crossing96/oncoscreening huggingface dataset:
Curcumin induces cell death in esophageal cancer cells through modulating Notch signaling.	BACKGROUND: Curcumin inhibits the growth of esophageal cancer cell lines; however, the mechanism of action is not well understood. It is becoming increasingly clear that aberrant activation of Notch signaling has been associated with the development of esophageal cancer. Here, we have determined that curcumin inhibits esophageal cancer growth via a mechanism mediated through the Notch signaling pathway. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we show that curcumin treatment resulted in a dose and time dependent inhibition of proliferation and colony formation in esophageal cancer cell lines. Furthermore, curcumin treatment induced apoptosis through caspase 3 activation, confirmed by an increase in the ratio of Bax to Bcl2. Cell cycle analysis demonstrated that curcumin treatment induced cell death and down regulated cyclin D1 levels. Curcumin treatment also resulted in reduced number and size of esophagospheres. Furthermore, curcumin treatment led to reduced Notch-1 activation, expression of Jagged-1 and its downstream target Hes-1. This reduction in Notch-1 activation was determined to be due to the down-regulation of critical components of the γ-secretase complex proteins such as Presenilin 1 and Nicastrin. The combination of a known γ-secretase inhibitor DAPT and curcumin further decreased proliferation and induced apoptosis in esophageal cancer cells. Finally, curcumin treatment down-regulate the expressions of Notch-1 specific microRNAs miR-21 and miR-34a, and upregulated tumor suppressor let-7a miRNA. CONCLUSION/SIGNIFICANCE: Curcumin is a potent inhibitor of esophageal cancer growth that targets the Notch-1 activating γ-secretase complex proteins. These data suggest that Notch signaling inhibition is a novel mechanism of action for curcumin during therapeutic intervention in esophageal cancers.	esophagus
Protection from intracellular oxidative stress by cytoglobin in normal and cancerous oesophageal cells.	Cytoglobin is an intracellular globin of unknown function that is expressed mostly in cells of a myofibroblast lineage. Possible functions of cytoglobin include buffering of intracellular oxygen and detoxification of reactive oxygen species. Previous work in our laboratory has demonstrated that cytoglobin affords protection from oxidant-induced DNA damage when over expressed in vitro, but the importance of this in more physiologically relevant models of disease is unknown. Cytoglobin is a candidate for the tylosis with oesophageal cancer gene, and its expression is strongly down-regulated in non-cancerous oesophageal biopsies from patients with TOC compared with normal biopsies. Therefore, oesophageal cells provide an ideal experimental model to test our hypothesis that downregulation of cytoglobin expression sensitises cells to the damaging effects of reactive oxygen species, particularly oxidative DNA damage, and that this could potentially contribute to the TOC phenotype. In the current study, we tested this hypothesis by manipulating cytoglobin expression in both normal and oesophageal cancer cell lines, which have normal physiological and no expression of cytoglobin respectively. Our results show that, in agreement with previous findings, over expression of cytoglobin in cancer cell lines afforded protection from chemically-induced oxidative stress but this was only observed at non-physiological concentrations of cytoglobin. In addition, down regulation of cytoglobin in normal oesophageal cells had no effect on their sensitivity to oxidative stress as assessed by a number of end points. We therefore conclude that normal physiological concentrations of cytoglobin do not offer cytoprotection from reactive oxygen species, at least in the current experimental model.	esophagus
Variation in lymph node examination after esophagectomy for cancer in the United States.	OBJECTIVES: To evaluate the quality of lymph node examination after esophagectomy for cancer in the United States based on current treatment guidelines (15 nodes) and to assess the association of patient, tumor, and hospital factors with the adequacy of lymph node examination. DESIGN: Retrospective observational study from 1998 to 2007. SETTING: National cancer database. PATIENTS: Patients with stage I through III esophageal cancer undergoing esophagectomy and not treated with neoadjuvant chemoradiotherapy. MAIN OUTCOME MEASURE: Rate of adequate lymph node examination (15 nodes). RESULTS: A total of 13 995 patients were identified from 639 hospitals. Overall, 4014 patients (28.7%) had at least 15 lymph nodes examined, which increased from 23.5% to 34.4% during the study period. At the hospital level, only 45 centers (7.0%) examined a median of at least 15 lymph nodes. In the most recent period (2005-2007), at least 15 nodes were examined in 38.9% of patients at academic centers vs 28.0% at community hospitals and in 44.1% at high-volume centers vs 29.3% at low-volume centers. On multivariable analysis, hospital type, surgical volume status, and geographic location remained significant predictors of having at least 15 lymph nodes examined. CONCLUSIONS: Fewer than one-third of patients and fewer than 1 in 10 hospitals met the benchmark of examining at least 15 lymph nodes. Hospitals should perform internal process improvement activities to improve guideline adherence.	esophagus
