IFN-γ was not always successful as an antitumor agent. It also can promote tumor cells to evade immune surveillance. Researchers should be cautious in using IFN-γ as a therapeutic agent for cancer treatment.
BackgroundD-dimer is a fibrin-degrading substance that is soluble and whose degradation is produced by plasma protein-mediated degradation of cross-linked fibrin. Previous investigations have shown a link between D-dimer and the mortality in lung cancer patients. However, different investigations varied whether D-dimer could predict prognosis in these patients.MethodsA meta-analysis and systematic review of all available cohort studies were performed on the link between circulating D-dimer levels and survival of lung cancer patients. Relevant studies were searched in Embase, Cochrane Library, and PubMed databases. Data from 540 lung cancer patients from the First Hospital of Soochow University and Sichuan Cancer Hospital were used for external validation.ResultsWe finally obtained 19 eligible cohort studies with pooled HR showing that high D-dimer levels contribute to death in tumor group (HR 1.62, 95% CI: 1.39–1.88, I2 = 75.0%). Further stratified analysis showed that higher circulating D-dimer in the advanced lung cancer group was linked to a 1.91-fold risk (HR = 2.91, 95% CI: 2.24–3.78, I2 = 6.0%). Incorporation of other variables, including days of follow-up, country, design, public year, population, disease status, and quality score, into the meta-regression model, indicated that disease status was an additional source of heterogeneity (p < 0.001). External validation of 540 patients also showed that high levels of D-dimer showed a higher risk of overall mortality (HR 1.39, 95% CI: 1.13–1.72, p = 0.002) and VTE events (HR 3.98, 95% CI: 1.99–8.70, p = 0.002) in lung cancer patients.ConclusionsHigh circulating plasma D-dimer levels independently predict long-term prognosis and the risk of venous thromboembolism in lung cancer.
Colorectal cancer (CRC), a common malignant disease, has the second highest mortality rate among all cancer types. Due to the diversity and heterogeneity of CRC, few effective treatment strategies have been developed in recent years, except for surgical resection. As immunotherapy has become a revolutionary treatment after surgery, along with chemoradiotherapy and targeted therapy, numerous basic research studies and clinical trials have been conducted on CRC. Therefore, immune checkpoint inhibitor (ICI) therapy has become the main anti-CRC immunotherapy method used at present. With the rapid development of biotechnology and cell research, an increasing number of monotherapy or combination therapy strategies using ICIs for CRC have been designed in recent years. Methods to classify and review ICI strategies for different types of CRC to better guide treatment are continuously investigated. However, the identification of why the ICIs would be more effective in targeting particular subtypes of CRC such as high microsatellite instability (MSI-H) is more important because of the different immune backgrounds in patients. This review intends to classify different subtypes of CRC and summarizes the basic and clinical studies on ICIs for each subtype of CRC currently available. In addition, we also attempt to briefly discuss the progress in immunotherapy methods other than ICI therapy, such as chemoimmunotherapy strategy, chimeric antigen receptor-modified T (CAR-T) cells, or immunotherapy based on oncolytic viruses. Finally, we provide a perspective on the development of immunotherapy in the treatment of CRC and attempt to propose a new systematic classification of CRC based on immunological strategies, which may improve guidance for the selection of immunotherapy strategies for different subtypes of CRC in the future.
Background Although voriconazole is a widely used azole antifungal agent in clinical practice, its side effect of muscle toxicity is extremely rare. The present study demonstrates an adverse effect of progressive myotoxicity induced by intravenous voriconazole in a cryptogenic organizing pneumonia patient misdiagnosed as suspected pulmonary fungal infection.Case presentation A 78-year-old male was admitted to our hospital due to recurrent cough and expectoration for four months. His previous chest CT scan indicated alveolar opacities and multiple cavitary nodules in the right lower lobe. Pulmonary fungal infection was considered due to weakly positive results of serum galactomannan and 1,3 β-D-glucan test,with no evidence of malignant tumor, tuberculosis, or Wegener's granulomatosis. The patient experienced diffuse myalgia with significantly elevated muscle enzymes after voriconazole administration for 13 days, and recovered uneventfully due to immediate voriconazole cessation and enhanced intravenous fluid infusion. Furthermore, the pulmonary cavitary nodules were consistent with the pathological findings of cryptogenic organizing pneumonia.Conclusions Voriconazole-associated myotoxicity should be considered when a patient presents with evidence of muscle injury during voriconazole administration. Morever, although invasive pulmonary fungal infection can often show multiple nodules with cavities in CT scan, the initiation of anti-fungal agents should be cautious before the pathological features of multiple cavitary nodules are identified, in order to avoid potential serious adverse events.
ObjectivesSmall cell lung cancer (SCLC) is a lethal human malignancy, and previous studies support the contribution of microRNA to cancer progression. The prognostic value of miR-219-5p in patients with SCLC remains unclear. This study aimed to evaluate the predictive value of miR-219-5p with respect to mortality in patients with SCLC and to incorporate miR-219-5p level into a prediction model and nomogram for mortality.DesignRetrospective observational cohort study.Setting and participantsOur main cohort included data from 133 patients with SCLC between 1 March 2010 and 1 June 2015 from the Suzhou Xiangcheng People’s Hospital. Data from 86 patients with non-SCLC at Sichuan Cancer Hospital and the First Affiliated Hospital of Soochow University were used for external validation.Outcome measuresTissue samples were taken during admission and stored, and miR-219-5p levels were measured at a later date. A Cox proportional hazard model was used for survival analyses and for analysing risk factors to create a nomogram for mortality prediction. The accuracy of the model was evaluated by C-index and calibration curve.ResultsMortality in patients with a high level of miR-219-5p (≥1.50) (n=67) was 74.6%, while mortality in the low-level group (n=66) was 100.0%. Based on univariate analysis, we included significant factors (p<0.05) in a multivariate regression model: patients with high level of miR-219-5p (HR 0.39, 95% CI 0.26–0.59, p<0.001), immunotherapy (HR 0.44, 95% CI 0.23–0.84, p<0.001) and prognostic nutritional index score >47.9 (HR=0.45, 95% CI 0.24–0.83, p=0.01) remained statistically significant factors for improved overall survival. The nomogram had good accuracy in estimating the risk, with a bootstrap-corrected C-index of 0.691. External validation indicated an area under the curve of 0.749 (0.709–0.788).ConclusionsThe miR-219-5p level was associated with a reduced risk of mortality in patients with SCLC. A nomogram incorporating MiR-219-5p level and clinical factors demonstrated good accuracy in estimating the risk of overall mortality. Prospective validation of the prognostic nomogram is needed.
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