Interferon-gamma in mobilized stem cells: A possible prognostic marker in early post-transplant management in multiple myeloma.

INTRODUCTION: A complex network of cytokines in the bone marrow microenvironment has been implicated as an important factor in the pathogenesis of multiple myeloma (MM). Different cytokines have been studied in MM, both in peripheral blood and/or bone marrow, but there are few data correlating cytokines in leukapheresis product with post-transplant response depth to treatment. MATERIALS AND METHODS: In a retrospective cross-sectional study, levels of tumor necrosis factor alpha (TNF-α), transforming growth factor beta-1 (TGF-ß1) and interferon gamma (IFN-γ) in peripheral hematopoietic stem cells/leukapheresis product (PHSC) of patients with MM eligible for transplantation were evaluated. Association of these cytokines with certain factors such as mobilized CD34 + cells/kg, staging, response to treatment and outcome were analyzed. RESULTS: The median baseline IFN-γ level was 826.4 pg/mL. IFN-γ levels in the leukapheresis product were significantly lower in patients who achieved complete response (CR) three months post-transplant when compared to patients with very good partial response (VGPR) (674.75 ±â€¯80.32 pg/mL versus 939.6 ±â€¯106.8 pg/mL, p = 0.02), respectively. Patients who lost depth of response at the third-month post-transplant had a median level of IFN-γ 1133, being considered "high-expressors" of IFN-γ, while those reaching improved response were called "low-expressors" (median level IFN-γ 485 pg/mL). Overall and progression-free survival did not have a statistically significant correlation with TNF-α, TGF-ß1 or IFN-γ, as well as TNF-α and TGF-ß1 levels in post-transplant response assessment. CONCLUSION: IFN-γ in PHSC seems to be an important biomarker of loss of response in MM, suggesting a role in early post-transplant therapeutic management.

Chemotherapy induces plasmatic antioxidant changes in pediatric patients with acute lymphoid leukemia B that correlate to disease prognosis.

Pediatric acute lymphoid leukemias (ALL) is the most common childhood cancer, and cytotoxic chemotherapy remains the primary treatment option. Chemotherapic drugs act by oxidative stress generation, but their clinical meaning is poorly understood. During the chemotherapy schedule, this study evaluated the antioxidant profile of peripheral blood samples from 34 patients diagnosed with type B-cell ALL (B-ALL). Peripheral blood samples were collected at diagnosis (D0) and during the induction, consolidation, and maintenance phases. The plasma total antioxidant capacity (TRAP) was determined using the high-sensitivity chemiluminescence technique. Antioxidant levels were higher on D0 compared to day 7 after treatment starting (D7) in the induction phase (28.68-1194.71 µM Trolox, p = 0.0178) and in the high-risk group (age > ten years and/or with white blood cell counts and/or > 50,000 white blood cells/m3 at diagnosis) concerning low-risk patients (253.79-1194.71 µM Trolox, p = 0.0314). Reduced TRAP was also detected in patients who died compared to those who survived (392.42-1194.71 µM Trolox, p = 0.0278). Patients under consolidation (56.14-352.05 µM Trolox, p=<0.0001) and maintenance (30.48-672.99 µM Trolox, p=<0.0001) showed a significant reduction in TRAP levels compared to those from the induction phase (28.68-1390.26 µM Trolox), reaching levels similar to cured patients out of treatment (64.82-437.82 µM Trolox). These findings suggest that the variation of the total antioxidant capacity in B-ALL during chemotherapy is a parameter that correlates to some predictors of disease prognosis.

Comparative Analysis of Systemic and Tumor Microenvironment Proteomes From Children With B-Cell Acute Lymphocytic Leukemia at Diagnosis and After Induction Treatment.

