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Regional lymph node status impacts survival in dogs with malignant mammary tumors. However, few studies have evaluated extracapsular extension and tumor implants in regional lymph node metastases in dogs with mammary carcinoma. Therefore, 84 cases of mammary carcinomas with metastases in inguinal and/or axillary lymph nodes from female dogs of different breeds and a total of 139 metastatic lymph nodes were evaluated by routine histological staining. Clinical and pathological characteristics of primary tumors as well as the presence of extracapsular extension and tumor implants in the lymph nodes were analyzed, in addition to survival. One to 5 lymph nodes were evaluated in each case. Extracapsular extension and tumor implants were present in 17.9% and 39.3% of cases, respectively. The simultaneous presence of extracapsular extension and tumor implants were associated with an increased risk of death (hazard ratio 10.46). In addition, "special type carcinomas", high histological grade (grade III), and presence of extracapsular extension associated with tumor implants were related to a worse prognosis and shorter survival times (p 0.05). Based on these results, we highlight the importance of identifying extracapsular extension and tumor implants in dogs with metastatic mammary carcinomas, as they are associated with a higher risk of death and shorter survival.

With advances in checkpoint inhibitor and CAR T-cell therapies, among other advances in immunotherapy, this is an exciting time to be a tumor immunologist. We are witnessing the transition of decades of work at the bench leading to substantial success in the clinic. While work continues developing new and improving existing immunotherapies, there remains a great deal of basic tumor immunology still to learn, information that can only lead to greater success in the clinic. One area in need of more attention is understanding the immune response at early stages of breast cancer. While there is no question that early diagnosis and treatment save lives, a greater understanding about the immune response during early stages of breast cancer may reveal information that could assist in monitoring individuals at risk of breast cancer, and could have implications for patients diagnosed at early stages of disease, and may provide important information about the origins of an immune-suppressive environment. Here, we review studies that have looked at the very early immune response to breast cancer focusing on patients with DCIS, before invasion in spontaneous transgenic murine mammary carcinoma models, and before transplantable or orthotopic murine mammary carcinoma models become palpable. The findings revealed that indicators of a pro-tumor immune response are already present at early stages of disease.

Background Differentiating benign from canine malignant mammary tumors requires invasive surgical biopsy. Circulating microRNAs (miRNA) may represent promising minimally invasive cancer biomarkers in people and animals. Objectives To evaluate the serum mRNA profile between dogs with and without mammary carcinoma, and to determine if any of these markers have prognostic significance. Animals Ten healthy client‐owned female dogs (5 intact, 5 spayed) and 10 dogs with histologically confirmed mammary carcinoma were included; 9 were client‐owned, whereas 1 was a research colony dog. Methods Retrospective study. Serum miRNA was evaluated by RNA deep‐sequencing (RNAseq) and digital droplet PCR (dPCR).Expression of candidate biomarkers miR‐18a, miR‐19b, miR‐29b, miR‐34c, miR‐122, miR‐125a, and miR‐181a was compared with clinical characteristics, including grade, metastasis, and survival. Results 452 unique serum miRNAs were detected by RNAseq. Sixty‐five individual miRNAs were differentially expressed (>±1.5‐fold) and statistically significant between groups. Serum miR‐19b (P = .003) and miR‐125a (P

HER2-positive breast cancers may lose HER2 expression in recurrences and metastases. In this work, we studied cell lines derived from two transgenic mammary tumors driven by human HER2 that showed different dynamics of HER2 status. MamBo89HER2stable cell line displayed high and stable HER2 expression, which was maintained upon in vivo passages, whereas MamBo43HER2labile cell line gave rise to HER2-negative tumors from which MamBo38HER2loss cell line was derived. Both low-density seeding and in vitro trastuzumab treatment of MamBo43HER2labile cells induced the loss of HER2 expression. MamBo38HER2loss cells showed a spindle-like morphology, high stemness and acquired in vivo malignancy. A comprehensive molecular profile confirmed the loss of addiction to HER2 signaling and acquisition of an EMT signature, together with increased angiogenesis and migration ability. We identified PDGFR-B among the newly expressed determinants of MamBo38HER2loss cell tumorigenic ability. Sunitinib inhibited MamBo38HER2loss tumor growth in vivo and reduced stemness and IL6 production in vitro. In conclusion, HER2-positive mammary tumors can evolve into tumors that display distinctive traits of claudin-low tumors. Our dynamic model of HER2 status can lead to the identification of new druggable targets, such as PDGFR-B, in order to counteract the resistance to HER2-targeted therapy that is caused by HER2 loss.

Triple-negative tumors are characterized immunohistochemically by the absence of positivity to sex hormone receptors and to human epidermal growth factor receptor 2. Additionally, they are differentiated into basal-like and non-basal (or null) subtypes, based on the presence of basal cytokeratin expression (CK5/6, 14, and17). Triple-negative subtypes are yet to be characterized in male dogs, to our knowledge. We report herein the clinical and pathologic findings and molecular characterization of carcinoma in the mammary glands of 2 male dogs. Case 1 was diagnosed as a grade II tubulopapillary carcinoma; case 2 was diagnosed as a grade II carcinoma in a mixed tumor. The tumors were characterized phenotypically as triple-negative basal and triple-negative non-basal, respectively.

Background Breast cancer is the most common malignancy in female patients worldwide. Because of its heterogeneity in terms of prognosis and therapeutic response, biomarkers with the potential to predict survival or assist in making treatment decisions in breast cancer patients are essential for an individualised therapy. Epigenetic alterations in the genome of the cancer cells, such as changes in DNA methylation pattern, could be a novel marker with an important role in the initiation and progression of breast cancer. Method DNA methylation and RNA-seq datasets from The Cancer Genome Atlas (TCGA) were analysed using the Least Absolute Shrinkage and Selection Operator (LASSO) Cox model. Applying gene ontology (GO) and single sample gene set enrichment analysis (ssGSEA) an epigenetic signature associated with the survival of breast cancer patients was constructed that yields the best discrimination between tumour and normal breast tissue. A predictive nomogram was built for the optimal strategy to distinguish between high- and low-risk cases. Results The combination of mRNA-expression and of DNA methylation datasets yielded a 13-gene epigenetic signature that identified subset of breast cancer patients with low overall survival. This high-risk group of tumor cases was marked by upregulation of known cancer-related pathways (e.g. mTOR signalling). Subgroup analysis indicated that this epigenetic signature could distinguish high and low-risk patients also in different molecular or histological tumour subtypes (by Her2-, EGFR- or ER expression or different tumour grades). Using Gene Expression Omnibus (GEO) the 13-gene signature was confirmed in four external breast cancer cohorts. Conclusion An epigenetic signature was discovered that effectively stratifies breast cancer patients into low and high-risk groups. Since its efficiency appears independent of other known classifiers (such as staging, histology, metastasis status, receptor status), it has a high potential to further improve likely individualised therapy in breast cancer.

