C-kit, flt-3, PDGFR-ß, and VEGFR2 expression in canine adrenal tumors and correlation with outcome following adrenalectomy.

The objective of this retrospective study was to evaluate the expression of receptor tyrosine kinases (RTKs) in canine adrenal tumors and correlate this expression with features of tumor aggressiveness and survival in dogs undergoing adrenalectomy. Forty-three canine adrenal tumors were evaluated for expression of c-kit, fms-like tyrosine kinase 3 (flt-3), platelet-derived growth factor receptor-ß (PDGFR-ß), and vascular endothelial growth factor receptor 2 (VEGFR2) using immunohistochemistry. Tumor RTK staining characteristics were compared to normal adrenals. Medical records were reviewed for data regarding patient outcome and tumor characteristics. Expression of c-kit, flt-3, PDGFR-ß, and VEGFR2 was detected in 26.9%, 92.3%, 96.2%, and 61.5% of cortical tumors and 0%, 63.2%, 47.4%, and 15.8% of pheochromocytomas, respectively. Expression of RTKs was not significantly increased when compared to normal adrenals and did not correlate with survival after adrenalectomy. Receptor tyrosine kinases are not overexpressed in canine adrenal tumors compared to normal adrenal tissue. Therapeutic inhibition of these receptors may still represent an effective approach in cases where receptor activation is present.

L'objectif de cette étude rétrospective était d'évaluer l'expression des récepteurs tyrosine kinases (RTKs) dans les tumeurs surrénales canines et de corréler cette expression avec des caractéristiques d'agressivité tumorale et de survie chez les chiens subissant une surrénalectomie.Quarante-trois tumeurs surrénales canines ont été évaluées pour l'expression de c-kit, de la tyrosine kinase 3 de type fms (flt-3), du récepteur du facteur de croissance dérivé des plaquettes-ß (PDGFR-ß) et du récepteur du facteur de croissance endothélial vasculaire 2 (VEGFR2) par immunohistochimie. Les caractéristiques de coloration de la tumeur RTK ont été comparées à celles des surrénales normales. Les dossiers médicaux ont été examinés pour les données concernant les résultats des patients et les caractéristiques de la tumeur. L'expression de c-kit, flt-3, PDGFR-ß et VEGFR2 a été détectée dans 26,9 %, 92,3 %, 96,2 % et 61,5 % des tumeurs corticales et 0 %, 63,2 %, 47,4 % et 15,8 % des phéochromocytomes, respectivement. L'expression des RTK n'était pas significativement augmentée par rapport aux surrénales normales et n'était pas corrélée avec la survie après surrénalectomie. Les récepteurs tyrosine kinases ne sont pas surexprimés dans les tumeurs surrénales canines par rapport au tissu surrénalien normal. L'inhibition thérapeutique de ces récepteurs peut encore représenter une approche efficace dans les cas où l'activation du récepteur est présente.(Traduit par Docteur Serge Messier).

Antitumor efficacy of CHMFL-KIT-110 solid dispersion in mouse xenograft models of human gastrointestinal stromal tumors.

PURPOSE: CHMFL-KIT-110, a selective c-KIT kinase inhibitor for gastrointestinal stromal tumors (GISTs), possesses a poorly water-soluble, limiting the further development of the drug. This study was to investigate the antitumor efficacy of CHMFL-KIT-110 and CHMFL-KIT-110 solid dispersion (laboratory code: HYGT-110 SD) in GIST tumor xenograft models and to explore the PK/PD relationship of HYGT-110 SD. METHODS: Plasma concentrations of HYGT-110 and HYGT-110 SD were determined by LC-MS/MS in KM mice. Antitumor activity was evaluated by measuring tumor volume and weight in c-KIT-dependent GIST xenograft models. PK/PD relationship was assessed by LC-MS/MS and Western Blot in the GIST-T1 xenografted mice. RESULTS: HYGT-110 exhibited a low oral bioavailability (10.91%) in KM mice. Compared with HYGT-110 treatment, the Cmax and AUC0-t of HYGT-110 SD in mice plasma were substantially increased by 18.81 and 6.76-fold, respectively. HYGT-110 SD (10, 30, and 100 mg/kg/day) also could dose-dependently decrease the tumor volume and weight in the GIST-882 cell-inoculated xenograft mouse models and show 86.35% tumor growth inhibition (TGI) at 28 days at a 25 mg/kg bid dosage in the GIST-T1 cell-inoculated xenograft mouse model. The free concentration of HYGT-110 in plasma was closely correlated with the inhibition of c-KIT phosphorylation levels in tumor tissues. CONCLUSIONS: In comparison with the HPMC formulation, both improved PK and PD characteristics of the solid dispersion formulation of CHMFL-KIT-110 were observed in in vivo animal experiments.

