Purpose: This study was to investigate the clinicopathologic significance and potential role of HOXB7 in the development and progression of colorectal cancer (CRC).Experimental Design: The relationship between HOXB7 expression and clinical characteristics of CRC was analyzed in 224 paraffin-embedded archived CRC specimens by immunohistochemistry (IHC). The effects of HOXB7 on cell growth and proliferation, as well as on tumorigenesis, were examined both in vitro and in vivo, using MTT assay, colony formation assay, cell cycle analysis, soft agar assay, and tumorigenesis in nude mice. Western blotting and real-time reverse transcriptase-PCR were performed to examine the impact of HOXB7 on the PI3K/Akt and MAPK signaling pathways.Results: HOXB7 protein level was significantly correlated with advanced Dukes stage (P < 0.001), T stage (P ¼ 0.012), distant metastasis (P ¼ 0.042), higher proliferation index (P ¼ 0.007) and poor survival of patients (P ¼ 0.005). Enforced expression of HOXB7 in CRC cell lines significantly enhanced cell growth, proliferation and tumorigenesis. Conversely, knockdown of HOXB7 caused an inhibition of cell growth, proliferation, and tumorigenesis. We also showed that HOXB7 accelerated G 0 -G 1 to S-phase transition concomitantly with upregulation of cyclin D1 and downregulation of p27Kip1. On the contrary, knockdown of HOXB7 caused G 1 -S-phase arrest, downregulation of cyclin D1 and upregulation of p27Kip1. Enforced expression of HOXB7 could enhance PI3K/AKT and MAPK pathway activity.Conclusion: Our findings suggest that HOXB7 protein, as a valuable marker of CRC prognosis, plays an important role in the development and progression of human CRC.

The development of hepatocellular carcinomas (HCC) depends on their local microenvironment and the induction of neovascularization is a decisive step in tumor progression, since the growth of solid tumors is limited by nutrient and oxygen supply. Hypoxia is the critical factor that induces transcription of the hypoxia inducible factor-1α (HIF-1α) encoding gene HIF1A and HIF-1α protein accumulation to promote angiogenesis. However, the basis for the transcriptional regulation of HIF1A expression in HCC is still unclear. Here, we show that Bclaf1 levels are highly correlated with HIF-1α levels in HCC tissues, and that knockdown of Bclaf1 in HCC cell lines significantly reduces hypoxia-induced HIF1A expression. Furthermore, we found that Bclaf1 promotes HIF1A transcription via its bZIP domain, leading subsequently to increased transcription of the HIF-1α downstream targets VEGFA, TGFB, and EPO that in turn promote HCC-associated angiogenesis and thus survival and thriving of HCC cells. Moreover, we demonstrate that HIF-1α levels and microvessel density decrease after the shRNA-mediated Bclaf1 knockdown in xenograft tumors. Finally, we found that Bclaf1 levels increase in hypoxia in a HIF-1α dependent manner. Therefore, our study identifies Bclaf1 as a novel positive regulator of HIF-1α in the hypoxic microenvironment, providing new incentives for promoting Bcalf1 as a potential therapeutic target for an anti-HCC strategy.

Our findings suggest that Bclaf1 affects HCC progression by manipulating c-MYC mRNA stability and that the Hsp90α/Bclaf1/c-Myc axis might be a potential target for therapeutic intervention in HCC.

SUMMARY: Extraventricular neurocytoma is a rare entity, most frequently occurring in brain parenchyma outside the ventricular system. The purpose of this study was to characterize the MR imaging findings in a series of 9 patients with EVN verified by results of pathologic examination. All 9 EVNs were solitary and intracranially located. Eight lesions were well demarcated, and 3 showed intratumoral hemorrhage. The solid parts of 7 tumors were primarily isointense on T1-weighted images and heterogeneously enhanced on T1WI with contrast. Although cerebral EVNs can present a wide spectrum of appearances on MR, the imaging patterns appear to vary according to anatomic location and cellularity. Lesions in frontal or parietal lobes often present as well-demarcated large masses with cystic degeneration, hemorrhage, mild-to-moderate edema, and inhomogeneous enhancement. Moreover, the general isointensity of the solid parts of EVN on T1WI may be of some specificity.

