Tyrosine kinase inhibitors as an alternative treatment in canine mast cell tumor.

The current gold standard treatment for canine mast cell tumors (MCT) uses vinblastine sulfate (VBL) as chemotherapy, although tyrosine kinase inhibitors (TKI) have recently been shown to be worthy candidates for treatment. This systematic review aimed to analyze the overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and complete (CR) or partial response (PR) in dogs with MCT treated with TKI compared to standard VBL treatment. The systematic review was registered in the Open Science Framework (OSF) database under the identifier 10.17605/OSF.IO/WYPN4 (https://osf.io/). An electronic search was performed in nine databases. References from eligible studies were also selected to find more registers. A total of 28 studies met the eligibility criteria, and one more was recovered from the references of eligible studies, totaling 29 selected studies. The overall response rate, complete response, and partial response were higher in dogs treated with tyrosine kinase inhibitors than in dogs treated with vinblastine. The overall survival and progression-free survival of vinblastine-treated dogs were higher compared to tyrosine kinase inhibitors-treated dogs. Dogs with mutated KIT treated with tyrosine kinase inhibitors have longer overall survival and progression-free survival compared to those treated with vinblastine. It is important to consider the limitation of the study which should temper the interpretation of the results, videlicet, the extracted data lacked sample standardization and included variables such as animal characteristics, mutation detection methods, tumor characteristics, and treatment types which may have influenced the outcome of the study. Systematic review registration: https://osf.io/, identifier: 10.17605/OSF.IO/WYPN4.

The impact of antifungal prophylaxis in patients diagnosed with acute leukemias undergoing induction chemotherapy: a systematic review and meta-analysis.

Acute leukemias are complex diseases to treat and have a high mortality rate. The immunosuppression caused by chemotherapy also causes the patient to become susceptible to a variety of infections, including invasive fungal infections. Protocols established in many countries attempt to prevent these infections through the use of pharmacological antifungal prophylaxis. This systematic review and meta-analysis investigates the existing evidence for the use of antifungal prophylaxis in patients undergoing induction chemotherapy for acute leukemia, and how prophylaxis can affect treatment response and mortality. Through the use of a population-variable-outcome strategy, keywords were utilized to search online databases. The included studies were selected and the data was collected to develop descriptive results for all studies, and, for studies that met the criteria, a meta-analysis of the Relative Risk (RR) was analyzed for infection rates, in-hospital mortality, and complete remission. A total of 33 studies were included in this systematic review, with most studies presenting positive results (n = 28/33) from the use of antifungal prophylaxis. Using a random effects model, the pooled results of the meta-analysis presented lower invasive fungal infections in AML (RR: 0.527 (95% CI: 0.391; 0.709). p < 0.001). p < 0.001) and ALL (RR: 0.753 (95% CI: 0.574; 0.988). p = 0.041). when antifungal prophylaxis was used. No discernible difference was encountered in the rate of complete remission when using prophylaxis. Antifungal prophylaxis provides a lower risk of invasive fungal infections and in-hospital mortality in acute leukemia patients undergoing induction chemotherapy.

Reactivation of natural killer cells with monoclonal antibodies in the microenvironment of malignant neoplasms.

Natural killer cells are critical players in the antitumor immune response due to their ability to destroy target cells through cytotoxic activity and other means. However, this response is inhibited in the tumor microenvironment, where a crippling hypoxic environment and several inhibitory molecules bind to NK cells to trigger an anergic state. Inhibitory receptors such as PD-1, NK2GA, KIR, TIGIT, and LAG-3 have been associated with inhibition of NK cells in multiple cancer types. Binding to these receptors leads to loss of cytotoxicity, lower proliferation and metabolic rates, and even apoptosis. While these receptors are important for avoiding auto-immunity, in a pathological setting like malignant neoplasms they are disadvantageous for the individual's immune system to combat cancer cells. The use of monoclonal antibodies to block these receptors contributes to cancer therapy by preventing the inhibition of NK cells. In this review, the impact of NK cell inhibition and activation on cancer therapy was summarized and an overview of the blockade of inhibitory pathways by monoclonal antibodies was provided.

Undetected αKlotho in serum is associated with the most aggressive phenotype of breast cancer.

