Vasculogenic mimicry-associated ultrastructural findings in human and canine inflammatory breast cancer cell lines.

BACKGROUND: Human inflammatory breast cancer (IBC) and canine inflammatory mammary cancer (IMC) are the most lethal mammary cancers. An exacerbated angiogenesis and the existence of vasculogenic mimicry (VM) are hallmarks of these tumors. The information regarding VM and ultrastructural characteristics of mammary cell lines is scant. METHODS: In this study, IBC cell line SUM149 and IMC cell line IPC-366 in adherent (2D) and non-adherent (3D) (mammospheres, cancer stem cells) conditions were analyzed by transmission and scanning electron microscopy (TEM and SEM, respectively). RESULTS: The TEM revealed round to oval shape cells with microvilli on the surface, high numbers of peroxisomes in close apposition to lipid droplets and some extracellular derived vesicles. The TEM and the SEM mammospheres revealed group of cells clumping together with a central lumen (resembling a mammary acini). The cells joint are tight junctions and zonula adherens. By SEM two cell morphologies were observed: spherical and flattened cells. There was evidence endothelial-like cells (ELCs), which is characteristic for this disease, showing several or unique cytoplasmic empty space. ELCs were more frequent in 3D than in 2D culture conditions and contained Weibel-Palade cytoplasmic bodies, which are exclusive structures of endothelial cells. CONCLUSIONS: Both cell lines, IPC-366 and SUM-149, shared ultrastructural characteristics, further supporting canine IMC as a model for the human disease. To the best of our knowledge, this is the first study that demonstrate the morphological differentiation of cultured cancer stem cells from cancer epithelial cell lines into endothelial-like cells, confirming the vasculogenic mimicry phenomenon from an ultrastructural point of view.

Different role of COX-2 and angiogenesis in canine inflammatory and non-inflammatory mammary cancer.

Human inflammatory breast cancer (IBC) and canine inflammatory mammary cancer (IMC) are the most aggressive and fatal types of mammary cancer, and both have a very poor prognosis and low survival rate. Human IBC is characterised by exacerbated angiogenesis, lymphangiogenesis, and lymphangiotropism. Lymphangiotropism is also characteristic of IMC, but microvascular density (MVD) and lymphangiogenesis have not been previously studied in canine IMC. In this study immunohistochemical expression of several angiogenesis-related factors (cyclooxygenase [COX]-2, vascular endothelial growth factors A and D [VEGF-A, VEGF-D], and vascular endothelial growth factor receptor 3 [VEGFR-3]), MVD, lymphatic proliferation index (LPI), and Ki-67 tumour proliferation index (PI) were studied in 21 canine IMC samples, 20 canine high-grade malignant non-IMC mammary tumours (MMTs), and four normal mammary gland samples (NMGs). All mammary neoplasms were histologically categorised as grade III. COX-2 values were also analysed by RT-PCR in seven IMCs, six MMTs and four NMGs. The expressions of COX-2, VEGF-A, and VEGF-D were significantly higher in IMC, MVD and LPI tumours, but not PI. In MMTs, COX-2 immunoexpression was significantly associated with VEGF-A, while in IMCs COX-2 was associated with VEGF-D (lymphangiogenic factor), its receptor VEGFR-3, and LPI. These results suggested that lymphangiogenic pathway stimulation isa specific role of COX-2 in IMC angiogenesis, which justifies the use of COX-2-based targeted palliative therapies in dogs. The exacerbated angiogenesis and lymphangiogenesis and the increased expression of angiogenesis-related factors further support canine IMC as a natural model for the study of human IBC.

Evaluation of the University of Florida lomustine, vincristine, procarbazine, and prednisone chemotherapy protocol for the treatment of relapsed lymphoma in dogs: 33 cases (2003-2009).

OBJECTIVE: To evaluate the toxicity and efficacy of a modification of a previously evaluated combination of lomustine, vincristine, procarbazine, and prednisone (LOPP) as a rescue protocol for refractory lymphoma in dogs. DESIGN: Retrospective case series. Animals-33 dogs with a cytologic or histologic diagnosis of lymphoma that developed resistance to their induction chemotherapy protocol. PROCEDURES: Lomustine was administered on day 0 of the protocol. Vincristine was administered on day 0 and again 1 time on day 14. Procarbazine and prednisone were administered on days 0 through 13 of the protocol. This cycle was repeated every 28 days. RESULTS: Median time from initiation to discontinuation of the University of Florida LOPP protocol was 84 days (range, 10 to 308 days). Overall median survival time was 290 days (range, 51 to 762 days). Overall response rate with this protocol was 61% (20/33), with 36% (12) having a complete response and 24% (8) having a partial response. Toxicosis rates were lower than for the previously published LOPP protocol. CONCLUSIONS AND CLINICAL RELEVANCE: The University of Florida LOPP protocol may be an acceptable alternative to the mechlorethamine, vincristine, procarbazine, and prednisone protocol as a rescue protocol for dogs with lymphoma.

Serum concentrations of IgG, IgA, and IgM in retired racing Greyhound dogs.

BACKGROUND: Greyhound dogs have significant physiologic, hematologic, and biochemical differences when compared with other breeds, including significantly lower serum globulin concentration owing to decreases in the α- and ß-globulin fractions. The specific proteins that account for differences in globulin concentrations are not known, but IgA and IgM, both ß-globulins, are potential candidates. OBJECTIVES: The aims of this study were to measure serum IgG, IgA, and IgM in clinically healthy retired racing Greyhounds and compare the results with those of age- and sex-matched non-Greyhound dogs. METHODS: Study animals included 25 Greyhound and 20 non-Greyhound dogs. Total protein, albumin, and total globulin concentrations were determined. IgG, IgA, and IgM concentrations were measured using a commercially available radial immunodiffusion kit. The Student t-test assuming equal variances was used to compare concentrations of immunoglobulins between groups. RESULTS: Serum concentrations of IgA and IgM in Greyhounds (IgA=49±20 mg/dL; IgM=132±47 mg/dL) were significantly lower than concentrations in non-Greyound dogs (IgA=70±39 mg/dL; Ig M=212±78 mg/dL). Concentrations of IgG did not differ between groups. CONCLUSIONS: Mean serum IgA and IgM concentrations in Greyhounds were lower than those in non-Greyhound dogs. This may contribute to low serum concentrations of ß-globulins in Greyhounds. Specific reference intervals are recommended for Greyhounds to avoid possible misdiagnosis of IgA or IgM deficiency.

Yoga e vigor: corporeidade pluridimensional e as novas práticas em saúde / Yoga and vigor: the multidimensionality of corporeality and the New Health practices

Esta tese é uma investigação teórico-conceitual sobre a corporeidade do tantra yoga. Nosso pressuposto é de que o corpo vivo desafia o dualismo mente corpo, assim o ser humano é presença como corporeidade, sendo sua presença integral a atualidade do saber e de ações sobre ele...

This thesis is a theoretical and concptual research of the corporeality proposed by tantra yoga. Our hypothesis is that the human being is a presence as corporeality, and its integral presence is the stage of knowledge and action above itself...