Intra-articular osteoid osteoma of the calcaneus: a case report and review

AbstractOsteoid osteoma of the calcaneus is rare and frequently misdiagnosed as arthritis because of similar symptoms. In addition, radiographic findings may be nonspecific, and magnetic resonance imaging (MRI) may show a bone marrow edema and changes in adjacent soft tissue. A 19-year-old man presented with a 6-month history of persistent pain and swelling in the left hind foot; diagnostic computed tomography and MRI analyses revealed lesions suggesting an intra-articular osteoid osteoma of the calcaneus. Initial MRI did not show specific findings. On operation, the tumor was removed by curettage; pathologic findings demonstrated woven bone trabeculae surrounded by connective tissue, confirming the diagnosis. To the best of our knowledge, MRI scans in all cases of calcaneal osteoid osteoma reported till 3 months after the injury exhibited a nidus. We believe that calcaneal osteoid osteoma should be considered as a differential diagnosis in patients undergoing MRI 3 months after symptom presentation; early computed tomography is critical in diagnosis

Additive Influence of Extracellular pH, Oxygen Tension, and Pressure on Invasiveness and Survival of Human Osteosarcoma Cells

Background/Purpose: The effects of chemical and physical interactions in the microenvironment of solid tumors have not been fully elucidated. We hypothesized that acidosis, hypoxia, and elevated interstitial fluid pressure (eIFP) have additive effects on tumor cell biology and lead to more aggressive behavior during tumor progression. We investigated this phenomenon using three human osteosarcoma (OS) cell lines and a novel in vitro cell culture apparatus. Materials and Methods: U2OS, SaOS, and MG63 cell lines were cultured in media adjusted to various pH levels, oxygen tension (hypoxia 2% O(2), normoxia 20% O(2)), and hydrostatic gage pressure (0 or 50 mmHg). Growth rate, apoptosis, cell cycle parameters, and expression of mRNA for proteins associated with invasiveness and tumor microenvironment (CA IX, VEGF-A, HIF-1A, MMP-9, and TIMP-2) were analyzed. Levels of CA IX, HIF-1α, and MMP-9 were measured using immunofluorescence. The effect of pH on invasiveness was evaluated in a Matrigel chamber assay. Results: Within the acidic–hypoxic–pressurized conditions that simulate the microenvironment at a tumor’s center, invasive genes were upregulated, but the cell cycle was downregulated. The combined influence of acidosis, hypoxia, and IFP promoted invasiveness and angiogenesis to a greater extent than did pH, pO(2), or eIFP individually. Significant cell death after brief exposure to acidic conditions occurred in each cell line during acclimation to acidic media, while prolonged exposure to acidic media resulted in reduced cell death. Furthermore, 48-h exposure to acidic conditions promoted tumor invasiveness in the Matrigel assay. Conclusion: Our findings demonstrate that tumor microenvironmental parameters – particularly pH, pO(2), and eIFP – additively influence tumor proliferation, invasion, metabolism, and viability to enhance cell survival and must be controlled in OS research

CD133 facilitates epithelial-mesenchymal transition through interaction with the ERK pathway in pancreatic cancer metastasis

BACKGROUND: Pancreatic cancer is a lethal disease due to the high incidence of metastasis at the time of detection. CD133 expression in clinical pancreatic cancer correlates with poor prognosis and metastasis. However, the molecular mechanism of CD133-regulated metastasis remains unclear. In recent years, epithelial-mesenchymal transition (EMT) has been linked to cancer invasion and metastasis. In the present study we investigated the role of CD133 in pancreatic cancer metastasis and its potential regulatory network. METHODS: A highly migratory pancreatic cancer cell line, Capan1M9, was established previously. After shRNA was stable transducted to knock down CD133 in Capan1M9 cells, gene expression was profiled by DNA microarray. Orthotopic, splenic and intravenous transplantation mouse models were set up to examine the tumorigenesis and metastatic capabilities of these cells. In further experiments, real-time RT-PCR, Western blot and co-immunoprecipitate were conducted to evaluate the interactions of CD133, Slug, N-cadherin, ERK1/2 and SRC. RESULTS: We found that CD133(+) human pancreatic cancer cells were prone to generating metastatic nodules in in vivo models using immunodeficient mice. In contrast, CD133 knockdown suppressed cancer invasion and metastasis in vivo. Gene profiling analysis suggested that CD133 modulated mesenchymal characteristics including the expression of EMT-related genes, such as Slug and N-cadherin. These genes were down-regulated following CD133 knockdown. Moreover, CD133 expression could be modulated by the extracellular signal-regulated kinase (ERK)1/2 and SRC signaling pathways. The binding of CD133 to ERK1/2 and SRC acts as an indispensable mediator of N-cadherin expression. CONCLUSIONS: These results demonstrate that CD133 plays a critical role in facilitating the EMT regulatory loop, specifically by upregulating N-cadherin expression, leading to the invasion and metastasis of pancreatic cancer cells. Our study provides a novel insight into the function of CD133 in the EMT program and a better understanding of the mechanism underlying the involvement of CD133 in pancreatic cancer metastasis

