EpCAM, a potential therapeutic target for esophageal squamous cell carcinoma.

BACKGROUND: Molecular-targeted drugs are not available for esophageal squamous cell carcinoma (ESCC), which has a poor prognosis. We investigated the clinicopathological significance of epithelial cell adhesion molecule (EpCAM) expression and the utility of EpCAM as a potential therapeutic target. METHODS: The relationship between EpCAM expression and clinicopathological factors was examined by immunohistochemistry in 74 patients with resectable ESCC. A total of ten ESCC cell lines were analyzed for EpCAM expression. The effects of EpCAM knockdown in TE4, TE10, and TE14 cells were examined with regard to cell proliferation and gene expression in vitro and tumor growth in vivo. The antitumor effect of catumaxomab in ESCC cell lines was examined. RESULTS: EpCAM overexpression was associated with poor survival in ESCC patients (P = 0.026). Multivariate Cox regression analysis showed that EpCAM overexpression was a significant and independent prognostic factor for surgically treated ESCC (P = 0.004). TE4 and TE10 cells showed high EpCAM expression, in contrast to TE14. EpCAM siRNA knockdown in TE4 and TE10 cells downregulated CCND1 and CCNE2 and suppressed cell proliferation. Low EpCAM expression reduced tumorigenesis; TE4 cells initiated tumorigenesis in seven of the ten mice injected, whereas shRNA knockdown resulted in smaller tumors in two of ten mice at 6 weeks after transplantation. Concentration- and time-dependent antitumor effects of catumaxomab were observed in TE4 and TE10 cells. CONCLUSIONS: EpCAM overexpression is an independent prognostic factor for surgically treated ESCC. EpCAM contributes to cell proliferation and tumorigenesis and may be a useful therapeutic target for ESCC.

Contribution of lung macrophages to the inflammatory responses induced by exposure to air pollutants.

Large population cohort studies have indicated an association between exposure to particulate matter and cardiopulmonary morbidity and mortality. The inhalation of toxic environmental particles and gases impacts the innate and adaptive defense systems of the lung. Lung macrophages play a critically important role in the recognition and processing of any inhaled foreign material such as pathogens or particulate matter. Alveolar macrophages and lung epithelial cells are the predominant cells that process and remove inhaled particulate matter from the lung. Cooperatively, they produce proinflammatory mediators when exposed to atmospheric particles. These mediators produce integrated local (lung, controlled predominantly by epithelial cells) and systemic (bone marrow and vascular system, controlled predominantly by macrophages) inflammatory responses. The systemic response results in an increase in the release of leukocytes from the bone marrow and an increased production of acute phase proteins from the liver, with both factors impacting blood vessels and leading to destabilization of existing atherosclerotic plaques. This review focuses on lung macrophages and their role in orchestrating the inflammatory responses induced by exposure to air pollutants.

Statins attenuate the development of atherosclerosis and endothelial dysfunction induced by exposure to urban particulate matter (PM10).

Exposure to ambient air particulate matter (particles less than 10µm or PM10) has been shown to be an independent risk factor for the development and progression of atherosclerosis. The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) have well-established anti-inflammatory properties. The aim of this study was to determine the impact of statins on the adverse functional and morphological changes in blood vessels induced by PM10. New Zealand White rabbits fed with a high fat diet were subjected to balloon injury to their abdominal aorta followed by PM10/saline exposure for 4weeks±lovastatin (5mg/kg/day) treatment. PM10 exposure accelerated balloon catheter induced plaque formation and increased intimal macrophages and lipid accumulation while lovastatin attenuated these changes and promoted smooth muscle cell recruitment into plaques. PM10 impaired vascular acetylcholine (Ach) responses and increased vasoconstriction induced by phenylephrine as assessed by wire myograph. Supplementation of nitric oxide improved the impaired Ach responses. PM10 increased the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in blood vessels and increased the plasma levels of endothelin-1 (ET-1). Incubation with specific inhibitors for iNOS, COX-2 or ET-1 in the myograph chambers significantly improved the impaired vascular function. Lovastatin decreased the expression of these mediators in atherosclerotic lesions and improved endothelial dysfunction. However, lovastatin was unable to reduce blood lipid levels to the baseline level in rabbits exposed to PM10. Taken together, statins protect against PM10-induced cardiovascular disease by reducing atherosclerosis and improving endothelial function via their anti-inflammatory properties.

Sentinel node mapping with thermoresponsive magnetic nanoparticles in rats.

BACKGROUND: In this study, we investigated the ability of magnetic resonance imaging (MRI) after interstitial administration of thermoresponsive magnetic nanoparticles to detect the sentinel lymph node (SLN). MATERIALS AND METHODS: Postcontrast MRI scans were acquired following subcutaneous injection of thermoresponsive magnetic nanoparticles into the thoracic wall of rats. The signal-to-noise ratio of axillary lymph nodes was calculated to assess whether the SLN could be detected by MRI. In a second experiment, after injecting thermoresponsive magnetic nanoparticles, i.e., Therma-Max 36, Therma-Max 42, Therma-Max 55, and Ferridex, into the subserosa of the cecum of rats, the injection sites, the SLNs, and the distant lymph nodes were resected and examined histologically in order to determine which nanoparticles, if any, were specifically retained in the SLN. RESULTS: MRI showed that the signal-to-noise ratio of axillary SLNs was significantly lower 24 h after injection of Therma-Max 42 than on the precontrast images (P < 0.05). Histologic evaluation revealed that Therma-Max 36 aggregated at body temperature and did not migrate to the SLN. Therma-Max 42, on the other hand, aggregated, and the particles became large enough to be retained in the SLNs. Therma-Max 55 and Ferridex did not aggregate, and they both migrated to the SLNs and the distant lymph nodes. CONCLUSIONS: The results of this study showed that thermoresponsive magnetic nanoparticles could be targeted to the SLN by adjusting the temperature at which they aggregate, and that they could be used as a contrast agent for SLN mapping by MRI.