Blood-based protein profiling identifies serum protein c-KIT as a novel biomarker for hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is one of the most common hereditary heart diseases and can be classified into an obstructive (HOCM) and non-obstructive (HNCM) form. Major characteristics for HCM are the hypertrophy of cardiomyocytes and development of cardiac fibrosis. Patients with HCM have a higher risk for sudden cardiac death compared to a healthy population. In the present study, we investigated the abundancy of selected proteins as potential biomarkers in patients with HCM. We included 60 patients with HCM and 28 healthy controls and quantitatively measured the rate of a set of 92 proteins already known to be associated with cardiometabolic processes via protein screening using the proximity extension assay technology in a subgroup of these patients (20 HCM and 10 healthy controls). After validation of four hits in the whole cohort of patients consisting of 88 individuals (60 HCM patients, 28 healthy controls) we found only one candidate, c-KIT, which was regulated significantly different between HCM patients and healthy controls and thus was chosen for further analyses. c-KIT is a tyrosine-protein kinase acting as receptor for the stem cell factor and activating several pathways essential for cell proliferation and survival, hematopoiesis, gametogenesis and melanogenesis. Serum protein levels of c-KIT were significantly lower in patients with HCM than in healthy controls, even after adjusting for confounding factors age and sex. In addition, c-KIT levels in human cardiac tissue of patients with HOCM were significant higher compared to controls indicating high levels of c-KIT in fibrotic myocardium. Furthermore, c-KIT concentration in serum significantly correlated with left ventricular end-diastolic diameter in HOCM, but not HCM patients. The present data suggest c-KIT as a novel biomarker differentiating between patients with HCM and healthy population and might provide further functional insights into fibrosis-related processes of HOCM.

Liquid biopsy based on small extracellular vesicles predicts chemotherapy response of canine multicentric lymphomas.

Lymphoma is the most common type of canine hematological malignancy where the multicentric (cMCL) form accounts for 75% of all cases. The standard treatment is the CHOP chemotherapy protocols that include cyclophosphamide, doxorubicin, vincristine and prednisone, where the majority of dogs achieve complete/partial response; however, it is very important to predict non-responsive cases to improve treatment and to develop new targeted therapies. Here we evaluate a liquid biopsy approach based on serum Small Extracellular Vesicles enriched for exosomes (SEVs) to predict cMCL chemotherapy response. Nineteen dogs at the end of the 19-week chemotherapy protocol (8 Complete Response and 11 Progressive Disease) were evaluated for serum SEVs size, concentration and screened for 95 oncomirs. PD patients had higher SEVs concentration at the diagnosis than CR patients (P = 0.034). The ROC curve was significant for SEVs concentration to predict the response to CHOP (AUC = 0.8011, P = 0.0287). A potential molecular signature based on oncomirs from SEVs (caf-miR-205, caf-miR-222, caf-mir-20a and caf-miR-93) is proposed. To the best of our knowledge, this is the first study demonstrating the potential of a liquid biopsy based on SEVs and their miRNAs content to predict the outcome of chemotherapy for canine multicentric lymphomas.

Report of a new six-panel flow cytometry marker for early differential diagnosis of APL from HLA-DR negative Non-APL leukemia.

