crossing96/oncoscreening huggingface dataset:
Phase I/II Trial of Chemotherapy with Docetaxel, Cisplatin, and S-1 for Unresectable Advanced Squamous Cell Carcinoma of the Esophagus.	Our previous trial with a docetaxel, cisplatin, and 5-fluorouracil (DCF) regimen showed high response rates in metastatic squamous cell carcinoma of the esophagus (SCCE). The observed increased toxicity of the DCF regimen, however, was clinically harmful. S-1, an oral anticancer drug, has been approved as a combination therapy for SCCE, and alternate-day regimen with S-1 has shown lower levels of toxicity. This prospective single-center phase I/II trial examines the efficacy and toxicity of a combination of docetaxel, cisplatin, and an alternate-day regimen of S-1 (modified DCS) for patients with metastatic SCCE. We use a two-stage design. Phase I is undertaken to determine the maximum tolerated dose and the recommended dose. The phase I trial adopts a three-patient cohort with escalating dose study design. In the phase II trial, the primary endpoint is the assessment of the overall response rate (Response Evaluation Criteria in Solid Tumors 1.1). The secondary endpoints are the evaluation of drug-related toxicity (National Cancer Institute Common Toxicity Criteria 4.0), overall survival, and progression-free survival. Fifty patients with metastatic SCCE participate in the phase II section. This study protocol is the first to test the effects of the modified DCS regimen for metastatic SCCE.	esophagus
MicroRNA-125a-5p enhances the sensitivity of esophageal squamous cell carcinoma cells to cisplatin by suppressing the activation of the STAT3 signaling pathway.	Increasing evidence has demonstrated that microRNAs (miRNAs or miRs) play a variety of roles in tumor development, progression and chemosensitivity in a wide range of tumors. In this study, we found that miR‑125a‑5p exhibited a low expression in esophageal squamous cell carcinoma (ESCC) tissues and cells, and that its low expression was associated with higher tumor staging and shorter a survival time of patients with ESCC. Moreover, miR‑125a‑5p overexpression contributed to the suppression of cell proliferation, cell cycle arrest, cell apoptosis and a decrease in cell migratory and invasive abilities, whereas the downregulation of miR‑125a‑5p promoted cell proliferation, accelerated cell cycle progression, suppressed apoptosis and enhanced the migratory and invasive abilities of ESCC EC1 and TE1 cells, which may be tightly associated with the epithelial‑mesenchymal transition (EMT) process in ESCC. Importantly, miR‑125a‑5p enhanced the cytotoxic effects of cisplatin on EC1 and TE1 cells, and co‑treatment with miR‑125a‑5p and cisplatin significantly induced cell apoptosis and reduced the cell migratory and invasive abilities of EC1 and TE1 cells, coupled with an increase in the E‑cadherin level and a decrease in the N‑cadherin and Vimentin levels. Most notably, signal transducer and activator of transcription‑3 (STAT3) was found to be a direct target of miR‑125a‑5p in ESCC cells, and miR‑125a‑5p overexpression significantly reduced the protein levels of t‑STAT3, p‑STAT3 and vascular endothelial growth factor (VEGF) in EC1 and TE1 cells. Furthermore, the combination of miR‑125a‑5p and cisplatin markedly inactivated the STAT3 signaling pathway; however, interleukin (IL)‑6, a widely reported activator of the STAT3 signaling pathway, reversed the suppressive effects of miR‑125a‑5p/cisplatin in ESCC cells on the activation of the STAT3 signaling pathway. Of note, we found that IL‑6 markedly reversed the altered cell phenotype mediated by the combination of miR‑125a‑5p and cisplatin in ESCC cells. These findings suggest that miR‑125a‑5p may play a pivotal role in the development and progression of ESCC, which may be achieved via the manipulation of the STAT3 signaling pathway.	esophagus
Novel long noncoding RNA NMR promotes tumor progression via NSUN2 and BPTF in esophageal squamous cell carcinoma.	Long noncoding RNAs (lncRNA) have been implicated in cancer but most of them remain largely unstudied. Here, we identified a novel NSUN2 methylated lncRNA (NMR), which was significantly upregulated in esophageal squamous cell carcinoma (ESCC), functioned as a key regulator of ESCC tumor metastasis and drug resistance. Upregulation of NMR correlated with tumor metastasis and indicated poor overall survival in ESCC patients. Functionally, NMR could promote tumor cell migration and invasion, inhibit cisplatin-induced apoptosis and increase drug resistance in ESCC cells. Mechanistically, transcription of NMR could be upregulated by NF-κB activation after IL-1β and TNF-α treatment. NMR was methylated by NSUN2 and might competitively inhibit methylation of potential mRNAs. NMR could directly bind to chromatin regulator BPTF, and potentially promote MMP3 and MMP10 expression by ERK1/2 pathway through recruiting BPTF to chromatin. Taken together, NMR functions as an oncogenic gene and may serve as new biomarker and therapeutic target in ESCC.	esophagus
