RESUMEN
The aim of this study was to evaluate renal hemodynamics, routine clinical and laboratory parameters used to estimate renal function, and clinical evolution during six months in bitches with mammary carcinomas that underwent mastectomy and were treated (TG) or not (CG) with carprofen for three months after surgery. Twenty-six bitches with mammary carcinoma were equally distributed into TG that received carprofen 4.4 mg/kg/day for 90 days and CG that did not receive anti-inflammatory medication. Renal artery Doppler flowmetry, contrast-enhanced ultrasound (CEUS) of renal parenchyma, haematological, biochemical and clinical analyses were obtained once a month. These data were compared between groups and time via analysis of variance (ANOVA) in a completely randomized design with repeated measures (P < 0.05). On B-mode ultrasound, the area of the renal artery was greater (P = 0.0003) in the TG. Regarding laboratory findings, haematocrit and haemoglobin were similar in both groups, showing a significant and gradual increase after three months of treatment; MCV, MHC, and MCHC were increased (P < 0.05) and lymphocyte and band counts decreased (P < 0.05) in the TG. Regarding biochemical tests, ALT was the only parameter with a significant difference, being higher (P = 0.0272) in the treated group. It can be concluded that the use of carprofen for 90 days causes minimal changes in renal perfusion, erythrocyte parameters and ALT activity, and reduces the proportion of blood inflammatory cells. Therefore, use of this medication can be carried out safely in patients who require auxiliary cancer treatment.
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Carbazoles/administración & dosificación , Carbazoles/efectos adversos , Carcinoma/tratamiento farmacológico , Enfermedades de los Perros/tratamiento farmacológico , Riñón/irrigación sanguínea , Riñón/diagnóstico por imagen , Neoplasias Mamarias Animales/tratamiento farmacológico , Circulación Renal/efectos de los fármacos , Ultrasonografía Doppler , Animales , Carcinoma/fisiopatología , Carcinoma/cirugía , Enfermedades de los Perros/fisiopatología , Enfermedades de los Perros/cirugía , Perros , Femenino , Glándulas Mamarias Animales/cirugía , Neoplasias Mamarias Animales/fisiopatología , Neoplasias Mamarias Animales/cirugía , Factores de TiempoRESUMEN
Pharmacological approaches to breast cancer risk-reduction for BRCA1 mutation carriers would provide an alternative to mastectomy. BRCA1-deficiency dysregulates progesterone signaling, promoting tumorigenesis. Selective progesterone receptor (PR) modulators (SPRMs) are therefore candidate prevention agents. However, their efficacy varies in different BRCA1-deficient mouse models. We examined chemopreventive efficacy of telapristone acetate (TPA), ulipristal acetate (UPA) and mifepristone (MFP) in mice with a conditional knockout of the Brca1 C-terminal domain. The SPRMs displayed a spectrum of efficacy: UPA was most effective, TPA less, and MFP ineffective. Compared to no-treatment controls, UPA reduced tumorigenesis (p = 0.04), and increased tumor latency (p = 0.03). In benign mammary glands, UPA decreased Ki67 (p < 0.001) and increased PR expression (p < 0.0001). RNA sequencing analysis revealed distinct gene expression in response to UPA and MFP. UPA downregulated glycolysis and extracellular matrix-inflammation genes (Fn1, Ptgs2, Tgfb2, Tgfb3) whereas MFP downregulated claudin genes and upregulated amino acid metabolism and inflammation genes. The anti-glucocorticoid effects of MFP appeared not to be tumor-protective, while altering estrogen receptor signaling and NF-kB activation. Our study points to an important role of epithelial PR and its paracrine action on the microenvironment in BRCA1-deficient mammary tumorigenesis, and prevention.
Asunto(s)
Proteína BRCA1/genética , Neoplasias de la Mama/tratamiento farmacológico , Receptores de Progesterona/genética , Microambiente Tumoral/genética , Animales , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Carcinogénesis/efectos de los fármacos , Carcinogénesis/genética , Modelos Animales de Enfermedad , Células Epiteliales/metabolismo , Células Epiteliales/patología , Femenino , Humanos , Glándulas Mamarias Animales/metabolismo , Glándulas Mamarias Animales/patología , Glándulas Mamarias Animales/cirugía , Mastectomía , Ratones , Mifepristona/farmacología , Norpregnadienos/farmacología , Células del Estroma/metabolismo , Células del Estroma/patología , Microambiente Tumoral/efectos de los fármacosRESUMEN
Failure of conventional clinical therapies such as tumor resection and chemotherapy are mainly due to the ineffective control of tumor metastasis. Metastasis consists of three steps: (i) tumor cells extravasate from the primary sites into the circulation system via epithelial-mesenchymal transition (EMT), (ii) the circulating tumor cells (CTCs) form "micro-thrombi" with platelets to evade the immune surveillance in circulation, and (iii) the CTCs colonize in the pre-metastatic niche. Here, we design a systemic metastasis-targeted nanotherapeutic (H@CaPP) composed of an anti-inflammatory agent, piceatannol, and an anti-thrombotic agent, low molecular weight heparin, to hinder the multiple steps of tumor metastasis. H@CaPP is found efficiently impeded EMT, inhibited the formation of "micro-thrombi", and prevented the development of pre-metastatic niche. When combined with surgical resection or chemotherapy, H@CaPP efficiently inhibits tumor metastasis and prolonged overall survival of tumor-bearing mice. Collectively, we provide a simple and effective systemic metastasis-targeted nanotherapeutic for combating tumor metastasis.
