BackgroundChemotherapy combined with immunotherapy becomes the main trend in lung cancer intervention; however, how chemotherapy promotes the immune function remains elusive. Therefore, we sought to determine how chemotherapy promotes the immune function.MethodsWe determined in 100 NSCLC patients the expression of CD8, functional markers (IFN-γ, Granzyme B, and Perforin) and specific chemokines by quantitative real-time reverse transcriptase-PCR. Functional experiments were carried out to check whether docetaxel (DOC), a chemotherapeutic agent, modifies the expression of HMGB1 and CXCL11, and influences the infiltration properties of CD8+ T cells to the tumor microenvironment. The mechanism of the release of HMGB1 and CXCL11 was determined by flow cytometry, immunofluorescence and western blotting. In in vivo experiment, we confirmed how DOC enhanced the recruitment of HER2-CAR T cells to tumor sites.ResultsWe found that DOC upregulated the expression of chemokine receptor ligand CXCL11 in tumor microenvironment and subsequently enhanced CD8+ T cell recruitment. DOC treatment significantly increased HMGB1 release in an ROS-dependent manner. Recombinant protein HMGB1 stimulated the secretion of CXCL11 via NF-κB activation in vitro. Tumors from DOC-treated mice exhibited higher expression of HMGB1 and CXCL11, more HER2-CAR T cell infiltration, and reduced progression, relative to control. Increased HMGB1 and CXCL11 expressions were positively correlated with prolonged overall survival of lung cancer patients.ConclusionsOur results demonstrate that DOC induces CD8+ T cell recruitment to the tumor microenvironment by enhancing the secretion of HMGB1 and CXCL11, thus improving the anti-tumor efficacy, indicating that modulating the HMGB1-CXCL11 axis might be helpful for NSCLC treatment.Electronic supplementary materialThe online version of this article (10.1186/s40425-019-0511-6) contains supplementary material, which is available to authorized users.
Background: Drug-refractory secondary hyperparathyroidism (SHPT) is the most common complication in patients with chronic renal failure (CRF). Although surgery is the most effective and safe method for drug-refractory SHPT, the condition may persist or recur after the primary surgery, and reoperation is often required in these patients. The purpose of our current study was to evaluate the safety and effectiveness of reoperation for drug-refractory SHPT.
Methods:The clinical data of 15 patients requiring reoperation after a surgery for drug-refractory SHPT in our hospital from 2010 to 2019 were retrospectively analyzed. Changes in biochemical markers including intact parathyroid hormone (iPTH), blood calcium (Ca), blood phosphorus (P), alkaline phosphatase (ALP), and blood calcium phosphorus product (Ca*P) were compared before and after the surgery, and the effectiveness and complications of the reoperation were summarized.
Results:The reoperation was successful in all the 15 patients after a single attempt. Routine pathological examinations identified a total of 25 parathyroid glands, of which 10 were in the neck in situ, 5 were ectopic in the neck, and 10 were in the forearm. The ectopic parathyroid glands were located inside the thyroid gland (n=1), anterior superior mediastinum (n=1), or thymus (n=3). Surgical treatment significantly improved clinical symptoms such as skin pruritus and bone pain. Blood iPTH, Ca, P, ALP, and Ca*P were significantly reduced (P<0.05 or P<0.01) after surgery. Hypothyroidism occurred in 1 patient; 4 patients undergoing orthotopic neck surgery developed transient hoarseness, which were alleviated within 6 months; no severe complications such as bleeding or death were noted. No recurrence occurred during the 6-month follow-up.Conclusions: Reoperation is safe and effective for drug-refractory SHPT. Preoperative imaging should be performed to achieve accurate positioning, and the recurrent laryngeal nerve should be closely monitored during surgery. The purpose of the reoperation is to remove all possible parathyroid tissues to avoid recurrence.
Objective To identify the clinicopathological features correlated to lymph node metastasis (LNM) in patients with papillary thyroid microcarcinoma (PTMC). Methods Clinical data of 785 PTMC patients who underwent surgical treatment at the Lishui Municipal Central Hospital from September 2008 to December 2017 were retrospectively analyzed. Clinical and pathological risk factors for lymph node metastasis (LNM), central lymph node metastasis (CLNM), and lateral lymph node metastasis (LLNM) were analyzed. Results LNM was found in 236 (30.2%) patients. Multivariate logistic regression analysis revealed that in PTMC, male gender, age < 55 years, tumor size > 5 mm, bilateral lesions, and extrathyroidal extension were independent risk factors for LNM in general and for CLNM. For LLNM, tumor size > 5 mm, multifocal lesions, and extrathyroidal extension were independent risk factors. Conclusions Identification of risk factors for cervical LNM could assist individualization of clinical management for PTMC.
This study analyzed the expression of membrane OX40 and OX40L (mOX40 and mOX40L) and levels of soluble OX40 and OX40L (sOX40 and sOX40L) in T1D patients to determine their clinical significance. Peripheral blood (PB) was collected from patients with T1D and healthy control participants. Expression of mOX40 and mOX40L on immune cells was detected by flow cytometry. Levels of sOX40 and sOX40L in sera were measured by ELISA. We demonstrated for the first time enhanced sOX40 and sOX40L expression and reduced mOX40 and mOX40L levels in T1D patients which correlated with the clinical characteristics and inflammatory factors. These results suggest that OX40/OX40L signal may be promising biomarkers and associated with the pathogenesis of T1D.
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