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1.
J Surg Res ; 256: 156-162, 2020 12.
Article in English | MEDLINE | ID: mdl-32707398

ABSTRACT

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 0.5Ā 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 2.19Ā Ā±Ā 0.78Ā mL in group 1, 1.43Ā Ā±Ā 0.35Ā mL in group 2, and 0.96Ā Ā±Ā 0.24Ā 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 6Ā Ā±Ā 0.75 in group 3. The other general adhesion scores were 5.25Ā Ā±Ā 0.70 and 2.12Ā Ā±Ā 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 0.87Ā Ā±Ā 0.83 in group 3, 2.0Ā Ā±Ā 0.92 in group 2, and 3.0Ā Ā±Ā 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 (2.50Ā Ā±Ā 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 2.25Ā Ā±Ā 1.16 and 2.12Ā Ā±Ā 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.


Subject(s)
Breast Neoplasms/surgery , Mastectomy/adverse effects , Platelet-Rich Plasma/physiology , Postoperative Complications/prevention & control , Seroma/prevention & control , Animals , Axilla , Disease Models, Animal , Female , Humans , Lymph Node Excision/adverse effects , Mammary Glands, Animal/pathology , Mammary Glands, Animal/surgery , Neovascularization, Physiologic/physiology , Postoperative Complications/etiology , Postoperative Complications/pathology , Rats , Rats, Wistar , Seroma/etiology , Seroma/pathology , Wound Healing/physiology
2.
Mol Biol Rep ; 46(5): 4909-4919, 2019 Oct.
Article in English | MEDLINE | ID: mdl-31264163

ABSTRACT

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 1230Ā 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.


Subject(s)
Mammary Neoplasms, Animal/diagnosis , Mammary Neoplasms, Animal/metabolism , Protein-Lysine 6-Oxidase/genetics , Animals , Biomarkers, Tumor/metabolism , Dogs/metabolism , Female , Gene Expression Regulation, Neoplastic/genetics , Mammary Glands, Animal/metabolism , Mammary Glands, Animal/surgery , Mammary Neoplasms, Animal/genetics , Prognosis , Protein-Lysine 6-Oxidase/analysis , RNA, Messenger/genetics , Real-Time Polymerase Chain Reaction/methods , Recombinant Proteins/genetics , Transcriptome/genetics
3.
Ann Plast Surg ; 82(4S Suppl 3): S264-S270, 2019 04.
Article in English | MEDLINE | ID: mdl-30855398

ABSTRACT

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 Ā± SD capsule thickness was 39.0 Ā± 9.0 Āµm in the SQ versus 37.6 Ā± 9.8 Āµm in the SM nonirradiated groups and 43.9 Ā± 14.9 Āµm in the SQ versus 34.3 Ā± 8.3 Āµm 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.


Subject(s)
Breast Implantation , Implant Capsular Contracture/etiology , Mammary Glands, Animal/radiation effects , Mammary Glands, Animal/surgery , Animals , Disease Models, Animal , Female , Mammaplasty , Radiotherapy , Random Allocation , Rats , Rats, Sprague-Dawley , Time Factors
4.
N Z Vet J ; 67(5): 234-240, 2019 Sep.
Article in English | MEDLINE | ID: mdl-31079570

ABSTRACT

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 2.5Ć¢Ā€Ā…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.


Subject(s)
Mammary Glands, Animal/surgery , Sheep Diseases/surgery , Suture Techniques/veterinary , Wound Healing , Animals , Disease Models, Animal , Female , Greece , Mammary Glands, Animal/microbiology , Mammary Glands, Animal/pathology , Mannheimia , Mastectomy/veterinary , Pasteurellaceae Infections/veterinary , Polypropylenes , Random Allocation , Sheep , Sheep Diseases/microbiology , Surgical Stapling/veterinary , Sutures , Treatment Outcome
5.
Ann Surg Oncol ; 25(12): 3740-3746, 2018 Nov.
Article in English | MEDLINE | ID: mdl-30178390

