates in Korean patients with osteoporosis. METHODS: We used the National Health Insurance Service-National Sample Cohort database of Korea from 2002 to 2013. Among osteoporotic patients (>40 years), cases were defined as incident diagnosis of esophageal or gastric cancer between 2006 and 2013. For each case, four controls were matched for age, sex, and income level by type of insurance. We categorized bisphosphonate use as non-user, recent user, past user, and past and recent user, depending on prescription in two periods (1 to 2 years and 2 to 4 years prior to the index date). We also assessed the duration of bisphosphonate use by measuring cumulative duration of exposure (CDE). To examine the association between oral bisphosphonates and esophageal or gastric cancer, we estimated adjusted odds ratios (aORs) and 95% confidence intervals (CIs) using conditional logistic regression analysis, adjusting for concomitant diseases. RESULTS: A total of 1,708 cases and 6,832 controls were identified. The aORs (95% CIs) of recent, past, and continuous bisphosphonate use compared to non-users were 1.18 (0.93-1.51), 1.04 (0.83-1.29), and 1.25 (0.95-1.58)), respectively. In addition, no significant association was observed by CDE, even when different outcome definitions were applied. CONCLUSIONS: This study did not prove an increased risk of esophageal or gastric cancer risk associated with bisphosphonate use, with respect to both risk windows and duration of exposure, in an Asian population-based, real-world setting.	esophagus
Sarcopenia as a predictor of pulmonary complications after esophagectomy for thoracic esophageal cancer.	BACKGROUND AND OBJECTIVES: Sarcopenia or loss of skeletal muscle mass has been identified as a poor prognostic factor for a wide variety of diseases and conditions. We investigated whether preoperative sarcopenia is associated with postoperative complications in patients undergoing esophagectomy for thoracic esophageal cancer. METHODS: We retrospectively reviewed the medical records of consecutive patients with thoracic esophageal cancer who underwent esophagectomy between September 2005 and July 2014 at Kyoto University Hospital. Skeletal muscle mass was assessed using preoperative computed tomographic scans by measuring the cross-sectional muscle area at the third lumbar vertebral level. RESULTS: Among the 199 eligible patients, 149 (75%) were classified as having sarcopenia. There was no difference in the incidence of overall complications between the groups (risk ratio [RR]: 1.10, 95% confidence interval [CI]: 0.80-1.53, P = 0.54). However, pulmonary complications were significantly more frequent in the sarcopenia group than in the nonsarcopenia group (RR: 2.63, 95% CI: 1.20-5.77, P = 0.007). Multivariate analyses demonstrated that sarcopenia was associated with a high adjusted risk of one or more pulmonary complications (odds ratio: 2.96, 95% CI: 1.14-7.69, P = 0.026). CONCLUSIONS: Sarcopenia independently predicts pulmonary complications after esophagectomy for thoracic esophageal cancer. J. Surg. Oncol. 2016;113:678-684. © 2016 Wiley Periodicals, Inc.	esophagus
Motion-robust intensity-modulated proton therapy for distal esophageal cancer.	PURPOSE: To develop methods for evaluation and mitigation of dosimetric impact due to respiratory and diaphragmatic motion during free breathing in treatment of distal esophageal cancers using intensity-modulated proton therapy (IMPT). METHODS: This was a retrospective study on 11 patients with distal esophageal cancer. For each patient, four-dimensional computed tomography (4D CT) data were acquired, and a nominal dose was calculated on the average phase of the 4D CT. The changes of water equivalent thickness (ΔWET) to cover the treatment volume from the peak of inspiration to the valley of expiration were calculated for a full range of beam angle rotation. Two IMPT plans were calculated: one at beam angles corresponding to small ΔWET and one at beam angles corresponding to large ΔWET. Four patients were selected for the calculation of 4D-robustness-optimized IMPT plans due to large motion-induced dose errors generated in conventional IMPT. To quantitatively evaluate motion-induced dose deviation, the authors calculated the lowest dose received by 95% (D95) of the internal clinical target volume for the nominal dose, the D95 calculated on the maximum inhale and exhale phases of 4D CT DCT0 andDCT50 , the 4D composite dose, and the 4D dynamic dose for a single fraction. RESULTS: The dose deviation increased with the average ΔWET of the implemented beams, ΔWETave. When ΔWETave was less than 5 mm, the dose error was less than 1 cobalt gray equivalent based on DCT0 and DCT50 . The dose deviation determined on the basis of DCT0 and DCT50 was proportionally larger than that determined on the basis of the 4D composite dose. The 4D-robustness-optimized IMPT plans notably reduced the overall dose deviation of multiple fractions and the dose deviation caused by the interplay effect in a single fraction. CONCLUSIONS: In IMPT for distal esophageal cancer, ΔWET analysis can be used to select the beam angles that are least affected by respiratory and diaphragmatic motion. To further reduce dose deviation, the 4D-robustness optimization can be implemented for IMPT planning. Calculation of DCT0 and DCT50 is a conservative method to estimate the motion-induced dose errors.	esophagus
