-
Actas Dermo-sifiliograficas 2016Mastocytosis is a term used to describe a heterogeneous group of disorders characterized by clonal proliferation of mast cells in different organs. The organ most often... (Review)
Review
Mastocytosis is a term used to describe a heterogeneous group of disorders characterized by clonal proliferation of mast cells in different organs. The organ most often affected is the skin. The World Health Organization classifies cutaneous mastocytosis into mastocytoma, maculopapular cutaneous mastocytosis, and diffuse mastocytosis. The systemic variants in this classification are as follows: indolent systemic mastocytosis (SM), aggressive SM, SM with an associated clonal hematological non-mast cell lineage disease, mast cell leukemia, mast cell sarcoma, and extracutaneous mastocytoma. The two latest systemic variants are rare. Although the course of disease is unpredictable in children, lesions generally resolve by early adulthood. In adults, however, the disease tends to persist. The goal of treatment should be to control clinical manifestations caused by the release of mast cell mediators and, in more aggressive forms of the disease, to reduce mast cell burden.
Topics: Humans; Leukemia, Mast-Cell; Mast Cells; Mast-Cell Sarcoma; Mastocytosis; Mastocytosis, Cutaneous; Mastocytosis, Systemic; Prognosis
PubMed: 26525106
DOI: 10.1016/j.ad.2015.09.009 -
Cancer Research Oct 2015There is a need in surgical oncology for contrast agents that can enable real-time intraoperative visualization of solid tumors that can enable complete resections while...
There is a need in surgical oncology for contrast agents that can enable real-time intraoperative visualization of solid tumors that can enable complete resections while sparing normal surrounding tissues. The Tumor Paint agent BLZ-100 is a peptide-fluorophore conjugate that can specifically bind solid tumors and fluoresce in the near-infrared range, minimizing light scatter and signal attenuation. In this study, we provide a preclinical proof of concept for use of this imaging contrast agent as administered before surgery to dogs with a variety of naturally occurring spontaneous tumors. Imaging was performed on excised tissues as well as intraoperatively in a subset of cases. Actionable contrast was achieved between tumor tissue and surrounding normal tissues in adenocarcinomas, squamous cell carcinomas, mast cell tumors, and soft tissue sarcomas. Subcutaneous soft tissue sarcomas were labeled with the highest fluorescence intensity and greatest tumor-to-background signal ratio. Our results establish a foundation that rationalizes clinical studies in humans with soft tissue sarcoma, an indication with a notably high unmet need.
Topics: Adolescent; Animals; Child; Child, Preschool; Contrast Media; Diagnostic Imaging; Disease Models, Animal; Dogs; Female; Fluorescent Dyes; Humans; Indocyanine Green; Intraoperative Care; Male; Neoplasms; Reproducibility of Results; Scorpion Venoms
PubMed: 26471914
DOI: 10.1158/0008-5472.CAN-15-0471 -
Human Vaccines & Immunotherapeutics 2015Oncolytic viruses are a relatively new class of anti-cancer immunotherapy agents. Several viruses have undergone evaluation in clinical trials in the last decades, and... (Review)
Review
Oncolytic viruses are a relatively new class of anti-cancer immunotherapy agents. Several viruses have undergone evaluation in clinical trials in the last decades, and the first agent is about to be approved to be used as a novel cancer therapy modality. In the current review, an overview is presented on recent (pre)clinical developments in the field of oncolytic viruses that have previously been or currently are being evaluated in clinical trials. Special attention is given to possible safety issues like toxicity, environmental shedding, mutation and reversion to wildtype virus.
Topics: Clinical Trials as Topic; Humans; Oncolytic Virotherapy; Oncolytic Viruses; Translational Research, Biomedical; Virus Shedding
PubMed: 25996182
DOI: 10.1080/21645515.2015.1037058 -
Journal of the American Veterinary... Jun 2015To evaluate the effectiveness of vinorelbine in the management of various malignant tumor types in dogs.
OBJECTIVE
To evaluate the effectiveness of vinorelbine in the management of various malignant tumor types in dogs.
