Linking periodontitis with 20 cancers, emphasis on oropharyngeal cancer: a Mendelian randomization analysis.

While associations between periodontitis and an elevated risk of cancer have been suggested, the results of existing observational studies have been inconsistent, also leaving room for further investigation into the underlying mechanisms. This study was designed to delve into the possible causal link between periodontitis and 20 standard cancers while concurrently identifying potential mediators. We initiated a Mendelian randomization analysis that drew from either publicly accessible or personally obtained genome-wide association study (GWAS) datasets. The inverse variance weighting (IVW) method served as our primary tool for analysis. To ensure the strength and consistency of our results, we implemented additional strategies, including weighted median, weighted mode, MR-Egger regression, and MR pleiotropy residual sum and outlier (MR-PRESSO), bolstered by funnel plots. Our analysis unveiled an elevated risk of head and neck cancer concomitant with periodontitis (p = 0.041, OR 0.999, 95% CI 0.999-1.000), specifically a heightened risk of oropharyngeal cancer (p = 0.022, OR 0.999, 95% CI 0.999-1.000). As a result of probing into potential mediators, Fusobacterium nucleatum emerged as a likely intermediary in the promoting effect of periodontitis on oropharyngeal cancer (p = 0.021, OR 0.999, 95% CI 0.998-1.000). Inversely, basal cell carcinoma and endometrial cancer demonstrated an association with an increased incidence of periodontitis (basal cell carcinoma: p = 0.020, OR 0.987, 95% CI 0.976-0.998; endometrial cancer: p = 0.027, OR 0.984, 95% CI 0.970-0.998). However, periodontitis exerted no significant causal impact on the 19 other common cancers or the three subtypes of head and neck cancer. To conclude, our results support the theory that periodontitis contributes to an enhanced risk of head and neck cancer, particularly oropharyngeal cancer, with Fusobacterium nucleatum functioning as a potential intermediary.

Does this child just have an atrial septal defect? More potentiality of interventional therapy: A rare case report.

INTRODUCTION AND IMPORTANCE: Partially anomalous pulmonary venous connection (PAPVC) is a rare congenital heart disease, often concomitant with atrial septal defects (ASDs). PAPVC usually tends to be treated by surgery, but the case we report will open up new perspectives for the interventional treatment of PAPVC present with ASD. CASE PRESENTATION: We present a case of a 2-year-old 11 kg boy transthoracic echocardiography showed secundum-type ASD. A supracardiac-PAPVC was accidentally detected during cardiac catheterization, and an abnormal pulmonary vein connection was detected with a vertical vein (VV) opening. Ultimately, ASD and VV were both occluded. CLINICAL DISCUSSION: Surgical therapy of PAPVC is the first line treatment of most centers in the world. However, the main complications after surgical repair of PAPVC raise our concerns, such as pulmonary stenosis, caval vein stenosis and sinus node dysfunction. Therefore, percutaneous closure of PAPVC can be an alternative method. This case of percutaneous interventional closure of ASD and supracardiac PAPVC through a vertical vein in the same surgery was first reported. Patients with ASD tend to have missed diagnoses of PAPVC. We can evaluate it by transesophageal echocardiography (TEE), cardiac magnetic resonance imaging (CMR) and computed tomography (CT). CONCLUSIONS: This case suggests that the effect of interventional therapy is quite reliable. For children with ASD, attention should be paid to the omission of the presence or absence of PAPVC before surgery. During interventional therapy, a guide wire rather than a catheter should be preferred to explore the atrial septum and pulmonary veins to avoid a missed diagnosis of PAPVC.

Molecular and immunological characteristics of patients with CMTM6 low expression colorectal cancer.

CKLF-like MARVEL transmembrane domain-containing 6 (CMTM6), a regulator of programmed cell death ligand 1 (PD-L1), has attracted extensive attention due to its role in tumors. However, research on the expression of CMTM6 in colorectal cancer (CRC) and its relationship with PD-L1 expression and immune cell infiltration is limited. We used The Cancer Genome Atlas database to mine and analyze data from patients with CRC using bioinformatics methods. We investigated the expression of CMTM6 in CRC and its relationship with PD-L1 expression and immune cell infiltration. Immunohistochemistry and PCR were performed to detect CMTM6 and PD-L1 expression in CRC tissues. Differential gene expression analysis was performed using the edgeR package in R and immune cell infiltration analysis was performed using the ssGSEA algorithm. Additionally, GO and KEGG enrichment analyses were conducted to identify the biological processes and pathways associated with low CMTM6 expression. Our study found that CMTM6 expression was significantly upregulated in CRC tissues compared to that in adjacent normal tissues. Patients with high CMTM6 expression exhibited significantly increased levels of PD-L1 expression and higher levels of tumor-infiltrating immune cells compared to patients with low CMTM6 expression. GO and KEGG analyses suggested that CMTM6 may be involved in multiple immune regulatory pathways in CRC.

