Contribution of non-steroidal anti-inflammatory drugs to breast cancer treatment: In vitro and in vivo studies.

Chronic inflammation plays a crucial role in carcinogenesis. High levels of serum prostaglandin E2 and tissue overexpression of cyclooxygenase-2 (COX-2) have been described in breast, urinary, colorectal, prostate, and lung cancers as being involved in tumor initiation, promotion, progression, angiogenesis, and immunosuppression. Non-steroidal anti-inflammatory drugs (NSAIDs) are prescribed for several medical conditions to not only decrease pain and fever but also reduce inflammation by inhibiting COX and its product synthesis. To date, significant efforts have been made to better understand and clarify the interplay between cancer development, inflammation, and NSAIDs with a view toward addressing their potential for cancer management. This review provides readers with an overview of the potential use of NSAIDs and selective COX-2 inhibitors for breast cancer treatment, highlighting pre-clinical in vitro and in vivo studies employed to evaluate the efficacy of NSAIDs and their use in combination with other antineoplastic drugs.

Açaí (Euterpe oleracea Mart.) Seed Oil and Its Nanoemulsion: Chemical Characterisation, Toxicity Evaluation, Antioxidant and Anticancer Activities.

This study explores a nanoemulsion formulated with açaí seed oil, known for its rich fatty acid composition and diverse biological activities. This study aimed to characterise a nanoemulsion formulated with açaí seed oil and explore its cytotoxic effects on HeLa and SiHa cervical cancer cell lines, alongside assessing its antioxidant and toxicity properties both in vitro and in vivo. Extracted from fruits sourced in Brazil, the oil underwent thorough chemical characterization using gas chromatography-mass spectrometry. The resulting nanoemulsion was prepared and evaluated for stability, particle size, and antioxidant properties. The nanoemulsion exhibited translucency, fluidity, and stability post centrifugation and temperature tests, with a droplet size of 238.37, PDI -9.59, pH 7, and turbidity 0.267. In vitro assessments on cervical cancer cell lines revealed antitumour effects, including inhibition of cell proliferation, migration, and colony formation. Toxicity tests conducted in cell cultures and female Swiss mice demonstrated no adverse effects of both açaí seed oil and nanoemulsion. Overall, açaí seed oil, particularly when formulated into a nanoemulsion, presents potential for cancer treatment due to its bioactive properties and safety profile.

Lifelong exercise training promotes the remodelling of the immune system and prostate signalome in a rat model of prostate carcinogenesis.

This work aimed to understand how lifelong exercise training promotes the remodelling of the immune system and prostate signalome in a rat model of PCa. Fifty-five male Wistar rats were divided into four groups: control sedentary, control exercised, induced PCa sedentary and induced PCa exercised. Exercised animals were trained in a treadmill for 53 weeks. Pca induction consisted on the sequential administration of flutamide, N-methyl-N-nitrosourea and testosterone propionate implants. Serum concentrations of C-reactive protein (CRP) and tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) were not different among groups. Peripheral levels of γδ T cells were higher in Pca exercised group than in the PCa sedentary group (p < 0.05). Exercise training also induced Oestrogen Receptor (ESR1) upregulation and Mitogen-activated Protein Kinase 13 (MAPK13) downregulation, changed the content of the phosphorylated (at Ser-104) form of this receptor (coded by the gene ESR1) and seemed to increase Erα phosphorylation and activity in exercised PCa rats when compared with sedentary PCa rats. Our data highlight the exercise-induced remodelling of peripheral lymphocyte subpopulations and lymphocyte infiltration in prostate tissue. Moreover, exercise training promotes the remodelling prostate signalome in this rat model of prostate carcinogenesis.

Current views on in vivo models for breast cancer research and related drug development.

INTRODUCTION: Animal models play a crucial role in breast cancer research, in particular mice and rats, who develop mammary tumors that closely resemble their human counterparts. These models allow the study of mechanisms behind breast carcinogenesis, as well as the efficacy and safety of new, and potentially more effective and advantageous therapeutic approaches. Understanding the advantages and disadvantages of each model is crucial to select the most appropriate one for the research purpose. AREA COVERED: This review provides a concise overview of the animal models available for breast cancer research, discussing the advantages and disadvantages of each one for searching new and more effective approaches to treatments for this type of cancer. EXPERT OPINION: Rodent models provide valuable information on the genetic alterations of the disease, the tumor microenvironment, and allow the evaluation of the efficacy of chemotherapeutic agents. However, in vivo models have limitations, and one of them is the fact that they do not fully mimic human diseases. Choosing the most suitable model for the study purpose is crucial for the development of new therapeutic agents that provide better care for breast cancer patients.

Klotho in Cancer: Potential Diagnostic and Prognostic Applications.