Acute Vertebral Artery Origin Occlusion Leading to Basilar Artery Thrombosis Successfully Treated by Angioplasty with Stenting and Intracranial Fibrinolysis

There are few reports describing stroke due to the acute occlusion of the vertebral artery (VA) origin successfully treated by endovascularily. The authors report a case of 78-year-old man suffering from stroke owing to acute VA origin occlusion associated with contralateral hypoplastic VA leading to basilar artery (BA) thrombosis. Cerebral angiography demonstrated that the right VA was occluded at its origin, the left VA was hypoplastic, and BA was filled with thrombus. The occlusion of VA origin was initially passed through with a microcatheter and microwire. Hereafter, angioplasty was performed followed by stenting with a coronary stent. The VA origin was successfully recanalized. Next, a microcatheter was navigated intracranially through the stent and fibrinolysis was performed for BA thrombus. The patient's symptoms gradually improved postoperatively. Stroke due to acute VA origin occlusion leading to BA thrombosis was successfully treated by angioplasty and stenting followed by intracranial fibrinolysis

The adverse effect of an unplanned surgical excision of foot soft tissue sarcoma

<p>Abstract</p> <p>Background</p> <p>Malignant soft tissue tumors of the foot are extremely rare and thus can be prematurely excised without appropriate preoperative evaluation. The present study compares adverse effects between unplanned and planned surgical excisions.</p> <p>Methods</p> <p>We retrospectively reviewed the clinical records, radiographs, pathology reports and pathological specimens of 14 consecutive patients with soft tissue sarcoma of the foot among 592 with sarcomas between 1973 and 2009. We then compared the incidence and clinical outcomes after unplanned (UT; n = 5) and planned (PT; n = 9) surgical excisions of foot sarcomas.</p> <p>Results</p> <p>The most frequent diagnosis was synovial sarcoma (n = 4; 28.6%). The overall 5-year survival rates of the PT and UT groups were 65.6% and 60.0%, respectively, and the event-free 5-year survival rates were 63.5% and 40.0%, respectively. Event-free and overall survival rates did not significantly differ between the two groups. However, tumors were significantly larger in the PT group than in the UT group (p < 0.05).</p> <p>Conclusions</p> <p>Unplanned resection lead to a relatively worse prognosis and a likelihood of recurrence despite additional resections. We recommend that soft tumors of the foot should only be excised after appropriate preoperative evaluation regardless of the size of the tumor.</p

Expression of MUC17 is regulated by HIF1α-mediated hypoxic responses and requires a methylation-free hypoxia responsible element in pancreatic cancer.

MUC17 is a type 1 membrane-bound glycoprotein that is mainly expressed in the digestive tract. Recent studies have demonstrated that the aberrant overexpression of MUC17 is correlated with the malignant potential of pancreatic ductal adenocarcinomas (PDACs); however, the exact regulatory mechanism of MUC17 expression has yet to be identified. Here, we provide the first report of the MUC17 regulatory mechanism under hypoxia, an essential feature of the tumor microenvironment and a driving force of cancer progression. Our data revealed that MUC17 was significantly induced by hypoxic stimulation through a hypoxia-inducible factor 1α (HIF1α)-dependent pathway in some pancreatic cancer cells (e.g., AsPC1), whereas other pancreatic cancer cells (e.g., BxPC3) exhibited little response to hypoxia. Interestingly, these low-responsive cells have highly methylated CpG motifs within the hypoxia responsive element (HRE, 5\u27-RCGTG-3\u27), a binding site for HIF1α. Thus, we investigated the demethylation effects of CpG at HRE on the hypoxic induction of MUC17. Treatment of low-responsive cells with 5-aza-2\u27-deoxycytidine followed by additional hypoxic incubation resulted in the restoration of hypoxic MUC17 induction. Furthermore, DNA methylation of HRE in pancreatic tissues from patients with PDACs showed higher hypomethylation status as compared to those from non-cancerous tissues, and hypomethylation was also correlated with MUC17 mRNA expression. Taken together, these findings suggested that the HIF1α-mediated hypoxic signal pathway contributes to MUC17 expression, and DNA methylation of HRE could be a determinant of the hypoxic inducibility of MUC17 in pancreatic cancer cells