DESIGN
Retrospective case series.
ANIMALS
58 dogs with malignant tumors, including pulmonary carcinoma (n = 31), histiocytic sarcoma (9), mast cell tumor (5), lymphoma (4), melanoma (2), and 7 other tumor types (1 each).
PROCEDURES
Medical records of dogs treated with vinorelbine from December 1997 to December 2012 were reviewed for data regarding signalment, clinical signs, physical examination findings, clinicopathologic test results, diagnostic imaging results, vinorelbine doses and dose frequency, surgery and radiotherapy details when applicable, other chemotherapeutics administered, and outcomes. Descriptive, comparative, and survival statistics were computed for all dogs and for dogs by histologic subgroup of tumors.
RESULTS
Vinorelbine was administered palliatively to 44 (76%) dogs. One (2%) dog had a complete response for 162 days, 5 (11%) dogs had a partial response for a median duration of 91 days, 19 (43%) dogs had stable disease for a median duration of 68 days, and 19 (43%) dogs developed progressive disease after a median duration of 21 days. Clinical benefit was more difficult to assess in the remaining 14 (24%) dogs that received vinorelbine as an adjuvant treatment. Overall median time to tumor progression was 103 days (range, 5 to 1,533 days).
CONCLUSIONS AND CLINICAL RELEVANCE
Vinorelbine appeared to be effective in the treatment of several tumor types in dogs. Follow-up prospective studies of the clinical benefit of the drug in specific clinical scenarios will be necessary to support this conclusion.
Topics: Animals; Antineoplastic Agents, Phytogenic; Dog Diseases; Dogs; Female; Male; Neoplasms; Retrospective Studies; Vinblastine; Vinorelbine
PubMed: 25970220
DOI: 10.2460/javma.246.11.1230 -
Tissue Barriers 2015The barrier properties of endothelial cells are critical for the maintenance of water and protein balance between the intravascular and extravascular compartments. An...
The barrier properties of endothelial cells are critical for the maintenance of water and protein balance between the intravascular and extravascular compartments. An impairment of endothelial barrier function has been implicated in the genesis and/or progression of a variety of pathological conditions, including pulmonary edema, ischemic stroke, neurodegenerative disorders, angioedema, sepsis and cancer. The altered barrier function in these conditions is often linked to the release of soluble mediators from resident cells (e.g., mast cells, macrophages) and/or recruited blood cells. The interaction of the mediators with receptors expressed on the surface of endothelial cells diminishes barrier function either by altering the expression of adhesive proteins in the inter-endothelial junctions, by altering the organization of the cytoskeleton, or both. Reactive oxygen species (ROS), proteolytic enzymes (e.g., matrix metalloproteinase, elastase), oncostatin M, and VEGF are part of a long list of mediators that have been implicated in endothelial barrier failure. In this review, we address the role of blood borne cells, including, neutrophils, lymphocytes, monocytes, and platelets, in the regulation of endothelial barrier function in health and disease. Attention is also devoted to new targets for therapeutic intervention in disease states with morbidity and mortality related to endothelial barrier dysfunction.
PubMed: 25838983
DOI: 10.4161/21688370.2014.978720 -
Veterinary Medicine (Auckland, N.Z.) 2014Feline injection site sarcoma is a common tumor among cats, for which existing medical treatments do not prove to be entirely satisfactory. In this tumor, the...
Feline injection site sarcoma is a common tumor among cats, for which existing medical treatments do not prove to be entirely satisfactory. In this tumor, the platelet-derived growth factor receptor, a tyrosine kinase receptor, is frequently hyperactivated. In the past, clinical case reports with imatinib, a tyrosine kinase inhibitor (TKI), have demonstrated tumoral stabilization. Here we describe the use of another TKI, masitinib, which specifically inhibits c-Kit, platelet-derived growth factor receptor, and Lyn, and is currently licensed for veterinary use in canine mast cell tumors. The therapeutic results were initially satisfactory, with regression of the tumor followed by tumoral recurrence which was stabilized and moderately reduced. Further studies are suggested, in order to evaluate the relevance of TKIs in the treatment and prevention of recurrences of feline injection site sarcoma. Tumoral stabilization by means of an inexpensive and reasonably well tolerated treatment would prove to be of true therapeutic relevance, in particular for inoperable feline injection site sarcomas. Another indication for such TKIs could be in preoperative treatment as a means of facilitating surgical excision by reduction of adhesions.