Although AML-M3 (APL) and HLA-DR negative non-APL are characterized by negative HLA-DR antigen, they are different entities with similar morphology in some cases. The aim of this study is the precise, differential diagnosis of APL from HLA-DR negative non-APL by flow cytometry to narrow the diagnosis window. Bone marrow or blood samples of 580 AML patients were analyzed, and flow cytometry and molecular analysis were performed for the diagnosis of blood disorders. In 105 HLA-DR negative AML patients, expression of HLA-DR, CD33, CD117, CD11b, CD64, CD34, CD9 and myeloperoxidase staining pattern were evaluated. Fifty-six patients were diagnosed with APL, and 49 patients were diagnosed with HLA-DR negative non-APL. The APL blasts expressed CD33, CD117, CD64, and CD9 in 100%, 80.3%, 94.6%, and 100% of the cases, respectively. HLA-DR negative non-APL blasts expressed CD33, CD117, CD64 and CD9 in 75.5%, 59.1%, 32.6%, and 73.4% of the cases, respectively. APL cells were negative for HLA-DR, CD11b, and CD34 in 96.4%, 94.6%, and 91.0%, respectively. Blasts in HLA-DR negative non M3-AML were negative for CD11b, CD117, and CD34 in 77.5%, 40.9%, and 22.4%, respectively. We also investigated myeloperoxidase (MPO) staining pattern and found strong diffuse reaction in APL cells while HLA-DR negative non-APL cells showed focal positive reaction. In all of the APL patients, except for one, PML/RARA translocation was positive, and in another case with HLA-DR negative non-APL, PML/RARA and other translocations were not detected. The six-panel combination profile rapidly and specifically identifies APL from other HLA-DR negative AML.

Does transrectal ultrasonography-guided biopsy of the prostate lead to possible further metastasis via circulating tumor cells?

Background/aim: We evaluate whether transrectal ultrasonography (TRUS)-guided prostate biopsy might lead to spillage of tumor cells into peripheral blood as a result of disruption of the epithelial barrier and ultimately result in metastasis. Materials and methods: Eighty-eight patients underwent TRUS-guided prostate needle biopsy due to prostate-specific antigen (PSA) increase or abnormal digital rectal examination at the Samsun Research and Training Hospital (Samsun, Turkey) between April 2016 and September 2018. Approximately 10 mL of whole blood was collected from patients before, 1 week after, and 1 month after biopsy. Samples were analyzed for CD117 positivity and prostate-specific membrane antigen (PSMA) levels using flow cytometry. Patients with pathologically determined prostate cancer and without CD117 positivity before biopsy were included in the study. The study group thus consisted of 55 patients. Results: Subjects' PSA levels ranged from 2.3 to 40.0 ng/mL (median: 7.9 ng/mL), and their Gleason score was a median of 7 (range: 5­9). PSMA levels ranged between 9.3 ng/mL and 118.5 ng/mL and CD117 antigen levels between 0 and 5. We detected no CD117- positive cells in blood samples collected 7 days or 1 month after biopsy. Conclusion: We detected no circulating tumor cells in the peripheral circulation following biopsy. Prostate needle biopsy seems to be a safe method in terms of spillage of tumor cells into blood circulation as a possible cause of further metastasis.

Serum level of stem cell factor and its soluble receptor in aspirin-exacerbated respiratory disease.

Aim: Stem cell factor (SCF) may be associated with inflammatory processes leading to aspirin-induced asthma. This study evaluated the relationship between serum level of SCF and its soluble receptor with aspirin-induced asthma. Methods & materials: Twenty-five patients and 25 healthy controls were enrolled in this study. The concentration of SCF and mast/stem cell growth factor receptor (C-kit) was determined in serum samples. Spirometry and rhinometry were performed to determine the severity of the disease. p < 0.05 were considered significant. Results: The serum levels of SCF and C-kit receptor were significantly higher in the case group. The serum SCF and C-kit level had a significant positive correlation with the severity of asthma, disease duration and nasal obstruction. Conclusion: Our findings suggest that SCF and C-kit receptors have a direct effect on the severity of aspirin-induced asthma.

CD34+ and CD34+VEGFR2+ cells in poorly controlled hypertensive patients.

