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Methoxychlor (MXC) and vinclozolin (VIN) are well-recognized endocrine disrupting chemicals known to alter epigenetic regulations and transgenerational inheritance; however, non-endocrine disruption endpoints are also important. Thus, we determined the effects of MXC and VIN on the dysregulation of gap junctional intercellular communication (GJIC) and activation of mitogen-activated protein kinases (MAPKs) in WB-F344 rat liver epithelial cells. Both chemicals induced a rapid dysregulation of GJIC at non-cytotoxic doses, with 30 min EC50 values for GJIC inhibition being 10 μM for MXC and 126 mM for VIN. MXC inhibited GJIC for at least 24 h, while VIN effects were transient and GJIC recovered after 4 h. VIN induced rapid hyperphosphorylation and internalization of gap junction protein connexin43, and both chemicals also activated MAPK ERK1/2 and p38. Effects on GJIC were not prevented by MEK1/2 inhibitor, but by an inhibitor of phosphatidylcholine-specific phospholipase C (PC-PLC), resveratrol, and in the case of VIN, also, by a p38 inhibitor. Estrogen (ER) and androgen receptor (AR) modulators (estradiol, ICI 182,780, HPTE, testosterone, flutamide, VIN M2) did not attenuate MXC or VIN effects on GJIC. Our data also indicate that the effects were elicited by the parental compounds of MXC and VIN. Our study provides new evidence that MXC and VIN dysregulate GJIC uia mechanisms involving rapid activation of PC-PLC occurring independently of ER- or AR-dependent genomic signaling. Such alterations of rapid intercellular and intracellular signaling events involved in regulations of gene expression, tissue development, function and homeostasis, could also contribute to transgenerational epigenetic effects of endocrine disruptors. [ABSTRACT FROM AUTHOR]

Background: Operability is difficult to determine in patients with additional pulmonary nodules in nonprimary lobes accompanying resectable lung cancer. Because these nodules could either be malignant or benign, the differential diagnosis is fundamental but still remains a diagnostic challenge. The aim of this study was to evaluate metastasissuspected solid nodules in nonprimary lobes accompanying resectable non-small cell lung cancer (NSCLC). Patients and Methods: From 2003 to 2009, 2,997 patients underwent pulmonary resection for NSCLC. Among them, 62 patients who underwent pulmonary resection for additional nodules in nonprimary lobes to exclude metastasis were identified. Their medical records were analyzed retrospectively. Results: There were 48 males and 14 females, with a mean age of 61 years (range, 35- 76 years). Tumors were located in ipsilateral nonprimary lobes in 16 patients, contralateral lobes in 21 patients, and bilateral lobes in 25 patients. Sixty-six resections were performed in the 62 patients including four cases of multiple resections. Forty-six nodules (70%) were pathologically confirmed as benign and 20 nodules (30%) were diagnosed with malignancy. The accuracy of radiologic malignancy diagnosis was 32% (20 out of 62). Two patients died of acute respiratory distress syndrome during the postoperative period. Both of these patients underwent lobectomy following additional resection for satellite nodules, which were located on the contralateral side. Conclusion: If patients have satellite nodules accompanying resectable NSCLC, aggressive pathological assessment should be considered. However, bilateral procedures can increase postoperative morbidity and mortality; therefore, staged operation or close follow-up might be the alternative strategy. [ABSTRACT FROM AUTHOR]

Purpose Parameters of positron emission tomography-computed tomography (PET-CT) were compared with the results of histopathologic examination in order to determine which can provide an objective indication of response after neoadjuvant chemoradiation for treatment of thoracic esophageal squamous cell carcinoma (SCC). Materials and Methods Between August 2003 and January 2010, data on 25 patients who underwent neoadjuvant chemoradiation and subsequent resection for treatment of esophageal SCC were retrospectively reviewed. Changes in maximum standardized uptake value (ΔSUVmax), metabolic tumor volume (ΔMTV), and total lesion glycolysis (ΔTLG) were analyzed by comparison with the histopathologic findings. Results Pathologic complete remission (CR) for the main tumor was achieved in 11 patients. Postradiation esophagitis was observed in 10 patients. ΔSUVmax of the main tumor was significantly greater in the CR group than in the partial response (PR) group (p=0.039), while ΔMTV and ΔTLG of the main tumor were not (p=0.141 and p=0.349, respectively). The cut-off ΔSUVmax value for CR was estimated as 72.1%, indicating significantly better accuracy than visual interpretation (p=0.045). Of the 48 involved lymph nodes, ΔSUVmax and ΔMTV of lymph nodes were significantly greater in the CR group than in the PR group (p=0.045 and p=0.014, respectively), while ΔTLG was not (p=0.063). The cut-off value of ΔSUVmax for prediction of CR in lymph nodes was calculated as 50.67%. Conclusion PET-CT could be used for prediction of response to neoadjuvant treatment in thoracic esophageal SCC. ΔSUVmax may be a more significant predictor for CR after neoadjuvant chemoradiation than ΔTLG and ΔMTV. [ABSTRACT FROM AUTHOR]

Background: Concerns remain unresolved regarding the safety of unplanned conversion to open thoracotomy during video-assisted thoracic surgery (VATS) lobectomy. We analyzed both early and late outcomes after thoracotomy conversion from VATS. Methods: From December 2003 to December 2008, a total of 738 VATS lobectomies were attempted. Among them were 34 unplanned conversions to open thoracotomy. Patient characteristics, operative data, and early and late postoperative outcomes were analyzed retrospectively. Results: Among the 34 conversion cases, 26 patients had lung cancer and 8 had benign lung disease. The conversion rate was 4.61%. Left and right upper lobectomies were most often associated with unplanned conversions. Conversion was classified into five groups: (1) problems related to anthracofibrosis of hilar lymph nodes in 14 patients; (2) intraoperative vessel or bronchus injury in 11 patients; (3) fused interlobar fissure in 4 patients; (4) oncologic problems, including mediastinal or hilar lymph node metastasis in 2 patients; and (5) vascular anomalies in 3 patients. There was one death due to postoperative pneumonia in a patient with multiple co-morbidities. Two patients had an episode of pneumonia. The mean hospital stay was 10 days, and the median follow-up period was 30.0 ± 11.47 months. Three patients with lung cancer developed recurrent disease, all of whom were found to have stage III disease. No cancer-related death occurred. There was no significant difference in survival or recurrence between patients with conversion and those with successful VATS. However, the operating time and hospital stay were significantly longer in conversion patients. Conclusions: Our data support the claim that VATS lobectomy can be safely performed with an acceptable conversion rate. Unplanned conversion to open thoracotomy does not appear to compromise the prognosis. [ABSTRACT FROM AUTHOR]

A toxicogenomics study was performed in the mouse liver after treatment of a bile-duct-damaging chemical, 4,4'-methylene dianiline (MDA), across multiple doses and sampling times in an acute phase using the AB Expression Array System. Imprinting control region (ICR) mice were given a single oral administration of a low (10 mg/kg b.w.) or high (100 mg/kg b.w.) dose of MDA. Mice were sacrificed six, twenty-four, and seventy-two hours after treatment for serum chemistry, histopathology, and mRNA preparation from liver samples. Treatment with MDA increased liver-toxicity-related enzymes in blood and induced bile-duct cell injury, followed by regeneration. To explore potential biomarker gene profiles, the altered genes were categorized into four expression patterns depending on dose and time. Numerous functionally defined and unclassified genes in each category were up- or down-regulated throughout the period from cellular injury to the recovery phase, verified by RT-PCR. Many genes associated with liver toxicity and diseases belonged to one of these categories. The chemokine-mediated Th1 pathway was implicated in the inflammatory process. The genes associated with oxidative stress, apoptosis, and cell-cycle regulation were also dynamically responsive to MDA treatment. The Wnt/β-catenin signaling pathway was likely responsible for the reconstitution process of the MDA-injured liver. [ABSTRACT FROM AUTHOR]

Background: Neogenin is expressed in cap cells that have been suggested to be mammary stem or precursor cells. Neogenin is known to play an important role in mammary morphogenesis; however its relationship to tumorigenesis remains to be elucidated. Methods: To compare the expression levels of neogenin in cells with different tumorigenicity, the expression levels in M13SV1, M13SV1R2 and M13SV1R2N1 cells, which are immortalized derivatives of type I human breast epithelial cells, were evaluated. Then we measured the expression level of neogenin in paired normal and cancer tissues from eight breast cancer patients. Tissue array analysis was performed for 54 human breast tissue samples with different histology, and the results were divided into four categories (none, weak, moderate, strong) by a single well-trained blinded pathologist and statistically analyzed. Results: The nontumorigenic M13SV1 cells and normal tissues showed stronger expression of neogenin than the M13SV1R2N1 cells and the paired cancer tissues. In the tissue array, all (8/8) of the normal breast tissues showed strong neogenin expression, while 93.5% (43/46) of breast cancer tissues had either no expression or only moderate levels of neogenin expression. There was a significant difference, in the expression level of neogenin, in comparisons between normal and infiltrating ductal carcinoma (p < 0.001). Conclusion: Neogenin may play a role in mammary carcinogenesis as well as morphogenesis, and the expression may be inversely correlated with mammary carcinogenicity. The value of neogenin as a potential prognostic factor needs further evaluation. [ABSTRACT FROM AUTHOR]