ABSTRACT

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 HydroMARKĀ® clips. We also assessed the safety and efficacy of SignalMark in the lung. METHODS: Twelve breasts of lactating pigs were injected with SignalMark or HydroMARKĀ® 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 300Ā 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 HydroMARKĀ® clips were placed in pig breasts. Overall, the surgeons correctly identified SignalMark 95.8% of the time (n = 23/24) and HydroMARKĀ® clips 41.7% of the time (n = 5/12) within 300 s (p < 0.001).Ā The mean time to identification was significantly faster for SignalMark, at 80.8 Ā± 20.1Ā s, than for HydroMARKĀ®, at 209.4 Ā± 35.2Ā 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 HydroMARKĀ® 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.


Subject(s)
Biopsy, Fine-Needle/instrumentation , Lung/diagnostic imaging , Mammary Glands, Animal/diagnostic imaging , Microspheres , Ultrasonography, Doppler/methods , Ultrasonography, Mammary/methods , Animals , Female , Hydrogels/chemistry , Intraoperative Period , Lung/surgery , Mammary Glands, Animal/surgery , Swine
6.
Vet Surg ; 47(3): 454-458, 2018 Apr.
Article in English | MEDLINE | ID: mdl-29119572

ABSTRACT

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.


Subject(s)
Cat Diseases/surgery , Dog Diseases/surgery , Surgical Flaps/veterinary , Animals , Cats , Dogs , Female , Mammary Glands, Animal/surgery , Mastectomy/methods , Mastectomy/veterinary , Wound Healing
7.
Bull Exp Biol Med ; 164(2): 186-190, 2017 Dec.
Article in English | MEDLINE | ID: mdl-29177878

ABSTRACT

The anterior mediastinal lymph nodes were analyzed morphometrically in rats with chemically provoked breast cancer. Rats with untreated breast cancer and animals receiving chemotherapy demonstrated decreased volumes of paracortical region and lymphoid nodules with the germinal centers accompanied by extended medullary thymic substance. Resection of largest focus of breast tumor improved the filtration barrier potential of anterior mediastinal lymph nodes, up-regulated the proliferative activity of lymphoid cells in T-cell zones, and down-regulated proliferation of plasmatic cells.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/pharmacology , Lymph Nodes/pathology , Mammary Glands, Animal/pathology , Mammary Neoplasms, Experimental/pathology , Mediastinum/pathology , Animals , Carcinogens/administration & dosage , Cell Proliferation/drug effects , Cyclophosphamide/pharmacology , Female , Fluorouracil/pharmacology , Injections, Subcutaneous , Lymph Nodes/drug effects , Lymph Nodes/surgery , Lymphatic Metastasis , Mammary Glands, Animal/drug effects , Mammary Glands, Animal/surgery , Mammary Neoplasms, Experimental/chemically induced , Mammary Neoplasms, Experimental/drug therapy , Mammary Neoplasms, Experimental/surgery , Mediastinum/surgery , Methotrexate/pharmacology , Methylnitrosourea/administration & dosage , Plasma Cells/drug effects , Plasma Cells/pathology , Rats , Rats, Wistar , T-Lymphocytes/drug effects , T-Lymphocytes/pathology
8.
BMC Vet Res ; 12(1): 285, 2016 Dec 12.
Article in English | MEDLINE | ID: mdl-27955650

ABSTRACT

BACKGROUND: Two mammary lymphatic cannulation models in sheep have been described with minimal use in the past 50Ā years. The purpose of this study was to investigate a new surgical technique to allow long term monitoring of mammary lymph flow and composition from the mammary glands, with rapid ewe recovery and minimal complications post-surgery. RESULTS: We developed a modified methodology for cannulating the efferent mammary lymphatic from the mammary lymph node with minimum tissue damage. Compared to the previous models, our method required only a small incision on the aponeurosis of the external abdominal oblique muscles and thus reduced the difficulties in suturing the aponeurosis. It allowed for lymph collection and assessment for at least one week post-surgery with concurrent milk collection. CONCLUSION: This method allows for good ewe recovery post-surgery and in vivo sampling of efferent mammary lymph from the mammary lymph nodes in real-time and comparison with milk parameters.