In stage IV pulmonary adenocarcinoma patients, treatment with Traditional Chinese Medicine alone gives prognostically superior results to treatment with Platinum-Based Chemotherapy alone.

BACKGROUND: About 30% of pulmonary stage IV adenocarcinomas die within 3 months of diagnosis. Western medical treatments with Platinum-Based Chemotherapy=PBC and tyrosine-kinase inhibitors Targeted Therapy=TT can improve prognosis. In China, Traditional Chinese Medicine herbal treatments (TCM) are often used in addition to PBC and TT. A considerable number of patients refuse Western medical treatments and use TCM alone. However, the survival impact of the latter is unknown. HYPOTHESES TESTED: Treatment with TCM alone is prognostically superior to PBC alone. Addition of PBC or TT or both TT to TCM improves survival. METHODS: In this prospective observational, non-interventional study of 1017 consecutive first-onset stage IV NSCLC patients with up to 10 years follow-up, 261 who Died of Disease (DOD) within 3 months were omitted, as they never got the optimal Western medical therapies. All 218 non-adenocarcinomas were also omitted, leaving 538 stage IV adenocarcinomas treated by TCM alone (n = 29), PBC alone (N = 19) and TCM and other Western medical combinations (299 TCM and PBC, 50 TCM and TT, 141 TCM and PBC and TT) with 3 - 120 months follow-up. Survivals were compared using Alive with Disease (AWD) and DOD as endpoints. RESULTS: The patients treated only with TCM had 7 months better median survival than those that received PBC alone (17 and 10 months). The patients that received TCM and PBC had a better median survival (24 months) than TCM alone and much better than PBC alone. None of the patients that received TCM alone survived > 54 months, whereas 18% of TCM and PBC patients survived much longer. Over the observation period of 3 - 120 months, survivals of TCM and TT, TCM and PBC and TT, and TCM and PBC were not different and therefore grouped as TCM and Western medicines. Median survival times of PBC alone and TCM alone were lower than that of TCM and Western medical treatments (p < 0.0001, 10, 17 and 27 months). CONCLUSIONS: Pulmonary stage IV adenocarcinoma patients with at least 3 months survival, treated with TCM alone have a significantly better survival than those treated with PBC alone. Adding Western PBC, TT or both to TCM further improves prognosis.

[Rapid determination of five halobenzoquinones in aquatic products by QuEChERS-ultra performance liquid chromatography-tandem mass spectrometry].

