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The present study was conducted to investigate the inhibitory effects of the cell-free culture supernatant of L. curvatus Wikim 38 (LC38-CS) on RANKL-induced osteoclast differentiation and bone loss in a mice model of ovariectomy-induced post-menopausal osteoporosis. LC38-CS inhibited the RANKL-induced differentiation of bone marrow-derived macrophages (BMDMs) into osteoclasts in a dose-dependent manner. F-actin ring formation and bone resorption were also reduced by LC38-CS treatment of RANKL-treated BMDMs. In addition, LC38-CS decreased the RANKL-induced activation of the TRAF6/NF-κB/MAPKs axis at the early stage and the expression of osteoclastogenesis-related genes in BMDMs treated with RANKL. PRMT1 and ADMA levels, new biomarkers for osteoclastogenesis, were decreased by LC38-CS treatment. The administration of LC38-CS increased bone volume and bone mineral density (BMD) in ovariectomized (OVX) mice in μ-CT analysis. These findings suggest that LC38-CS inhibited RANKL-induced osteoclast differentiation via the downregulation of molecular mechanisms and exerted anti-osteoporotic effects.

The gut microbiome can influence the development of tumours and the efficacy of cancer therapeutics1-5; however, the multi-omics characteristics of antitumour bacterial strains have not been fully elucidated. In this study, we integrated metagenomics, genomics and transcriptomics of bacteria, and analyses of mouse intestinal transcriptome and serum metabolome data to reveal an additional mechanism by which bacteria determine the efficacy of cancer therapeutics. In gut microbiome analyses of 96 samples from patients with non-small-cell lung cancer, Bifidobacterium bifidum was abundant in patients responsive to therapy. However, when we treated syngeneic mouse tumours with commercial strains of B. bifidum to establish relevance for potential therapeutic uses, only specific B. bifidum strains reduced tumour burden synergistically with PD-1 blockade or oxaliplatin treatment by eliciting an antitumour host immune response. In mice, these strains induced tuning of the immunological background by potentiating the production of interferon-γ, probably through the enhanced biosynthesis of immune-stimulating molecules and metabolites.

Glycosylphosphatidylinositol-anchored sperm hyaluronidases (HYAL) assist sperm penetration through the cumulus–oocyte complex (COC), but their role in mammalian fertilization remains unclear. Previously, we demonstrated that sperm from HYAL 5 and 7 double-knockout (dKO) mice produced significantly less offspring than sperm from wild-type mice due to defective COC dispersal. However, the HYAL6 gene remained active in the sperm from the dKO mice, indicating that they were not entirely infertile. This study explored the role of HYAL6 in fertilization by analyzing HYAL6-mutant mice. In this mouse model, HYAL5 and HYAL7 were present in the HYAL6-knockout sperm, and they could disperse hyaluronic acid. We found that HYAL6 was present on the surface of sperm. However, male mice lacking the HYAL6 gene had normal fertility, testicular integrity, and sperm characteristics. Furthermore, in vitro fertilization assays demonstrated that HYAL6-deficient epididymal sperm functioned normally. Therefore, HYAL6 is dispensable for fertilization.

Inflammation is a multifaceted response of the immune system at the site of injury or infection caused by pathogens or stress via immune cells. Due to the adverse effects of chemical drugs, plant-based compounds are gaining interest in current research. Prunetinoside or prunetin-5-O-glucoside (PUG) is a plant-based active compound, which possesses anti-inflammatory effects on immune cells. In this study, we investigate the effect of PUG on mouse macrophage RAW264.7 cells with or without stimulation of lipopolysaccharide (LPS). Cytotoxicity results showed that PUG is non-cytotoxic to the cells and it reversed the cytotoxicity in LPS-stimulated cells. The levels of nitric oxide (NO) and interleukin-6 (IL-6) were determined using a NO detection kit and IL-6 ELISA kit, respectively, and showed a significant decrease in NO and IL-6 in PUG-treated cells. Western blot and qRT-PCR were performed for the expression of two important pro-inflammatory cytokines, COX2 and iNOS, and found that their expression was downregulated in a dose-dependent manner. Other pro-inflammatory cytokines, such as IL-1β, IL-6, and TNFα, had reduced mRNA expression after PUG treatment. Furthermore, a Western blot was performed to calculate the expression of NF-κB and MAPK pathway proteins. The results show that PUG administration dramatically reduced the phosphorylation of p-Iκbα, p-NF-κB 65, and p-JNK. Remarkably, after PUG treatment, p-P38 and p-ERK remain unchanged. Furthermore, docking studies revealed that PUG is covalently linked to NF-κB and suppresses inflammation. In conclusion, PUG exerted the anti-inflammatory mechanism by barring the NF-κB pathway and activating JNK. Thus, prunetinoside could be adopted as a therapeutic compound for inflammatory-related conditions.

The gut microbiome can influence the development of tumours and the efficacy of cancer therapeutics

Recurrent hyperhidrosis after thoracic sympathectomy is an uncomfortable condition, and compensatory hyperhidrosis (CH) is one of the most troublesome side effects. Here, we describe two patients with recurrent palmar hyperhidrosis (PH) and CH over the whole body simultaneously. They were treated with bilateral T4 sympathetic clipping and reconstruction of the sympathetic nerve from a T5 to T8 sympathetic nerve graft, which was transferred to the resected T3 sympathetic bed site. They reported improvements in sweating and were fully satisfied with the results. Our method can be considered as an alternative approach for patients with recurrent PH and CH.