A case of a superficial carcinoma of the esophagus with isolated lymph node metastasis around the abdominal aorta.	Superficial carcinoma of the esophagus with isolated para-aortic lymph node metastasis is quite rare. A 56-year-old female demonstrated a type 0-IIa+IIb lesion in the middle thoracic esophagus on endoscopic examination. Enhanced computed tomography and positron emission tomography demonstrated two swollen lymph nodes on the right side of the inferior vena cava, but did not demonstrate either a primary lesion or regional lymph node metastasis. A retroperitoneal videoscopic lymph node biopsy was thus performed, and the histopathological diagnosis was metastasis of squamous cell carcinoma. Induction chemotherapy was administered with cisplatin/5-FU, and followed by definitive chemoradiotherapy with cisplatin/5-FU plus 60 Gy radiation. The patient showed satisfactory responses in both the primary and metastatic lesions. This is the first case report describing superficial carcinoma of the esophagus with isolated lymph node metastasis around the abdominal aorta. A precise histological diagnosis of the lymph node is quite important in such cases, and an adequate curative effect can be expected.	esophagus
Human papillomavirus infection and esophageal squamous cell carcinoma: a case-control study.	"BACKGROUND: The risk factors for esophageal squamous cell carcinoma (ESCC) in the high-incidence areas of China remain unclear. METHODS: A total of 300 patients with ESCC and 900 controls matched for age and sex were enrolled in Anyang (China), a high-risk area for ESCC in China. In tumor tissue of the cases and in esophageal biopsies of controls, the presence of human papillomavirus (HPV) DNA was assessed by an SPF1/GP6(+)-mediated PCR followed by sequencing. The presence of serum antibody against the HPV-16 E7 oncoprotein was assessed by use of the ELISA. ORs with 95% confidence intervals (CI) were calculated via unconditional logistic regression models. RESULTS: The presence of HPV in the esophagus (OR, 6.4; 95% CI, 4.4-9.2) was associated with increased risk of ESCC. Moreover, infection with ""oncogenic"" types of HPV (OR, 10.3; 95% CI, 6.3-16.8) was more strongly associated with ESCC than other types of HPV (OR, 2.4; 95% CI, 1.4-4.2). The presence of HPV-16 (OR, 12.8; 95% CI, 7.6-21.7) was particularly strongly associated with ESCC. In addition, a higher proportion of cases than controls had serum antibodies against HPV-16 E7 (OR, 6.1; 95% CI, 3.7-10.0). CONCLUSION AND IMPACT: This study provides the strongest epidemiologic evidence to date in support of the important role of HPV in the development of ESCC in high-incidence areas of China."	esophagus
[The role of percutaneous endoscopic gastrostomy(PEG)in palliative care].	The role of percutaneous endoscopic gastrostomy(PEG)in palliative care has not been well discussed. With the evolution of endoscopic techniques and PEG devices, we can perform PEG more safely, even in difficult cases. Actually, PEG is very useful in home care of cancer patients. We should discuss the indications of PEG in the field of palliative medicine. We suggest the following indications for PEG: 1.Difficulty in ingestion of sufficient quantities of food and water because of pain on swallowing, or an obstruction caused by cancer. 2.Normal gastrointestinal function. 3.Expected survival time of more than four weeks in addition to absence of cachexia. 4.Patient's consent for PEG.	esophagus
[Docetaxel plus S-1 as a second-line chemotherapy for metastasis or recurrence of esophageal cancer].	Although chemotherapy consisting of cisplatin and 5-fluorouracil(CF)has been a standard regimen for esophageal cancer, it might be difficult to use continuously. This study evaluated the response and safety of docetaxel plus S-1 used as a second line therapy. We reviewed 21 patients(postoperatively, 11; after definitive chemoradiotherapy, 8; after chemotherapy, 2) who received chemotherapy between 2006 and 2010. Metastatic or recurrent disease was detected in the organs(n=8), lymph nodes(n=8), main tumors(n=3), mediastinum(n=1), and pleura(n=1). Docetaxel 30mg/m2 was infused every 2 weeks, and S-1 80mg/m2 was taken for 2 weeks, then with 2 weeks rest until progression. Almost all of the patients received docetaxel in the outpatient chemotherapy room. The median number of treatment cycles was 3, ranging from 1-12. Among the 14 patients with a therapeutic response, three(21%)achieved PR, 8 showed SD, and 3 had PD. Toxicity which included grade 3/4 was neutropenia in 6 patients, and anemia in one patient. After a follow-up of over one year, the median overall survival was 10 months, and the one-year survival rate was 38%. Docetaxel plus S-1 might be a feasible regimen as a second-line chemotherapy for metastasis or recurrence of esophageal cancer.	esophagus
