crossing96/oncoscreening huggingface dataset:
Molecular mechanisms of acid exposure in Barrett's esophagus.	Esophageal adenocarcinoma is one of the most deadly gastrointestinal tumors. Gastroesophageal reflux has been established as a major risk factor for esophageal adenocarcinoma and Barrett's esophagus, the condition in which the normal squamous cells of the esophagus are replaced by metaplastic, specialized intestinal cells that are predisposed to malignancy. Data from ex vivo and in vitro model systems suggests that acid exposure has pro-proliferative and anti-apoptotic effects which may facilitate neoplastic progression of Barrett's esophagus. Such data have led some authorities to propose complete elimination of gastric acid production as a chemopreventive strategy for Barrett's patients. However, it is not clear whether the effects of acid exposure on proliferation and apoptosis are a direct result of the acid exposure itself, or whether they result indirectly from the effects of acid on inducing esophageal inflammation. Such distinction may help in optimizing the level of gastric acid suppression for the prevention of cancer in Barrett's esophagus. This report describes the molecular mechanisms whereby acid exposure directly and indirectly, through inducing inflammation, may contribute to the neoplastic progression of Barrett's esophagus and the potential role for acid suppression as a chemopreventive strategy in patients with Barrett's esophagus.	esophagus
An HSV-2-based oncolytic virus deleted in the PK domain of the ICP10 gene is a potent inducer of apoptotic death in tumor cells.	The N-terminus of the ICP10 gene of type 2 herpes simplex virus (HSV-2) encodes a serine/threonine protein kinase (PK) domain that facilitates HSV-2 replication by activating the Ras/MEK/MAPK mitogenic pathway and suppressing apoptosis. We recently demonstrated that deletion of this oncogenic PK domain converts it to a potent oncolytic agent. This mutant, which we have designated FusOn-H2, preferentially replicates in and thus lyses tumor cells in which the Ras signaling pathway is constitutively activated. Here we show that FusOn-H2 exerts strong ability in inducing apoptosis in different lines of human tumor cells and in esophageal tumors growing in mice. The apoptotic effect produced by FusOn-H2 was not restricted to infected cells but extended to uninfected bystander cells, thereby increasing the lethality of the virus. These results add a novel killing mechanism to those previously assigned to FusOn-H2, rendering it an attractive candidate for clinical trials.	esophagus
Reactive oxygen species and mitochondrial membrane potential are modulated during CDDP-induced apoptosis in EC-109 cells.	cis-Diamminedichloroplatinum (CDDP), commonly know as cisplatin, is a well known DNA-damaging agent, which is highly active in suppressing the proliferation of tumor cells. However, it is not clear that CDDP can induce growth inhibition of esophagus cancer cells. Using the cell line EC-109 from the esophagus, we found that CDDP would induce apoptotic responses. The addition of CDDP to cells led to the inhibition of growth in a time- and dose-dependent manner. CDDP generated reactive oxygen species (ROSs) in cells, which brought about a reduction in the intracellular mitochondrial transmembrane potential (Deltapsim), leading to apoptosis. Our findings demonstrate that ROSs, and the resulting oxidative stress, play a pivotal role in apoptosis. Preincubation of EC-109 cells with the hydrogen-peroxide-scavenging enzyme catalase partially inhibited the following: (i) the production of ROS; (ii) the disruption of the Deltapsim; and (iii) apoptosis. These results indicate that the enhancement of the generation of ROS and the disruption of Deltapsim are events involved in the apoptotic pathway of EC-109 induced by CDDP.	esophagus
Endoscopic ultrasound compared with laparoscopy for staging esophageal cancer.	