Our aim was to determine the usefulness of fluorescence examination and photodynamic therapy (PDT) for the management of perianal extramammary Paget's disease. A 75-year-old woman underwent two courses of PDT. The first treatment was carried out with topically applied 5-aminolevulinic acid (ALA) to the affected area (2.5 x 2.5 cm(2)) 3 h before light treatment. We used ALA/protoporphyrin IX (PpIX)-mediated fluorescence to visualize the lesion and its margins. The lesion was treated with a 630 nm laser at 120 J/cm(2). Forty days later, the residual lesion was given a second treatment at the same light dose after topical application of ALA and intravenous injection of HiPorfin. ALA/PpIX-mediated fluorescence served as a useful tool to visualize the lesion's location. Complete cure was achieved after the second course of PDT. During 7 months of follow up, no recurrence, scarring or functional loss was noticed. We concluded that ALA-assisted fluorescence examination can be a useful tool to determine the lesion and its margins. ALA-PDT is effective for superficial lesions, but, for thicker and deeper lesions, the systemic administration of photosensitizer is needed.

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Nasopharyngeal carcinoma (NPC), one of the most common cancers in population with Chinese or Asian progeny, poses a serious health problem for southern China. It is unfortunate that most NPC victims have had lymph node metastasis (LNM) when first diagnosed. We believe that the 2D based serum proteome analysis can be useful in discovering new biomarkers that may aid in the diagnosis and therapy of NPC patients. To filter the tumor specific antigen markers of NPC, sera from 42 healthy volunteers, 27 non-LNM NPC patients and 37 LNM NPC patients were selected for screening study using 2D combined with MS. Pretreatment strategy, including sonication, albumin and immunoglobulin G (IgG) depletion, was adopted for screening differentially expressed proteins of low abundance in serum. By 2D image analysis and MALDI-TOF-MS identification, twenty-three protein spots were differentially expressed. Three of them were further validated in the sera using enzyme-linked immunosorbent assay (ELISA). Our research demonstrates that HSP70, sICAM-1 and SAA, confirmed with ELISA at sera and immunohistochemistry, are potential NPC metastasis-specific serum biomarkers which may be of great underlying significance in clinical detection and management of NPC.

The human cortical regions for processing high-level visual (HLV) functions of different categories remain ambiguous, especially in terms of their conjunctions and specifications. Moreover, the neurobiology of declined HLV functions in patients with Alzheimer's disease (AD) has not been fully investigated. This study provides a functionally sorted overview of HLV cortices for processing “what” and “where” visual perceptions and it investigates their atrophy in AD and MCI patients. Based upon activation likelihood estimation (ALE), brain regions responsible for processing five categories of visual perceptions included in “what” and “where” visions (i.e., object, face, word, motion, and spatial visions) were analyzed, and subsequent contrast analyses were performed to show regions with conjunctive and specific activations for processing these visual functions. Next, based on the resulting ALE maps, the atrophy of HLV cortices in AD and MCI patients was evaluated using voxel-based morphometry. Our ALE results showed brain regions for processing visual perception across the five categories, as well as areas of conjunction and specification. Our comparisons of gray matter (GM) volume demonstrated atrophy of three “where” visual cortices in late MCI group and extensive atrophy of HLV cortices (25 regions in both “what” and “where” visual cortices) in AD group. In addition, the GM volume of atrophied visual cortices in AD and MCI subjects was found to be correlated to the deterioration of overall cognitive status and to the cognitive performances related to memory, execution, and object recognition functions. In summary, these findings may add to our understanding of HLV network organization and of the evolution of visual perceptual dysfunction in AD as the disease progresses.