Introduction:The breast cancer is from the 2006 first cause of death by malignant neoplasies in México. The survival of the mammary carcinoma depends mainly on the preventive actions that are carried out; due to the lack of technological infrastructure in our country, the herself breast exploration, is the method more used and recommended for the opportune detection of the Cancer (CaMA). Objective:Knowledge of NOM-041-SSA2-2011 in health students. Material and Methods:A study non comparative to 105 students was made descriptive, cross-sectional applying them to a questionnaire that included social-demographic variables and questions with respect to the correct application of the herself exploration technique as well as questions about the practice, personal opinion of the same one and with base to the NOM-041-SSA2-2011; In the application test on line date April – May 2021. Results:With respect to the level of knowledge with function to the ages, the level between the 18 and the 20 years was deficient with respect to herself breast exploration (CaMA). It is important note that with respect to the scholastic degree there was a deficient level of knowledge about of the breast exploration in the second and 6 to fourth month period in the students of the area of the health.

Abstract FigureGraphical abstractIndividualized neoantigen vaccination against mammary carcinomaBackgroundHarnessing the immune system to purposely recognize and destroy tumours represents a significant breakthrough in clinical oncology. Nonsynonymous mutations (neoantigenic peptides) were identified as powerful cancer targets. This knowledge can be exploited for further improvements of active immunotherapies, including cancer vaccines as T cells specific for neoantigens are not attenuated by immune tolerance mechanism and do not harm healthy tissues. The current study aimed at developing an optimized multi-target vaccine using short or long neoantigenic peptides utilizing virus-like particles (VLPs) as an efficient vaccine platform.MethodsHere we identified mutations of murine mammary carcinoma cells by integrating mass spectrometry-based immunopeptidomics and whole exome sequencing. Neoantigenic peptides were synthesized and covalently linked to virus-like nanoparticles using a Cu-free click-chemistry method for easy preparation of vaccines against mouse mammary carcinoma.ResultsAs compared to short peptides, vaccination with long peptides was superior in the generation of neoantigen-specific CD4+ and CD8+ T cells which readily produced IFN-γ and TNF-α. The resulting anti-tumour effect was associated with favourable immune re-polarization in the tumour microenvironment through reduction of myeloid-derived suppressor cells. Vaccination with long neoantigenic peptides also decreased post-surgical tumour recurrence and metastases, and prolonged mouse survival, despite the tumour’s low mutational burden.ConclusionIntegrating mass spectrometry-based immunopeptidomics and whole exome-sequencing is an efficient technique for identifying neoantigenic peptides. A multi-target VLP-based vaccine shows a promising anti-tumour results in an aggressive murine mammary carcinoma cell line. Future clinical application using this strategy is readily feasible and practical, as click-chemistry coupling of personalized synthetic peptides to the nanoparticles can be done at the bedside directly before injection.

BackgroundCurrently, over half of breast cancer cases are unrelated to known risk factors, highlighting the importance of discovering other cancer-promoting factors. Since crosstalk between gut microbes and host immunity contributes to many diseases, we hypothesized that similar interactions could occur between the recently described breast microbiome and local immune responses to influence breast cancer pathogenesis.MethodsUsing 16S rRNA gene sequencing, we characterized the microbiome of human breast tissue in a total of 221 patients with breast cancer, 18 individuals predisposed to breast cancer, and 69 controls. We performed bioinformatic analyses using a DADA2-based pipeline and applied linear models with White’stor Kruskal–WallisH-tests with Benjamini–Hochberg multiple testing correction to identify taxonomic groups associated with prognostic clinicopathologic features. We then used network analysis based on Spearman coefficients to correlate specific bacterial taxa with immunological data from NanoString gene expression and 65-plex cytokine assays.ResultsMultiple bacterial genera exhibited significant differences in relative abundance when stratifying by breast tissue type (tumor, tumor adjacent normal, high-risk, healthy control), cancer stage, grade, histologic subtype, receptor status, lymphovascular invasion, or node-positive status, even after adjusting for confounding variables. Microbiome–immune networks within the breast tended to be bacteria-centric, with sparse structure in tumors and more interconnected structure in benign tissues. Notably,Anaerococcus,Caulobacter, andStreptococcus, which were major bacterial hubs in benign tissue networks, were absent from cancer-associated tissue networks. In addition,PropionibacteriumandStaphylococcus, which were depleted in tumors, showed negative associations with oncogenic immune features;StreptococcusandPropionibacteriumalso correlated positively with T-cell activation-related genes.ConclusionsThis study, the largest to date comparing healthy versus cancer-associated breast microbiomes using fresh-frozen surgical specimens and immune correlates, provides insight into microbial profiles that correspond with prognostic clinicopathologic features in breast cancer. It additionally presents evidence for local microbial–immune interplay in breast cancer that merits further investigation and has preventative, diagnostic, and therapeutic potential.

A large, firm, multi-cystic mammary gland mass grew slowly over 4 y in a 12-y-old, female Finn–Shetland cross sheep. A diagnosis of epithelial malignancy was suspected following fine-needle aspiration cytology at 30 mo after initial observation. The sheep was euthanized when the flock was downsized 18 mo later. A field postmortem examination revealed a large mammary mass, but an absence of metastases to internal organs. Imprint cytology of the mammary tissue supported a benign proliferative process. Histologically, mammary tissue was obliterated by cystic, tubular, and papillary adenomatous arrangements of mammary epithelium, with an anaplastic component, consistent with mammary carcinoma arising in an adenoma. IHC showed strong nuclear positivity to the antibody against progesterone receptor and minimal positivity to the antibody against estrogen receptor alpha expression. Intrinsic subtyping for basal or luminal epithelial origin was attempted through adaptation of companion animal IHC classification panels; high- and low-molecular-weight cytokeratins (CK5, CK8, CK18) failed to stain, but p63 expression for basal epithelium was positive.

Senescence marker protein 30 (SMP30) is a cell survival factor playing an important role in vitamin C synthesis and antiapoptosis. Moreover, its cytoprotective role suggests a possibility to be related to cancer cell survival. Mammary carcinoma is a common cancer in both humans and animals. Because of its histopathological diversity, especially in the early stage, histopathological diagnosis may be complicated, therefore, a diagnostic marker is helpful for confirmation. The present study analyzed the expression pattern of SMP30 in mammary carcinoma in humans, dogs, and cats. Immunohistochemistry, immunofluorescence, and western blot analysis were used to investigate SMP30 expression patterns. The expression was specifically observed in neoplastic glandular epithelial cells. The expression increased with the malignancy of glandular epithelial cells with a highly proliferative status. However, SMP30 expression was low in normal mammary gland tissues or well-differentiated adenoma tissues. The patterns were consistently reproduced in canine primary mammary carcinoma cells and MCF-7 and MDA-MB-231 human carcinoma cell lines. This study provides useful information to understand SMP30 expression in various stages of mammary carcinoma and to suggest its utility as a pan-species diagnostic marker, thereby helping to establish strategies for diagnosing mammary carcinoma in several species.