BACKGROUND: Endoscopic ultrasonography (EUS) is an accurate modality for locoregional staging of esophageal cancer. Given an increasing prevalence of distal esophageal adenocarcinoma, some centers employ laparoscopic staging (LS) in addition to noninvasive staging methods. We sought to compare EUS and LS for nodal staging in patients with esophageal cancer. METHODS: All newly diagnosed, EUS-staged esophageal cancer cases during an 18-month period were reviewed. Patients who underwent both EUS and LS comprised the study cohort; EUS records, operative notes, and pathology reports were reviewed. Inability to pass the radial echoendoscope through the malignant stricture despite dilation was considered an incomplete EUS examination. RESULTS: Forty-seven patients were identified who underwent both modalities for staging; of these, 70% had complete EUS evaluation. For nodal staging, EUS-fine-needle aspiration was 90% accurate as compared with LS. Overall, staging accuracy of EUS compared with LS was 72%. Accuracy was 76% for patients with complete EUS staging compared with 64% for patients with incomplete EUS examinations. Staging differences were mostly reflected in distant metastases detected at LS (17%). CONCLUSIONS: Endoscopic ultrasonography is nearly as accurate as LS in nodal staging for esophageal cancer. The value of LS is accurate abdominal nodal staging and detection of occult distant metastases. Laparoscopic staging should, therefore, be incorporated into staging algorithms for neoadjuvant protocols. In the absence of preoperative therapy, LS should be performed at the time of planned esophagectomy. In those without occult metastases, curative resection may be attempted.	esophagus
Setup variations in radiotherapy of esophageal cancer: evaluation by daily megavoltage computed tomographic localization.	PURPOSE: To use pretreatment megavoltage computed tomography (MVCT) scans to evaluate setup variations in anterior-posterior (AP), lateral, and superior-inferior (SI) directions and rotational variations, including pitch, roll, and yaw, for esophageal cancer patients treated with helical tomotherapy. METHODS AND MATERIALS: Ten patients with locally advanced esophageal cancer treated by combined chemoradiation using helical tomotherapy were selected. After patients were positioned using their skin tattoos/marks, MVCT scans were performed before every treatment and automatically registered to planning kilovoltage CT scans according to bony landmarks. Image registration data were used to adjust patient setups before treatment. A total of 250 MVCT scans were analyzed. Correlations between setup variations and body habitus, including height, weight, relative weight change, body surface area, and patient age, were evaluated. RESULTS: The standard deviations for systematic setup corrections in AP, lateral, and SI directions and pitch, roll, and yaw rotations were 1.5, 3.7, and 4.8 mm and 0.5 degrees, 1.2 degrees, and 0.8 degrees, respectively. The appropriate averages of random setup variations in AP, lateral, and SI directions and pitch, roll, and yaw rotations were 2.9, 5.2, and 4.4 mm, and 1.0 degrees, 1.2 degrees, and 1.1 degrees, respectively. Setup variations were stable throughout the entire course of radiotherapy in all three translational and three rotational displacements, with little change in magnitude. No significant correlations were found between setup variations and body habitus variables. CONCLUSIONS: Daily MVCT scans before each treatment can effectively detect setup errors and thereby reduce planning target volume (PTV) margins. This will reduce radiation dose to critical organs and may translate into lower treatment-related toxicities.	esophagus
Optimal markers for real-time quantitative reverse transcription PCR detection of circulating tumor cells from melanoma, breast, colon, esophageal, head and neck, and lung cancers.	BACKGROUND: The detection of circulating tumor cells (CTCs) may prove useful for screening, prognostication, and monitoring of response to therapy. However, given the large background of circulating cells, it is probably necessary to detect 1 cancer cell in >10(6) leukocytes. Although reverse transcription (RT)-PCR is potentially sensitive and specific enough to achieve this goal, success will require the use of appropriate mRNA markers. The goal of this study was to identify optimal marker combinations for detection of CTCs. METHODS: An extensive literature and internet database survey was conducted to identify potential markers. We then used real-time quantitative RT-PCR to test for expression of selected potential markers in tissue samples from primary tumors of breast, colon, esophagus, head and neck, lung, and melanoma and normal blood samples. Markers with high expression in tumors and a median 1000-fold lower expression in normal blood were considered potentially useful for CTC detection and were tested further in an expanded sample set. RESULTS: A total of 52 potential markers were screened, and 3-8 potentially useful markers were identified for each tumor type. The mRNAs for all but 2 markers were found in normal blood. Marker combinations were identified for each tumor type that had a minimum 1000-fold higher expression in tumors than in normal blood. CONCLUSIONS: Several mRNA markers may be useful for RT-PCR-based detection of CTCs from each of 6 cancer types. Quantification of these mRNAs is essential to distinguish normal expression in blood from that due to the presence of CTCs. Few markers provide adequate sensitivity individually, but combinations of markers may produce good sensitivity for detection of the presence of these 6 neoplasms.	esophagus