Age and body mass index: significant predictive factors for successful laparoscopic antireflux surgery.

PURPOSE: Laparoscopic antireflux surgery (LARS) is a feasible treatment for gastroesophageal reflux disease (GERD) patients, but it is unclear who will benefit from the surgery. This study investigated patients' GERDspecific quality of life (GsQOL) and analyzed the factors leading to the performance of successful LARS. METHODS: Twenty-six (57.8%) of 45 consecutive patients who underwent LARS for GERD during the last decade were enrolled. All patients were evaluated by 24-h pH monitoring, esophageal manometry, esophagogastro-duodenoscopy and physical examinations. GsQOL was assessed by a visual analog scale, and the difference between the pre- and postoperative scores was defined as the visual analog scale improvement score (VASIS). The patients were classified into three groups based on the VASIS, and their clinical factors and surgical outcomes were compared. RESULTS: The high VASIS group patients (>70 VASIS; Excellent group) patients were significantly younger and obese in comparison to low the VASIS group (<30 VASIS; Poor group) consisting of older nonobese patients (P < 0.05). A multiple regression analysis revealed that age <60 years and body mass index (BMI) >25 kg/m(2) were significant factors that affected postoperative GsQOL. No other clinical or surgical factors had any influence on the postoperative GsQOL. CONCLUSION: These results suggest that age and BMI can be predictive factors for the performance of successful LARS.

Clinical significance of circulating tumor cells in blood from patients with gastrointestinal cancers.

BACKGROUND: Circulating tumor cells (CTCs) measured by the CellSearch system in metastatic breast cancer have been reported to correlate with shorter overall survival. The purpose of this study was to clarify the clinicopathologic characteristics of CTCs in gastrointestinal cancers. METHODS: Pre- and postoperative CTCs from 130 gastrointestinal cancer patients and 41 healthy volunteers were measured by this system. Correlation between CTC counts and clinicopathologic variables was examined. RESULTS: The number of CTCs in metastatic patients (n = 79) was larger than in nonmetastatic patients (n = 35) and in healthy donors (n = 41) (P < 0.001). CTC counts were larger in metastatic gastric cancer (n = 27) than in nonmetastatic gastric cancer (n = 14) (P = 0.016). Two or more CTCs was significantly correlated with advanced tumor stage in all gastrointestinal cancers (P < 0.001) and in gastric cancer (P = 0.032). Two or more CTCs had significant correlation with peritoneal dissemination of gastric or colorectal cancer (P = 0.007) and pleural dissemination of esophageal cancer (P = 0.033). The survival of patients with > or =2 CTCs was shorter than that of patients with <2 CTCs (P = 0.005). The change in CTCs tended to correlate with disease progression and chemotherapeutic effect. CONCLUSION: This study suggests that measurement of CTCs in gastrointestinal cancer patients could be useful as a tool for judging tumor stage, predicting the presence of peritoneal or pleural dissemination and patients' survival, and monitoring response to cancer therapy.

Isolated splenic vein thrombosis secondary to splenic metastasis: a case report.

A 49-year-old, previously healthy woman sought treatment for abdominal pain. Colonoscopy revealed ascending colon cancer. Computed tomography and angiography showed splenic metastasis and thrombosis extending from the splenic vein to the portal vein. She underwent right hemicolectomy, splenectomy, and distal pancreatomy. Histological findings showed no malignant cell in the splenic vein which was filled with organizing thrombus. We postulate the mechanism of splenic vein thrombosis in our case to be secondary to the extrinsic compression of the splenic vein by the splenic metastasis or by the inflammatory process produced by the splenic metastasis. In conclusion, we suggest that splenic metastasis should be added to the list of differential diagnosis which causes splenic vein thrombosis. In the absence of other sites of neoplastic disease, splenectomy seems to be the preferred therapy because it can be performed with low morbidity and harbors the potential for long-term survival.

Strangulated hernia through a defect of the broad ligament and mobile cecum: a case report.

We report a case of 28-year-old woman presenting with small bowel obstruction. She had neither prior surgery nor delivery. An upright abdominal radiograph revealed several air-fluid levels in the small bowel in the midabdomen and the pelvic cavity. Computed tomography demonstrated a dilated small bowel loop in the Douglas's fossa,but no definite diagnosis could be made. Supportive therapy with draining the intestinal fluid by a long intestinal tube did not result in improvement,which suggested the possibility of a strangulated hernia. Exploratory laparotomy revealed mobile cecum and a 20-cm length of the ileum herniated into a defect of the right broad ligament. As a gangrenous change was recognized in the incarcerated bowel, its resection was carried out,followed by end-to-end anastomosis and closure of the defects of the broad ligament. The postoperative course was uneventful. Intestinal obstruction is a very common cause for presentation to an emergency department,while internal hernia is a rare cause of obstruction. Among internal hernias, those through defects of the broad ligament are extremely rare. Defects of the broad ligament can be either congenital or secondary to surgery, pelvic inflammatory disease,and delivery trauma. In conclusion, we emphasize that hernia of the broad ligament should be added to the list of differential diagnosis for female patients presenting with an intestinal obstruction. Early diagnosis and surgical repair reduce morbidity and mortality from strangulation.