Animal models for studying human breast cancer carcinogenesis and testing drug candidates on human breast cancer have extensively been proposed. Especially, chemically induced breast tumor models have been used because they can mimic the progression of clinical cancer from the beginning and can be generated with a facile procedure. Pristane is a hydrocarbon oil that is used as a chemical carcinogen to induce tumorigenesis in mice as well as arthritis and lupus nephritis in rats. In only a few studies, pristane-induced breast cancer models have been reported. This chapter is designated to describe pristane-induced mammary carcinoma models. Here, we provide a protocol for generating pristane-induced breast tumors in mice models for analyzing and for testing potential therapeutics on them. The given protocol can be applied to other animal models with some changes.

Breast cancer is the leading cause of cancer death in women, and while metastasis is common to areas like the bone, lungs, and brain, it is rare to metastasize to the gastrointestinal tract and especially to the rectum. Due to the rarity of this condition and its resemblance clinically and radiologically to primary gastrointestinal tract tumors, diagnosis and treatment are challenging. We present a case of metastatic lobular mammary carcinoma in a 52-year-old Bahraini woman who presented with an obstructing rectal mass.

Background: Sex-determining Region Y (SRY)-box transcription factor-2 (Sox2) belongs to the “Yamanaka's factors,” necessary and sufficient to convert somatic cells into pluripotent stem cells. In breast cancers, Sox2 expression has been associated with poor prognosis, and resistance to therapy. The aims of this study were to determine the frequency of Sox2 positivity in feline invasive mammary carcinomas (FMCs), its relationships with other clinical-pathologic variables, and with patient outcomes.Materials and Methods: This study relies on a previously described retrospective cohort of 180 FMCs, diagnosed in female cats treated by mastectomy alone, with 2-year follow-up. Sox2 (clone SP76), Estrogen Receptor alpha (ER), Progesterone Receptor (PR), Ki-67, Human Epidermal growth factor Receptor 2 (HER2), Androgen Receptor (AR), Bcl-2, Forkhead box protein A1 (FOXA1), basal markers and FoxP3-positive regulatory T cells (Tregs) were detected by automated immunohistochemistry. Sox2 expression was quantitated as an index (percentage of neoplastic cells demonstrating a positive nuclear signal). The FMCs were considered Sox2-positive at threshold >42%.Results: Sox2 was not expressed in the normal mammary gland or in mammary hyperplasia without atypia, but was occasionally detected in atypical hyperplasia. In FMCs, the mean Sox2 index was 38 ± 30%, and 79/180 FMCs (44%) were Sox2-positive. Sox2 expression was associated with older age at diagnosis, lymphovascular invasion, high Ki-67 proliferation indexes, low PR and FOXA1 expression, and increased numbers of tumor-associated Tregs, but was not significantly associated with the clinical stage, histological types, and histological grade. By multivariate survival analysis, Sox2 was associated with poor cancer-specific survival (Hazard Ratio = 1.48, 95% confidence interval 1.04–2.11, p = 0.0292), independently of the pathologic tumor size, pathologic nodal stage, distant metastasis, and AR expression. A rare subgroup of FMCs characterized by an AR+Sox2–phenotype (19/180 cases, 11%) was associated with very favorable outcomes.Conclusion: Sox2 expression was associated with poor cancer-specific survival of female cats with invasive mammary carcinomas, as previously reported in human breast cancer, but was more commonly expressed in cats than reported in breast cancers. Sox2 showed complementarity with AR in FMC prognostication.

Perioperative administration of desmopressin has shown to significantly decrease rates of local recurrence and metastasis, and increase survival times in dogs with grade II and III mammary carcinomas. The objective of this study was to compare the oncologic outcome of cats with mammary carcinoma treated with bilateral mastectomy with or without perioperative administration of desmopressin. Medical records from nine veterinary institutions were searched to identify cats diagnosed with mammary carcinoma treated with bilateral mastectomy. Sixty cats treated with single-session or staged bilateral mastectomy were included. There were no significant differences in oncologic outcomes found between cats treated and not treated with desmopressin. No adverse effects were seen in any of the cats treated with perioperative desmopressin. Postoperative complications occurred in 18 cats (38.3%) treated with single-session bilateral mastectomy and in three cats (23.1%) treated with staged bilateral mastectomy (P = .48). Histologic grade and a modification of a proposed five-stage histologic staging system were both prognostic for disease-free interval. Incomplete histologic excision was associated with significantly increased rates of metastasis and tumour progression, and a shorter median survival time (MST). Cats that developed local recurrence also had a significantly shorter MST. The results of this study do not support the use of perioperative desmopressin to improve outcome when performing bilateral mastectomy for the treatment of mammary carcinoma in cats.

Patients with dominantly inherited Li-Fraumeni syndrome have a loss-of-function mutation in TP53 and develop diverse mesenchymal and epithelial neoplasms at multiple sites. Trp53 +/- female mice with the BALB/c background provide unique characteristics for the study of breast cancer in Li-Fraumeni syndrome; however, we previously found that female C3H-Trp53+/ - mice did not spontaneously develop mammary tumors. Therefore, we obtained F1 and N2-N4 female mice by backcrossing the BALB/c strain and examined the incidence of mammary and other tumors in lifetime studies. Malignant lymphomas, osteosarcomas, and uterine adenocarcinomas spontaneously developed in approximately 20% or more of Trp53+/ - mice with the C3H background. In contrast, the incidence of uterine adenocarcinomas showed a tendency to decrease, while that of mammary adenocarcinomas gradually increased in mice with the BALB/c strain backcross. Wild-type BALB/c female mice are predisposed to a wide spectrum of neoplasms, including mammary tumors, partly due to genetic factors, whereas uterine tumors are uncommon not only in BALB/c mice but also C3H mice. Thus, genetic factors appear to contribute to a strain-specific predisposition to malignant neoplasms in Trp53+/- mice, and further studies are needed to clarify the detailed mechanisms.

Breast carcinomas often metastasize into various organs, most commonly into the lung and rather infrequently into the pineal gland. There were only 20 cases of the latter recorded until 1950. Currently, the total number of reported cases, including this report, is 74. At Sunnybrook Health Science Centre, between 1984 and 1992, 27 patients died of disseminated breast cancer; 2 patients had metastases to the pineal gland. Five patients had metastatic deposits in the pituitary and J had metastases in both organs. Average survival time from diagnosis of breast tumor to death was nearly 3 years. In contrast, the 2 patients with pineal metastasis lived for 1 and 7 months, respectively, after diagnosis. The significance of pineal metastases with regard to short survival may be related to the fact that destruction of the pineal parenchyma reduced melatonin production, thereby decreasing the nonspecific oncostatic effect normally exerted by pineal gland secretions.