Klotho proteins, αKlotho, ßKlotho, and γKlotho, exert tumor-suppressive activities via the fibroblast growth factor receptors and multiple cell-signaling pathways. There is a growing interest in Klotho proteins as potential diagnostic and prognostic biomarkers for multiple diseases. However, recent advances regarding their roles and potential applications in cancer remain disperse and require an integrated analysis. The present review analyzed research articles published between 2012 and 2022 in the Cochrane and Scopus scientific databases to study the role of Klotho in cancer and their potential as tools for diagnosing specific cancer types, predicting tumor aggressiveness and prognosis. Twenty-six articles were selected, dealing with acute myeloid leukemia and with bladder, breast, colorectal, esophageal, gastric, hepatocellular, ovarian, pancreatic, prostatic, pulmonary, renal, and thyroid cancers. αKlotho was consistently associated with improved prognosis and may be useful in estimating patient survival. A single study reported the use of soluble αKlotho levels in blood serum as a tool to aid the diagnosis of esophageal cancer. γKlotho was associated with increased aggressiveness of bladder, breast, and prostate cancer, and ßKlotho showed mixed results. Further clinical development of Klotho-based assays will require careful identification of specific tumor subtypes where Klotho proteins may be most valuable as diagnostic or prognostic tools.

A spontaneous ovarian teratoma in an FVB/n female mouse: Case report and literature review.

Background: Teratomas are rare types of germ cell neoplasms composed of various differentiated or undifferentiated tissues. Case Description: A 25-week-old female control FVB /n mouse in a 4-week toxicity study presented abdominal distension and poor body condition. It was euthanized, and the necropsy examination revealed a large mass connected to the tip of the right uterine horn, occupying the entire abdominal cavity. Microscopically, this mass showed areas of epidermal differentiation, with laminated keratin and sebaceous glands, differentiation into respiratory and digestive epithelium, cartilage, bone, and extensive areas of differentiation into the nervous tissue, being classified as an ovarian teratoma. Conclusion: As far as authors know, the occurrence of ovarian teratomas in the FVB/n mouse strain has never been previously described.

Malignancy Associated with Low-Risk HPV6 and HPV11: A Systematic Review and Implications for Cancer Prevention.

High-risk human papillomavirus (HPV) is etiologically related to cervical cancer, other anogenital cancers and oropharyngeal carcinomas. Low-risk HPV, especially HPV6 and HPV11, cause genital warts and laryngeal papillomas. However, the accumulating data suggests that HPV6 and HPV11 may cause malignant lesions at non-cervical anatomic sites. This review aims to estimate the proportions of single and dual HPV6/11 infections in multiple cancers reported in the last 10 years in the Cochrane, Embasa and PubMed databases. Secondly, the genomes of HPV6/11 were compared with the most common high-risk genotype, HPV16, to determine the similarities and differences. A total of 11 articles were selected, including between one and 334 HPV+ cancer patients. The frequencies of single or dual HPV6/11 infections ranged between 0-5.5% for penile and 0-87.5% for laryngeal cancers and were null for vulvar, vaginal and oral cancers. The genomic similarities between HPV6/11 and HPV16 mainly involved the E7 gene, indicating a limited ability to block cell differentiation. The presence of single or dual HPV6/11 infections in variable proportions of penile and laryngeal cancers support the vaccination strategies that cover these genotypes, not only for preventing genital warts but also for cancer prevention. Other risk factors and co-carcinogens are likely to participate in epithelial carcinogenesis associated with low-risk HPV.

Quercus spp. extract as a promising preventive or therapeutic strategy for cancer: A systematic review.

Acorns have traditionally been used in the human diet and for the treatment of specific diseases. Therefore, the present study performed a systematic review of studies which investigated the effects of Quercus spp. extracts in cancer prevention and treatment. A systematic literature search was performed for original records which addressed the anticancer effects of Quercus spp. extract in in vitro and in vivo cancer models. Body composition, food consumption, tumor development and/or toxicity were evaluated in in vivo studies, while cytotoxicity was evaluated in in vitro studies. Few studies and low sample sizes presented a challenge in the drawing of solid conclusions. Overall, the results suggested a positive impact of Quercus spp. extract, by reducing cancer development. Therefore, more studies with different cancer cell lines and animal models to address the efficacy of the acorn extracts in several types of cancer are required. Furthermore, the effects of acorn flour, incorporated in the diet, in an animal model of mammary cancer should be evaluated.

Pharmacological NF-κB inhibition decreases cisplatin chemoresistance in muscle-invasive bladder cancer and reduces cisplatin-induced toxicities.

Most patients with muscle-invasive bladder cancer (MIBC) are not cured with platinum chemotherapy. Up-regulation of nuclear factor kappa light-chain enhancer of activated B cells (NF-κB) is a major mechanism underlying chemoresistance, suggesting that its pharmacological inhibition may increase platinum efficacy. NF-κB signaling was investigated in two patient cohorts. The Cancer Genome Atlas (TCGA) was used to correlate NF-κB signaling and patient survival. The efficacy of cisplatin plus the NF-κB inhibitor dimethylaminoparthenolide (DMAPT) versus cisplatin or DMAPT alone was tested in vitro. Xenografted and immunocompetent MIBC mouse models were studied in vivo. Platinum-naive claudin-low MIBC showed constitutive NF-κB signaling and this was associated with reduced disease-specific survival in TCGA patients. Chemotherapy up-regulated NF-κB signaling and chemoresistance-associated genes, including SPHK1, PLAUR, and SERPINE1. In mice, DMAPT significantly improved the efficacy of cisplatin in both models. The combination preserved body weight, renal function, and morphology, reduced muscle fatigue and IL-6 serum levels, and did not aggravate immuno-hematological toxicity compared with cisplatin alone. These data provide a rationale for combining NF-κB inhibition with platinum-based chemotherapy and conducting a clinical trial in MIBC patients.

Realistic aspects behind the application of the rat model of chemically-induced mammary cancer: Practical guidelines to obtain the best results.

Cancer is one of the most important public health problems worldwide. Despite the great contribution of in-vitro studies for biomedical research, animals are essential to study diseases' biopathology and diagnosis, and searching for new preventive and therapeutic strategies. Breast cancer is currently the most common cancer globally, accounting for 12.5% of all new annual cancer cases worldwide. Although the rat model of mammary cancer chemically-induced is widely used to study this disease, there is a lack of standardization in procedures for cancer induction, sample collection, and analysis. Therefore, it is important to provide a practical guide for researchers aiming to work with this model to make the analysis of results more uniform. Thus, in this review, we provide the researchers with a detailed step-by-step guide to implement a rat model of mammary cancer, based on our wide experience in this field, to obtain the best results, maximum throughput of each experiment, and easy comparison among researches.

An Antibody-Based Survey of Toxoplasma gondii and Neospora caninum Infection in Client-Owned Cats from Portugal.

Toxoplasma gondii and Neospora caninum are obligate intracellular protozoan parasites infecting a wide range of hosts worldwide. However, information on the epidemiology of toxoplasmosis and neosporosis in cats from Portugal is limited. Thus, this study aims to evaluate anti-T. gondii and anti-N. caninum seroprevalence in client-owned cats from Portugal and to identify risk factors using a panel of well-characterized sera. A total of 183 domestic cats were sampled and screened for antibodies against T. gondii and N. caninum using commercial ELISA assays, and their owners answered an online questionnaire designed to obtain background information. The overall anti-T. gondii and anti-N. caninum seroprevalences were 13.1% (CI: 8.97-18.77) and 3.8% (CI: 1.87-7.68), respectively. Univariate analysis revealed that living strictly indoors was a significant protection factor (cOR: 0.053; CI: 0.005-0.627), and the presence of a chronic disease a significant risk factor (cOR: 3.106; CI: 1.062-9.082) to T. gondii seroprevalence. When performing multivariate analysis, only chronic disease (aOR: 57.527; CI: 1.7-1976.7) and seropositivity to N. caninum (aOR: 7.929; CI:0.8-82.9) were found to be a significant risk factor to anti-T. gondii antibodies. To the best of our knowledge, this is the first report of N. caninum seropositivity in cats from Portugal.

Canine and feline papillomaviruses: an update.

Papillomaviruses are small viruses able to cause disease not only in mammalians, but also in birds and reptiles. In recent years, a rising number of papillomaviruses have been identified in dogs and cats, totaling 24 canine papillomavirus (CPV) and six feline papillomavirus (FcaPV). The canine and feline papillomaviruses (CPVs and FcaPVs, respectively) are responsible for multiple lesions in these domestic species but the potential pathological relevance of some recently identified types remains to be determined. CPVs are associated with oral papillomatosis, cutaneous papillomas and viral pigmented plaques, and have been rarely associated with the development of oral and cutaneous squamous cell carcinomas in their canine hosts. FcaPVs are associated with oral papillomas, viral plaques, and Bowenoid in situ carcinomas. The present review provides readers with the more recent advances on dog and cat papillomavirus research, bringing an update on this field to both veterinary practitioners and the virology community at large.

Mammary Glands of Women, Female Dogs and Female Rats: Similarities and Differences to Be Considered in Breast Cancer Research.

