Light Bulb Procedure for the Treatment of Tarsal Navicular Osteonecrosis After Failed Percutaneous Decompression: A Case Report.

Tarsal navicular osteonecrosis in adults is a rare condition with unclear etiology, and the optimal treatment has not been established. Here we report a case of tarsal navicular osteonecrosis with a complete course of treatment and comprehensive imaging studies starting at an early stage. A 37-year-old female diagnosed with tarsal navicular osteonecrosis was first treated with percutaneous decompression, but her symptoms persisted postoperatively. The tarsal navicular showed no further collapse, but follow-up magnetic resonance imaging (MRI) at 6 months postoperatively revealed persistent osteonecrotic changes. Debridement of the necrotic bone with preservation of the cortical shell and bone substitute packing for the defect (light bulb procedure) were performed. The symptoms resolved by 3 months postoperatively, and the patient could return to work. At a 6-year follow-up visit, the patient was free of symptoms, and MRI showed remodeling of the tarsal navicular without further collapse.

Claudin-1 is a metastasis suppressor and correlates with clinical outcome in lung adenocarcinoma.

RATIONALE: Claudin (CLDN)-1, a key component of tight junction complexes, was down-regulated in human lung adenocarcinomas. OBJECTIVES: To investigate the clinical significance of CLDN1 expression in patients with lung adenocarcinoma and its role in cancer invasion and metastasis. METHODS: We examined the CLDN1 mRNA expression in tumor specimens from 64 patients with lung adenocarcinoma and protein expression by immunohistochemistry in an independent cohort of 67 patients with lung adenocarcinoma. CLDN1 functions in cancer cell migration, invasion, and metastatic colonization were studied by overexpression and knockdown of CLDN1. Affymetrix microarrays were performed to identify gene expression changes associated with CLDN1 overexpression. MEASUREMENTS AND MAIN RESULTS: We found that low-CLDN1 mRNA expression had shorter overall survival (P = 0.027, log-rank test) in 64 patients with lung adenocarcinoma, and we confirmed by immunohistochemistry that low CLDN1 expression had shorter overall survival (P = 0.024, log-rank test) in an independent cohort of 67 patients with lung adenocarcinoma. Overexpression of CLDN1 inhibited cancer cell dissociation in time-lapse imaging of wound healing, and suppressed cancer cell migration, invasion, and metastasis. Knockdown CLDN1 expression increased cancer cell invasive and metastatic abilities. Affymetrix microarrays identified a panel of genes altered by CLDN1 overexpression. CLDN1 increased expressions of cancer invasion/metastasis suppressors (e.g., connective tissue growth factor [CTGF], thrombospondin 1 [THBS1], deleted in liver cancer 1 [DLC1], occludin [OCLN], zona occludens 1 [ZO-1]) and suppressed expressions of invasion/metastasis enhancers (e.g., secreted phosphoprotein 1 [SPP1], cut-like homeobox 1 [CUTL1], transforming growth factor alpha [TGF-alpha], solute carrier family 2 [faciliated glucose transporter] member 3 [SLC2A3], placental growth factor [PGF]), supporting a role for CLDN1 as an invasion and metastasis suppressor. CONCLUSIONS: CLDN1 is a cancer invasion/metastasis suppressor. CLDN1 is also a useful prognostic predictor and potential drug treatment target for patients with lung adenocarcinoma.

miR-524-5p reduces the progression of the BRAF inhibitor-resistant melanoma.

BRAF inhibitors were approved for the treatment of BRAF-mutant melanoma. However, most patients acquire the resistance to BRAF inhibitors after several months of treatment. miR-524-5p is considered as a tumor suppressor in many cancers, including melanoma. In this study, we investigated the biological functions of miR-524-5p in melanoma with acquired resistance to BRAF inhibitor and evaluated the endogenous miR-524-5p expression as a biomarker for melanoma. The results showed that the expression of miR-524-5p was 0.481-fold lower in melanoma tissues (n = 117) than in nevus tissues (n = 40). Overexpression of miR-524-5p significantly reduced proliferative, anchorage-independent growth, migratory and invasive abilities of BRAF inhibitor-resistant melanoma cells. Moreover, the introduction of miR-524-5p led to a reduced development of BRAF inhibitor-resistant melanoma in vivo. Remarkably, the MAPK/ERK signaling pathway was decreased after treatment with miR-524-5p. Furthermore, next-generation sequencing analysis implied that the complement system, leukocyte extravasation, liver X receptor/retinoid-X-receptor activation, and cAMP-mediated signaling may be related to miR-524-5p-induced pathways in the resistant cells. The miR-524-5p level was higher on average in complete response and long-term partial response patients than in progressive disease and short-term partial response patients treated with BRAF inhibitors. Our results proposed that miR-524-5p could be considered as a target for treatment BRAF inhibitor-resistant melanoma and a prognostic marker in the response of patients to BRAF inhibitors for melanoma.

Nuclear immunoreactivity of BLM-s, a proapoptotic BCL-2 family member, is specifically detected in salivary adenoid cystic carcinoma.