Radiosensitization of esophageal carcinoma cells by knockdown of RNF2 expression.	Radiotherapy has been widely used for the treatment of cancer patients, especially for esophageal cancer patients. Ring finger protein 2 (RNF2) plays an important role in promoting the growth of cancer cells after exposure to irradiation. The present study aims to characterize the proliferative effects of RNF2 on cancer cells, and its mechanisms on the growth of esophageal cancer cells. We demonstrate that expression of RNF2 was markedly upregulated in esophageal cancer cell lines and surgically resected cancer specimens. In addition, RNF2 expression level is positively correlated with the presence of tumor size, lymph node metastases and negatively correlated with patient survival rates, suggesting that it plays an important role in the progression of esophageal cancer. Furthermore, the expression of RNF2 at both mRNA and protein levels in esophageal cancer ECA109 and TE13 cells was detected by real-time PCR and western blot assay after shRNA targeting RNF2. Co-immunoprecipitation (Co-IP) assay and western blot analysis were employed to detect the interaction between RNF2 and r-H2AX, H2AK119ub, and the expression of proteins associated with cell cycle and apoptosis, respectively. We used flow cytometry assay to analyze cell cycle and apoptosis of transfected cells, and further examined cellular growth in vitro and in vivo. shRNA targeting RNF2 gene and protein downregulated RNF2 expression after transfection for 24 h. The proliferation of tumor cells in RNF2-shRNA group was suppressed after radiotherapy. In addition, the interaction of RNF2, H2AK119ub, r-H2AX was increased after exposure to IR, followed by increasing apoptosis rates and inducing the arrest at G0/G1 phase after irradiation and shRNA targeting RNF2. Expression of the short-hairpin RNA is also correlated with the upregulation of p16 and Bax, and the downregulation of cyclin D2, cyclin-dependent kinase (CDK)-4, H2AX and Bcl-2. RNF2 gene knockdown induces radiosensitivity of esophageal cancer cells in vitro and significantly inhibits the growth of tumor cells. The mechanisms include inducing the cell cycle arrest at G0/G1 phase and promoting apoptosis.	esophagus
Secreted recombinant human IL-24 protein inhibits the proliferation of esophageal squamous cell carcinoma Eca-109 cells in vitro and in vivo.	Interleukin-24 (IL-24) displays cancer-specific apoptosis-inducing properties in a broad spectrum of human tumors without harmful effects on normal cells. The human IL-24 protein is secreted as a glycosylated protein and functions as a pro-Th1 cytokine and a potent antiangiogenic molecule. However, the function of secreted recombinant human IL-24 (srhIL-24) protein in esophageal squamous cell carcinoma (ESCC) cells has not been studied. In the present study, we prepared a stable site-specific-integrated cell line, Flp-InTMCHO/IL-24 (FCHO/IL-24), which secreted rhIL-24 at a higher level than three random-integrated cell lines. In vitro, we identified that the purified srhIL-24 inhibited proliferation and induced the apoptosis of ESCC Eca-109 cells and activated STAT3, which was related with the IL-20 receptors. In vivo, the tumorigenicity of Eca-109 cells was significantly inhibited by s.c. injection of FCHO/IL-24 cells. Decreased tumor microvessel density and an increased number of TUNEL-positive tumor cells were associated with tumor growth inhibition, indicating the presence of antiangiogenic activity and induction of apoptotic activity. In summary, the present study demonstrated that srhIL-24 induced growth inhibition and apoptosis in ESCC Eca-109 cells in vitro and in vivo, which may be mediated by the receptor pathway.	esophagus