CD34+ and CD34+VEGFR2+ cells participate in the repair of damaged endothelium and vascular remodelling. As their number and activity change due to the development of cardiovascular diseases, they are recognised as useful markers of cardiovascular health. As ineffective blood pressure control concerns high percentage of hypertensive patients, the purpose of our study was to investigate if proportions of various CD34+ and CD34+VEGFR2+ populations change due to hypertension occurrence and the effectiveness of the therapy. We also wanted to establish which factors impact these cells. Circulating populations of CD34+ and CD34+VEGFR2+ cells were analysed in peripheral blood samples by flow cytometry. Serum/plasma levels of sICAM-1, sVCAM-1 and vWF were determined using immunoenzymatic assay. We did not observe differences in CD34+ populations, but proportions of CD34+VEGFR2+ (p = 0.006), CD34+VEGFR2+CD133+ (p = 0.002) and CD34+VEGFR2+c-Kit+ (p = 0.003) cells were reduced in patients with poorly controlled blood pressure. We have also established that these cells exhibit connections with age, blood pressure and sICAM-1 serum levels. However, multiparametric regression analyses did not indicate any of the analysed variables as independent factors affecting CD34+VEGFR2+ populations. CD34+VEGFR2+, CD34+VEGFR2+CD133+ and CD34+VEGFR2+c-Kit+ cells are reduced in poorly controlled hypertensive patients, which may be partially connected with increased cardiovascular complications and mortality observed in this group.

Serum miR-518e-5p is a potential biomarker for secondary imatinib-resistant gastrointestinal stromal tumor.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumor of the intestinal tract. Imatinib is used as first-line therapy for GIST patients; however, secondary imatinib resistance poses a significant clinical challenge. Here, we analyzed serum miRNA expression profiles to identify specific serum miRNAs that could be used as early diagnostic markers. Candidate miRNAs were validated using Taqman quantitative PCR with serum samples from secondary imatinibresistant GIST patients (n = 39), imatinib-sensitive GIST patients (n = 37), and healthy controls (n = 28). Serum miR- 518e-5p and miR-548e levels were higher in secondary imatinib-resistant GIST than imatinib-sensitive GIST patients or healthy controls (P less than 0.0001). However, ROC analysis indicated that only miR-518e-5p could distinguish imatinibresistant GIST. To discriminate imatinib-resistant from imatinib-sensitive GIST patients, the AUC for serum miR-518e-5p was 0.9938, with 99.8% sensitivity and 82.1% specificity. Serum miR-518e-5p could also discriminate imatinib-resistant GIST patients from healthy controls with 99.9% sensitivity and 97.4% specificity. These data indicate that serum miR-518e- 5p is a potentially promising non-invasive biomarker for early detection and diagnosis of secondary imatinib-resistant GIST.

The effect of transient oxygenation on stem cell mobilization and ischemia/reperfusion heart injury.

For general anesthesia, pre-oxygenation is routinely performed prior to intubation. It is well-known that ischemic/hypoxic preconditioning induces stem cell mobilization and protects against ischemia/reperfusion (I/R) injury. In this study, we investigated the effect of transient oxygenation on stem cell mobilization and I/R injury of the heart. Mice were exposed to 100% oxygen for 5 or 20 minutes. We evaluated the number of c-kit+ stem/progenitor cells and the levels of SDF-1α and VEGF in peripheral blood at 1, 3, 6, and 24 hours after oxygenation. We also induced I/R injury of the heart at 3 hours post-oxygenation for 5 minutes and then examined stem cell recruitment and fibrotic changes in the heart 3 or 14 days later. The number of c-kit+ cells in peripheral blood was significantly increased at 1 or 24 hours after oxygenation for either 5 or 20 minutes. Oxygenation for 5 or 20 minutes did not significantly change the SDF-1α level measured in plasma. However, the plasma VEGF level was decreased at 3 hours post-oxygenation for 20 minutes (p = 0.051). Oxygenation for 5 minutes did not significantly alter the fibrotic area or cell apoptosis. Although oxygenation for 5 minutes increased the number of c-kit+ cells in hearts damaged by I/R injury, this difference was not significant between groups due to large variation between individuals (p = 0.14). Although transient oxygenation induces stem cell mobilization, it does not appear to protect against I/R injury of the heart in mice.

[Gastrointestinal stromal tumor and renal transplant]. / Tumor del estroma gastrointestinal y trasplante renal.

