Metastasis-associated lung adenocarcinoma transcript 1 molecular mechanisms in gastric cancer progression

Gastric cancer(GC)remains among the most common cancers worldwide with a high mortality-to-incidence ratio.Accumulated evidence suggests that long noncoding RNAs(lncRNAs)are involved in gastric carcinogenesis.These transcripts are longer than 200 nucleotides and modulate gene expression at multiple molecular levels,inducing or inhibiting biological processes and diseases.Metastasis-associated lung adenocarcinoma transcript 1(MALAT1)is one of the best-studied lncRNAs with comprehensive actions contributing to cancer progression.This lncRNA regulates gene expression at the transcriptional and posttranscriptional levels through interactions with microRNAs and proteins.In the present review,we discussed the molecular mechanism of MALAT1 and summarized the current knowledge of its expression in GC.Moreover,we highlighted the potential use of MALAT1 as a biomarker,including liquid biopsy.

Foods and Herbs That May Interact with Medications Used for Arterial Hypertension and Dyslipidemia

The aim of this review was to verify the risks of drug-nutrient interactions in the elderly. This is an integrative literature review, with a descriptive approach, carried out through research in indexed databases, legislation and pharmacopoeias. Data collection took place in the year 2022, through the analysis of literature collected of the last 10 years collected. The data showed that many of the continuous drugs use by the elderly can lead to interactions of different orders with nutrients, increasing the risk of plasmatic fluctuation as grapefruit, orange, lemon and lime interact with systemic arterial hypertension, increasing the risk of drug intoxication in the elderly. The action of the health team is essential, through the careful evaluation of the administered drugs, diet therapy and the interaction between them, to benefit the elderly with better use of the therapy and improvement of nutritional conditions.

Three-dimensional models of antigens with serodiagnostic potential for leprosy:An in silico study

BACKGROUND Leprosy is a disease caused by Mycobacterium leprae(M.leprae),an intracellular pathogen that has tropism and affects skin and nervous system cells.The disease has two forms of presentation:Paucibacillary and multibacillary,with different clinical and immunological manifestations.Unlike what occurs in the multibacillary form,the diagnostic tests for the paucibacillary form are nonspecific and not very sensitive,allowing the existence of infected individuals without treatment,which contributes to the spread of the pathogen in the population.To mitigate this contamination,more sensitive diagnostic tests capable of detecting paucibacillary patients are needed.AIM To predict the three-dimensional structure models of M.leprae antigens with serodiagnostic potential for leprosy.METHODS In this in silico study,satisfactory templates were selected in the Protein Data Bank(PDB)using Basic Local Alignment Search Tool to predict the structural templates of ML2038,ML0286,ML0050,and 85B antigens by comparative modeling.The templates were selected according to general criteria such as sequence identity,coverage,X-ray resolution,Global Model Quality Estimate value and phylogenetic relationship;Clustal X 2.1 software was used in this analysis.Molecular modeling was completed using the software Modeller 9v13.Visualization of the models was made using ViewerLite 4.2 and PyMol software,and analysis of the quality of the predicted models was performed using the QMEAN score and Z-score.Finally,the three-dimensional moels were validated using the MolProbity and Verify 3D platforms.RESULTS The three-dimensional structure models of ML2038,ML0286,ML0050,and 85B antigens of M.leprae were predicted using the templates PDB:3UOI(90.51%identity),PDB:3EKL(87.46%identity),PDB:3FAV(40.00%identity),and PDB:1F0N(85.21%identity),respectively.The QMEAN and Z-score values indicated the good quality of the structure models.These data refer to the monomeric units of antigens,since some of these antigens have quaternary structure.The validation of the models was performed with the final three-dimensional structure-monomer(ML0050 and 85B antigens)and quaternary structures(ML2038 and ML0286).The majority of amino acid residues were observed in favorable and allowed regions in the Ramachandran plot,indicating correct positioning of the side chain and absence of steric impediment.The MolProbity score value and Verify 3D results of all models indicated a satisfactory prediction.CONCLUSION The polarized immune response against M.leprae creates a problem in leprosy detection.The selection of immunodominant epitopes is essential for the development of more sensitive serodiagnostic tests,for this it is important to know the three-dimensional structure of the antigens,which can be predicted with bioinformatics tools.