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Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Portadores de Fármacos/química , Neoplasias Mamarias Experimentales/terapia , Metástasis de la Neoplasia/terapia , Nanomedicina Teranóstica/métodos , Animales , Antiinflamatorios/administración & dosificación , Anticoagulantes/administración & dosificación , Línea Celular Tumoral/trasplante , Quimioterapia Adyuvante/métodos , Modelos Animales de Enfermedad , Transición Epitelial-Mesenquimal/efectos de los fármacos , Femenino , Heparina de Bajo-Peso-Molecular/administración & dosificación , Células Endoteliales de la Vena Umbilical Humana , Humanos , Masculino , Glándulas Mamarias Animales/patología , Glándulas Mamarias Animales/cirugía , Neoplasias Mamarias Experimentales/patología , Ratones , Nanopartículas/química , Células Neoplásicas Circulantes/efectos de los fármacos , Paclitaxel/administración & dosificación , Prueba de Estudio Conceptual , Ratas , Estilbenos/administración & dosificaciónRESUMEN
Multiphoton intravital imaging is essential for understanding cellular behavior and function in vivo. The adipose-rich environment of the mammary gland poses a unique challenge to in vivo microscopy due to light scattering that impedes high-resolution imaging. Here we provide a protocol for high-quality, six-color 3D intravital imaging of regions across the entire mouse mammary gland and associated tissues for several hours while maintaining tissue access for microdissection and labeling. An incision at the ventral midline and along the right hind leg creates a skin flap that is then secured to a raised platform skin side down. This allows for fluorescence-guided microdissection of connective tissue to provide unimpeded imaging of mammary ducts. A sealed imaging chamber over the skin flap creates a stable environment while maintaining access to large tissue regions for imaging with an upright microscope. We provide a strategy for imaging single cells and the tissue microenvironment utilizing multicolor Confetti lineage-tracing and additional dyes using custom-designed filters and sequential excitation with dual multiphoton lasers. Furthermore, we describe a strategy for simultaneous imaging and photomanipulation of single cells using the Olympus SIM scanner and provide steps for 3D video processing, visualization and high-dimensional analysis of single-cell behavior. We then provide steps for multiplexing intravital imaging with fixation, immunostaining, tissue clearing and 3D confocal imaging to associate cell behavior with protein expression. The skin-flap surgery and chamber preparation take 1.5 h, followed by up to 12 h of imaging. Applications range from basic filming in 1 d to 5 d for multiplexing and complex analysis.
Asunto(s)
Microscopía Intravital/métodos , Glándulas Mamarias Animales/citología , Análisis de la Célula Individual , Anestesia , Animales , Células Epiteliales/citología , Femenino , Colorantes Fluorescentes/química , Proteínas Fluorescentes Verdes/metabolismo , Imagenología Tridimensional , Glándulas Mamarias Animales/cirugía , Ratones Endogámicos C57BL , Ratones Transgénicos , Células del Estroma/citologíaRESUMEN
Rationale: Tumors are commonly treated by resection, which usually leads to massive hemorrhage and tumor cell residues, thereby increasing the risk of local recurrence and distant metastasis. Methods: Herein, an intelligent 3D-printed poly(lactic-co-glycolic acid), gelatin, and chitosan scaffold loaded with anti-cancer drugs was prepared that showed hemostatic function and good pH sensitivity. Results: Following in situ implantation in wounds, the scaffolds absorbed hemorrhage and cell residues after surgery, and promoted wound healing. In an in vivo environment, the scaffold responded to the slightly acidic environment of the tumor to undergo sustained drug release to significantly inhibit the recurrence and growth of the tumor, and reduced drug toxicity, all without causing damage to healthy tissues and with good biocompatibility. Conclusions: The multifunctional intelligent scaffold represents an excellent treatment modality for breast cancer following resection, and provides great potential for efficient cancer therapy.