Halobenzoquinones (HBQs), which are emerging chlorinated disinfection byproducts (DBPs), have attracted increasing attention because they are frequently detected in treated tap water, entrainment water, etc. These compounds are mainly generated during the water treatment process using chlorine, chloramine, and chlorine dioxide as disinfectants, and display more toxic effects than regulated DBPs, such as trihalomethane and haloacetic acid. HBQs have been recognized as potential bladder carcinogens and are harmful to the nervous system. Additionally, they can exert genotoxic effects and cause oxidative damage to DNA and proteins. The risk of HBQs in aquatic products is expected to rise because the disinfection of public facilities has significantly increased in recent years. Therefore, developing a sensitive and accurate analytical method to detect HBQs in aquatic products is of great importance. Several analytical methods, including gas chromatography, gas chromatography-mass spectrometry, electrochemical methods, liquid chromatography, and liquid chromatography-tandem mass spectrometry, can be used to identify and quantify HBQs in water. However, to the best of our knowledge, no reports on the determination of HBQ levels in aquatic products are yet available. Further, pretreatment is essential for HBQ determination because of the complex matrix effects of aquatic products. Herein, a sensitive and accurate method based on the QuEChERS technique coupled with ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was developed for the simultaneous determination of five HBQs in aquatic products. For the QuEChERS procedure, the pretreatment conditions, such as the extraction solvent and adsorbent species, were systematically optimized. The sample was extracted with 10 mL of 10% methanol acetonitrile solution (containing 0.1% formic acid), dehydrated, and centrifuged with sodium chloride and anhydrous magnesium sulfate. The supernatant was purified using a QuEChERS packing material consisting of 50 mg N-propylethylenediamine (PSA), 30 mg of graphitized carbon black (GCB), and 30 mg of neutral alumina (Al2O3), dried with nitrogen, and concentrated. The five HBQs were separated on a Waters ACQUITY UPLC BEH C18 column (100 mm×2.1 mm, 1.7 µm) using 0.25% acetonitrile formate solution and 0.25% formic acid aqueous solution as the mobile phase under a gradient elution program and then detected using UPLC-MS/MS with negative electrospray ionization (ESI-) under multiple reaction monitoring (MRM) mode. Quantitative analysis was performed using a matrix-matched external standard method. The five HBQs achieved rapid separation within 6 min, indicating that the proposed method has a much shorter separation time compared with previous studies. The matrix effect was evaluated by establishing a matrix-matched calibration curve. The results showed that 2,5-dichloro-1,4-benzoquinone (2,5-DCBQ) presented a matrix-enhancing effect, whereas the other HBQs displayed matrix-inhibiting effects. In particular, tetrachlorobenzoquinone (TCBQ) exhibited strong inhibitory effects. Under the optimized experimental conditions, the five HBQs demonstrated good linear relationships in the range of 1.0-50.0 µg/L, with correlation coefficients (r)≥0.9992. The detection limits of the method were 0.15-0.8 µg/kg, and the recoveries of the target compounds were 85.9%-116.5%. The relative standard deviations were 1.4%-8.2%, which indicates good reproducibility. The proposed method was successfully applied to actual sample detection, and 2,6-dichloro-3-methyl-1,4-benzoquinone (2,6-DCMBQ) was detected in grass carp. The proposed method is convenient, sensitive, accurate, and suitable for the simultaneous determination of five HBQs in aquatic products. Moreover, the developed method provides a reliable reference for the routine monitoring of trace HBQs in food samples.

[Determination of kojic acid in fermented foods by solid-phase extraction coupled with ultra performance liquid chromatography-tandem mass spectrometry].

Kojic acid naturally appears in fermented foods and can be formed during the aerobic fermentation process induced by Aspergillus and Penicillium fungi. It is widely used in the food industry because it exhibits antibacterial and antifungal properties and does not affect food taste. However, recent studies indicate that kojic acid may be a potential carcinogen. Therefore, assessing the health risks of kojic acid in fermented foods are of great importance, and developing a sensitive and accurate analytical method for this compound is a significant endeavor. Much efforts have been devoted to the detection of kojic acid using electrochemistry, high performance liquid chromatography (HPLC), gas chromatography-mass spectrometry (GC-MS), and high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). HPLC and HPLC-MS/MS are the analytical techniques most often employed for this purpose. Of these two methods, HPLC-MS/MS displays excellent sensitivity and is the optimal selective technique. Pretreatment is usually necessary for kojic acid determination because of the complex matrix effects of fermented foods. However, few researches on the determination of kojic acid in food are available, and, to the best of our knowledge, the determination of kojic acid using solid-phase extraction (SPE) pretreatment has not been reported yet. Herein, a convenient, sensitive, and accurate method was developed to determine kojic acid in fermented foods using solid-phase extraction-ultra performance liquid chromatography-tandem mass spectrometry (SPE-UPLC-MS/MS). The pretreatment conditions, such as the extraction solvent, cartridge, rinse solvent, and eluent, were systematically optimized. The samples, including soy sauce, vinegar, liquor, sauce, fermented soya bean, and fermented bean curd, were extracted with 0.1% formic acid-absolute ethyl alcohol and purified using a PRiME HLB cartridge. Kojic acid was separated using an ACQUITY UPLC® BEH C18 column (100 mm×2.1 mm, 1.7 µm) with formic acid-acetonitrile (1∶999, v/v) and formic acid-5 mmol/L ammonium acetate (1∶999, v/v) solutions as the mobile phases under gradient elution mode. MS was performed in electrospray positive ionization (ESI+) and multiple reaction monitoring (MRM) modes. An internal standard method was used for quantification. Under optimized conditions, good linearity was achieved at mass concentrations of 5.0-100.0 µg/L, with a correlation coefficient (r) of 0.9994. The limits of detection and quantification of the method for kojic acid were 2-5 µg/kg and 6-15 µg/kg, respectively. Good recoveries of 86.8%-111.7%, intra-day precisions of 1.0%-7.9% (n=6), and inter-day precisions of 2.7%-10.2% (n=5) were also obtained. The matrix effect was evaluated by establishing a matrix-matching calibration curve, and weak inhibitory effects were found in vinegar and liquor; moderate inhibitory effects in fermented bean curd, fermented soya bean, and soy sauce; and a strong inhibitory effect in sauce. The developed method was used to detect kojic acid in 240 fermented foods, and the results showed that the detection rate of vinegar was the highest, followed by liquor, sauce, soy sauce, fermented soya bean, and fermented bean curd, the contents were 5.69-2272 µg/kg. Matrix interferences can be significantly reduced by optimizing the pretreatment and detection procedures. The proposed method is sensitive, accurate, and can be used to analyze kojic acid in fermented foods.

