The anticancer/cytotoxic effect of a novel gallic acid derivative in non-small cell lung carcinoma A549 cells and peripheral blood mononuclear cells from healthy individuals and lung cancer patients.

Gallic acid (GA) is a naturally occurring polyphenol with a strong antioxidant capacity. GA stimulates the apoptosis of cancer cells, thereby suppressing cancer cell invasion. However, the low oral permeability of GA limits its therapeutic use. In order to enhance the antioxidant capacity and oral permeability of GA, a series of compounds analogous to GA were synthesized: 4-methoxybenzenesulfonamide (MBS), 3,4-dimethoxybenzenesulfonamide (DMBS) and 3,4,5-trimethoxybenzenesulfonamide (TMBS). In the new compounds, hydroxyl groups were replaced with various numbers of methoxy groups (stronger electron-donating groups), to increase hydrophobicity and oral permeability compared to GA. In addition, the carboxylic group was replaced with a sulfonyl group (a stronger electron-withdrawing group), to increase the molecular polarity and antioxidative activities of the compounds. The cell counting kit-8 (CCK-8) assay was used to detect the effect of GA, MBS, DMBS, and TMBS on cell proliferation and apoptosis in peripheral blood mononuclear cells (PBMCs) from healthy individuals and non-small cell lung carcinoma A549 cells. Additionally, the comet assay was used to assess the genotoxicity of these compounds in PBMCs from healthy individuals, lung cancer patients, and A549 cells. Compared to untreated cells, TMBS reduced DNA damage more effectively than GA in PBMCs from lung cancer patients and healthy donors. Furthermore, in comparison to GA, TMBS was more cytotoxic in A549 cells. Moreover, TMBS was not cytotoxic in healthy PBMCs, suggesting that TMBS demonstrates therapeutic potential in cancer.

Interferon-γ liposome: a new system to improve drug delivery in the treatment of lung cancer.

Lung cancer is one of the main causes of death worldwide. Published data show the use of interferons (IFNs) in treating lung tumours. IFNs also have potential for their antiproliferative, antiangiogenic, immunoregulatory and proapoptotic effects. IFN-γ functions as an anticancer agent against various forms of cancer. This study aimed to investigate the effect of IFN-γ liposome (nano) on peripheral lymphocytes from 20 individuals in each group: lung cancer patients compared to healthy individuals. The effectiveness of IFN-γ liposome against oxidative stress was also evaluated in this study. A concentration of 100 U·mL-1 of IFN-γ liposome was used to treat the lymphocytes in the Comet and micronucleus assays based on the preliminary test for the optimal dose. The lymphocytes from lung cancer patients presented with higher DNA damage levels than those of healthy individuals. In healthy individuals, IFN-γ liposome did not cause any DNA damage in the lymphocytes. Also, it caused a significant reduction in DNA damage in the lymphocytes from lung cancer patients in both the Comet and micronucleus assays. The 100 U·mL-1 of IFN-γ liposome significantly reduced the oxidative stress caused by H2O2 and appeared to be effective in both groups using the Comet and micronucleus assays. Results from both Comet and micronucleus assays were consistent. The data obtained indicated that IFN-γ in both forms (IFN-γ bulk and IFN-γ nanoliposome) may potentially be effective for the treatment of lung cancer and showed the ability of IFN-γ liposome to reduce DNA damage more than the bulk form.

Infective endocarditis in an intravenous drug user: multiple fatal complications.

Here, we present a case of a 43-year-old patient with a background of active intravenous drug use who was diagnosed with aortic valve endocarditis. This was complicated by extensive acute embolic stroke and acute splenic, renal and liver infarction. This case highlights the difficulties in managing infective endocarditis in intravenous drug users and the importance of a comprehensive approach, addressing both the intracardiac infection and the underlying issue of substance misuse, to ensure best patient outcomes.

Using a Modified Lymphocyte Genome Sensitivity (LGS) test or TumorScan test to detect cancer at an early stage in each individual.