Gastrointestinal stromal tumor (GIST) accounts for nearly 1% of all gastrointestinal tumors. Its association with renal transplantation is not frequent. Approximately 95% of GIST show staining for CD177. DOG1 is a recently described monoclonal antibody that shows positivity even in the absence of CD177 staining. The diagnosis of GIST should be pursued because of the availability of very effective treatments with tyrosine-kinase inhibitors. Herein, we describe the case of a woman with renal transplant who presented a small bowel GIST and weak positivity for CD177, treated initially with surgery. Tumor recurrence was documented 3 years later and histopatology showed loss of CD177 staining and positivity for DOG1. She was treated with imatimib without further recurrence after five years of follow up.

Tumor del estroma gastrointestinal y trasplante renal / Gastrointestinal stromal tumor and renal transplant

El tumor estromal gastrointestinal (GIST) representa alrededor del 1% de todos los tumores digestivos y su aparición en pacientes trasplantados renales es infrecuente. Aproximadamente el 95% muestra tinción positiva para c-kit/CD117. DOG1 es un anticuerpo recientemente descrito que se sobre-expresa en los GIST, incluso en c-kit/ CD117 negativos. El diagnóstico preciso de GIST resulta imperativo, debido a la disponibilidad y la creciente eficacia de los inhibidores de la tirosina quinasa en estos tumores, incluso en el subgrupo c-kit/ CD117 negativo. Se presenta el caso de una mujer trasplantada renal inicialmente con GIST en intestino delgado y débil positividad para CD117 tratada con cirugía y recidiva tumoral a los tres años, pérdida de la expresión CD117 y tinción positiva para DOG1. Recibió tratamiento exitoso con imatimib sin presentar recaída tumoral durante un seguimiento de cinco años.

Gastrointestinal stromal tumor (GIST) accounts for nearly 1% of all gastrointestinal tumors. Its association with renal transplantation is not frequent. Approximately 95% of GIST show staining for CD177. DOG1 is a recently described monoclonal antibody that shows positivity even in the absence of CD177 staining. The diagnosis of GIST should be pursued because of the availability of very effective treatments with tyrosine-kinase inhibitors. Herein, we describe the case of a woman with renal transplant who presented a small bowel GIST and weak positivity for CD177, treated initially with surgery. Tumor recurrence was documented 3 years later and histopatology showed loss of CD177 staining and positivity for DOG1. She was treated with imatimib without further recurrence after five years of follow up.

Importance of CD117 in the Assignation of a Myeloid Lineage in Acute Leukemias.

The correct classification of acute leukemias (AL) is an essential part in the evaluation of any patient with this disease. Historically, CD117 has been an important asset in the diagnosis of patients with mixed-phenotype acute leukemia (MPAL). In an attempt to simplify the diagnosis of MPAL with fewer and more lineage specific markers, the World Health Organization (WHO) proposed in 2008 a new criteria for the diagnosis of this type of AL, which excluded CD117 from the myeloid markers that are utilized to diagnose MPAL. In order to assess whether CD117 is necessary in the diagnosis of MPAL, we evaluated the sensitivity and specificity of CD117 for acute myeloid leukemia (AML) in 331 patients with AL. The calculated sensitivity of CD117 for AML was 85.88% (103/120), while the specificity was 83.9% (177/211). Besides myeloperoxidase (MPO), which was used as the gold standard in differentiating AML from other type of ALs, the most specific markers for AML in our study were CD14 and CD64 (99.5 and 95.6%). Although the specificity of CD117 in this study is not as high as CD14 and CD64, markers concomitantly used in this this study and in the WHO classification, based on the results of other researches (i.e. the specificity of CD117 for AML was 100% in one study) and due to the fact that its specificity for AML in this study is relatively high, we recommend the use CD117 in assigning a myeloid lineage in MPAL.

Prospective evaluation of the diagnostic value of sensitive KIT D816V mutation analysis of blood in adults with suspected systemic mastocytosis.