Modification of the Rb-binding domain of replication-competent adenoviral vector enhances cytotoxicity against human esophageal cancers via NF-kappaB activity.	A replication-competent adenoviral vector deficient for expression of the early E1B55K protein has been applied in clinical studies. The vector, however, was not fully effective for the treatment of human cancer. In this study, the E1A gene (which encodes an Rb-binding domain protein) of the adenoviral vector AxE1AdB was further engineered with a point mutation designed to abolish binding to Rb protein (pRb) and arrest the cell cycle (AxdAdB-3). The difference in the cytotoxicity of these vectors in two cancer cell lines was observed in association with differences in replication, infection efficiency, and expression levels of adenovirus receptors. Relative to the parent vector (AxE1AdB), which worked in a manner similar to ONYX-015, AxdAdB-3 with the mutated pRb-binding motif demonstrated increased cytotoxicity against p53-mutant human esophageal cancer cell lines EC-GI-10 and T.Tn. AxdAdB-3 showed a greater oncolytic effect than AxE1AdB in vivo despite almost the same replication efficiency in vitro. Unexpectedly, cell cycle arrest in AxdAdB-3-infected cells was less efficient than that in cell lines infected with AxE1AdB. However, AxdAdB-3 strongly reduced NF-kappaB activity and thereby enhanced apoptosis more than AxE1AdB did. These data demonstrate that the Rb-binding domain of E1A can regulate NF-kappaB activity and that modifications to this domain may lead to advances in gene therapies for the treatment of human cancers.	esophagus
Oesophageal cancer in The Netherlands: increasing incidence and mortality but improving survival.	AIM: Oesophageal cancer is highly lethal with a 5-year relative survival of 10-15%. An increasing incidence has been reported for several parts of the Western world. We studied time trends in incidence, mortality and survival for oesophageal cancer in the Netherlands during 1989-2003. METHODS: Data on incidence and survival were obtained from the Netherlands Cancer Registry and mortality data from Statistics Netherlands. RESULTS: The age standardised incidence increased by 3.4% (p<0.001) and 1.9% (p=0.003) per year for males and females, respectively. This increase was almost exclusively caused by oesophageal adenocarcinomas. Age standardised mortality increased 2.5% (p<0.001) per year among males and 1.7% (p=0.002) per year among females. Relative survival improved significantly from 8.1% in 1989-1993 to 12.6% in 1999-2003 (p<0.001). Adjusted for age, stage, tumour location and surgery, the excess risk of death decreased by 22%. CONCLUSION: Oesophageal carcinoma incidence is rising in the Netherlands. Mortality increased at a slightly lower pace due to improving survival.	esophagus
Risk for cancer in Barrett's esophagus: medical versus surgical therapy.	Esophageal adenocarcinoma associated with Barrett's esophagus has been increasing in incidence over the past three decades. Our understanding of the risks for the development of esophageal adenocarcinoma in Barrett's esophagus is evolving. Newer treatment options for Barrett's esophagus are being developed in all areas, including endoscopic therapy, surgery, and chemoprevention trials.	esophagus
Minimally invasive management of chylous fistula after esophagectomy.	Chyle leak is an unwelcome complication of esophagectomy that is associated with a high mortality. The diagnosis of this condition may be difficult or delayed and requires a high index of suspicion. Management varies from conservative treatment with drainage, intravenous nutrition, treatment and prevention of septic complications, to re-operation, either by thoracotomy or laparotomy to control the fistula. To reduce the mortality, early surgical intervention is advised and a minimally invasive approach has recently been reported in several cases. From June 2002 through August 2005 we have used video-assisted thoracoscopic surgery to diagnose and treat chyle fistulas from 6/129 (5%) patients who underwent esophagectomy for resectable carcinoma of the esophagus or high-grade dysplasia. The fistula was successfully controlled in 5/6 cases by direct thoracoscopic application of a suture, clips or fibrin glue. One patient required a laparotomy and ligation of the cysterna chyli after thoracoscopy failed to identify an intrathoracic source of the leak. An early minimally invasive approach can be safely and effectively applied to the diagnosis and management of post-esophagectomy chylous fistula in the majority of cases. Open surgery may be appropriate where minimally invasive approaches fail or where the availability of such skills is limited.	esophagus
