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Background: While single-incision laparoscopic cholecystectomy (SILC) has gained more popularity in recent years, its application to elderly patients needs further evaluation. Few SILC studies regarded this rapidly growing vulnerable population, and single-incision laparoscopic common bile duct exploration (SILCBDE) was never mentioned. We conducted an observational study of 146 routine SILCBDE to address this issue. Methods: One hundred forty-six consecutive patients underwent SILCBDE with concomitant cholecystectomies during a period of 6 years (July 2012–June 2016 and July 2018–July 2020). Forty patients with an age of 65 years or older were the study target. Characteristics and operative outcomes were compared with the remaining 106 younger patients by retrospective chart review. The primary outcomes include complications and mortality, while the secondary outcomes contain intraoperative blood loss, operative time, procedural conversions, postoperative length of hospital stay, and bile duct stone recurrence. Results: There was no mortality. The bile duct stone clearance rate was 98.6%. The elderly group had higher American Society of Anesthesiologists (ASA) scores, higher comorbidity rate, higher acute cholangitis rate, lower completion intraoperative cholangiography (IOC) rate, longer operative time, more blood loss, longer postoperative hospital stay (p <.001), longer total hospital stay (p <.001), higher procedural conversion rate (p <.05), higher complication rate (p <.001), and the exclusive open conversion (2.5%). The difference in complications derived from Clavien–Dindo grade I. Conclusion: Routine SILCBDE with concomitant cholecystectomy by experienced surgeons is safe and efficacious for elderly patients as for younger patients. Randomized controlled trials are anticipated. [ABSTRACT FROM AUTHOR]

Background: We developed laparoscopic transfistulous bile duct exploration (LTBDE) for Mirizzi syndrome (MS) McSherry type II in September 2011. Then, single-incision LTBDE (SILTBDE) was adopted as a preferred technique since August 2013. This retrospective study aims to analyze the outcome of LTBDE in 7.7 years and to compare SILTBDE with four-incision LTBDE (4ILTBDE). Methods: Seventeen consecutive patients underwent LTBDE for MS McSherry type II from September 2011 to May 2019. Transfistulous removal of the impacted stone(s), choledochoscopic bile duct exploration, and primary closure of the gallbladder remnant were performed without biliary drainage. Results: The sex ratio is 12:5 (male: female) with an average age of 39.4 ± 10.3 (24–56) years. Ten patients (58.8%) had their diagnoses of MS established by preoperative imaging. According to the Csendes classification, three type II (17.6%), nine type III (52.9%), and five type IV (29.4%) were identified. The operative time was 264.8 ± 60.3 min (156–358 min). The stone clearance rate was 100%. The postoperative hospital stay was 4.7 ± 1.9 (2–10) days. No procedure was converted to an open operation. Two postoperative transient hyperamylasemia (11.8%) and one superficial wound infection (5.9%) occurred and all recovered well under conservative treatment (Clavien-Dindo grade I). During an average 2.2-year follow-up period, no biliary stricture or stone recurrence occurred. No significant difference exists between the SILTBDE and 4ILTBDE groups. Nevertheless, an insignificant trend of shorter postoperative hospital stay was observed in the former. A diagnosis of MS Csendes type IV implicates prolonged total and postoperative hospital stays (p < 0.01). Conclusions: LTBDE is safe and efficacious for MS McSherry type II. It provides a simple solution for various types of MS and avoids undesirable complications following bilioenteric anastomosis. SILTBDE is comparable to 4ILTBDE for selected patients. Patients with MS Csendes type IV need more time to recover after surgery. [ABSTRACT FROM AUTHOR]

