crossing96/oncoscreening huggingface dataset:
Expression of chemokine receptor CXCR4 in esophageal squamous cell and adenocarcinoma.	BACKGROUND: Prognosis of esophageal cancer is poor despite curative surgery. The chemokine receptor CXCR4 has been proposed to distinctly contribute to tumor growth, dissemination and local immune escape in a limited number of malignancies. The aim of our study was to evaluate the role of CXCR4 in tumor spread of esophageal cancer with a differentiated view of the two predominant histologic types--squamous cell and adenocarcinoma. METHODS: Esophageal cancer tissue samples were obtained from 102 consecutive patients undergoing esophageal resection for cancer with curative intent. The LSAB+ System was used to detect the protein CXCR4. Tumor samples were classified into two groups based on the homogeneous staining intensity. A cut-off between CXCR4w (= weak expression) and CXCR4s (= strong expression) was set at 1.5 (grouped 0-1.5 versus 2.0-3). Long-term survival rates were calculated using life tables and the Kaplan-Meier method. Using the Cox's proportional hazards analysis, a model of survival prediction was established. RESULTS: The overall expression rate for CXCR4 in esophageal squamous cell carcinoma was 94.1%. Subdividing these samples, CXCR4w was found in 54.9% and CXCR4s in 45.1%. In adenocarcinoma, an overall expression rate of 89.1% was detected with a weak intensitiy in 71.7% compared to strong staining in 29.3% (p = 0.066 squamous cell versus adenocarcinoma). The Cox's proportional hazards analysis identified the pM-category with a hazard ratio (HR) of 1.860 (95% CI: 1.014-3.414) (p = 0.045), the histologic tumor type (HR: 0.334; 95% CI: 0.180-0.618) (p = 0.0001) and the operative approach (transthoracic > transhiatal esophageal resection) (HR: 0.546; 95% CI: 0.324-0.920) (p = 0.023) as independent factors with a possible influence on the long-term prognosis in patients with esophageal carcinoma, whereas CXCR4 expression was statistically not significant (>0.05). CONCLUSION: Expression of the chemokine receptor CXCR4 in esophageal cancer is of major relevance in both histologic entities--squamous cell and adenocarcinoma. Though with lack of statistical significance, strong CXCR4 expression revealed a poorer long-term prognosis following curative esophagectomy in both histologic subtypes. Thus, the exact biological functions of CXCR4 in terms of tumor dissemination of esophageal cancer is yet undetermined. Inhibition of esophageal cancer progression by CXCR4 antagonists might be a promising therapeutic option in the future.	esophagus
Enhancement of Apo2L/TRAIL-mediated cytotoxicity in esophageal cancer cells by cisplatin.	Although expressing adequate levels of functional tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptors DR4/DR5, significant proportion of cancer cells exhibit resistance to the cytotoxic effect of this ligand. Exposure of Apo2L/TRAIL-refractory cancer cells to cytotoxic chemotherapeutic agents enhances their sensitivity to Apo2L/TRAIL cytotoxicity. This study aims to elucidate the molecular mechanism responsible for the cisplatin-mediated enhancement of Apo2L/TRAIL sensitivity in cultured esophageal cancer cells. Exposure of cancer cells to sublethal concentrations of cisplatin resulted in profound potentiation of their susceptibility to Apo2L/TRAIL cytotoxicity as indicated by 2- to >20-fold reduction in Apo2L/TRAIL IC50 values. Significant activation of caspase-8, caspase-9, and caspase-3 was observed only in cells treated with cisplatin/Apo2L/TRAIL combination and not in those exposed to either agent alone. More importantly, activation of these key caspases was significantly abrogated by overexpression of Bcl2 or by the selective caspase-9 inhibitor. This observation strongly suggested that caspase-8 activation in cells treated with the cisplatin/Apo2L/TRAIL combination was secondary to the mitochondria-mediated amplification feedback loop and activation of the executioner caspase-3 was dependent on the recruitment of the intrinsic pathway characteristic of the type II cell. Profound combination-mediated cytotoxicity and induction of apoptosis was completely suppressed either by Bcl2 overexpression or by inhibition of caspase-9 activity, which conclusively pointed to the essential role of the mitochondria-dependent death signaling cascade in this process. Cisplatin sensitizes esophageal cancer cells to Apo2L/TRAIL cytotoxicity by potentiation of the mitochondria-dependent death signaling pathway that leads to amplification of caspase activation, particularly caspase-8, by the feedback loop to efficiently induce apoptosis.	esophagus