Information needs following a diagnosis of oesophageal cancer; self-perceived information needs of patients and family members compared with the perceptions of healthcare professionals: a pilot study.	This pilot study was undertaken to describe patients' and family members' information needs following a diagnosis of oesophageal cancer and healthcare professionals' (HCP) perceptions concerning patients' and family members' information needs. Another aim was to describe patients' and family members' satisfaction with information provided. Data were collected by means of a self-report questionnaire. A total of 15 patients, 16 family members and 34 HCP participated. Patients and family members consider most information to be important. The high rating for information about tests/treatment and self-care means that both patients and family members consider this to be the most important areas of information. Healthcare professionals tend to underestimate both patients' and family members' needs for information. Patients and family members were only partly satisfied with the information received, with patients in general more satisfied with information given compared with family members. Patients' and family members' needs for information following a diagnosis of oesophageal cancer are substantial and have not been adequately met by HCP. A qualitative study might be helpful to complete the description of patients' and family members' needs. If a questionnaire is employed, it ought to be less extensive.	esophagus
Trends in the incidence of adenocarcinoma of the oesophagus and cardia in the Netherlands 1989-2003.	Over the 15-year period 1989-2003, the incidence of oesophagus-cardia adenocarcinoma in the Netherlands rose annually by 2.6% for males and 1.2% for females. This was the net outcome of annual increases in the incidence of adenocarcinoma of the oesophagus (ACO) of 7.2% for males and 3.5% for females and annual declines in the incidence of adenocarcinoma of the gastric cardia (AGC) of more than 1% for both genders. Nonlinear cohort patterns were found in females with ACO and for both genders in AGC; a nonlinear period pattern was observed only in males with AGC. These differing epidemiological patterns for ACO and AGC do not support a common aetiology. Proposed underlying factors for the rise in ACO incidence appear to have little effect on AGC incidence. This and the secular decline in smoking among males may have led to the decline in AGC incidence.	esophagus
Carcinoma arising from an epiphrenic diverticulum: a frequently misdiagnosed disease.	Epiphrenic diverticulum is rare, comprising of about 10% of all esophageal diverticula. Carcinoma arising within such a diverticulum is even less common. We report on two patients with squamous cell carcinoma arising from an epiphrenic diverticulum. Some features of malignant change related to the epiphrenic diverticula were misdiagnosed or missed in our cases and other reports due to lack of clinical experience. It is important to exclude the possibility of malignancy as this is vital for surgical planning. Although the prognosis for patients with malignancy arising from an epiphrenic diverticulum is generally poor, a high index of suspicion may increase the chance of cure.	esophagus
Nuclear expression of phosphorylated EGFR is associated with poor prognosis of patients with esophageal squamous cell carcinoma.	OBJECTIVES: Although it has been reported that epidermal growth factor receptor (EGFR) is able to translocate from the plasma membrane to the nucleus, the pathophysiological role of this translocation in tumorigenicity is still unclear. In the present study, to elucidate the pathophysiological significance of EGFR translocation, we investigated the expression not only of conventional EGFR but also its phosphorylated form (pEGFR), focusing on its cellular localization in esophageal cancer tissues. METHODS: Fifty-two specimens of esophageal squamous cell carcinoma (SCC) obtained by surgery were examined immunohistochemically for their EGFR and pEGFR immunostaining patterns. The relationships between clinicopathological parameters and EGFR or pEGFR immunostaining patterns were then analyzed. RESULTS: In 37 (71.2%) of the 52 esophageal SCCs, EGFR immunoreactivity was clearly localized at the plasma membrane of the cancer cells, whereas pEGFR immunoreactivity was clearly localized in the nucleus in 19 (36.5%) cases. Nuclear expression of pEGFR significantly correlated with TNM stage and lymph node metastasis, and moreover was associated with a poor outcome of esophageal SCC. CONCLUSIONS: Nuclear translocalization of pEGFR is associated with an increase in the malignant potential of esophageal SCC and may affect prognosis in patients with esophageal SCC.	esophagus