Extrahepatic cholestasis associated with paracoccidioidomycosis:Challenges in the differential diagnosis of biliopancreatic neoplasia

BACKGROUND Paracoccidioidomycosis(PCM)may involve the hepatic pedicle and peripan creatic lymph nodes,cause damage to the bile duct and manifest,exceptionally,in combination with extrahepatic cholestasis(EHC),making investigation and treatment challenging.AIM To investigate the management of patients with visceral PCM admitted with EHC.METHODS All patients diagnosed with PCM treated in a public,tertiary teaching hospital between 1982 and 2020 were retrospectively evaluated.Those also identified with EHC were allocated to two groups according to the treatment approach for the purpose of comparing clinical,laboratory,and imaging findings,resources used for etiological diagnosis,treatment results,and prognosis.Statistical analyses were performed using the linear mixed-effects model(random and fixed effects),which was adjusted using the PROC MIXED procedure of the SAS®9.0 software,and Fisher’s exact test.RESULTS Of 1645 patients diagnosed with PCM,40(2.4%)had EHC.Of these,20(50.0%)lived in the rural area and 29(72.5%)were men,with a mean age of 27.1 years(3-65 years).Jaundice as first symptom and weight loss of at least 10 kg were observed in 16 patients(40.0%),and a mass in the head of the pancreas was observed in 8(20.0%).The etiological diagnosis was made by tissue collection during surgery in 4 cases(10.0%)and by endoscopic methods in 3 cases(7.5%).Twenty-seven patients(67.5%)received drug treatment alone(Group 1),whereas 13(32.5%)underwent endoscopic and/or surgical procedures in combination with drug treatment(Group 2).EHC was significantly reduced in both groups(40.7% in Group 1,with a mean time of 3 months;and 38.4% in Group 2,with a mean time of 7.5 months),with no statistically significant difference between them.EHC recurrence rates,associated mainly with treatment nonadherence,were similar in both groups:37% in Group 1 and 15.4% in Group 2.The mortality rate was 18.5% in Group 1 and 23% in Group 2,with survival estimates of 71.3% and 72.5%,respectively,with no statistically significant difference.CONCLUSION Although PCM-related EHC is rare,it needs to be included in the differential diagnosis of malignancies,as timely treatment can prevent hepatic and extrahepatic sequelae.

Role of the Wnt/β-catenin pathway in gastric cancer: An indepth literature review

Gastric cancer remains one of the most common cancers worldwide and one of the leading cause for cancerrelated deaths. Gastric adenocarcinoma is a multifactorial disease that is genetically, cytologically and architecturally more heterogeneous than other gastrointestinal carcinomas.The aberrant activation of the Wnt/β-catenin signaling pathway is involved in the development and progression of a significant proportion of gastric cancer cases. This review focuses on the participation of the Wnt/b-catenin pathway in gastric cancer by offering an analysis of the relevant literature published in this field. Indeed, it is discussed the role of key factors in Wnt/β-catenin signaling and their downstream effectors regulating processes involved in tumor initiation, tumor growth, metastasis and resistance to therapy. Available data indicate that constitutive Wnt signalling resulting from Helicobacter pylori infection and inactivation of Wnt inhibitors(mainly by inactivating mutations and promoter hypermethylation) play an important role in gastric cancer. Moreover, a number of recent studies confirmed CTNNB1 and APC as driver genes in gastric cancer. The identification of specific membrane, intracellular, and extracellular components of the Wnt pathway has revealed potential targets for gastric cancer therapy. High-throughput "omics" approaches will help in the search for Wnt pathway antagonist in the near future.

