crossing96/oncoscreening huggingface dataset:
Gossypol, a phytochemical with BH3-mimetic property, sensitizes cultured thoracic cancer cells to Apo2 ligand/tumor necrosis factor-related apoptosis-inducing ligand.	OBJECTIVES: Chemotherapeutic agents sensitize cancer cells to Apo2 ligand/tumor necrosis factor-related apoptosis-inducing ligand (Apo2L/TRAIL) via recruitment of the mitochondria-dependent activation of caspase and induction of apoptosis. This study was designed to evaluate whether gossypol, a phytochemical compound with BH3-mimetic property that functions as an inhibitor of Bcl2/BclXL, would sensitize cultured thoracic cancer cells to this death-inducing ligand. METHODS: Cancer cell lines from the lung (H460, H322), the esophagus (TE2, TE12), and the pleura (H290, H211) or primary normal cells were treated with gossypol+Apo2L/TRAIL combinations. Cell viability and apoptosis were evaluated by (4,5-dimethylthiazo-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling (TUNEL) assays, respectively. Caspase 9 and 3 specific proteolytic activity in combination-treated cells was determined by fluorometric enzymatic assay. RESULTS: Gossypol, selectively cytotoxic to cancer cells and not primary normal cells, significantly sensitized thoracic cancer cells to Apo2L/TRAIL as indicated by 1.5- to more than 10-fold reduction of Apo2L/TRAIL 50% inhibitory concentration values in cells treated with gossypol+Apo2L/TRAIL combinations. Whereas less than 20% of cancer cells exposed to either gossypol (5 micromol/L) or Apo2L/TRAIL (20 ng/mL) were dead, more than 90% of cells treated with the drug combinations were apoptotic. Combination-induced cytotoxicity and apoptosis was completely abrogated either by overexpression of Bcl2 or by the selective caspase 9 inhibitor. This combination was not toxic to normal cells. CONCLUSION: Gossypol profoundly sensitizes thoracic cancer cells to the cytotoxic effect of Apo2L/TRAIL via activation of the mitochondria-dependent death signaling pathway. This study provides evidence for the profound anticancer activity of this drug combination and should be further evaluated as a novel targeted molecular therapeutic for thoracic cancers.	esophagus
Prognostic factors for survival after stereotactic radiosurgery vary with the number of cerebral metastases.	BACKGROUND: Little is understood about the factors that influence survival in patients who undergo gamma-knife stereotactic radiosurgery (SRS) for brain metastases. METHODS: Demographic, disease, treatment, and survival data on 334 patients with intracranial metastases who underwent initial SRS from 1998 to 2004 were abstracted from treatment records and from the Connecticut Tumor Registry. Multivariate survival analysis was used to identify factors that independently affected survival. RESULTS: The median age of the patient population was 57.3 years. The median number of lesions treated in a single session was 2 (range, 1-36 lesions treated). The most common tumor histologies were nonsmall cell lung carcinoma (36%), breast cancer (16%), and melanoma (16%). Three hundred patients (90%) had confirmed deaths; the median survival after SRS was 8.1 months. Survival was significantly better in patients who had from 1 to 3 metastases (median, 8.5 months) compared with patients who had > or =4 metastases (median, 6.3 months; hazard ratio [HR], 0.65; P = .003). In the subgroup of patients who had from 1 to 3 metastases, systemic control (HR, 0.49; P < .001), breast cancer (HR, 0.57; P = .003), and total tumor volume < 5 cc (HR, 0.65; P = .002) were associated independently with increased survival, and esophageal cancer (HR, 2.36; P = .042) was associated with decreased survival. In the subgroup of patients who had > or =4 metastases, only age <45 years was associated independently with increased survival (HR, 0.39; P = .006); and melanoma (HR, 2.32; P = .008) and the receipt chemotherapy (HR, 2.59; P = .077) were associated with decreased survival. Sex, race, metastases location, whole-brain radiation, and cranial surgery had no independent associations with altered survival. CONCLUSIONS: The data from this study suggested that different factors affected survival in patients who had from 1 to 3 metastases and patients who had > or =4 metastases. Further research into this area may clarify causes for this discrepancy and improve prognostication.	esophagus