PubMed: 32670851
DOI: 10.2147/VMRR.S67118 -
Annals of Oncology : Official Journal... Sep 2014Mast cell leukemia (MCL), the leukemic manifestation of systemic mastocytosis (SM), is characterized by leukemic expansion of immature mast cells (MCs) in the bone... (Review)
Review
Mast cell leukemia (MCL), the leukemic manifestation of systemic mastocytosis (SM), is characterized by leukemic expansion of immature mast cells (MCs) in the bone marrow (BM) and other internal organs; and a poor prognosis. In a subset of patients, circulating MCs are detectable. A major differential diagnosis to MCL is myelomastocytic leukemia (MML). Although criteria for both MCL and MML have been published, several questions remain concerning terminologies and subvariants. To discuss open issues, the EU/US-consensus group and the European Competence Network on Mastocytosis (ECNM) launched a series of meetings and workshops in 2011-2013. Resulting discussions and outcomes are provided in this article. The group recommends that MML be recognized as a distinct condition defined by mastocytic differentiation in advanced myeloid neoplasms without evidence of SM. The group also proposes that MCL be divided into acute MCL and chronic MCL, based on the presence or absence of C-Findings. In addition, a primary (de novo) form of MCL should be separated from secondary MCL that typically develops in the presence of a known antecedent MC neoplasm, usually aggressive SM (ASM) or MC sarcoma. For MCL, an imminent prephase is also proposed. This prephase represents ASM with rapid progression and 5%-19% MCs in BM smears, which is generally accepted to be of prognostic significance. We recommend that this condition be termed ASM in transformation to MCL (ASM-t). The refined classification of MCL fits within and extends the current WHO classification; and should improve prognostication and patient selection in practice as well as in clinical trials.
Topics: Bone Marrow Examination; Diagnosis, Differential; Disease Progression; Humans; Leukemia, Mast-Cell; Leukemia, Myelomonocytic, Acute; Leukemia, Myelomonocytic, Chronic; Mast Cells; Mastocytosis
PubMed: 24675021
DOI: 10.1093/annonc/mdu047 -
Journal of the American Veterinary... Feb 2014A 10-year-old spayed female Jack Russell Terrier and a 7-year-old neutered male mixed-breed dog were evaluated because of acute, progressive, unilateral forelimb...
CASE DESCRIPTION
A 10-year-old spayed female Jack Russell Terrier and a 7-year-old neutered male mixed-breed dog were evaluated because of acute, progressive, unilateral forelimb lameness associated with signs of pain and turgid antebrachial swelling.
CLINICAL FINDINGS
For either dog, there were no salient pathological or diagnostic imaging abnormalities. A diagnosis of compartment syndrome was confirmed on the basis of high caudal antebrachial compartmental pressure in the affected forelimb.
TREATMENT AND OUTCOME
Both dogs underwent surgical exploration of the affected forelimb. In each case, an intramuscular tumor (mast cell tumor in the Jack Russell Terrier and suspected sarcoma in the mixed-breed dog) was detected and presumed to be the cause of the high compartmental pressure. At 6 months following tumor excision, the dog with the mast cell tumor did not have any clinical signs of disease. The dog with a suspected sarcoma underwent tumor excision and forelimb amputation at the proximal portion of the humerus followed by chemotherapy; the dog was euthanized approximately 1 year following treatment because of pulmonary metastasis.
CLINICAL RELEVANCE
Compartment syndrome is a serious but rarely reported condition in dogs and is typically ascribed to intracompartmental hemorrhage. These 2 cases illustrate the potential for expansile intramuscular antebrachial tumors to cause compartment syndrome in dogs.