Surgical treatment of esophageal cancer in the era of multimodality management.	Over the last decades, the treatment of resectable esophageal cancer has evolved into a multidisciplinary process in which all players are essential for treatment to be successful. Medical oncologists and radiation oncologists have been increasingly involved since the implementation of neoadjuvant therapy, which has been shown to improve survival. Although esophagectomy is still considered the cornerstone of curative treatment for locally advanced esophageal cancer, it remains associated with considerable postoperative morbidity, despite promising results of minimally invasive techniques. In this light, both physical status and response to neoadjuvant therapy may be important factors for selecting patients who will benefit from surgery. Furthermore, it is important to optimize the entire perioperative trajectory: from the initial outpatient clinic visit to postoperative discharge. Enhanced recovery after surgery is increasingly recognized for esophagectomy and emphasizes perioperative aspects, such as nutrition, physiotherapy, and pain management. To date, several facets of esophageal cancer treatment remain topics of debate, such as the preferred neoadjuvant treatment, anastomotic technique, extent of lymphadenectomy, organization of postoperative care, and the role of surgery beyond locally advanced disease. Here, we describe the current and future perspectives in the surgical treatment of patients with esophageal cancer in the context of the available literature.	esophagus
Tumour volume of resectable oesophageal squamous cell carcinoma measured with MRI correlates well with T category and lymphatic metastasis.	OBJECTIVES: To determine association of gross tumour volume (GTV) of resectable oesophageal squamous cell carcinoma (SCC) measured on T(2)-weighted imaging (T(2)WI), contrast-enhanced T(1)-weighted imaging (CE-T(1)WI) and diffusion-weighted imaging (DWI) with T category and lymphatic metastasis (LM). METHODS: Sixty oesophageal SCC patients underwent fat-suppressed T(2)WI, CE-T(1)WI and DWI with b values of 0, 500 and 800 s/mm(2). GTV was measured on three sequences. Statistical analyses were performed to determine association of GTV with T category and LM. RESULTS: Spearman's rank correlation analysis showed positive association of GTV with T category and LM (all p values < 0.01). Differences in GTV were found between T1 and T2 or T3 categories shown by Kruskal-Wallis H and one-way ANOVA tests, and between T1/T2 and T3 and between tumours with and without LM by Mann-Whitney U tests (all p values < 0.05). Receiver operating characteristic analyses showed cut-off GTVs of 5.795, 5.276 and 10.11 cm(3) on CE-T(1)WI could better differentiate T1 from T2 categories, T1 from T3, and T1-2 from T3 than those of 7.066, 7.045 and 8.504 cm(3) on T(2)WI, of 5.793, 6.609 and 6.989 cm(3) on DWI with b value of 500 s/mm(2), and of 4.156, 4.519 and 4.985 cm(3) with b value of 800 s/mm(2), respectively. Cut-off of 10.462 cm(3) on DWI with b value of 500 s/mm(2) could better identify LM than of 12.38, 8.793 and 9.600 cm(3) on T(2)WI, CE-T(1)WI and DWI with b value of 800 s/mm(2), respectively. CONCLUSIONS: GTVs on T(2)WI, CE-T(1)WI and DWI are associated with T category of and LM of oesophageal SCC. KEY POINTS: • GTV is associated with T category and lymphatic metastasis of oesophageal SCC • GTV measured on contrast-enhanced T (1) -weighted imaging better identifies T category • GTV measured on DWI with b value of 500 s/mm (2) better identifies lymphatic metastasis.	esophagus
Lorenz Curves and Gini Coefficient Analyses Indicate Inefficiencies in Esophageal Adenocarcinoma Screening.	Rates of esophageal adenocarcinoma (EAC) have increased rapidly in the United States and much of western Europe, and 5-year survival continues to be poor.(1) Prevention and early detection efforts for EAC have focused on identifying persons with EAC precursor state, Barrett's esophagus, but the survival benefit has been disappointingly low.	esophagus
