Hematological ratios as prognostic indicators in patients with triple-negative breast cancer in southern Brazil

Introduction: The heterogeneous nature and intrinsically aggressive tumor pathology of the triple negative breast cancer subtype results in an unfavorable prognosis and limited clinical success. The use of hematological components of the systemic inflammatory response for patients with triple-negative breast cancer can add important prognostic information to the criteria traditionally used for cancer patients, since inflammation can promote tumor progression support by affecting the stages of tumorigenesis. Objectives: The aim of this study was to evaluate the hematological parameters neutrophil/lymphocyte, monocyte/lymphocyte and platelet/lymphocyte ratios as prognostic indicators in patients with triple-negative breast cancer. Methods: This was a singlecenter retrospective observational study in an oncology referral hospital in the South region of Brazil. Electronic medical records of patients diagnosed with triple-negative breast cancer from 2012 to 2016 were reviewed and analyzed using SPSS. Results: The low blood cell ratio groups had significantly higher overall survival than the high blood cell ratio groups. Univariate analysis also confirmed the correlation of patients in the high blood cell ratio groups with unfavorable results. Conclusions: Hematological components of the systemic inflammatory response are promising prognostic indicators. More studies on the subject should be carried out to assist in future medical decision-making so these parameters of easy assessment and low cost can be introduced in clinical practice.

Impact of Her-2 Overexpression on Survival of Patients with Metastatic Breast Cancer

Introduction: Breast cancer is a complex and heterogeneous disease which is increasingly important as a public health problem. In Brazil, 57,960 new cases have been estimated to be the burden in 2016 and 2017. Despite advances in early diagnosis and therapy, approximately 20-30% of patients, even with early stage lesions, will develop distant metastatic disease. Tumors with similar clinical and pathological presentations may have differing behavior, so it is important to understand specific biological characteristics. Objective: To investigate tumor markers of primary tumors featuring pleural metastasis to identify organ-specific characteristics of metastatic breast cancer. Methods: In a historical cohort study, immunohistochemistry was performed on cell blocks of neoplastic pleural effusions and results were compared with clinicopathological data. Results: The median survival time with Her-2 overexpression in malignant pleural effusions was 2.2 months, whereas cases without overexpression survived, on average, for seven months (p = 0.02). Conclusions: We emphasize that metastases may behave independently of primary tumors, but the present results indicate that therapeutic agents targeting Her-2 overexpression could increase survival in metastatic breast cancer cases.

Superoxide-hydrogen peroxide imbalance interferes with colorectal cancer cells viability, proliferation and oxaliplatin response.

The role of superoxide dismutase manganese dependent enzyme (SOD2) in colorectal cancer is presently insufficiently understood. Some studies suggest that high SOD2 levels found in cancer tissues are associated with cancer progression. However, thus far, the role of colorectal cancer superoxide-hydrogen peroxide imbalance has not yet been studied. Thus, in order to address this gap in extant literature, we performed an in vitro analysis using HT-29 colorectal cell line exposed to paraquat, which generates high superoxide levels, and porphyrin, a SOD2 mimic molecule. The effect of these drugs on colorectal cancer cell response to oxaliplatin was evaluated. At 0.1 µM concentration, both drugs exhibited cytotoxic and antiproliferative effect on colorectal cancer cells. However, this effect was more pronounced in cells exposed to paraquat. Paraquat also augmented the oxaliplatin cytotoxic and antiproliferative effects by increasing the number of apoptosis events, thus causing the cell cycle arrest in the S and M/G2 phases. The treatments were also able to differentially modulate genes related to apoptosis, cell proliferation and antioxidant enzyme system. However, the effects were highly variable and the results obtained were inconclusive. Nonetheless, our findings support the hypothesis that imbalance caused by increased hydrogen peroxide levels could be beneficial to cancer cell biology. Therefore, the use of therapeutic strategies to decrease hydrogen peroxide levels mainly during oxaliplatin chemotherapy could be clinically important to the outcomes of colorectal cancer treatment.

The effect of superoxide anion and hydrogen peroxide imbalance on prostate cancer: an integrative in vivo and in vitro analysis.

The epidemiological impact of SOD2 imbalance on prostate cancer (PC) risk associated with genetic variations has previously been studied. However, we found no previous studies clarifying the nature of SOD2 effects on prostate cancer. Here, we performed integrated in vivo and in vitro protocols that analyzed the association between Ala16Val-SOD2 polymorphism and prostate cancer aggressiveness at the time of diagnosis and evaluated the effect of the imbalance on PC proliferation using the DU-145 PC cell line treated with paraquat and porphyrin. In the pharmacological model, paraquat was used to increase superoxide anion levels and porphyrin was the SOD2 analog. The results confirmed the impact of superoxide-hydrogen peroxide imbalance on PC cell biology since porphyrin decreased cell proliferation and both treatments modulated antioxidant genes. Therefore, our results corroborate previous suggestions that alteration of redox status could be exploited therapeutically in the treatment of PC.