Breast cancer is one of the most common and well-known types of cancer among women worldwide and is the most frequent neoplasm in intact female dogs. Female dogs are considered attractive models or studying spontaneous breast cancer, whereas female rats are currently the most widely used animal models for breast cancer research in the laboratory context. Both female dogs and female rats have contributed to the advancement of scientific knowledge in this field, and, in a "One Health" approach, they have allowed broad understanding of specific biopathological pathways, influence of environmental factors and screening/discovery of candidate therapies. This review aims to clearly showcase the similarities and differences among woman, female dog and female rat concerning to anatomical, physiological and histological features of the mammary gland and breast/mammary cancer epidemiology, in order to better portray breast tumorigenesis, and to ensure appropriate conclusions and extrapolation of results among species. We also discuss the major aspects that stand out in these species. The mammary glands of female dogs and women share structural similarities, especially with respect to the lactiferous ducts and lymphatic drainage. In contrast, female rats have only one lactiferous duct per nipple. A comprehensive comparison between humans and dogs is given a special focus, as these species share several aspects in terms of breast/mammary cancer epidemiology, such as age of onset, hormonal etiology, risk factors, and the clinical course of the disease. Holistically, it is clear that each species has advantages and limitations that researchers must consider during the development of experimental designs and data analysis.

The Impact of Resveratrol-Enriched Bread on Cardiac Remodeling in a Preclinical Model of Diabetes.

The World Health Organization aims to stop the rise of diabetes by 2025, and diet is one of the most efficient non-pharmacological strategies used to prevent it. Resveratrol (RSV) is a natural compound with anti-diabetic properties, and incorporating it into bread is a suitable way to make it more accessible to consumers as it can be included as part of their daily diet. This study aimed to evaluate the effect of RSV-enriched bread in preventing early type 2 diabetes cardiomyopathy in vivo. Male Sprague Dawley rats (3 weeks old) were divided into four groups: controls with plain bread (CB) and RSV bread (CBR), and diabetics with plain bread (DB) and RSV bread (DBR). Type 2 diabetes was induced by adding fructose to the drinking water for two weeks followed by an injection of streptozotocin (STZ) (40 mg/kg). Then, plain bread and RSV bread (10 mg RSV/kg body weight) were included in the rats' diet for four weeks. Cardiac function, anthropometric, and systemic biochemical parameters were monitored, as well as the histology of the heart and molecular markers of regeneration, metabolism, and oxidative stress. Data showed that an RSV bread diet decreased the polydipsia and body weight loss observed in the early stages of the disease. At the cardiac level, an RSV bread diet diminished fibrosis but did not counteract the dysfunction and metabolic changes seen in fructose-fed STZ-injected rats.

Studying and Analyzing Humane Endpoints in the Fructose-Fed and Streptozotocin-Injected Rat Model of Diabetes.

This work aimed to define a humane endpoint scoring system able to objectively identify signs of animal suffering in a rat model of type 2 diabetes. Sprague-Dawley male rats were divided into control and induced group. The induced animals drink a 10% fructose solution for 14 days. Then, received an administration of streptozotocin (40 mg/kg). Animals' body weight, water and food consumption were recorded weekly. To evaluate animal welfare, a score sheet with 14 parameters was employed. Blood glucose levels were measured at three time points. After seven weeks of initiating the protocol, the rats were euthanized. The induced animals showed weight loss, polyuria, polyphagia, and polydipsia. According to our humane endpoints table, changes in animal welfare became noticeable after the STZ administration. None of the animals hit the critical score limit (four). Data showed that the most effective parameters to assess welfare in this type 2 diabetes rat induction model were dehydration, grooming, posture, abdominal visualization, and stool appearance. The glycemia was significantly higher in the induced group when compared to the controls (p < 0.01). Induced animals' murinometric and nutritional parameters were significantly lower than the controls (p < 0.01). Our findings suggest that in this rat model of type 2 diabetes with STZ-induced following fructose consumption, our list of humane endpoints is suitable for monitoring the animals' welfare.

Editorial: Special Issue "Addressing New Therapeutic Strategies Using Models".

A disease model displays pathological processes observed in human or animal diseases [...].

Evolution of Models of Prostate Cancer: Their Contribution to Current Therapies.

Prostate cancer (PCa) is among the most frequent cancers worldwide. Nowadays, several therapeutic strategies are available for PCa treatment, namely chemotherapy, immunotherapy, radiotherapy, and hormonal therapy. Despite existing therapeutic approaches, in vitro and in vivo models are essential to better understand cancer development and search for more effective therapies, with a positive impact in cancer patient survival and quality of life. Among several models available, the rat model is the one most frequently used, since it shares anatomical, physiological, pathological, and behavioral features with humans. Animal models can be classified as: spontaneous, chemically-induced; hormonally-induced; implantation of cancer cell lines obtained from humans or from the same species, in the place of disease development or in a different place; and genetically-modified models. The chemically-induced models are among the most frequently used for PCa research. This manuscript provides a comprehensive overview of PCa models, presenting their application, advantages, and disadvantages, and their importance for the development of current therapies for prostate cancer.