A prospective comparison of multidisciplinary treatment of oesophageal cancer with curative intent in a UK cancer network.	AIMS: Combined modality therapy (with chemotherapy+/-radiotherapy) has become a standard treatment for locally advanced oesophageal cancer. However, there appears to be no compelling evidence for one treatment type or combination to suit all and at this time the clinical multi-disciplinary team (MDT) forms an important role in selecting optimal therapies for the individual. This prospective comparison in one cancer network, looks at the outcomes of this decision making process. METHODS: Over a five year period 1998-2003, data were prospectively collected on all 330 consecutive patients, referred to a tertiary specialised MDT for whom curative treatment was the planned intent. Patients were managed according to an agreed local protocol and allocated to receive one of 5 treatments: surgery alone (S), pre-operative chemotherapy (C+S), pre-operative chemo-radiotherapy (CRT+S), definitive chemo-radiotherapy (CRT) and radiotherapy alone (RT). RESULTS: The 2 and 5 year survival for all patients receiving potentially curative treatment were 49% and 26% respectively. With 2 and 5 year survival for S, CRT+S, C+S, CRT and RT being 53,21; 57,40; 37,27; 50,27; 23,0 months respectively. Of the surgical therapies, mortality was highest in the CRT+S group, versus C+S and S; 12.5%, 1.6%, 4.5% respectively (p=0.025). Non-surgical based therapies had more than double the incidence of local relapses compared to surgical based therapies; however the CRT group had an overall survival comparable with S alone. The commonest sites of distant relapse were liver (56%), lung (38%), bone (32%) and non-regional lymph nodes (24%). CONCLUSION: The results suggest that in patients who are deemed unfit for surgical intervention, definitive chemoradiotherapy remains a viable alternative; they also lend further support to selected case triple modality therapy. These areas should be further examined in the context of randomised controlled phase III trials.	esophagus
Pretherapy nuclear factor-kappaB status, chemoradiation resistance, and metastatic progression in esophageal carcinoma.	BACKGROUND: Transcriptional factor nuclear factor-kappaB (NF-kappaB) seems to be associated with aggressive clinical biology (chemoradiation resistance and metastatic progression) of esophageal cancer. We hypothesized that activated NF-kappaB would define clinical biology irrespective of the type of chemotherapy or sequence administered. METHODS: Pretherapy and/or posttherapy cancer specimens were examined for activated NF-kappaB and correlated with pathologic response to chemoradiation, metastatic potential, overall survival, disease-free survival, and type of chemotherapy or sequence used. FINDINGS: Eighty patients undergoing chemotherapy and concurrent radiation were studied. Activated NF-kappaB prior to any therapy was associated with the lack of complete pathologic response (pathCR, P = 0.006). Forty-five (78%) of 58 patients achieving <pathCR had activated NF-kappaB in pretherapy and/or posttherapy cancer specimens versus 2 (9%) of 22 patients with pathCR (P = 0.001). Twenty-four (51%) of 47 patients with activated NF-kappaB in cancer developed metastases versus 7 (21%) of 22 patients with negative NF-kappaB in cancer (P = 0.01). At a median follow-up of 32 months, 25 (53%) of 47 patients with activated NF-kappaB cancer had died versus 3 (9%) of 33 patients with negative NF-kappaB cancer. NF-kappaB activation was the only independent predictor of disease-free survival (P = 0.01) and overall survival (P = 0.007) in a multivariate model. The class of chemotherapy or its sequence had no effect on NF-kappaB expression or patient outcome. CONCLUSIONS: Our data are the first to show that pretreatment-activated NF-kappaB significantly correlates with clinical biology of esophageal cancer, and most importantly, with pathCR. To therapeutically exploit NF-kappaB-regulated genes and their pathways, further research is warranted.	esophagus
[Endoscopic treatment of squamous cell esophageal cancer].	OBJECTIVE: In this article, it was evaluated the role of endoscopic procedures for the management of squamous cell esophageal cancer. DATA SOURCE: Relevant publications cited at PubMed database in the last 10 years were analyzed and compared with the experience developed at the Gastrointestinal Endoscopy Division of the Department of Gastroenterology of the University of São Paulo School of Medicine. Mucosectomy and advanced tumor tunnelization were the most important developments in that area. DATA SYNTHESIS: Endoscopic mucosal resection of early epidermoid cancer of the esophagus is indicated when the lesion is confined to the epithelium (m1) or to the lamina propria (m2). The described 5-year survival rate after endoscopic mucosal resection of intramucosal epidermoid tumor of the esophagus approaches 95%. Based on the available evidence, it seems reasonable to indicate endoscopic mucosal resection as a first-choice treatment for patients with intramucosal epidermoid esophageal carcinoma. There are a variety of endoscopic palliative methods for dysphagia relief in advanced esophageal cancer. CONCLUSIONS: The choice will vary according to the anatomical features and location of the tumor, patient preferences, local and expertise availability. The technical success rate for placement of metal stents across the malignant stenosis is close to 100%. The rate of long-term palliation of dysphagia approaches 80% which makes expandable metal stents the treatment of choice for palliation of obstructive symptoms caused by advanced squamous cell cancer of the esophagus.	esophagus