Electrochemical treatment has been suggested as an effective alternative to local cancer therapy. Nevertheless, its effectiveness decreases when highly aggressive primary tumors are treated. The aim of this research was to understand the growth kinetics of the highly aggressive and metastatic primary F3II tumor growing in male and female BALB/c/Cenp mice under electrochemical treatment. Different amounts of electric charge (6, 9, and 18 C) were used. Two electrodes were inserted into the base, perpendicular to the tumor's long axis, keeping about 1 cm distance between them. Results have shown that the F3II tumor is highly sensitive to direct current. The overall effectiveness (complete response + partial response) of this physical agent was ≥75.0% and observed in 59.3% (16/27) of treated F3II tumors. Complete remission of treated tumors was observed in 22.2% (6/27). An unexpected result was the death of 11 direct current-treated animals (eight females and three males). It is concluded that direct current may be addressed to significantly affect highly aggressive and metastatic primary tumor growth kinetics, including the tumor complete response. Bioelectromagnetics. 39:460-475, 2018. © 2018 Wiley Periodicals, Inc.

Invasive papillary carcinoma (IPC) and glycogen-rich clear cell carcinoma (GRCCC) are rare primary breast carcinomas. IPC typically have favorable prognosis, whereas the prognosis of GRCCC is less established. We report a unique case of high-grade invasive mammary carcinoma with mixed IPC and GRCCC features. We review the imaging and pathologic features and discuss prognosis of these unusual breast cancer subtypes.

Inflammatory breast cancer (IBC) in humans is the most aggressive form of mammary gland cancer and shares clinical, pathologic, and molecular patterns of disease with canine in flammatory mammary carcinoma (CIMC). Despite the use of multimodal therapeutic approaches, including targeted therapies,the prognosis for IBC/CIMC remains poor. The aim of this review is to critically analyze IBC and CIMC in terms of biology and clinical features. While rodent cancer models have formed the basis of our understanding of cancer biology, the translation of this knowledge into improved outcomes has beenlimited. However, it is possible that a comparative “one health” approach to research, using a natural canine model of the disease, may help advance our knowledge on the biology of the disease. This will translate into better clinical outcomes for both species. We propose that CIMC has the potential to be auseful model for developing and testing novel therapies for IBC. Further, this strategy could significantly improve and accelerate the design and establishment of new clinical trials to identify novel and improved therapies for this devastating disease in a more predictable way.

Mammary carcinoma arising in microglandular adenosis (MGA) is extremely rare, and MGA is regarded as a non-obligate precursor of triple-negative breast cancer. We report five cases of carcinoma arising in MGA of the breast. All cases showed a spectrum of proliferative lesions ranging from MGA to atypical MGA, ductal carcinoma in situ or invasive carcinoma. Immunohistochemically, all cases were triple-negative and expression of S-100 protein gradually decreased as the lesions progressed from MGA to atypical MGA and carcinoma. Three cases showed acinic cell differentiation with reactivity to α1-antitrypsin, and one case was metaplastic carcinoma. During clinical follow-up, one patient developed local recurrence. Carcinoma arising in MGA is a rare but distinct subset of triple-negative breast cancer with characteristic histologic and immunohistochemical findings.

The present work describes a rare case of a spontaneous high-grade carcinoma in a seven-week-old Sprague-Dawley female rat that had been included in the control group of an assay of mammary carcinogenesis. The mass was detected at 50days of age, it grown quickly and the animal was humanely sacrificed eight days later. The tumor was located in the left cervical region, in the vicinity of the left submandibular and sublingual glands. It was soft and reddish and had several dens with a bloody content. The tumor was PAS negative and exhibited immunostaining for ER-α. The histopathologic and immunohistochemical data are suggestive of a high-grade carcinoma from mammary gland. It was the first report of a spontaneous mammary tumor in such a young rat.

A case of a primary lung carcinoma with histologic and immunohistochemical features of a mammary carcinoma is presented. The patient is a 72-year-old man who presented with symptoms of cough and dyspnea. Diagnostic imaging showed a bronchial tumor in the left lower lobe that was surgically resected by a left lower lobectomy. The tumor was characterized by a homogenous cellular proliferation composed of small to medium-sized cells with round nuclei and inconspicuous nucleoli. Multiple immunohistochemical stains were performed, and the tumor was notably positive for estrogen receptor, progesterone receptor, GATA3, and pan-keratin, while molecular analysis showed somatic mutation in ARID1A. Clinical follow-up showed that the patient is alive and well 18 months post-surgical resection without evidence of recurrence or metastatic disease. Based on the overall features of this neoplasm, we consider that the tumor herein presented represents an unusual type of lung carcinoma that we refer to as primary mammary-like carcinoma of the lung.

A 12 yr old intact female Siberian husky was referred with a 2 wk history of progressive weakness, paraparesis, anorexia, and panting. A 4 cm diameter grade 3 mammary solid carcinoma involving the fifth right mammary gland had been removed 2 days prior to the current visit. While hospitalized, the dog was diagnosed with Addison’s disease based on electrolyte disturbances and low serum cortisol levels following adrenocorticotropic hormone stimulation test. An abdominal ultrasound revealed adrenal glands at the upper limit of normal size. Despite treatment, the dog deteriorated and died 4 days after presentation. A postmortem examination revealed a neoplastic infiltrate of epithelial malignant cells in both adrenal glands, popliteal lymph nodes, vertebral bodies, and paralumbar musculature, compatible with metastasis from mammary carcinoma. To our knowledge, this is the first reported case of Addison’s disease secondary to metastatic mammary carcinoma in a dog.

As evidenced by numerous case reports from zoos, neoplasia in felids is common, but most reports are limited to Panthera species in North America or Europe. In order to obtain a wider epidemiologic understanding of neoplasia distribution, necropsy records at seven facilities (USA, Mexico, Colombia, Peru, and Brazil) were evaluated. In contrast to others, this study population (195 cases, 16 species), included many non-Panthera felids. Overall neoplasia prevalence was 28.2% (55/195). Panthera species had a higher prevalence of neoplasia than non-Panthera species (52.5%, vs. 13.0%). Lions (66.7%), jaguars (55.0%), and tigers (31.3%) had the highest species-specific prevalence of neoplasia. Neoplasms in Panthera species were more frequently malignant than in non-Panthera (86.1% vs. 55.6%). The systems most commonly affected were the reproductive, hematolymphoid, and respiratory. The range of management conditions and more varied genetic backgrounds support a robust taxonomic pattern and suggest that the reported propensity for neoplasia in jaguars may have a genetic basis at a taxonomic level higher than species, as lions and tigers also have high prevalence. Given the high prevalence of neoplasia and high likelihood of malignancy, routine medical exams in all nondomestic felids, but Panthera species in particular, should include thorough assessments of any clinical signs of neoplasia.