BACKGROUND: Sensitive KIT D816V mutation analysis of blood has been proposed to guide bone marrow (BM) investigation in suspected systemic mastocytosis (SM). The aim of this prospective study was for the first time to compare the D816V status of the "screening blood sample" used to guide BM biopsy in suspected SM to the outcome of the subsequent BM investigation. METHODS: Fifty-eight adult patients with suspected SM were included. The outcome of sensitive KIT D816V analysis of blood was compared to the result of the BM investigation. RESULTS: Screening blood samples from 44 of 58 patients tested D816V-positive. In 43 of these, SM was subsequently diagnosed in the BM investigation. One patient with a D816V-positive screening sample was diagnosed with monoclonal MC activation syndrome. Screening blood samples from 14 patients tested D816V-negative. SM was subsequently diagnosed in five of these, whereas nine patients did not fulfill any diagnostic SM criteria (excluding tryptase criterion). Of the 48 SM patients, 90% tested D816V-positive. Thirteen SM patients presented with Hymenoptera venom-induced anaphylaxis, no skin lesions, and baseline serum tryptase ≤20 ng/mL. Of these, 92% tested D816V-positive in the screening blood sample. CONCLUSION: This prospective study demonstrates that a D816V-positive result in a screening blood sample identifies SM among patients with hymenoptera venom-induced anaphylaxis in whom the diagnosis would most probably have been missed, with potential severe implications. The observed false-negative screening results also underline that BM investigation is mandatory in all adult patients with clear signs of, or highly suspected SM, regardless of the KIT mutation status.

Primary Sinonasal Malignant Melanoma: Effect of Clinical and Histopathologic Prognostic Factors on Survival.

BACKGROUND: Mucosal melanoma is a rare malignancy arising from melanocytes of the mucosal surfaces. The pattern and frequency of oncogenic mutations and histopathological biomarkers have a role on distinct tumour behaviour and survival. AIMS: To assess the rate of C-KIT positivity and its effect on survival of surgically treated sinonasal malignant melanoma patients with other histopathological biomarkers and clinical features. STUDY DESIGN: Retrospective cross-sectional study. METHODS: Seventeen sinonasal malignant melanoma patients with a mean age of 65.41 (39-86) years were included. Overall survival and disease-specific survival rates were calculated. The impact of age, gender, stage and extent of the disease, type of surgery, and adjuvant therapies were also taken into consideration. The effect of mitotic index, pigmentation, S100, HMB-45, Melan-A and C-KIT on survival were evaluated. RESULTS: Median tumour size was 20 mm (interquartile range=27.5 mm). Pigmentation was present in 7 (41.2%) cases. Median number of mitoses per millimetre squared was 11 (interquartile range=13). Melan A was positive in 7 (41.2%) patients, ulceration was present in 6 cases (35.3%), and necrosis was present in (47.1%) 8 cases. Six patients (35.3%) were positive for S100, 14 (82.4%) specimens stained positive for HMB-45 and C-KIT (CD117) was positive in 9 cases (52.9%). Three patients (16.7%) developed distant metastasis. Five year overall and disease free survival rates were 61.4% and 43.8%, respectively. CONCLUSION: Although C-KIT positive sinonasal malignant melanoma patients (52.9%) can be candidates for targeted tumour therapies, the studied clinical or histopathological features along with C-KIT seem to have no significant effect on survival in a small group of patients with sinonasal malignant melanoma.

The Assessment of CD56 and CD117 Expressions at the Time of the Diagnosis in Multiple Myeloma Patients.

OBJECTIVE: The purpose of this study is to investigate the relationship between the CD56 and CD117 expressions and the clinical and laboratory findings in multiple myeloma (MM) patients. MATERIALS AND METHODS: Analyses of multiparametric flow cytometry data obtained from the diagnostic bone marrow aspirations of a total of 34 newly diagnosed MM patients were assessed retrospectively. CD56 and CD117 expressions of the patients were compared with their stages and clinical parameters. The staging was performed according to the International Staging System (ISS). RESULTS: Of the patients, 58.8% had ISS stage 1-2 MM while 41.2% had stage 3 MM. The number of CD56-positive patients was 29, whereas the number of CD117-positive patients was 13. There was no statistical difference between the CD56 and CD117 expressions and extramedullary involvement and lytic bone lesions. The median beta-2 microglobulin level was higher in the CD117-negative group (p=0.047). CD56 and CD117 expression levels were found to be lower in advanced-stage patients than in early-stage ones (p=0.026 and p=0.017). The lactate dehydrogenase (LDH) levels were high in advanced-stage patients, and an inverse relationship was found between LDH level and CD117 expression. CONCLUSION: Our findings that the CD56 and CD117 expression levels are lower in advanced stages than earlier stages and that LDH level and CD117 expression have an inverse relationship in patients with newly diagnosed MM suggest that CD56 and CD117 expressions may be prognostic markers for MM.