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Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias de la Mama/terapia , Portadores de Fármacos/química , Recurrencia Local de Neoplasia/prevención & control , Materiales Inteligentes/química , Herida Quirúrgica/terapia , Animales , Neoplasias de la Mama/patología , Línea Celular Tumoral , Quimioterapia Adyuvante/métodos , Quitosano/química , Doxiciclina/administración & dosificación , Composición de Medicamentos/métodos , Femenino , Fluorouracilo/administración & dosificación , Gelatina/química , Humanos , Glándulas Mamarias Animales/patología , Glándulas Mamarias Animales/cirugía , Mastectomía , Ratones , Metástasis de la Neoplasia/patología , Metástasis de la Neoplasia/prevención & control , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Impresión Tridimensional , Andamios del Tejido/química , Cicatrización de Heridas/efectos de los fármacos , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Breast cancer is the most common cause of cancer-related deaths in women worldwide. Identification of reliable prognostic indicators and therapeutic targets is critical for improving patient outcome. Cancer in companion animals often strongly resembles human cancers and a comparative approach to identify prognostic markers can improve clinical care across species. Feline mammary tumors (FMT) serve as models for extremely aggressive triple negative breast cancer (TNBC) in humans, with high rates of local and distant recurrence after resection. Despite the aggressive clinical behavior of most FMT, current prognostic indicators are insufficient for accurately predicting outcome, similar to human patients. Given significant heterogeneity of mammary tumors, there has been a recent focus on identification of universal tumor-permissive stromal features that can predict biologic behavior and provide therapeutic targets to improve outcome. As in human and canine patients, collagen signatures appear to play a key role in directing mammary tumor behavior in feline patients. We find that patients bearing FMTs with denser collagen, as well as longer, thicker and straighter fibers and less identifiable tumor-stromal boundaries had poorer outcomes, independent of the clinical variables grade and surgical margins. Most importantly, including the collagen parameters increased the predictive power of the clinical model. Thus, our data suggest that similarities with respect to the stromal microenvironment between species may allow this model to predict outcome and develop novel therapeutic targets within the tumor stroma that would benefit both veterinary and human patients with aggressive mammary tumors.
Asunto(s)
Colágeno/metabolismo , Neoplasias Mamarias Animales/cirugía , Pronóstico , Neoplasias de la Mama Triple Negativas/cirugía , Animales , Gatos , Colágeno/genética , Modelos Animales de Enfermedad , Femenino , Humanos , Glándulas Mamarias Animales/metabolismo , Glándulas Mamarias Animales/patología , Glándulas Mamarias Animales/cirugía , Neoplasias Mamarias Animales/genética , Neoplasias Mamarias Animales/metabolismo , Neoplasias Mamarias Animales/patología , Neoplasias de la Mama Triple Negativas/genética , Neoplasias de la Mama Triple Negativas/metabolismo , Neoplasias de la Mama Triple Negativas/patología , Microambiente Tumoral/genéticaRESUMEN
BACKGROUND: Seroma, which is the most common complication after mastectomy and axillary dissection, is the leakage of the lymphovascular fluid into the dead space. It can cause local complications varying from delayed wound healing to infection and skin flap necrosis. The aim of this study was to evaluate whether platelet-rich plasma (PRP) reduces the risk of seroma formation. MATERIALS AND METHODS: A total of 24 Wistar albino rats were randomly divided into three groups of eight rats in each. For the rats in group 1, no additional procedures were carried out. The rats in groups 2 and 3 were applied with 0.25 and 0.5 mL/cm2 PRP, respectively, to the operation site. The groups were compared in respect of adhesion scores, histopathologic examination, and tissue seroma volume. RESULTS: The mean seroma volume was 2.19 ± 0.78 mL in group 1, 1.43 ± 0.35 mL in group 2, and 0.96 ± 0.24 mL in group 3. The seroma volumes of groups 3 and 2 were significantly lower than those in group 1. In the macroscopic assessment the mean general adhesion score was 6 ± 0.75 in group 3. The other general adhesion scores were 5.25 ± 0.70 and 2.12 ± 0.64 in groups 2 and 1, respectively. The adhesion scores of groups 3 and 2 were significantly higher than those of group 1. The mean inflammatory cell score was 0.87 ± 0.83 in group 3, 2.0 ± 0.92 in group 2, and 3.0 ± 0.53 in group 1. There were significantly lower levels of inflammatory cells in group 3 than in the other groups and the group 2 inflammatory cell count was lower than that of group 1. Fibroblast density score was significantly higher in group 3 (2.50 ± 1.06) compared with the other groups. Neovascularization was significantly higher in groups 3 and 2 compared with group 1. The mean neovascularization score was 2.25 ± 1.16 and 2.12 ± 1.12 in groups 2 and 3, respectively. There were no statistically significant differences between the groups in respect of collagen levels. CONCLUSIONS: Local application of PRP in rats after experimental mastectomy and axillary dissection was observed to decrease seroma formation and to increase neovascularization and fibroblast density.