Neuroinflammation and oxidative stress act in concert to promote neurodegeneration in the diabetic retina and optic nerve:galectin-3 participation

Diabetes is a lifelong disease characterized by glucose metabolic imbalance,in which low insulin levels or impaired insulin signaling lead to hyperglycemic state.Within 20 years of diabetes progression,95%of patients will have diabetic retinopathy,the leading cause of visual defects in working-age people worldwide.Although diabetes is considered a microvascular disease,recent studies have shown that neurodegeneration precedes vascular changes within the diabetic visual system,albeit its mechanisms are still under investigation.Neuroinflammation and oxidative stress are intrinsically related phenomena,since macrophage/microglia and astrocytes are the main sources of reactive oxygen species during central nervous system chronic degenerative diseases,and both pathological processes are increased in the visual system during diabetes.The present review will focus on recent findings of the contribution of oxidative stress derived from neuroinflammation in the early neurodegenerative aspects of the diabetic visual system and their relationship with galectin-3.

Determination of Paraquat in Several Commercially Available Types of Rice

Introduction: Paraquat (1,1’-dimethyl-4,4’-bipyridine-dichloride) is a herbicide used to combat weeds and improve crop productivity. Its acute toxicity can cause fatal poisoning in humans and animals and several studies have shown a strong correlation between paraquat and Parkinson’s disease. Objective: To determine the concentration of paraquat in different types of rice in Brazil. Method: Paraquat quantification is based on a complexation reaction with sodium dithionite, which generates a blueish color compound, whose absorbance was read in a spectrophotometer at the 600 nm wavelength. Results: Five samples were found to be above the maximum allowed limit, while one sample had a concentration in the upper allowed limit. The method employed did not allow quantification of black rice. Conclusion: There is a need for identification of the type of pesticide used in each examined crop as well as their respective dates of remission in order to improve the safety of agricultural practices.

Live and Inactivated Salmonella Enteritidis Vaccines:Immune Mechanisms in Broiler Breeders

Salmonella is a ubiquitous pathogen which, in addition to causing poultry diseases, has a growing zoonotic impact. It has demanded the implementation of diverse control strategies, in which vaccines play a major role. The understanding of the immune pathways elicited by the different vaccines is important, contributing for the establishment of strong immune correlates of protection, for instance. With the purpose of determining the dynamics of the humoral and cellular immune responses to vaccination, broiler breeders (Cobb Slow) were immunized with live or inactivated vaccines against Salmonella Enteritidis. Lymphocyte and macrophage subsets were analyzed in the peripheral blood by flow cytometry and antigen-specific circulating IgY and mucosal IgA were quantified. The markers analyzed by flow cytometry were CD8/CD28, CD4/TCRVβ1, Kul/ MHC II and Bu-1. Both live and inactivated vaccines induced an increase in the proportion of circulating monocytes (Kul+MHCII+) in some time points compared to non-vaccinated controls. However, whereas the live vaccine leads to an increase in CD8-CD28+ and Bu-1+ lymphocytescompared to the control group, the inactivated vaccine prompteda reduction in the percentage of severalleucocyte subsets (Kul-MHCII+, Bu-1+, CD8+CD28+, CD8-CD28+, CD4+TCRVβ1-, CD4+TCRVβ1+, CD4-TCRVβ1+) after the boost dose. Both vaccines induced specific serum IgY and mucosal IgA production;however, the inactivated vaccine stimulated higher titers in a shorter period. These results contribute to the understanding of mechanisms of action of live and inactivated Salmonella vaccines in chickens.