Simple Summary This case report describes the unusual presentation of two rare tumors in a mare diagnosed over a short period of time (9 months), affecting the eye and the mammary gland, with a relapse of the ocular tumor presenting histological features that cannot be attributed to any specific neoplastic entity. In the study, we describe the in vivo diagnosis and treatment of the neuroepithelial intraocular tumor and the post mortem detection of a metastatic malignant mammary carcinoma. Abstract A 24-year-old Irish Cob mare was presented with a peripheral iris mass, which was surgically resected and diagnosed as an undifferentiated neuroepithelial tumor. A few months later, a relapse occurred with histological features characterized by a more solid appearance and squamous differentiation. Subsequently, the mare was presented with rapidly spreading multiple subcutaneous masses and, at the onset of neurological signs, was humanely euthanized and subjected to a complete post mortem examination. The necropsy confirmed the presence of numerous widespread masses in the subcutaneous tissue, several internal organs, and mammary gland. Histological and immunohistochemical (IHC) examinations were performed on all masses, allowing the diagnosis of mammary carcinoma with several visceral and subcutaneous metastases. Considering the post mortem findings, the second intraocular mass was submitted to histological and IHC re-evaluation to differentiate it from an intraocular metastasis of the mammary carcinoma. The results of the histological and IHC analyses confirmed the diagnosis of neuroepithelial tumor relapse. This is the first case of a metastatic mammary carcinoma concurrent with a recurrent intraocular neuroepithelial tumor in a mare. This case was a challenge for both clinicians and pathologists involved and highlighted the importance of post mortem and IHC evaluations.

Background: The nipples-saving mastectomy (NSM), most recent technique, allows the whole mammary gland removal preserving the nipple-areola compound (NAC), obtaining oncologic safe results. When indicated, NSM is validated by the great aesthetic results obtained. Objectives: The objective of this review is the evaluation of the effectiveness and oncologic safety of the nipple-saving mastectomy, marking the most frequent complications. Moreover, the possibility to use the NSM procedure as prophylactic mastectomy in patients at high risk has been evaluated. Research Methods: A bibliographic research about clinical studies and previous reviews related to nipplessaving mastectomy has been conducted. No limitation about language was performed. Results: The study included 12 articles, for a total of 2859 patients and 3849 NSM. Patients candidate to NSM, either as a prophylactic or curative treatment of mammary carcinoma, must undergo a careful selection screening. Most frequently occurring surgery-related complications were necrosis and infections; though not altering the cosmetic results, that have been positively evaluated in almost all patients. Conclusion: Preservation of the areola-nipple compound seems to be oncologically safe and does not increase local recurrences, compared to the previous techniques. Moreover, it is associated with better aesthetic results and patients’ higher satisfaction.

Breast cancer is the commonest cause of cancer-related deaths in women globally. It is seen to affect average 1 in every 8 women (12% lifetime risk in average risk population). Invasive mammary carcinoma is of two types: ductal or lobular type and these may further show various histological subtypes. Invasive ductal carcinomas show invasion of tumor cells beyond basement membrane. The commonest variety is the no special type (NST) or not otherwise specified (NOS). Special types like medullary, mucinous, and tubular carcinoma are seen in 10%. ILC is more common in older age group and represents about 8–10% of all breast cancers. ILC invades surrounding breast tissue in “single cell fashion” without invoking much desmoplastic tissue reaction and often coexists with lobular neoplasia (LCIS and ALH).

Background The modified Gompertz equation has been proposed to fit experimental data for direct current treated tumors when multiple-straight needle electrodes are individually inserted into the base perpendicular to the tumor long axis. The aim of this work is to evaluate the efficacy of direct current generated by multiple-electrode arrays on F3II mammary carcinoma that grow in the male and female BALB/c/Cenp mice, when multiple-straight needle electrodes and multiple-pairs of electrodes are inserted in the tumor. Methods A longitudinal and retrospective preclinical study was carried out. Male and female BALB/c/Cenp mice, the modified Gompertz equation, intensities (2, 6 and 10 mA) and exposure times (10 and 20 min) of direct current, and three geometries of multiple-electrodes (one formed by collinear electrodes and two by pair-electrodes) were used. Tumor volume and mice weight were measured. In addition, the mean tumor doubling time, tumor regression percentage, tumor growth delay, direct current overall effectiveness and mice survival were calculated. Results The greatest growth retardation, mean doubling time, regression percentage and growth delay of the primary F3II mammary carcinoma in male and female mice were observed when the geometry of multiple-pairs of electrodes was arranged in the tumor at 45, 135, 225 and 325o and the longest exposure time. In addition, highest direct current overall effectiveness (above 66%) was observed for this EChT scheme. Conclusions It is concluded that electrochemical therapy may be potentially addressed to highly aggressive and metastic primary F3II murine mammary carcinoma and the modified Gompertz equation may be used to fit data of this direct current treated carcinoma. Additionally, electrochemical therapy effectiveness depends on the exposure time, geometry of multiple-electrodes and ratio between the direct current intensity applied and the polarization current induced in the tumor.

Focal radiation therapy has the potential to generate systemic tumor-targeting immune responses so potent as to eradicate anatomically distant, non-irradiated malignant lesions, a phenomenon commonly referred to as “the abscopal response.” In cancer patients, bona fide abscopal responses are rare, although the recent introduction of immune checkpoint blockers into the clinical practice has significantly increased their incidence. In rodents, abscopal responses can be conveniently modeled by establishing two, slightly asynchronous and anatomically distant subcutaneous tumors in syngeneic immunocompetent hosts, provided that the therapeutic partners of radiation potentially included in the regimen of choice do not mediate systemic anticancer effects per se. Here, we describe such method to monitor abscopal responses based on mammary carcinoma TSA cells implanted in syngeneic immunocompetent BALB/c mice. With minor variations, the same technique can be conveniently applied to a variety of transplantable mouse tumors.

Made available in DSpace on 2020-12-12T01:58:41Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-01-01 Tumor-associated macrophages (TAM) are related to poor prognosis in canine mammary tumors (CMT). An association between TAM and sustained angiogenesis has been implicated with malignancy; however, comparison of the expression of TAM and vascular endothelial growth factor (VEGF) in different histologic types of CMT has not been completely studied. The objective of this study was to evaluate the immunostaining of TAM and VEGF in four different types of malignant CMT. Ninety-nine mammary carcinomas [tubular (29), tubulopapillary (22), mixed-type (28) and solid carcinoma (20)] were evaluated by immunohistochemical staining using MAC387 and VG-1 to detect TAM and VEGF immunoexpression, respectively. The total number of positive macrophages within the tumor was used for TAM immunolabeling and a score of four categories was used for VEGF immunolabeling. TAM immunoexpression was found to be statistically higher in tubular carcinomas than in solid carcinomas (P=0.0015). Differences between other types of carcinoma were not statistically significant. VEGF score was higher in tubular, papillary and mixed-type carcinomas than in solid carcinomas (P

Cancer of unknown provenance is a rare disease, accounting approximately for up to 1% of all breast cancers. A 68-year-old female was admitted to the Medical Oncology Unit of Policlinico Universitario G.Martino because of diffused bone-involvement, with mixed (osteolytic/osteoblastic) features, which interested almost every skeletal structure of the body (vertebral bodies of the entire column, costal skeleton, sternum, proximal third of both humeri, scapulae, clavicles, pelvis and femurs), suspicious for metastatic disease.