Treatment results of radiotherapy for carcinoma of the cervical esophagus.	The methods and results of treatment for cancer of the cervical esophagus differ from those for cancer of the thoracic esophagus. Our objective was to retrospectively review the outcome for cervical esophageal cancer patients treated with radiotherapy. Twenty-seven patients with carcinoma of the cervical esophagus treated with definitive radiotherapy from 1988 to 2002 were enrolled in the study. Clinical stage (UICC 1997) was stage I in five, II in six, III in 12 and IV in four. Concurrent head and neck malignancy was found in six patients (22%). The mean radiation dose was 66 Gy. Concurrent chemotherapy (cisplatin and 5-fluorouracil) was performed in 23 patients. The actuarial overall survival rates at 1, 3 and 5 years were 55.6%, 37.9% and 37.9%, respectively, with a median survival of 13.9 months. In the patients with stage I, the 3-year and 5-year survival rates were 75% and 75%, respectively. With univariate analysis, only two of the possible prognostic factors were found to actually influence survival: performance status (p < 0.01) and tumor length (p < 0.01). The survival of patients with cervical esophageal cancer remains poor. It is thought that organ preservation is possible by definitive chemoradiation for early cancer.	esophagus
[An unusual case of upper GI bleeding: esophageal cancer metastasis at a percutaneous endoscopic gastrostomy site--case report and review of the literature].	"We present the case of a patient with an esophageal squamous cell carcinoma, who was treated primarily by radiotherapy. Due to dysphagia, the patient received a percutaneous endoscopic gastrostomy (PEG) without any sign of tumour at that time. Five months later the patient presented with an upper GI bleeding from a gastric ulcer, which histologically turned out to be a metastasis of the previously diagnosed squamous cell carcinoma. So-called ""implantation metastases"" at the percutaneous endoscopic gastrostomy site are rare and most of the cases have been described in patients with head and neck tumours. Moreover, the presentation as an upper GI bleed is very uncommon and needs the attention of both endoscopists as well as gastrointestinal oncologists. Clinicopathological features of this case with a brief review of the literature are presented."	esophagus
Delays in diagnosis and therapy of gastric cancer and esophageal adenocarcinoma.	BACKGROUND AND STUDY AIMS: In the past, there were long delays in the diagnosis of patients with cancer of the stomach or esophagus. The objective of this study was to describe current delays in the diagnosis and treatment of gastric and esophageal adenocarcinoma and to compare the findings with those from an historical control population treated at the same institutions 10 years earlier. PATIENTS AND METHODS: Patients with biopsy-proven gastric cancer or esophageal adenocarcinoma who were treated at two academic medical centers in Germany between April and October 2003 were consecutively screened for eligibility to take part in the study. Medical charts for each patient were reviewed. Additional data were obtained via structured interviews. Main outcome measures were the total delay, and the delays related to patients themselves, to doctors, and to the hospital. Data were compared with those from a historic control group assessed in 1993. RESULTS: The median total delay for patients with gastric cancer (n = 104) was 3.5 months (range 0.3 - 29.6), and in patients with esophageal adenocarcinoma (n = 22) the total delay was significantly shorter (median 2.2 months, range 1.2 - 11.7; P < 0.05). Comparing these findings with those from an historic cohort of patients with gastric cancer (n = 100) revealed a significant decrease in the total delay (3.5 versus 8.0 months, P < 0.001). CONCLUSIONS: The current findings indicate that delays in the diagnosis and treatment of gastric cancer have become significantly shorter within the last 10 years as our understanding of and ability to treat this form of cancer have improved.	esophagus