Subject(s)
Catheterization/veterinary , Lymph Nodes/immunology , Lymph Nodes/surgery , Mammary Glands, Animal/immunology , Mammary Glands, Animal/surgery , Models, Animal , Sheep/immunology , Sheep/surgery , Animals , Catheterization/standards , Female , Milk/chemistry
9.
Can Vet J ; 57(8): 853-9, 2016 Aug.
Article in English | MEDLINE | ID: mdl-27493285

ABSTRACT

This study evaluated the long-term prognosis of return to normal mechanical milking after reconstructive teat surgery and determined the factors that have an impact on the outcome. A retrospective study of 67 dairy cows with teat lacerations was performed. Milking status at discharge and at long-term follow-up was adequate for 83% and 75% of the cows, respectively. No statistically significant differences were detected between the long-term prognosis and the age of the cow, the stage of lactation at presentation, or the configuration of the laceration. Lacerations repaired more than 24 hours after the trauma were more frequently associated with a negative outcome (P = 0.05). Mastitis was the most frequent complication (n = 17) and had a statistically significant negative impact on long-term prognosis (P = 0.02). Reconstructive surgery of lacerated teat in dairy cows can help establish return to normal mechanical milking.


Ɖvaluation du pronostic Ć  long terme en regard de la traite mĆ©canique des trayons lacĆ©rĆ©s rĆ©parĆ©s chirurgicalement chez la vache : 67 cas (2003Ā­2013). Les objectifs de cette Ć©tude sont d'Ć©valuer le pronostic Ć  long terme, en regard de la traite mĆ©canique, suivant la reconstruction d'un trayon lacĆ©rĆ© et de dĆ©terminer les critĆØres associĆ©s Ć  un pronostic nĆ©gatif. Une Ć©tude rĆ©trospective sur 67 vaches laitiĆØres a Ć©tĆ© rĆ©alisĆ©e. La traite mĆ©canique Ć©tait adĆ©quate pour 83 et 75 % des vaches Ć  leur sortie de l'hĆ“pital et lors du suivi Ć  long terme. Pas de diffĆ©rences statistiques ont Ć©tĆ© trouvĆ©es entre le pronostic Ć  long terme et l'Ć¢ge des vaches, leur stade de lactation et la configuration de la lacĆ©ration. Les lacĆ©rations rĆ©parĆ©es plus de 24 heures aprĆØs le trauma avaient un pronostic moins bon (P = 0,05). La complication la plus frĆ©quente Ć©tait la mammite (n = 17). Elle avait un effet nĆ©gatif sur le pronostic Ć  long terme (P = 0,02). Reconstruire chirurgicalement un trayon lacĆ©rĆ© peut rĆ©tablir la traite mĆ©canique.(Traduit par les auteurs).


Subject(s)
Animal Husbandry , Cattle Diseases/surgery , Dairying , Lacerations/veterinary , Mammary Glands, Animal/surgery , Milk , Animals , Cattle , Female , Lacerations/surgery , Mammary Glands, Animal/injuries , Prognosis , Retrospective Studies
10.
Breast Cancer Res Treat ; 147(3): 501-12, 2014 Oct.
Article in English | MEDLINE | ID: mdl-25200444

ABSTRACT

Breast cancer drug development costs nearly $610 million and 37 months in preclinical mouse model trials with minimal success rates. Despite these inefficiencies, there are still no consensus breast cancer preclinical models. Murine mammary adenocarcinoma 4T1-luc2 cells were implanted subcutaneous (SQ) or orthotopically percutaneous (OP) injection in the area of the nipple, or surgically into the chest 2nd mammary fat pad under direct vision (ODV) in Balb/c immunocompetent mice. Tumor progression was followed by in vivo bioluminescence and direct measurements, pathology and survival determined, and tumor gene expression analyzed by genome-wide microarrays. ODV produced less variable-sized tumors and was a reliable method of implantation. ODV implantation into the chest 2nd mammary pad rather than into the abdominal 4th mammary pad, the most common implantation site, better mimicked human breast cancer progression pattern, which correlated with bioluminescent tumor burden and survival. Compared to SQ, ODV produced tumors that differentially expressed genes whose interaction networks are of importance in cancer research. qPCR validation of 10 specific target genes of interest in ongoing clinical trials demonstrated significant differences in expression. ODV implantation into the chest 2nd mammary pad provides the most reliable model that mimics human breast cancer compared from subcutaneous implantation that produces tumors with different genome expression profiles of clinical significance. Increased understanding of the limitations of the different preclinical models in use will help guide new investigations and may improve the efficiency of breast cancer drug development .