[Short-term efficacy and toxicity of Nimotuzumab combined with simultaneous integrated boost intensity-modulated radiotherapy for locally advanced esophageal cancer].	OBJECTIVE: To evaluate the short-term efficacy and toxicity of Nimotuzumab combined with simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) in the treatment of locally advanced esophageal carcinoma. METHODS: Twenty-nine patients with esophageal carcinoma were treated with SIB-IMRT. Planning gross target volume (PGTV) was given at a dose of 60 Gy/2.4 Gy/25 F and planning target volume (PTV) was given at a dose of 50 Gy/2 Gy/25 F. Nimotuzumab was given by intravenous drip at the dose of 200 mg, once a week before radiotherapy. Short-term efficacy and toxicity were evaluated in all patients. RESULTS: All patients completed the treatment successfully. Fourteen of them achieved a complete response (CR, 48.3%), 13 had a partial response (PR, 44.8%), 1 showed stable disease (SD, 3.6%), and 1 showed progressive disease (PD, 3.6%). The overall response rate (CR+ PR) was 93.1%. Most adverse reactions were radioactive esophagitis, radioactive dermatitis and bone marrow suppression (grade 1-2). Only 1 patient developed a slight skin rash. CONCLUSION: Nimotuzumab combined with SIB-IMRT is a safe and effective modality for locally advanced esophageal cancer. The patient is well tolerated and worthy of further clinical study.	esophagus
Cell Sheet Transplantation for Esophageal Stricture Prevention after Endoscopic Submucosal Dissection in a Porcine Model.	BACKGROUND & AIMS: Extended esophageal endoscopic submucosal dissection (ESD) is highly responsible for esophageal stricture. We conducted a comparative study in a porcine model to evaluate the effectiveness of adipose tissue-derived stromal cell (ADSC) double cell sheet transplantation. METHODS: Twelve female pigs were treated with 5 cm long hemi-circumferential ESD and randomized in two groups. ADSC group (n = 6) received 4 double cell sheets of allogenic ADSC on a paper support membrane and control group (n = 6) received 4 paper support membranes. ADSC were labelled with PKH-67 fluorophore to allow probe-based confocal laser endomicroscopie (pCLE) monitoring. After 28 days follow-up, animals were sacrificed. At days 3, 14 and 28, endoscopic evaluation with pCLE and esophagography were performed. RESULTS: One animal from the control group was excluded (anesthetic complication). Animals from ADSC group showed less frequent alimentary trouble (17% vs 80%; P = 0.08) and higher gain weight on day 28. pCLE demonstrated a compatible cell signal in 4 animals of the ADSC group at day 3. In ADSC group, endoscopy showed that 1 out of 6 (17%) animals developed a severe esophageal stricture comparatively to 100% (5/5) in the control group; P = 0.015. Esophagography demonstrated a decreased degree of stricture in the ADSC group on day 14 (44% vs 81%; P = 0.017) and day 28 (46% vs 90%; P = 0.035). Histological analysis showed a decreased fibrosis development in the ADSC group, in terms of surface (9.7 vs 26.1 mm²; P = 0.017) and maximal depth (1.6 vs 3.2 mm; P = 0.052). CONCLUSION: In this model, transplantation of allogenic ADSC organized in double cell sheets after extended esophegeal ESD is strongly associated with a lower esophageal stricture's rate.	esophagus
Risk factors for Barrett's esophagus.	Barrett's esophagus (BE) is a well-recognized precursor of esophageal adenocarcinoma (EAC) and is defined as ≥1 cm segment of salmon-colored mucosa extending above the gastroesophageal junction into the tubular esophagus with biopsy confirmation of metaplastic replacement of the normal squamous epithelium by intestinal-type columnar epithelium. The incidence of both BE and EAC has been increasing over the past few decades. As a result, preventing the development of BE by identifying and understanding its modifiable and non-modifiable risk factors may help reduce the incidence of EAC. Over the recent past, a tremendous amount of progress has been made towards improving our knowledge of risk factors and pathogenesis of BE. This article reviews the evidence for the various risk factors for developing BE.	esophagus
Local efficacy and survival outcome of salvage endoscopic therapy for local recurrent lesions after definitive chemoradiotherapy for esophageal cancer.	BACKGROUND: Salvage endoscopic therapy (SET), such as endoscopic mucosal resection (EMR) and photodynamic therapy (PDT), is a less-invasive treatment for local failure at the primary site after chemoradiotherapy (CRT) for esophageal squamous cell carcinoma (ESCC). We conducted this retrospective study to clarify the risk factors for local recurrence along with the long term results after SET for recurrent lesions after definitive CRT for ESCC. METHODS: We enrolled 77 consecutive patients who underwent EMR or PDT for local recurrence without any metastasis after definitive CRT at our institution. We evaluated the local efficacy, local recurrence-free survival (LRFS), and overall survival (OS), and investigated the risk factors associated with survival outcome using a multivariate analysis. RESULTS: The complete resection rate of EMR was 84.6 % (33/39), and the complete response rate for PDT was 65.8 % (25/38). Twenty-two patients (28.6 %) exhibited local recurrence without metastasis. Thirty-four patients (44.2 %) were alive at 5 years after undergoing only initial SET or with repeated SET. The 5-year LRFS rate was 59.6 %, and the presence of lesions occupying an esophageal circumference of 1/4 or larger was the only significant risk factor (HR: 3.10, 95 % CI: 1.35-7.15, P = 0.008). The 5-year OS rate was 48.4 %, and an advanced T factor before CRT was marginally associated with a poor OS (HR: 1.96, 95 % CI: 0.98-3.92, P = 0.055). CONCLUSIONS: SET enabled a preferable local control and survival outcome for patients with local recurrence after definitive CRT for ESCC. Careful endoscopic follow-up is needed for patients with a large lesion before SET and those with an advanced T factor before CRT.	esophagus