Context.—Invasive micropapillary carcinoma (IMPC) is a distinct variant of mammary carcinoma in which tumor cells are arranged in morulelike clusters devoid of fibrovascular cores and situated within empty stromal spaces. Identification of IMPC can be achieved by the assessment of morphologic features in conjunction with the characteristic “inside-out” staining pattern of epithelial membrane antigen and sialyl Lewis X highlighted by immunohistochemical analysis. Although recognizing micropapillary architecture is often not challenging, the criteria for distinguishing between mixed and pure IMPC remain imprecise. Some mucin-producing carcinomas can also have micropapillary histology, but there is no consensus on whether these tumors are variants of IMPC or mucinous carcinomas. The molecular genetic studies demonstrate that IMPCs have distinct molecular genetic profiles, supporting the theory that they constitute distinct pathologic entities. However, genomic analyses have not identified any specific genomic aberration that may explain the distinctive morphology and clinical behavior of IMPC.Objective.—To provide an overview on the current concepts in the diagnosis and pathogenesis of IMPC of the breast, incorporating recent molecular genetic advances and prognosis-based reclassification.Data Sources.—PubMed search and the cited references were reviewed.Conclusions.—The recent evolution of prognosis-based reclassification and molecular genetic advances has enhanced our knowledge of the pathogenesis of IMPC of the breast. Additional studies might reveal consistent molecular alterations that underlie the formation of the inside-out growth pattern, and they might elucidate the molecular mechanisms responsible for the unfavorable clinical behavior of IMPC.

In human breast cancer, both circulating tumour cells (CTCs) in peripheral blood and disseminated tumour cells (DTCs) in the bone marrow are predictive of short survival and may be used as liquid biopsy to guide therapy. Herein we investigate, for the first time, the feasibility to quantify CTCs and DTCs in canine metastatic mammary carcinoma (MMC) with the automated CellSearch platform, which identifies tumour cells by immune-magnetic enrichment and fluorescent labelling. Using this approach before start of treatment, we could detect at least 1 CTC per 7.5 mL of peripheral blood in 12 out of 27 evaluable samples (44.4%) and at least 1 DTC per 1 mL of bone marrow in 11 out of 14 evaluable samples (78.6%). Conversely, we did not find any CTCs in the healthy, negative control dogs (n = 5) that we analysed in parallel. Interestingly, the levels of CTCs/DTCs and the prevalence of positive dogs closely resemble results obtained by CellSearch assay in metastatic breast cancer patients at diagnosis. Moreover, in the canine cohort, the presence of CTCs was significantly associated with poor outcome. These observations identify the first actionable marker in veterinarian oncology to guide treatment of canine MMC. Furthermore, our findings have important implications for human research, since it reinforce the value of canine MMC as model useful to speed up pharmacological studies with primary endpoint of overall survival, given the reduced life-span of the canine species.

The aim of this study was to relate the serum concentration IL-6, IGF-1, leptin and estrogen in non-castrated bitches with or without overweight and early stage mammary carcinomas. Forty-three bitches were divided into four groups, two groups without mammary carcinomas with and without overweight, and two groups with mammary carcinomas with and without overweight. Overweight bitches, with or without mammary carcinomas, were statistically different from bitches by ideal weight, in relation to ECC, IMCC and body fat percentages (P< 0.0001). There was a positive correlation between ECC and IMCC (P< 0.0001), ECC and % GC (P< 0.0001), and IMCC and % GC (P< 0.0001). A positive correlation was found between serum leptin and IL-6 (P= 0.0451) and leptin and IGF-1 (P= 0.05). A positive correlation (P= 0.0053) between ECC and leptin was found in the analysis of body evaluation methods and serum concentrations, and a negative correlation between ECC and IL-6 (P= 0.0435). Among the fat percentage and the leptin concentration, there was a positive correlation (P= 0.0016), as found between the IMCC and leptin (P= 0, 0209). In this study, no association was observed between excessive weight and the presence of early stage mammary carcinomas. O objetivo deste estudo foi relacionar a concentração sérica de IL-6, IGF-1, leptina e estrogênio em cadelas não castradas com ou sem excesso de peso e carcinomas mamários em estágio inicial. Quarenta e três cadelas foram divididas em quatro grupos, dois grupos sem carcinoma mamário com e sem sobrepeso e dois grupos com carcinoma mamário com e sem sobrepeso. Cadelas com excesso de peso, com ou sem carcinoma mamário, foram estatisticamente diferentes das cadelas quanto ao peso ideal, em relação ao ECC, IMCC e percentuais de gordura corporal (P< 0,0001). Houve correlação positiva entre ECC e IMCC (P

International audience; Background: Feline mammary carcinomas (FMCs) are characterized by a high frequency of metastatic spread. The clinical TNM (Tumor, Node, Metastasis) system is used to describe local, regional, and distant tumor extent within the patient, but few publications confirmed its association with survival in cats with FMC. The purpose of this study was to determine if the histological staging system proposed for dogs in part 1 of this article had significant association with prognosis in cats.Materials and Methods: This retrospective study included 395 female cats with a surgically removed mammary carcinoma, with a 2-year follow-up. Invasiveness (distinction between in situ and invasive FMCs), the pathologic tumor size (pT), lymphovascular invasion (LVI), and the pathologic nodal stage (pN) defined a 5-stage system: Stage 0 (FMCs in situ), Stage I (pT1, LVI–, pN0–pNX), Stage II (pT2, LVI–, pN0–pNX), Stage IIIA (pT1, LVI+ and/or pN+), and Stage IIIB (pT2, LVI+ and/or pN+), where pT1 was ≤20 mm, pT2 was >20 mm, and pNX corresponded to unsampled draining lymph node.Results: Higher histological stages were associated with reduced disease-free interval, overall survival, and specific survival. For cancer-specific survival, by univariate analysis (p < 0.0001), median survival times and 1-year specific survival rates (1ySSR) were: stage 0 (1484 days; 1ySSR = 85%; N = 55; 14% of the cats), stage I (808 days; 1ySSR = 76%; N = 103; 26%), stage II (377 days; 1ySSR = 51%; N = 56; 14%), stage IIIA (448 days; 1ySSR = 60%; N = 83; 21%), and stage IIIB (207 days; 1ySSR = 29%; N = 98; 25%). The histological stages were also associated with specific survival by multivariate analysis (Hazard Ratio (HR) = 2.72 for stage IIIB, HR = 1.76 for stage IIIA, HR = 1.50 for stage II compared with stage I), independently of Progesterone Receptor expression (HR = 0.34 for PR+ compared with PR– FMCs) and tumor-associated inflammation (HR = 1.33 when moderate to severe compared with absent to mild).Conclusion: A same histological staging system could be applied in dogs and cats with mammary carcinoma to refine prognosis assessment. In the near future, a preoperative complete tumor clinical staging and treatment based on the published standard of care should be performed in order to better validate the histological staging system here proposed.