We report the synthesis of a macrocyclic Gd chelate based on a 1,4,7,10-tetraazacyclododecane-1,4,7-trisacetic acid (DO3A) coordinationn cage bearing an ethoxybenzyl (EOB) moiety and discuss its use as a T1 hepatobiliary magnetic resonance imaging (MRI) contrast agent. The new macrocyclic liver agent shows high chelation stability and high r1 relaxivity compared with linear-type Gd chelates, which are the current clinically approved liver agents. Our macrocyclic, liver-specific Gd chelate was evaluated in vivo through biodistribution analysis and liver MRI, which demonstrated its high tumor detection sensitivity and suggested that the new Gd complex is a promising contrast agent for liver cancer imaging.

A novel manganese(II) complex based on an ethylenediaminetetraacetic acid (EDTA) coordination cage bearing a benzothiazole aniline (BTA) moiety (Mn-EDTA-BTA) was designed and synthesized for use as a liver-specific MRI contrast agent with high chelation stability. In addition to forming a hydrophilic, stable complex with Mn2+, this new Mn chelate was rapidly taken up by liver hepatocytes and excreted by the kidneys and biliary system. The kinetic inertness and R1 relaxivity of the complex were much higher than those of mangafodipir trisodium (MnDPDP), a clinically approved liver-specific MRI contrast agent. The diagnostic utility of this new Mn complex in MRI was demonstrated by high-sensitivity tumor detection in an animal model of liver cancer.

A 52-year-old male patient who underwent multiple wedge resections experienced postoperative acute respiratory distress syndrome in both lungs after Viscum album pleurodesis. Despite initial rapid deterioration in clinical condition and rapid progression of bilateral lung infiltration, he exhibited a relatively smooth clinical recovery with marked response to glucocorticoid treatment. Our case report suggests that care must be taken to guard against the development of acute respiratory complications in the use of Viscum album for pleurodesis. However, in view of the clinically benign course, initial aggressive management of complications can prevent suffering and sequelae.

Persistently activated STAT3 is a promising target for a new class of anticancer drug development and cancer therapy, as it is associated with tumor initiation, progression, malignancy, drug resistance, cancer stem cell properties, and recurrence. Here, we discovered 3-(2,4-dichloro-phenoxymethyl)-5-trichloromethyl-[1,2,4]oxadiazole (ODZ10117) as a small-molecule inhibitor of STAT3 to be used in STAT3-targeted cancer therapy. ODZ10117 targeted the SH2 domain of STAT3 regardless of other STAT family proteins and upstream regulators of STAT3, leading to inhibition of the tyrosine phosphorylation, dimerization, nuclear translocation, and transcriptional activity of STAT3. The inhibitory effect of ODZ10117 on STAT3 was stronger than the known STAT3 inhibitors such as S3I-201, STA-21, and nifuroxazide. ODZ10117 suppressed the migration and invasion, induced apoptosis, reduced tumor growth and lung metastasis, and extended the survival rate in both in vitro and in vivo models of breast cancer. Overall, we demonstrated that ODZ10117 is a novel STAT3 inhibitor and may be a promising agent for the development of anticancer drugs.

Schwannomas originate from Schwann cells, and they are the most common benign neoplasms of the peripheral nerves. They can occur in most parts of the body but have a predilection for the head, the neck, and the flexor aspects of the extremities. Pancreatic schwannomas are uncommon, and only a few cases have been reported in the English literature. Approximately two-thirds of pancreatic schwannomas undergo cystic degeneration, and they should be considered in the differential diagnosis of solid pancreatic tumors with cystic changes to facilitate accurate diagnosis and optimal treatment. We report a case of a pathologically proven schwannoma in the pancreatic tail with multiple cystic and hemorrhagic changes followed by a review of relevant literature.

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 µM 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 via 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.

The objective of this study was to report on a new surgical technique, hybrid laparoscopic myomectomy that integrates the advantages of transumbilical laparoendoscopic single-site surgery and those of isobaric laparoscopy, and the initial experience with 14 cases. All of the procedures were performed by a single surgeon who has over 18 years of experience in laparoscopic surgery and 4 years of experience in laparoendoscopic single-site surgery. All cases of hybrid laparoscopic myomectomy were completed safely and effectively without conversion to conventional laparoscopic procedure. The median operative time was 75 minutes (range, 30 to 100 minutes). No postoperative complication was observed. The findings show that hybrid laparoscopic myomectomy is a safe and feasible surgical technique, and therefore can be a feasible, minimally invasive alternative to either abdominal or laparoendoscopic single-site surgery myomectomy.

Curcumin (cur) has been comprehensively studied for its various biological properties, more precisely for its antitumor potential and it has shown the promising results as well. On the other hand, Chlorin e6 (Ce6) has mostly been used as a photosensitizer in photodynamic therapy (PDT) against a variety of carcinomas. In the present study, we have synthesized a series of Chlorin e6-curcumin (Ce6-cur) conjugates and investigated their photosensitizing potential against pancreatic cancer cell lines. All the synthesized compounds were characterized by UV, 1H NMR, 13C NMR and LC-MS. These Ce6-cur conjugates showed better physicochemical properties and higher singlet oxygen generation capability. The cellular uptake was studied in AsPC-1 cells using fluorescence-activated cell sorting (FACS). Compound 17 was rapidly internalized within 30 min and sustained for 24 h. Compound 17 showed excellent PDT efficacy with IC50 of 40, 35 and 41 nM against AsPC-1, MIA PaCa-2 and PANC-1 respectively with exceptional dark/phototoxicity ratio in the range of 2371–7500. Moreover, the treatment of compound 17 upregulated the expression of BAX, Cytochrome-C and cleaved caspase 9 while downregulating the Bcl-2 expression an anti-apoptotic protein marker. These results demonstrate outstanding capability of compound 17 as a potent photosensitizer which could improve the PDT efficacy in pancreatic cancer patients.