Background: Most liver resections are currently performed using an open approach. Robotic hepatectomy has been suggested as a safe and effective approach for hepatocellular carcinoma; however, studies regarding oncological and surgical outcomes are still limited. Accordingly, we performed this study to compare the surgical and oncological outcomes between robotic and open approaches.Methods: Between June, 2013 and July, 2016, a total of 63 HCC patients undergoing robotic hepatectomy, and 177 patients undergoing open hepatectomy were included in this study to assess the surgical and oncological outcomes after hepatectomy. The data of demographic, clinical features, hepatitis profile, tumor characters, TNM stage, surgical type, pathological outcomes, and postoperative results were collected prospectively and analyzed retrospectively.Results: The demographic and clinical features of patients with HCC in both groups were statistically comparable. The robotic group had longer operative times (296 ± 84 vs. 182 ± 51 min, p = 0.032). The postoperative complications rate was slightly lower in the robotic group (11.1 vs. 15.3%, p = 0.418). The rate of Ro resection was similar in both groups (93.7 vs. 96%, p = 0.56). The length of hospital stay was significantly shorter in the robotic group (6.21 ± 2.06 vs. 8.18 ± 6.99 days, p = 0.001). The overall recurrence rate of HCC was lower in the robotic group (27 vs. 37.3%, p = 0.140). The 1, 2, 3 year disease-free survival rates were 72.5, 64.3, and 61.6%, respectively, for the open group, while they were 77.8, 71.9, and 71.9%, respectively, for the robotic group, (p = 0.325). The 1, 2, 3 year overall survival rates were 95.4, 92.3, and 92.3%, respectively, for the open group, while they were 100, 97.7, and 97.7%, respectively, for the robotic group (p = 0.137).Conclusion: Robotic surgery is a safe and feasible procedure for liver resection in selected patients. The oncological and surgical outcomes of robotic hepatectomy were comparable to open surgery. The robotic hepatectomy carried significantly shorter length of hospital stay. [ABSTRACT FROM AUTHOR]

A new one-pot synthetic methodology has been developed to construct the triazole-linked urea derivatives. In the same step, triazole forms from azide and alkyne via click reaction and urea forms from addition reaction of amines and isocyanates. The notable features of this work include wide substrate scope, atom economy, environmental friendliness, and easily accessible starting materials. The preliminary biological screening of synthesized compounds show promising cytotoxic activity in basal cell carcinoma (BCC) cell lines. [ABSTRACT FROM PUBLISHER]

The development of effective adjuvant is the key factor to boost the immunogenicity of tumor cells as a tumor vaccine. In this study, we expressed membrane-bound granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-18 (IL-18) as adjuvants in tumor cells to stimulate immune response. B7 transmembrane domain fused GM-CSF and IL-18 was successfully expressed in the cell membrane and stimulated mouse splenocyte proliferation. Co-expression of GM-CSF and IL-18 reduced tumorigenesis (P<0.05) and enhanced tumor protective efficacy (P<0.05) significantly in comparison with GM-CSF alone. These results indicated that the combination of GM-CSF andIL-18 will enhance the immunogenicity of a cell-based anti-tumor vaccine. This membrane-bound approach can be applied to other cytokines for the development of novel vaccine strategies. [ABSTRACT FROM AUTHOR]

Aim Hairy/enhancer-of-split related with YRPW motif-like ( HEYL) protein was first identified as a transcriptional repressor. It is a downstream gene of the Notch and transforming growth factor-β pathways. Little is known about its role in the pathogenesis of hepatocellular carcinoma ( HCC). Methods Eighty surgically resected paired HCC and adjacent non-cancerous tissues were analyzed for HEYL expression by reverse transcription quantitative polymerase chain reaction ( RT- qPCR) and immunohistochemistry ( IHC). HCC cells were transfected with pHEYL- EGFP vector to overexpress the HEYL gene or infected with specific sh HEYL lentiviral vector to silence HEYL gene expression. HEYL expressional analysis and functional characterization were assessed by 3-(4 5-dimethylthiazol-2-yl)-2 5-diphenyltetrazolium bromide assays, flow cytometry, RT- qPCR, western blotting and methylation-specific PCR. Results We determined that HEYL expression was inactivated in more than 75% of HCC. In addition, overexpression of HEYL in SK-Hep 1 cells caused apoptosis by the cleavage of caspase 3 and poly ( ADP-ribose) polymerase. We discovered that HEYL apoptosis was preceded by serine 15 phosphorylation and accumulation of P53. Molecular analysis revealed that HEYL overexpression led to increased p16, p19, p21, p27 and Bad protein expression, and reduced c- Myc, Bcl-2 and Cyclin B1 expression. Epigenetic silencing of HEYL expression by DNA hypermethylation in HCC directly correlated with loss of HEYL expression in HCC. Conclusion HEYL is frequently downregulated by promoter methylation in HCC. HEYL may be a tumor suppressor of liver carcinogenesis through upregulation of P53 gene expression and activation of P53-mediated apoptosis. [ABSTRACT FROM AUTHOR]

Abstract: The objective was to investigate the upstream apoptotic mechanisms that were triggered by a styrylpyrone derivative, goniothalamin (GTN), in tumor protein p53 (TP53)-positive and -negative hepatocellular carcinoma (HCC)-derived cells. Effects of GTN were evaluated by the flow cytometry, alkaline comet assay, immunocytochemistry, small-hairpin RNA interference, mitochondria/cytosol fractionation, quantitative reverse transcription-polymerase chain reaction, immunoblotting analysis and caspase 3 activity assays in two HCC-derived cell lines. Results indicated that GTN triggered phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1, also known as NOXA)-mediated apoptosis via TP53-dependent and -independent pathways. In TP53-positive SK-Hep1 cells, GTN furthermore induced TP53 transcription-dependent and -independent apoptosis. After GTN treatment, accumulation of reactive oxygen species, formation of DNA double-strand breaks, transactivation of TP53 and/or PMAIP1 gene, translocation of TP53 and/or PMAIP1 proteins to mitochondria, release of cytochrome c from mitochondria, cleavage of caspases and induction of apoptosis in both cell lines were sustained. GTN might represent a novel class of anticancer drug that induces apoptosis in HCC-derived cells through PMAIP1 transactivation regardless of the status of TP53 gene. [Copyright &y& Elsevier]

Simple Summary: Tumor suppressor genes are critical in the control of many biological functions. They can be classified based on their roles in proliferation, cell-cycle progression, DNA repair/damage, and crucial signaling functions, including apoptosis, autophagy, and necrosis. The absence of functional tumor suppressor genes entails a higher risk of dysfunction of cell growth, differentiation, cell death, and cancer development. Loss of function or mutations of such genes has been identified in many types of cancer, such as breast, bladder, colorectal, head and neck, lung, ovarian, uterine, and pancreatic cancers. Familial cancer syndromes, such as Li–Fraumeni syndrome, are associated with loss of TP53 function. Extensive studies have been carried out to clarify the roles of the products of these genes, as well as their mechanistic link to cancers, to identify novel targets for specific cancer types. Here, we introduce the roles of tumor suppressor gene products in pancreatic cancer development and its therapeutics for tumorigenesis prevention. The high mortality of pancreatic cancer is attributed to the insidious progression of this disease, which results in a delayed diagnosis and advanced disease stage at diagnosis. More than 35% of patients with pancreatic cancer are in stage III, whereas 50% are in stage IV at diagnosis. Thus, understanding the aggressive features of pancreatic cancer will contribute to the resolution of problems, such as its early recurrence, metastasis, and resistance to chemotherapy and radiotherapy. Therefore, new therapeutic strategies targeting tumor suppressor gene products may help prevent the progression of pancreatic cancer. In this review, we discuss several recent clinical trials of pancreatic cancer and recent studies reporting safe and effective treatment modalities for patients with advanced pancreatic cancer. [ABSTRACT FROM AUTHOR]

30973388 3 Chatzizacharias NA, Dajani K, Koong JK, Jah A. The role of the single incision laparoscopic approach in liver and pancreatic resectional surgery. The high lymph node retrieval numbers and low lymph node ratios (22, 15, and 24; 0.091, 0.067, and 0.042 on Patient No. 1, 2, and 3 respectively) revealed the qualified D2 lymph node dissections during the SILPD.[4] A low threshold of procedure conversion should be kept in mind for patient and oncologic safety. Keywords: Distal cholangiocarcinoma; Single-incision laparoscopic surgery; Pancreatic ductal adenocarcinoma; Pancreatoduodenectomy; Whipple procedure EN Distal cholangiocarcinoma Single-incision laparoscopic surgery Pancreatic ductal adenocarcinoma Pancreatoduodenectomy Whipple procedure 2402 2408 7 11/10/22 20221101 NES 221101 Previous Presentation: This report was presented in part at the 32 nd World Congress of International Association of Surgeons, Gastroenterologists and Oncologists (IASGO) in Taipei, Taiwan, November 20-22, 2021. 5 A In a multi-incision laparoscopic surgery, the instruments make a loop with transverse and vertical movements. [Extracted from the article]

For the first time, a metal-free alcohol-azide cycloaddition is presented. [ABSTRACT FROM AUTHOR]

Gastric cancer (GC) organoids are frequently used to examine cell proliferation and death as well as cancer development. Invasion/migration assay, xenotransplantation, and reactive oxygen species (ROS) production were used to examine the effects of antioxidant drugs, including perillaldehyde (PEA), cinnamaldehyde (CA), and sulforaphane (SFN), on GC. PEA and CA repressed the proliferation of human GC organoids, whereas SFN enhanced it. Caspase 3 activities were also repressed on treatment with PEA and CA. Furthermore, the tumor formation and invasive activities were repressed on treatment with PEA and CA, whereas they were enhanced on treatment with SFN. These results in three-dimensional (3D)-GC organoids showed the different cancer development of phase II enzyme ligands in 2D-GC cells. ROS production and the expression of TP53, nuclear factor erythroid 2-related factor (NRF2), and Jun dimerization protein 2 were also downregulated on treatment with PEA and CA, but not SFN. NRF2 knockdown reversed the effects of these antioxidant drugs on the invasive activities of the 3D-GC organoids. Moreover, ROS production was also inhibited by treatment with PEA and CA, but not SFN. Thus, NRF2 plays a key role in the differential effects of these antioxidant drugs on cancer progression in 3D-GC organoids. PEA and CA can potentially be new antitumorigenic therapeutics for GC. [ABSTRACT FROM AUTHOR]

A novel method for the preparation of (Z)-isomers of 4-(iodomethylidene)-1,3-benzoxazines (II) via 6-exo-dig cyclization is reported. [ABSTRACT FROM AUTHOR]

[Display omitted] Aryl hydrocarbon receptor (AHR) and nuclear factor-erythroid 2-related factor 2 (NRF2) can regulate a series of genes encoding the detoxifying phase I and II enzymes, via a signaling crosstalk known as the "AHR–NRF2 gene battery". The chromatin transcriptional regulator Jun dimerization protein 2 (JDP2) plays a central role in the transcription of AHR gene in response to the phase I enzyme ligand 2,3,7,8-tetrachlorodibenzo- p -dioxin. It forms a transcriptional complex with AHR–AHR nuclear translocator (ARNT) and NRF2-small musculoaponeurotic fibrosarcoma proteins (sMAF), which are then recruited to the respective cis -elements, such as dioxin response elements and antioxidant response elements, respectively, in the AHR promoter. Here, we present a revised description of the AHR–NRF2 gene battery as the AHR–NRF2–JDP2 gene battery for transactivating the AHR promoter by phase I enzyme ligands. The chromatin regulator JDP2 was found to be involved in the movement of AHR–NRF2 complexes from the dioxin response element to the antioxidant response element in the AHR promoter, during its activation in a spatiotemporal manner. This new epigenetic and chromatin remodeling role of AHR–NRF2–JDP2 axis is useful for identifying new therapeutic targets for various diseases, including immunological response, detoxification, development, and cancer-related diseases. [ABSTRACT FROM AUTHOR]

Regorafenib is a multikinase inhibitor that was approved by the US Food and Drug administration in 2017. Cancer stem cells (CSCs) are a small subset of cancer-initiating cells that are thought to contribute to therapeutic resistance. The forkhead box protein M1 (FOXM1) plays an important role in the regulation of the stemness of CSCs and mediates resistance to chemotherapy. However, the relationship between FOXM1 and regorafenib resistance in liver cancer cells remains unknown. We found that regorafenib-resistant HepG2 clones overexpressed FOXM1 and various markers of CSCs. Patients with hepatocellular carcinoma also exhibited an upregulation of FOXM1 and resistance to regorafenib, which were correlated with a poor survival rate. We identified a close relationship between FOXM1 expression and regorafenib resistance, which was correlated with the survival of patients with hepatocellular carcinoma. Thus, a strategy that antagonizes FOXM1–CD44 signaling would enhance the therapeutic efficacy of regorafenib in these patients. [ABSTRACT FROM AUTHOR]

Stomach cancer has a high mortality, which is partially caused by an absence of suitable biomarkers to allow detection of the initiation stages of cancer progression. Thus, identification of critical biomarkers associated with gastric cancer (GC) is required to advance its clinical diagnoses and treatment. Recent studies using tracing models for lineage analysis of GC stem cells indicate that the cell fate decision of the gastric stem cells might be an important issue for stem cell plasticity. They include leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5+), Cholecystokinin receptor 2 (Cckr2+), and axis inhibition protein 2 (Axin2+) as the stem cell markers in the antrum, Trefoil Factor 2 (TFF2+), Mist1+ stem cells, and Troy+ chief cells in the corpus. By contrast, Estrogen receptor 1 (eR1), Leucine-rich repeats and immunoglobulin-like domains 1 (Lrig1), SRY (sex determining region Y)-box 2 (Sox2), and B lymphoma Mo-MLV insertion region 1 homolog (Bmi1) are rich in both the antrum and corpus regions. These markers might help to identify the cell-lineage identity and analyze the plasticity of each stem cell population. Thus, identification of marker genes for the development of GC and its environment is critical for the clinical application of cancer stem cells in the prevention of stomach cancers. [ABSTRACT FROM AUTHOR]

BACKGROUND: Effective prognostic biomarkers and powerful target-therapeutic drugs are needed for improving the treatment of Hepatocellular carcinoma (HCC). OBJECTIVE: This study aimed to evaluate the expression of FOXM1 and Aurora-A and their prognostic value in HCC. METHODS: We determined the differentially expressed genes signature in HCC using the Gene Set Enrichment Analysis (GSEA), and then evaluated the expression of FOXM1 and Aurora-A in TCGA and KMUH cohort. Associations between co-expression of FOXM1 and Aurora-A and clinical variables were calculated. Overall survival (OS) and recurrence-free survival (RFS) were estimated with different FOXM1 and Aurora-A expression status. RESULTS: FOXM1-related gene sets were mostly associated with cell cycle regulation in HCC tissues. We found a positive correlation between the expression of FOXM1 and Aurora-A. Overexpression of FOXM1 and Aurora-A was associated with larger tumor size, advanced stage, higher grade, and double-positive for HBV and HCV. The coordinated overexpression of FOXM1 and Aurora-A was the most significant independent prognostic factor for OS and RFS. Furthermore, the concomitant high expression of FOXM1 and Aurora-A predicted the worst OS of sorafenib-treated patients with HCC. CONCLUSIONS: The co-expression of FOXM1 and Aurora-A could be a reliable biomarker to predict the sorafenib response and prognosis of HCC patients. [ABSTRACT FROM AUTHOR]

Mixed corticomedullary tumor is an adrenal tumor intermixed with cortical and medullary cells. It is extremely rare with unclear tumorigenesis. We reported a 32-year-old female, manifested with typical Cushing's syndrome and hypertension, to be diagnosed with right huge adrenal mixed corticomedullary tumor (8.8 cm). Right adrenalectomy was done to document the tumor intimately admixed with adrenal cortical adenoma and pheochromocytoma by biochemistry and immunohistochemistry. A case-control study was designed to explore the tumorigenesis of mixed corticomedullary tumor by whole exome sequencing. Expression of the stemness markers was controlled by a tissue array of 80 adrenal tumors. Overall, 1559 identical variants coexisted in parts of adrenal cortical adenoma and pheochromocytoma, which mainly (85.8%) originated from germline mutations. These enriched mutations were engaged in stemness control, coherent with substantial expression of the stemness markers (SOX2, CD44 and OCT4) in both parts. The differential stemness expressions were demonstrated in other adrenal tumors as well. The germline mutations were also enriched in signaling involving cancer proliferation, hypoxia inducible factor-1, focal adhesion and extracellular matrix receptor interaction. Somatic mutations affecting mitogen-activated protein kinase signaling, glycolysis and the citrate cycle were found in some tumor elements. This is the first study to verify the rare mixed corticomedullary tumor by molecular and genetic evidence to link with its phenotype. Germline mutations involving the stemness regulation and cancer proliferative signaling may drive intermixed tumor formation. Somatic mutations related to glycolysis and the citrate cycle may contribute to greater tumor outgrowth. [ABSTRACT FROM AUTHOR]

The ability to control the transition from an undifferentiated stem cell to a specific cell fate is one of the key techniques that are required for the application of interventional technologies to regenerative medicine and the treatment of tumors and metastases and of neurodegenerative diseases. Reprogramming technologies, which include somatic cell nuclear transfer, induced pluripotent stem cells, and the direct reprogramming of specific cell lineages, have the potential to alter cell plasticity in translational medicine for cancer treatment. The characterization of cancer stem cells (CSCs), the identification of oncogene and tumor suppressor genes for CSCs, and the epigenetic study of CSCs and their microenvironments are important topics. This review summarizes the application of cell reprogramming technologies to cancer modeling and treatment and discusses possible obstacles, such as genetic and epigenetic alterations in cancer cells, as well as the strategies that can be used to overcome these obstacles to cancer research. [ABSTRACT FROM AUTHOR]

Early detection of cancerous cells is crucial for successful treatment, hence active research has been focused on developing biomarkers based biosensors. Herein, we report the use of antibody-functionalized AlGaN/GaN high electron mobility transistor (HEMT) for a fast detection of the prominent tumor marker of carbohydrate antigen 19-9 (CA 19-9). The antibody of CA 19-9 was embedded to the sensing gate area of the HEMT device through self-assembled monolayer (SAM) technique. The source-drain current showed a swift response when the target CA 19-9 in a buffer solution at analytic concentrations was added to the antibody-immobilized surface. The lowest detectable concentration was 15 U/mL suitable for clinical detection of pancreatic cancer. Our experimental results clearly demonstrate the possibility of development of a portable HEMT sensor for rapid cancer screening and post-treatment tracking. [ABSTRACT FROM AUTHOR]

A new class of pyrrolo[2,1- c ][1,4]benzodiazepine-Gallic hybrid agents (PBD-GA) conjugated through alkyl spacers has been designed and synthesized. The combination of these two core pharmacophores with modification in the C-8 position of the PBD ring with alkyl spacers afforded oxygen-tethered compounds 5a – 5d and amide-tethered analogues 11a – 11d with improved anticancer activity for two melanoma cell lines, A375 and RPMI7951, differing in their p53 status. The agents 5a–5d were cytotoxic in melanoma compared to agents 11a–11d . In particular, compounds 5b and 5c were found to possess the most potent activity compared with other hybrid agents and were proved with the help of quantitative structure activity relationship studies (QSAR). These PBD conjugates caused S phase arrest for the A375 cell line via increased reactive oxygen species (ROS) generation, deoxyribonucleic acid (DNA) damage, ataxia telangiectasia mutated (ATM)/ATM-Rad3-related (ATR) and checkpoint kinases 1 (Chk1) activation. Moreover, the PBD-GA induced A375 apoptotic cell death followed through p53 (ATM downstream target) increase, B-cell leukemia-xL (Bcl-xL) and mitochondrial membrane potential (ΔΨ mt ) decrease, cytochrome c release, and caspase-3/Poly Adp Ribose Polymerase (PARP) cleavage. On the other hand, mutant p53 RPMI7951 cell death occurred by PBD-GA-mediated mitochondria- and caspase-dependent pathways via lysosomal membrane permeabilization (LMP), but not through p53 signaling. Finally, compound 5b was shown to reduce murine melanoma size in a mouse model. These results suggest that the PBD-GA could be used as a useful chemotherapeutic agent in melanoma with activated p53 or mutant p53. [ABSTRACT FROM AUTHOR]

A mildand efficient synthetic development of 2-arylbenzothiazoles 5mediated by ceric ammonium nitrate (CAN) via intramolecularcyclization of N-phenyl-thiobenzamides 4was achieved. Further compounds 5were reduced to correspondingamines 6, and their photodynamic therapy (PDT) effectwas evaluated on malignant human melanoma A375 cells. Amine 6lplus ultraviolet A (UVA) induced caspase-3 activity, poly(ADP-ribose)polymerasecleavage, M30 positive CytoDeath staining, and subsequent apoptoticcell death. Our data disclosed that treatment of A375 cells with 6lplus UVA resulted in a decrease in mitochondrial membranepotential (ΔΨmt), oxidative phosphorylationsystem (OXPHOS) subunits, and adenosine triphosphate (ATP) but anincrease in mitochondrial DNA 4977-bp deletion via reactive oxygenspecies (ROS) generation. Transmission electron microscopy (TEM) observationsalso showed major ultrastructural alterations of mitochondria. Additionally, 6lplus UVA was also shown to reduce murine melanoma sizein a mouse model. The present study supports the hypothesis that 6l-PDT may serve as a potential ancillary modality for thetreatment of melanoma. [ABSTRACT FROM AUTHOR]

Novelbicyclic[1,2,3]triazoles (4, 7, 11, 15) have been synthesized using a one-potmetal free strategy with high structural diversity as photoprotectiveagents, and their effect on UVA-induced senescence in human dermalfibroblast cells (FB) and the associated mechanism are delineated. 11dplus UVA can induce a decrease in reactive oxygen species(ROS) production and senescence-associated β-galactosidase (SA-β-gal)activity but an increase in adenosine triphosphate (ATP) synthesisand mitochondrial membrane potential (ΔΨmt).The mRNA levels of six senescence-associated genes, matrix metalloproteinase-1(MMP-1), was decreased, while elastin, procollagen I type I, fibronectin,COL1α1, and tissue inhibitor of metalloproteinase-1 (TIMP-1)were increased. 11dplus UVA also decreased MMP-1 andincreased TIMP-1 protein levels. Additionally, the thickness of themurine dorsal skin and epidermis, by UVA, was decreased by topical 11dtreatment. Our results indicate that bicyclic[1,2,3]triazolesprotect UVA-induced senescence-like characteristics in FB cells, whichmay provide potential prevention against photoaging. [ABSTRACT FROM AUTHOR]

Summary: Peribiliary cysts are cystic dilatations of the peribiliary glands, which are normal structures of the bile ducts. There are most often multiple lesions in patients presenting with obstructive jaundice. Most patients have underlying liver diseases. In our patient, obstructive jaundice was first noted. There were no associated liver diseases. Imaging studies showed a solitary hypodense lesion in the hilar area, and the first impression was of a Klatskin tumor. During the operation, a peribiliary cyst was noted and, after fenestration of the cyst, the obstructive jaundice subsided. There are, to the best of our knowledge, only two cases such as ours in the English-language literature. [Copyright &y& Elsevier]

Abstract: Background: The aim of this prospective randomized study was to investigate the necessity and impact of prophylactic antibiotics on postoperative infection complications in elective laparoscopic cholecystectomy. Methods: At the time of induction of anesthesia, group A patients (n = 141) received 1 g cefazolin, and group B patients (control; n = 136) received 10 mL isotonic sodium chloride solution. Patients’ characteristics and general operative outcomes were compared and analyzed. Results: The overall rate of infection was 1.1% for total 277 patients (0.7% for group A patients and 1.5 % for group B patients). No significant difference in infection complications was found between these 2 groups. Also any risk factors contributing to infection complications could not be found. Conclusions: We do not recommend the use of prophylactic antibiotics in elective laparoscopic cholecystectomy because they will not decrease the already-low rate of postoperative infectious complications. [Copyright &y& Elsevier]

Background: SMAD4 is a gastrointestinal malignancy-specific tumor suppressor gene found mutated in one third of colorectal cancer specimens and half of pancreatic tumors. SMAD4 inactivation by allelic deletion or intragenic mutation mainly occurs in the late stage of human pancreatic ductal adenocarcinoma (PDAC). Various studies have proposed potential SMAD4-mediated anti-tumor effects in human malignancy; however, the relevance of SMAD4 in the PDAC molecular phenotype has not yet been fully characterized.Methods: The AsPC-1, CFPAC-1 and PANC-1 human PDAC cell lines were used. The restoration or knockdown of SMAD4 expression in PDAC cells were confirmed by western blotting, luciferase reporter and immunofluorescence assays. In vitro cell proliferation, xenograft, wound healing, quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR), Western blotting, and immunohistochemistry analysis were conducted using PDAC cells in which SMAD4 was either overexpressed or knocked down.Results: Here, we report that re-expression of SMAD4 in SMAD4-null PDAC cells does not affect tumor cell growth in vitro or in vivo, but significantly enhances cells migration in vitro. SMAD4 restoration transcriptionally activates the TGF-β1/Nestin pathway and induces expression of several transcriptional factors. In contrast, SMAD4 loss in PDAC leads to increased expression of E-cadherin, vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR) and CD133. Furthermore, SMAD4 loss causes alterations to multiple kinase pathways (particularly the phosphorylated ERK/p38/Akt pathways), and increases chemoresistance in vitro. Finally, PDAC cells with intact SMAD4 are more sensitive to TGF-β1 inhibitor treatment to reduced cell migration; PDAC cells lacking SMAD4 showed decreased cell motility in response to EGFR inhibitor treatment.Conclusions: This study revealed the molecular basis for SMAD4-dependent differences in PDAC with the aim of identifying the subset of patients likely to respond to therapies targeting the TGF-β or EGFR signaling pathways and of identifying potential therapeutic interventions for PDAC patients with SMAD4 defects. [ABSTRACT FROM AUTHOR]

Background: The widespread use of phthalates as plasticizers has raised public health concerns regarding their adverse effects, including an association with cancer. Although animal investigations have suggested an association between phthalate exposure and hepatocellular carcinoma, the mechanisms are unknown.Methods: The hepatocellular carcinoma cell line Huh7 was treated with benzyl butyl phthalate (BBP), and then analyzed by total internal reflection fluorescence microscopy, confocal microscopy and double immunogold transmission electron microscopy. Following BBP treatment, mRNA levels were measured by RT-PCR, protein levels were measured using western blot, and vascular endothelial growth factor levels were measured by an enzyme-linked immunosorbent assay. Cell migration and invasion assays were evaluated by transwell, and angiogenesis were performed by a tube formation assay. Nude mice were used to investigate metastasis and angiogenesis in vivo.Results: BBP affected hepatocellular carcinoma progression through the aryl hydrocarbon receptor (AhR) and that benzyl butyl phthalate (BBP) stimulated AhR at the cell surface, which then interacted with G proteins and triggered a downstream signaling cascade. BBP activated AhR through a nongenomic action involving G-protein signaling rather than the classical genomic AhR action. BBP treatment promoted cell migration and invasion in vitro and metastasis in vivo via the AhR/Gβ/PI3K/Akt/NF-κB pathway. In addition, BBP induced both in vitro and in vivo angiogenesis through the AhR/ERK/VEGF pathway.Conclusions: These findings suggest a novel nongenomic AhR mechanism involving G-protein signaling induced by phthalates, which contributes to tumor progression of hepatocellular carcinoma. [ABSTRACT FROM AUTHOR]