Pseudosarcomatous Proliferation of Cx43- and Kit-Expressing Interstitial Cell in the Urinary Bladder

The authors report a case showing proliferation of KIT- and connexin 43-expressing mesenchymal cells of the urinary bladder. A 75-year-old woman had an ulcerated endophytic mass (size, approximately 2 × 2 cm) in the left posterolateral wall. She underwent transurethral resection and subsequent partial cystectomy. The suburothelial mass extended to the muscularis propria. The histopathological analysis revealed spindle-shaped mesenchymal cells that were loosely arranged with myxoid stroma and showed a focal compact fascicular arrangement. In the immunohistochemical analysis, these spindle cells were stained with specific antibodies to KIT and connexin 43. The patient is currently free of disease at 5 years after operation. The proliferating spindle cells in the present case might represent a phenotype of interstitial cells of the lamina propria

Immunohistochemical study of epithelioid hemangioendothelioma in the leg: a case report.

Epithelioid hemangioendothelioma is a relatively rare lesion. Although its histogenesis has been well described, its immunohistochemical characteristics remain controversial. A case of epithelioid hemangioendothelioma of the soft tissue of the right leg in a 67-year-old Chinese woman is reported. Histologic findings of intracytoplasmic lumina in the tumor cells and positive immunostaining for vimentin, factor VIII-related antigen. CD34 and Ulex europaeus agglutinin 1 (UEA-1) were obtained, demonstrating differentiation of the tumor cells to endothelial cells, although staining for antibodies to cytokeratins AE1/AE3 and CAM5.2 was weak. CD34 as well as Factor VIII-related antigen is a useful marker of endothelial differentiation in this tumor. A review of the literature is also presented. </p

Overexpression of c-Met/hepatocyte growth factor receptors in human prostatic adenocarcinoma.

Hepatocyte growth factor (HGF) and c-met proto-oncogene product (c-Met) have varied biological functions in different tissues and have been implicated in mitogenic, motogenic and morphogenic responses in both organ regeneration and carcinogenesis. Some studies have suggested that the overexpression of c-Met and epidermal growth factor receptor (EGFR) are associated with growth advantage, while transforming growth factor-beta receptor II (TGF beta R II) is associated with growth disadvantage of human prostatic adenocarcinoma. However, it is unclear if the expression of c-Met correlates with the expression of EGFR and TGF beta R II, and with the proliferative status of human prostatic adenocarcinoma. Using immunohistochemical staining with anti-c-Met (C-12), anti-EGFR (NCL-EGFR) and anti-TGF beta R II (L-21) antibodies, we determined the frequency of expression of c-MET, EGFR, and TGF beta R II respectively in a series of 134 radical prostatectomy specimens. We evaluated the relationship between the expression of these receptors and clinicopathological characteristics. Overall, c-Met immunostaining was detected in 54 of 134 (40.3%) cases, EGFR in 45 (33.6%) and TGF beta R II in 64 (48.4%). The overexpression of c-Met was significantly more common in poorly differentiated (P &#60; 0.0001) and in the diffusely infiltrated specimens (P &#60; 0.0005). In contrast, TGF beta R II was significantly overexpressed in the well differentiated specimens (P &#60; 0.0001) and associated negatively with c-Met (P &#60; 0.0001). Overall, these data suggest that c-Met/HGF receptor and TGF beta R II overexpression may be involved in the differentiation of human prostatic adenocarcinoma, c-Met with de-differentiation and TGF beta R II with differentiation.</p

Rapid radiation of treponema pallidum pertenue in wild non-human primates

Bacteria of the species Treponema pallidum are causative agents of venereal syphilis (Treponema pallidum pallidum), Bejel (T. p. endemicum), and yaws (T. p. pertenue) in humans. We documented Treponema pallidum infections associated with disease in wild sooty mangabeys (Cercocebus atys) in Taï National Park, Côte d’Ivoire, and green monkeys (Chlorocebus sabaeus) from Bijilo Forest Park, Gambia and Niokolo-Koba National Park, Senegal. To examine the evolutionary relatedness of these treponemes to those responsible for diseases in humans and for previously documented infections in baboons (Papio papio), we conducted a hybridization capture experiment to enrich Treponema pallidum DNA from samples collected from symptomatic individuals. This approach allowed us to sequence the full genomes of Treponema pallidum strains infecting sooty mangabeys (n = 2) and green monkeys (n = 4). Phylogenomic analyses revealed that all Treponema pallidum strains infecting non-human primates are most closely related to the sub-species T. p. pertenue. Strains infecting humans and non-human primates do not appear to be reciprocally monophyletic. The star-like phylogenetic branching pattern of the T. p. pertenue clade, with short basal branches receiving low statistical support, suggests a rapid initial radiation across humans and non-human primates. These results greatly broaden the known host range of T.p. pertenue and suggest the existence of a vast zoonotic reservoir that could possibly contribute to the failure of global eradication efforts