Rupture of the aorta is a relatively rare complication of blunt chest trauma, and traumatic rupture of the aortic valve is even rarer. Even though both result from blunt chest trauma, the causative mechanisms of aortic valve injury differ from those of descending aortic rupture. There are no previous reports in the literature of simultaneous injuries to both the descending aorta and the aortic valve. We report a case of a 70-year-old man who presented with traumatic aortic regurgitation combined with traumatic pseudoaneurysm of the aortic isthmus following blunt chest trauma, and its successful repair with a hybrid surgical strategy.

Background and Objectives The purpose of this study was to present clinical outcomes of malignant tumors involving the carina after surgery in order to establish the management guidelines. Methods Between 1996 and 2011, 30 patients underwent carinal resection and reconstruction for malignancy involving carina. We retrospectively analyzed their medical records. There were 22 cases of common type of NSCLC (squamous cell carcinoma/adenocarcinoma/large cell neuroendocrine carcinoma) and eight cases of carcinomas of salivary gland type (adenoid cystic carcinoma/mucoepidermoid carcinoma). Results Seventeen right sleeve pneumonectomies, two left sleeve pneumonectomies, nine carinal sleeve right upper lobectomies, and two airway resections and reconstructions without lung resection were performed. There were no in-hospital mortalities. Eleven postoperative morbidities occurred including three cases of acute respiratory distress syndrome following pneumonectomy. Late complications occurred in eight patients including three cases of anastomotic stenosis. During follow-up, 12 mortalities occurred, including 6 cancer-related mortalities. The 5-year overall survival rate (OS) and disease-free survival rate (DFS) were 66.3% and 52.9%, respectively. Conclusions Malignant tumors involving the carina can be controlled with carinal surgery with acceptable mortality and morbidity. Patients with thoracic malignancy involving the carina should be considered as surgical candidate based on disease extent and functional status. J. Surg. Oncol. 2014 110:239–244. © 2014 Wiley Periodicals, Inc.

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 metastasis-suspected 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.

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.

Repeated resection of colorectal cancer pulmonary metastasis is associated with long-term survival. Nevertheless, very limited data addressing the best candidates for repeated pulmonary resection is available.We searched the PubMed database for retrospective studies evaluating lung metastasectomy for metastatic colorectal cancer (CRC). We included studies with available data about repeated pulmonary metastasectomy. Potential prognostic factors were analyzed for possible impact on survival following the second metastasectomy through univariate and multivariate analysis.Between 1983 and 2008, 944 lung metastasectomies were carried out on 759 patients. Of those, 148 patients had a second metastasectomy. The 5-year survival rate was 52 % for patients who had 1 metastasectomy and 57.9 % from the second metastasectomy for patients who had repeated resection. More than 2 metastatic pulmonary nodules and maximum diameter of largest pulmonary nodule ≥3 cm were the only independent factors associated with inferior survival following repeated pulmonary resection.In selected patients with metastatic CRC, repeated pulmonary metastasectomy offers an excellent chance for long-term survival and is associated with a quite low operative mortality. Patients with more than 2 metastatic nodules and a maximum diameter of the largest metastatic lung nodule of ≥3 cm have a significantly inferior survival.

// Joon-Suk Park 1, * , ChuHee Lee 2, * , Hyun-Kyoung Kim 3, * , Dayea Kim 3 , Jung Beom Son 3 , Eunhwa Ko 3 , Joong-Heui Cho 3 , Nam-Doo Kim 3 , Hong-Yan Nan 2 , Choong-Yong Kim 1 , Sukkyoon Yoon 3 , Sun-Hwa Lee 3 , Hwan Geun Choi 3 1 Laboratory Animal Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu, South Korea 2 Department of Biochemistry and Molecular Biology, School of Medicine, Yeungnam University, Daegu, South Korea 3 New Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu, South Korea * These authors have contributed equally to this work Correspondence to: Sun-Hwa Lee, email: sunhlee@dgmif.re.kr Hwan Geun Choi, email: hgchoi@dgmif.re.kr Keywords: breast cancer, metastasis, AXL, signal transduction, kinase inhibitor Received: April 25, 2016 Accepted: October 21, 2016 Published: November 04, 2016 ABSTRACT Breast cancer is the most common malignant disease occurring in women and represents a substantial proportion of the global cancer burden. In these patients, metastasis but not the primary tumor is the main cause of breast cancer-related deaths. Here, we report the novel finding that DN10764 (AZD7762, a selective inhibitor of checkpoint kinases 1 and 2) can suppress breast cancer metastasis. In breast cancer cells, DN10764 inhibited cell proliferation and GAS6-mediated AXL signaling, consequently resulting in suppressed migration and invasion. In addition, DN10764 induced caspase 3/7-mediated apoptosis in breast cancer cells and inhibited tube formation of human umbilical vein endothelial cells. Finally, DN10764 significantly suppressed the tumor growth and metastasis of breast cancer cells in in vivo metastasis models. Taken together, these data suggest that therapeutic strategies targeting AXL in combination with systemic therapies could improve responses to anti-cancer therapies and reduce breast cancer recurrence and metastases.

Background: Treatment of pulmonary metastasis from urothelial cell carcinoma has been mostly palliative chemotherapy and the role of pulmonary metastasectomy has not been investigated much. Materials and Methods: This study is a retrospective interim review of pulmonary metastasectomy from urothelial carcinoma at single institution between 1998 and 2010. Overall 16 patients underwent pulmonary metastasectomies. Results: There was no postoperative complication or hospital mortality. Mean hospital stay was 6 days. Overall and disease-free 5-year survival were 65.3% and 37.5%, respectively. Conclusion: In selected patients with pulmonary metastasis from urothelial carcinoma, surgical treatment is feasible and could contribute to long-term survival in selected patients.