Oncogenic properties of a novel gene JK-1 located in chromosome 5p and its overexpression in human esophageal squamous cell carcinoma.	Esophageal squamous cell carcinoma (ESCC) shows high frequency and mortality in Asian regions, including China. Previous analysis of genomic DNA of ESCC using comparative genomic hybridization indicated that amplification of the chromosome 5p regions is a common event in ESCC cell lines and patient cases of Hong Kong Chinese origin, and the results suggested that the genes located in the chromosome 5p regions may play crucial roles in the molecular pathogenesis of ESCC. Our previous studies on ESCC confirmed the tumorigenic and overexpression properties of a novel gene JS-1 located in chromosome 5p15.2 upstream to delta-catenin. In the present study, another novel gene JK-1 which is located at 5p15.1 downstream to delta-catenin was characterized for its roles in the pathogenesis of ESCC. Thirteen ESCC cell lines and 30 surgical specimens of esophageal tumors were studied for the overexpression of JK-1 using multiplex RT-PCR analysis. The transforming capacity of overexpression of JK-1 was also investigated by transfecting NIH 3T3 and HEK 293 cells with the expression vector cloned with JK-1, followed by the soft agar and foci formation assays. JK-1 was overexpressed in 9/13 (69%) of the ESCC cell lines and 9/30 (30%) of the ESCC patient cases. Both NIH 3T3 and HEK 293 cells acquired the properties of anchorage-dependent and -independent growth when JK-1 was overexpressed. Most significantly, subcutaneous sarcomas were formed in all (3/3) the athymic nude mice after NIH 3T3 cells overexpressing JK-1 were injected subcutaneously. Our results thus indicated that JK-1 is commonly overexpressed in ESCC and has a prominent capacity to transform normal cells. Our overall results thus provide the first evidence that the overexpression of JK-1 and its transforming capacity in normal cells may play a critical role in the molecular pathogenesis of ESCC.	esophagus
[Chemoprevention in adenocarcinoma of the esophagus].	The incidence of the adenocarcinoma of the esophagus (ACE) has dramatically for the last decades in western countries, which has been associated with a parallel increase in the incidence and prevalence of symptoms associated with gastroesophageal reflux diseases (GERD) and Barrett's esophagus (BE). Both conditions are now considered risk factors for ACE. Different pathways, including overexpression of cyclooxygenase (COX) isoenzymes, has been proposed to explain the carcinogenic process leading from normal esophagus to esophagitis, BE and ACE. The survival rate in patients with ACE is very low because of the poor outcomes of surgery and the limited benefits obtained with concomitant chemo-radiotherapy Several strategies based on early detection and surveillance of preneoplastic lessions have failed to have a global and significant impact on the prognosis of the ACE. Recent epidemiological and experimental studies suggest that chemoprevention could be useful in the management of patients with GERD and especially in those with BE. The current therapy with protom pump inhibitors (PPI) is effective to reduce the esophageal acid exposure, to improve reflux symptoms, and to heal inflammatory injuries, but probably is not enough to avoid the dysplastic progression of the metaplastic epithelium. Regular use of COX inhibitors (aspirin and other non steroid antiinflamatory drugs) has been associated with reduction of the risk of ACE and to decrease the incidence of ACE in animal models. In humans, the association of PPI with COX inhibitors could be a cost-effectiveness strategy but direct evidence is lacking. Other potential agents that have shown some chemoprevention potential include troglitazone, free radical scavengers, tamoxifen or prostaglandin receptor blockers, but the available scientific evidence is still poor and not ready to be tested in humans.	esophagus