portuguesOs tumores mamarios caninos sao considerados os mais frequentes em cadelas, alem de apresentarem grande relevância na oncologia veterinaria, porem a doenca metastatica ainda e um desafio que compreende mecanismos moleculares nao totalmente esclarecidos. Um numero crescente de estudos na medicina humana tem sugerido que alteracoes epigeneticas, tais como metilacao do DNA e modificacao das histonas sao eventos predominantes na celula tumoral para aquisicao do fenotipo metastatico, participando da regulacao de sinais oncogenicos associados com a disseminacao do tumor. Dentre as alteracoes epigeneticas, os miRNAs se destacaram nos ultimos anos apresentando um papel fundamental na tumorigenese. Ainda existem poucos estudos avaliando o papel dos miRNAs em tecidos mamarios caninos. Assim, com este trabalho objetiva-se revisar o papel dos miRNAs no câncer com foco especial nos tumores de mama de cadelas. Palavras-chave: oncologia; cao; carcinoma mamario e miRNA EnglishMammary tumors are the most frequent tumors reported in female dogs and have great relevance in veterinary oncology; however, little is known about the molecular mechanisms involved in the development of metastasis. An increasing number of human studies have suggested that epigenetic alterations, such as DNA methylation, miRNA, and histone modifications, are the predominant events leading to the metastatic phenotype in tumor cells and participate in regulating oncogenic signals associated with tumor spread. Among these epigenetic alterations, miRNAs have stood out in recent years, presenting a fundamental role in tumorigenesis. There are still few studies evaluating the role of miRNAs in canine mammary tissues. Thus, this paper aims to review the role of miRNAs in cancer with a special focus on canine mammary tumors. Key words: oncology; dog; mammary carcinoma; miRNA

Made available in DSpace on 2019-10-06T15:26:28Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-10-01. Added 1 bitstream(s) on 2019-10-09T18:34:48Z : No. of bitstreams: 1 S0100-736X2018001001949.pdf: 836234 bytes, checksum: b5f89c23f187e225d1b4a30e3eec6399 (MD5) In view of the fact that cancer is considered a chronic disease that can interfere with hormonal homeostasis by means of cytokines, we hypothesized that, even at early stages, mammary carcinoma is able to alter the balance of the hypothalamic-pituitary-thyroid and hypothalamic-pituitary-adrenal axes. To test this hypothesis, the serum concentrations of basal cortisol, thyroxine (T4), free thyroxine (fT4), and thyroid-stimulating hormone (TSH) were evaluated in 20 unspayed bitches that had a histopathological diagnosis of grade 1 mammary carcinoma at clinical stage I according to the World Health Organization (WHO) classification (T1N0M0). The control animals comprised 10 unspayed bitches in perfect health conditions that were matched with those with mammary carcinoma by age. No significant differences regarding the concentrations of basal cortisol, TSH, t4, and fT4 were found between the bitches carrying early stage mammary carcinoma when compared to the control group. This suggests that, even if malignant, early-stage mammary carcinomas do not exhibit the ability to alter the concentrations of hormones produced by the hypothalamic-pituitary-adrenal or hypothalamic-pituitary-thyroid axes. Universidade de Franca (Unifran), Avenida Dr. Armando de Sáles Oliveira 201 Faculdade de Ciências Agrárias e Veterinária (FCAV) Universidade Estadual Paulista (Unesp) Campus Jaboticabal, Via de Acesso Prof. Paulo Donato Castelane s/n Faculdade de Medicina Veterinária Universidade Federal de Uberlândia, Avenida Pará 1720 Faculdade de Ciências Agrárias e Veterinária (FCAV) Universidade Estadual Paulista (Unesp) Campus Jaboticabal, Via de Acesso Prof. Paulo Donato Castelane s/n

In tumor microenvironment, tumor-associated macrophages (TAMs) are implicated in cancer sustainment, metastasis, and drug resistance, raising a growing interest as targets in cancer therapy. Since the bisphosphonate zoledronate has proven to affect TAMs’ functions, the anti-tumor effect of single or repeated administrations of red blood cells (RBCs) encapsulating zoledronate was evaluated in a mouse model of mammary carcinoma. The obtained results showed that loaded RBCs, but not free zoledronate, caused a significant (p

Relative to the dog, integration of the cat into the “One Health” concept has been more restricted, particularly in the field of molecular oncology. Beyond the continual need to enhance the sophistication of feline healthcare per se, the unique spectrum of naturally-occurring cancers in the cat offers tremendous opportunities for comparative and translational advances that may have mutual benefit for human and veterinary medicine. The study of feline cancers additionally may generate new insight into underexplored aspects of tumor biology that are less accessible in other species, such as the relationship between chronic inflammation and neoplasia, and the role of viruses in malignant transformation. Several factors that have hindered molecular studies of feline cancers have now been surmounted, with the most fundamental step forward coming from the development of a high-quality reference genome sequence assembly for the cat. This article reviews landmark studies that have led to our current appreciation of feline genome architecture, and outlines techniques used in cancer cytogenomics, from conventional karyotyping analysis through to the development of genomic microarrays and beyond. A summary of progress in the identification and characterization of chromosomal aberrations in feline cancers is provided using examples from studies of injection-site sarcomas, lymphomas and mammary tumors.

Two male rats (Rattus norvegicus; 18 and 24 months old), were referred for treatment of large masses located in the axillary area. Following total body radiography and hematological and serum biochemical analysis, the rats were anesthetized, and the masses were surgically removed. Both lesions were diagnosed as mammary carcinoma based on histopathological diagnosis. The tumor beds were treated with two sessions of electrochemotherapy (ECT), two weeks apart. ECT involved cisplatin administration in the tumor bed, followed by a series of eight biphasic electric pulses. The treatment was well tolerated, and the rats were disease-free after 10 and 14 months. Therefore, adjuvant ECT resulted in good local control of mammary carcinoma and can potentially be used for adjuvant treatment of pet rats with cutaneous and adnexal tumors.

Anthropogenic carbon nanotubes, with a fibrous structure and physical properties similar to asbestos, have recently been found within human lung tissues. However, the reported carbon-nanotube-elicited pulmonary pathologies have been mostly confined to inflammatory or neoplastic lesions in the lungs or adjacent tissues. In the present study, we demonstrate that a single pulmonary exposure to multi-walled carbon nanotubes dramatically enhances angiogenesis and the invasiveness of orthotopically implanted mammary carcinoma, leading to metastasis and rapid colonization of the lungs and other organs. Exposure to multi-walled carbon nanotubes stimulates local and systemic inflammation, contributing to the formation of pre-metastatic and metastatic niches. Our study suggests that nanoscale-material-elicited pulmonary lesions may exert complex and extended influences on tumour progression. Given the increasing presence of carbon nanotubes in the environment, this report emphasizes the urgent need to escalate efforts assessing the long-term risks of airborne nanomaterial exposure in non-lung cancer progression.