Concurrent multiple myeloma and mast cell neoplasia in a 13-year-old castrated male Maine Coon cat.

A 13-year-old, castrated male Maine Coon cat was presented to Oklahoma State University Boren Veterinary Medical Teaching Hospital for yearly echocardiographic examination monitoring hypertrophic cardiomyopathy (HCM) diagnosed in 2003. Physical examination revealed a heart murmur and premature beats, likely related to HCM, but was otherwise unremarkable. A biochemistry profile revealed a hyperglobulinemia (6.3 g/dL). Cytologic examination of fine-needle aspirates from liver and spleen revealed increased numbers of plasma cells and mast cells, confirmed with subsequent histologic examination. Immunohistochemistry (IHC) for c-kit in the spleen and liver showed mast cells predominantly exhibiting type I staining pattern, with moderate numbers exhibiting type II pattern in spleen, and scattered cells exhibiting type II and III patterns in liver. Bone marrow cytology and core biopsy documented approximately 22% plasma cells. Cutaneous masses on the cat's left shoulder and right carpus were cytologically confirmed mast cell tumors. Serum protein electrophoresis with immunofixation confirmed an IgG monoclonal gammopathy. This is an example of 2 hematologic neoplasms occurring simultaneously in a cat. Concurrent pathologies may be overlooked if a single disease is diagnosed and suspected of causing all clinical signs. Both neoplasms were well differentiated, and neoplastic cells could have easily been interpreted as a reactive population had a full workup not been performed. Missing either diagnosis could result in a potentially lethal outcome. Eleven months after diagnoses, the cat was clinically doing well following a splenectomy and oral prednisolone and chlorambucil chemotherapy. Globulins decreased to 4.9 g/dL.

Effect of hyperglycemia on the number of CD117+ progenitor cells and their differentiation toward endothelial progenitor cells in young and old ages.

Dysfunction of endothelial progenitor cells (EPCs) has been reported either in aging or diabetes, though the influence of an "old" environment on numerical and functional changes of diabetes associated EPCs is not known. We evaluated the effect of both aging and early stage of streptozotocin-induced diabetes on the number of bone marrow-derived CD117+ progenitor cells, and on their differentiation in vitro toward EPCs. The phenotype of progenitor cells and the uptake of acetylated-low density lipoprotein (Ac-LDL) were evaluated after cell culture in VEGF, FGF-1, and IGF-1 supplemented medium. Hyperglycemia similarly reduced the number of CD117+ cells both in young and old mice. CD117+ cells from young mice differentiated better than those from old animals "in vitro", with a greater reduction of CD117+ cells and an higher increase of CD184+VEGFR-2+ cells. In diabetic mice, in vitro CD117+ cells differentiation was significantly reduced in young animals. Diabetes did not impact on the scarce differentiation of CD117+ cells from old mice. Hyperglycemia reduced the uptake of acLDL by EPCs greatly in young than in old mice. These findings indicate that part of the EPCs functional alterations induced by hyperglicemia in young mice are observed in normal aged mice.

Masitinib monotherapy in canine epitheliotropic lymphoma.

This study evaluated efficacy and side effects of masitinib in canine epitheliotropic lymphoma. Complete remission occurred in 2 of 10 dogs and lasted for median 85 days. Five dogs went into partial remission for median 60.5 days. Three pretreated dogs did not respond to therapy. Side effects occurred in six dogs and were mostly mild to moderate. Immunohistochemistry was available for eight dogs. KIT receptor was negative in all of them, six of eight lymphomas stained strongly positive for stem cell factor (SCF). platelet-derived growth factor (PDGF)-AA was weakly positive in two and negative in six. PDGF-BB was negative in four tumours, weakly positive in one and strongly positive in three. One was strongly positive for PDGF receptor (PDGFR)-ß, seven were negative for that receptor. Five showed strong expression of PDGFR-α, two showed weak expression, one was negative. In conclusion, masitinib is effective in treating canine epitheliotropic lymphoma. But its effects are most likely not generated through the KIT receptor.