Subject(s)
Breast Neoplasms/pathology , Cell Transplantation/methods , Mammary Neoplasms, Experimental/genetics , Mammary Neoplasms, Experimental/pathology , Animals , Cell Line, Tumor , Female , Gene Expression Regulation, Neoplastic , Gene Regulatory Networks , Humans , Luminescent Measurements , Mammary Glands, Animal/surgery , Mammary Neoplasms, Experimental/mortality , Mice, Inbred BALB C , Mice, Inbred C57BL , Transplantation, Heterologous/methods , Tumor Burden
11.
Article in German | MEDLINE | ID: mdl-22134601

ABSTRACT

Endoscopy in the field of buiatrics has gained growing importance in recent years. Parts of the upper respiratory and gastrointestinal tract, the urethra and urinary bladder, the abdomen and the teat are all accessible by means of endoscopy. The direct visualisation of inner or outer organ surfaces allows for rapid diagnosis and even prognosis of different pathological conditions. Flexible endoscopes of different dimensions are used for endoscopic examination of the upper respiratory tract. Examining this region, endoscopy is in some cases superior to other imaging techniques because of the direct visualization of surfaces and their pathological conditions and the possibility of collecting biopsies under visual control. The same is documented for diseases of the oesophagus. On the other hand, rumenoscopy is of experimental character so far. Urethrocystoscopy is mainly performed for diagnostic purposes with either flexible or rigid optics. Theloscopy represents the "gold standard" for surgical intervention in cases of disturbance of milk flow, since mucosal tissue can be removed under visual control. Therefore, this indication is one of the most important applications for endoscopy performed by practitioners. Another important field for the application of therapeutic endoscopy is the treatment of left displaced abomasum by repositioning and fixation to the abdominal wall under endoscopic control.


Subject(s)
Cattle/anatomy & histology , Endoscopy/veterinary , Abomasum/anatomy & histology , Abomasum/pathology , Abomasum/surgery , Animals , Cystoscopy/veterinary , Endoscopy/instrumentation , Esophagoscopy/veterinary , Female , Laparoscopy/veterinary , Laryngoscopy/veterinary , Mammary Glands, Animal/anatomy & histology , Mammary Glands, Animal/pathology , Mammary Glands, Animal/surgery , Respiratory System/anatomy & histology , Respiratory System/pathology , Rumen/anatomy & histology , Rumen/pathology
12.
Nat Protoc ; 16(4): 1907-1935, 2021 04.
Article in English | MEDLINE | ID: mdl-33627843

ABSTRACT

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.


Subject(s)
Intravital Microscopy/methods , Mammary Glands, Animal/cytology , Single-Cell Analysis , Anesthesia , Animals , Epithelial Cells/cytology , Female , Fluorescent Dyes/chemistry , Green Fluorescent Proteins/metabolism , Imaging, Three-Dimensional , Mammary Glands, Animal/surgery , Mice, Inbred C57BL , Mice, Transgenic , Stromal Cells/cytology
13.
Sci Rep ; 11(1): 23277, 2021 12 02.
Article in English | MEDLINE | ID: mdl-34857853

ABSTRACT

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 4.4Ā mg/kg/day for 90Ā 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 90Ā 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.