A retrospective study of treatment for curative synchronous double primary cancers of the head and neck and the esophagus.	OBJECTIVE: Curative synchronous double primary cancers of the head and neck and the esophagus (CSC-HE) are frequently detected, but a standard treatment remains to be established. We studied the clinical course to explore appropriate treatment strategies. METHODS: We retrospectively studied consecutive 33 patients who had CSC-HE. The disease stage was classified into 4 groups: group A, early head and neck cancer (HNC) and early esophageal cancer (EC); group B, early HNC and advanced EC; group C, advanced HNC and early EC; and group D, advanced HNC and advanced EC. As induction chemotherapy, the patients received 3 courses of TPF therapy (docetaxel 75mg/m(2) on day 1, cisplatin 75mg/m(2) on day 1, and 5-fluorouracil 750mg/m(2) on days 1-5) at 3-week intervals. The clinical courses and treatment outcomes were studied according to the disease stage of CSC-HE. RESULTS: The disease stage of CSC-HE was group A in 1 patient (3%), group B in 9 patients (27.3%), group C in 3 patients (9.1%), and group D in 20 patients (60.6%). The median follow-up was 26months, and the 2-year overall survival rate was 67.4%. In groups A, B, and C, the 2-year overall survival rate was 83.3%. In group D, the 2-year overall survival rate was 62.6%. Ten of 20 patients in group D received induction chemotherapy with TPF, and 6 patients were alive and disease free at the time of this writing. CONCLUSION: The treatment outcomes of patients with CSC-HE were relatively good. TPF induction chemotherapy might be an effective treatment for patients with advanced HNC and advanced EC.	esophagus
MiR-23b-3p induces the proliferation and metastasis of esophageal squamous cell carcinomas cells through the inhibition of EBF3.	MicroRNAs (miRNAs), some small non-coding RNAs that regulate gene expression at the posttranscriptional level, are always aberrantly expressed in carcinomas. In this study, we found that miR-23b-3p was remarkably up-regulated in human esophageal squamous cell carcinoma cells and tissues. Moreover, miR-23b-3p could induce the proliferation, invasion, and metastasis in vitro. EBF3 was identified as the direct downstream target gene of miR-23b-3p and ectogenic EBF3 could strongly inhibit the proliferation, invasion, and metastasis in vitro. Furthermore, it was found that miR-23b-3p could regulate epithelial-to-mesenchymal transition progress by blocking EBF3. Therefore, it was concluded that miR-23b-3p targeted EBF3 to accelerate the proliferation, invasion, and metastasis in ESCC.	esophagus
Stable silencing of dll4 gene suppresses the growth and metastasis of esophagus cancer cells by attenuating Akt phosphorylation.	δ‑Like ligand 4 (DLL4) has recently been reported to be involved in the process of cancer angiogenesis and considered to play a vital role in vascular endothelial growth factor (VEGF) signaling, while the role of DLL4 in cancer metastasis and growth has not been systematically studied. In the present study, the esophagus cancer cell line Eca109 was infected in vitro with a lentiviral vector loaded with dll4‑shRNA to obtain a stable cell line of DLL4 expression which was downregulated through puromycin screening. The migration and invasion ability of the Eca109 dll4‑shRNA cells were evaluated by scratch and Transwell assays, respectively. The underlying signaling pathway was further explored by western blotting. Subsequently, to explore the role of dll4 in the development of esophagus cancer cells in vivo, a xenograft model was established by intraperitoneal injection with Eca109 dll4‑shRNA cells containing luciferase activity in nude mice. Then, small animal imaging system was used to evaluate the volume and metastatic potential of the tumors. Additionally, the overall survival rate of the nude mice was also recorded. Following infection with lentivirus, the expression of DLL4 in the Eca109 cells could be stably silenced through screening with puromycin, which was confirmed by western blotting. The scratch and Transwell assays demonstrated that downregulated DLL4 significantly diminished the aggressive invasion and migration properties of the Eca109 cells. The underlying mechanisms may be attributed to the inactivation of the PI3K/Akt/E‑cadherin pathway by western blotting. Finally, the results from the in vivo study indicated that the tumor growth rate in the Eca109 dll4‑shRNA group, as displayed by the tumor volume and the weak staining of the proliferating cell nuclear antigen (PCNA), was significantly slower than the control group, and the metastasis ability of the Eca109 dll4‑shRNA cells was also dramatically abolished in vivo. It was also observed that downregulated DLL4 led to the formation of less pulmonary nodules in mice lungs and to a prolonged survival rate of nude mice. In summary, this study revealed that DLL4 has pathophysiological roles on the progression of esophagus cancer cells, including migration, invasion and apoptosis, which indicated that DLL4 may be considered as a potent therapeutic target for the treatment of malignant esophageal cancer.	esophagus