Rapid determination of 14 odorous compounds in drinking water using gas chromatography-mass spectrometry coupled with headspace solid-phase microextraction pretreatment.

A sensitive and effective method was developed for the simultaneous determination of 14 odorous compounds in drinking water using gas chromatography-mass spectrometry (GC-MS) coupled with headspace solid phase microextraction (HS-SPME) pretreatment. The influencing factors including SPME fiber, ionic strength, temperature and time on the pretreatment procedure were evaluated systematically. Under the optimized conditions, 10 mL of the samples added with 1.0 g sodium chloride was extracted by CAR/PDMS fiber at 60 °C for 30 min and then desorbed at 280 °C for 3 min. The analytes achieved good linearity as the mass concentrations were in the range of 0.0020-10.0 µg L-1 with correlation coefficients higher than 0.9990. The limits of detection (LODs) ranging between 0.2 and 50 ng L-1 were lower than the olfactory threshold of these studied compounds. Satisfactory recoveries were obtained ranging from 84.8% to 110.6%, and good reproducibility indicated by relative standard deviation (RSD) in the range of 0.50-9.5% was obtained as well. The proposed method was convenient, sensitive and accurate, which was suitable for the routine monitoring 14 odorous compounds in water.

Characterization of cellular senescence in doxorubicin-induced aging mice.

With a rise in the need to develop anti-aging drugs, a growing number of in vivo studies evaluating the efficacy of potential drug candidates have used doxorubicin-induced aging mice. However, changes in the biomarkers of senescent cells have not been reported in detail in these animals. To lay a foundation for the use of doxorubicin-induced aging mice, we examined the biomarkers of hepatic and renal senescent cells in these mice. We found that the 5 mg/kg doxorubicin dose is optimal to induce cellular senescence in mice. Subsequently, using this dose, we found that doxorubicin-induced an increase in senescence-associated ß-galactosidase (SA-ß-gal) positive cells in the kidney and lipofuscin accumulation in the liver. Some markers of senescent cells (p21WAF1/CIP1, p16INK4A, and γH2AX) were also significantly upregulated by doxorubicin and then counteracted by metformin treatment. These preliminary findings support the application of doxorubicin-induced aging mice as an animal model to evaluate the efficacy of anti-aging drug candidates.

Association between plasma glycocalyx component levels and poor prognosis in severe influenza type A (H1N1).

Influenza A virus infection causes a series of diseases, but the factors associated with disease severity are not fully understood. Disruption of the endothelial glycocalyx contributes to acute lung injury in sepsis, but has not been well studied in H1N1 influenza. We aim to determine whether the plasma glycocalyx components levels are predictive of disease severity in H1N1 influenza. This prospective observational study included 53 patients with influenza A (H1N1) during the influenza season, and 30 healthy controls in our hospital. Patients were grouped by severity and survival. We collected clinical data and blood samples at admission. Inflammatory factors (tumor necrosis factor-α, interleukin-6, interleukin-10) and endothelial glycocalyx components (syndecan-1, hyaluronan, heparan sulfate) were measured. The plasma levels of syndecan-1, hyaluronan, and heparan sulfate were significantly higher in patients with severe influenza A (H1N1) than in mild cases. Syndecan-1 and hyaluronan were positively correlated with disease severity, which was indicated by the APACHE II and SOFA scores and lactate levels, and negatively correlated with albumin levels. At a cutoff point ≥ 173.9 ng/mL, syndecan-1 had a 81.3% sensitivity and 70.3% specificity for predicting of 28-day mortality. Kaplan-Meier analysis demonstrated a strong association between syndecan-1 levels and 28-day mortality (log-rank 11.04, P = 0.001). Elevated plasma levels of syndecan-1 has a potential role in systemic organ dysfunction and may be indicative of disease severity in patients with influenza A (H1N1).