Asunto(s)
Neoplasias de la Mama/cirugía , Mastectomía/efectos adversos , Plasma Rico en Plaquetas/fisiología , Complicaciones Posoperatorias/prevención & control , Seroma/prevención & control , Animales , Axila , Modelos Animales de Enfermedad , Femenino , Humanos , Escisión del Ganglio Linfático/efectos adversos , Glándulas Mamarias Animales/patología , Glándulas Mamarias Animales/cirugía , Neovascularización Fisiológica/fisiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/patología , Ratas , Ratas Wistar , Seroma/etiología , Seroma/patología , Cicatrización de Heridas/fisiologíaRESUMEN
Genomic and precision medicine research has afforded notable advances in human cancer treatment, yet applicability to other species remains uncertain. Through whole-exome and transcriptome analyses of 191 spontaneous canine mammary tumors (CMTs) that exhibit the archetypal features of human breast cancers, we found a striking resemblance of genomic characteristics including frequent PIK3CA mutations (43.1%), aberrations of the PI3K-Akt pathway (61.7%), and key genes involved in cancer initiation and progression. We also identified three gene expression-based CMT subtypes, one of which segregated with basal-like human breast cancer subtypes with activated epithelial-to-mesenchymal transition, low claudin expression, and unfavorable disease prognosis. A relative lack of ERBB2 amplification and Her2-enrichment subtype in CMT denoted species-specific molecular mechanisms. Taken together, our results elucidate cross-species oncogenic signatures for a better understanding of universal and context-dependent mechanisms in breast cancer development and provide a basis for precision diagnostics and therapeutics for domestic dogs.
Asunto(s)
Biomarcadores de Tumor/genética , Neoplasias de la Mama/genética , Carcinogénesis/genética , Regulación Neoplásica de la Expresión Génica , Neoplasias Mamarias Animales/genética , Animales , Mama/patología , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Fosfatidilinositol 3-Quinasa Clase I/genética , Estudios de Cohortes , Variaciones en el Número de Copia de ADN , Análisis Mutacional de ADN , Conjuntos de Datos como Asunto , Perros , Transición Epitelial-Mesenquimal , Femenino , Humanos , Glándulas Mamarias Animales/patología , Glándulas Mamarias Animales/cirugía , Neoplasias Mamarias Animales/mortalidad , Neoplasias Mamarias Animales/patología , Neoplasias Mamarias Animales/cirugía , Mutación , Pronóstico , RNA-Seq , Especificidad de la Especie , Secuenciación del ExomaRESUMEN
BACKGROUND: One of the most common complications of the use of foreign material, in both reconstructive and cosmetic breast surgery, is capsular contracture. Historically, research on capsular contracture has focused mainly on reducing bacterial contamination through antibiotic solutions. Only secondary studies have focused on pharmacological control of the inflammation process, with particular attention paid to the main inflammation pathway, the arachidonic acid cascade. An important role in the arachidonic acid cascade is played by the omega-3 fatty acids, which are found mainly in oily fish and food supplements. The goal of the present study was to investigate the effects of omega-3 supplements on capsule contraction. METHODS: Female C57BL/6 mice were implanted with custom-made silicone gel implants and divided into two groups. The treated group received omega-3 oil daily while the control group received water daily by gavage. After mice were euthanized, samples of capsules were collected to evaluate thickness and transforming growth factor (TGF)-ß expression. RESULTS: The results showed that capsules in the omega-3 group were thinner and more transparent than those found in the control group. In addition, a significant downregulation of the TGF-ß2 gene transcript was observed in the omega-3 group. CONCLUSIONS: Omega-3 supplementation seems to be effective in reducing the occurrence of capsular formation, mainly through inhibition of the TGF-ß pathway and impairment of collagen deposit. Omega-3 supplementation is a simple and promising method that could be used to prevent or at least reduce capsular contracture after silicone implant surgery.
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Implantación de Mama/efectos adversos , Implantes de Mama/efectos adversos , Suplementos Dietéticos , Ácidos Grasos Omega-3/administración & dosificación , Contractura Capsular en Implantes/prevención & control , Administración Oral , Animales , Implantación de Mama/instrumentación , Modelos Animales de Enfermedad , Femenino , Humanos , Contractura Capsular en Implantes/etiología , Contractura Capsular en Implantes/patología , Glándulas Mamarias Animales/efectos de los fármacos , Glándulas Mamarias Animales/patología , Glándulas Mamarias Animales/cirugía , Ratones , Ratones Endogámicos C57BL , Geles de Silicona/efectos adversosRESUMEN
Surgical removal of the primary tumor is a common practice in breast cancer treatment. However, postsurgical metastasis poses an immense setback in cancer therapy. Considering that 90% of cancer-related deaths are due to metastasis, antimetastatic therapeutic strategies that can target disseminating tumor cells in the circulation before they can form secondary tumors hold preclinical and clinical potential for cancer patients. Our current work uses a liposomal formulation functionalized with the adhesion receptor E-selectin and the apoptosis-inducing ligand TNF (tumor necrosis factor)-related apoptosis-inducing ligand (TRAIL) to reduce metastasis following tumor resection in an aggressive triple-negative breast cancer (TNBC) mouse model. We demonstrate that minimal administration of E-selectin-TRAIL liposomes can target metastasis in a TNBC model, with primary tumor resection to mimic clinical settings. Our study indicates that TRAIL liposomes, alone or in combination with existing clinically approved therapies, may neutralize distant metastasis of a broad range of tumor types systemically.