Molecular approaches for spinal cord injury treatment

Injuries to the spinal cord result in permanent disabilities that limit daily life activities.The main reasons for these poor outcomes are the limited regenerative capacity of central neurons and the inhibitory milieu that is established upon traumatic injuries.Despite decades of research,there is still no efficient treatment for spinal cord injury.Many strategies are tested in preclinical studies that focus on ameliorating the functional outcomes after spinal cord injury.Among these,molecular compounds are currently being used for neurological recovery,with promising results.These molecules target the axon collapsed growth cone,the inhibitory microenvironment,the survival of neurons and glial cells,and the re-establishment of lost connections.In this review we focused on molecules that are being used,either in preclinical or clinical studies,to treat spinal cord injuries,such as drugs,growth and neurotrophic factors,enzymes,and purines.The mechanisms of action of these molecules are discussed,considering traumatic spinal cord injury in rodents and humans.

Injection of bone marrow mesenchymal stem cells by intravenous or intraperitoneal routes is a viable alternative to spinal cord injury treatment in mice

In spite of advances in surgical care and rehabilitation, the consequences of spinal cord injury （SCI） are still challenging. Several experimental therapeutic strategies have been studied in the SCI field, and recent advances have led to the development of therapies that may act on the inhibitory microenvironment. Assorted lineages of stem cells are considered a good treatment for SCI. This study investigated the effect of systemic transplantation of mesenchymal stem cells （MSCs） in a compressive SCI model. Here we present results of the intraperitoneal route, which has not been used previously for MSC administration after compressive SCI. We used adult female C57BL/6 mice that underwent laminectomy at the T9 level, followed by spinal cord compression for 1 minute with a 30-g vascular clip. The animals were divided into five groups： sham （anesthesia and laminectomy but without compression injury induction）, MSC i.p. （intraperitoneal injection of 8×10^5 MSCs in 500 μL of DMEM at 7 days after SCI）, MSC i.v. （intravenous injection of 8 × 10^5 MSCs in 500μL of DMEM at 7 days after SCI）, DMEM i.p. （intraperitoneal injection of 500μL of DMEM at 7 days after SCI）, DMEM i.v. （intravenous injection of 500 μL of DMEM at 7 days after SCI）. The effects of MSCs transplantation in white matter sparing were analyzed by luxol fast blue staining. The number of preserved fibers was counted in semithin sections stained with toluidine blue and the presence of trophic factors was analyzed by immunohistochemistry. In addition, we analyzed the locomotor performance with Basso Mouse Scale and Global Mobility Test. Our results showed white matter preservation and a larger number of preserved fibers in the MSC groups than in the DMEM groups. Furthermore, the MSC groups had higher levels of trophic factors （brain-derived neurotrophic factor, nerve growth factor, neurotrophin-3 and neurotrophin-4） in the spinal cord and improved locomotor performance. Our results indicate that injection of MSCs by either intraperitoneal or intravenous routes results in beneficial outcomes and can be elected as a choice for SCI treatment.

Hepatic encephalopathy:Lessons from preclinical studies

Hepatic encephalopathy(HE) is a major complication that is closely related to the progression of end-stage liver disease.Metabolic changes in advanced liver failure can promote cognition impairment,attention deficits and motor dysfunction that may result in coma and death.HE can be subdivided according to the type of hepatic injury,namely,type A,which results from acute liver failure,type B,which is associated with a portosystemic shunting without intrinsic liver disease,and type C,which is due to chronic liver disease.Several studies have investigated the pathogenesis of the disease,and most of the mechanisms have been explored using animal models.This article aimed to review the use of preclinical models to investigate HE.The most used animal species are rats and mice.Experimental models of type A HE include surgical procedures and the administration of hepatotoxic medications,whereas models of types B and C HE are generally surgically induced lesions in liver tissue,which evolve to hepatic cirrhosis.Preclinical models have allowed the comprehension of the pathways related to HE.