Statin use and survival among women with ovarian cancer: an Australian national data-linkage study.

BACKGROUND: Five-year ovarian cancer survival rates are below 50%; there is considerable interest in whether common medications like statins may improve survival. METHODS: We identified women diagnosed with ovarian cancer in Australia from 2003 to 2013 through the Australian Cancer Database and linked these records to national medication and death databases. We used Cox proportional hazards regression to estimate hazard ratios (HR) and confidence intervals (CI) for associations between statins and survival. RESULTS: Pre-diagnosis statin use was not associated with survival overall but was associated with better survival among women with endometrioid cancers. Statin use after diagnosis was associated with better ovarian cancer-specific survival (OVS, HR = 0.87, 95%CI 0.81-0.94), but this association was largely restricted to women who started using statins after their cancer diagnosis (OVS HR = 0.68, 0.57-0.81 vs. HR = 0.94, 0.87-1.01 for continuing users). The association was strongest for endometrioid cancers (OVS HR = 0.48, 0.29-0.77). CONCLUSIONS: Use of statins may confer a survival benefit for women with ovarian cancer but it is impossible to rule out bias in observational studies. Particularly problematic are reverse causation where disease status affects statin use, confounding by indication and the absence of data for women with normal cholesterol levels. A randomised trial is required to provide definitive evidence.

Metformin and cancer-specific survival among breast, colorectal, or endometrial cancer patients: A nationwide data linkage study.

AIMS: Equivocal results of association between metformin and cancer-specific survival need more investigation. We tested the hypothesis that adherence to the drug had a lower cancer-specific mortality in a homogeneous population (i.e. regular users). METHODS: The Australian Cancer database was linked to the Pharmaceutical Benefits Scheme data and the National Death Index. Adherence to metformin was calculated by proportion of days covered. Cox regression models with time-varying covariates were used to estimate multivariable-adjusted cause-specific hazard ratios (HRs) and 95% confidence intervals (CI) for the association of adherence to metformin and cancer-specific mortality. RESULTS: Between 2003 and 2013, three separate cohorts of 6717, 3121, and 1854 female patients were identified with newly diagnosed breast, colorectal, or endometrial cancer. The 1-year adherence was similar at baseline in three cohorts, on average 75%. Each 10% increase in 1-year adherence to metformin reduced cancer-specific mortality among women with breast cancer (adjusted HR = 0.95; 95% CI, 0.93-0.97), colorectal cancer (adjusted HR = 0.94; 95% CI, 0.91-0.96), or endometrial cancer (adjusted HR = 0.95; 95% CI, 0.90-0.99). The inverse associations remained unchanged in most subgroup analyses. CONCLUSIONS: Among metformin users, adherence to this drug is inversely associated with reduced cancer-specific mortality. If confirmed, metformin could be considered as an adjuvant treatment.

Is there sufficient evidence to recommend women diagnosed with endometrial cancer take a statin: Results from an Australian record-linkage study.

OBJECTIVE: A recent paper suggested all women with endometrial cancer should take statins but it is unclear whether there is sufficient evidence to justify this recommendation. METHODS: We identified all women diagnosed with uterine cancer in Australia between July 2003 and December 2013 (2012 in New South Wales) through the Australian Cancer Database (N = 16,501) and linked these to the national prescription database and National Death Index to identify statin use and survival outcomes to December 2015. We used Cox proportional hazards regression to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the associations between statin use and survival. RESULTS: Among the 15,703 women with endometrial cancer, pre-diagnosis statin use was not associated with survival. Endometrial cancer-specific mortality was lower among women who used statins after diagnosis (time-varying models: HR = 0.92; 95%CI 0.82-1.03) but the association was only seen among women with type 1 cancers (0.87; 0.76-1.00), for hydrophilic statins (0.84; 0.68-1.03) and for new use of statins after diagnosis (0.75; 0.59-0.95). There was a weak dose-response with increasing number of statin prescriptions. Sensitivity analyses using inverse probability of treatment weights were similar. CONCLUSION: Women with endometrial cancer who take statins after diagnosis may have better survival than those who do not use statins. However, it is impossible to completely rule out bias, particularly reverse causation where disease status may affect statin use. We believe it is too early to recommend all women with endometrial cancer take statins, but there is sufficient evidence to justify a randomized trial.

Sensitive Mercury Speciation Analysis in Water by High-Performance Liquid Chromatography-Atomic Fluorescence Spectrometry Coupling with Solid-Phase Extraction.

An efficient method based on high-performance liquid chromatography coupled with atomic fluorescence spectrometry (HPLC-AFS) was successfully developed for the simultaneous determination of four mercury species including Hg2+, methylmercury (MeHg), ethylmercury (EtHg), and phenylmercury (PhHg) in water. Samples were enriched and cleaned up with a solid-phase extraction (SPE) pretreatment using a thiol cartridge. Some key parameters including the selection of a SPE cartridge, eluent type, eluent volume, and interference factors were systematically investigated. Chromatographic separation was achieved on a C18 column using a mobile phase consisting of methanol and 60 mmol L-1 ammonium acetate with 10 mmol L-1 L-cysteine by gradient elution. Under the optimized conditions, good linearity (r ≥ 0.9991) was observed between 0.20 to 10.0 µg L-1. The limits of detection were in the range of 0.001 - 0.002 µg L-1. High recoveries (87.2 to 111%) and good reproducibility (1.1 - 6.5%) were obtained. Such a method is sensitive, selective and accurate, which can be applied to the quantification of mercury species in water samples.

"How Long Have I Got?" in Stage IV NSCLC Patients With at Least 3 Months Up to 10 Years Survival, Accuracy of Long-, Intermediate-, and Short-Term Survival Prediction Is Not Good Enough to Answer This Question.

BACKGROUND: Most lung cancer patients worldwide [stage IV nonsmall cell lung cancer (NSCLC)] have a poor survival: 25%-30% die <3 months. Yet, of those surviving >3 months, 10%-15% (70,000-105,000 new patients worldwide per year) survive (very) long. Surprisingly, little scientific attention has been paid to the question, which factors cause the good prognosis in these NSCLC stage IV long survivors. Therefore, "How long do I still have?" currently cannot be accurately answered. We evaluated in a large group of 737 stage IV NSCLC patients surviving 3.2-120.0 months, the accuracies of short- and long-term survival predictive values of baseline factors, radiotherapy (RT), platinum-based chemotherapy (PBT), and tyrosine kinase inhibitor targeted therapy (TKI-TT). METHODS: This is a noninterventional study of 998 consecutive first-onset stage IV NSCLC patients. A total of 737 (74%) survived 3.2-120.0 months, 47 refused RT, PBT, and TKI-TT. Single and multivariate survival analysis and receiver operating curve (ROC) analysis were used with dead of disease (DOD) or alive with disease (AWD) as endpoints. RESULTS: The median survival (16.1 months) of 47 patients who refused PBT, RT, and TKI-TT was significantly worse than those with RT, PBT, and/or TKI-TT (23.3 months, HR = 1.60, 95% CI = 1.06-2.42, p = 0.04). Of these latter 690 patients, 42% were females, 58% males, median age 63 years (range 27-85), 1-, 2-, 5-, and 10-year survival rates were 74%, 49%, 16%, and 5%. In total, 16% were alive with disease (AWD) at the last follow-up. Pathology subtype (adenocarcinoma vs. all others), performance score, TNM substage, the number of PBT cycles and TKI-TT had independent predictive value. However, with the multivariate combination of these features, identification results of short-term nonsurvivors and long-term survivors were poor. CONCLUSIONS: In stage IV NSCLC patients with >3 months survival, baseline features, and systemic therapeutic modalities have strong survival predictive value but do not accurately identify short- and long-term survivors. The predictive value of other features and interventions discussed should be investigated in the worldwide very large group of stage IV NSCLC patients with >3 months survival.

Does adherence to lipid-lowering medications improve cancer survival? A nationwide study of breast and colorectal cancer, and melanoma.

