Cell-free DNA in blood and urine as a diagnostic tool for bladder cancer: a meta-analysis.

OBJECTIVE: To assess the diagnostic performance of cell-free DNA assays in the detection of bladder cancer. PATIENTS AND METHODS: The quality of the studies included in this meta-analysis was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Statistical analyses were performed using the software RevMan 5.3 and Stata 14.0. We assessed the pooled sensitivity and specificity, positive/negative likelihood ratios (PLRs/NLRs), diagnostic odds ratios (DORs), and corresponding 95% confidence intervals (95% CIs). Summary receiver operating characteristic curve (ROC curve) and area under the curve (AUC) were used to summarize the overall test performance. Heterogeneity and publication bias were also examined. RESULTS: Eleven studies included 802 bladder cancer patients and 668 controls met the eligibility criteria. The overall diagnostic accuracy was measured as follows: sensitivity 0.71 (95% CI = 0.64-0.77), specificity 0.78 (95% CI = 0.70-0.85), PLR 3.3 (95% CI = 2.4-54.5), NLR 0.37 (95% CI = 0.30-0.46), DOR 9 (95% CI = 6-14), and AUC 0.80 (95% CI = 0.77-0.83). Subgroup analysis suggested that ethnicity significantly accounted for the heterogeneity of specificity. The Deeks' funnel plot asymmetry test (P = 0.97) suggested no potential publication bias. CONCLUSIONS: Cell-free DNA has a high diagnostic value in bladder cancer.

A highly integrated precision nanomedicine strategy to target esophageal squamous cell cancer molecularly and physically.

The prognosis of esophageal squamous cell carcinoma is poor. We hereby presented a highly integrated and clinically relevant precision nanomedicine strategy to target ESCC molecularly and physically for significant improvement of the treatment efficacy. We firstly identified PI3K overexpression in patient samples and its relation to poor patient survival. With our highly versatile tumor-targeted drug delivery platform (DCM), we were able to load a potent but toxic docetaxel (DTX) and a PI3K inhibitor (AZD8186) with favorable physical properties. The combination of the DTX-DCM and AZD8186-DCM showed a highly efficacious and synergistic anti-tumor effect and decreased hematotoxicity. A pro-apoptotic protein, Bax was significantly upregulated in ESCC cells treated with combination therapy compared to that with monotherapy. This study utilized a highly integrated precision nano-medicine strategy that combines the identification of cancer molecular target from human patients, precision drug delivery and effective combination therapy for the development of better ESCC treatment.

Nanoformulated paclitaxel and AZD9291 synergistically eradicate non-small-cell lung cancers in vivo.

AIM: This study aims to develop new nanoformulations of EGFR T790M targeted inhibitor AZD9291 and paclitaxel (PTX) for combination therapy of lung cancer. MATERIALS & METHODS: We prepared and characterized PTX- and AZD9291-loaded disulfide cross-linking micelles (DCMs), and evaluate their combination effect and toxicity in vitro and in lung cancer-bearing mice. RESULTS: Drug-loaded DCMs were relatively small in size, and possessed glutathione-responsive drug release. The combination of PTX-DCMs and AZD92921-DCMs exhibited strong synergistic effects in both cell line and in vivo without additional toxicity. Molecular studies demonstrated the synergistic modification in both IKB-α/NF-κB/Bcl-2 and EGFR/Akt pathways. CONCLUSION: The combination of DCM-loaded AZD9291 and PTX could potentially offer more effective and less toxicity treatment options for lung cancer patients.

Preoperative serum immunoglobulin G and A antibodies to Porphyromonas gingivalis are potential serum biomarkers for the diagnosis and prognosis of esophageal squamous cell carcinoma.

BACKGROUND: The key-stone-pathogen, Porphyromonas gingivalis associates not only with periodontal diseases but with a variety of other chronic diseases such as cancer. We previously reported an association between the presence of Porphyromonas gingivalis in esophageal squamous cell carcinoma (ESCC) and its progression. We now report the diagnostic and prognostic potential of serum immunoglobulin G and A antibodies (IgG/A) against Porphyromonas gingivalis for ESCC. METHODS: An enzyme-linked immunosorbent assay (ELISA) was used to determine the serum levels of Porphyromonas gingivalis IgG and IgA in 96 cases with ESCC, 50 cases with esophagitis and 80 healthy controls. RESULTS: The median serum levels of IgG and IgA for P. gingivalis were significantly higher in ESCC patients than non-ESCC controls. P. gingivalis IgG and IgA in serum demonstrated sensitivities/specificities of 29.17%/96.90% and 52.10%/70.81%, respectively, and combination of IgG and IgA produced a sensitivity/specificity of 68.75%/68.46%. The diagnostic performance of serum P. gingivalis IgA for early ESCC was superior to that of IgG (54.54% vs. 20.45%). Furthermore, high serum levels of P. gingivalis IgG or IgA were associated with worse prognosis of ESCC patients, in particular for patients with stage 0-IIor negative lymphnode metastasis, and ESCC patients with high levels of both IgG and IgA had the worst prognosis. Multivariate analysis revealed that lymph node status, IgG and IgA were independent prognostic factors. CONCLUSIONS: The IgG and IgA for P. gingivalis are potential serum biomarkers for ESCC and combination of IgG and IgA improves the diagnostic and prognostic performance. Furthermore, serum P. gingivalis IgG and IgA can detect early stage ESCC.

A versatile nanoplatform for synergistic combination therapy to treat human esophageal cancer.

One of the major goals of precision oncology is to promote combination therapy to improve efficacy and reduce side effects of anti-cancer drugs based on their molecular mechanisms. In this study, we aimed to develop and validate new nanoformulations of docetaxel (DTX) and bortezomib (BTZ) for targeted combination therapy to treat human esophageal cancer. By leveraging our versatile disulfide cross-linked micelles (DCMs) platform, we developed nanoformulations of DTX and BTZ (named DTX-DCMs and BTZ-DCMs). Their physical properties were characterized; their anti-cancer efficacies and mechanisms of action were investigated in a human esophageal cancer cell line in vitro. Furthermore, the in vitro anti-tumor activities of combination therapies (concurrent drug treatment, sequential drug treatment, and treatment using different ratios of the drugs) were examined in comparison with the single drug treatment and free drug strategies. These drug-loaded nanoparticles were spherical in shape and relatively small in size of approximately 20-22 nm. The entrapment efficiencies of DTX and BTZ into nanoparticles were 82.4% and 84.1%, respectively. The drug release rates of DTX-DCMs and BTZ-DCMs were sustained, and greatly increased in the presence of GSH. These nanodrugs were effectively internalized by KYSE30 esophageal cancer cells, and dose-dependently induced cell apoptosis. We further revealed a strong synergistic effect between DTX-DCMs and BTZ-DCMs against KYSE30 esophageal cancer cells. Sequential combination therapy with DTX-DCMs followed by BTZ-DCMs exhibited the best anti-tumor efficacy in vitro. This study demonstrates that DTX and BTZ could be successfully nanoformulated into disulfide cross-linked micelles. The nanoformulations of DTX and BTZ demonstrate an immense potential for synergistic combination therapy to treat human esophageal cancer.