Two new hederagenin-type saponins, staunoside G (1) and staunoside H (2), along with twelve known triterpenoid saponins, were isolated from stems of Stauntonia obovatifoliola Hayata ssp. intermedia. Their structures were determined by analysis of HR-EI-MS, and 1D- and 2D-NMR data, and comparison with those in literature. The two new compounds showed moderate cytotoxicities against three tumor cells, i.e., A549 (lung carcinoma), 4T1 (mammary carcinoma), and HeLa (cervical carcinoma).

Patient: Female, 70 Final Diagnosis: Primary invasive mucinous carcinoma arising from ectopic breast tissue Symptoms: Axillary mass Medication: Adjuvant hormonal therapy and irradiation to the ipsilateral axilla Clinical Procedure: Wide local excision of ectopic breast carcinoma with lymphatic mapping and sentinel lymphadenectomy Specialty: Surgery Objective: Rare disease Background: Invasive mucinous carcinoma arising in ectopic axillary breast tissue is an uncommon diagnosis. While some published medical literature makes recommendations regarding the management of ectopic primaries, many of these recommendations are outdated. We therefore hope to provide general guidance with the management of this rare entity. Case Report: We report a case of a 70-year-old woman with primary invasive mucinous carcinoma of ectopic breast tissue. A literature study was performed on primary ectopic breast carcinoma. This case report with review of the literature was performed to provide rationales for a more conservative treatment based upon current data and treatment paradigms. Although the diagnosis of primary ectopic breast carcinoma is uncommon, the presence of a suspicious nodule along the mammary ridge should alert the clinician to consider the possibility of this diagnosis. A mammogram and ultrasound of the nodule were performed and the suspicious nodule was biopsied, confirming the diagnosis. Breast conservation was performed with standard nodal evaluation. Conclusions: The management of primary ectopic breast carcinoma should be based upon current breast conservation techniques of orthotopic breast cancer. Current data suggest that standard treatment paradigms remain applicable to this rare clinical entity.

Background: The GRPR-antagonist-based radioligands [67/68Ga/111In/177Lu]NeoBOMB1 have shown excellent theragnostic profiles in preclinical prostate cancer models, while [68Ga]NeoBOMB1 effectively visualized prostate cancer lesions in patients. We were further interested to explore the theragnostic potential of NeoBOMB1 in GRPR-positive mammary carcinoma, by first studying [67Ga]NeoBOMB1 in breast cancer models; Methods: We investigated the profile of [67Ga]NeoBOMB1, a [68Ga]NeoBOMB1 surrogate, in GRPR-expressing T-47D cells and animal models; Results: NeoBOMB1 (IC50s of 2.2 ± 0.2 nM) and [natGa]NeoBOMB1 (IC50s of 2.5 ± 0.2 nM) exhibited high affinity for the GRPR. At 37 °C [67Ga]NeoBOMB1 strongly bound to the T-47D cell-membrane (45.8 ± 0.4% at 2 h), internalizing poorly, as was expected for a radioantagonist. [67Ga]NeoBOMB1 was detected >90% intact in peripheral mouse blood at 30 min pi. In mice bearing T-47D xenografts, [67Ga]NeoBOMB1 specifically localized in the tumor (8.68 ± 2.9% ID/g vs. 0.6 ± 0.1% ID/g during GRPR-blockade at 4 h pi). The unfavorably high pancreatic uptake could be considerably reduced (206.29 ± 17.35% ID/g to 42.46 ± 1.31% ID/g at 4 h pi) by increasing the NeoBOMB1 dose from 10 pmol to 200 pmol, whereas tumor uptake remained unaffected. Notably, tumor values did not decline from 1 to 24 h pi; Conclusions: [67Ga]NeoBOMB1 can successfully target GRPR-positive breast cancer in animals with excellent prospects for clinical translation.

Mammary carcinomas are relatively common ailments among female canines aged around 10 years old, presenting an important morbidity with an average survival of five years. The cytoinclusion technique is frequently employed in human medicine as the investigative method of choice as it quickly provides resources for the determination of the correct therapeutic response, however, the effectiveness of the technique in canines remains understudied in veterinary medicine. This study aims at evaluating the degree of correlation with immunohistochemical marking for cytokeratin 5 (CK5), oestrogen and progesterone receptors (ER and PR) between the cytoinclusion and the histopathology technique in mammary carcinomas. Twenty-five samples of mammary carcinoma, both for the cytoinclusion and histopathological techniques were submitted for histological processing; microscope slides were created for hematoxylin-eosin (HE) staining and the immunohistochemical technique (IHC) was assessed for the ER, PR and CK5 receptors. Through the HE staining, we reached a concordance rate of 100% between the cytoinclusion and the histopathological analysis in the diagnosis of carcinomas. The immunohistochemical assay presented sensitivity of 85.71%, 95.45% and 100% and Cohen’s kappa of 0.78, 0.84 and 0.95 for ER, PR and CK5, respectively, as well as 100% specificity and P

The aim of this study was to determine whether α-linolenic acid (ALA ω-3 fatty acid) enriched diet affects growth parameters when applied to a syngeneic model of mammary carcinoma. Materials and methods: BALB/c mice were divided and fed with: 1) a chia oil diet, rich in ALA or 2) a corn oil diet, rich in linoleic acid (LA ω-6 fatty acid). Mice were subcutaneously inoculated with a tumor cell line LM3, derived from a murine mammary adenocarcinoma. Results: After 35 days, tumor incidence, weight, volume and metastasis number were lower in the ALA-fed mice, while tumor latency time was higher, and the release of pro-tumor metabolites derived from ω-6 fatty acids decreased in the tumor. Compared to the control group, a lower number of mitosis, a higher number of apoptotic bodies and higher T-lymphocyte infiltration were consistently observed in the ALA group. An ALA-rich diet decreased the estrogen receptor (ER) α expression, a recognized breast cancer promotor while showing an opposite effect on ERβ in tumor lysates. Conclusion: These data support the anticancer effect of an ALA-enriched diet, which might be used as a dietary strategy in breast cancer prevention. Fil: Vara Messler, Marianela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina. Università di Padova; Italia. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas; Argentina Fil: Pasqualini, María Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas; Argentina Fil: Comba, Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas; Argentina Fil: Silva, Renata Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina. Universidad Nacional de Cordoba. Facultad de Medicina. Instituto de Biologia Celular; Argentina Fil: Buccellati, Carola. Università degli Studi di Milano; Italia Fil: Trenti, Annalisa. Università di Padova; Italia Fil: Trevisi, Lucia. Università di Padova; Italia Fil: Eynard, Aldo Renato. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina Fil: Sala, Angelo. Università degli Studi di Milano; Italia. Italian National Research Council. Institute of Biomedicine and Molecular Immunology; Italia Fil: Bolego, Chiara. Università di Padova; Italia Fil: Valentich, Mirta Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina