MedWorm: Fibrosarcoma

SMYD3 Promotes Cancer Invasion by Epigenetic Upregulation of the Metalloproteinase MMP-9

Cancer Research — Tue, 31 Jan 2012 05:00:00 +0100

Upregulation of the matrix metalloproteinase (MMP)–9 plays a central role in tumor progression and metastasis by stimulating cell migration, tumor invasion, and angiogenesis. To gain insights into MMP-9 expression, we investigated its epigenetic control in a reversible model of cancer that is initiated by infection with intracellular Theileria parasites. Gene induction by parasite infection was associated with trimethylation of histone H3K4 (H3K4me3) at the MMP-9 promoter. Notably, we found that the H3K4 methyltransferase SMYD3 was the only histone methyltransferase upregulated upon infection. SMYD3 is overexpressed in many types of cancer cells, but its contributions to malignant pathophysiology are unclear. We found that overexpression of SMYD3 was sufficient to induce MMP-9 expression...

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Functional characterization of protein variants of the human multidrug transporter ABCC2 by a novel targeted expression system in fibrosarcoma cells

Human Mutation — Mon, 30 Jan 2012 05:00:00 +0100

AbstractThe multidrug resistance protein 2 (MRP2/ABCC2) is involved in the efflux of endogenous and xenobiotic substrates, including several anticancer and antiviral drugs. The functional consequences of ABCC2 protein variants remain inconsistent, which may be due to shortcomings of the in vitro assays used. To study systematically the functional consequences of nonsynonymous ABCC2 variants, we used a novel “Screen and Insert” (ScIn) technology to achieve stable and highly reproducible expression of thirteen ABCC2 variants in HT1080 cells. Western blotting revealed lower (30‐65%) ABCC2 expression for D333G, R1174H, and R1181L as compared to wild‐type (100%), whereas the linked variant V1188E/C1515Y resulted in higher expression (150%). R1174H caused mislocalization of ABCC2 to the ...

Alternative ferritin mRNA translation via internal initiation.

RNA — Mon, 23 Jan 2012 05:00:00 +0100

Authors: Daba A, Koromilas AE, Pantopoulos K Abstract Ferritin stores and detoxifies an excess of intracellular iron, and thereby plays an important role in the metabolism of this metal. As unshielded iron promotes oxidative stress, ferritin is crucial in maintaining cellular redox balance and may also modulate cell growth, survival, and apoptosis. The expression of ferritin is controlled by transcriptional and post-transcriptional mechanisms. In light of the well-established transcriptional induction of ferritin by inflammatory signals, we examined how ferritin mRNA translation responds to stress conditions. We first used HT1080 fibrosarcoma cells engineered for coumermycin-inducible expression of PKR, a stress kinase that inhibits protein synthesis in virus-infected cells by phos...

Intraosseous Fibrosarcoma of Maxilla in an HIV Patient.

Archives of Iranian Medicine — Sun, 01 Jan 2012 05:00:00 +0100

Authors: Kotrashetti VS, Kale AD, Hallikeremath SR, Mane DR, V Angadi P, Bhatt P Abstract Fibrosarcoma is a malignant mesenchymal neoplasm of fibroblasts that rarely affects the oral cavity and can cause local recurrences or metastasis. Fibrosarcomas account for 15% of all soft tissue sarcomas, which represent only 1% of all malignant tumors of the head and neck region. The clinical behavior of the fibrosarcoma is characterized by a high local recurrence rate, and low incidence of loco regional lymph node and/or distant hematogenous metastasis. The etiology for fibrosarcoma has no definite cause but is thought to occur from preexisting lesions or in previously irradiated areas of bone lesions. Immunosuppression associated with HIV infection and acquired immune deficiency syndrome (...

Composite biological reconstruction following total calcanectomy of primary calcaneal tumors

Journal of Surgical Oncology — Tue, 27 Dec 2011 05:00:00 +0100

ConclusionsVascularized fibular flaps in combination with massive allografts provide an excellent option for biological reconstruction after total calcanectomy in tumor situation and have proven to be a successful limb salvage procedure, which result in earlier patient recovery and return of function.Level of EvidenceTherapeutic Level IV. J. Surg. Oncol © 2011 Wiley Periodicals, Inc. (Source: Journal of Surgical Oncology)

Overexpression of FoxO1 in the Hypothalamus and Pancreas Causes Obesity and Glucose Intolerance.

Endocrinology — Tue, 20 Dec 2011 05:00:00 +0100

Authors: Kim HJ, Kobayashi M, Sasaki T, Kikuchi O, Amano K, Kitazumi T, Lee YS, Yokota-Hashimoto H, Susanti VY, Kitamura YI, Nakae J, Kitamura T Abstract Recent studies have revealed that insulin signaling in pancreatic β-cells and the hypothalamus is critical for maintaining nutrient and energy homeostasis, the failure of which are hallmarks of metabolic syndrome. We previously reported that forkhead transcription factor forkhead box-containing protein of the O subfamily (FoxO)1, a downstream effector of insulin signaling, plays important roles in β-cells and the hypothalamus when we investigated the roles of FoxO1 independently in the pancreas and hypothalamus. However, because metabolic syndrome is caused by the combined disorders in hypothalamus and pancreas, to elucidate the...

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Islet-enriched gene expression and glucose-induced insulin secretion in human and mouse islets

Diabetologia — Tue, 13 Dec 2011 17:05:12 +0100

Conclusions/interpretation Our results suggest that human islets have a distinctive distribution and function of key regulators of the glucose-stimulated insulin secretion pathway, emphasising the urgent need to understand the processes that regulate human islet beta cell function. Content Type Journal ArticleCategory ArticlePages 1-12DOI 10.1007/s00125-011-2369-0Authors C. Dai, Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Vanderbilt University, 7435 MRBIV, Nashville, TN 37232, USAM. Brissova, Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Vanderbilt University, 7435 MRBIV, Nashville, TN 37232, USAY. Hang, Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, T...

Cytotoxic effect of some pentacyclic triterpenes and hemisynthetic derivatives of stigmasterol

Chemistry of Natural Compounds — Tue, 13 Dec 2011 17:02:41 +0100

Two different oxidation reactions (PCC and KMnO4) of stigmasterol gave three products, stigmasta-4,22-dien-3-one (1a), stigmasta-4,22-diene-3,6-dione (1b), and 3-O-acetyl-5β,6β-epoxystigmast-22-ene-3-ol (1c). The cytotoxic activities of hemisynthetic compounds, stigmasterol, and four pentacyclic triterpens 2–5 previously isolated from cultivated and wild Triumfetta cordifolia and identified were investigated against human fibrosarcoma cell line (HT1080). Most of the drugs showed moderate cytotoxic activity. It was also notice that the triterpene skeleton had a range of number of OH functions in which activity was observed. Spectroscopic analyses (1H and 13 C NMR) and mass were used to elucidate the structure of hemisynthetic compounds. Content Type Journal ArticlePages 1-4DOI ...

MT1-MMP Phosphorylation and Trafficking [Signal Transduction]

Journal of Biological Chemistry — Fri, 09 Dec 2011 05:00:00 +0100

In multicellular organisms, uncontrolled movement of cells can contribute to pathological conditions, such as multiple sclerosis and cancer. In highly aggressive tumors, the expression of matrix metalloproteinases (MMPs) is linked to the capacity of tumor cells to invade surrounding tissue and current research indicates that the membrane-anchored membrane type 1-matrix metalloproteinase (MT1-MMP) has a central role in this process. Endocytosis and trafficking of MT1-MMP are essential for its proper function, and here we examine the phosphorylation, internalization, and recycling of this enzyme, and the associated biochemical signaling in HeLa and HT-1080 fibrosarcoma cells. Activation of protein kinase C with phorbol 12-myristate 13-acetate resulted in phosphorylation of endogenous MT1-MMP...

Oncogenic stress sensitizes murine cancers to hypomorphic suppression of ATR

Journal of Clinical Investigation — Fri, 02 Dec 2011 08:01:27 +0100

Oncogenic Ras and p53 loss-of-function mutations are common in many advanced sporadic malignancies and together predict a limited responsiveness to conventional chemotherapy. Notably, studies in cultured cells have indicated that each of these genetic alterations creates a selective sensitivity to ataxia telangiectasia and Rad3-related (ATR) pathway inhibition. Here, we describe a genetic system to conditionally reduce ATR expression to 10% of normal levels in adult mice to compare the impact of this suppression on normal tissues and cancers in vivo. Hypomorphic suppression of ATR minimally affected normal bone marrow and intestinal homeostasis, indicating that this level of ATR expression was sufficient for highly proliferative adult tissues. In contrast, hypomorphic ATR reduction potentl...

A facial dismasking approach for resection of an infratemporal fossa sclerosing epithelioid fibrosarcoma

ANZ Journal of Surgery — Thu, 01 Dec 2011 05:00:00 +0100

(Source: ANZ Journal of Surgery)

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[Primary malignant bone tumors].

Der Orthopade — Thu, 01 Dec 2011 05:00:00 +0100

Authors: von Eisenhart-Rothe R, Toepfer A, Salzmann M, Schauwecker J, Gollwitzer H, Rechl H Abstract Among human neoplasms, primary malignant bone tumors are fairly rare. They present an incidence rate of roughly 10 cases per 1 million inhabitants per year. During childhood (<15 years), the percentage of malignant bone tumors amounts to 6% of all infantile malignancies. Only leukemia and lymphoma show a higher incidence in adolescence. Of all primary malignant bone tumors, 60% affect patients younger than 45 years and the peak incidence of all bone tumors occurs between 15 and 19 years. The most common primary malignant bone tumors are osteosarcoma (35%), chondrosarcoma (25%), and Ewing's sarcoma (16%). Less frequently (≤ 5%) occurring tumors are chordoma, malignant fibro...

Differential inhibition of tumour cell‐induced platelet aggregation by nicotinate aspirin prodrug (st0702) and aspirin

British Journal of Pharmacology — Tue, 29 Nov 2011 05:00:00 +0100

Conclusions and implications: Our results show that ST0702 is an effective inhibitor of TCIPA in vitro. The salicylate metabolite may contribute to the effects of ST0702 by inhibiting ADP‐mediated TCIPA. (Source: British Journal of Pharmacology)

Sclerosing epithelioid fibrosarcoma: Cytogenetic analysis of FUS rearrangement

Pathology International — Thu, 24 Nov 2011 05:00:00 +0100

Sclerosing epithelioid fibrosarcoma (SEF) is a rare but distinct variant of fibrosarcoma. A 43‐year‐old man presented with a lesion in his back that had been present for three years but had recently increased in size. Magnetic resonance imaging (MRI) revealed a 6‐cm sized ovoid mass showing low intensities on T1 and T2 weighted images. Histologically, the tumor was of moderate cellularity, and the cells were relatively uniform in size and shape. The cells were epithelioid, round, oval and polygonal with clear and slightly eosinophilic cytoplasm, forming nests, cords, or sheet‐like patterns with a dense collagenous and hyalinized matrix. The tumor was positive for vimentin, but negative for smooth muscle actin, desmin, HMB45, and CD34. Although the tumor showed nuclear overexpressio...

miR‐520c and miR‐373 upregulate MMP9 expression by targeting mTOR and SIRT1, and activate the Ras/Raf/MEK/Erk signaling pathway and NF‐κB factor in human fibrosarcoma cells

Journal of Cellular Physiology — Thu, 24 Nov 2011 01:42:10 +0100

In conclusion, miR‐520c and miR‐373 increased the expression of MMP9 by directly targeting the 3′‐UTRs of mRNAs of mTOR and SIRT1 and suppressing their translation; resulting in activation of the Ras/Raf/MEK/Erk signaling pathway and NF‐κB; and, finally, increasing the mRNA, protein, and activity of MMP9 and enhancing cell migration and cell growth in 3D type I collagen gels. J. Cell. Physiol. 227: 867–876, 2012. © 2011 Wiley Periodicals, Inc. (Source: Journal of Cellular Physiology)

Loss of implant‐bone interface following distal radial locking‐plate endoprosthesis limb‐sparing surgery in a dog

The Journal of Small Animal Practice — Sat, 19 Nov 2011 05:00:00 +0100

An eight‐year‐old, neutered female Rottweiler was presented with lameness of seven days duration. Radiographs were consistent with a distal radial bone tumour. Limb‐sparing surgery was performed using a commercially available endoprosthesis with a locking bone plate. Histopathological examination of the resected bone revealed an intraosseous fibrosarcoma, and postoperative adjuvant chemotherapy was initiated three weeks after surgery. Despite initial satisfactory limb function, lameness worsened four months after surgery. Radiographs revealed large areas of bone lysis around the proximal and distal screws, leading to significant resorption of the radius and radial carpal bone with subsequent construct failure. Further treatment was declined by the owner and the dog was subsequently e...

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Loss of heterozygosity (LOH) in tumour suppressor genes in benign and malignant mixed odontogenic tumours

Journal of Oral Pathology and Medicine — Tue, 15 Nov 2011 05:00:00 +0100

In conclusion, our results show a higher FAL in AFS compared to its benign counterparts and reveal a different pattern of LOH of tumour suppressor genes in AFS, which may regulate changes in tumour behaviour. (Source: Journal of Oral Pathology and Medicine)

Peritoneal Sarcomatosis Associated with Telemetry Implants in Sprague Dawley CD Rats: A Reveiw of Eight Cases.

Toxicologic Pathology — Mon, 14 Nov 2011 05:00:00 +0100

In this study, the incidence of peritoneal sarcomatosis arising secondary to surgically implanted telemetry devices (< 15% of implanted Sprague Dawley rats) is considered to represent a significant issue for both animal welfare and data validity in affected animals. Macroscopically, the telemetry-associated fibrosarcomas spread along the visceral and parietal peritoneum and mesentery surrounding abdominal organs. The histologic morphology of these sarcomas was typically an undifferentiated sarcoma, although well-differentiated fibrosarcomas and telangiectatic and pleomorphic variants were noted. Using special stains such as Masson's Trichrome demonstrated a collagenous extracellular matrix in 50% of these rats, which is consistent with a fibroblastic origin. Immunohistochemical studies ...

Differentiating aortic fibrosarcoma from acute intramural hematoma

The Journal of Thoracic and Cardiovascular Surgery — Mon, 07 Nov 2011 05:00:00 +0100

An 86-year-old woman with a medical history of hypertension was transferred to the Hennepin County Medical Center for severe substernal chest pain radiating to her back, associated with coughing. Physical examination revealed normal heart sounds with irregular heart rate, symmetric pulses, and intact neurologic examination. Electrocardiogram on admission showed atrial fibrillation. Chest computed tomography (CT) with contrast obtained before her transfer demonstrated soft tissue surrounding her ascending aorta, which was diagnosed as an aortic intramural hematoma () and a small pericardial effusion. An aortic dissection flap was not observed. Transthoracic echocardiography before emergency surgical exploration showed a soft tissue collection posterior to the ascending aorta without a disse...

Plasminogen Receptor S100A10 Is Essential for the Migration of Tumor-Promoting Macrophages into Tumor Sites.

Cell Research — Tue, 01 Nov 2011 04:00:00 +0100

In this study, we offer genetic evidence that plasminogen receptor S100A10 is essential for recruitment of macrophages to the tumor site. Growth of murine Lewis lung carcinomas or T241 fibrosarcomas was dramatically reduced in S100A10-deficient mice compared with wild-type mice. The tumor growth deficit corresponded with a decrease in macrophage density that could be rescued by intraperitoneal injection of wild-type but not S100A10-deficient macrophages. Notably, macrophages of either genotype could rescue tumor growth if they were injected into the tumor itself, establishing that S100A10 was required specifically for the migratory capability needed for tumor homing. Conversely, selective depletion of macrophages from wild-type mice phenocopied the tumor growth deficit seen in S100A10-defi...

Sarcoma with true epithelial differentiation secondary to irradiated glioblastoma.

Clinical Neuropathology — Tue, 01 Nov 2011 04:00:00 +0100

We report a case of a 48-year-old male operated on a primary glioblastoma, followed by radiotherapy. A local recurrence occurred 23 months later that was operated too, and a second diagnosis of a fibrosarcoma with true epithelial differentiation was made. Primary systemic neoplasms were largely excluded. The patient died shortly after, and postmortem showed another cerebral dural-attached mass corresponding to a sarcoma without epithelial differentiation, and leptomeningeal seeding composed of malignant epithelial elements only. Cytogenetics, however, disclosed the second tumor to be similar to the primary one. PMID: 22011736 [PubMed - in process] (Source: Clinical Neuropathology)

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Congenital-infantile fibrosarcoma masquerading as sacrococcygeal teratoma

Journal of Pediatric Surgery — Tue, 01 Nov 2011 04:00:00 +0100

We report a rare case of infantile fibrosarcoma masquerading as sacrococcygeal teratoma in a newborn. The literature on the subject is also reviewed. (Source: Journal of Pediatric Surgery)

Plasminogen Receptor S100A10 Is Essential for the Migration of Tumor-Promoting Macrophages into Tumor Sites

Cancer Research — Sun, 30 Oct 2011 04:00:00 +0100

Immunohistochemical characterisation of cells co-producing insulin and glucagon in the developing human pancreas

Diabetologia — Fri, 28 Oct 2011 16:46:03 +0100

Conclusions/interpretation Our results indicate that cells co-producing insulin and glucagon in the developing human pancreas share a transcription factor profile that is similar to that of mature alpha cells and suggest that some maturing alpha cells briefly exhibit ectopic insulin expression. Thus cells that co-produce insulin and glucagon may represent a transient cell population, which gives rise to mature alpha cells. Content Type Journal ArticleCategory ArticlePages 1-10DOI 10.1007/s00125-011-2344-9Authors M. J. Riedel, Laboratory of Molecular and Cellular Medicine, Department of Cellular and Physiological Sciences, Life Sciences Institute, 2350 Health Sciences Mall, University of British Columbia, Vancouver, BC, Canada V6T 1Z3A. Asadi, Laboratory of Molecula...

Magnetic resonance imaging of malignant soft tissue neoplasms in the adult.

Radiologic Clinics of North America — Fri, 28 Oct 2011 04:06:09 +0100

Authors: Walker EA, Salesky JS, Fenton ME, Murphey MD Abstract This review addresses the spectrum of malignant soft tissue tumors frequently found in adults. Rather than presenting a complete review, the focus of this discussion is on common lesions or lesions in which the diagnosis may be suggested on the basis of imaging. Diagnoses covered include undifferentiated high-grade pleomorphic sarcoma, fibrosarcoma, dermatofibrosarcoma protuberans, liposarcoma, synovial sarcoma, malignant peripheral nerve sheath tumor, clear cell sarcoma, hemangioendothelioma, hemangiopericytoma, angiosarcoma, and leiomyosarcoma. PMID: 22024296 [PubMed - in process] (Source: Radiologic Clinics of North America)

HA/RHAMM Regulate Fibrosarcoma Cell Adhesion [Signal Transduction]

Journal of Biological Chemistry — Fri, 28 Oct 2011 04:00:00 +0100

In conclusion, our results suggest that RHAMM/HA interaction regulates fibrosarcoma cell adhesion via the activation of FAK and ERK1/2 signaling pathways. (Source: Journal of Biological Chemistry)

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Magnetic Resonance Imaging of Malignant Soft Tissue Neoplasms in the Adult

Radiologic Clinics of North America — Thu, 27 Oct 2011 08:56:33 +0100

This review addresses the spectrum of malignant soft tissue tumors frequently found in adults. Rather than presenting a complete review, the focus of this discussion is on common lesions or lesions in which the diagnosis may be suggested on the basis of imaging. Diagnoses covered include undifferentiated high-grade pleomorphic sarcoma, fibrosarcoma, dermatofibrosarcoma protuberans, liposarcoma, synovial sarcoma, malignant peripheral nerve sheath tumor, clear cell sarcoma, hemangioendothelioma, hemangiopericytoma, angiosarcoma, and leiomyosarcoma. (Source: Radiologic Clinics of North America)

Novel octahedral Pt(IV) complex with di-n-propyl-(S,S)-ethylenediamine-N,N'-di-2-(3-cyclohexyl)propanoato ligand exerts potent immunomodulatory effects.

European Journal of Medicinal Chemistry — Tue, 25 Oct 2011 04:00:00 +0100

Authors: Miljković D, Poljarević JM, Petković F, Blaževski J, Momčilović M, Nikolić I, Saksida T, Stošić-Grujičić S, Grgurić-Šipka S, Sabo TJ Abstract We have recently reported that a novel octahedral Pt(IV) complex with di-n-propyl-(S,S)-ethylenediamine-N,N'-di-2-(3-cyclohexyl)propanoato ligand has a potent cytotoxic effect on glioma, melanoma and fibrosarcoma cell lines. In this work, we investigated the influence of the Pt(IV) compound on immune cells. We determined its effect on the viability of spleen cells and lymph node cells and on their capability to produce interferon (IFN)-γ and interleukin (IL)-17. Also, we researched the compound's impact on peritoneal macrophages and generation of NO in these cells. Our results show that the complex has limited influence...

Post‐radiation sarcomas. Clinical outcome of 52 Patients

Journal of Surgical Oncology — Wed, 19 Oct 2011 04:00:00 +0100

ConclusionsPrognosis of post‐radiation sarcomas is poor; the type of the sarcomas is the only significant variable for survival. J. Surg. Oncol © 2011 Wiley Periodicals, Inc. (Source: Journal of Surgical Oncology)

Maintenance of hepatic differentiation by hepatocyte attachment peptides derived from laminin chains.

Cell Research — Fri, 14 Oct 2011 15:10:29 +0100

Authors: Kikkawa Y, Kataoka A, Matsuda Y, Takahashi N, Miwa T, Katagiri F, Hozumi K, Nomizu M Abstract Hepatocytes rapidly lose hepatic functions upon isolation from liver, perhaps due to disrupted cell/matrix interactions. The matrix macromolecule laminin-111 consists of three chains, α1, β1, and γ1; it is a major component of Matrigel, which can maintain hepatic differentiation. We previously showed that the A13 peptide (RQVFQVAYIIIKA, α1 chain 121-133) derived from mouse laminin α1 exhibits hepatocyte attachment activity and maintains hepatic differentiation. Here, we sought to identify hepatocyte adhesive sequences from the mouse laminin β1 and γ1 chains using 22 synthetic peptides that show biological activity for fibrosarcoma cells. Nine peptides showed hepatocyte atta...

Identification of proteins that associate with integrin α2 by proteomic analysis in human fibrosarcoma HT‐1080 cells

Journal of Cellular Physiology — Fri, 14 Oct 2011 03:10:45 +0100

In this study, we expressed integrin α2 fused at the C terminus to a FLAG peptide in HT1080 cells. Cells stably expressing the chimeric protein were lysed with 1% Brij‐98 and affinity purified using anti‐FLAG antibody. Integrin β1 co‐purified with integrin α2 confirming the specificity of the purification procedure. Analysis of the purified mixture by nano‐LC/MS/MS identified 70 proteins. Nineteen of these were membrane proteins, including adhesion proteins, receptors, transporters, proteinases, and ion channel receptors, and the balance were cytoplasmic. Interestingly, eight of the proteins had previously been shown to associate with MT1‐MMP. We believe the present study provides a platform to facilitate the study of the mechanisms of cell adhesion, migration and invasion. ...

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Membrane-type 1 matrix metalloproteinase regulates fibronectin assembly to promote cell motility

FEBS Letters — Wed, 05 Oct 2011 04:00:00 +0100

Highlights: ► MT1-MMP inhibition induces fibronectin assembly in tumor cells. ► MT1-MMP expression in fibroblasts reduces fibronectin assembly. ► MT1-MMP degrades assembled fibronectin to promote cell motility. ► MT1-MMP inhibition generates a robust fibronectin assembly in collagen gel matrix, which restricts tumor cell invasion.Abstract: Fibronectin (FN) matrix assembly is an essential process in normal vertebrate development, which is frequently lost in tumor cells. Here we show that membrane-type 1 matrix metalloproteinase (MT1-MMP) regulates FN matrix assembly. MT1-MMP knockdown induced FN assembly in breast carcinoma cells. Ectopic expression of MT1-MMP reduced specifically the assembled FN matrix level without affecting whole FN production in fibroblasts. Treatment of fibros...

Imaging of Thoracic Sarcomas of the Chest Wall, Pleura, and Lung

Seminars in Ultrasound CT and MRI — Sat, 01 Oct 2011 04:00:00 +0100

Primary sarcomas of the thorax are uncommon. The purpose of this review is to describe the radiologic findings of sarcomas affecting the thorax, in particular the chest wall, pleura, and lungs. Most primary sarcomas affecting the thorax arise in the chest wall, and the most common sarcomas of the chest wall are chondrosarcoma, osteosarcoma, Ewing's sarcoma/primitive neuroectodermal tumor, malignant fibrous histiocytoma, and fibrosarcoma. Primary pleural and pulmonary sarcomas are rare. Although histologic analysis is almost always required for accurate diagnosis, imaging is important for staging of these tumors, and several of these tumors have distinctive radiologic features, allowing the radiologist to narrow the differential diagnosis. (Source: Seminars in Ultrasound CT and MRI)

Pediatric Soft Tissue Sarcomas

Seminars in Ultrasound CT and MRI — Sat, 01 Oct 2011 04:00:00 +0100

After a brief discussion of the rarity of soft tissue sarcomas in children and of the limited ability of magnetic resonance imaging to provide a tissue diagnosis, this article discusses the incidence, presentation, treatment, prognosis, and imaging characteristics of the more common and unusual pediatric soft tissue sarcomas. It begins with extensive discussion of rhabdomyosarcoma, synovial sarcoma, and congenital/infantile fibrosarcoma. It then presents a more abbreviated discussion of uncommon tumors such as alveolar soft part sarcoma, epithelioid sarcoma, extraosseous Ewing's sarcoma, granulocytic sarcoma, hemangiopericytoma, liposarcoma, malignant fibrous histiocytoma, malignant peripheral nerve sheath tumor, and undifferentiated sarcoma. (Source: Seminars in Ultrasound CT and MRI)

Case report of primitive myxoid mesenchymal tumor of infancy in a 2-month-old infant

International Journal of Oral and Maxillofacial Surgery — Sat, 01 Oct 2011 04:00:00 +0100

Primitive myxoid mesenchymal tumor of infancy (PMMTI) is rare with aggressive clinical course and a new category of pediatric fibroblastic–myofibroblastic tumor. It previously may have been included under the diagnostic categories of congenital-infantile fibrosarcoma, undifferentiated sarcoma or infantile fibromatosis. The tumors occurred on the trunk, extremities and head and neck. There are no reported case of this tumor occurring in the facial–buccal region. After surgery and regular follow up the patient is still alive until 3 years old now. (Source: International Journal of Oral and Maxillofacial Surgery)

Successful treatment of very large congenital infantile fibrosarcoma

Pediatrics International — Thu, 29 Sep 2011 18:46:12 +0100

(Source: Pediatrics International)

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The interaction of the second Kunitz-type domain (KD2) of TFPI-2 with a novel interaction partner, prosaposin, mediates the inhibition of the invasion and migration of human fibrosarcoma cells

BJ Cell — Mon, 26 Sep 2011 04:00:00 +0100

Tissue factor pathway inhibitor-2 (TFPI-2) has recently been recognized as a new tumor suppressor gene. Low expression of this protein in several types of cancers allows for enhanced tumor growth, invasion and metastasis. To investigate the molecular mechanism responsible for the tumor-suppressor effects of TFPI-2, we performed yeast two-hybrid analysis and identified prosaposin (PSAP) as a TFPI-2-interacting partner. This interaction was confirmed by co-immunoprecipitation and immunofluorescence. The region of TFPI-2 that interacts with PSAP is located in the second Kunitz-type domain (KD2). Further study showed that PSAP does not affect TFPI-2’s function as serine proteinase inhibitor but that TFPI-2 could inhibit the invasion-promoting effects of PSAP in human HT1080 fibrosarcoma...

Historical control data of neoplastic lesions in the Wistar Hannover Rat among eight 2-year carcinogenicity studies.

Experimental and Toxicologic Pathology — Sat, 24 Sep 2011 04:00:00 +0100

Authors: Carlus M, Elies L, Fouque MC, Maliver P, Schorsch F Abstract Incidences of neoplastic lesions were evaluated in untreated Hannover Wistar Rats RjHan: WI (470 males and 470 females) used as control animals in eight carcinogenicity studies. All these studies were performed in a similar environment either for the in vivo and the postmortem evaluation. The major neoplastic lesions were found in the endocrine, integumentary and reproductive systems. Pituitary adenoma was the most frequent neoplasm and occurred in 33.9% of the males and 54.6% of the female rats. The other most frequent tumors in males were thyroid C-cell adenoma (8.6%), pancreatic islet cell adenoma (8.1%), subcutaneous fibrosarcoma (6.6%), subcutaneous fibroma (4.7%), benign pheochromocytoma (3.4%), and cutaneo...

Arachidonic acid metabolism via cytosolic phospholipase A2α induces cytotoxicity in Niemann‐Pick disease type C cells

Journal of Cellular Physiology — Fri, 16 Sep 2011 04:00:00 +0100

AbstractNiemann‐Pick disease type C (NPC) is a neurodegenerative lipid storage disorder caused by mutations in NPC1 or NPC2 genes. Loss of function of either protein results in the endosomal accumulation of cholesterol and other lipids. Here, we report that NPC1‐deficient Chinese hamster ovary cells exhibit increased release of arachidonic acid (AA) and synthesis of prostaglandin E2 compared with wild‐type cells. The enhanced release of AA was inhibited by both treatment with the selective inhibitor of cytosolic phospholipase A2α (cPLA2α) and cultivation in lipoprotein‐deficient medium. There was no difference in the expression of both cyclooxygenase‐1 and ‐2 between NPC cells and wild‐type cells. U18666A, a cholesterol transport‐inhibiting agent commonly used to mimic NP...

Electrochemotherapy with cisplatin enhances local control after surgical ablation of fibrosarcoma in cats: an approach to improve the therapeutic index of highly toxic chemotherapy drugs

Journal of Translational Medicine — Wed, 14 Sep 2011 04:00:00 +0100

Conclusions We conclude that ECT is a safe and efficacious therapy for solid tumors; its use may be considered as part of strategies for the reintroduction of drugs with a narrow therapeutic index in the clinical protocols. (Source: Journal of Translational Medicine)

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NHS News Feed — Mon, 12 Sep 2011 17:22:00 +0100

This study focused on the effects of a derivative of colchicine, which the researchers called ICT2588, on one type of tumour in mice (fibrosarcoma), and did not appear to report all the results quoted in the press release. Until the full results are published, including a full investigation of potential adverse effects, they should be seen as preliminary. What did their published work find? The published research used a derivative of colchicine, which the researchers called ICT2588. This drug is inactive until metabolised by a member of the MMP family called MT1-MMP. The paper describes the level of production of the MMPs in different human cancer cells grown in the laboratory and on tumours grown from these human cancer cells in mice. They also looked at the effects of ICT2588 on the f...

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'Crocus drug' studied for cancer

NHS News Feed — Mon, 12 Sep 2011 17:22:00 +0100

Transcriptomes of the major human pancreatic cell types

Diabetologia — Thu, 01 Sep 2011 06:15:06 +0100

Conclusions/interpretation This is the first comprehensive analysis of the transcriptomes of human exocrine and endocrine pancreatic cell types—including beta cells—and provides a useful resource for diabetes research. In addition, paracrine signalling pathways within the pancreas are shown. These results will help guide efforts to specify human beta cell fate by embryonic stem cell or induced pluripotent stem cell differentiation or genetic reprogramming. Content Type Journal ArticleCategory ArticlePages 1-13DOI 10.1007/s00125-011-2283-5Authors C. Dorrell, Papé Family Pediatric Research Institute, Oregon Health and Science University, 3181 SW Sam Jackson Park Rd, L321, Portland, OR 97239, USAJ. Schug, Department of Genetics and Institute for Diabetes, Obesity...

Spindle Cell Sarcomas

Surgical Pathology Clinics — Thu, 01 Sep 2011 04:00:00 +0100

Abstract: Information is presented on the pathology of spindle cell sarcomas. Synovial sarcoma, malignant peripheral nerve sheath tumor, fibrosarcoma, inflammatory myofibroblastic tumor, low-grade myofibrosarcoma, leiomyosarcoma, spindle cell rhabdomyosarcoma, and endothelial neoplasms are discussed in terms of an overview of the tumor, microscopic and gross features, diagnostic techniques, genetic markers, differential diagnosis, clinical details, and prognosis. (Source: Surgical Pathology Clinics)

Epithelioid Lesions

Surgical Pathology Clinics — Thu, 01 Sep 2011 04:00:00 +0100

Abstract: Epithelioid variants have been described for most mesenchymal tumors, including leiomyosarcoma, pleomorphic liposarcoma, epithelioid fibrous histiocytoma, and myxofibrosarcoma. Soft tissue tumors that commonly show epithelioid morphology include epithelioid vascular lesions, epithelioid sarcoma, sclerosing epithelioid fibrosarcoma, and epithelioid malignant peripheral nerve sheath tumor. Many of the entities described in this review were originally described as “simulating carcinoma” or “often mistaken for carcinoma” and this pitfall should be considered when evaluating epithelioid lesions in soft tissue. Many epithelioid soft tissue tumors express epithelial antigens to a varying degree and an immunohistochemical panel is essential for correct classification. (Source: Su...

Preferential Uptake of L- versus D-Amino Acid Cell-Penetrating Peptides in a Cell Type-Dependent Manner.

Chemistry and Biology — Thu, 25 Aug 2011 23:00:00 +0100

Authors: Verdurmen WP, Bovee-Geurts PH, Wadhwani P, Ulrich AS, Hällbrink M, van Kuppevelt TH, Brock R Abstract The use of protease-resistant D-peptides is a prominent strategy for overcoming proteolytic sensitivity in the use of cell-penetrating peptides (CPPs) as delivery vectors. So far, no major differences have been reported for the uptake of L- and D-peptides. Here we report that cationic L-CPPs are taken up more efficiently than their D-counterparts in MC57 fibrosarcoma and HeLa cells but not in Jurkat T leukemia cells. Reduced uptake of D-peptides co-occurred with persistent binding to heparan sulfates (HS) at the plasma membrane. In vitro binding studies of L- and D-peptides with HS indicated similar binding affinities. Our results identify two key events in the uptake of...

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Fine needle aspiration cytology in ovarian lesions: an institutional experience of 584 cases

Cytopathology — Wed, 24 Aug 2011 23:00:00 +0100

Conclusion: FNAC has a high specificity for diagnosis of ovarian/adnexal lesions but greater experience is required for the accurate subtyping of neoplasms and sensitivity is limited by inconclusive/inadequate results. (Source: Cytopathology)

miR‐520c and miR‐373 target mTOR and SIRT1, activate the Ras/Raf/MEK/Erk pathway and NF‐κB, with up‐regulation of MMP9 in human fibrosarcoma cells

Journal of Cellular Physiology — Tue, 23 Aug 2011 23:00:00 +0100

In conclusion, miR‐520c and miR‐373 increased the expression of MMP9 by directly targeting the 3'UTRs of mRNAs of mTOR and SIRT1 and suppressing their translation; resulting in activation of the Ras/Raf/MEK/Erk signaling pathway and NF‐κB; and finally increasing the mRNA, protein, and activity of MMP9 and enhancing cell migration and cell growth in 3‐D type I collagen gels. J. Cell. Physiol. © 2011 Wiley‐Liss, Inc. (Source: Journal of Cellular Physiology)

Spontaneous Nonthymic Tumors in SCID Mice.

Comparative Medicine — Fri, 19 Aug 2011 17:48:03 +0100

Authors: Huang P, Westmoreland SV, Jain RK, Fukumura D Abstract SCID mice provide an excellent platform for cancer research. Because of their lack of immunity, SCID mice readily succumb to infectious pathogens and therefore must be maintained in an SPF, barrier-protected environment. Although SPF and barrier facilities prevent infection, SCID mice remain prone to premature death due in part to a high prevalence of spontaneous thymic lymphomas. However, little is known about spontaneous nonthymic tumors in SCID mice. We therefore analyzed the incidence of nonthymic tumor in our defined-flora C.B-17/Icr-SCID/Sed mice and examined their histopathologic characteristics. We necropsied 1060 retired SCID breeders (506 males, 554 females; average ages of 325 and 320 d, respectively) and fo...

Cardiac metastasis and hypertrophic osteoarthropathy in recurrent infantile fibrosarcoma

Pediatric Blood and Cancer — Wed, 17 Aug 2011 23:00:00 +0100

We describe a patient presenting with hypertrophic osteoarthropathy as the first symptom of recurrent infantile fibrosarcoma (IF). During surgical resection of lung metastasis, the patient suffered sudden cardiac arrest. Autopsy demonstrated a metastatic lesion in the intraventricular septum of the heart, which is previously undescribed in the literature. This case demonstrates that IF can be aggressive despite its more typical benign course. Pediatr Blood Cancer © 2011 Wiley‐Liss, Inc. (Source: Pediatric Blood and Cancer)

Maximal T Cell-Mediated Antitumor Responses Rely upon CCR5 Expression in Both CD4+ and CD8+ T Cells

Cancer Research — Wed, 10 Aug 2011 23:00:00 +0100

Immune responses against cancer rely upon leukocyte trafficking patterns that are coordinated by chemokines. CCR5, the receptor for chemotactic chemokines MIP1alpha, MIP1beta, and RANTES (CCL3, CCL4, CCL5), exerts major regulatory effects on CD4+- and CD8+ T cell-mediated immunity. Although CCR5 and its ligands participate in the response to various pathogens, its relevance to tumoral immune control has been debated. Here, we report that CCR5 has a specific, ligand-dependent role in optimizing antitumor responses. In adoptive transfer studies, efficient tumor rejection required CCR5 expression by both CD4+ and CD8+ T cells. CCR5 activation in CD4+ cells resulted in CD40L upregulation, leading to full maturation of antigen-presenting cells and enhanced CD8+ T-cell crosspriming and tumor inf...

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Conjugation of substituted ferrocenyl to thiadiazine as apoptosis-inducing agents targeting the Bax/Bcl-2 pathway.

European Journal of Medicinal Chemistry — Wed, 10 Aug 2011 23:00:00 +0100

This study investigated the induction of apoptosis in human fibrosarcoma cells (HT1080) after treatment with a series of 6-ferrocenyl-3-subsituted7H-1,2,4-triazolo[3,4-b]- 1,3,4-thiadiazine (FTFs). We found that FTFs could suppress the viability of HT1080 cells. Cell cycle analysis showed that proliferative inhibition of HT1080 cells occurred through apoptosis, as the cells were blocked in G1 phase. Moreover, mitochondrial membrane staining assay demonstrated that FTFs exposure significantly decreased mitochondrial membrane potential. Finally, under the stress of FTFs, Bax/Bcl-2 ratio in HT1080 cells was significantly increased. These results suggested that FTFs-induced apoptosis in HT1080 cells may work dependent on a Bax/Bcl-2 pathway. PMID: 21864950 [PubMed - as supplied by publishe...

Role of JNK-1 regulation in the protection of contact-inhibited fibroblasts from oxidative stress.

Molecular and Cellular Biochemistry — Fri, 05 Aug 2011 23:00:00 +0100

Authors: Gaballah M, Slisz M, Hutter-Lobo D Abstract The molecular signaling events leading to protection from oxidative stress-induced apoptosis upon contact inhibition have not been fully investigated. Previous research has indicated a role for mitogen-activated protein kinases (MAPKs) in the regulation of contact inhibition, and these proteins have also been associated with cell cycle regulation and stress-induced apoptosis. The potential role of the MAPK JNK-1 in the stress-response of actively proliferating and contact-inhibited cells was investigated. Actively proliferating normal fibroblasts (BJ) and fibrosarcoma cells (HT-1080) were stressed with H(2)O(2), and levels of activated JNK-1 and cleaved PARP were ascertained. Similarly, these results were compared with levels of ...

c-Maf plays a crucial role for the definitive erythropoiesis that accompanies erythroblastic island formation in the fetal liver

Blood — Wed, 03 Aug 2011 23:00:00 +0100

In conclusion, these results strongly suggest that c-Maf is crucial for definitive erythropoiesis in fetal liver, playing an important role in macrophages that constitute erythroblastic islands. (Source: Blood)

[Forequarter amputation of the right upper chest : Limitations of ultra radical interdisciplinary oncological surgery.]

Der Chirurg — Wed, 03 Aug 2011 23:00:00 +0100

Authors: Dragu A, Hohenberger W, Lang W, Schmidt J, Horch RE Total forearm free flap procedures after forequarter amputations have been sparsely described in the literature. Using the amputated arm as a "free filet flap" remains a viable surgical option after radical forequarter amputations performed for the resection of large, invasive tumors of the shoulder or thoracic wall region. Using the forequarter specimen as a donor site seems favorable in that it eliminates the usual donor site morbidity. Nevertheless, in our patient with invasive ductal carcinoma of the breast and a fibrosarcoma suffering from severe pain and septic conditions - which failed to respond properly to conservative therapy - as well as rapidly progressive tumor ulceration despite repeated radiation therapy, we de...

Peptide from the C-terminal domain of tissue inhibitor of matrix metalloproteinases-2 (TIMP-2) inhibits membrane activation of matrix metalloproteinase-2 (MMP-2).

Matrix Biology — Wed, 03 Aug 2011 23:00:00 +0100

In this study, we tested the feasibility of inhibiting activation of proMMP-2 by exogenous inhibitors, which block the binding between PEX and TIMP-2. The recombinant C-TIMP-2 and synthetic peptides from C-TIMP-2 were used as inhibitors for proMMP-2 activation. Recombinant C-TIMP-2 bound specifically to both the catalytically inactive MMP-2(E404A) and the C-terminal domain of MMP-2 (PEX) in a concentration dependent manner with apparent K(d) of 3.9×10(-7)M and 1.7×10(-7)M, respectively. Moreover, C-TIMP-2 competed the binding between MMP-2(E404A) and full-length TIMP-2. Finally, activity assays showed that addition of C-TIMP-2 to HT-1080 fibrosarcoma cells inhibited proMMP-2 activation in a concentration-dependent manner. We then designed a synthetic peptide, P175L, consisting of 20 resi...

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Correlation Between Antioxidant Activity of Garlic Extracts and WEHI-164 Fibrosarcoma Tumor Growth in BALB/c Mice

Journal of Medicinal Food — Wed, 03 Aug 2011 19:04:31 +0100

Journal of Medicinal Food , Vol. 0, No. 0. (Source: Journal of Medicinal Food)

Chemical sympathectomy suppresses fibrosarcoma development and improves survival of tumor-bearing rats.

Neoplasma — Tue, 26 Jul 2011 02:00:05 +0100

Authors: Lackovicova L, Banovska L, Bundzikova J, Janega P, Bizik J, Kiss A, Mravec B Both experimental and clinical data indicate that the sympathetic nervous system may affect the development of certain tumors. To test this, in the present study we combined in vivo and in vitro approaches to study the effect of the sympathetic nervous system on proliferation of BP6-TU2 fibrosarcoma cells. First, we investigated the effect of 6-hydroxydopamine-induced sympathectomy on tumor development and survival of tumor-bearing rats. One week after chemical sympathectomy, we injected the BP6-TU2 fibrosarcoma cells intraperitoneally into male Wistar rats. The sympathectomy significantly reduced the incidence of intraperitoneal tumors and resulted in significantly improved survival of tumor-bearing ...

Serum alkaline phosphatase activity is not a marker for neoplastic transformation of esophageal nodules in canine spirocercosis

Veterinary Clinical Pathology — Mon, 25 Jul 2011 23:00:00 +0100

Conclusion: ALP is a poor marker of malignant transformation in canine spirocercosis. (Source: Veterinary Clinical Pathology)

The antiproliferative function of violacein‐like purple violet pigment (PVP) from an Antarctic Janthinobacterium sp. Ant5‐2 in UV‐induced 2237 fibrosarcoma

International Journal of Dermatology — Mon, 25 Jul 2011 23:00:00 +0100

Conclusions We describe the anti‐cancer mechanism of the PVP for the first time from an Antarctic bacterium and suggest that the PVP could be used as a potent chemotherapeutic agent against nonmelanoma skin cancers. (Source: International Journal of Dermatology)

Pivotal Role of Innate and Adaptive Immunity in Anthracycline Chemotherapy of Established Tumors

Cancer Research — Wed, 13 Jul 2011 23:00:00 +0100

We show, in a series of established experimental breast adenocarcinomas and fibrosarcomas induced by carcinogen de novo in mice, that the therapeutic efficacy of doxorubicin treatment is dependent on CD8 T cells and IFN-γ production. Doxorubicin treatment enhances tumor antigen–specific proliferation of CD8 T cells in tumor-draining lymph nodes and promotes tumor infiltration of activated, IFN-γ–producing CD8 T cells. Optimal doxorubicin treatment outcome also requires both interleukin (IL)-1β and IL-17 cytokines, as blockade of IL-1β/IL-1R or IL-17A/IL-17Rα signaling abrogated the therapeutic effect. IL-23p19 had no observed role. The presence of γδ T cells, but not Jα18+ natural killer T cells, at the time of doxorubicin treatment was also important. In tumor samples taken fr...

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Fibrosarcoma of Mandible: A Case Report

Infectious Diseases in Obstetrics and Gynecology — Thu, 07 Jul 2011 15:54:48 +0100

Fibrosarcoma is a malignant mesenchymal neoplasm of fibroblasts that rarely affects the oral cavity and can cause local recurrences or metastasis. In this paper, a case of fibrosarcoma in the posterior area of mandible in a 44-year-old woman is described. Clinical examination revealed a growth on right mandibular third molar region extending on the buccal and the lingual side. There was history of extraction of posterior teeth. Radiologically, there was a diffuse bone loss. Microscopically, the tumor showed an intense proliferation of fibroblasts of variable size and shape. These cells were arranged in parallel bands and partly crossing each other. The cells exhibited increased mitotic activity and nuclear pleomorphism. Immunohistochemically the cells showed immunoreactivity only for vimen...

A previously unreported malignancy of the thyroid

Medical Oncology — Thu, 07 Jul 2011 05:48:57 +0100

We report a case of an ameloblastic fibrosarcoma arising from thyroid gland in a 44 year-old woman. Following total thyroidectomy, a histopathologic, immunohistologic, and genotypic examination revealed ameloblastic fibrosarcoma. The tumor was composed of odontogenic epithelium, resembling that of ameloblastoma, and a mesenchymal part exhibiting features of fibrosarcoma. To our review, our case represents the first report of ameloblastic fibrosarcoma of the thyroid gland. Ameloblastic fibrosarcoma may arise from thyroid gland. Content Type Journal ArticlePages 1-3DOI 10.1007/s12032-011-0020-zAuthors Bulent Cetin, Department of Internal Medicine, Division of Medical Oncology, Gazi University Medical School, Besevler, Ankara, 06500 TurkeySuleyman Buyukberber, Department of In...

Tumor-Recruited Neutrophils and Neutrophil TIMP-Free MMP-9 Regulate Coordinately the Levels of Tumor Angiogenesis and Efficiency of Malignant Cell Intravasation.

The American Journal of Pathology — Wed, 06 Jul 2011 23:00:00 +0100

Authors: Bekes EM, Schweighofer B, Kupriyanova TA, Zajac E, Ardi VC, Quigley JP, Deryugina EI Neutrophils, recruited to sites of tumor development, might contribute to tumor neovascularization by supplying matrix metalloproteinase-9 (MMP-9), a protease that has been genetically and biochemically linked to induction of angiogenesis. Specific roles for inflammatory neutrophils and their distinct proMMP-9 in the coordinated regulation of both tumor angiogenesis and tumor cell dissemination, however, have not been addressed. We demonstrate that highly disseminating variants of human fibrosarcoma and human prostate carcinoma recruit enhance levels of MMP-9-positive neutrophils concomitant with exhibition of enhanced levels of tumor angiogenesis and intravasation. Neutralization of interleuk...

Enhancement of Toll-like receptor 2-mediated immune responses by AIMP1, a novel cytokine, in mouse dendritic cells.

Immunology — Tue, 28 Jun 2011 23:00:00 +0100

In this study, we attempted to determine whether AIMP1 is capable of regulating the expression of TLRs, and also capable of affecting the TLR-mediated activation of DCs. Expression of TLR1, -2, -3 and -7 was highly induced by AIMP1 treatment in BM-DCs, whereas the expression of other TLRs was either down-regulated or remained unchanged. In particular, the expression of the TLR2 protein was up-regulated by AIMP1 in a time-dependent and dose-dependent manner, and was suppressed upon the addition of BAY11-7082, an inhibitor of nuclear factor-κB. AIMP1 was also shown to increase nuclear factor-κB binding activity. Importantly, AIMP1 enhanced the production of interleukin-6 and interleukin-12, and the expression of co-stimulatory molecules on BM-DCs when combined with lipoteichoic acid or Pam...

MafA and MafB activity in pancreatic β cells.

Trends in Endocrinology and Metabolism: TEM — Mon, 27 Jun 2011 23:00:00 +0100

Authors: Hang Y, Stein R Analyses in mouse models have revealed crucial roles for MafA (musculoaponeurotic fibrosarcoma oncogene family A) and MafB in islet β cells, with MafB being required during development and MafA in adults. These two closely related transcription factors regulate many genes essential for glucose sensing and insulin secretion in a cooperative and sequential manner. Significantly, the switch from MafB to MafA expression also appears to be vital for functional maturation of β cells produced by human embryonic stem (hES) cell differentiation. This review summarizes the discovery, distribution, and function of MafA and MafB in rodent pancreatic β cells, and describes some key questions regarding their importance to β cells. PMID: 21719305 [PubMed - as supplied...

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Chromanols from Sargassum siliquastrum and Their Antioxidant Activity in HT 1080 Cells.

Chemical and Pharmaceutical Bulletin — Mon, 27 Jun 2011 16:30:03 +0100

Authors: Lee JI, Seo Y Six meroterpenoids (compounds 1-6) of chromene class, including three known compounds (1-3), were isolated from Sargassum siliquastrum. The structure of these compounds was established by extensive 2D-NMR experiments such as (1)H gradient double quantum filtered correlation spectroscopy (gDQCOSY), total correlation spectroscopy (TOCSY), nuclear Overhauser effect spectroscopy (NOESY), gradient heteronuclear multiple quantum coherence (gHMQC), and gradient heteronuclear multiple bond correlation (gHMBC), and by comparison with published spectral data. The antioxidant activity of these compounds was evaluated by various antioxidant tests, such as scavenging effects on generation of intracellular reactive oxygen species (ROS), increments of intracellular glutathione ...

Survivin Monomer in Apoptosis Regulation [Molecular Bases of Disease]

Journal of Biological Chemistry — Thu, 23 Jun 2011 23:00:00 +0100

Survivin was initially described as an inhibitor of apoptosis and attracted growing attention as one of the most tumor-specific genes in the human genome and a promising target for cancer therapy. Lately, it has been shown that survivin is a multifunctional protein that takes part in several crucial cell processes. At first, it was supposed that survivin functions only as a homodimer, but now data indicate that many processes require monomeric survivin. Moreover, recent studies reveal a special mechanism regulating the balance between monomeric and dimeric forms of the protein. In this paper we studied the mutant form of survivin that was unable to dimerize and investigated its role in apoptosis. We showed that survivin monomer interacts with Smac/DIABLO and X-linked inhibitor of apoptosis...

Sclerosing Epithelioid Fibrosarcoma of the Oral Cavity

Head and Neck Pathology — Tue, 21 Jun 2011 18:33:58 +0100

We present an example of a rare FUS-positive SEF that arose in the floor of mouth of a 56 year old male. Light microscopy, exhaustive immunohistology, and FISH examination showing chromosome rearrangement using the FUS break-apart probe led to an erroneous diagnosis of LGFMS with giant collagen rosettes. An outside expert agreed with that diagnosis citing the FISH results as confirmatory. Upon review almost 2 years later after local recurrence, the classic histopathologic features of SEF were noted instead. This example suggests that at least a subset if not most examples of SEF are part of the LGFMS “family” of neoplasms, and reiterates the value of careful histologic examination in an age of increasingly sophisticated and presumably specific molecular results. Co...

Suppression of hepatitis B virus replication in Tupaia hepatocytes by tumor necrosis factor alpha of Tupaia belangeri.

Comparative immunology, microbiology and infectious diseases. — Thu, 16 Jun 2011 23:00:00 +0100

Authors: Xu Y, Köck J, Lu Y, Yang D, Lu M, Zhao X Recently, Tupaia belangeri was used to study the full replication cycle of hepatitis B virus (HBV) in the primary hepatocyte cultures. Thus, the Tupaia model represents a suitable model to study the effects of cytokines on HBV infection. Here, Tupaia tumor necrosis factor-alpha (TNF-α) was molecularly cloned and expressed in mammalian cells. A test system for the biological activity of Tupaia TNF-α was established on the basis of its cytotoxic effect to the murine fibrosarcoma cell line L929. Recombinant Tupaia TNF-α was able to suppress HBV replication in primary Tupaia hepatocytes (PTH). However, the formation of HBV covalently closed circular DNA (cccDNA) and viral RNA was not completely prevented. Therefore, Tupaia TNF-α may co...

Differential dependency of human cancer cells on vascular endothelial growth factor-mediated autocrine growth and survival

Cancer Letters — Thu, 16 Jun 2011 23:00:00 +0100

Abstract: Analysis using the public microarray database Gene Expression Omnibus indicates significantly higher mRNA expression of VEGF and VEGFRs in colorectal cancer and high grade astrocytoma but not in hepatocellular carcinoma compared to normal tissue. Human malignant astrocytoma cell lines (U251-MG and U373-MG) and HT-1080 fibrosarcoma cells expressed relatively higher levels of VEGF and VEGFRs compared to hepatocellular and colorectal cancer cell lines. Administration of exogenous VEGF-A induced cell growth in a dose-dependent fashion in astrocytoma and fibrosarcoma cells but not in colorectal and hepatocellular cancer cells. The blockade of VEGF inhibited cell survival only in U251-MG, U373-MG and HT-1080 cells. These results collectively suggest the role of autocrine VEGF signaling...

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Glypican-3 is expressed in rhabdomyosarcomas but not adult spindle cell and pleomorphic sarcomas

Journal of Clinical Pathology — Wed, 15 Jun 2011 23:00:00 +0100

Conclusions This is the first study of GPC3 in a large series of sarcomas, and highlights expression of GPC3 in RMS but not other STS. As glypicans are rarely expressed in mature tissue, GPC3 may be a therapeutic target in RMS, and as the protein can be shed from the cell surface, it may have future application as a biomarker for this disease. (Source: Journal of Clinical Pathology)

Pycnogenol (PYC) Induces Apoptosis in Human Fibrosarcoma (HFS) Cells Under Metal-mediated Oxidative Stress

Journal of Complementary and Integrative Medicine — Tue, 14 Jun 2011 15:59:31 +0100

Pycnogenol (PYC), polyphenolic compounds with antioxidant activity, acted as a prooxidant. PYC caused oxidative stress in human fibrosarcoma cells (HFS) when administered following pre-treatment with iron chloride. The generated reactive oxygen species (ROS) caused the formation of 8-hydroxy-2’-deoxyguanosine (8-OHdG) in DNA and resulted in more apoptosis in HFS cells than in the human fibroblastoma (HFB) cells. DNA damage and cellular viability at different PYC concentrations were closely consistent with cell growth, high performance liquid chromatography (HPLC), Enzyme Linked Immunosorbent Assay (ELISA) and assays of two major antioxidant enzymes, superoxide dismutase (SOD) and catalase. Although the presence of PYC induced total SOD and catalase activities under oxidative stress in do...

Rhapontigenin Inhibited Hypoxia Inducible Factor 1 Alpha Accumulation and Angiogenesis in Hypoxic PC-3 Prostate Cancer Cells.

Biological and Pharmaceutical Bulletin — Mon, 13 Jun 2011 23:45:03 +0100

Authors: Jung DB, Lee HJ, Jeong SJ, Lee HJ, Lee EO, Kim YC, Ahn KS, Chen CY, Kim SH Hypoxia inducible factor 1 alpha (HIF-1α) is frequently over-expressed in the numerous types of cancer and plays an important role in angiogenesis. In the present study, the inhibitory mechanism of rhapontigenin isolated from Vitis coignetiae was investigated on HIF-1α stability and angiogenesis in human prostate cancer PC-3 cells. Rhapontigenin significantly suppressed HIF-1α accumulation at protein level but not at mRNA level in PC-3 cells under hypoxia. Also, rhapontigenin suppressed hypoxia-induced HIF-1α activation in various cancer cells, such as colorectal adenocarcinoma (SW620), breast adenocarcinoma (MCF-7), fibrosarcoma (HT-1080) and prostate carcinoma (LNCaP). Interestingly, rhapontigenin...

Low concentrations of alendronate increase the local invasive potential of osteoblastic sarcoma cell lines via connexin 43 activation.

Pathology, Research and Practice — Thu, 09 Jun 2011 23:00:00 +0100

Authors: Yoshitani K, Kido A, Honoki K, Akahane M, Fujii H, Tanaka Y Bisphosphonates (BPs) are agents used for treating disorders of excessive bone resorption. In addition, due to their cell-killing activity, BPs were potent candidates for adjuvant cancer therapy. On the other hand, low-concentrations of BPs have been reported to increase cellular viability in several types of tumor cells. Therefore, we focused on the effect of BPs on cellular aggressiveness of malignant bone tumors at low concentrations. MTS assay was performed using osteosarcoma cell lines MG63 and HOS, fibrosarcoma cell line HT1080, and prostate cancer cell line PC3. All the cell lines showed toxicity at high concentrations. On the other hand, at lower concentrations, the cellular viabilities of HOS and MG63 were ra...

Low-grade fibromyxoid sarcoma of the perineum with heterotopic ossification: case report and review of the literature

Human Pathology — Thu, 09 Jun 2011 04:00:00 +0100

We present a case of an ossifying tumor of the perineum that required an open biopsy and fluorescent in situ hybridization testing for FUS and CREB3L2 for diagnosis as a variant of low-grade fibromyxoid sarcoma. Subsequent excision revealed characteristic areas with collagen rosettes as well as foci of heterotopic ossification. Significant ossification, which is well documented in entities such as synovial sarcoma, ossifying fibromyxoid tumor, and extraskeletal osteosarcoma, has not been reported previously in low-grade fibromyxoid sarcoma. This case demonstrates the value of having a distinctive confirmatory molecular pathology test for diagnosis and expands our knowledge of the histologic variants possible in low-grade fibromyxoid sarcoma. (Source: Human Pathology)

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Prenatal management of congenital infantile fibrosarcoma: unexpected outcome.

The Ultrasound Review of Obstetrics and Gynecology — Tue, 31 May 2011 23:00:00 +0100

We report the case of a large leg tumor in a fetus at 36 weeks of gestation. The tumor's location, ultrasound characteristics and magnetic resonance imaging (MRI) findings enabled a prenatal diagnosis of congenital fibrosarcoma and allowed us to establish the prognosis. After multidisciplinary discussion, it was decided that the pregnancy should continue to 38 weeks, with surgery or neo-adjuvant chemotherapy scheduled after delivery. Unfortunately, the tumor unexpectedly burst in utero and the newborn died of the consequences of hemorrhagic shock, despite rapid amputation. Histological examination confirmed the nature of the tumor. The prognosis of congenital fibrosarcoma is generally good when there are no metastases. MRI is key to establishing a prenatal diagnosis. However, rupture of th...

Prenatal management of congenital infantile fibrosarcoma: unexpected outcome

Ultrasound in Obstetrics and Gynecology — Wed, 25 May 2011 18:07:58 +0100

We report the case of a large leg tumor in a fetus at 36 weeks of gestation. The tumor's location, ultrasound characteristics and magnetic resonance imaging (MRI) findings enabled a prenatal diagnosis of congenital fibrosarcoma and allowed us to establish the prognosis. After multidisciplinary discussion, it was decided that the pregnancy should continue to 38 weeks, with surgery or neo‐adjuvant chemotherapy scheduled after delivery. Unfortunately, the tumor unexpectedly burst in utero and the newborn died of the consequences of hemorrhagic shock, despite rapid amputation. Histological examination confirmed the nature of the tumor. The prognosis of congenital fibrosarcoma is generally good when there are no metastases. MRI is key to establishing a prenatal diagnosis. However, rupture of ...

New microtubule polymerization inhibitors comprising a nitrooxymethylphenyl group.

Bioorganic and Medicinal Chemistry — Sun, 22 May 2011 23:00:00 +0100

Authors: Kawaratani Y, Harada T, Hirata Y, Nagaoka Y, Tanimura S, Shibano M, Taniguchi M, Yasuda M, Baba K, Uesato S We have designed cancer antiproliferative compounds, starting from aniline or phenol derivative, which comprise one or two nitrooxymethylphenyl groups as do the hybrid drugs NCX4040 and NCX530. Compound 2a with p-nitrooxymethylbenzoyl-oxy and -amino groups as well as 8a with a p-nitrooxymethylbenzoylamino group showed more promising effects than NCX4040 against human colon and breast cancer cells. Since 2a and 8a, but not NCX4040, arrested human colon carcinoma HCT116 cells in the M phase, the former two compounds may inhibit cell growth differently from NCX4040. Merged images of immunofluorescence-stained α-tubulin and Hoechst-stained nuclei in human fibrosarcoma HT108...

u-Slide Chemotaxis: A new chamber for long-term chemotaxis studies

BMC Cell Biology - Latest articles — Tue, 17 May 2011 23:00:00 +0100

Conclusions: Compared to the Boyden chamber assay, this innovative system allows for the generation of a stable gradient for a much longer time period as well as for the tracking of cell locomotion along this gradient and over long distances. Finally, random migration can be distinguished from primed and directed migration along chemotactic gradients in the same experiment, a feature, which can be qualified via cell morphology imaging. (Source: BMC Cell Biology - Latest articles)

Anticancer effects of fullerene [C60] included in polyethylene glycol combined with visible light irradiation through ROS generation and DNA fragmentation on fibrosarcoma cells with scarce cytotoxicity to normal fibroblasts.

Oncology Research — Fri, 13 May 2011 22:30:04 +0100

Authors: Liao F, Saitoh Y, Miwa N Fullerene [C60] included in polyethylene glycol (PEG) at a composing ratio of 1:350 w/w was examined for anticancer effects upon photodynamic therapy (PDT). Human connective tissue-derived fibrosarcoma cells HT1080 were decreased for a viability of 50% or 30%, by 3-h administration with PEG-fullerene [C60] at 50 or 100 ppm fullerene [C60] equivalent, respectively, subsequent rinsing out and irradiation with visible light (400-600 nm, 140 J/cm2: 450-fold as intense as in average outdoor), whereas the same tissue type-derived normal fibroblastic cells DUMS16 retained a viability of 93% or 85% under the same conditions. Anticancer effects were dependent on PEG-fullerene [C60] concentrations and irradiation doses, and scarcely exerted by PEG-fullerene [C60...

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53BP1 and MDC1 foci formation in HT-1080 cells for low- and high-LET microbeam irradiations.

Radiation and Environmental Biophysics — Tue, 10 May 2011 23:00:00 +0100

Authors: Mosconi M, Giesen U, Langner F, Mielke C, Dalla Rosa I, Dirks WG An improved assessment of the biological effects and related risks of low doses of ionizing radiation is currently an important issue in radiation biology. Irradiations using microbeams are particularly well suited for precise and localized dose depositions, whereas recombinant cell lines with fluorescent proteins allow the live observation of radiation-induced foci. Living cells of the fibrosarcoma cell line HT-1080 stably expressing 53BP1 or full-length reconstituted MDC1 fused to Green Fluorescent Protein (GFP) were irradiated with protons and α-particles of linear energy transfers (LETs) of 15 and 75 keV/μm, respectively. Using a microbeam, the irradiations were carried out in line patterns, which facilit...

Low-grade fibromyxoid sarcoma: a clinicopathologic study of 18 cases, including histopathologic relationship with sclerosing epithelioid fibrosarcoma in a subset of cases

Annals of Diagnostic Pathology — Mon, 09 May 2011 04:00:00 +0100

Abstract: Low-grade fibromyxoid sarcoma (LGFMS) is an uncommon tumor with diverse histopathologic features. It has been found to be histopathologically and genetically related to hyalinizing spindle cell tumor with giant rosettes. Lately, sclerosing epithelioid fibrosarcoma (SEF) has been identified as another rare variant of fibrosarcoma. Very few studies have addressed the aspect of its histopathologic relationship with LGFMS. The present study was conducted to critically analyze the clinicopathologic features of a series of LGFMS cases, including identification of cases with histopathologic similarity with SEF. During a 7-year period, 18 LGFMS cases were diagnosed in 9 male and 9 female patients, had ages ranging from 10 to 69 years (median, 32.5 years), and were most commonly identifie...

CD248 facilitates tumor growth via its cytoplasmic domain

BMC Cancer — Sat, 07 May 2011 23:00:00 +0100

Conclusions: The multiple pathways regulated by the cytoplasmic domain of CD248 highlight its potential as a therapeutic target to treat cancer. (Source: BMC Cancer)

Immunotherapy eradicates metastases with reversible defects in MHC class I expression

Cancer Immunology, Immunotherapy — Sat, 07 May 2011 15:45:03 +0100

In this study, we have used an MHC-I-positive murine fibrosarcoma tumor clone, GR9-A7, which generates multiple lung and lymph node metastases with reversible MHC-I alterations after treatment with IFN-γ. Four different antitumor treatments were carried out after primary tumor excision to determine their capacity to inhibit spontaneous metastatic colonization of the GR9-A7 tumor clone. We found that 2 different immunotherapy protocols (CpG plus autologous irradiated-GR9-A7 cells and protein-bound polysaccharide K (PSK) and 1 chemoimmunotherapy (docetaxel plus PSK) induced eradication of metastases. In contrast, chemotherapy with docetaxel alone produced only partial reduction in the number of metastases. Flow cytometric analysis of lymphocyte populations showed an immunosuppression ...

Microchip-associated fibrosarcoma in a cat.

Veterinary Dermatology — Sun, 01 May 2011 23:00:00 +0100

Authors: Carminato A, Vascellari M, Marchioro W, Melchiotti E, Mutinelli F A 9-year-old, neutered male cat was presented for a subcutaneous mass on the neck. After surgical removal of the mass, a pet identification microchip was found within the tumour. Histological examination of the mass revealed typical features of the feline postinjection sarcoma. The cat had never received injections at the tumour site; all routine vaccinations were administered in the hindlimbs. Few cases of sarcomas developing at the site of microchip application have been reported in animals, although the contributory role of vaccine administrations has not been ruled out. This is the first report of a microchip-associated fibrosarcoma in a cat. Adherence to American Association of Feline Practitioners vaccinat...

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Reversible pulmonary hypertension in a cat

The Journal of Small Animal Practice — Sat, 30 Apr 2011 23:00:00 +0100

A 13‐year‐old, neutered female domestic shorthair cat was presented for sudden respiratory distress following palliative radiotherapy and the combined administration of a single dose of carboplatin for the treatment of recurrent fibrosarcoma. Clinical and radiographic findings were suggestive of pleural effusion. Echocardiography revealed marked right‐sided cardiac enlargement associated with tricuspid regurgitation and Doppler evidence of pulmonary hypertension. After 25 days of treatment for congestive heart failure and suspected pulmonary thromboembolism, clinical signs and echocardiographic and Doppler evidence of right‐sided cardiac enlargement and pulmonary hypertension had completely resolved. To the best of the authors' knowledge, this is the first report of reversible pulm...

A rare sinonasal neoplasm: Fibrosarcoma.

Ear, Nose and Throat Journal — Sat, 30 Apr 2011 23:00:00 +0100

We report a case involving a 47-year-old woman with a 2-year history of left nasal obstruction and proptosis, as well as diplopia for the 2 months preceding her visit. Computed tomography and magnetic resonance imaging showed a neoplasm occupying the left nasal cavity, ethmoid sinuses, and bilateral frontal sinuses. The neoplasm also was eroding the medial wall of the maxillary sinus, the lamina papyracea, the cribriform plate, and the anterior wall of the frontal sinus. Complete removal of the tumor was achieved both endoscopically and through a Lynch incision. Sinonasal fibrosarcoma was found on histopathologic examination. PMID: 21563082 [PubMed - in process] (Source: Ear, Nose and Throat Journal)

Monoamine carboxylate transporters are involved in BI-1-associated cancer metastasis in HT1080 colon fibrosarcoma cells.

International Journal of Oncology — Thu, 28 Apr 2011 23:00:00 +0100

In this study, ion transporters such as sodium hydrogen exchangers (NHE) and monoamine carboxylate transporters (MCTs) were studied in BI-1-overexpressing HT1080 cells (BI-1 cells). The extracellular pH became acidic as culture time of BI-1 cells increased, while intracellular pH stayed relatively stable at pH 7.2. The expression of MCTs increased in BI-1 cells as culture time passed. 5-(N-ethyl-N-isopropyl) amiloride or dimethylamiloride, NHE inhibitor, abrogated the elevated MCT expression, indicating that MCT followed NHE activation. An MCT inhibitor, lonidamine, regulated the acidification of extracellular pH, also inhibiting both increased cancer cell migration and infiltration and MMP2/9 activity. The inhibition of either NHE or MCT affected the intracellular pH, leading to a severel...

Orbital Infantile Myofibroma: a Case Report and Clinicopathologic Review of 24 Cases from the Literature

Head and Neck Pathology — Thu, 21 Apr 2011 18:01:26 +0100

Abstract Isolated orbital infantile myofibroma are rare tumors in the head and neck. The mass-like clinical presentation and variable histologic features result in frequent misdiagnosis and potentially inappropriate clinical management. There are only a few reported cases in the English literature. Twenty-four patients with orbital infantile myofibroma or myofibromatosis were compiled from the English literature (Medline 1960–2011) and integrated with this case report. The patients included 14 males and 10 females, aged newborn to 10 years (mean, 34.8 months), who presented with a painless mass in the infra- or supraorbital regions, usually increasing in size andassociated with exophthalmos (n = 5). Females were on average older than their male counter...

Schistosoma mansoni U6 gene promoter-driven short hairpin RNA induces RNA interference in human fibrosarcoma cells and schistosomules.

International Journal for Parasitology — Fri, 08 Apr 2011 23:00:00 +0100

Authors: Ayuk MA, Suttiprapa S, Rinaldi G, Mann VH, Lee CM, Brindley PJ RNA interference (RNAi) mediated by short hairpin-RNA (shRNA) expressing plasmids can induce specific and long-term knockdown of specific mRNAs in eukaryotic cells. To develop a vector-based RNAi model for Schistosoma mansoni, the schistosome U6 gene promoter was employed to drive expression of shRNA targeting reporter firefly luciferase. An upstream region of a U6 gene predicted to contain the promoter was amplified from genomic DNA of S. mansoni. A shRNA construct driven by the predicted U6 promoter targeting luciferase was assembled and cloned into plasmid pXL-Bac II, the construct termed pXL-BacII_SmU6-shLuc. Luciferase expression in transgenic fibrosarcoma HT-1080 cells was significantly reduced 96h following ...

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Primary congenital infantile fibrosarcoma of the heart: the first confirmed case.

The Annals of Thoracic Surgery — Thu, 31 Mar 2011 20:01:01 +0100

We describe an infant with congenital infantile fibrosarcoma of the heart who was treated with chemotherapy and who had a life-threatening complication develop that was successfully corrected by surgery. This demonstrates an unusual presentation, remarkable imaging, and diagnostic and treatment dilemmas. More significantly, this emphasizes the importance of a multidisciplinary approach for successful treatment of congenital infantile fibrosarcoma. PMID: 21440163 [PubMed - in process] (Source: The Annals of Thoracic Surgery)

Unusual Presentation of a Rare Tumor of the Dorsal Surface of the Foot

Clinical and Developmental Immunology — Thu, 31 Mar 2011 13:57:45 +0100

We report a case of this rare condition with an unusual presentation in a 60-year-old woman affecting the dorsal surface of the foot. It is a relatively benign condition with a good prognosis following complete surgical excision. It may have a slightly increased incidence in males. The accurate diagnosis is based only on histology but it is essential to differentiate it from other sinister lesions such as fibrosarcoma that may lead to amputation. (Source: Clinical and Developmental Immunology)

Primary Congenital Infantile Fibrosarcoma of the Heart: The First Confirmed Case [CASE REPORTS]

The Annals of Thoracic Surgery — Mon, 28 Mar 2011 23:00:00 +0100

Primary Fibrosarcoma of the Mitral Valve

Journal of Cardiac Surgery — Sun, 27 Mar 2011 23:00:00 +0100

Abstract A case of primary fibrosarcoma of the mitral valve is reported, which was resected and the valve was replaced. Adjuvant chemotherapy was admisinistered, and at one year the patient remains symptom free without evidence of recurrent disease. (J Card Surg 2011;**:***‐***) (Source: Journal of Cardiac Surgery)

Small Interfering RNA Targeting HIF-1α Reduces Hypoxia-Dependent Transcription and Radiosensitizes Hypoxic HT 1080 Human Fibrosarcoma Cells in vitro

Strahlentherapie und Onkologie — Fri, 25 Mar 2011 06:01:05 +0100

Conclusion: Inhibition of HIF-1 activation by using HIF-1α-targeted siRNA clearly acts synergistically with radiotherapy and increase radiosensitivity of hypoxic cells in vitro. Content Type Journal ArticlePages 1-8DOI 10.1007/s00066-011-2167-0Authors Adrian Staab, Department of Radiation Oncology, University of Würzburg, Würzburg, GermanyMarkus Fleischer, Department of Radiation Oncology, University of Würzburg, Würzburg, GermanyJuergen Loeffler, Medical Clinic II, University of Würzburg, Würzburg, GermanyHarun M. Said, Department of Radiation Oncology, University of Würzburg, Würzburg, GermanyAstrid Katzer, Department of Radiation Oncology, University of Würzburg, Würzburg, GermanyChristian Plathow, Department of Nuclear Medicine, University of Freibur...

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Directed Evolution of Protease Beacons that Enable Sensitive Detection of Endogenous MT1-MMP Activity in Tumor Cell Lines.

Chemistry and Biology — Fri, 25 Mar 2011 00:00:00 +0100

Authors: Jabaiah A, Daugherty PS Directed evolution was applied to identify peptide substrates with enhanced hydrolysis rates by MT1-MMP suitable for protease beacon development. Screening of a random pentapeptide library, using two-color CLiPS, yielded several substrates identical to motifs in distinct collagens that shared the consensus sequence P-x-G↓L. To identify substrates with enhanced cleavage rates, a second-generation decapeptide library incorporating the consensus was screened under stringent conditions, which resulted in a MxPLG↓(M)/(L)M(G)/(A)R consensus motif. These substrates are hydrolyzed by human-MT1-MMP up to six times faster than reported peptide substrates and are stable in plasma. Finally, incubation of soluble protease beacons incorporating the optimized subs...

Invasion Inhibitors of Human Fibrosarcoma HT 1080 Cells from the Rhizomes of Zingiber cassumunar: Structures of Phenylbutanoids, Cassumunols.

Chemical and Pharmaceutical Bulletin — Fri, 18 Mar 2011 12:45:02 +0100

Authors: Matsuda H, Nakamura S, Iwami J, Li X, Pongpiriyadacha Y, Nakai M, Kubo M, Fukuyama Y, Yoshikawa M The methanolic extract and its EtOAc-soluble fraction from the rhizomes of Zingiber cassumunar inhibited invasion of human fibrosarcoma HT 1080 cells. From the EtOAc-soluble fraction, eight new phenylbutanoids, cassumunols A-H, were isolated together with 30 known constituents. The structures of new phenylbutanoids were elucidated on the basis of chemical and physicochemical evidence. Principal constituents were examined the inhibitory effects on the invasion of HT 1080 cells. Among them, phlain I and III, (E)-1-(3,4-dimethoxyphenyl)buta-1,3-diene, (E)-1-(2,4,5-trimethoxyphenyl)buta-1,3-diene, and (-)-β-sesquiphellandrene showed anti-invasion effects. Interestingly, (E)-1-(2,4,5-...

Epigenetic regulation of proMMP-1 expression in the HT1080 human fibrosarcoma cell line.

International Journal of Oncology — Thu, 17 Mar 2011 00:00:00 +0100

Authors: Poplineau M, Dufer J, Antonicelli F, Trussardi-Regnier A The matrix metalloproteinase (MMP) family members play an important role in various physiological and pathological processes. Although MMP-1 (collagenase-1) has been shown to be involved in tumor invasiveness, the regulation of its expression is still not fully elucidated and could implicate epigenetic mechanisms. The aim of this study was to analyze the effects of the Histone Deacetylase Inhibitor (HDI) trichostatin A (TSA) and the inhibitor of DNA methylation 5-aza-2'-deoxycytidine (5-azadC) on the proMMP-1 expression in the human HT1080 fibrosarcoma cell line. Real-time RT-PCR revealed that 5-azadC or 5-azadC + TSA but not TSA alone, despite global histone H4 hyperacetylation, increased proMMP-1 mRNA levels. This tran...

Characterization of a newly identified ETV6-NTRK3 fusion transcript in acute myeloid leukemia

Diagnostic Pathology — Tue, 15 Mar 2011 00:00:00 +0100

Conclusion: We have characterized a novel ETV6-NTRK3 fusion transcript which has not been previously described in AML FAB M0 by FISH and RACE PCR. ETV6-NTRK3 rearrangements have been described in secretory breast carcinoma and congenital fibrosarcoma. (Source: Diagnostic Pathology)

Molecular cytogenetics reveals complex karyotype in apparent t(8;13) therapy-related acute myeloid leukemia M2 after fibrosarcoma

Leukemia Research — Mon, 07 Mar 2011 00:00:00 +0100

Therapy-related acute myeloid leukemia (t-AML) accounts for 10–30% of all AML and it is a known complication derived from cytotoxic chemotherapy and radiation therapy, which are known mutagenic causative agents, namely, alkylanting agents and DNA-topoisomerase II inhibitors . In childhood, most cases of t-AML occur following soft tissue sarcoma such as osteosarcoma and rabdomiosarcoma, although it is rarely observed after fibrosarcoma cases. The fibrosarcoma is a neoplasm derived from fibroblasts in soft tissue such as muscles, connective tissues, blood vessels, joints and/or fat and occurs in approximately 5% of all primary bone sarcomas . (Source: Leukemia Research)

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Cranial fasciitis resembling infantile fibrosarcoma differentiated by genetic assay

The Journal of Dermatology — Wed, 02 Mar 2011 00:00:00 +0100

(Source: The Journal of Dermatology)

Formation of solid tumors by a single multinucleated cancer cell

Cancer — Tue, 01 Mar 2011 00:00:00 +0100

CONCLUSIONS:The current results indicated that the growth of MNCs may be arrested under stress and that MNCs are highly resistant to chemotherapy and can generate clonal, orthotopic, metastatic tumors. Cancer 2011. © 2011 American Cancer Society. (Source: Cancer)

Spatiotemporal investigations of DNA damage repair using microbeams

Radiation Protection Dosimetry — Tue, 01 Mar 2011 00:00:00 +0100

Cellular response to radiation damage is made by a complex network of pathways and feedback loops whose spatiotemporal organisation is still unclear despite its decisive role in determining the fate of the damaged cell. Revealing the dynamic sequence of the repair proteins is therefore critical in understanding how the DNA repair mechanisms work. There are also still open questions regarding the possible movement of damaged chromatin domains and its role as trigger for lesion recognition and signalling in the DNA repair context. The single-cell approach and the high spatial resolution offered by microbeams provide the perfect tool to study and quantify the dynamic processes associated with the induction and repair of DNA damage. We have followed the development of radiation-induced foci fo...

Outcome in dogs with surgically resected oral fibrosarcoma (1997–2008)*

Veterinary and Comparative Oncology — Tue, 01 Mar 2011 00:00:00 +0100

Oral fibrosarcoma (FSA) is a common oral tumour in dogs, and historically reported survival times after surgical excision range from 7.0 to 12.2 months with local recurrence rates of 32–57%. The purpose of this retrospective study was to report outcome in a cohort of dogs with oral FSA treated with surgical excision with or without adjuvant radiation therapy. Twenty‐nine dogs with a histological diagnosis of FSA arising from the oral cavity that underwent surgical resection of their oral FSA were included in this study. Twenty‐one dogs were treated with surgical excision alone and eight dogs with both surgery and radiation therapy. The median progression‐free interval was >653 days. The median survival time was 743 days. The 1‐ and 2‐year survival rates were 87.7 and 57.8%, ...

A mass of myxofibrosarcoma in the lung.

Tuberkuloz ve Toraks — Tue, 01 Mar 2011 00:00:00 +0100

Authors: Hasanoğlu HC, Karalezli A, Tanrıverdio E, Gümüş M, Aydın M Fibrosarcoma is a mesenchymal tumor constituted by malignant fibroblasts. Myxofibrosarcoma is one of the fibrosarcoma variants that mostly develops from dermal/subcutaneous tissues. The most common locations are the limbs, with rare occurrences in the chest, head, and neck. Since, to best of our knowledge, there is no such report in English literature, we hereby present a case of lung myxofibrosarcoma. A 47-year-old man who had chest pain for 4 months was admitted to our clinic. The chest X-ray revealed a homogeneous density in the left upper lung. His chest computed tomography (CT) scan showed a solid mass lesion of 52 x 58 mm in size at the apical segment of the left upper lobe. There was tumor invasion at the ...

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Mevalonate pathway inhibitors affect anticancer drug-induced cell death and DNA damage response of human sarcoma cells

Cancer Letters — Mon, 28 Feb 2011 00:00:00 +0100

Abstract: Lovastatin (Lov), bisphosphonates (BP) and metformin (Met) are widely used drugs, having in common that they interfere with the mevalonate pathway (MP). The MP generates isoprene moieties required for the function of regulatory GTPases controlling cell proliferation and survival. Here, we addressed the question whether MP inhibitors interfere with the anti-tumor efficacy of anticancer drugs. We comparatively analyzed the effect of equitoxic doses of Lov, BP and Met on cell viability, cell cycle progression, apoptosis and DNA damage response (DDR) of human osteo- and fibrosarcoma cells exposed to doxorubicin or cisplatin. We found that Lov, BP and Met modulated the anticancer drug sensitivity of sarcoma cells in an agent-, dose and time-dependent fashion. Mostly, the MP inhibitors...

Tumor imaging with multicolor fluorescent protein expression

International Journal of Clinical Oncology — Thu, 24 Feb 2011 08:04:10 +0100

Abstract Imaging with fluorescent proteins has been revolutionary and has led to the new field of in vivo cell biology. Many new applications of this technology have been developed. Green fluorescent protein (GFP)-labeled or red fluorescent protein (RFP)-labeled HT-1080 human fibrosarcoma cells were used to determine clonality of metastasis by imaging of metastatic colonies after mixed implantation of the red and green fluorescent cells. Resulting pure red or pure green colonies were scored as clonal, whereas mixed yellow colonies were scored as nonclonal. Dual-color fluorescent cancer cells expressing GFP in the nucleus and RFP in the cytoplasm were engineered. The dual-color cancer cells enable real-time nuclear–cytoplasmic dynamics to be visualized in living cells in ...

A mechanistic rationale for MEK inhibitor therapy in myeloma based on blockade of MAF oncogene expression

Blood — Thu, 24 Feb 2011 00:00:00 +0100

Modulating aberrant transcription of oncogenes is a relatively unexplored opportunity in cancer therapeutics. In approximately 10% of multiple myelomas, the initiating oncogenic event is translocation of musculoaponeurotic fibrosarcoma oncogene homolog (MAF), a transcriptional activator of key target genes, including cyclinD2. Our prior work showed that MAF is up-regulated in an additional 30% of multiple myeloma cases. The present study describes a common mechanism inducing MAF transcription in both instances. The second mode of MAF transcription occurred in myelomas with multiple myeloma SET domain (MMSET) translocation. MMSET knockdown decreased MAF transcription and cell viability. A small-molecule screen found an inhibitor of mitogen-activated protein kinase kinase (MEK), which activa...

Suppression of phorbol-12-myristate-13-acetate-induced tumor cell invasion by piperine via the inhibition of PKCα/ERK1/2-dependent matrix metalloproteinase-9 expression.

Toxicology Letters — Thu, 24 Feb 2011 00:00:00 +0100

In conclusion, we demonstrated that the anti-invasive effects of piperine may occur through inhibition of PKCα and ERK phosphorylation and reduction of NF-κB and AP-1 activation, leading to down-regulation of MMP-9 expression. Thus, piperine has potential as a potent anti-cancer drug in therapeutic strategies for fibrosarcoma metastasis. PMID: 21354279 [PubMed - as supplied by publisher] (Source: Toxicology Letters)

Infantile Fibrosarcoma: 2 Case Reports and Literature Review

European Journal of Pediatric Surgery — Fri, 18 Feb 2011 00:00:00 +0100

Eur J Pediatr SurgDOI: 10.1055/s-0031-1271734© Georg Thieme Verlag KG Stuttgart · New YorkArticle in Thieme eJournals:Table of contents | Full text (Source: European Journal of Pediatric Surgery)

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Anti-metastatic Activity of the Recombinant Disintegrin, r-Mojastin 1, from the Mohave Rattlesnake.

Toxicon — Thu, 17 Feb 2011 00:00:00 +0100

In conclusion, our studies suggest that r-mojastin could be a useful tool to develop novel antitumor agents by virtue of its ability to inhibit tumor cell adhesion, migration and invasion. PMID: 21334359 [PubMed - as supplied by publisher] (Source: Toxicon)

Congenital infantile fibrosarcoma of the forearm.

Chirurgie de la Main — Tue, 15 Feb 2011 00:00:00 +0100

We report a case of a congenital infantile fibrosarcoma of the forearm, which was initially confused with a hemangioma, treated successfully by surgical resection. PMID: 21411358 [PubMed - as supplied by publisher] (Source: Chirurgie de la Main)

Differential utilization of NF-kappaB RELA and RELB in response to extracellular versus intracellular polyIC stimulation in HT1080 cells

BMC Immunology — Thu, 10 Feb 2011 00:00:00 +0100

Conclusions: Our study suggests that extracellular and intracellular dsRNA signaling pathways may utilize different NF-kB members, and particularly the differential utilization of RELB may be a key mechanism for powerful inductions of NF-kB regulated genes in the intracellular dsRNA signaling pathway. (Source: BMC Immunology)

Eriobotrya japonica hydrophilic extract modulates cytokines in normal tissues, in the tumor of Meth-A-fibrosarcoma bearing mice, and enhances their survival time

BMC Complementary and Alternative Medicine — Fri, 04 Feb 2011 00:00:00 +0100

Background: Cytokines play a key role in the immune response to developing tumors, and therefore modulating their levels and actions provides innovative strategies for enhancing the activity of antigen presenting cells and polarizing towards T helper 1 type response within tumor microenvironment. One of these approaches could be the employment of plant extracts that have cytokine immunomodulation capabilities. Previously, we have shown that the Eriobotrya japonica hydrophilic extract (EJHE) induces proinflammatory cytokines in vitro and in vivo. Methods: The present study explored the in vivo immunomodulatory effect on interferon-gamma (IFN-gamma), interleukin-17 (IL-17), and transforming growth factor-beta 1 (TGF-beta1) evoked by two water-extracts prepared from EJ leaves in the tissues o...

Interplay between steroid receptors and neoplastic progression in sarcoma tumors

Journal of Cellular Physiology — Tue, 01 Feb 2011 00:00:00 +0100

AbstractSteroid hormones are expressed at low levels in mesenchimal cells and are highly expressed in soft tissue sarcoma. In human soft tissue fibrosarcoma cell line (HT‐1080), the epidermal growth factor (EGF) stimulates the express of matrix metal (MMPs) expression through a Src‐dependent mechanism. In human fibrosarcomas, increased expression of MMPs correlates with the metastatic progression. Our recent data in human breast cancer cell line MCF‐7, demonstrates that EGF stimulates estradiol receptor (ER) phosphorylation on tyrosine at position 537 thereby promoting the association of a complex among EGF receptor (EGFr), androgen receptor (AR), ER and Src that activates EGF‐dependent signaling pathway. In the present study, we demonstrate that, in HT‐1080 cells, the Src kinase...

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A phase 2 study of temsirolimus (CCI‐779) in patients with soft tissue sarcomas

Cancer — Tue, 01 Feb 2011 00:00:00 +0100

ETV6-NTRK3-Mediated Breast Epithelial Cell Transformation Is Blocked by Targeting the IGF1R Signaling Pathway

Cancer Research — Tue, 01 Feb 2011 00:00:00 +0100

In this study, we analyzed EN expressing murine and human mammary epithelial cell lines for transformation properties. Various IGF1R signaling inhibitors, including the dual specificity IGF1R/insulin receptor (INSR) inhibitor BMS-536924, were then tested for effects on three-dimensional Matrigel cell growth, migration, and tumor formation. We found that EN expression increased acinar size and luminal filling in Matrigel cultures and promoted orthotopic tumor growth in mice. Tumors were well differentiated and nonmetastatic, similar to human SBC. The known EN effector pathway, PI3K-Akt, was activated in an IGF1- or insulin-dependent manner. BMS-536924 blocked EN transformation in vitro, whereas BMS-754807, another IGIFR/INSR kinase inhibitor currently in clinical trials, significantly reduc...

CREG1 enhances p16INK4a induced cellular senescence.

Cell Cycle — Sat, 29 Jan 2011 02:00:12 +0100

In conclusion, this is the first evidence to demonstrate that CREG1 enhances p16 (INK4a) -induced senescence by transcriptional repression of cell cycle-regulated genes. PMID: 21263217 [PubMed - as supplied by publisher] (Source: Cell Cycle)

Solitary infantile myofibromatosis of the cranial vault: case report

Child's Nervous System — Fri, 28 Jan 2011 20:31:01 +0100

We report the case of a 9-year-old boy who came to our attention with a solitary infantile myofibroma of the calvarium, appearing as a tight–elastic, lightly tender mass in the left frontal area, eroding both the inner and the outer tables. Histopathologically, the specimens showed a spindle-cell tumor with dense reticulin fiber network and expression of smooth muscle actin. Fifty-eight months MR follow-up after total removal showed no residual or relapse. Content Type Journal ArticlePages 1-5DOI 10.1007/s00381-010-1382-9Authors Paolo Merciadri, Department of Neurosurgery, Giannina Gaslini Children’s Research Hospital (IRCSS), Genoa, ItalyMarco Pavanello, Department of Neurosurgery, Giannina Gaslini Children’s Research Hospital (IRCSS), Genoa, ItalyPaolo Nozza, Department o...

Proliferative and Molecular Effects of the Dual PPAR{alpha}/{gamma} Agonist Tesaglitazar in Rat Adipose Tissues: Relevance for Induction of Fibrosarcoma.

Toxicologic Pathology — Wed, 26 Jan 2011 00:00:00 +0100

Authors: Glinghammar B, Andersson U, Hellmold H The dual peroxisome-proliferator-activated receptor (PPAR) α/γ agonist tesaglitazar has been shown to produce fibrosarcomas in rats. Here, the authors studied morphology, proliferation, differentiation, and inflammation markers in adipose tissue from rats exposed to 1, 3, or 10 µmol/kg tesaglitazar for 2 or 12 weeks, including recovery groups (12 weeks treatment followed by 12 weeks recovery), and 3 or 10 µmol/kg tesaglitazar for 24 weeks. Subcutaneous white and brown fat revealed reversible dose-related histopathological alterations and after 12 and 24 weeks developed areas of thickened skin (fatty lumps). There was a dose-dependent increase in proliferation of interstitial cells in white and brown fat as shown by increased mitotic i...

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p27RF-Rho Is Required for Melanoma Metastasis [Cell Biology]

Journal of Biological Chemistry — Fri, 21 Jan 2011 00:00:00 +0100

Rho family proteins regulate multiple cellular functions including motility and invasion through regulation of the actin cytoskeleton and gene expression. Activation of Rho proteins is controlled precisely by multiple regulators in a spatiotemporal manner. RhoA and/or RhoC are key players that regulate the metastatic activity of malignant tumor cells, and it is therefore of particular interest to understand how activation of these Rho proteins is controlled. We recently identified an upstream regulator of RhoA activation, p27RF-Rho (p27kip1 releasing factor from RhoA) that acts by freeing RhoA from inhibition by p27kip1. p27kip1 is a cell cycle regulator when it is localized to the nucleus, but it binds RhoA and inhibits activation of the latter when it is localized to the cytoplasm. Here,...

Array comparative genomic hybridization reveals frequent alterations of G1/S checkpoint genes in undifferentiated pleomorphic sarcoma of bone

Genes, Chromosomes and Cancer — Thu, 20 Jan 2011 14:14:24 +0100

Inflammatory pseudotumor of uterus: an unusual pelvic mass

European Journal of Obstetrics, Gynecology, and Reproductive Biology — Thu, 20 Jan 2011 00:00:00 +0100

Inflammatory pseudotumors (IPTs), also known by the synonym inflammatory myoblastic tumors (IMT), are a histologically heterogenous group of benign lesions of diverse nature and etiology, occurring at almost all anatomical locations of the body. Sufficient data are available on differences in clinical behavior to warrant their separation . The term IPT is applied to a variety of neoplastic and non-neoplastic entities, from which an entity with distinct clinical, pathological and molecular features has emerged, known as IMT. IPTs may be preceded by an acute infection and represent an immunologic post-inflammatory reparative response process or a low grade malignancy of spindle cells, or may harbor occult fibrosarcomas. They are classified into pulmonary and extrapulmonary IPTs. Extrapulmona...

Infantile Fibrosarcoma: The American Experience

Journal of Surgical Research — Wed, 19 Jan 2011 20:27:10 +0100

(Source: Journal of Surgical Research)

Chemical Genetic Screening for Compounds That Preferentially Inhibit Growth of Methylthioadenosine Phosphorylase (MTAP)-Deficient Saccharomyces cerevisiae

Journal of Biomolecular Screening — Fri, 07 Jan 2011 00:00:00 +0100

Methylthioadenosine phosphorylase (MTAP), a key enzyme in the methionine salvage pathway, is inactivated in a variety of human cancers. Since all human tissues express MTAP, it would be of potential interest to identify compounds that selectively inhibit the growth of MTAP-deficient cells. To determine if MTAP inactivation could be targeted, the authors have performed a differential chemical genetic screen in isogenic MTAP+ and MTAP– Saccharomyces cerevisiae. A low molecular weight compound library containing 30,080 unique compounds was screened for those that selectively inhibit growth of MTAP– yeast using a differential growth assay. One compound, containing a 1,3,4-thiadiazine ring, repeatedly showed a differential dose response, with MTAP– cells exhibiting a 4-fold sh...

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Ovarian fibrosarcoma with metastasis after 12 years

The Australian and New Zealand Journal of Obstetrics and Gynaecology — Wed, 05 Jan 2011 00:00:00 +0100

(Source: The Australian and New Zealand Journal of Obstetrics and Gynaecology)

Suppression of EGF‐induced tumor cell migration and matrix metalloproteinase‐9 expression by capsaicin via the inhibition of EGFR‐mediated FAK/Akt, PKC/Raf/ERK, p38 MAPK, and AP‐1 signaling

Molecular Nutrition — Sat, 01 Jan 2011 00:00:00 +0100

Conclusion: Capsaicin inhibited the EGF‐induced invasion and migration of human fibrosarcoma cells via EGFR‐dependent FAK/Akt, PKC/Raf/ERK, p38 mitogen‐activated protein kinase (MAPK), and AP‐1 signaling, leading to the down‐regulation of MMP‐9 expression. These results indicate the role of capsaicin as a potent anti‐metastatic agent, which can markedly inhibit the metastatic and invasive capacity of fibrosarcoma cells. (Source: Molecular Nutrition)

Gliosarcoma with prominent smooth muscle component (gliomyosarcoma): A report of 10 cases.

Indian Journal of Pathology and Microbiology — Sat, 01 Jan 2011 00:00:00 +0100

Conclusion: GMS containing prominent smooth muscle component may not be as rare as has been reported in the literature. Both GS and GMS appear to arise from the vessel wall at least in some cases, suggesting their possible vascular origin. PMID: 21393877 [PubMed - in process] (Source: Indian Journal of Pathology and Microbiology)

High-Grade Myofibroblastic Sarcoma of the Palate and Maxillary Sinus: Case Report With Literature Review

Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics — Thu, 30 Dec 2010 00:33:40 +0100

Background. Myofibroblastic sarcoma (MS) represents a distinct malignant mesenchymal neoplasm composed of myofibroblasts and is different from fibrosarcoma and leiomyosarcoma. MS may arise in soft tissue or bone in adults or children. There is a predilection for the head and neck region. Most MSs are low grade, mimicking of nodular fasciitis, and possibly inflammatory myofibroblastic tumors; a less differentiated high-grade variant exists. High-grade MS is hypercellular, has less collagen production, may exhibit necrosis, and demonstrates hyperchromasia and increased mitotic activity. Marked pleomorphism and multinucleated giant cells that characterize high-grade pleomorphic sarcoma are lacking. The cells of MS express smooth muscle actin and calponin and lack h-caldesmon. MS lacks specifi...

Endobronchial fibrosarcoma presenting as recurrent left‐sided pneumonia

Pediatric Pulmonology — Thu, 30 Dec 2010 00:00:00 +0100

We report a 6‐year old girl with recurrent and non‐resolving left‐sided “pneumonia” over a 3‐year period who was diagnosed with an endobronchial low‐grade fibrosarcoma. This highlights the importance of considering underlying localized airway obstruction in any case of clinically or radiologically atypical pneumonia in a child and therefore the need for careful follow‐up of all but the most typical cases. Pediatr. Pulmonol. © 2010 Wiley‐Liss, Inc. (Source: Pediatric Pulmonology)

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Primary malignant clavicular tumours: a clinicopathological analysis of six cases and evaluation of surgical management

Archives of Orthopaedic and Trauma Surgery — Tue, 28 Dec 2010 15:02:58 +0100

Abstract Primary malignant tumours of the clavicle are extremely rare and little is known regarding their clinicopathological characteristics and outcomes of surgical management. The aim of the study is to analyse the clinical, imaging, and histological features of six patients with malignant tumours of the clavicle and present the outcome of cleidectomy in four of them. A review of the literature is also provided. Six cases were included in this series: two plasmocytomas; three PNETs, one non-Hodgkin lymphoma, one high-grade chondrosarcoma and one post-irradiation fibrosarcoma. Apart from one patient with plasmocytoma and another one with non-Hodgkin lymphoma, the remaining four patients underwent partial or complete cleidectomy according to tumour location. At the time o...

Radiation-induced Cancer Cell Repopulation: A possible mechanism implied by experiments using transplantable mouse-derived sarcoma cell line.

Cell Structure and Function — Sat, 25 Dec 2010 00:00:00 +0100

Conclusions: This study implies that repopulation is not a temporary reaction to irradiation. It is caused probably by "clonal" gene-expression changes, though it remains unknown whether the changes are attributable to tolerant cell selection or to gene mutation/modification. PMID: 21206131 [PubMed - as supplied by publisher] (Source: Cell Structure and Function)

Elucidation of flow‐mediated tumour cell‐induced platelet aggregation using an ultrasound standing wave trap

British Journal of Pharmacology — Thu, 23 Dec 2010 00:00:00 +0100

Conclusion and implications. Our results show for the first time, that during TCIPA, platelet activation disrupts cancer cell clusters and this can contribute to metastasis. Thus, selective targeting of platelet aggregate‐cancer cell clusters may be an important strategy to control metastasis. (Source: British Journal of Pharmacology)

AAV2-mediated in vivo immune gene therapy of solid tumours

Genetic Vaccines and Therapy — Mon, 20 Dec 2010 00:00:00 +0100

Conclusions: Overall, this study demonstrates the potential for in vivo AAV2 mediated immune gene therapy, and provides data on the inter-relationship between tumour vasculature and immune cell recruitment. (Source: Genetic Vaccines and Therapy)

Lymphadenectomy exacerbates tumor growth while lymphadenectomy plus the adoptive transfer of autologous cytotoxic cells and low-dose cyclophosphamide induces regression of an established murine fibrosarcoma

Cancer Immunology, Immunotherapy — Tue, 14 Dec 2010 04:19:32 +0100

Abstract Tumor-draining lymph node (TDLN) ablation is routinely performed in the management of cancer; nevertheless, its usefulness is at present a matter of debate. TDLN are central sites where T cell priming to tumor antigens and onset of the antitumor immune response occur. However, tumor-induced immunosuppression has been demonstrated at TDLN, leading to downregulation of antitumor reaction and tolerance induction. Tolerance in turn is a main impairment for immunotherapy trials. We used a murine immunogenic fibrosarcoma that evolves to a tolerogenic state, to study the cellular and molecular mechanisms underlying tolerance induction at the level of TDLN and to design an appropriate immunotherapy. We determined that following a transient activation, the established tumo...

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Functional and biochemical studies of CD9 in fibrosarcoma cell line.

Molecular and Cellular Biochemistry — Tue, 14 Dec 2010 00:00:00 +0100

In this study, stable cell lines for CD9 overexpression and vector were generated in HT1080, a human fibroscarcoma cell line, and cellular functions were widely investigated. In CD9-HT1080 cells, CD9 mainly localized in the membrane and co-localized with F-actin in the filopodia of cell surface. In functional assays, we demonstrated that CD9 could up-regulate total and active caspase-3 expression and induce cell apoptosis, but cell proliferation remained unchanged. CD9 overexpression inhibited HT1080 cell adhesion to FN but promoted cell spreading on FN. We also observed CD9 reduced cell migration using FN a chemoattractant and inhibited cell colony formation in soft agar medium. To explore the biochemical mechanism for functional changes, we investigated the effects of CD9 overexpression ...

Invasion and destruction of a murine fibrosarcoma by Salmonella-induced effector CD8 T cells as a therapeutic intervention against cancer

Cancer Immunology, Immunotherapy — Mon, 06 Dec 2010 14:43:15 +0100

Abstract We have developed a new vaccination strategy by using the Salmonella type III secretion system (T3SS) to translocate heterologous antigens into the cytosol of host cells. This leads to an efficient antigen-specific CD8 T cell induction. Recently, we have demonstrated the use of Salmonella’s T3SS for the immunoprophylaxis of a solid tumor. The murine fibrosarcoma WEHI 164 was transfected with the DNA sequence encoding the MHC class I-peptide p60217–225 from Listeria monocytogenes. In the present study, we used this tumor model to investigate the potential of vaccination with recombinant Salmonella in a therapeutic setting. BALB/c mice were subcutaneously challenged with WEHI-p60 cells. Simultaneously or 4 days later, these mice received either an orogastric o...

Identification of a New Peptide for Fibrosarcoma Tumor Targeting and Imaging In Vivo

Journal of Biomedicine and Biotechnology — Sun, 05 Dec 2010 20:20:35 +0100

A 12-mer amino acid peptide SATTHYRLQAAN, denominated TK4, was isolated from a phage-display library with fibrosarcoma tumor-binding activity. In vivo biodistribution analysis of TK4-displaying phage showed a significant increased phage titer in implanted tumor up to 10-fold in comparison with normal tissues after systemic administration in mouse. Competition assay confirmed that the binding of TK4-phage to tumor cells depends on the TK4 peptide. Intravenous injection of 131I-labeled synthetic TK4 peptide in mice showed a tumor retention of 3.3% and 2.7% ID/g at 1- and 4-hour postinjection, respectively. Tumor-to-muscle ratio was 1.1, 5.7, and 3.2 at 1-, 4-, and 24-hour, respectively, and tumors were imaged on a digital γ-camera at 4-hour postinjection. The present data sugge...

Chaotic neovascularization induced by aggressive fibrosarcoma cells overexpressing S-adenosylmethionine decarboxylase.

The International Journal of Biochemistry and Cell Biology — Fri, 03 Dec 2010 00:00:00 +0100

Authors: Paasinen-Sohns A, Kääriäinen E, Yin M, Järvinen K, Nummela P, Hölttä E S-adenosylmethionine decarboxylase is a key enzyme in the biosynthesis of polyamines essential for cell proliferation. Overexpression of S-adenosylmethionine decarboxylase in rodent fibroblasts led to aggressive transformants (Amdc-s cells) that had unforeseen high invasive capacity in nude mice, invading rapidly from the subcutaneous injection site into the peritoneal cavity and its organs. In vitro, these cells were much more invasive than Ras-oncogene-transformed fibroblasts, or human HT-1080 fibrosarcoma and MDA-MB-231 breast cancer cells. In immunohistological characterization, Amdc-s-induced tumors showed chaotic neovascularization, with abundant pleomorphic vessel-like structures that had nonco...

Dermatofibrosarcoma protuberans‐derived fibrosarcoma: Clinical history, biological profile and sensitivity to imatinib

International Journal of Cancer — Thu, 02 Dec 2010 00:00:00 +0100

In conclusion DFSP‐derived FS maintains the fusion‐gene, being sensitive to imatinib. Responses, however, are short‐lasting. Secondary resistance to imatinib is not related to PDGFRB. (Source: International Journal of Cancer)

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C‐terminal domain of p16INK4a is adequate in inducing cell cycle arrest, growth inhibition and CDK4/6 interaction similar to the full length protein in HT‐1080 fibrosarcoma cells

Journal of Cellular Biochemistry — Wed, 01 Dec 2010 01:38:06 +0100

AbstractThe tumor suppressor p16INK4a has earned widespread attention in cancer studies since its discovery as an inhibitor of cyclin‐dependent kinases (CDKs) 4/6. Structurally, it consists of four complete ankyrin repeats, believed to be involved in CDK4 interaction. According to the previous disparities concerning the importance of domains and inactivating mutations in p16, we aimed to search for the domain possessing the functional properties of the full length protein. Upon our in silico screening analyses followed by experimental assessments, we have identified the novel minimum functional domain of p16 to be the C‐terminal half including ankyrin repeats III, IV and the C‐terminal flanking region accompanied by loops 2 and 3. Transfection of this truncated form into HT‐1080 hu...

High-Grade Myofibroblastic Sarcoma of the Palate and Maxillary Sinus: Case Report With Literature Review

Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics — Tue, 30 Nov 2010 08:28:30 +0100

Background. Myofibroblastic sarcoma (MS) represents a distinct malignant mesenchymal neoplasm composed of myofibroblasts different from fibrosarcoma and leiomyosarcoma. MS may arise in soft tissue or bone in adults or children. There is a predilection for the head and neck region. Most MS are low grade, mimicking nodular fasciitis and possibly inflammatory myofibroblastic tumor; yet a less differentiated high-grade variant exists. High-grade MS is hypercellular, has less collagen production, may exhibit necrosis, and demonstrates hyperchromasia, and increased mitotic activity. Marked pleomorphism and multinucleated giant cells that characterize high grade pleomorphic sarcoma are lacking. The cells of MS express smooth muscle actin and calponin and lack h-caldesmon. MS lacks specific cytoge...

Metformin reduces cisplatin-mediated apoptotic death of cancer cells through AMPK-independent activation of Akt.

European Journal of Pharmacology — Fri, 26 Nov 2010 00:00:00 +0100

In conclusion, the antidiabetic drug metformin reduces cisplatin in vitro anticancer activity through AMPK-independent upregulation of Akt survival pathway. These data warrant caution when considering metformin for treatment of diabetic cancer patients receiving cisplatin or as a potential adjuvant in cisplatin-based chemotherapeutic regimens. PMID: 21114978 [PubMed - as supplied by publisher] (Source: European Journal of Pharmacology)

Dissociation of lipotoxicity and glucotoxicity in a mouse model of obesity associated diabetes: role of forkhead box O1 (FOXO1) in glucose-induced beta cell failure

Diabetologia — Wed, 24 Nov 2010 18:48:58 +0100

Conclusions/interpretation The dietary regimen dissociates the effects of obesity (lipotoxicity) from those of hyperglycaemia (glucotoxicity) in NZO mice. Obese NZO mice are unable to compensate for the carbohydrate challenge by increasing insulin secretion or synthesising adequate amounts of insulin. In response to the hyperglycaemia, FOXO1 is dephosphorylated, leading to reduced levels of beta cell-specific transcription factors and to apoptosis of the cells. Content Type Journal ArticleDOI 10.1007/s00125-010-1973-8Authors O. Kluth, Departments of Pharmacology and Experimental Diabetology, German Institute of Human Nutrition Potsdam-Rehbruecke, Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, GermanyF. Mirhashemi, Departments of Pharmacology and Experimental Diabe...

Acteoside inhibits PMA‐induced matrix metalloproteinase‐9 expression via CaMK/ERK‐ and JNK/NF‐κB‐dependent signaling

Nahrung / Food — Thu, 18 Nov 2010 00:00:00 +0100

Conclusion: Acteoside inhibited PMA‐induced invasion and migration of human fibrosarcoma cells via Ca2+‐dependent CaMK/ERK and JNK/NF‐κB‐signaling pathways. Acteoside therefore has the potential to be a potent anticancer agent in therapeutic strategies for fibrosarcoma metastasis. (Source: Nahrung / Food)

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An automatic algorithm for the segmentation and morphological analysis of microvessels in immunostained histological tumour sections

Journal of Microscopy — Thu, 18 Nov 2010 00:00:00 +0100

SummaryA fully automatic segmentation and morphological analysis algorithm for the analysis of microvessels from CD31 immunostained histological tumour sections is presented. Development of the algorithm exploited the distinctive hues of stained vascular endothelial cells, cell nuclei and background, to provide the seeds for a ‘region‐growing’ method for object segmentation in the 3D hue, saturation, value (HSV) colour model. The segmented objects, identified as microvessels by CD31 immunostaining, were post‐processed with three morphological tasks: joining separate objects that were likely to belong to a single vessel, closing objects that had a narrow gap around their periphery, and splitting objects with multiple lumina into individual vessels. The automatic segmentation was val...

Clinical features of nonpituitary sellar lesions in a large surgical series

Clinical Endocrinology — Wed, 17 Nov 2010 09:45:34 +0100

Conclusions A substantial minority of sellar masses are not pituitary adenomas. While they frequently present with the symptoms, hormone abnormalities and radiographical appearance typical of pituitary tumours, the possibility of a nonadenomatous lesion needs to be considered in the differential diagnosis. (Source: Clinical Endocrinology)

A Case of Aborted Sudden Cardiac Death and Consequent Extreme Electrical Storm Secondary to a Metastatic Cardiac Tumor

Pacing and Clinical Electrophysiology : PACE — Wed, 17 Nov 2010 00:00:00 +0100

We report a 43‐year‐old man with an implantable cardioverter defibrillator for aborted sudden cardiac death. He represents in extreme electrical storm with 111 different ventricular fibrillation episodes. Successful treatment was achieved with multiple antiarrhythmic agents, mechanical ventilation, external shocks, and ultimately overdrive pacing. A cardiac magnetic resonance scan revealed two cardiac lesions that were later diagnosed as metastatic fibrosarcoma. This case highlights two very important and increasingly common cardiological dilemmas: the management of extreme electrical storm and the role of magnetic resonance imaging in aborted cardiac death patients with an apparent “normal” heart. (PACE 2010; 1–4) (Source: Pacing and Clinical Electrophysiology : PACE)

[Molecular biology of soft-tissue sarcomas.]

Bulletin du Cancer — Wed, 17 Nov 2010 00:00:00 +0100

Authors: Coindre JM Sarcomas represent a heterogeneous group of tumors with a complex and poorly reproducible classification. However, in the last ten years, several specific genetic alterations have been described allowing a molecular classification with: 1) sarcomas with a specific translocation which can be used as a diagnostic marker. These translocations can be demonstrated by RT-PCR or by FISH with commercially available break apart probes ; 2) sarcomas with simple genomic profile showing amplification of a few genes. Well differentiated liposarcomas, dedifferentiated liposarcomas and intimal sarcomas show a simple genomic profile characterised by MDM2 and CDK4 amplifications associated with amplification of other genes in dedifferentiated liposarcomas ; 3) sarcomas with activati...