AIMS: Inconclusive findings of lipid-lowering medications (LLMs) on cancer survival benefit require more evidence. We tested the hypothesis that adherence to this drug is associated with reduced cancer-specific mortality in a homogeneous population who had used this drug before cancer diagnosis. METHODS: The Australian Cancer Database was linked to the Pharmaceutical Benefits Scheme database, and to the National Death Index (up to 2015). Medication adherence was calculated by proportion of days covered. Cox regression models with time-varying covariates were used to derive multivariable-adjusted cause-specific hazard ratio (HR) and 95% confidence interval (CI) for the associations between adherence to LLMs, statins, lipophilic, and hydrophilic statins and cancer-specific mortality. RESULTS: From 2003 to 2013, 3 separate cohorts of 20 046, 11 719 and 6430 female patients with newly diagnosed breast, colorectal cancer, and melanoma respectively were identified. The 1-year adherence was similar at 1-year prediagnosis in the 3 cohorts, on average 82%. Each 10% increase in 1-year adherence to LLMs was inversely associated with cancer-specific mortality among women with breast cancer (fully adjusted HR = 0.92, 95% CI 0.91-0.93), colorectal cancer (fully adjusted HR = 0.92, 95% CI 0.91-0.93), or melanoma (fully adjusted HR = 0.97, 95% CI 0.94-1.00). The reductions in cancer-specific mortality were more pronounced for women who adhered to lipophilic than hydrophilic statins in all 3 cancers albeit not statistically significant for melanoma. CONCLUSION: Among LLM users, adherence to this drug is associated with a decrease in cancer-specific mortality. If confirmed, LLMs could be considered as an adjuvant cancer therapy to improve prognosis in cancer survivors.

Lipid-lowering medication use and cancer-specific survival among endometrial or lung cancer patients: an Australian nationwide cohort study.

PURPOSE: Inconsistent results of lipid-lowering medications (LLMs) on improved cancer survival need more investigations. We tested the hypothesis that adherence to the drug would be associated with a lower cancer-specific mortality in a homogeneous population who has ever used the drug. METHODS: Utilising data from the Australian Cancer database, linked to the Pharmaceutical Benefits Scheme data and the National Death Index, we identified two separate cohorts of 4519 and 3083 women patients with newly diagnosed endometrial and lung cancer respectively between 2003 and 2013. Adherence to this drug was calculated by proportion of days covered. Cox regression models with time-varying covariates were used to estimate the multivariable-adjusted cause-specific hazard ratios (HRs) and 95% confidence intervals (CIs) for the association of adherence to LLMs, statins, lipophilic and hydrophilic statins, and cancer-specific mortality. RESULTS: Each 10% increase in 1-year adherence to LLMs reduced cancer-specific mortality among women with endometrial cancer (adjusted HR=0.93, 95% CI 0.90-0.96) or lung cancer (adjusted HR=0.95, 95% CI 0.93-0.97). The inverse associations remained unchanged in different subgroup analyses. The reductions in lung cancer mortality were not apparent for women who adhered to lipophilic statins albeit better endometrial cancer survival appeared in the lipophilic statin group and borderline statistical improvement in the hydrophilic statin group. CONCLUSIONS: Among LLM users, adherence to this drug is inversely associated with reduced cancer-specific mortality. Together with previous evidence, randomised controlled trials are called for to confirm whether LLMs could be considered as an adjuvant treatment to improve prognosis.

CLIC1 promotes the progression of oral squamous cell carcinoma via integrins/ERK pathways.

Chloride intracellular channel 1 (CLIC1), a member of the chloride channel protein family, acts as a promoter in many malignancies, but its role in oral cancer remains unclear. Hence, this research aimed to explore the effects of CLIC1 on the progression of oral cancer cells in vitro, and we assessed its role in cell proliferation, apoptosis, migration, invasion, angiogenesis, and chemosensitivity to cisplatin and possible signaling pathways. The results demonstrated that CLIC1 depletion inhibited the proliferation, invasion, migration and angiogenesis of oral squamous cell carcinoma (OSCC) cells in vitro, but promoted cell apoptosis and increased the drug susceptibility to cisplatin. In contrast, CLIC1 upregulation was positively correlated with cell proliferation, invasion and migration and angiogenesis. Mechanistically, CLIC1 silencing decreased the levels of ITGαv, ITGß1, p-ERK, vimentin, MMP2 and MMP9, and increased the levels of p-p38, E-cadherin, caspase3 and caspase9. CLIC1 overexpression enhanced the ITGαv, ITGß1, p-ERK, vimentin, MMP2 and MMP9 levels and decreased E-cadherin expression. Overall, these results indicated that CLIC1 promotes the progression of OSCC, and we speculated that its potential mechanism may be related to the regulation of ITGαv and ITGß1, which led to activation of the MAPK/ERK and MAPK/p38 signal pathways.