Klotho, a cellular anti-senescence protein, is related to antitumor actions, growth regulation, proliferation and invasiveness in several types of tumor, including breast cancer. The present study aimed to analyze the serum levels of αKlotho in patients with breast cancer according to histopathological and immunohistochemical variables. A total of 74 patients and 60 healthy controls were recruited. Peripheral blood samples were collected and serum levels were assessed by sandwich ELISA. Clinical and diagnostic data were obtained from medical records and databases of the Clinical Hospital of the Federal University of Uberlândia (Uberlândia, Brazil). The results indicated no difference in the levels of αKlotho between patients and controls (P=0.068); however, the number of patients with breast cancer with undetectable αKlotho was high (n=52). Thus, the variables that were associated with the lowest survival rates were analyzed, relating them to undetectable αKlotho. Among cases of metastatic tumors or tumors with poor differentiation, positive lymph node status and triple-negative status, patients with undetectable αKlotho predominated and had unfavorable overall survival. Due to the significant results obtained in triple-negative patients, an in vitro analysis was performed to determine whether estrogen receptors (ERs) have a role in αKlotho production. Treatment of MCF-7 cells with ER agonists, estradiol (E2) and diarylpropionitrile (DPN), resulted in increases in αKlotho expression and supernatant levels of both agonists, demonstrating a direct association between the ER and Klotho production; of note, the ERß-specific agonist DPN tripled αKlotho expression when compared to E2 (P=0.078). These data suggested that undetectable αKlotho in the serum of patients with breast cancer is related to unfavorable histopathological variables and poor prognosis and ERs possibly have an important role in maintaining adequate quantities of αKlotho.

Chemokines and the extracellular matrix: Set of targets for tumor development and treatment.

The extracellular matrix (ECM) consists of various molecules that support tissue cells, including proteins, fibronectin, laminin, collagen IV, and glycosaminoglycans. In addition to interactions between the ECM and cells, the ECM also interacts with chemokines, and growth factors, and these interactions ensure cell survival, development, differentiation, and migration of both immune system cells and tumor cells. This review provides an overview of the mechanisms of interaction between the ECM and chemokines, focusing on the tumor microenvironment and the modulation of these elements as a target for therapies in several types of cancer.

Current perspectives of osteoclastogenesis through estrogen modulated immune cell cytokines.

Estrogen is a hormone responsible for modulating several physiological processes such as immune response and bone homeostasis. Physiological fluctuations of estrogen concentration are one of the defining principles behind its mechanism. In cases of estrogen deficiency, such as in menopausal women, a more intense bone resorption may occur due to an increase in osteoclast activity. One of the main factors that influence osteoclast formation and response is the immune system, mainly through cytokines secreted by B and T cells. The purpose of this review is to highlight how estrogen can modulate the secretion of cytokines that can alter bone physiology, thereby establishing an axis between estrogen, immune cells, and osteoclastogenesis.

Correlation Between First Morning Single Void and 24-Hour Urines: The Reliability to Quantify Niacin Status.

BACKGROUND The current common practice when using urine as a biomarker for vitamin excretion is to use a 24-hour sample for analysis. Due to the difficulty involved in this process, we attempted to find an alternative solution through the use of a single first morning void. The aim of our study was to investigate if there is a correlation between the first morning single void and the 24-hour collections of urines for the urine metabolite of niacin, N-1-methylnicotinamide (N1MN), and to test the reliability of utilizing a method using first morning single void collections corrected with the concentration of urine creatinine. MATERIAL AND METHODS All urine samples were collected from 30 healthy adult volunteers over the age of 18 years: 20 females and 10 males. Samples were collected after discarding the first morning urine and collecting every other urine voided during the next 24 hours including the first morning urine of the day after in 2 separate vessels. We analyzed the concentration of N1MN by high performance liquid chromatography and the concentration of creatinine by a commercial kit by spectrophotometry. The B3 excretion was expressed as the ratio of N1MN to creatinine. RESULTS We found a significant correlation between the ratios of first morning single void and 24-hour urines. When comparing males and females, the ratio demonstrated a significant correlation as well. CONCLUSIONS Our results demonstrated that it is possible to substitute a 24-hour collection with a first morning single void urine for the estimation of N1MN excretion.