Malignant melanoma and adenocarcinoma of a Barrett oesophagus.	An adenocarcinoma with a malignant melanoma in a Barrett oesophagus is extremely rare. We did not find any other cases in the English literature. The diagnosis of a malignant melanoma can be difficult but can be made by tissue examination with a special immunoreaction with several markers to see it expresses S-100, but lacks activity for KER and EMA. S-100 is relatively non-specific as a single immunodeterminant in the diagnostic separation of melanoma and anaplastic carcinoma, but very sensitive. Immunohistochemically, these tumours react to S-100 protein, neuron-specific enolase and HMB-45 antibody (less sensitive than S-100), but not to cytokeratin or CEA. In our case it was obvious that there were two different tumours because the MM was negative for cytokeratin, but the adenocarcinoma was positive for cytokeratin.	esophagus
[Relationship between quinone oxidoreductase1 gene ns-cSNP and genetic susceptibility of esophageal cancer].	OBJECTIVE: To explore the relationship between quinone oxidoreductase1 (NQO1) gene nonsynonymous cSNP and the genetic susceptibility of esophageal cancer. METHODS: Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and Allele-Specific PCR (AS-PCR) were employed to assess the polymorphism of NQO1 genes both in 106 patients with esophageal cancer and control subjects matched by age, gender and origin. RESULTS: It was shown that no C/C genotype was found at 406 of NQO1. The allelic frequency of NQO1 609T was significantly higher in patients with esophageal cancer than in the control subjects (P < 0.005) and the individuals with 609T allelic genotype of NQO1 gene were at greater risk to develop esophageal cancer (OR = 4.76, 95% CI = 1.064 - 3.397). But Individuals with mutant allele of NQO1 465 genotype did not show the rising risk of esophageal cancer. CONCLUSIONS: The NQO1 C609T polymorphisms should likely be associated with the genetic susceptibility of esophageal cancer.	esophagus
Phase II study of cetuximab in combination with FOLFIRI in patients with untreated advanced gastric or gastroesophageal junction adenocarcinoma (FOLCETUX study).	BACKGROUND: The purpose of this phase II study was to evaluate the efficacy and safety of cetuximab combined with FOLFIRI as a first-line treatment of advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma. PATIENTS AND METHODS: Untreated patients with confirmed advanced gastric or gastroesophageal adenocarcinoma received cetuximab at an initial dose of 400 mg/m(2) intravenously (i.v.) followed by weekly doses of 250 mg/m(2), CPT 11 180 mg/m(2) i.v. on day 1, LFA 100 mg/m(2) i.v. followed by 5-FU 400 mg/m(2) i.v. bolus, and 600 mg/m(2) i.v. 22-h continuous infusion on days 1 and 2 (FOLFIRI) every 2 weeks, for a maximum of 24 weeks, then cetuximab alone was allowed in patients with a complete response, partial response, or stable disease. Antitumor activity was assessed by computed tomography (CT) and positron emission tomography (PET) at baseline and after 6 weeks, and further by CT alone or CT and PET every 6 weeks. RESULTS: Thirty-eight patients were enrolled (median age 63.5 years, range 39-83; median Karnofsky performance status 90, range 70-100; stomach 89.5% and GEJ 10.5%; locally advanced disease 13.2% and metastatic disease 86.8%). All 38 patients were assessed for safety and survival, and 34 patients were assessed for overall response rates (ORR). The ORR was 44.1% [95% confidence interval (CI) 27.5% to 60.9%]. The median time-to-progression was 8 months (95% CI 7-9). At the median follow-up time of 11 months, 55.3% of patients were alive, with a median expected survival time of 16 months (95% CI 9-23). Grade 3-4 toxicity included neutropenia (42.1%), acne-like rash (21.1%), diarrhea (7.9%), asthenia (5.3%), stomatitis (5.3%), and hypertransaminasemia (5.3%). There was one (2.6%) treatment-related death. CONCLUSIONS: The combination of cetuximab and FOLFIRI is active in gastric and GEJ adenocarcinoma. The higher toxicity appears to be limited to neutropenia.	esophagus
