Pelvic Abscess after Cesarean Section Treated with Laparoscopic Drainage.

Cesarean section (CS), the rate of which is increasing worldwide, may be associated with complications. Although pelvic abscess after CS is rare, it is difficult to treat. We herein report two cases of pelvic abscess treated laparoscopically after CS. The abscesses of the patients were located in the pouch of Douglas and the uterine scar after CS, respectively. Several days after CS, the patients presented with lower abdominal pain and fever. Laparoscopic drainage was performed because imaging revealed a pelvic abscess that was not amenable to drainage through interventional radiology. The patients recovered from infection and were discharged four days after drainage.

A case of pyometra with a colouterine fistula due to rectal cancer presenting as acute abdomen.

Pyometra usually develops in elderly women, and it can be caused by various etiologies. We describe a rare case of pyometra with a colouterine fistula due to rectal cancer presenting as acute abdomen. A 67-year-old woman with purulent vaginal discharge and abdominal distension was referred to our hospital for suspected pyometra. Because the vaginal echogram showed pyometra at her initial medical examination, drainage was performed. Her symptoms subsequently disappeared temporarily, but 4 months later, she developed acute abdomen. The computed tomography scan showed a pelvic mass with expansion of the intestine. The patient underwent en bloc resection of the mass. Histopathologic analysis of the tumor showed rectal cancer with invasion of the uterus and ileum, and a colouterine fistula. Although pyometra due to a colouterine fistula is a very rare condition, the incidence of associated malignancy is considerable. Physicians should be aware of this potential presentation of colorectal cancer.

ZIC5 Drives Melanoma Aggressiveness by PDGFD-Mediated Activation of FAK and STAT3.

Insights into mechanisms of drug resistance could extend the efficacy of cancer therapy. To probe mechanisms in melanoma, we performed siRNA screening of genes that mediate the development of neural crest cells, from which melanocytes are derived. Here, we report the identification of ZIC5 as a mediator of melanoma drug resistance. ZIC5 is a transcriptional suppressor of E-cadherin expressed highly in human melanoma. ZIC5 enhanced melanoma cell proliferation, survival, drug resistance, in vivo growth and metastasis. Microarray analysis revealed that ZIC5 downstream signaling included PDGFD and FAK activation, which contributes to drug resistance by enhancing STAT3 activation. Silencing of ZIC5 or PDGFD enhanced the apoptotic effects of BRAF inhibition and blocked survival of melanoma cells resistant to BRAF inhibitors. Furthermore, inhibition of FAK or STAT3 suppressed expression of ZIC5, which was positively regulated by PDGFD, FAK, and STAT3 in a positive feedback loop. Taken together, our results identify ZIC5 and PDGFD as candidate therapeutic targets to overcome drug resistance in melanoma. Cancer Res; 77(2); 366-77. ©2016 AACR.

Phospholipase Cδ1 induces E-cadherin expression and suppresses malignancy in colorectal cancer cells.

Colorectal cancer (CRC) is one of the most common causes of cancer-related deaths worldwide, and Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations in CRC predict the ineffectiveness of EGF receptor-targeted therapy. Previous transcriptional microarray analysis suggests the association between phospholipase Cδ1 (PLCδ1) expression and KRAS mutation status in CRC. However, both the roles and the regulatory mechanisms of PLCδ1 in CRC are not known. Here, we found that the expression of PLCδ1, one of the most basal PLCs, is down-regulated in CRC specimens compared with normal colon epithelium by immunohistochemistry. Furthermore, we examined the roles of PLCδ1 in CRC cell lines that harbor an activating KRAS mutation. Ectopic expression of PLCδ1 in CRC cells induced the expression of E-cadherin, whereas knockdown of PLCδ1 repressed the expression of E-cadherin. Moreover, the overexpression of PLCδ1 suppressed the expression of several mesenchymal genes and reduced cell motility, invasiveness, and in vivo tumorigenicity of SW620 CRC cells. We also showed that PLCδ1 expression is repressed by the KRAS/mitogen-activated protein kinase kinase (MEK) pathway. Furthermore, PLCδ1 suppressed the phosphorylation of extracellular signal-regulated kinase (ERK)1/2 through E-cadherin induction in CRC cells, suggesting the presence of a negative regulatory loop between KRAS/MEK/ERK signaling and PLCδ1. These data indicate that PLCδ1 has tumor-suppressive functions in CRC through E-cadherin induction and KRAS/MEK/ERK signal attenuation.

Identification of novel small compounds that restore E-cadherin expression and inhibit tumor cell motility and invasiveness.

Tumor dissemination and invasive behavior are associated with a majority of cancer-related mortality cases. Loss of E-cadherin, which is caused by several tumor-promoting factors, is associated with metastasis and poor prognosis in many neoplasms. In this study, we aimed to identify small molecule compounds that restore the expression of E-cadherin, because these molecules are most likely to suppress tumor malignancy by restoring E-cadherin function and/or by inhibiting signals that suppress E-cadherin expression. Here, we developed a fluorescence screen system based on E-cadherin expression. A pilot drug library screen revealed that methotrexate (MTX) strongly induces E-cadherin expression in a colorectal cancer cell line, SW620. From the screen for 9600 compounds, we identified 9 hit compounds, which restored the expression of E-cadherin in SW620 and/or a melanoma cell line, SK-MEL-28. We confirmed that MTX and the other identified compounds transcriptionally promote E-cadherin expression. Among these, 2 compounds suppressed migration/invasion capacity in colorectal cancer cells and 3 in melanoma cells. A compound reduced SW620 migration and invasion with subtle effects on cell viability in SW620, SK-MEL-28, and a non-tumor cell line, HaCaT, with decrease in AKT and ERK1/2 protein levels. One of the other compounds reduced SK-MEL-28 cell migration and invasion and affected the viability only of SW620 and SK-MEL-28 cells but not HaCaT cells. These results suggest that these compounds would be attractive lead molecules as anti-metastasis agents.

A NIRS-based brain-computer interface system during motor imagery: system development and online feedback training.

A brain-computer interface (BCI) to detect motor imagery from cerebrum hemodynamic data measured by NIRS (near-infrared spectroscopy) was constructed and the effect of the online feedback training for subjects was evaluated. Concentrations of Oxy- and deOxy-hemoglobin in the motor cortex during motor imagery of subject's right hand was measured by 52-channel NIRS system, and the mean magnitude of measured signal near C3 in the International 10-20 System was visually fed back online to the subject. On two out of three subjects, it was shown that the ratio between the averaged value and the standard deviation over trials (S/N ratio) of Oxy-hemoglobin signal elicited by the imagery of subject's right hand was increased by the 5-day online feedback training. Detailed investigation of the effect of the online feedback training on brain activities was left for further study.