Cromakalim, a vasodilator, differentially inhibits Ca2+ currents in NG108-15 neuroblastoma × glioma hybrid cells

AbstractExtracellular perfusion with the antihypertensive agent cromakalim produced an inhibition of 22–66% in the low-threshold transient Ca2+ (T-like) current in NG108-15 hybrid cells. Cromakalim suppressed the high-threshold and long-lasting Ba2+ current (L-like Ca2+ current) by 29–73%, but had almost no effect on the high-threshold and inactivating Ba2+ current (N-like Ca2+ current). IC50 for T-like and L-like currents was the same at about 100 μM. The inhibitory effect developed relatively fast and was reversible. These results indicate that cromakalim can selectively inhibit the activity of inward Ca2+ currents

Quantitative characterization of the Antarctic ozone hole

The long-term evolution of the Antarctic ozone hole is studied based on the TOMS data and the JMA data-set of stratospheric temperature in relation with the possible role of polar stratospheric clouds (PSC's). The effective mass of depleted ozone in the ozone hole at its annual mature stage reached a historical maximum of 55 Mt in 1991, 4.3 times larger than in 1981. The ozone depletion rate during 30 days before the mature ozone hole does not show any appreciable long-term trend but the interannual fluctuations do, ranging from 0.169 to 0.689 Mt/day with the average of 0.419 Mt/day for the period of 1979 - 1991. The depleted ozone mass has the highest correlation with the region below 195 K on the 30 mb surface in June, whereas the ozone depletion rate correlates most strongly with that in August. The present result strongly suggests that the long-term evolution of the mature ozone hole is caused both by the interannual change of the latitudinal coverage of the early PSC's, which may control the latitude and date of initiation of ozone decrease, and by that of the spatial coverage of the mature PSC's which may control the ozone depletion rate in the Antarctic spring

Intra-articular osteoid osteoma of the calcaneus: A case report and review

Osteoid osteoma of the calcaneus is rare and frequently misdiagnosed as arthritis because of similar symptoms. In addition, radiographic findings may be nonspecific, and magnetic resonance imaging (MRI) may show a bone marrow edema and changes in adjacent soft tissue. A 19-year-old man presented with a 6-month history of persistent pain and swelling in the left hind foot; diagnostic computed tomography and MRI analyses revealed lesions suggesting an intra-articular osteoid osteoma of the calcaneus. Initial MRI did not show specific findings. On operation, the tumor was removed by curettage; pathologic findings demonstrated woven bone trabeculae surrounded by connective tissue, confirming the diagnosis. To the best of our knowledge, MRI scans in all cases of calcaneal osteoid osteoma reported till 3 months after the injury exhibited a nidus. We believe that calcaneal osteoid osteoma should be considered as a differential diagnosis in patients undergoing MRI 3 months after symptom presentation; early computed tomography is critical in diagnosis. © 2016 The Authors.Embargo Period 12 month

Cast: a novel protein of the cytomatrix at the active zone of synapses that forms a ternary complex with RIM1 and munc13-1

The cytomatrix at the active zone (CAZ) has been implicated in defining the site of Ca2+-dependent exocytosis of neurotransmitter. We have identified here a novel CAZ protein of ∼120 kD from rat brain and named it CAST (CAZ-associated structural protein). CAST had no transmembrane segment, but had four coiled-coil domains and a putative COOH-terminal consensus motif for binding to PDZ domains. CAST was localized at the CAZ of conventional synapses of mouse brain. CAST bound directly RIM1 and indirectly Munc13-1, presumably through RIM1, forming a ternary complex. RIM1 and Munc13-1 are CAZ proteins implicated in Ca2+-dependent exocytosis of neurotansmitters. Bassoon, another CAZ protein, was also associated with this ternary complex. These results suggest that a network of protein–protein interactions among the CAZ proteins exists at the CAZ. At the early stages of synapse formation, CAST was expressed and partly colocalized with bassoon in the axon shaft and the growth cone. The vesicles immunoisolated by antibassoon antibody–coupled beads contained not only bassoon but also CAST and RIM1. These results suggest that these CAZ proteins are at least partly transported on the same vesicles during synapse formation