Among the childhood diseases, B-cell acute lymphocytic leukemia (B-ALL) is the most frequent type of cancer. Despite recent advances concerning disease treatment, cytotoxic chemotherapy remains the first line of treatment in several countries, and the modifications induced by such drugs in the organism are still poorly understood. In this context, the present study provided a comparative high-throughput proteomic analysis of the cumulative changes induced by chemotherapeutic drugs used in the induction phase of B-ALL treatment in both peripheral blood (PB) and bone marrow compartment (BM) samples. To reach this goal, PB and BM plasma samples were comparatively analyzed by using label-free proteomics at two endpoints: at diagnosis (D0) and the end of the cumulative induction phase treatment (D28). Proteomic data was available via ProteomeXchange with identifier PXD021584. The resulting differentially expressed proteins were explored by bioinformatics approaches aiming to identify the main gene ontology processes, pathways, and transcription factors altered by chemotherapy, as well as to understand B-ALL biology in each compartment at D0. At D0, PB was characterized as a pro-inflammatory environment, with the involvement of several downregulated coagulation proteins as KNG, plasmin, and plasminogen. D28 was characterized predominantly by immune response-related processes and the super expression of the transcription factor IRF3 and transthyretin. RUNX1 was pointed out as a common transcription factor found in both D0 and D28. We chose to validate the proteins transthyretin and interferon-gamma (IFN-γ) by commercial kits and expressed the results as PB/BM ratios. Transthyretin ratio was augmented after induction chemotherapy, while IFN-γ was reduced at the end of the treatment. Considering that most of these proteins were not yet described in B-ALL literature, these findings added to understanding disease biology at diagnosis and highlighted a possible role for transthyretin and IFN-γ as mechanisms related to disease resolution.

Role of leptin in the pathogenesis of breast cancer / Papel da leptina na patogênese do câncer de mama

A leptina é um pequeno polipeptídeo codificado pelo gene OB, profundamente relacionado com a massa de gordura corporal e o balanço energético. Devido aos seus diversos efeitos biológicos e transdutores de sinal regulados, múltiplas classificações biológicas tem sido atribuídas à leptina, incluindo hormônio,citocina, adipocina, fator de crescimento, e fator de desenvolvimento, dentre outros. Este cenário nos dá uma idéia do tamanho do potencial de efeitos biológicos gerados por esta molécula. A concentração de leptina no corpo é determinada pela quantidade de tecido adiposo; portanto, hiperleptinemia é um achado comum em indivíduos obesos. Além disso, níveis elevados de leptina circulante pode conferirum pior prognóstico para qualquer condição patológica. Apesar da história da leptina ter sido reportada por mais de 20 anos, sua relação com o câncer ganhou notoriedade nos últimos 10 anos, quando estudos focaram e discutiram o papel da obesidade com um forte fator de risco para o desenvolvimento de câncer.Adicionalmente, evidências crescentes apontam a leptina como mediador primordial da resposta imune, oque agrava o cenário da ocorrência de câncer na presença de obesidade. Assim, a leptina pode apresentar pelo menos duas faces na patogênese do câncer, agindo através de mecanismos imunológicos e não imunológicos.Neste trabalho, revisamos a dinâmica do eixo leptina no câncer de mama e discutimos seu papel na doença, imunopatogênese e prognóstico.

Leptin is a small polypeptide codified by the Obese Gene (OB), deeply related with the body fat massand energetic balance. Due to its diverse biological effects and downstream signal transducers, multipleclassifications have been attributed to leptin, as hormone, cytokine, adypokine, growth factor, anddevelopmental factor, among others. This scenario gives us an idea of the size of the potential biological effects generated by this molecule. The concentration of leptin in the body is determined by the amountof adipose tissue; the refore, hyperleptinemia is a common finding in obese individuals. In addition, highlevels of circulating leptin may confer a poor prognosis for any pathological condition. Although leptin history has been reported for more than 20 years, its relationship with cancer has gained notoriety in the past ten years, where studies focused on discussing the issue of obesity as a strong risk factor for cancer developing. Further, growing evidences have pointed leptin as a pivotal mediator of immune response, which aggravates the scenario of cancer occurrence in the presence of obesity. Therefore, leptin can present at least two faces in the pathogenesis of breast cancer, acting by immune and non-immune mechanisms. In this paper we review the dynamic of the leptin axis in breast cancer and further discussits role in disease, immunopathogenesis and prognosis.