Tumor cells frequently evade apoptosis triggered by cellular stress via aberrant regulation of the BCL-2 family members, which are key players in regulating cell death under physiological and pathological situations. Previously, we have identified a novel BH3-only protein of the BCL-2 family, BLM-s (BCL-2-like molecule, short form), that modulates apoptosis of postmitotic immature neurons during corticohistogenesis. Whether BLM-s expression correlates with any subtype of human tumors has not been investigated. Here, via BLM-s immunohistochemistry performed in various kinds of human tumors, we demonstrate that BLM-s is specifically expressed in tumors derived from salivary gland (specificity, 0.76 [95% confidence interval, or CI], 0.65-0.85]; sensitivity, 1 [95% CI, 0.99-1]). Stratification of BLM-s immunointensity and its subcellular localization in correlation with salivary gland tumor subtype shows a statistically significant increase in proportion and in intensity of nuclear staining for adenoid cystic carcinoma (ACC; specificity, 0.92 [95% CI, 0.88-0.95]; sensitivity, 0.82 [95% CI, 0.66-0.92]), a locally aggressive head and neck malignancy. Comparison among salivary ACC in correlation with MYB/MYBL fluorescence in situ hybridization, c-KIT immunohistochemistry, and BLM-s immunohistochemistry shows that BLM-s' nuclear immunoreactivity has lower false-negative detection rate (18.5% compared with 26.3% [MYB/MYBL fluorescence in situ hybridization] and 34.2% [c-KIT], respectively). Intriguingly, ACC derived from other cell origins such as breast shows negative BLM-s immunoreactivity. We thus propose that nuclear localization of BLM-s detected by immunohistochemistry could be potentially used as an ancillary diagnostic marker for ACC originating from the salivary gland, especially when the biopsy specimen is small with an unknown tumor origin.

miR-596 Modulates Melanoma Growth by Regulating Cell Survival and Death.

Tumors grow because cancer cells lack the ability to balance cell survival and death signaling pathways. miR-596, a microRNA located at the 8p23.3 locus, has been shown by the TCGA-Assembler to be deleted in a significant number of melanoma samples. Here, we also validated the low levels of miR-596 in melanoma compared to tissue nevi, and Kaplan-Meier curve analysis revealed that low miR-596 expression was associated with worse overall survival. Moreover, we showed that miR-596 overexpression effectively inhibited MAPK/ERK signaling, cell proliferation, migration, and invasion and increased the cell apoptosis of melanoma cells. In addition, we found that miR-596 directly targets MEK1 and two apoptotic proteins, MCL1, and BCL2L1, in melanoma cells. Our findings indicated that miR-596 is an important miRNA that both negatively regulates the MAPK/ERK signaling pathway by targeting MEK1 and modulates the apoptosis pathway by targeting MCL1 and BCL2L1, suggesting that miR-596 could be a therapeutic candidate for treating melanoma, and a prognostic factor for melanoma patients.

FoxO6 and PGC-1α form a regulatory loop in myogenic cells.

Transcription factors of the FoxO (forkhead box O) family regulate a wide range of cellular physiological processes, including metabolic adaptation and myogenic differentiation. The transcriptional activity of most FoxO members is inhibitory to myogenic differentiation and overexpression of FoxO1 inhibits the development of oxidative type I fibres in vivo. In this study, we found that FoxO6, the last discovered FoxO family member, is expressed ubiquitously in various tissues but with higher expression levels in oxidative tissues, such as brain and oxidative muscles. Both the expression level and promoter activity of FoxO6 were found to be enhanced by PGC-1α (peroxisome-proliferator-activated receptor γ co-activator 1α), thus explained its enriched expression in oxidative tissues. We further demonstrated that FoxO6 represses the expression of PGC-1α via direct binding to an upstream A/T-rich element (AAGATATCAAAACA,-2228-2215) in the PGC-1α promoter. Oxidative low-intensity exercise induced PGC-1α but reduced FoxO6 expression levels in hind leg muscles, and the binding of FoxO6 to PGC-1α promoter was also prevented by exercise. As FoxO6 promoter can be co-activated by PGC-1α and its promoter in turn can be repressed by FoxO6, it suggests that FoxO6 and PGC-1α form a regulatory loop for setting oxidative metabolism level in the skeletal muscle, which can be entrained by exercise.

Angiosarcoma of sigmoid colon with intraperitoneal bleeding: case report and literature review.

Primary angiosarcomas arising from the alimentary tract are rare and only a few cases have been reported in the literature. We report a case of an angiosarcoma of the sigmoid colon with intraperitoneal bleeding but not rectal bleeding. A 21-year-old female patient received a laparotomy and a mass lesion over the sigmoid colon was found with active bleeding. A sigmoid colectomy was performed as a curative resection. Grossly, the sigmoid colon contained a kidney shaped, hemorrhagic tumour from the submucosal layer extension to the antimesenteric side. Intraluminally, the mucosa of the colon was intact. Microscopic examination revealed a high grade angiosarcoma composed of fascicles of spindle cells and solid sheets of epithelioid cells. Immunohistochemical stains revealed a positive result for CD31 and the endothelial nature of the malignancy was confirmed. Smooth muscle antigens, desmins, cytokeratins AE1/AE3 and CD117 were all negative. The patient is still alive without evidence of recurrence or metastasis at a three-year follow-up appointment. Owing to the availability of immunohistochemical studies, some atypical sarcomas would now be correctly classified as angiosarcomas. Since no optimal adjuvant treatment is effective, curative surgical excision is still the best choice of treatment.