Anti‑metastatic effects of Aidi on human esophageal squamous cell carcinoma by inhibiting epithelial‑mesenchymal transition and angiogenesis.	Aidi injection, a proprietary Chinese medicine, has been widely used for the treatment of cancer. However, its effects and potential mechanism in esophageal squamous cell carcinoma (ESCC) have not yet been characterized. The aim of the present study was to identify the mechanism underlying the anti‑metastatic effects of treatment with Aidi. To test the effects and mechanism, EC9706 and KYSE70 cells were selected for in vitro experiments. In vivo, the anti‑metastatic effects of Aidi injection on a nude mouse peritoneal metastasis model were examined, and the mechanisms were assessed with immunohistochemical staining. A cell proliferation assay demonstrated that treatment with more than 3 mg/ml Aidi for 24 or 48 h significantly inhibited the proliferation of EC9706 (P<0.01) and KYSE70 cells (P<0.05, P<0.01). Subsequent experiments assessed cell migration, invasion and vasculogenic mimicry (VM) formation, with 5‑fluorouracil serving as a positive control. It was observed that treatment with Aidi inhibited cell migration, invasion and VM formation. Furthermore, it was identified that treatment with Aidi inhibited epithelial‑mesenchymal transition (EMT) signaling and the expression of vascular endothelial growth factor A (VEGF‑A) in EC9706 and KYSE70 cells, using western blotting. In the in vivo experiments, Aidi injection effectively suppressed tumor metastasis in the mouse tumor model. Additionally, the expression of vimentin and vascular endothelial growth factor was decreased, and the expression of cadherin‑1 was increased in the tumor tissue. The present results suggested that treatment with Aidi may inhibit tumor metastasis in ESCC through the inhibition of EMT signaling and angiogenesis.	esophagus
Oncogenic IL7R is downregulated by histone deacetylase inhibitor in esophageal squamous cell carcinoma via modulation of acetylated FOXO1.	The interleukin-7 receptor (IL7R) is generally expressed in immune cells and is critical in survival, development and homeostasis in the immune system. Advanced genome-wide cancer studies have reported that IL7R is genetically amplified in human esophageal squamous cell carcinoma (ESCC), however, the exact role of IL7R in ESCC has not been investigated. In the present study, it was found that IL7R was overexpressed in ESCC cohorts and the loss of IL7R induced anti-oncogenic effects in ESCC cell lines. A small panel of epigenetic drugs were screened for their ability to downregulate the expression of IL7R. Unexpectedly, apicidin, a histone deacetylase (HDAC) inhibitor, effectively downregulated the expression of IL7R in a dose-dependent manner at an early time-point, as determined by quantitative polymerase chain reaction and IL7R immunostaining, and did not require de novo protein synthesis. Of note, apicidin induced the acetylation of Forkhead box-containing protein, O subfamily 1, which acts as a repressor at the IL7R promoter, accompanied with depleted active histone modifications based on chromatin immunoprecipitation assay. Taken together, these results demonstrated that targeting oncogenic IL7R in ESCC by HDAC inhibitors may be a valuable therapeutic approach.	esophagus
Prevalence of the integration status for human papillomavirus 16 in esophageal carcinoma samples.	BACKGROUND/AIMS: To investigate the etiology of esophageal cancer (EC) related with human papillomavirus (HPV) infection. MATERIALS AND METHODS: Fresh surgically resected tissue samples and clinical information were obtained from 189 patients. Genomic DNA was extracted, and HPV was detected using polymerase chain reaction (PCR) with HPV L1 gene primers of MY09/11; HPV16 was detected using HPV16 E6 type-specific primer sets. Copies of HPV16 E2, E6, and the human housekeeping gene β-actin were tested using quantitative PCR to analyze the relationship between HPV16 integration and esophageal squamous cell carcinoma and the relationship between the HPV16 integration status and clinical information of patients. RESULTS: Of the 189 samples, 168 HPV-positive samples were detected, of which 76 were HPV16 positive. Among the HPV16 positive samples, 2 cases (E2/E6 ratio>1) were 2.6% (2/76) purely episomal, 65 (E2/E6 ratio between 0 and 1) were 85.6% (65/76) mixture of integrated and episomal, and 9 (E2/E6 ratio=0) were 11.8% (9/76) purely integrated. The results indicate that integration of HPV16 was more common in the host genome than in the episome genome. The prevalence rate of HPV16 integration is increasing with the pathological stage progression of esophageal carcinoma (EC). CONCLUSION: A high prevalence of HPV16 suggested that HPV16 has an etiological effect on the progress of EC. Integration of HPV16 is more common than episome genome in the host cells, indicating that continuous HPV infection is the key to esophageal epithelial cell malignant conversion and canceration.	esophagus
The Negative Survival Impact of Infectious Complications After Surgery is Canceled Out by the Response of Neoadjuvant Chemotherapy in Patients with Esophageal Cancer.	BACKGROUND: This study was designed to investigate whether postoperative infectious complications (ICs) are a risk factor for the prognosis in esophageal cancer patients who receive neoadjuvant chemotherapy by stratifying the response to neoadjuvant chemotherapy. METHODS: The present study retrospectively examined patients who received neoadjuvant chemotherapy followed by esophagectomy between January 2011 and September 2015. Risk factors for overall survival (OS) were examined by Cox proportional hazard analyses. Pathological responders to neoadjuvant chemotherapy were defined as those with a tumor disappearance of more than one-third of the initial tumor. Postoperative ICs were defined using the Clavien-Dindo classification. RESULTS: Of the 111 patients examined, 45 (40.5%) developed postoperative ICs. A pathological response to neoadjuvant chemotherapy was observed in 54 (48.6%) patients. The multivariate analysis demonstrated that postoperative ICs were a significant independent risk factor for the OS (hazard ratio [HR] 2.359; 95% confidence interval [CI] 1.057-5.263, p = 0.036). In the subset analysis, postoperative ICs were a marginally significant independent risk factor for OS in the nonresponders (HR 2.862; 95% CI 0.942-8.696, p = 0.063) but not in the responders (HR 0.867; 95% CI 0.122-6.153, p = 0.886). CONCLUSIONS: These results suggested that the negative survival impact of postoperative ICs can be canceled out in esophageal cancer patients who respond to neoadjuvant chemotherapy.	esophagus
Prognosis of oesophageal adenocarcinoma and squamous cell carcinoma following surgery and no surgery in a nationwide Swedish cohort study.	OBJECTIVES: To assess the recent prognostic trends in oesophageal adenocarcinoma and oesophageal squamous cell carcinoma undergoing resectional surgery and no such surgery. Additionally, risk factors for death were assessed in each of these patient groups. DESIGN: Cohort study. SETTING: A population-based, nationwide study in Sweden. PARTICIPANTS: All patients diagnosed with oesophageal adenocarcinoma and oesophageal squamous cell carcinoma in Sweden from 1 January 1990 to 31 December 2013, with follow-up until 14 May 2017. OUTCOME MEASURES: Observed and relative (to the background population) 1-year , 3-year and 5-year survivals were analysed using life table method. Multivariable Cox regression provided HR with 95% CI for risk factors of death. RESULTS: Among 3794 patients with oesophageal adenocarcinoma and 4631 with oesophageal squamous cell carcinoma, 82% and 63% were men, respectively. From 1990-1994 to 2010-2013, the relative 5-year survival increased from 12% to 15% for oesophageal adenocarcinoma and from 9% to 12% for oesophageal squamous cell carcinoma. The corresponding survival following surgery increased from 27% to 45% in oesophageal adenocarcinoma and from 24% to 43% in oesophageal squamous cell carcinoma. In patients not undergoing surgery, the survival increased from 3% to 4% for oesophageal adenocarcinoma and from 3% to 6% for oesophageal squamous cell carcinoma. Women with oesophageal squamous cell carcinoma had better prognosis than men both following surgery (HR 0.71, 95% CI 0.61 to 0.83) and no surgery (HR 0.86, 95% CI 0.81 to 0.93). CONCLUSIONS: The prognosis has improved over calendar time both in oesophageal adenocarcinoma and oesophageal squamous cell carcinoma in Sweden that did and did not undergo surgery. Women appear to have better prognosis in oesophageal squamous cell carcinoma than men, independent of treatment.	esophagus