Subject(s)
Carbazoles/administration & dosage , Carbazoles/adverse effects , Carcinoma/drug therapy , Dog Diseases/drug therapy , Kidney/blood supply , Kidney/diagnostic imaging , Mammary Neoplasms, Animal/drug therapy , Renal Circulation/drug effects , Ultrasonography, Doppler , Animals , Carcinoma/physiopathology , Carcinoma/surgery , Dog Diseases/physiopathology , Dog Diseases/surgery , Dogs , Female , Mammary Glands, Animal/surgery , Mammary Neoplasms, Animal/physiopathology , Mammary Neoplasms, Animal/surgery , Time Factors
14.
Cancer Lett ; 520: 255-266, 2021 11 01.
Article in English | MEDLINE | ID: mdl-34329741

ABSTRACT

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 (pĀ =Ā 0.04), and increased tumor latency (pĀ =Ā 0.03). In benign mammary glands, UPA decreased Ki67 (pĀ <Ā 0.001) and increased PR expression (pĀ <Ā 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.


Subject(s)
BRCA1 Protein/genetics , Breast Neoplasms/drug therapy , Receptors, Progesterone/genetics , Tumor Microenvironment/genetics , Animals , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Breast Neoplasms/surgery , Carcinogenesis/drug effects , Carcinogenesis/genetics , Disease Models, Animal , Epithelial Cells/metabolism , Epithelial Cells/pathology , Female , Humans , Mammary Glands, Animal/metabolism , Mammary Glands, Animal/pathology , Mammary Glands, Animal/surgery , Mastectomy , Mice , Mifepristone/pharmacology , Norpregnadienes/pharmacology , Stromal Cells/metabolism , Stromal Cells/pathology , Tumor Microenvironment/drug effects
15.
Nat Commun ; 12(1): 3187, 2021 05 27.
Article in English | MEDLINE | ID: mdl-34045459

ABSTRACT

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.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Drug Carriers/chemistry , Mammary Neoplasms, Experimental/therapy , Neoplasm Metastasis/therapy , Theranostic Nanomedicine/methods , Animals , Anti-Inflammatory Agents/administration & dosage , Anticoagulants/administration & dosage , Cell Line, Tumor/transplantation , Chemotherapy, Adjuvant/methods , Disease Models, Animal , Epithelial-Mesenchymal Transition/drug effects , Female , Heparin, Low-Molecular-Weight/administration & dosage , Human Umbilical Vein Endothelial Cells , Humans , Male , Mammary Glands, Animal/pathology , Mammary Glands, Animal/surgery , Mammary Neoplasms, Experimental/pathology , Mice , Nanoparticles/chemistry , Neoplastic Cells, Circulating/drug effects , Paclitaxel/administration & dosage , Proof of Concept Study , Rats , Stilbenes/administration & dosage
16.
Plast Reconstr Surg ; 145(3): 701-710, 2020 03.
Article in English | MEDLINE | ID: mdl-32097310

ABSTRACT

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)-Ɵ 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-Ɵ2 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-Ɵ 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.


Subject(s)
Breast Implantation/adverse effects , Breast Implants/adverse effects , Dietary Supplements , Fatty Acids, Omega-3/administration & dosage , Implant Capsular Contracture/prevention & control , Administration, Oral , Animals , Breast Implantation/instrumentation , Disease Models, Animal , Female , Humans , Implant Capsular Contracture/etiology , Implant Capsular Contracture/pathology , Mammary Glands, Animal/drug effects , Mammary Glands, Animal/pathology , Mammary Glands, Animal/surgery , Mice , Mice, Inbred C57BL , Silicone Gels/adverse effects
17.
PLoS One ; 15(8): e0236516, 2020.
Article in English | MEDLINE | ID: mdl-32776970

ABSTRACT

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.


Subject(s)
Collagen/metabolism , Mammary Neoplasms, Animal/surgery , Prognosis , Triple Negative Breast Neoplasms/surgery , Animals , Cats , Collagen/genetics , Disease Models, Animal , Female , Humans , Mammary Glands, Animal/metabolism , Mammary Glands, Animal/pathology , Mammary Glands, Animal/surgery , Mammary Neoplasms, Animal/genetics , Mammary Neoplasms, Animal/metabolism , Mammary Neoplasms, Animal/pathology , Triple Negative Breast Neoplasms/genetics , Triple Negative Breast Neoplasms/metabolism , Triple Negative Breast Neoplasms/pathology , Tumor Microenvironment/genetics
18.
Nat Commun ; 11(1): 3616, 2020 07 17.
Article in English | MEDLINE | ID: mdl-32680987

ABSTRACT

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.


