Verification and unmasking of widely used human esophageal adenocarcinoma cell lines.

For decades, hundreds of different human tumor type-specific cell lines have been used in experimental cancer research as models for their respective tumors. The veracity of experimental results for a specific tumor type relies on the correct derivation of the cell line. In a worldwide effort, we verified the authenticity of all available esophageal adenocarcinoma (EAC) cell lines.

Met receptor signaling: a key effector in esophageal adenocarcinoma.

Purpose: The incidence of esophageal adenocarcinoma is rising, and survival rates remain poor. The hepatocyte growth factor (HGF) receptor Met has been detected in esophageal cancer. The perturbation of cadherin/catenin complexes has also been shown.

Tissue inhibitor of metalloproteinase-3 (TIMP-3) gene is methylated in the development of esophageal adenocarcinoma: loss of expression correlates with poor prognosis.

Amongst involvement in diverse physiological and pathological processes, TIMP-3 may have an important role in tumour development, growth and metastasis by interaction with metalloproteases in the extracellular matrix. We studied the role and prognostic effect of TIMP-3 in esophageal adenocarcinoma (EADC). TIMP-3 gene methylation and TIMP-3 mRNA expression were analysed in 5 esophageal cell lines and 24 resected EADCs.

p16 expression in Barrett's esophagus and esophageal adenocarcinoma: association with genetic and epigenetic alterations.

Alteration of the p16 tumor suppressor gene has been implicated as a critical lesion in the molecular pathogenesis of esophageal adenocarcinoma. The aim of this study was to characterize the spectrum of p16 alterations in surgically resected esophageal tissues, comprising histologically normal esophageal squamous and gastric epithelia, premalignant Barrett's epithelia, and associated esophageal adenocarcinomas, and to explore associations between p16 mRNA expression and p16 mutations, deletions, promoter hypermethylation, p16 protein expression, and clinico-pathologic features for the same tissues. We have shown that while p16 mutations are uncommon (2%; 1/54), hypermethylation of the p16 promoter is detected in 43% (9/21) of histologically normal epithelia, in 77% (14/18) of associated Barrett's epithelia, and in 85% (18/21) of esophageal adenocarcinomas.

The metabolic marker tumour pyruvate kinase type M2 (tumour M2-PK) shows increased expression along the metaplasia-dysplasia-adenocarcinoma sequence in Barrett's oesophagus.

Background: Proliferating and tumour cells express the glycolytic isoenzyme, pyruvate kinase type M2 (M2-PK). In tumours cells, M2-PK usually exists in dimeric form (tumour M2-PK), causing the accumulation of glycolytic phosphometabolites, which allows cells to invade areas with low oxygen and glucose concentrations.

Aims: To investigate the expression of tumour M2-PK during the metaplasia-dysplasia-adenocarcinoma sequence of Barrett's oesophagus, and to assess the prognostic usefulness of tumour M2-PK in oesophageal cancer.

Preoperative mitomycin, ifosfamide, and cisplatin followed by esophagectomy in squamous cell carcinoma of the esophagus: pathologic complete response induced by chemotherapy leads to long-term survival.

Purpose: Squamous cell carcinoma of the esophagus remains an aggressive disease with a poor prognosis, even after curative-intent surgery. This article analyzes the impact of preoperative chemotherapy with mitomycin, ifosfamide, and cisplatin (MIC) on a cohort of 68 patients.

Patients And Methods: From 1988 to 1994, 68 patients with potentially operable squamous cell carcinoma of the esophagus were entered onto two phase II trials of neoadjuvant chemotherapy with mitomycin 6 mg/m2, ifosfamide 3 g/m2, and cisplatin 50 mg/m2 and received between two and four cycles of treatment at 3-weekly intervals.

Clinical implications of p53 tumor suppressor gene mutation and protein expression in esophageal adenocarcinomas: results of a ten-year prospective study.

Objective: This study was undertaken to characterize the spectrum of p53 alterations (mutations and protein expression) in surgically resected esophageal adenocarcinomas, and to correlate molecular alterations with clinicopathologic findings and outcome.