Frequency of Barrett's neoplasia after initial negative endoscopy with biopsy: a long-term histopathological follow-up study.	BACKGROUND: Barrett's adenocarcinoma is being diagnosed increasingly. We examine possible differences between long segment and short-segment Barrett esophagus (LSBE and SSBE) in long-term follow-up on the basis of our histopathology registry. METHODS AND PATIENTS: All Barrett's esophagus patients diagnosed histologically between 1990 and 1995 (n = 1071) were selected. Long-term follow-up data from endoscopy with biopsy were sought on all patients without neoplasia on initial endoscopic biopsy (n = 1003). A total of 255 individuals (25.4 %) were regarded as drop-outs (201 lost and 54 without further endoscopy). Of the remaining 748 patients with follow up for more than 5 years, 315 had documented LSBE, 246 had SSBE, and 187 had no length of Barrett esophagus recorded (NLBE). RESULTS: In the study cases (male : female ratio 2.1 : 1, mean age +/- SD 60.9 +/- 14.2 years), the biopsy procedure was fully compliant with guidelines in only 32.5 %. Only 5 cases (0.6 %) had visible lesions reported on endoscopy, but all were negative for neoplasia. Over a mean follow-up of 78.2 +/- 35.6 months (range 0-240), 7 new cases of low grade intraepithelial neoplasia (LGIN) and 15 cancer cases developed, accounting for a yearly incidence of 0.2 % (LGIN) or 0.4 % (cancer) after an initial negative endoscopy. When the cases with initial diagnosis of neoplasia were included, this yearly incidence rose to 0.5 % (LGIN), 0.3 % (high grade intraepithelial neoplasia [HGIN]) or 1.7 % (cancer). Differences between SSBE and LSBE were only encountered for cancer incidence. CONCLUSION: The yearly incidence of Barrett esophagus cancer varies between 0.4 % and 1.7 %. Despite the limitations of this retrospective and pathology-based study, the observed risk of developing cancer in Barrett esophagus without neoplasia is comparable to that found in other studies, mainly from the US and the UK, and varies between 0.7 % and 1.0 % of yearly incidence.	esophagus
Management of high-grade dysplasia in patients with Barrett's esophagus.	In the past, the standard management for patients with high-grade dysplasia in Barrett's esophagus was esophagectomy, in part on the basis of the assumption that the patient was likely to harbor an undetected carcinoma. With better awareness of the safety of surveillance protocols, improved prospective surveillance, and experience with cohorts of patients in whom incident early lesions unassociated with invasive carcinomas are detected, endoscopic techniques for treatment of Barrett-associated neoplasia have become excellent alternatives to esophagectomy for appropriately selected patients. Emerging endoscopic techniques offer an opportunity for better evaluation of patients with Barrett's-associated neoplasia.	esophagus
Current treatment approach to locally advanced esophageal cancer: is resection mandatory?	Ongoing controversy surrounds the question of whether locally advanced cancer of the esophagus should be resected or treated with nonsurgical methods. Survival after resection, particularly of patients with squamous cell cancer, remains poor. Results of recent studies suggest that in cases of squamous cell cancer there is no clear survival advantage favoring surgery, but local tumor control is significantly improved after resection. Besides this clinically relevant difference, important issues concerning the design and conduct of the most recent studies have not been investigated carefully and deserve critical discussion. Of particular note is the fact that surgery has not yet been compared with a nonsurgical approach in treating adenocarcinoma of the esophagus. Consequently, surgery remains the standard approach, at least for this cancer subtype. Response to induction chemotherapy and radiation will determine future treatment algorithms, and promising tools for predicting response are currently being investigated.	esophagus
Loss of MAL expression in precancerous lesions of the esophagus.	BACKGROUND: We have identified a novel function of MAL (T-cell differentiation-related gene) as a candidate suppressor gene in esophageal cancer. As the role of MAL expression in esophageal carcinogenesis is as yet undetermined, MAL expression in a rat multi-step carcinogenic model and in precancerous lesions of the human esophagus was investigated. Microarray analysis between MAL-transfectant and control cells was also carried out to clarify how MAL confers its anti-tumor effects. MATERIALS AND METHODS: (1) In the rat model, MAL expression levels in laser microdissected normal esophageal epithelium, dysplastic tissues and carcinoma tissues were examined by reverse transcription (RT)-PCR. (2) Immunostaining with MAL antibody was performed in 10 dysplastic