Thorsenwollesen2782
Cancer has been as one of common comorbidities of diabetes. Long-term antidiabetic treatment may potentially exert uncertain impacts on diabetic patients with cancer including breast cancer (BC). Dipeptidyl peptidase-4 inhibitors (DPP-4i) are currently recommended by the AACE as first-line hypoglycemic drugs in type 2 diabetes mellitus (T2DM). Although the safety of DPP-4i has been widely evaluated, the potential side-effects of DPP-4i in cancer metastasis were also reported and remain controversial. Here, we revealed that Saxagliptin (Sax) and Sitagliptin (Sit), two common DPP-4i compounds, potentially promoted murine BC 4T1 metastasis in vitro and in vivo under immune-deficient status. Mechanically, we observed that DPP-4i treatment induced aberrant oxidative stress by triggering ROS overproduction, as well as ROS-dependent NRF2 and HO-1 activations in BC cells, while specific inhibition of ROS, NRF2 or HO-1 activations abrogated DPP-4i-driven BC metastasis and metastasis-associated gene expression in vitro. Furthermore, ALA, a NRF2 activator significantly promoted BC metastasis in vitro and in vivo, which can be abrogated by specific HO-1 inhibition in vitro. Moreover, specific HO-1 inhibition not only reversed DPP-4i-induced NRF2 activation but also abrogated ALA-induced NRF2 activation, resulting in a decrease of metastasis-associated genes, indicating a positive-feedback NRF2-HO-1 loop. Our findings suggest that DPP-4i accelerates murine BC metastasis through an oncogenic ROS-NRF2-HO-1 axis via a positive-feedback NRF2-HO-1 loop. Therefore, this study not only offers novel insights into an oncogenic role of DPP-4i in BC progression but also provides new strategies to alleviate the dark side of DPP-4i by targeting HO-1.
Venous thromboembolic events (VTE) are commonly encountered in patients with lymphoma. Several risk assessments models (RAM) had attempted to identify higher risk patients with varying success. The International Prognostic Index (IPI) is a clinicopathological tool developed to help predict both response to treatment and prognosis of patients with diffuse large B-cell lymphoma (DLBCL).
In this study, we utilize the IPI index to identify group of patients with DLBCL at higher risk for VTE.
Patients with pathologically-confirmed diagnosis of DLBCL and with image-confirmed VTE, treated and followed at our institution were included. Rates of VTE was calculated for each risk category.
A total of 373 patients, median age 49 (range 18-90) years were included. VTE were reported in 56 (15.0%) patients; 51 (91.1%) had active disease while 29 (51.8%) were ambulatory at time of VTE diagnosis. VTE rates were particularly high among patients with poor performance status (26.2%, P=0.028) and high LDH (19.0%, P=0.023). Applying the age-adjusted IPI separated patients into two risk categories; VTE were diagnosed in 9.7% in patients with "low and low-intermediate" scores compared to 19.8% in patients with "high and high-intermediate" scores, P=0.020.
The original IPI and its modified versions, routinely used at diagnosis as a prognostic and predictive tool for patients with DLBCL, can also be utilized to define high risk patients for VTE; the risk of whom might be high enough to recommend thromboprophylaxis even in the ambulatory settings. More work is needed to refine and improve currently available RAMs.
The original IPI and its modified versions, routinely used at diagnosis as a prognostic and predictive tool for patients with DLBCL, can also be utilized to define high risk patients for VTE; the risk of whom might be high enough to recommend thromboprophylaxis even in the ambulatory settings. More work is needed to refine and improve currently available RAMs.Risk stratification of men with clinically localized prostate cancer has historically relied on basic clinicopathologic parameters such as prostate specific antigen level, grade group, and clinical stage. However, prostate cancer often behaves in ways that cannot be accurately predicted by these parameters. Thus, recent efforts have focused on developing tissue-based genomic tests that provide greater insights into the risk of a given patient's disease. Multiple tests are now commercially available and provide additional prognostic information at various stages of the care pathway for prostate cancer. Indeed, early evidence suggests that these assays may have a significant impact on patient and physician decision-making. However, the impact of these tests on oncologic outcomes remains less clear. In this review, we highlight recent advances in the use of tissue-based biomarkers in the treatment of prostate cancer and identify the existing evidence supporting their clinical use.
Atypical meningioma is a non-benign tumor, and its prognostic factors and treatment strategies are unclear.
Patients with atypical meningioma, between 2004 and 2016, were collected from the Surveillance, Epidemiology, and End Results database. Then, we randomly divided patients into a training set and a validation set at a ratio of 82. Y-27632 The nomogram was constructed based on the multivariate Cox regression analyses. And the concordance index, calibration curves, and receiver operating character were used to assess the predictive ability of the nomogram. We divided the patient scores into three groups and constructed a survival curve using Kaplan-Meier analysis.
After our inclusion and exclusion criteria, 2358 patients were histologically diagnosed of atypical meningioma. The prognostic nomogram comprised factors of overall survival, including age, tumor size and surgery. The concordance index was 0.715 (95%CI=0.688-0.742) for overall survival in the training set and 0.688 (95%CI=0.629-0.747) for overall survival in the validation set. The calibration curves and receiver operating character also indicated the good predictability of the nomogram. Risk stratification revealed a statistically significant difference among the three groups of patients according to quartiles of risk score.
Gross total resection is an independent factor for survival, and radiation after non-gross total resection potentially confers a survival advantage for patients with atypical meningioma.
Gross total resection is an independent factor for survival, and radiation after non-gross total resection potentially confers a survival advantage for patients with atypical meningioma.