[A comparison and significance of plasma riboflavin levels in patients with esophageal squamous cell carcinoma versus Linzhou healthy migrants in Changzhi of Shanxi].	OBJECTIVE: To study the relationship between plasma riboflavin levels and esophageal squamous cell carcinoma. METHODS: We detected and compared plasma concentrations of riboflavin in patients with esophageal squamous cell carcinoma (ESCC) and immigrants of Linzhou living in Changzhi. Plasma riboflavin levels were quantified in 445 ESCC patients, 689 healthy control subjects and 347 immigrants of Linzhou living in Changzhi by using enzyme-linked immunosorbent assay. RESULTS: The plasma riboflavin levels in patients with ESCC were significantly lower than those in the healthy controls and immigrants of Linzhou living in Changzhi [(731.69 ± 330.67) µg/L vs (1090.43 ± 445.08) µg/L, (731.69 ± 330.67) µg/L vs (897.58 ± 177.78) µg/L, respectively, all P < 0.05], and the plasma riboflavin levels of the healthy controls were higher than those in the immigrants of Linzhou living in Changzhi (P < 0.05). CONCLUSION: Patients with ESCC have decreased plasma riboflavin levels as compared with the healthy controls and immigrants of Linzhou living in Changzhi, there exists a lack of riboflavin in ESCC patients, but the specific mechanism needs further study.	esophagus
Integrative genomics identified RFC3 as an amplified candidate oncogene in esophageal adenocarcinoma.	PURPOSE: Esophageal adenocarcinoma (EAC) is a lethal malignancy that can develop from the premalignant condition, Barrett's esophagus (BE). Currently, there are no validated simple methods to predict which patients will progress to EAC. A better understanding of the genetic mechanisms driving EAC tumorigenesis is needed to identify new therapeutic targets and develop biomarkers capable of identifying high-risk patients that would benefit from aggressive neoadjuvant therapy. We employed an integrative genomics approach to identify novel genes involved in EAC biology that may serve as useful clinical markers. EXPERIMENTAL DESIGN: Whole genome tiling-path array comparative genomic hybridization was used to identify significant regions of copy number alteration in 20 EACs and 10 matching BE tissues. Copy number and gene expression data were integrated to identify candidate oncogenes within regions of amplification and multiple additional sample cohorts were assessed to validate candidate genes. RESULTS: We identified RFC3 as a novel, candidate oncogene activated by amplification in approximately 25% of EAC samples. RFC3 was also amplified in BE from a patient whose EAC harbored amplification and was differentially expressed between nonmalignant and EAC tissues. Copy number gains were detected in other cancer types and RFC3 knockdown inhibited proliferation and anchorage-independent growth of cancer cells with increased copy number but had little effect on those without. Moreover, high RFC3 expression was associated with poor patient outcome in multiple cancer types. CONCLUSIONS: RFC3 is a candidate oncogene amplified in EAC. RFC3 DNA amplification is also prevalent in other epithelial cancer types and RFC3 expression could serve as a prognostic marker.	esophagus
[Aberrant methylation of T-cadherin gene in human esophageal carcinoma cells].	OBJECTIVE: To explore the methylation status of T-cadherin promoter region in human esophageal carcinoma cell lines EC1 and EC109 and elucidate the effects of 5-azacytidine-2'-deoxycytidine (5-Aza-CdR) on their abilities of proliferation and invasion, the methylation status and the expression of T-cadherin. METHODS: The expression level of T-cadherin was measured by Western blot. And the methylation status of T-cadherin promoter region was analyzed by methylation-specific PCR (polymerase chain reaction), separately before and after a treatment of demethylating agent 5-Aza-CdR. RESULTS: The T-cadherin gene was hypermethylated in EC109 cells but semi-methylated in EC1 cells. After a treatment of 5-Aza-CdR, T-cadherin gene methylation was reversed. And the gene expression was strongly up-regulated in both cells. 5-Aza-CdR could decrease the proliferation and effectively inhibit the ability of cell invasion (P < 0.01). CONCLUSION: The aberrant methylation in promoter region is an important mechanism of T-cadherin gene inactivation in human esophageal carcinoma cells. 5-Aza-CdR can increase the expression of T-cadherin by a reversal of hypermethylation and effectively inhibit the proliferation and invasion of tumor cells.	esophagus