lesions adjacent to cancer in six cases of esophageal cancer. (3) We established a MAL transfectant using a Tet-off vector in esophageal cancer cells and performed microarray analysis under MAL-positive and MAL-negative conditions. RESULTS: (1) In the rat model, MAL mRNA expression was observed only in the normal samples. (2) MAL expression was observed distinctively in differentiated or keratinized normal tissues and was not observed in either dysplastic lesions or carcinoma tissue. (3) Up-regulated genes in MAL-positive cells included keratin 18 (transfectant/control = 2.94) and keratin 10 (t/c = 2.82). CONCLUSION: MAL expression was lost in dysplastic lesions of the rat carcinoma model as well as the human esophagus. The up-regulated keratins revealed by microarray analysis and the strong staining of the differentiated normal tissues in immunohistochemical study support the role of MAL as a regulator of differentiation in esophageal epithelium.	esophagus
Nodal staging in adenocarcinoma of the gastro-esophageal junction. Proposal of a specific staging system.	PURPOSE: This study was aimed at developing a proper nodal staging system for GEJ adenocarcinoma. METHODS: The study analyzed 113 patients with GEJ adenocarcinoma consecutively resected at the Department of General Surgery and Surgical Oncology of the University of Siena and at the Department of General Surgery of the University of Verona. Both the number (TNM) and site (JGCA) of lymph node metastasis was evaluated in considering nodal staging. RESULTS: The TNM and JGCA staging systems coincided only in 56.3% of cases. Nodal involvement resulted to be the most important prognostic factor considering both the staging systems (P < 0.001). An extremely poor prognosis and a prominent risk of death were observed for patients with more than six metastatic nodes (TNM pN2-3) as well as for patients with involvement of second and third tier nodes (JGCA pN2-3) (P < 0.001). The combined prognostic significance of the two classifications showed a similar risk of death for patients with less than seven metastatic nodes (TNM pN1) located beyond the first tier (JGCA pN2-3) and for patients with more than six involved nodes (TNM pN2-3) independently from the interested level (JGCA pN1-3). Accordingly, these classes were pooled together and four classes considered: pN0, TNM-JGCA pN1, TNM pN2-3 or JGCA pN2-3, M1a (P < 0.001). CONCLUSIONS: The combination of the TNM and JGCA staging systems herein proposed is extremely practical from a clinical point of view and leads to the stratification of pN+ patients in two classes only with very different risk of death.	esophagus
[Place of neoadjuvant treatments in oesophageal cancers care].	Esophageal cancer has a poor prognosis. Recent epidemiological data has shown a modification of histologic types, as adenocarcinoma represents more than 50% of all patients newly diagnosed. Despite progress of surgery, overall survival at 5 years is still about 20% for resectable tumors, supporting the need for additional therapies. Objectives for neoadjuvant treatments are to increase the rate of resectability R0, to decrease the rate of local failure, to treat precociously the micrometastatic disease especially since adjuvant therapies were inefficient or inapplicable. This work is a review of main data from the literature about preoperative treatments : radiotherapy, chemotherapy and chemoradiotherapy for both adenocarcinoma and squamous cell cancers. New therapeutic strategies are arising in order to optimize these results including new drugs as irinotecan, taxans and targeted therapies. Moreover it is necessary to question the place of surgery in locally advanced but resectable tumors.	esophagus
Serum anti-myomegalin antibodies in patients with esophageal squamous cell carcinoma.	In order to identify new serum markers of esophageal squamous cell carcinoma (SCC), we performed serological identification of antigens by recombinant cDNA expression cloning (SEREX). E. coli was transformed with a lambdaZAPII phage cDNA library prepared from mRNA of an esophageal cancer cell line (T.Tn), and IPTG-induced cDNA products were screened for interaction with antibodies in allogeneic sera of patients with esophageal SCC. We identified myomegalin (MMGL, phosphodiesterase 4D interacting protein/PDE4DIP) as a new SEREX antigen for esophageal SCC. Western blot analysis revealed that serum anti-myomegalin antibodies (s-MMGL-Abs) were present in 43 (47%) of 91 patients, but in only one (2.2%) of 45 