Relationship between head and neck cancer therapy and some genetic endpoints

Head and neck cancer(HNC) is the sixth most common human malignancy worldwide. The main forms of treat ment for HNC are surgery, radiotherapy(RT) and che motherapy(CT). However, the choice of therapy de pends on the tumor staging and approaches, which are aimed at organ preservation. Because of systemic RT and CT genotoxicity, one of the important side effects is a secondary cancer that can result from the activity of radiation and antineoplastic drugs on healthy cells Ionizing radiation can affect the DNA, causing single and double-strand breaks, DNA-protein crosslinks and oxidative damage. The severity of radiotoxicity can be directly associated with the radiation dosimetry and the dose-volume differences. Regarding CT, cisplatin is stil the standard protocol for the treatment of squamous cell carcinoma, the most common cancer located in theoral cavity. However, simultaneous treatment with cisplatin, bleomycin and 5-fluorouracil or treatment with paclitaxel and cisplatin are also used. These drugs can interact with the DNA, causing DNA crosslinks, double and single-strand breaks and changes in gene expression. Currently, the late effects of therapy have become a recurring problem, mainly due to the increased survival of HNC patients. Herein, we present an update of the systemic activity of RT and CT for HNC, with a focus on their toxicogenetic and toxicogenomic effects.

TCF7L2 rs7903146 polymorphism is associated with gastric cancer: a case-control study in the Venezuelan population

AIM: To explore the association between TCF7L2 rs12255372 and rs7903146 single nucleotide polymorphisms(SNPs) and gastric cancer risk in Venezuelan patients.METHODS: We performed a case-control study including 122 paraffin-embedded archived intestinaltype gastric cancer samples and 129 biopsies obtained by superior endoscopy from chronic gastritis patients. Gastric cancer samples were classified according the degree of carcinoma differentiation. Genomic DNA was extracted from tissues, and the two SNPs of TCF7L2 gene(rs12255372 and rs7903146) were genotyped by polymerase chain reaction-restriction fragment length polymorphism reactions. Multiple regression analysis with adjustments for age and gender were performed and best-fitting models of inheritance were determined.RESULTS: After adjusting for age and sex the TCF7L2 rs7903146 TT genotype was associated with gastric cancer risk under the recessive genetic model(OR = 3.11, 95%CI: 1.22-7.92, P = 0.017). We further investigated the distribution of rs12255372 and rs7903146 genotypes according gastric cancer stratified by degree of differentiation, and we observed that carriers of rs7903146 T allele(CT + TT vs CC) had a significantly increased risk of moderate/well differentiated gastric cancer(dominant model, OR = 2.55, 95%CI: 1.35-4.80, P = 0.004), whereas the rs7903146 TT genotype was associated with poorly differentiated gastric cancer in the recessive model(OR = 3.65, 95%CI: 1.25-10.62, P = 0.018). We did not find association between rs12255372 SNP and the susceptibility of developing gastric cancer. CONCLUSION: TCF7L2 rs7903146 polymorphism is associated with gastric cancer risk in the Venezuelan population, and could be related to determine the degree of differentiation of tumor cells.

Tubular conduits,cell-based therapy and exercise to improve peripheral nerve regeneration

Peripheral nerve injuries （PNI） are a major clinical prob- lem. In general, PNI results from motor vehicle accidents, lacerations with sharp objects, penetrating trauma （gunshot wounds） and stretching or crushing trauma and fractures. It is estimated that PNI occur in 2.8% of trauma patients and this number reaches 5% if plexus and root lesions are in- cluded. However, due to lack of recent epidemiological stud- ies, these data probably underestimate the actual number of nerve injuries