Host cytokine genotype is related to adverse prognosis and systemic inflammation in gastro-oesophageal cancer.	BACKGROUND: Systemic inflammation has been linked with reduced survival in cancer, however, the role of the host cytokine genotype versus tumour phenotype in the generation of this response is not clearly established. This study examined the relationship between cytokine polymorphisms (IL-1beta 511, IL-6 174, IL-10 1082, TNFalpha 308 and LTalpha +252) and serum cytokine concentrations, serum CRP concentration and survival duration in patients with gastro-oesophageal malignancy. METHODS: Two hundred and three newly diagnosed patients with gastric or oesophageal cancer had serum CRP and cytokine concentrations determined by ELISA. SNP genotyping was performed by Taqman allelic discrimination genotyping and compared with the genotype observed in 266 healthy volunteers. Clinico-pathological information was collected prospectively and survival duration was recorded. RESULTS: Distribution of the cytokine genotypes was similar between patients and controls. The IL-6 174 CC and IL-10 1082 GG genotypes were associated with elevated serum CRP (P = .03, P = .01, respectively; Mann-Whitney U test) and sTNF-R (P = .015, P = .02) concentrations. These genotypes were also associated with reduced survival duration (P = .01, P = .047; log-rank test). TNFalpha AA genotype was also associated with reduced survival duration on univariate (P = .032) and multivariate analysis (P = .006, multivariate model), but not with inflammatory markers. No other cytokine polymorphisms were associated with systemic inflammatory markers or prognosis. CONCLUSIONS: There is a pro-inflammatory cytokine haplotype (IL-6 CC, IL-10 GG, TNFalpha AA) that is associated with adverse prognosis that may act, at least in part, through an inflammatory mediated mechanism. Determining patients' cytokine haplotype may improve prognostication and allow stratification for intervention studies.	esophagus
Reduced incidence of nodal micrometastasis after major response to neoadjuvant chemoradiation in locally advanced esophageal cancer.	BACKGROUND: Neoadjuvant treatment modalities for esophageal cancer were developed to improve local tumor control as well as to reduce lymph node metastases and distant metastases in patients with locally advanced esophageal cancer. The influence on nodal micrometastasis has not yet been evaluated. METHODS: This study includes 52 patients with localized (cT2-4, Nx, M0) esophageal cancers (21 adenocarcinomas, 31 squamous cell cancers) who received neoadjuvant chemoradiation (36Gy, 5-FU, cisplatin) followed by transthoracic en bloc esophagectomy with two field lymphadenectomy. The extent of histomorphologic regression was categorized into major (< 10%) and minor response (>10% vital residual tumor cells) as recently reported. A total of 1186 lymph nodes were diagnosed as negative for metastases by routine histopathological analysis and were further examined for the presence of isolated tumor cells with the monoclonal anti-epithelial antibody AE1/AE3. RESULTS: Twenty-two tumors (42.3%) showed a major histopathologic response whereas in 30 tumors (57.7%) only a minor response was present. Of 32 patients with a pN0 category, major response was present in 19 (59.4%) tumors, whereas 13 (40.6%) tumors showed minor response. Nine (69%) out of 13 patients with minor response had AE1/AE3-positive cells in their lymph nodes, whereas only four (21%) out of 19 pN0-patients with major response showed nodal micrometastasis (P = 0.013, chi(2)-test). CONCLUSIONS: If tumors show a major histomorphologic response following neoadjuvant chemoradiation, the presence of nodal micrometastasis is significantly reduced compared to those with minor response.	esophagus
Alvocidib (Flavopiridol) suppresses tumor growth in SCID mice with human esophageal cancer xenografts without inducing apoptosis.	Alvocidib (Flavopiridol, HMR1275) is a potent inhibitor of multiple cyclin-dependent kinases and has been identified recently as an antitumor agent in several cancers. Previous studies have shown that alvocidib could potentially treat esophageal cancer in vitro. This study evaluates alvocidib for its ability to suppress tumor growth in severe combined immunodeficiency (SCID) mice bearing TE8 human esophageal squamous cell carcinoma (SCC) xenografts. Alvocidib treatment of 10mg/kg body weight reduced tumor volume significantly. Immunohistochemistry analysis of alvocidib-treated tumor sections showed significant reductions in cyclin D1, VEGF, and Rb levels. Alvocidib treatment did not cause a marked increase in apoptotic tumor cells by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) analysis, yet hematoxylin and eosin staining revealed tumor necrosis. In vivo investigation of alvocidib treatment confirmed antitumor activity in TE8 esophageal xenografts. These findings suggest that alvocidib could be a useful anti-cancer agent for esophageal cancer.	esophagus