healthy controls. Of the 21 patients with stage I disease, 8 (38%) were sero-positive. The positive rate of s-MMGL-Abs was greater than those of other conventional tumor markers. Reverse transcription-PCR analysis suggested that alternative splicing from myomegalin variant 1 to variant 5 may explain, in part, the development of s-MMGL-Abs. Although the presence of s-MMGL-Abs was not related to any clinicopathological features of the patients, multivariate analysis indicated that the presence of s-MMGL-Abs was significantly associated with a favorable prognosis. Consequently, s-MMGL-Abs may be a useful tumor marker to diagnose and establish a prognosis in patients with esophageal SCC.	esophagus
Neutrophil elastase induces cell proliferation and migration by the release of TGF-alpha, PDGF and VEGF in esophageal cell lines.	Rapid regrowth or recurrent growth of occult cancer cells are often observed after esophagectomy or postoperative complications. In order to clarify the mechanism of such oncological circumstances, we focused on neutrophil elastase (NE), which degrades a broad spectrum of extracellular matrix and cell surface proteins. In the present study, we demonstrated that NE stimulated the growth of all of the five esophageal cell lines (TE-1, -7, -8, -12 and -13) by MTT assay and promoted cell invasion by cell migration assay. Pro-transforming growth factor-alpha (pro-TGF-alpha) from the cell membrane was released to the culture medium as a mature form after treatment with 5 microg/ml NE, and it reached the maximum level of 153% compared to the control values at 15 min of treatment in TE-13 cells. The phosphorylation of epidermal growth factor receptor (EGFR) rapidly occurs after treatment with NE and triggered the extracellular signal-regulated kinases 1 and 2 (ERK) signaling pathway. Moreover, NE induced release of platelet-derived growth factor-AA (PDGF-AA), PDGF-BB and vascular endothelial growth factor (VEGF) to 141.9, 227.7, and 171.6% of the control values, respectively. A specific NE inhibitor, sivelestat, significantly inhibited the NE-induced cell proliferation, cell invasion and subsequently inhibited the signal transduction pathway. Furthermore, sivelestat significantly inhibited NE-induced release of TGF-alpha, PDGF-AA, PDGF-BB and VEGF in the medium in TE-13 esophageal carcinoma cells. These results strongly indicate that NE released from activated neutrophils stimulates the growth and progression of esophageal cancer cells by releasing the growth factors on the cell surface and that sivelestat, a specific NE inhibitor, blocks these processes. Furthermore, we postulate that postoperative administration of sivelestat might be useful as a new molecular-targeting cancer therapy as well as for the treatment of postoperative respiratory complications.	esophagus
Frequent homogeneous HER-2 amplification in primary and metastatic adenocarcinoma of the esophagus.	HER-2 is the target for antibody based treatment of breast cancer (Herceptin). In order to evaluate the potential role of such a treatment in esophageal cancers, HER-2 amplification and overexpression was investigated in primary and metastatic cancers of the esophagus. A tissue microarray was constructed from 255 primary esophageal cancers (110 adenocarcinomas and 145 squamous cell carcinomas), 89 nodal and 33 distant metastases. Slides were analyzed by immunohistochemistry (HercepTest; DAKO) and fluorescence in situ hybridization (FISH; PathVysion; Vysis-Abbott) for HER-2 amplification and overexpression. Amplification was seen in 16/110 (15%) adenocarcinomas and in 7/145 (5%) squamous cell carcinomas. There was a strong association between HER-2 amplification and overexpression, especially in adenocarcinomas (P<0.0001, log rank). There was a 100% concordance of the HER-2 results in primary tumor and corresponding metastases in 84 analyzed pairs. Amplification was typically high-level with more than 10-15 HER-2 copies per tumor cell. Amplification was unrelated to survival, grading, pT, pN, pM or UICC stage. We conclude that esophageal adenocarcinomas belong to those cancer types with relevant frequency high-level HER-2 gene amplification clinical trials or individual case studies investigating the response of metastatic HER-2-positive esophageal cancers to Herceptin((R)) should be undertaken. The strong concordance of the HER-2 status in primary and metastatic cancers argues for a possible response of metastases from patients with HER-2-positive primary tumors to Herceptin.	esophagus