KIF20A-Mediated RNA Granule Transport System Promotes the Invasiveness of Pancreatic Cancer Cells

Pancreatic cancers are aggressive because they are highly invasive and highly metastatic; moreover, effective treatments for aggressive pancreatic cancers are lacking. Here, we report that the motor kinesin protein KIF20A promoted the motility and invasiveness of pancreatic cancer cells through transporting the RNA-binding protein IGF2BP3 and IGF2BP3-bound transcripts toward cell protrusions along microtubules. We previously reported that IGF2BP3 and its target transcripts are assembled into cytoplasmic stress granules of pancreatic cancer cells, and that IGF2BP3 promotes the motility and invasiveness of pancreatic cancer cells through regulation of localized translation of IGF2BP3-bound transcripts in cell protrusions. We show that knockdown of KIF20A inhibited accumulation of IGF2BP3-containing stress granules in cell protrusions and suppressed local protein expression from specific IGF2BP3-bound transcripts, ARF6 and ARHGEF4, in the protrusions. Our results provide insight into the link between regulation of KIF20A-mediated trafficking of IGF2BP3-containing stress granules and modulation of the motility and invasiveness in pancreatic cancers

Expression of Cadherin-17 Promotes Metastasis in a Highly Bone Marrow Metastatic Murine Breast Cancer Model

We previously established 4T1E/M3 highly bone marrow metastatic mouse breast cancer cells through in vivo selection of 4T1 cells. But while the incidence of bone marrow metastasis of 4T1E/M3 cells was high (~80%) when injected intravenously to mice, it was rather low (~20%) when injected subcutaneously. Therefore, using 4T1E/M3 cells, we carried out further in vitro and in vivo selection steps to establish FP10SC2 cells, which show a very high incidence of metastasis to lungs (100%) and spines (85%) after subcutaneous injection into mice. qRT-PCR and western bolt analysis revealed that cadherin-17 gene and protein expression were higher in FP10SC2 cells than in parental 4T1E/M3 cells. In addition, immunostaining revealed the presence of cadherin-17 at sites of bone marrow and lung metastasis after subcutaneous injection of FP10SC2 cells into mice. Suppressing cadherin-17 expression in FP10SC2 cells using RNAi dramatically decreased the cells’ anchorage-independent growth and migration in vitro and their metastasis to lung and bone marrow in vivo. These findings suggest that cadherin-17 plays a crucial role in mediating breast cancer metastasis to bone marrow

WAVE2 is associated with poor prognosis in pancreatic cancers and promotes cell motility and invasiveness via binding to ACTN4

Abstract WAVE2 is a member of the WASP/WAVE family of actin cytoskeletal regulatory proteins; unfortunately, little is known about its function in pancreatic cancers. In this study, we report the role of WAVE2 in the motility and invasiveness of pancreatic cancer cells. High WAVE2 expression in human pancreatic cancer tissues was correlated with overall survival. WAVE2 accumulated in the cell protrusions of pancreatic cancer cell lines. Downregulation of WAVE2 by small interfering RNA decreased the cell protrusions and inhibited the motility and invasiveness of pancreatic cancer cells. WAVE2 promoted pancreatic cancer cell motility and invasion by forming a complex with the actin cytoskeletal protein alpha‐actinin 4 (ACTN4). Downregulation of ACTN4 by small interfering RNA also inhibited the motility and invasiveness of the cells through a decrease in cell protrusions. Further investigation showed that WAVE2/ACTN4 signaling selectively stimulated p27 phosphorylation and thereby increased the motility and invasiveness of the cells. These results suggest that WAVE2 and ACTN4 stimulate p27 phosphorylation and provide evidence that WAVE2 promotes the motility and invasiveness of pancreatic cancer cells