SUMMARY Common hepatic artery lymph node dissection is regarded as a standard procedure in esophageal cancer surgery because of aggressive lymphatic dissemination of esophageal cancer. However, lymph node dissection can prolong operation time and may be associated with complications such as chylous ascites. Here, we aimed to evaluate the effectiveness of common hepatic artery lymph node dissection in clinical T1N0 thoracic esophageal squamous cell carcinoma. Between 1996 and 2009, 1390 patients underwent surgery for esophageal cancer in our institution, and 209 were found to have clinical T1N0 disease. Exclusion criteria were nonsquamous carcinoma, double primary cancer, definite distant metastasis, administration of neoadjuvant treatment, and incomplete abdominal lymph node dissection. We retrospectively analyzed medical records, operative and pathologic data, and follow-up information. Forty-two patients were excluded from the study. Among the 167 enrolled patients, preoperative endoscopic ultrasound evaluation was performed in 160 patients. Fifty-two patients had distal esophageal or esophagogastric junction tumor. Surgery included 2 cases of tri-incisional esophagectomy, 17 cases of transhiatal esophagectomy, and 148 cases of two-field esophagectomy (Ivor Lewis operation). Common hepatic artery lymph node dissection was performed in all cases, and none of the patients had metastasis. Mean follow-up period was 35.4 ± 28.7 months. In-hospital mortality was one, and 5-year survival rate was 80.6%. Among the 15 patients with recurrence, there were two distant metastases and five distant and local recurrences but no intra-abdominal recurrence with common hepatic artery lymph node. Common hepatic artery lymph node dissection may be safely omitted in surgery for clinical T1N0 esophageal squamous cell carcinoma when preoperative evaluations including chest computed tomography, positron emission tomography and computed tomography, and esophagogastroduodenoscopy or endoscopic ultrasound are performed.

Objectives: There is no standard treatment for recurrent thymoma, but treatment is usually palliative therapy. For this article, we retrospectively reviewed our experiences to examine the efficacy of surgical treatment and the extent of adequate resection. Methods: From 1997 to 2007, 15 patients underwent surgical resection for locoregional recurrence of thymoma in the Samsung Medical Center. The tumors at the initial resection were B1 in two patients, B2 in six, B3 in three and C in four according to the World Health Organization histological classification. Complete resection was achieved in 12 patients with pleurectomy (n = 11) or extrapleural pneumonectomy (n = 1). Results: There was neither perioperative mortality nor significant immediate postoperative morbidity. After discharge, chest computed tomography scans were evaluated after a minimum of 6 months and the median follow-up duration was 45 months. At the time of writing, 10 patients had survived with (n = 5) or without (n = 5) rerecurrence (3-year survival = 84.0%). Survival was significantly superior in patients with complete resection compared with those with incomplete resection (P= 0.008). Conclusions: Surgical resection could be considered in patients with locoregionally recurrent thymoma because it can be performed safely and offers a chance of long-term survival to some patients. To achieve complete resection, more extended surgery must be considered for multiple pleural metastases.

Background: Video-assisted thoracic surgery (VATS) lobectomy has been performed with increasing frequency over the last decade. However, there is still controversy as to its indications, safety, and feasibility. Especially regarding lung cancer surgery, it is not certain whether it can reduce local recurrences and improve overall survival. Materials and Methods: We retrospectively reviewed 1,067 cases of VATS lobectomy performed between 2003 and 2009, including the indications, postoperative morbidity, mortality, recurrence, and survival rate. Results: One thousand and sixty seven patients underwent VATS lobectomy for the following indications: non-small cell lung cancer (NSCLC) (n=832), carcinoid tumors (n=12), metastatic lung cancer (n=48), and benign or other diseases (n=175). There were 63 cases (5.9%) of conversion to open thoracotomy during VATS lobectomy. One hundred thirty one (15.7%) of the 832 NSCLC patients experienced pathologic upstaging postoperatively. The hospital mortality rate was 0.84% (9 patients), and all of them died of acute respiratory distress syndrome. One hundred forty-nine patients (14.0%) experienced postoperative complications. The median follow-up was 22.9 months for patients with NSCLC. During follow-up, 120 patients had a recurrence and 55 patients died. For patients with pathologic stage I, the overall survival rate and disease-free survival rate at 3 years was 92.2±1.5% and 86.2±1.9%, respectively. For patients with pathologic stage II disease, the overall survival rate and disease-free survival rate at 3 years was 79.2±6.5% and 61.9±6.6%, respectively. Conclusion: Our results suggest that VATS lobectomy is a technically feasible and safe operation, which can be applied to various lung diseases. In patients with early-stage lung cancer, excellent survival can be also achieved.

Background: Surgical treatment of stage I non-small cell lung cancer (NSCLC) can be performed either by thoracotomy or by employing video-assisted thoracic surgery (VATS). The aim of this study was to evaluate the feasibility of VATS lobectomy for pathologic stage I NSCLC. Material and Methods: Between December 2003 and December 2007, 529 patients with pathologic stage I NSCLC underwent lobectomies (373 thoracotomy, 156 VATS). Patients in both groups were selected after being matched by age, gender and pathologic stage using propensity score method, to create two comparable groups: thoracotomy and VATS groups, and the overall survival, recurrence-free survival, complication and length of hospitalization were compared between these two groups. Results: After the patients were matched by age, gender and pathologic stage, 272 patients remained eligible for analysis, 136 in each group (mean age of 59.5 years; 70 men, 66 women; 80 stage IA, 56 stage IB). There was no statistical difference in other preoperative clinical characteristics between the two groups. No hospital mortality was observed in both groups. Overall 3-year survival rate was 97.4% in thoracotomy group and 96.6% in VATS groups (p=0.76). During the follow-up, 20 patients (14.7%) developed recurrence in thoracotomy group, including loco-regional recurrence in 7, distant metastasis in 13. In VATS group, 13 patients (9.6%) developed recurrence, including loco-regional recurrence in 4, distant metastasis in 9. Three-year recurrence-free survival rate was 81.8% in thoracotomy group and 85.3% in VATS groups (p=0.43). There was no significant difference in postoperative complications between thoracotomy and VATS groups (30 cases in 22 patients vs. 19 cases in 17 patients, p=0.65, odds ratio=1.19). The mean hospital stay of VATS group was 2 days shorter than that of thoracotomy group (8.8±6.5 days vs. 6.3±3.3 days, p＜0.05). Conclusion: VATS lobectomy for pathologic stage I lung cancer is a feasible operation with shorter hospitalization, while surgical outcome is comparable to thoracotomy lobectomy.

Objectives: Sarcomatoid carcinoma of the lung is a very rare and aggressive subtype of non-small cell lung cancer. We explored the clinicopathologic characteristics and surgical outcome of this tumor. Methods: Among 4,212 patients who underwent curative resection for non-small cell lung cancer from September 1994 to December 2009, 99 patients had sarcomatoid carcinoma. Medical records of patients were reviewed retrospectively. Results: The mean follow-up period was 16.07 months. Thirty-six patients had pathologic stage I disease, and 63 had more advanced disease. Surgery included 2 wedge resections, 67 lobectomies, 17 bilobectomies, and 13 pneumonectomies. There were 90 pleomorphic carcinomas, 6 spindle cell carcinomas, 1 giant cell carcinoma, 1 carcinosarcoma, and 1 pulmonary blastoma. Overall 5-year survival was 54.3%. Forty-three patients experienced recurrence and 42 of these died of the cancer. Pathologic T stage as defined by the 7th TNM staging system was significantly associated with survival and recurrence (p = 0.004 and 0.002, respectively). Mean positron emission tomography uptake was significantly higher than in other types of lung cancer (p < 0.0001). Conclusions: Our results implied that surgery for sarcomatoid carcinoma must be carefully planned after extensive preoperative evaluation. Efforts should be made for accurate preoperative histological diagnosis of large peripheral tumor with exceedingly high positron emission tomography uptake.

Background During the past decade, video-assisted thoracic surgery (VATS) lobectomy has been performed with increasing frequency in patients with early-stage non–small cell lung cancer (NSCLC). However, questions remain as to whether VATS lobectomy reduces local recurrence and improves long-term survival in patients with NSCLC. Methods We retrospectively reviewed short-term and midterm outcomes, including postoperative morbidity, mortality, recurrence rate, and survival, in patients undergoing VATS lobectomy. Results Between 2003 and 2008, 704 patients underwent VATS lobectomy for the following indications: NSCLC (n = 548), carcinoid tumors (n = 7), pulmonary metastases (n = 22), and benign diseases (n = 127). One hundred eleven of 548 clinical stage I NSCLC patients (20.3%) experienced pathologic upstaging postoperatively. There were 9 in-hospital deaths (1.3%); all of these patients died of acute respiratory distress syndrome. Sixty-four patients experienced postoperative complications (9.1%). The median follow-up was 20 months for patients with NSCLC. During follow-up, 54 patients had a recurrence, and 13 patients died. Disease-free survival for patients with pathologic stage I disease was 92.7% at 1 year and 87.6% at 3 years. For patients with pathologic N1 (n = 55) and N2 diseases (n = 41), disease-free survival at 3 years was 79.3% and 57.1%, respectively. Conclusions Video-assisted thoracoscopic surgery lobectomy is a technically feasible and safe operation with excellent survival for early-stage lung cancer. For patients with pathologic N1 or N2 diseases after VATS lobectomy, survival was not compromised by this minimally invasive approach.

Optimal duct design of a HVAC system requires analysis technology to accurately evaluate its pressure losses, flow rate and velocity for making a compromised design among fan capacity and duct size affecting initial manufacturin g and operation costs, and noise induced by the HVAC system.In this paper, we carry out initial duct design using the equal friction method. Using the result, the T-method is applied for accurate analysis of flow r ate. Then, the duct size is modified using the difference between the required and the calc ulated flow rate, which can guarantee required flow rate, reduce the pressure unbalance amo ng duct paths and lead to select optimal fan performance. To verify the validity and effectiveness of the proposed design method, an example for HVAC system design including nois e analysis is demonstrated. ※Keywords: HVAC(공조 시스템), Duct design(배관 설계), Equal friction method(등압법), T-method(T-방법), Pressure loss(압력손실), Noise(소음) 접수일: 2009년 3월 4일, 승인일: 2009년 6월 23일✝교신저자: daecho@pusan.ac.kr, 051-510-2482