Epidemiologic risk factors for esophageal cancer development.	In retrospective studies of esophageal cancer (EC), cigarettes and hookah smoking, nass use (a chewing tobacco product), opium consumption, hot tea drinking, poor oral health, low intake of fresh fruit and vegetables, and low socioeconomic status have been associated with a higher risk of esophageal squamous cell carcinoma. Barrett's esophagus is clearly recognized as a risk factor for EC, and dysplasia remains the only factor useful for identifying patients at increased risk, for the development of esophageal adenocarcinoma in clinical practice. Here, we review the epidemiologic studies that have investigated the epidemiologic patterns and causes of EC.	esophagus
Trends in digestive cancer mortality, Cuba 1987-2008.	BACKGROUND: Gastrointestinal malignancies are among the most common cancers suffered by Cubans. The purpose of our study is to analyse the evolution of digestive cancer mortality in Cuba. METHODS: Mortality data for this study were obtained from the National Medical Records and Health Statistic Bureau. Trends (1987-2008) in age-standardized cancer mortality were described using joinpoint regression. RESULTS: In the data set of digestive cancer mortality, in the period 1987-2008, colorectal/anal cancer was the most frequent cause of cancer mortality in males and females. In men, a rise in mortality was observed for cancer of the oesophagus between 2001 and 2008, and pancreatic cancer showed a slight mortality rise for the period 1987-2008. In women, colorectal/anal cancer increased from 1989 to 2001. A mortality increase was observed for oesophageal cancer in the period 2005-08. The result of the joinpoint analysis for the age group of 35-64 years was consistent with those for overall mortality. CONCLUSION: The trend in mortality from digestive cancer in Cuba shows differences depending on sex, age and type of tumour. The Cuban health system has seen improvements in diagnostic systems, which has contributed even better diagnoses of digestive diseases.	esophagus
Pingyangmycin downregulates the expression of EGFR and enhances the effects of cetuximab on esophageal cancer cells and the xenograft in athymic mice.	PURPOSE: As reported, epidermal growth factor receptor (EGFR) is over expressed in a variety of cancers including esophageal squamous cell carcinoma. Therefore, it becomes one of the potential targets for treating esophageal cancer. Pingyangmycin (PYM), a single A5 component of bleomycin, is currently used for the treatment of different types of cancers of epidermal origin, especially for head and neck cancers. In this report, the effect of PYM on EGFR expression in human esophageal cancer cells and the therapeutic efficacy of the combination of PYM and cetuximab on esophageal cancer xenograft were investigated. METHODS: The effects of PYM, cetuximab and the combination on EGFR signaling, proliferation, cell cycle, apoptosis were evaluated by using MTT, Western blotting, RT-PCR assays and flow cytometry assays, respectively, in vitro and the therapeutic efficacy by a xenograft model in athymic mice. RESULTS: Cell volume and nucleus were enlarged after PYM treatment. PYM showed potent cytotoxicity in both cell lines of Kyse-150 and Eca-109 in time and dosage-depended manner in MTT assay. PYM treatment induced G(2)/M phase arrest and apoptosis. Notably, the expression of EGFR was down-regulated by PYM in EGFR highly expression esophageal cancer cells. PYM plus cetuximab resulted in a potentiation of antiproliferative activity. PYM combined with cetuximab displayed a much higher therapeutic effect than that of the single agent on esophageal cancer xenograft in athymic mice. CONCLUSIONS: PYM could down-regulate the expression of EGFR in esophageal cancer cells and potentiate the effects of cetuximab on esophageal cancer xenograft in nude mice. The combination of PYM and cetuximab, the EGFR-targeted combination of a chemotherapeutic agent and an antibody-based drug, might be useful in cancer therapy.	esophagus