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Apoptosis/efectos de los fármacos , Neoplasias Experimentales/tratamiento farmacológico , Ligando Inductor de Apoptosis Relacionado con TNF/genética , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Animales , Aspirina/farmacología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Curcumina/farmacología , Dioxolanos/farmacología , Selectina E/química , Selectina E/genética , Femenino , Humanos , Leucocitos/efectos de los fármacos , Leucocitos/patología , Liposomas/química , Liposomas/farmacología , Glándulas Mamarias Animales/efectos de los fármacos , Glándulas Mamarias Animales/patología , Glándulas Mamarias Animales/cirugía , Ratones , Metástasis de la Neoplasia , Neoplasias Experimentales/genética , Neoplasias Experimentales/patología , Neoplasias Experimentales/cirugía , Ligando Inductor de Apoptosis Relacionado con TNF/antagonistas & inhibidores , Neoplasias de la Mama Triple Negativas/genética , Neoplasias de la Mama Triple Negativas/patología , Neoplasias de la Mama Triple Negativas/cirugíaRESUMEN
Lysyl oxidase (LOX) is an extracellular metalloenzyme which mediates crosslinking of collagen and elastin. It has been reported to play a pivotal role in cancer metastasis especially in women suffering from breast cancer. The present study is the first to evaluate the gene expression levels of LOX by Real time-polymerase chain reaction (Real time-PCR) in dogs with mammary tumor besides molecular cloning and expression of canine lysyl oxidase gene (lox). Real time-PCR studies showed a significant upregulation (threefold higher) of lox in mammary tumor cases as compared to healthy dogs indicating its possible diagnostic and prognostic role in canine mammary tumors (CMTs). Cloning and sequencing of lox gene revealed 1230 bp CDS which is mostly conserved in C-terminal region. Sequence analysis of canine lox showed that it shares 99% homology with the predicted sequence available on NCBI and had greatest identity with the lox gene from cat. Protein structure predicted with homology modelling was validated by Ramachandran plot analysis which revealed most (approximately 95%) of the amino acids in favoured region. Additionally, recombinant lysyl oxidase expressed as His-tagged fusion protein in prokaryotic expression vector (pPROExHTa) was used in an ELISA for detection of circulating protein LOX in serum of CMT subjects. Receiver operating characteristics analysis of the ELISA revealed high sensitivity (90%) and specificity (85%) with histopathology as reference standard. Taken together, we propose LOX as a diagnostic biomarker and a putative prognostic candidate in CMT cases.
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Neoplasias Mamarias Animales/diagnóstico , Neoplasias Mamarias Animales/metabolismo , Proteína-Lisina 6-Oxidasa/genética , Animales , Biomarcadores de Tumor/metabolismo , Perros/metabolismo , Femenino , Regulación Neoplásica de la Expresión Génica/genética , Glándulas Mamarias Animales/metabolismo , Glándulas Mamarias Animales/cirugía , Neoplasias Mamarias Animales/genética , Pronóstico , Proteína-Lisina 6-Oxidasa/análisis , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Proteínas Recombinantes/genética , Transcriptoma/genéticaRESUMEN
AIMS: To compare stainless steel staples and polypropylene suture material for primary closure of wounds after teat amputation in ewes and to assess progress of healing in the presence or absence of intramammary infection (IMI). METHODS: Chios-cross ewes, aged 3-5 years were randomly allocated to be infected in one teat with 1,200-1,500 cfu of Mannheimia haemolytica 5 days after parturition (groups A and B; n = 8 in each group) or remain uninfected (groups C and D; n = 4 in each group). On the following 4 days one teat from each ewe was amputated 2.5â cm from the teat end and the wound was closed using skin staples (groups A and C) or polypropylene sutures (groups B and D). Clinical evaluation of wound healing was performed between 1-21 days after surgery. On day 21 tissue sections were collected for tensiometric and histological evaluation. RESULTS: The mean interval from the start to finish of wound closure was shorter when staples were used than when sutures were used (p < 0.001). Healing scores were lower (improved) for ewes in group A than B between days 1-7 after surgery (p = 0.005), but were similar between days 10-21 (p = 0.43). Healing scores were similar in groups C and D (p = 0.98). The tensile strain at maximum load was higher in tissue from group A than B (p = 0.001) and D (p = 0.004), but all other tensiometric measures were similar between groups. Histologically, collagen density was higher in sections from group A than B (p = 0.05) and D (p = 0.01), and angiogenesis was lower in sections from group A than B (p = 0.03) and D (p = 0.01). CONCLUSIONS AND CLINICAL RELEVANCE: Skin staples and polypropylene sutures can be used effectively for primary closure of teat wounds, even in the presence of IMI. Skin staples had the advantage of a reduction in surgical time. ABBREVIATION: IMI: intramammary infection.
Asunto(s)
Glándulas Mamarias Animales/cirugía , Enfermedades de las Ovejas/cirugía , Técnicas de Sutura/veterinaria , Cicatrización de Heridas , Animales , Modelos Animales de Enfermedad , Femenino , Grecia , Glándulas Mamarias Animales/microbiología , Glándulas Mamarias Animales/patología , Mannheimia , Mastectomía/veterinaria , Infecciones por Pasteurellaceae/veterinaria , Polipropilenos , Distribución Aleatoria , Ovinos , Enfermedades de las Ovejas/microbiología , Grapado Quirúrgico/veterinaria , Suturas , Resultado del TratamientoRESUMEN
INTRODUCTION: Capsular contracture (CC) is the most common complication of breast implantation, with an incidence of nearly 50% in patients undergoing breast reconstruction with subsequent radiotherapy. Although the move toward submuscular (SM) device placement led to a decreased incidence of CC, subcutaneous (SQ) implantation has seen a resurgence. The purpose of this study was to use a rodent model of breast reconstruction with smooth silicone implants and delayed radiotherapy to assess the occurrence of CC in SQ versus SM implantation. METHODS: Custom 2 mL smooth round silicone implants were placed bilaterally into 12 female Sprague Dawley rats that were randomized into 4 groups of 3, with each group differing by implantation plane (SQ vs SM) and irradiation status (irradiated vs nonirradiated). Rats from the SQ group received implants bilaterally underlying the skin on the flank. Rats in the SM groups received implants bilaterally under the latissimus dorsi muscle. Irradiated rats received 20 Gy localized to each implant on postoperative day 10. One rat from each group was imaged with a micro-computed tomography scanner at baseline and at explant 3 months later, whereupon capsules from all rats were examined histologically. RESULTS: Rats in the SQ group showed evidence of contracture on gross examination and greater evidence of morphologic disruption per micro-computed tomography scan. There was no evidence of contracture or morphologic disruption in either SM group. Mean ± SD capsule thickness was 39.0 ± 9.0 µm in the SQ versus 37.6 ± 9.8 µm in the SM nonirradiated groups and 43.9 ± 14.9 µm in the SQ versus 34.3 ± 8.3 µm in the SM irradiated groups (all P > 0.05). CONCLUSIONS: In a rodent model of smooth silicone breast implantation and delayed radiotherapy, although there did not appear to be differences in capsule thickness regardless of device placement plane, SQ implants demonstrated gross evidence of CC. These data indicate that capsule thickness is only part of a larger pathogenetic picture, which should take into consideration the contribution from all peri-implant tissue.
Asunto(s)
Implantación de Mama , Contractura Capsular en Implantes/etiología , Glándulas Mamarias Animales/efectos de la radiación , Glándulas Mamarias Animales/cirugía , Animales , Modelos Animales de Enfermedad , Femenino , Mamoplastia , Radioterapia , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Factores de TiempoRESUMEN
Breast cancer survivors display altered inflammatory responses to immune challenges relative to cancer-naive controls likely due to previous cancer treatments, stress associated with cancer, and/or tumor physiology. Proper inflammatory responses are necessary for adaptive sickness behaviors (e.g., fatigue, anorexia, and fever) and neuroinflammatory pathways are also implicated in mental health disturbances (e.g., cognitive impairment, depression) suffered by cancer patients and survivors. Rodent cancer models indicate that tumors are sufficient to exacerbate neuroinflammatory responses after an immune challenge, however primary tumors are not usually present in cancer survivors, and the behavioral consequences of these brain changes remain understudied. Therefore, we tested the extent to which mammary tumor resection attenuates tumor-induced neuroinflammation and sickness behavior following an immune challenge (i.p. lipopolysaccharide [LPS] injection) in mice. Tnf-α, Il-1ß, and Il-6 mRNA decreased in multiple brain regions of LPS-treated tumor-bearing mice relative to LPS-treated controls; tumor resection attenuated these effects in some cases (but not Tnf-α). Tumors also attenuated sickness behaviors (hypothermia and lethargy) compared to LPS-treated controls. Tumor resection reversed these behavioral consequences, although basal body temperature remained elevated, comparable to tumor-bearing mice. Thus, tumors significantly modulate neuroinflammatory pathways with functional consequences and tumor resection mitigates most, but not all, of these changes.
Asunto(s)
Neoplasias de la Mama/inmunología , Conducta de Enfermedad , Inflamación/inmunología , Glándulas Mamarias Animales/inmunología , Animales , Neoplasias de la Mama/complicaciones , Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Supervivientes de Cáncer , Depresión/etiología , Depresión/inmunología , Depresión/patología , Femenino , Hipocampo/inmunología , Hipocampo/patología , Humanos , Inflamación/inducido químicamente , Inflamación/patología , Inflamación/cirugía , Interleucina-1beta/inmunología , Lipopolisacáridos/toxicidad , Glándulas Mamarias Animales/patología , Glándulas Mamarias Animales/cirugía , Neoplasias Mamarias Animales/inmunología , Neoplasias Mamarias Animales/patología , Neoplasias Mamarias Animales/cirugía , Ratones , Factor de Necrosis Tumoral alfa/inmunologíaRESUMEN
The optical properties of tissue change during thermal ablation. Multi-modal methods such as acousto-optic (AO) and photo-acoustic (PA) imaging may provide a real-time, direct measure of lesion formation. Baseline changes in optical properties have been previously measured over limited ranges of thermal dose for tissues exposed to a temperature-controlled water bath, however, there is scant data for optical properties of lesions created by HIFU. In this work, the optical scattering and absorption coefficients from 400-1300 nm of excised chicken breast exposed to HIFU were measured using an integrating sphere spectrophotometric technique. HIFU-induced spatiotemporal temperature elevations were measured using an infrared camera and used to calculate the thermal dose delivered to a localized region of tissue. Results obtained over a range of thermal dose spanning 9 orders of magnitude show that the reduced scattering coefficient increases for HIFU exposures exceeding a threshold thermal dose of CEM43 = 600 ± 81 cumulative equivalent minutes. HIFU-induced thermal damage results in changes in scattering over all optical wavelengths, with a 2.5-fold increase for thermal lesions exceeding 70 °C. The tissue absorption coefficient was also found to increase for thermally lesioned tissue, however, the magnitude was strongly dependent on the optical wavelength and there was substantial sample-to-sample variability, such that the existence of a threshold thermal dose could not be determined. Therapeutic windows, where the optical penetration depth is expected to be greatest, were identified in the near infrared regime centered near 900 nm and 1100 nm. These data motivate further research to improve the real-time AO and PA sensing of lesion formation during HIFU therapy as an alternative to thermometry.
Asunto(s)
Ultrasonido Enfocado de Alta Intensidad de Ablación/instrumentación , Ultrasonido Enfocado de Alta Intensidad de Ablación/métodos , Hipertermia Inducida , Glándulas Mamarias Animales/metabolismo , Óptica y Fotónica , Animales , Pollos , Femenino , Glándulas Mamarias Animales/cirugía , EspectrofotometríaRESUMEN
BACKGROUND: Preoperative breast and lung markers have significant drawbacks, including migration, patient discomfort, and scheduling difficulties. SignalMark is a novel localizer device with a unique signal on Doppler ultrasound. OBJECTIVE: We aimed to evaluate intraoperative identification of SignalMark microspheres compared with HydroMARK® clips. We also assessed the safety and efficacy of SignalMark in the lung. METHODS: Twelve breasts of lactating pigs were injected with SignalMark or HydroMARK® by a breast radiologist, and subsequently identified using a standard ultrasound machine by three surgeons blinded to marker location. Time to identification of each marker was recorded, with a maximum allotted time of 300 s. To further demonstrate efficacy in lung parenchyma, a second cohort of pigs underwent lung injections. RESULTS: A total of eight SignalMark markers and four HydroMARK® clips were placed in pig breasts. Overall, the surgeons correctly identified SignalMark 95.8% of the time (n = 23/24) and HydroMARK® clips 41.7% of the time (n = 5/12) within 300 s (p < 0.001). The mean time to identification was significantly faster for SignalMark, at 80.8 ± 20.1 s, than for HydroMARK®, at 209.4 ± 35.2 s (p < 0.002). For the lung injections, all 10 SignalMark markers were visible on Doppler ultrasound at the time of placement, and at the 7- and 21-day time points. CONCLUSIONS: Surgeons identified SignalMark in significantly less time than HydroMARK® clips in a simulated intraoperative setting, and SignalMark was easily viewed in the lung. These results suggest that SignalMark is a feasible option for efficient intraoperative localization of non-palpable breast and lung tumors using ultrasound guidance.
Asunto(s)
Biopsia con Aguja Fina/instrumentación , Pulmón/diagnóstico por imagen , Glándulas Mamarias Animales/diagnóstico por imagen , Microesferas , Ultrasonografía Doppler/métodos , Ultrasonografía Mamaria/métodos , Animales , Femenino , Hidrogeles/química , Periodo Intraoperatorio , Pulmón/cirugía , Glándulas Mamarias Animales/cirugía , PorcinosRESUMEN
The present retrospective study was conducted from 2003 to 2015 in Egypt to document common surgical affections of the udder and teat in cattle and buffaloes, and determine medical and surgical treatment options that are feasible in a field setting. We diagnosed 19 different surgical affections and classified them into 4 groups according to their location. Teat orifice affections (12.41%) included imperforate teat, contracted teat orifice, enlarged teat orifice, and black spot. Teat cistern affections (23.76%) included teat fistula, dilated teat cistern, teat polypi, and webbed teat. Teat surface affections (50.35%) included sore teat, supernumerary teat, sloughed teat, teat papilloma and fibropapilloma, teat wounds, and teat viral lesions. Udder affections (13.48%) included hypermastia, udder wounds, and suppurative and gangrenous mastitis. In cattle, the number of surgical affections located on the teat surface (20 ± 5.4) was significantly higher compared with other locations as well as compared with buffaloes (P<0.05). No treatment was indicated in 24% of recorded cases. Medical and surgical treatment was indicated in 73.75% of affected animals. Favorable results were achieved with the recommended treatments when applied in the field.