Updated incidence rates and risk factors of esophageal cancer in Nan'ao Island, a coastal high-risk area in southern China.	Esophageal cancer (EC) is one of the most common cancers in China. The purpose of this study was to investigate the updated incidence rates and risk factors of EC in Nan'ao Island, where the EC incidence rate was chronically the highest in southern China. To calculate the annual incidence rate, data on 338 EC cases from Nan'ao Cancer Registry system diagnosed during 2005-2011 were collected. A case-control study was conducted to explore the EC risk factors. One hundred twenty-five alive EC patients diagnosed during 2005-2011 and 250 controls were enrolled into the case-control study. A pre-test questionnaire on demography, dietary factors, drinking water treatment, and behavioral factors was applied to collect information of all participants. The average EC incidence rates during 2005-2011 were 66.09/105, 94.62/105, 36.83/105 for both genders, males and females, respectively, in Nan'ao Island. The EC incidence rate in males was 2.40- to 4.55-fold higher than that in females in the period from 2006 to 2011 (P < 0.05). Considering the onset age, males tend to be much younger than females and reached peak incidence rate at a younger age (P < 0.05). Drinking water treatment by filter (odds ratio [OR] = 0.28, 95% confidence interval [95% CI] = 0.13-0.58) and fruit consumption (OR = 0.55, 95% CI = 0.32-0.94) reduced the risk for EC. On the contrary, the pickled vegetables consumption (OR = 2.64, 95% CI = 1.46-4.76) and liquor drinking (OR = 2.32, 95% CI = 1.21-4.44) increased the risk for EC. These results may be of importance for future research on EC etiology and prevention strategies.	esophagus
Immuno-PET Imaging and Radioimmunotherapy of 64Cu-/177Lu-Labeled Anti-EGFR Antibody in Esophageal Squamous Cell Carcinoma Model.	Immuno-PET provides valuable information about tumor location, phenotype, susceptibility to therapy, and treatment response, especially to targeted radioimmunotherapy. In this study, we prepared antiepidermal growth factor receptor (EGFR) antibody via identical chelator, 3,6,9,15-tetraazabicyclo[9.3.1]-pentadeca-1(15),11,13-trience-3,6,9,-triacetic acid (PCTA), labeled with (64)Cu or (177)Lu to evaluate the EGFR expression levels using immuno-PET and the feasibility of radioimmunotherapy in an esophageal squamous cell carcinoma (ESCC) model. METHODS: Cetuximab was conjugated with p-SCN-Bn-PCTA and radiolabeled with (64)Cu or (177)Lu. In vitro EGFR expression levels were determined and compared using flow cytometry and cell binding assay. In vivo EGFR expression levels were evaluated via immuno-PET imaging of (64)Cu-cetuximab and biodistribution analysis. Micro-SPECT/CT imaging, biodistribution, and radioimmunotherapy studies of (177)Lu-cetuximab were performed in the ESCC model. Therapeutic responses were monitored using (18)F-FDG PET and immunohistochemical staining. RESULTS: (64)Cu- or (177)Lu-labeled antibodies showed high radiolabeling yield (>98%), stability (>90%), and favorable immunoreactivity. In vitro EGFR status measured by cell binding assay was correlated with the flow cytometry data. Immuno-PET, micro-SPECT/CT, and biodistribution demonstrated specific uptake in ESCC tumors depending on the EGFR expression levels. Tumor accumulation of (64)Cu- and (177)Lu-cetuximab was peaked at 48 and 120 h, respectively. Radioimmunotherapy with (177)Lu-cetuximab showed significant inhibition of tumor growth (P < 0.01) and marked reduction of (18)F-FDG SUV compared with that of control (P < 0.05). Terminal deoxynucleotidyl transferase dUTP nick-end labeling positivity and Ki-67 staining indices increased and decreased, respectively, in the radioimmunotherapy group compared with other groups (P < 0.01). CONCLUSION: (64)Cu-cetuximab immuno-PET represented EGFR expression levels in ESCC tumors, and (177)Lu-cetuximab radioimmunotherapy effectively inhibited the tumor growth. The diagnostic and therapeutic convergence radiopharmaceutical (64)Cu-/(177)Lu-PCTA-cetuximab may be useful as a diagnostic tool in patient selection and a potent radioimmunotherapy agent in EGFR-positive ESCC tumors.	esophagus