口腔原发性恶性黑色素瘤:1例报道

A 43-year-old white man was referred to the Special Care Dentistr y Center of the School of Dentistry,University of Sao Paulo, Brazil, for the diagnosis o f an extensive nodular lesion of the maxillary gingiva. The patient complained t hat his left maxilla had swollen over the last 4 months, with some exudation fro m the gingival crevice, sporadic bleeding, and slight tooth mobility, but no pai n. An extra-oral examination confirmed expressive swelling of the left side of the face (Fig. 1A). Palpation disclosed bilateral enlargement of the submandibu lar lymph nodes. An intra-oral examination showed an extensive, reddish, nodul ar mass (around 11 cm in diameter) that extended from the last left maxillary mo lar to the right maxillary incisor, covered by a mucosa that was ulcerated in so me areas (Fig. 1B,C). Palpation revealed a painless, soft, bleeding tissue that seemed to arise in the periodontal ligaments, extending to the palate and vestibular area. A small pigmented spot was found in the palat al mass. Histopathologically, the biopsy revealed a proliferation of neoplastic cells that exhibited a wide variety of shapes, including spindle, plasmacytoid, and epithelioid forms. The atypical cells showed enlarged and pleomorphic nuclei . Mitotic activity and pigmented areas were observed (Fig. 2A,B). Immunohistoche mistry was used to establish the final diagnosis. The tumor cells strongly expre ssed S100 protein, gp100 (HMB- 45), melan A, and tyrosine antibodies (Fig. 2C,D ). With the diagnosis of malignant melanoma, the patient was referred to an onco logist for treatment. As computed tomography revealed that the lesion was deeply inserted into the skull surface (Fig. 1D), surgical intervention was not possib le. The patient underwent radiotherapy, but died 14 months later.

Galectin-3 expression favors metastasis in murine melanoma

Galectin-3 is a member of the lectin family that binds β-galactosides and plays an important role in several types of tumors. Melanoma is an invasive cancer responsible for 80% of deaths associated to skin cancers. There are some evidences that galectin-3 interacts with β-catenin, a molecule involved with Wnt signaling pathway. Here, we evaluate the role of galectin-3 intumor growth and metastasis, as well as its interaction with β-catenin. Murine melanoma cells (B16F10) were injected subcutaneously and intravenously in male C57BL/6 wild-type (WT) and galectin-3 knock-out (KO) mice. Tumor growth and lung melanoma colonies were assessed. The expression of galectin-3 and β-catenin was evaluated by immuno-histochemistry. We observed that tumor growth did not differ between the groups. However, to metastasis, the number of lung colonies in WT mice was significantly increased in comparison to that observed in KO mice. The cytoplasm expression of galectin-3 was observed in subcutaneous and metastatic tumors,w in both groups. We observed its nuclear expression in some of subcutaneous tumors of KO mice. The expression of β-catenin was detected in cell membrane of all subcutaneous tumors analyzed, whereas in the metastatic tumors we observed both cytoplasm and cell membrane staining. Altogether, our data suggest that galectin-3 favors the metastasis of melanoma cells and this process is not associated with β-catenin.

Snai-1 and Epithelial-Mesenchymal Transition-Related Protein Immunoexpression in Canine Mammary Carcinomas

Epithelial-mesenchymal transition (EMT) is defined as switching of polarized epithelial cells to a migratory fibroblastoid phenotype. EMT is known to be involved in the progression and metastasis of various cancers in humans, but this specific process is still little explored in the veterinary literature. The aim of this research was to evaluate the expression of EMT-related proteins in canine mammary carcinomas (CMCs). The expression of six EMT-related proteins in 94 CMCs of female dogs was evaluated by immunohistochemistry using a tissue array method. Additionally, clinicopathological characteristics were compared with the expression of EMT-related proteins. Loss of epithelial protein and/or acquisition of the expression of mesenchymal proteins were observed in CMCs. Loss of epithelial protein and/or acquisition of the expression of mesenchymal proteins were observed, particularly in tumors with evidence of stromal invasion;however, significance was only observed between the S100A4 and vascular invasion. In addition, Snai-1 nuclear immunoexpression was significantly related to E-cadherin loss. In conclusion, loss of epithelial proteins and/or the acquisition of mesenchymal proteins are associated with EMT and may have an important role in the evaluation of CMC patients. The unique immunoexpression pattern of Snai-1 could help to distinguish between an adenoma and a non-metastatic carcinoma and seems to be related to conversion of myoepithelial cells to a complete mesenchymal-like phenotype. Loss of E-cadherin and cytokeratin and change of immunoexpression pattern of Snai-1, N-cadherin, S100A4 and MMP-2 indicate the occurrence of EMT in canine mammary carcinomas and should result in an en bloc resection or a close follow-up.