Angiotensin-I converting enzyme inhibitors suppress angiogenesis and growth of esophageal carcinoma xenografts.	It has recently been suggested that angiotensin-I converting enzyme (ACE) inhibitors decrease the risk of cancer. However, studies to date have not investigated esophageal carcinoma. Therefore, we investigated the inhibitory effect of ACE inhibitors on growth of esophageal carcinoma xenografts. We used the EC9706 cell line, which expresses the highest vascular endothelial growth factor (VEGF) mRNA level, to establish xenografts in 21 BALB/c nude mice. The mice were then randomly allocated to receive normal saline, perindopril (4 mg/kg), or benazepril (6 mg/kg). Five weeks later, the nude mice were sacrificed and all tumors were dissected and weighed. The number of microvessels was counted by immunostaining endothelial cells for CD31 and the microvessel density was assessed. The EC9706 cell line showed the highest expression of VEGF mRNA of four esophageal squamous cell carcinoma lines. After treatment, the average tumor inhibitory rate in the benazepril group was 45.4%, which was significantly higher than that of the control group (P < 0.05). Similar findings were observed when we used tumor weight as an index for tumor growth inhibition (P < 0.05). By contrast, there was no significant difference between the perindopril group and the control group (P > 0.05). The benazepril group appeared to show less vascularization than the control group (P < 0.05), but we did not find a significant difference between the perindopril group and the control group (P > 0.05). The EC9706 cell line showed the highest expression of VEGF mRNA level of the four esophageal squamous cell carcinoma cell lines examined. Benazepril inhibited the growth of esophageal carcinoma in vivo. The potential mechanism of benazepril seems to involve suppression of new vessel formation. Therefore, benazepril could be used as an effective agent for the treatment of esophageal carcinoma.	esophagus
Comparison between radical esophagectomy and definitive chemoradiotherapy in patients with clinical T1bN0M0 esophageal cancer.	BACKGROUND: Esophagectomy remains the mainstay treatment for clinical T1bN0M0 esophageal cancer because pathologic lymph node metastases in these patients are not negligible. Recently, chemoradiotherapy (CRT), which can preserve the esophagus, has been reported to be a promising therapeutic alternative to esophagectomy. However, to our knowledge, no comparative studies of esophagectomy and CRT have been reported in clinical T1bN0M0 esophageal cancer. METHODS: A total of 173 patients with clinical T1bN0M0 squamous cell carcinoma of the thoracic esophagus were enrolled in this study, 102 of whom were treated with radical esophagectomy (S group) and 71 with definitive CRT (CRT group). Treatment results of both groups were retrospectively compared. RESULTS: No statistically significant difference was found in overall survival, but the S group displayed significantly better progression-free survival than the CRT group. Disease recurrence was observed in 12 S group patients and 20 CRT group patients. The incidence of distant recurrence was similar, while local recurrence and lymph node recurrence were significantly more frequent in the CRT group. In the S group, 20 patients had pathologic lymph node metastasis. The progression-free survival of patients with pathologic lymph node metastasis did not differ from those without nodal metastasis. In the CRT group, local recurrence could be controlled by salvage esophagectomy, but treatment results of lymph node recurrence were poor; only 4 of 12 patients with lymph node recurrences were cured. CONCLUSIONS: Selection of patients at high risk of pathologic lymph node metastasis is essential when formulating treatment decisions for clinical T1bN0M0 esophageal cancers.	esophagus
"""Drop in"" gastroscopy outpatient clinic--experience after 9 months."	"BACKGROUND: Logistics handling referrals for gastroscopy may be more time consuming than the examination itself. For the patient, ""drop in"" gastroscopy may reduce uncertainty, inadequate therapy and time off work. METHODS: After an 8-9 month run-in period we asked patients, hospital staff and GPs to fill in a questionnaire to evaluate their experience with ""drop in"" gastroscopy and gastroscopy by appointment, respectively. The diagnostic gain was evaluated. RESULTS: 112 patients had ""drop in"" gastroscopy and 101 gastroscopy by appointment. The number of ""drop in"" patients varied between 3 and 12 per day (mean 6.5). Mean time from first GP consultation to gastroscopy was 3.6 weeks in the ""drop in"" group and 14 weeks in the appointment group. The half-yearly number of outpatient gastroscopies increased from 696 before introducing ""drop in"" to 1022 after (47% increase) and the proportion of examinations with pathological findings increased from 42% to 58%. Patients and GPs expressed great satisfaction with ""drop in"". Hospital staff also acclaimed although it caused more unpredictable working days with no additional staff. CONCLUSIONS: ""Drop in"" gastroscopy was introduced without increase in staff. The observed increase in gastroscopies was paralleled by a similar increase in pathological findings without any apparent disadvantages for other groups of patients. This should legitimise ""drop in"" outpatient gastroscopies, but it requires meticulous observation of possible unwanted effects when implemented."	esophagus