Background: Plasminogen activator inhibitor (PAI)-1 levels and activity are known to increase during metabolic syndrome and obesity. In addition, previous studies have implicated PAI-1 in adipose tissue (AT) expansion while also contributing to insulin resistance. As inflammation is also known to occur in AT during obesity, we hypothesized that in a high-fat diet (HFD)-induced obese mouse model PAI-1 contributes to macrophage-mediated inflammation and metabolic dysfunction.Methods: Four- to five-weeks-old male C57B6/6J mice were fed a HFD (45%) for 14 weeks, while age-matched control mice were fed a standard laboratory chow diet (10% fat). Additional studies were performed in PAI-1 knockout mice and wild type mice treated with an inhibitor (PAI-039) of PAI-1. Macrophage polarization were measured by real time PCR.Results: HFD mice showed increased expression of PAI-1 in visceral white AT (WAT) that also displayed increased macrophage numbers. PAI-1 deficient mice exhibited increased numbers of anti-inflammatory macrophages in WAT and were resistant to HFD-induced obesity. Similarly, pharmacological inhibition of PAI-1 using PAI-039 significantly decreased macrophage infiltration in WAT and improved metabolic status in HFD-induced wild-type mice. Importantly, the numbers of M1 macrophages appeared to be increased by the HFD and decreased by either genetic PAI-1 depletion or PAI-039 treatment.Conclusions: Collectively, our findings provide support for PAI-1 contributing to the development of inflammation in adipose tissue and explain the mechanism of inflammation modulated by PAI-1 in the disordered metabolism in HFD-induced obesity.
Background: 18-fluorodeoxyglucose positron emission tomography/computed tomography ( 18 F-PET/CT) has been widely applied for the imaging of head and neck squamous cell carcinoma (HNSCC). This study examined whether pre- and post-treatment 18 F-PET/CT features can help predict the survival of HNSCC patients. Results: Three radiomics features were identified as prognostic factors. Radiomics score calculated from these features significantly predicted overall survival (OS) and disease-free disease (DFS). The clinicopathological characteristics combined with pre- or post-treatment nomograms showed better ROC curves and decision curves than the nomogram based only on clinicopathological characteristics. Conclusions: Combining clinicopathological characteristics with radiomics features of pre-treatment PET/CT or post-treatment PET/CT assessment of primary tumor sites as positive or negative may substantially improve prediction of OS and DFS of HNSCC patients. Methods: 171 patients who received pre-treatment 18 F-PET/CT scans and 154 patients who received post-treatment 18 F-PET/CT scans with HNSCC in the Cancer Imaging Achieve (TCIA) were included. Nomograms that combined clinicopathological features with either pre-treatment PET/CT radiomics features or post-treatment assessment of primary tumor sites were constructed using data from 154 HNSCC patients. Receiver operating characteristic (ROC) curves and decision curves were used to compare the predictions of these models with those of a model incorporating only clinicopathological features.
Background: Vitamin D deficiency is related to increased cancer risk and deaths. However, whether vitamin D supplementation reduces cancer mortality remains unclear, and several randomized controlled trials yield inconsistent results. Methods: Medline, Embase, and the Cochrane Central Register of Controlled Trials were searched from their inception until 28 June 2022, for randomized controlled trials investigating vitamin D supplementation. Pooled relative risks (RRs) and their 95% confidence intervals (CIs) were estimated. Trials with vitamin D supplementation combined with calcium supplementation versus placebo alone and recruiting participants with cancer at baseline were excluded in the present study. Results: This study included 12 trials with a total of 72,669 participants. Vitamin D supplementation did not reduce overall cancer mortality (RR 0.96, 95% CI 0.80–1.16). However, vitamin D supplementation was associated with a reduction in lung cancer mortality (RR 0.63, 95% CI 0.45–0.90). Conclusions: Vitamin D supplementation could not reduce cancer mortality in this highly purified meta-analysis. Further RCTs that evaluate the association between vitamin D supplementation and total cancer mortality are still needed.
BackgroundInduction chemotherapy followed by concurrent chemoradiotherapy is one of the standards of care for patients with nasopharyngeal carcinoma, but the optimal number of induction cycles is unclear. Here we compared survival data from patients treated with 2 to 4 cycles.MethodsPatients with nasopharyngeal carcinoma at West China Hospital of Sichuan University between January 2009 and December 2015 were retrospectively analyzed.ResultsSix hundred and seventy three patients met eligibility criteria. After a median follow‐up of 53 months (interquartile range, 38‐74), there was no difference between 2 and 3 cycles in overall survival (88.14% vs 91.24%). But four cycles were associated with worse overall survival (79.12%) and higher incidence of treatment‐related toxicities. Multivariate analysis showed that the number of induction cycles and lymph node classification were prognostic factors.ConclusionsTwo and three cycles of induction chemotherapy are associated with similar survival, while four cycles reduce survival and increase treatment‐related toxicity in endemic regions.
Nasopharyngeal carcinoma (NPC) is a severe malignancy arising from the nasopharyngeal epithelium and is southern China’s third most common cancer. With the advancement of treatment methods, early-stage NPC patients usually have a better prognosis and more prolonged survival period than those with other malignant tumors. Most treatment failures are due to distant metastasis or a locally advanced stage of NPC in the initial diagnosis. In addition, approximately 10% of patients develop local recurrence, and 10%–20% of patients experience distant metastasis after treatment. These patients have a poor prognosis, with a median survival of only approximately 10–15 months. In the rapid development of treatment options, the efficacy and safety of some treatments have been validated and approved for first-line treatment, while those of other treatments remain unclear. The present study aims to provide a comprehensive overview of recent advances in NPC treatment and explain the various therapeutic possibilities in treating locally advanced, recurrent, and metastatic NPC patients.
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