IntroductionDysregulation of the insulin-like growth factor-1 receptor (IGF-1R)/phosphatidylinositol-3-kinase (PI3K)/Akt pathway was shown to correlate with breast cancer disease progression. Cancer stem cells are a subpopulation within cancer cells that participate in tumor initiation, radio/chemoresistance and metastasis. In breast cancer, breast cancer stem cells (BCSCs) were identified as CD24-CD44+ cells or cells with high intracellular aldehyde dehydrogenase activity (ALDH+). Elucidation of the role of IGF-1R in BCSCs is crucial to the design of breast cancer therapies targeting BCSCs.MethodsIGF-1R expression in BCSCs and noncancer stem cells sorted from xenografts of human primary breast cancers was examined by fluorescence-activated cell sorting (FACS), western blot analysis and immunoprecipitation. The role of IGF-1R in BCSCs was assessed by IGF-1R blockade with chemical inhibitor and gene silencing. Involvement of PI3K/Akt/mammalian target of rapamycin (mTOR) as the downstream pathway was studied by their phosphorylation status upon IGF-1R inhibition and the effects of chemical inhibitors of these signaling molecules on BCSCs. We also studied 16 clinical specimens of breast cancer for the expression of phosphor-Akt in the BCSCs by FACS.ResultsExpression of phosphorylated IGF-1R was greater in BCSCs than in non-BCSCs from xenografts of human breast cancer, which were supported by western blot and immunoprecipitation experiments. The sorted IGF-1R-expressing cells displayed features of cancer stem/progenitors such as mammosphere formation in vitro and tumorigenicity in vivo, both of which were suppressed by knockdown of IGF-1R. A specific inhibitor of the IGF-1R, picropodophyllin suppressed phospho-AktSer473 and preferentially decreased ALDH+ BCSC populations of human breast cancer cells. Furthermore, picropodophyllin inhibited the capacity of CD24-CD44+ BCSCs to undergo the epithelial-mesenchymal transition process with downregulation of mesenchymal markers. Inhibitors of signal molecules downstream of IGF-1R including PI3K/Akt/mTOR also reduced the ALDH+ population of breast cancer cells. Furthermore, the mTOR inhibitor, rapamycin, suppressed BCSCs in vitro and in vivo.ConclusionOur data support the notion that IGF-1R is a marker of stemness, and IGF-1R and its downstream PI3K/Akt/mTOR pathway are attractive targets for therapy directed against breast cancer stem/progenitors.

Approximately half (42%) of SAP deaths occur within 14 d and most were due to multiple organ failure. The late deaths of SAP were mostly due to infected necrosis.

Gallbladder torsion is a rare, acute abdominal disease. It was first reported by Wendell in 1898. Since then, only 500 cases have been reported. Gallbladder torsion occurs in all age groups, although it usually appears in the latter stages of life. The occurrence ratio between women and men is 3:1. Most cases are diagnosed during surgery. The main treatment is surgical detorsion and cholecystectomy. Despite progress in radiologic imaging diagnosis, it is not easy to obtain a precise preoperative diagnosis of gallbladder torsion. In previous reports, only 9.8% of all gallbladder torsion cases were diagnosed preoperatively. We present a case of acute body-neck gallbladder torsion in an elderly man, and we review the radiologic findings of magnetic resonance imaging, computed tomography, and ultrasonography. The radiologic findings in the present case were helpful in obtaining a preoperative diagnosis of gallbladder torsion. The diagnosis was confirmed by T2-weighted magnetic resonance images, which showed an intra-gallbladder segment located between the body and neck of the gallbladder, with a notable crease within this segment.

Overexpression of SH2-containing-5 0 -inositol phosphatase-2 (SHIP2) correlates with poor survival in breast cancer. However, its role in breast cancer stem cells (BCSCs) remains unclear. Here, we showed that the percentage of SHIP2 1 cells was positively correlated with that of CD24 2 CD44 1 cells in 60 breast cancer specimens. Among 20 estrogen receptor (ER)-negative samples, 17 had greater SHIP2 expression in CD24 2 CD44 1 subpopulation than the remaining subpopulation. Data mining of microarray analysis of 295 breast tumors showed a significant correlation of higher SHIP2 expression with distant metastasis. Examination of patient-derived mouse xenografts revealed that SHIP2 protein and its tyrosine 1135 phosphorylation were significantly higher in BCSCs, identified as CD24 2 CD44 1 or aldehyde dehydrogenase (ALDH 1 ), than non-BCSCs. SHIP2 silencing or inhibitor of SHIP2 phosphatase significantly decreased mammosphere-forming efficiency, ALDH 1 subpopulation in vitro and tumorigenicity of BCSCs in vivo. Overexpression of SHIP2 enhanced the expression of epithelial-mesenchymal transition markers including vimentin (VIM), which was mainly expressed in ER-negative breast cancer cells with higher level in mammospheres than monolayer culture. Ablation of c-Jun N-terminal kinase 1 (JNK1), JNK2, or VIM diminished the increased ALDH 1 population and tumorigenicity, induced by SHIP2 overexpression. BCSCs displayed greater expression of phospho-JNK than nonBCSCs and silencing of JNK suppressed SHIP2-mediated upregulation of VIM. Furthermore, SHIP2 overexpression enhanced Akt activation, but Akt inhibition failed to influence SHIP2-induced phospho-JNK/VIM upregulation. In conclusion, SHIP2 plays a key role in BCSCs of ERnegative breast cancers through activation of Akt and JNK with upregulation of VIM and may serve as a target for therapy directed at BCSCs.

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In this study and literature review, patients had laparoscopic repair with a smooth recovery. Laparoscopy provides good surgical exposure, allowing easy repositioning of the herniated content and a smooth repair of the defect without the morbidity of laparotomy. For CTDH, with caution, we can apply this technique with an acceptable result.

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