Methods: Between 1991 and 2001, 91 consecutive patients with esophageal adenocarcinomas underwent subtotal esophagectomy. No patient received induction therapy.

Tumour necrosis factor-alpha in Barrett's oesophagus: a potential novel mechanism of action.

Barrett's metaplasia (BM) is an early lesion in the progression from oesophageal inflammation through dysplasia to the development of Barrett's adenocarcinoma (BA). Previous work indicates that BM and BA are associated with reduced E-cadherin expression and increased cytoplasmic/nuclear pools of its associated protein beta-catenin. beta-catenin participates in Wnt signalling and activates oncogene transcription by complexing with T-cells factors (TCF).

A primary tumour of the oesophagus with both melanocytic and schwannian differentiation. Melanocytic schwannoma or malignant melanoma?

A 76 year old white woman presented with a four month history of dysphagia and weight loss. Clinical, radiological, and endoscopic examination revealed a pigmented mass in the lower third of the oesophagus. The preoperative diagnosis, including biopsy examination, was that of malignant melanoma.

Combined results from three phase II trials of neoadjuvant chemotherapy in operable adenocarcinoma of the oesophagus.

Adenocarcinoma of the oesophagus is a systemic disease at presentation in the majority of patients. This article analyses the impact of preoperative chemotherapy on a cohort of 68 patients. From 1990 to 1996, 68 patients with potentially operable adenocarcinoma of the oesophagus were entered into three sequential Phase II trials of neoadjuvant chemotherapy with cisplatin/mitomycin C/ifosfamide, cisplatin/5-fluorouracil (5-FU) and mitomycin C/cisplatin/5-FU.

Human oesophageal adenocarcinoma cell lines JROECL 47 and JROECL 50 are admixtures of the human colon carcinoma cell line HCT 116.

In two recently described human oesophageal adenocarcinoma cell lines JROECL 47 and JROECL 50, derived from one tumour, we detected identical E-cadherin and beta-catenin gene mutations as in colon carcinoma cell line HCT 116. We demonstrate by HLA-typing, mutation analysis and microsatellite analysis that cell lines JROECL 47 and JROECL 50 are admixtures of the human colon adenocarcinoma cell line HCT 116.

The use of an anabolic steroid (nandrolone decanoate) to improve nutritional status after esophageal resection for carcinoma.

Anabolic steroids increase appetite and muscle mass. This randomized, double-blind trial investigates any nutritional benefits of anabolic steroid in patients after surgery for esophageal cancer. Forty patients were recruited: 19 patients had five injections of 50 mg nandrolone decanoate and 21 patients received placebo over 3 months, starting 1 month after surgery.

What is the optimal distal resection margin for esophageal carcinoma?

Background: Whereas a proximal resection margin of 12 cm is recommended for complete resection of esophageal cancer, the extent of distal resection is unclear.

Methods: We examined distal resection margins in a consecutive series of patients who underwent esophagectomy for squamous cell carcinomas (n = 50), primary esophageal adenocarcinomas (n = 100), and adenocarcinomas of the cardia (n = 39), in whom all macroscopic tumor was judged to be completely resected.

Results: Microscopic tumor was found at a 3-cm distal resection margin for one multifocal squamous cell carcinoma.

A phase II trial of preoperative mitomycin, cisplatin and 5-fluorouracil in adenocarcinoma of the oesophagus.

The effect of neoadjuvant chemotherapy in patients with apparently operable adenocarcinoma of the oesophagus has been investigated. Two courses of mitomycin, cisplatin and 5-fluorouracil (MCF) were given, followed by a radiological evaluation of response. Twenty-two of 25 patients completed both courses.

Sequential changes in cadherin-catenin expression associated with the progression and heterogeneity of primary oesophageal squamous carcinoma.

Maintenance of an adhesive function for cadherins requires appropriate membranous cellular expression and intact cadherin-catenin complexes. In normal squamous mucosa of the oesophagus there is membranous co-expression of E- and P-cadherin (E-cad, P-cad) in the basal compartment, whereas suprabasal stratification is associated with preservation of E-cad expression but loss of P-cad. Immunohistochemical staining of squamous dysplasia/carcinoma in situ shows a striking increase in the proportion of cells within the epithelial compartment showing co-expression of E- and P-cad with strong appropriate membranous expression of beta and gamma catenin.