Inhibition of gap junctional intercellular communication (GJIC) and the activation of intracellular mitogenic pathways are common hallmarks of epithelial derived cancer cells. We previously determined that the 1-methyl and not the 2-methyl isomer of anthracene, which are prominent cigarette smoke components, activated extracellular receptor kinase, and inhibited GJIC in WB-F344 rat liver epithelial cells. Using these same cells, we show that an immediate upstream response to 1-methylanthracene was a rapid ( LT 1 min) release of arachidonic acid. Inhibition of phosphatidylcholine-specific phospholipase C prevented the inhibition of GJIC by 1-methylanthracene. In contrast, inhibition of phosphatidylinositol specific phospholipase C, phospholipase A(2), diacylglycerol lipase, phospholipase D, protein kinase C, and tyrosine protein kinases had no effect on 1-methylanthracene-induced inhibition of GJIC. Inhibition of protein kinase A also prevented inhibition of GJIC by 1-methylanthracene. Direct measurement of phosphatidylcholine-specific phospholipase C and sphingomyelinase indicated that only phosphatidylcholine-specific phospholipase C was activated in response to 1-methylanthracene, while 2-methylanthracene had no effect. 1-methylanthracene also activated p38-mitogen activated protein kinase; however, like extracellular kinase, its activation was not involved in 1-methylanthracene-induced regulation of GJIC, and this activation was independent of phosphatidylcholine-specific phospholipase C. Although mitogen activated protein kinases were activated, Western blot analyzes indicated no change in connexin43 phosphorylation status. Our results indicate that phosphatidylcholine-specific phospholipase C is an important enzyme in the induction of a tumorigenic phenotype, namely the inhibition of GJIC; whereas mitogen activated protein kinases triggered in response to 1-methylanthracene, were not involved in the deregulation of GJIC.

Dysregulation of gap junctional intercellular communication (GJIC) has been associated with different pathologies, including cancer; however, molecular mechanisms regulating GJIC are not fully understood. Mitogen Activated Protein Kinase (MAPK)-dependent mechanisms of GJIC-dysregulation have been well-established, however recent discoveries have implicated phosphatidylcholine-specific phospholipase C (PC-PLC) in the regulation of GJIC. What is not known is how prevalent these two signaling mechanisms are in toxicant/toxin-induced dysregulation of GJIC, and do toxicants/toxins work through either signaling mechanisms or both, or through alternative signaling mechanisms. Different chemical toxicants were used to assess whether they dysregulate GJIC via MEK or PC-PLC, or both Mek and PC-PLC, or through other signaling pathways, using a pluripotent rat liver epithelial oval-cell line, WB-F344. Epidermal growth factor, 12-O-tetradecanoylphorbol-13-acetate, thrombin receptor activating peptide-6 and lindane regulated GJIC through a MEK1/2-dependent mechanism that was independent of PC-PLC; whereas PAHs, DDT, PCB 153, dicumylperoxide and perfluorodecanoic acid inhibited GJIC through PC-PLC independent of Mek. Dysregulation of GJIC by perfluorooctanoic acid and R59022 required both MEK1/2 and PC-PLC; while benzoylperoxide, arachidonic acid, 18β-glycyrrhetinic acid, perfluorooctane sulfonic acid, 1-monolaurin, pentachlorophenol and alachlor required neither MEK1/2 nor PC-PLC. Resveratrol prevented dysregulation of GJIC by toxicants that acted either through MEK1/2 or PC-PLC. Except for alachlor, resveratrol did not prevent dysregulation of GJIC by toxicants that worked through PC-PLC-independent and MEK1/2-independent pathways, which indicated at least two other, yet unidentified, pathways that are involved in the regulation of GJIC. In conclusion: the dysregulation of GJIC is a contributing factor to the cancer process; however the underlying mechanisms by which gap junction channels are closed by toxicants vary. Thus, accurate assessments of risk posed by toxic agents, and the role of dietary phytochemicals play in preventing or reversing the effects of these agents must take into account the specific mechanisms involved in the cancer process.

Chaga mushroom (Inonotus obliquus) has continued to receive attention as a folk medicine with indications for the treatment of cancers and digestive diseases. The anticarcinogenic effect of Chaga mushroom extract was investigated using a model system of gap junctional intercellular communication (GJIC) in WB-F344 normal rat liver epithelial cells. The cells were pre-incubated with Chaga mushroom extracts (5, 10, 20 microg/ml) for 24 h and this was followed by co-treatment with Chaga mushroom extracts and TPA (12-O-tetradecanoylphorbol-13-acetate, 10 ng/ml) for 1 h. The inhibition of GJIC by TPA (12-O-tetradecanoylphorbol-13-acetate), promoter of cancer, was prevented with treatment of Chaga mushroom extracts. Similarly, the increased phosphorylated ERK1/2 and p38 protein kinases were markedly reduced in Chaga mushroom extracts-treated cells. There was no change in the JNK kinase protein level, suggesting that Chaga mushroom extracts could only block the activation of ERK1/2 and p38 MAP kinase. The Chaga mushroom extracts further prevented the inhibition of GJIC through the blocking of Cx43 phosphorylation. Indeed cell-to-cell communication through gap junctional channels is a critical factor in the life and death balance of cells because GJIC has an important function in maintaining tissue homeostasis through the regulation of cell growth, differentiation, apoptosis and adaptive functions of differentiated cells. Thus Chaga mushroom may act as a natural anticancer product by preventing the inhibition of GJIC through the inactivation of ERK1/2 and p38 MAP kinase.

Although 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has a variety of carcinogenic and noncarcinogenic effects in experimental animals, its role in human carcinogenicity remain controversial. A simian virus 40-immortalized cell line from normal human breast epithelial cells with stem cells and luminal characteristics (M13SV1) was used to study whether TCDD can induce AIG positive colony formation and cause increased cell numbers in a inverted U-shaped dose-response manner. TCDD activated Akt, ERK2, and increased the expression of CYP1A1, PAI-2, IL-lb mRNA, and ERK2 protein levels. TCDD was able to increased phosphorylation and expression of ERK2 in same dose-response manner as AIG positive colony formation. Thus, TCDD induced tumorigenicity in M13SV1, possibly through the phosphorylation of ERK2 and/or Akt. Further, cDNA microarray with 7448 sequence-verified clones was used to profile various gene expression patterns after treatment of TCDD. Three clear patterns could be delineated: genes that were dose-dependently up-regulated, genes expressed in either U-shape and/or inverted U-shape. The fact that these genes are intrinsically related to breast epithelial cell proliferation and survival clearly suggests that they may be involved in the TCDD-induced breast tumorigenesis.

Gap junctional intercellular communications (GJIC) contributes to neural function in development and differentiation of CNS. In this study, we have investigated the expression of GJIC during the differentiation of neuronal stem cells and 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced neuronal stem cell-derived cells from rat brain. During neuronal stem cell differentiation, expressions of Cx43 and 32 were increased for the duration of 72 hr, however the effect were decreased on the 7d. In the neuronal stem cell-derived cells, pretreatments with p38 MAP kinase inhibitor, SB203580, and MEK inhibitor, PD98059, could protect GJIC against TPA-induced inhibition of GJIC. Our data suggest that GJIC plays an important role during neuronal stem cell differentiation, and ERK1/2 and p38 MAP kinase signaling pathway may be closely related functionally to regulate gap junction in rat neuronal stem cell-derived cells.

Scope Indole-3-carbinol (I3C), a derivative abundant in cruciferous vegetables such as cabbage, is well known for its various health benefits such as chemo-preventive and anti-obesity effects. I3C is easily metabolized to 3,3'-diindolylmethane (DIM), a more stable form, in acidic conditions of the stomach. However, the anti-obesity effect of DIM has not been investigated clearly. We sought to investigate the effect of DIM on diet-induced obesity and to elucidate its underlying mechanisms. Methods and results High-fat diet (HFD)-fed obese mouse and MDI-induced 3T3-L1 adipogenesis models were used to study the effect of DIM. We observed that the administration of DIM (50 mg/kg BW) significantly suppressed HFD-induced obesity, associated with a decrease in adipose tissue. Additionally, we observed that DIM treatment (40 and 60 μM), but not I3C treatment, significantly inhibited MDI-induced adipogenesis by reducing the levels of several adipogenic proteins such as PPAR-γ and C/EBPα. DIM, but not I3C, suppressed cell cycle progression in the G1 phase, which occurred in the early stage of adipogenesis, inducing post-translational degradation of cyclin D1 by inhibiting ubiquitin specific peptidase 2 (USP2) activities. Conclusion Our findings indicate that cruciferous vegetables, which can produce DIM as a metabolite, have the potential to prevent or treat chronic obesity.

Rupture of the aorta is a relatively rare complication of blunt chest trauma, and traumatic rupture of the aortic valve is even rarer. Even though both result from blunt chest trauma, the causative mechanisms of aortic valve injury differ from those of descending aortic rupture. There are no previous reports in the literature of simultaneous injuries to both the descending aorta and the aortic valve. We report a case of a 70-year-old man who presented with traumatic aortic regurgitation combined with traumatic pseudoaneurysm of the aortic isthmus following blunt chest trauma, and its successful repair with a hybrid surgical strategy.

The purpose of this study was to present clinical outcomes of malignant tumors involving the carina after surgery in order to establish the management guidelines.Between 1996 and 2011, 30 patients underwent carinal resection and reconstruction for malignancy involving carina. We retrospectively analyzed their medical records. There were 22 cases of common type of NSCLC (squamous cell carcinoma/adenocarcinoma/large cell neuroendocrine carcinoma) and eight cases of carcinomas of salivary gland type (adenoid cystic carcinoma/mucoepidermoid carcinoma).Seventeen right sleeve pneumonectomies, two left sleeve pneumonectomies, nine carinal sleeve right upper lobectomies, and two airway resections and reconstructions without lung resection were performed. There were no in-hospital mortalities. Eleven postoperative morbidities occurred including three cases of acute respiratory distress syndrome following pneumonectomy. Late complications occurred in eight patients including three cases of anastomotic stenosis. During follow-up, 12 mortalities occurred, including 6 cancer-related mortalities. The 5-year overall survival rate (OS) and disease-free survival rate (DFS) were 66.3% and 52.9%, respectively.Malignant tumors involving the carina can be controlled with carinal surgery with acceptable mortality and morbidity. Patients with thoracic malignancy involving the carina should be considered as surgical candidate based on disease extent and functional status.

PURPOSE Although the use of a minimally invasive approach in esophageal cancer surgery is gradually increasing, it is generally performed using cervical anastomosis because of the difficulty of intrathoracic anastomosis. Here, we describe our technique for performing intrathoracic esophagogastrostomy using a typical video-assisted thoracic surgery (VATS) approach. METHODS Between September 2009 and July 2011, VATS esophagectomy and intrathoracic anastomosis was performed in 31 esophageal cancer patients with a utility incision made by a segmental rib resection to enhance the extracorporeal insertion of the end-to-end stapler. We retrospectively reviewed the clinical records of these patients. RESULTS There were no intraoperative events related to the VATS procedure. The mean VATS time was 180.2 ± 39.2 min. The mean postoperative hospital stay was 15.2 days (range, 11 to 38 d). No significant pulmonary complications were observed. Five patients developed vocal cord palsy due to radical mediastinal lymphadenectomy. No anastomotic complications such as leaking or stricture were observed. Only 1 patient had postoperative pain requiring analgesics. CONCLUSIONS Our technique can be safely and effectively performed for intrathoracic anastomosis in esophageal surgery with favorable early outcomes and reduced postoperative pulmonary complications.

Some patients with primary spontaneous pneumothorax suffer from recurrence of bullous lesions of the lung after resection. Mechanical pleurodesis by pleural abrasion is one of the standard procedures to prevent recurrence. However, there is actually little evidence that pleural abrasion reduces the recurrence of primary spontaneous pneumothorax. Our aim was to evaluate the efficacy of mechanical pleurodesis by pleural abrasion during thoracoscopic procedures for primary pneumothorax.From January 2003 to December 2009, 263 patients underwent 294 initial thoracoscopic wedge resections with or without pleural abrasion for primary spontaneous pneumothorax at the Samsung Medical Center. Medical records of patients were reviewed retrospectively.Thirty-one patients were excluded from the study due to various comorbidities. The remaining 232 patients underwent 257 thoracoscopic wedge resections with (165) or without (92) pleural abrasion. No mortality was observed. Seven additional chemical pleurodesis and 3 reoperations were performed due to persistent air leakage after initial surgery. There were 18 instances of recurrence, and the overall recurrence rate was 7.1%. Twelve additional wedge resections were performed because of recurrence after initial surgery. The mean duration of postoperative pleural drainage was 2.86 days. There were no significant differences in the recurrence rate (P=0.9499), and duration of chest tube drainage (P=0.5200) between the patients with and without pleural abrasion. Younger patients, especially below 17 years of age, had significant risk of recurrence (P0.0001).Thoracoscopic wedge resection alone successfully controlled primary spontaneous pneumothorax. Additional pleural abrasion did not decrease the recurrence of pneumothorax after wedge resection of bullae for primary spontaneous pneumothorax. Younger age was associated with higher risk of recurrence.

In metastatic colorectal cancers, tumor cells are disseminated prior to surgical resection of the primary tumor but remain dormant until proper colonization mechanisms are activated. To identify the colonization mechanisms of the metastatic tumors, we conducted a pairwise comparison between primary colorectal cancers and metastatic tumors (n=12 pairs), including six hepatic pairs and six pulmonary pairs. The mRNA levels of 224 genes previously reported to be associated with metastasis, cytokines and angiogenesis were quantitatively determined by PCR arrays. Among them, 27 genes were duplicated or triplicated to show consistent expression. Unsupervised hierarchical clustering of the Ct values of metastasis-related genes revealed that liver metastases were indistinguishable from primary colorectal cancers (n=5/6), whereas lung metastases were highly diversified from one another and from the primary tumors (n=6/6). Cytokines and receptor gene expression array data also confirmed the divergence of pulmonary metastases from primary colorectal cancers (n=6/6). Heat map analyses of ΔCt values of the metastasis-related genes identified a 17-gene tropism signature that was sufficient not only to distinguish liver and the lung metastases, but also reconstituted the clustering of primary tumors with the hepatic metastases (n=17/18). In this pilot experiment, pulmonary metastases were significantly diverged from hepatic metastases that were indistinguishable from primary colorectal cancers. Further genomic and clinical studies are in progress to evaluate the potential of the tropism signature as a therapeutic target to inhibit the colonization of metastatic colorectal cancers.

There is no standard treatment for recurrent thymoma, but treatment is usually palliative therapy. For this article, we retrospectively reviewed our experiences to examine the efficacy of surgical treatment and the extent of adequate resection. From 1997 to 2007, 15 patients underwent surgical resection for locoregional recurrence of thymoma in the Samsung Medical Center. The tumors at the initial resection were B1 in two patients, B2 in six, B3 in three and C in four according to the World Health Organization histological classification. Complete resection was achieved in 12 patients with pleurectomy (n = 11) or extrapleural pneumonectomy (n = 1). There was neither perioperative mortality nor significant immediate postoperative morbidity. After discharge, chest computed tomography scans were evaluated after a minimum of 6 months and the median follow-up duration was 45 months. At the time of writing, 10 patients had survived with (n = 5) or without (n = 5) rerecurrence (3-year survival = 84.0%). Survival was significantly superior in patients with complete resection compared with those with incomplete resection (P= 0.008). Surgical resection could be considered in patients with locoregionally recurrent thymoma because it can be performed safely and offers a chance of long-term survival to some patients. To achieve complete resection, more extended surgery must be considered for multiple pleural metastases.

OBJECTIVE: Primary leiomyoma of the respiratory tract is a rare disease. Based on our experience, we investigated its clinical characteristics and outcomes of treatment. METHODS: Between 1997 and 2008, 16 patients in our institution (nine male, seven female) were found to have primary leiomyoma of the respiratory tract. The median patient age was 46.5 years (range 17–66 years). The tumor was located in the trachea in four patients, in the carina and main bronchus in four, in the bronchus intermedius in four, in the lobar or segmental bronchus in two, and in the lung parenchyma in two. RESULTS: Tumor removal through bronchoscopic intervention using Nd–YAG (neodymium–yttrium–aluminum–garnet) laser cauterization was attempted in 11 patients; it failed in two with wide-based tumors. Surgical resection was performed in seven patients. Operative procedures included tracheal resection and end-to-end anastomosis (n = 3), lobectomy (n = 3), and bilobectomy (n = 1). There were no in-hospital mortalities. During a median follow-up duration of 43.2 months, one patient who underwent bronchoscopic removal had recurrence, for which segmental resection of the trachea and main bronchus with carinal reconstruction was performed. CONCLUSIONS: Bronchoscopic intervention can offer successful control of primary leiomyoma of the main airway stem; however, in cases of a wide-based tumor, bronchoscopic intervention can result in incomplete resection or recurrence. Surgical complete resection can yield satisfactory outcomes in patients with primary leiomyoma occurring in the respiratory tract.

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.