Subject(s)
Biomarkers, Tumor/genetics , Breast Neoplasms/genetics , Carcinogenesis/genetics , Gene Expression Regulation, Neoplastic , Mammary Neoplasms, Animal/genetics , Animals , Breast/pathology , Breast Neoplasms/mortality , Breast Neoplasms/pathology , Class I Phosphatidylinositol 3-Kinases/genetics , Cohort Studies , DNA Copy Number Variations , DNA Mutational Analysis , Datasets as Topic , Dogs , Epithelial-Mesenchymal Transition , Female , Humans , Mammary Glands, Animal/pathology , Mammary Glands, Animal/surgery , Mammary Neoplasms, Animal/mortality , Mammary Neoplasms, Animal/pathology , Mammary Neoplasms, Animal/surgery , Mutation , Prognosis , RNA-Seq , Species Specificity , Exome Sequencing
19.
Theranostics ; 10(23): 10652-10664, 2020.
Article in English | MEDLINE | ID: mdl-32929372

ABSTRACT

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.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Breast Neoplasms/therapy , Drug Carriers/chemistry , Neoplasm Recurrence, Local/prevention & control , Smart Materials/chemistry , Surgical Wound/therapy , Animals , Breast Neoplasms/pathology , Cell Line, Tumor , Chemotherapy, Adjuvant/methods , Chitosan/chemistry , Doxycycline/administration & dosage , Drug Compounding/methods , Female , Fluorouracil/administration & dosage , Gelatin/chemistry , Humans , Mammary Glands, Animal/pathology , Mammary Glands, Animal/surgery , Mastectomy , Mice , Neoplasm Metastasis/pathology , Neoplasm Metastasis/prevention & control , Polylactic Acid-Polyglycolic Acid Copolymer/chemistry , Printing, Three-Dimensional , Tissue Scaffolds/chemistry , Wound Healing/drug effects , Xenograft Model Antitumor Assays
20.
J Vasc Interv Radiol ; 20(11): 1477-82, 2009 Nov.
Article in English | MEDLINE | ID: mdl-19875066

ABSTRACT

PURPOSE: To investigate the radiofrequency (RF) effects on the nonlactating and lactating ex vivo bovine udder as a model for normal breast tissue. MATERIALS AND METHODS: RF ablation in three lactating and three nonlactating ex vivo bovine udders (ie, six udders) was performed. The opening of the electrodes was 3 cm. The temperature was applied in 10 degrees C increasing steps between 60 degrees C and 100 degrees C and each temperature was maintained for 15 minutes. The experiment was repeated three times for each temperature step in the lactating and nonlactating udder. Resected specimens were assessed histologically. The maximum diameter of the ablation zone and maximum width of the transition zone with respect to the temperature applied were measured. RESULTS: In the nonlactating tissue, there was a correlation of the temperature and diameter of tissue damage. There was a narrow transition zone of 0.10 cm in all cases except at 100 degrees C, when it was 0.17 cm. In the lactating udder, no correlation was seen. The transition zone was not well visualized at temperatures less than 80 degrees C, ranging in overall size between 0.15 cm and 0.20 cm. CONCLUSIONS: The results of the study, with clear demarcation of the ablation zones and transition zones in the normal breast tissue, support the potential of breast thermal ablation as a viable treatment for further study. Lactating tissue does not seem ideal for thermal ablation. The discrepancy of the extent of ablation and the length of the electrodes is an important finding in this study. Further in vivo studies in normal glandular tissue and tumor are necessary.


Subject(s)
Breast/pathology , Breast/surgery , Catheter Ablation/methods , Mammary Glands, Animal/pathology , Mammary Glands, Animal/surgery , Mastectomy, Segmental/methods , Animals , Cattle , In Vitro Techniques
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