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Enfermedades de la Mama/veterinaria , Búfalos/cirugía , Enfermedades de los Bovinos/cirugía , Glándulas Mamarias Animales/cirugía , Animales , Enfermedades de la Mama/epidemiología , Enfermedades de la Mama/patología , Enfermedades de la Mama/cirugía , Bovinos , Enfermedades de los Bovinos/epidemiología , Enfermedades de los Bovinos/patología , Egipto/epidemiología , Femenino , Glándulas Mamarias Animales/patología , Prevalencia , Estudios RetrospectivosRESUMEN
OBJECTIVE: To describe the application of skin stretchers for closure of single-stage bilateral mastectomies in a dog and a cat. STUDY DESIGN: Clinical case report. ANIMALS: A 12-year-old intact female Miniature Dachshund and a 13-year-old spayed female domestic short-hair cat. METHODS: Skin stretchers were applied to the site of the skin adjacent to mammary glands for 2-4 days before surgery. Cable tension was adjusted every 6-8 hours to elongate the skin and to achieve primary closure of single-stage bilateral mastectomy without tension. RESULTS: Wound closure after single-stage bilateral mastectomy was achieved without tension or major complication in both animals. CONCLUSION: Use of skin stretchers allows primary closure of single-stage bilateral mastectomy in dogs and cats.
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Enfermedades de los Gatos/cirugía , Enfermedades de los Perros/cirugía , Colgajos Quirúrgicos/veterinaria , Animales , Gatos , Perros , Femenino , Glándulas Mamarias Animales/cirugía , Mastectomía/métodos , Mastectomía/veterinaria , Cicatrización de HeridasRESUMEN
Bovine mammary gland biopsies allow researchers to collect tissue samples to study cell biology including gene expression, histological analysis, signaling pathways, and protein translation. This article describes two techniques for biopsy of the bovine mammary gland (MG). Three healthy Holstein dairy cows were the subjects. Before biopsies, cows were milked and subsequently restrained in a cattle chute. An analgesic (flunixin meglumine, 1.1 to 2.2 mg/kg of body weight) was administered via jugular intravenous [IV] injection 15-20 min prior to biopsy. For standing sedation, xylazine hydrochloride (0.01-0.05 mg/kg of body weight) was injected via the coccygeal vessels 5-10 min before the procedure. Once adequately sedated, the biopsy site was aseptically prepared and locally anaesthetized with 6 mL of 2% lidocaine hydrochloride via subcutaneous injection. Using aseptic technique, a 2 to 3 cm vertical incision was made using a number 10 scalpel. Core and needle biopsy tools were used. The core biopsy tool was attached to a cordless drill and inserted into the MG tissue through the incision using a clock-wise drill action. The needle biopsy tool was manually inserted into the incision site. Immediately after the procedure, an assistant applied pressure on the incision site for 20 to 25 min using a sterile towel to achieve hemostasis. Stainless steel surgical staples were used to oppose the skin incision. The staples were removed 10 days post-procedure. The main advantages of core and needle biopsies is that both approaches are minimally invasive procedures that can be safely performed in healthy cows. Milk yield following the biopsy was unaffected. These procedures require a short recovery time and result in fewer risks of complications. Specific limitations may include bleeding after the biopsy and infection on the biopsy site. Applications of these techniques include tissue collection for clinical diagnosis and research purposes, such as primary cell culture.
Asunto(s)
Biopsia/veterinaria , Glándulas Mamarias Animales/cirugía , Animales , Biopsia/métodos , Bovinos , Femenino , Glándulas Mamarias Animales/patologíaRESUMEN
BACKGROUND: The important goal of modern research in the field of surgical oncology is the quest for a tool that could improve the outcomes of tumour excision. AIMS: The aim of this study was to compare the usefulness of the CO2 laser with flexible hollow waveguide and scalpel in mammary tumour excision. MATERIALS & METHODS: A total of 112 female BALB/c mice with implanted orthotopically 4T1-luc2-tdTomato tumour cells were included in the research. Tumours were excised in 48 mice using the CO2 laser and in 48 through scalpel surgery. The control group consisted of 16 untreated mice. The evaluation of surgical outcome was obtained by in vivo bioluminescence and fluorescence imaging and post-mortem histopathological examination. RESULTS: There were no significant differences between recurrence rates, metastases and survival time in groups excised with the scalpel and CO2 laser. CONCLUSION: The CO2 laser has similar efficacy compared with conventional scalpel excision for local recurrence rates, incidence of distant metastases and survival time and can be safely applied in oncological surgery.