Phase II study of preoperative paclitaxel/cisplatin with radiotherapy in locally advanced esophageal cancer.	PURPOSE: Preoperative paclitaxel-based chemoradiotherapy may improve the response rates and survival in patients with localized esophageal cancer. We evaluated paclitaxel-based induction chemoradiotherapy in patients with localized esophageal cancer to determine its feasibility, clinical response, pathologic response, and overall survival. METHODS AND MATERIALS: Between 1995 and 1998, 50 patients were enrolled in this study. At study entry, patients were categorized as either resectable or unresectable according to evaluation by an experienced thoracic surgeon. All patients were treated with paclitaxel 175 mg/m2 and cisplatin 75 mg/m2 on Day 1, 29 with radiotherapy to 3,000 cGy in 15 fractions. Resectable patients underwent esophagectomy 4 weeks later. Postoperatively, patients received two cycles of paclitaxel 175 mg/m2 on Day 1 and 5-fluorouracil 350 mg/m2 and leucovorin 300 mg on Days 1-3, given every 28 days. Patients who were deemed unsuitable for resection from the outset continued radiotherapy to a total dose of 6,000 cGy. RESULTS: Of the 50 patients, all began neoadjuvant chemoradiotherapy, 40 patients underwent surgery, and 25 patients completed postoperative chemotherapy. A pathologic complete response was seen in 7 patients (17.5%). Patients with a pathologic response had a median survival of 32.4 months vs. 14.4 months for nonresponders (p < 0.001). Patients with a clinical response had a median survival of 25.2 months compared with 15.6 months for nonresponders (p = 0.002). At a median follow up of 19.8 months (range 2.4-100.8), the median survival was 20.4 months and the 3-year overall survival rate was 23.2%. CONCLUSION: Although preoperative cisplatin/paclitaxel with 3,000 cGy was tolerable, this multimodality regimen did not appear to be superior to standard cisplatin/5-fluorouracil-containing regimens and its use is not recommended.	esophagus
[Effect of concurrent chemoradiotherapy on serum vascular endothelial growth factor in esophageal squamous cell carcinoma patients--a report of 43 cases].	BACKGROUND & OBJECTIVE: The prognosis of esophageal cancer is not only affected by TNM stage but also by the level of serum vascular endothelial growth factor (S-VEGF). This study was to investigate the effect of concurrent chemoradiotherapy on S-VEGF in esophageal squamous cell carcinoma (ESCC), and to explore the correlation of S-VEGF to the prognosis of ESCC. METHODS: Serum samples were obtained from ESCC patients, treated with concurrent chemoradiotherapy in Cancer Center of Sun Yat-sen University from Dec. 2002 to May 2004, before treatment and 1 month after treatment. The serum samples from sex- and age-matched healthy donors were used as controls. Two courses of chemotherapy, comprised of cisplatin and 5-fluorouracil, were given during radiotherapy at 4-week intervals. S-VEGF level was measured by ELISA. The changes of S-VEGF level before and after treatment were observed, and its correlation to progress-freely survival rate of ESCC patients was analyzed. RESULTS: S-VEGF level was significantly higher in ESCC patients before and 1 month after treatment than in healthy controls [(516.27+/-67.89) ng/L and (347.19+/-35.42) ng/L vs. (294.20+/-23.40) ng/L, P<0.01, P=0.002]; concurrent chemoradiotherapy significantly reduced S-VEGF level (P<0.01). S-VEGF level before treatment was significantly lower in the patients achieved complete remission than in those achieved partial remission or had progressive disease [(345.82+/-76.29) ng/L vs. (669.37+/-99.04) ng/L, P =0.020]. The 1-year progress-freely survival rate was 0 in the patients with S-VEGF level of > 516.27 ng/L before treatment and >347.19 ng/L after treatment, 17% in the patients with S-VEGF level of > 516.27 ng/L and <347.19 ng/L, respectively, 57% in the patients with S-VEGF level of < 516.27 ng/L and >347.19 ng/L, respectively, and 72% in the patients with S-VEGF level of < 516.27 ng/L and <347.19 ng/L, respectively (P= 0.005). CONCLUSIONS: S-VEGF level is higher in ESCC patients than in healthy control. Concurrent chemoradiotherapy could reduce S-VEGF level in ESCC. The changes of S-VEGF level before and after treatment may provide prognostic information for ESCC patients.	esophagus