A phase II trial of cisplatin and 5-fluorouracil in adenocarcinoma of the oesophagus.

The effect of brief neoadjuvant chemotherapy in patients with apparently operable adenocarcinoma of the oesophagus has been investigated. Two courses of cisplatin and 5-fluorouracil (CFu) were given, followed by evaluation of the response by barium swallow. Twenty-one of 23 patients completed both courses.

A phase II trial of four courses of preoperative chemotherapy in squamous or anaplastic carcinoma of the oesophagus.

We have reported the results of a previous Phase II trial of two courses of neoadjuvant mitomycin (6 mg/m2), ifosfamide (3 g/m2) and cisplatin (50 mg/m2) (MIC) in squamous or anaplastic carcinoma of the oesophagus. In this current study, we have investigated whether there was any clinical benefit in extending the preoperative treatment to four courses for patients who responded after two courses. Response was assessed by barium swallow, which was compared with previous barium swallows performed prior to any treatment and after the second course of MIC.

A case of systemic pseudo-pseudoxanthoma elasticum with diverse symptomatology caused by long-term penicillamine use.

A 47 year old man presented with a two year history of increasing cervical dysphagia, dyspnoea, and cutaneous signs. He had been diagnosed 27 years previously with Wilson's disease and was treated with penicillamine (1.5 g daily).

Expression of E-cadherin in oesophageal carcinomas from the UK and China: disparities in prognostic significance.

Aims: To study the expression and prognostic significance of the cell adhesion molecule E-cadherin in oesophageal tumours from the UK (low risk area) and China (high risk area).

Methods: E-cadherin expression was measured immunohistochemically in resected tumours from 17 patients in the UK with adenocarcinoma, 23 patients from the UK with squamous carcinoma, and 30 patients from China with squamous carcinomas who survived for five years postoperatively and compared with similar tumours from patients in the same regions who did not survive (140 tumours in all).

Results: Normal squamous epithelial cells and well differentiated areas of tumours showed membranous staining for E-cadherin expression.

Five newly established oesophageal carcinoma cell lines: phenotypic and immunological characterization.

The derivation of permanent cell lines from 40 resected oesophageal carcinomas has been attempted. Five long-term lines have been established from three adenocarcinomas, one mixed carcinoma and one squamous carcinoma. Molecular and cellular analyses have been carried out on the lines and clones derived from them.

Lymphocyte infiltration in oesophageal carcinoma: lack of correlation with MHC antigens, ICAM-1, and tumour stage and grade.

Infiltration by T lymphocytes into oesophageal carcinomas was assessed immunohistochemically, total T lymphocyte numbers by staining for CD3 and activated T lymphocytes by staining for CD25. Five squamous carcinomas and seven adenocarcinomas, resected without neoadjuvant treatment, were studied. Computer aided quantitation showed that total numbers of tumour infiltrating CD3 positive cells were highly variable (range 48-1673 cells/mm2).

Tumour heterogeneity: a problem in biopsy assessment of the proliferation index of oesophageal adenocarcinomas.

Tumour heterogeneity may pose a problem when biopsy specimens are taken to measure proliferation (for example, in assessing response to therapy). Two "biopsy specimens" were taken from the centre and two from the edge of the luminal surface of 20 resected oesophageal adenocarcinomas. The proliferation index for each "biopsy specimen" was measured by counting Ki67 labelled nuclei in histological sections.

Phase II study of mitomycin, ifosfamide and cisplatin in adenocarcinoma of the oesophagus.

We evaluated the effect of brief neoadjuvant chemotherapy in patients with apparently operable adenocarcinoma of the oesophagus. Two courses of mitomycin (6 mg/m2), ifosfamide (3 g/m2) and cisplatin (50 mg/m2;MIC) were given followed by evaluation of response by barium swallow and computed tomography scan. Of 20 patients, 17 completed both courses and 4 (20%) showed a partial response.