Topics: Animals; Compartment Syndromes; Dog Diseases; Dogs; Female; Male; Mastocytoma; Sarcoma
PubMed: 24432967
DOI: 10.2460/javma.244.3.346 -
PloS One 2013Gammaherpesvirinae, such as the human Epstein-Barr virus (EBV) and the Kaposi's sarcoma associated herpesvirus (KSHV) are highly prevalent pathogens that have been...
Gammaherpesvirinae, such as the human Epstein-Barr virus (EBV) and the Kaposi's sarcoma associated herpesvirus (KSHV) are highly prevalent pathogens that have been associated with several neoplastic diseases. As EBV and KSHV are host-range specific and replicate poorly in vitro, animal counterparts such as Murid herpesvirus-4 (MuHV-4) have been widely used as models. In this study, we used MuHV-4 in order to improve the knowledge about proteins that compose gammaherpesviruses virions. To this end, MuHV-4 extracellular virions were isolated and structural proteins were identified using liquid chromatography tandem mass spectrometry-based proteomic approaches. These analyses allowed the identification of 31 structural proteins encoded by the MuHV-4 genome which were classified as capsid (8), envelope (9), tegument (13) and unclassified (1) structural proteins. In addition, we estimated the relative abundance of the identified proteins in MuHV-4 virions by using exponentially modified protein abundance index analyses. In parallel, several host proteins were found in purified MuHV-4 virions including Annexin A2. Although Annexin A2 has previously been detected in different virions from various families, its role in the virion remains controversial. Interestingly, despite its relatively high abundance in virions, Annexin A2 was not essential for the growth of MuHV-4 in vitro. Altogether, these results extend previous work aimed at determining the composition of gammaherpesvirus virions and provide novel insights for understanding MuHV-4 biology.
Topics: Animals; Capsid; Cell Line; Cricetinae; Extracellular Space; Glycosylation; Mass Spectrometry; Proteomics; Rhadinovirus; Viral Proteins; Virion
PubMed: 24386290
DOI: 10.1371/journal.pone.0083842 -
Journal of Veterinary Internal Medicine 2014Mutation analysis of proto-oncogene c-kit (c-kit) is advisable before starting treatment with tyrosine kinase inhibitors in dogs with mast cell tumor (MCT), including...
BACKGROUND
Mutation analysis of proto-oncogene c-kit (c-kit) is advisable before starting treatment with tyrosine kinase inhibitors in dogs with mast cell tumor (MCT), including those with metastatic disease. Testing is usually performed on primary tumors, assuming that c-kit mutation status does not change in metastasis.
HYPOTHESIS/OBJECTIVES
To give an insight into the mutational processes and to make a recommendation on the use of c-kit mutational analysis in the clinical setting.
ANIMALS
Twenty-one client-owned dogs with metastatic MCT.
METHODS
Dogs undergoing resection or biopsy for both primary and matched metastatic MCT were prospectively enrolled. Total RNA or DNA was extracted from primary MCT and corresponding metastases. Exons 8, 9, and 11 were amplified by PCR and sequenced. Genetic features between primary MCT and metastases were compared. Their correlation with clinicopathologic features was investigated.
RESULTS
Concordance (mutated or wild-type) of mutational status, evaluable in 21 primary and matched metastatic (20 nodal and 1 splenic) MCTs, was 100%. Three new c-kit mutations were identified. No significant correlation was detected between c-kit mutation and clinicopathologic features.
CONCLUSIONS AND CLINICAL IMPORTANCE
Proto-oncogene c-kit mutational status is conserved between any primary and its matched secondary tumor, suggesting that both can be used for c-kit mutational testing. Targeted therapies might be also used to treat metastatic disease.
Topics: Animals; Dog Diseases; Dogs; Exons; Female; Genetic Testing; Genotyping Techniques; Male; Mast-Cell Sarcoma; Mastocytoma; Mutation; Proto-Oncogene Proteins c-kit
PubMed: 24372836
DOI: 10.1111/jvim.12266