Nanotoxicology and Exposure in the Occupational Setting

Nanotechnology refers to the ability to control the composition of molecules and atoms within the range of 1.00 - 100 nm. At this scale, many materials exhibit novel properties when compared with their micro or macro-sized equivalents, including, for example, chemical reactivity, strength, mobility and solubility. Nanoparticles are prime candidates for toxicity because they possess a much greater surface to volume ratio (i.e. the surface area compared to the volume) than larger particles of that same material;they can have biopersistance and higher oxidant capacity, penetrate epithelium and reach interstitial pulmonary region. In an industrial setting, workers may present the main exposure risk potential among humans, and they may be involved in the entire product life cycle. There are needs to protect public and environmental health and safety. Currently, no standards or regulations exist that apply or refer specifically to nanomaterials impacts.

Expression of Multidrug Resistance ATP-Binding Cassette(ABC)Transporters in Canine Mammary Tumors

Mammary neoplasms are the most common tumors in female dogs. They are usually treated using solely surgical mastectomy—which is recognized as unsatisfactory in many cases. Given this, the benefits of chemotherapy in dogs with mammary cancer need to be further explored. Some drugs that can be used for treating canines with mammary tumors may be substrates of uptake and/or efflux transporters such as the ATP-binding cassette (ABC) transporters. Unfortunately, very little is known regarding the pathobiology of such proteins in canine tumors, including mammary cancer. Accordingly, this study was designed to characterize the expression of ABC transporters P-glycoprotein, MRP1, and MRP2 and their relation with clinicopathologic factors in order to allow a better understanding of their influence in canine mammary cancer. P-glycoprotein was expressed in tumors from 55.8% of patients, while MRP1 and MRP2 were expressed in 37.2% and 39.5% of tumors, respectively. P-glycoprotein expression showed to be related with regional lymph node spread (P = 0.0038), as well as with tumor grade (P = 0.0353) and with a shorter survival (P = 0.0245). MRP1 revealed a strong association with a higher histological grade (P < 0.0001) and overall survival (P = 0.0002). Additionally, MRP1 was determined as prognostic indicator independent of lymph node status using Cox proportional-hazards regression multivariate analysis (P = 0.0216). No relations between MRP2 and clinicopathologic features were observed. We have found that P-glycoprotein and MRP1 are expressed in highly aggressive canine mammary tumors and are related with poor prognosis. Our results suggest that they may play a significant role in the course of canine mammary cancer progression and be promising candidate markers for a validation study on therapy outcome.

Immunoexpression of Cathepsin D and S100A4 Protein and Their Molecular Subtyptes in Canine Mammary Carcinomas

Cathepsin D (CD), a lysosomal protease, and S100A4 protein, a calcium binding motif, are considered to be involved in metastasis in various human cancers. No data regarding such proteins are available for canine mammary carcinomas (CMCs). Accordingly, their expression in association with known factors of prognosis was investigated in this study. For that, 66 surgically resected CMCs were submitted to an immunohistochemical evaluation using anti CD, S100A4 protein, HER2, estrogen receptor α, cytokeratin 5, and p63 antibodies, further characterizing the tumors' molecular subtype. An increase in S100A4 immunoexpression by neoplastic luminal mammary cells was associated with an infiltrative tumor mode of growth, consequently leading us to conclude that S100A4 protein could be related to progression in CMCs. Additionally, the occurrence of the luminal A molecular subtype was associated with the complex histotype in CMCs. Although we have demonstrated that changes in S100A4 protein immunoexpression occurs in CMCs, further studies are needed to determine whether this represents important independent biomarkers for CMCs.