SDF-1-loaded PLGA nanoparticles for the targeted photoacoustic imaging and photothermal therapy of metastatic lymph nodes in tongue squamous cell carcinoma.

The combination of photothermal therapy and targeted chemotherapy can produce much greater cytotoxicity than chemotherapy. Herein, we developed multifunctional targeted polymeric nanoparticles (NPs) loaded with indocyanine green (ICG) and doxorubicin (DOX) for the targeted photoacoustic imaging and photothermal ablation of oral cancer cells. The chemokine SDF-1, a specific antibody, was conjugated to NPs by the carbodiimide method. The NPs were automatically targeted to tumour tissue in vitro and in vivo through CXCR4-SDF-1 interactions. The results of in vivo and in vitro photoacoustic imaging and photothermal therapy experiments showed that the multifunctional NPs had excellent photoacoustic imaging characteristics and photothermal therapy capabilities. The photothermal material heated rapidly after laser irradiation, and the resulting heat increased cell metabolism and membrane permeability, which increased cellular NP uptake. The encapsulated drug (DOX) was released immediately after the liquid core was transformed into a gas via laser effects, which killed tumour cells while producing strong photoacoustic signals in vitro and in vivo. Thus, we concluded that the chemokine SDF-1 can be applied for the targeted chemotherapy of metastatic lymph nodes of oral squamous cell carcinoma (OSCC) and is more effective for treating oral cancer when combined with photothermal therapy than when used alone.

Expression of CLIC1 as a potential biomarker for oral squamous cell carcinoma: a preliminary study.

PURPOSE: CLIC1, a member of the highly conserved class ion-channel protein family, is frequently upregulated in multiple human malignancies and has been demonstrated to play a critical role in cell proliferation, apoptosis, and invasion. However, limited is known about its expression, biological functions, and action mechanism in oral malignancies. We aimed to evaluate whether CLIC1 could be a biomarker for oral squamous cell carcinoma (OSCC). METHODS: Immunohistochemistry was used to analyze the expression of CLIC1 in tissue. CLIC1 protein and mRNA were measured through Western immunoblotting and quantitative real-time PCR. CLIC1 protein expression in plasma was detected via ELISA. A total of 72 OSCC specimens were recruited in this study for evaluation of correlations of CLIC1 with clinicopathological features and survival. RESULTS: CLIC1 was significantly overexpressed in tissue and plasma of OSCC patients. It was found that upregulated CLIC1 was distinctly correlated with histological grade, TNM stage, and tumor size. Meanwhile, Kaplan-Meier survival analysis showed that OSCC patients with high CLIC1 expression had remarkably poorer overall survival rate than those with low CLIC1 expression. Multivariate Cox regression analysis revealed that CLIC1 was the independent prognostic factor for overall survival rate of OSCC patients. In addition, Pearson correlation analysis showed that CLIC1 was associated with multiple tumor-associated genes. CONCLUSION: These results indicated that CLIC1 acts as a molecular target in OSCC and may present a novel diagnostic marker and therapeutic target for OSCC.

Combined effects of aspirin and vitamin D3 on two OSCC cell lines: a preliminary study.

OBJECTIVES: We evaluated the potential effects of aspirin combined with vitamin D3 on cell proliferation and apoptosis in oral cancer cells. RESULTS: Compared to the untreated control or individual drug, the combinations of aspirin and vitamin D3 significantly decreased the rates of cell proliferation by CCK-8 assay, and caused higher rates of cell apoptosis in both CAL-27 and SCC-15 cells by Annexin V-FITC apoptosis assay and flow cytometry. Remarkably, the combined treatment with aspirin and vitamin D3 significantly suppressed the expression of Bcl-2 protein and p-Erk1/2 protein, examined by western blot analysis. CONCLUSIONS: Our study demonstrates that aspirin and vitamin D3 have biological activity against two human OSCC cell lines and their activity is synergistic or additive when two drugs used in combination with therapeutic concentrations. The combination of aspirin and vitamin D3 may be an effective approach for inducing cell death in OSCC.