Our previous case-control study observed isolated lymphocytes from 208 individuals and determined the differences in the sensitivity to genomic damage of lymphocytes derived from cancer patients, pre/suspect cancer patients and healthy volunteers using the Comet assay (Anderson et al, 2014). We adapted the LGS technique using a slightly different method and examined 700 more blood samples from 598 patients with cancer or suspected cancer and 102 healthy individuals. To help increase the sensitivity of the test and detect cancer at the level of each individual, we joined with the IMSTAR team who analysed our cells with their fully automated Pathfinder™ cell reader-analyser system. With this reading and analysis system 4,000 to 10,000 cells were able to be read per slide. The new test which is called TumorScan is a highly sensitive test to detect any cancer at an early stage through the response of the white blood cells to UV treatment. These patient blood samples have also been collected at the stage before confirming diagnosis and treatment. There were four of these individuals with cancer who had received anti-cancer treatment. The results from these patients showed a reverse pattern compared to non-treated cancer patients and followed the pattern seen in healthy individuals. The results are consistent with the early results as reported in the above 2014 paper. Given the results from these samples were in a particularly challenging subgroup, whose cancer status was difficult to distinguish, the data suggest that the technique using the TumorScan system could exceed the area under the ROC curve >93% obtained in the earlier study on a group basis, whereas this present study was to detect cancer at an early stage in each individual.

DNA damage protection by bulk and nano forms of quercetin in lymphocytes of patients with chronic obstructive pulmonary disease exposed to the food mutagen 2-amino-3-methylimidazo [4,5-f]quinolone (IQ).

Chronic obstructive pulmonary disease (COPD) in humans, describes a group of lung conditions characterised by airflow limitation that is poorly reversible. The airflow limitation usually progresses slowly and is related to an abnormal inflammatory response of the lung to toxic particles. COPD is characterised by oxidative stress and an increased risk of lung carcinoma. The 2-amino-3-methylimidazo [4,5-f]quinoline (IQ) is one of a number of mutagenic/carcinogenic heterocyclic amines found mainly in well-cooked meats which are thus part of the regular diet. Antioxidants are very important in order to protect the cells against oxidative damage. The aim of the present study was to assess the effects of IQ on the level of DNA damage and susceptibility to a potent mutagen in peripheral blood cells of COPD patients. DNA damage and the frequency of micronuclei (MNi) were evaluated using the Comet and micronucleus assays, respectively. Differential expressions of both mRNA and protein of the endogenous antioxidant enzyme catalase were evaluated with quantitative polymerase chain reaction (qPCR) and Western blot analysis, respectively. Furthermore, the effect of bulk and nano forms of quercetin and their combination with IQ were examined. Results of the present study clearly demonstrated that MNi frequency in the peripheral blood lymphocytes exhibited a positive correlation with the DNA damage as evident from the different Comet assay parameters. Increase of the endogenous antioxidant catalase also showed there was a stimulation of this enzyme system by IQ. Whereas, the endogenous antioxidant quercetin significantly reduced oxidative stress in COPD patients and healthy individuals.

DNA Damage in Healthy Individuals and Respiratory Patients after Treating Whole Blood In vitro with the Bulk and Nano Forms of NSAIDs.

Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit COX enzyme activity which affects the inflammatory response. Inflammation is associated with increasing cancer incidence. Pre-clinical and clinical studies have shown that NSAID treatment could cause an anti-tumor effect in cancers. In the present study, blood was taken from healthy individuals (n = 17) and patients with respiratory diseases or lung cancer (n = 36). White blood cells (WBC) were treated with either a micro-suspension, i.e., bulk (B) or nano-suspension (N) of aspirin (ASP) or ibuprofen (IBU) up to 500 µg/ml in the comet assay and up to 125 µg/ml in the micronucleus assay. In this study results were compared against untreated lymphocytes and their corresponding treated groups. The results showed, that NSAIDs in their nano form significantly reduced the DNA damage in WBCs from lung cancer patients in bulk and nano compared to untreated lymphocytes. Also, there was a decrease in the level of DNA damage in the comet assay after treating WBCs from healthy individuals, asthma and COPD groups with aspirin N (ASP N) but not with IBU N. In addition, the number of micronuclei decreased after treatment with NSAIDs in their nano form (ASP N and IBU N) in the healthy as well as in the lung cancer group. However, this was not the case for micronucleus frequency in asthma and COPD patients. These data show that lymphocytes from different groups respond differently to treatment with ASP and IBU as measured by comet assay and micronucleus assay, and that the size of the suspended particles of the drugs affects responses.

Zinc oxide nanoparticles affect the expression of p53, Ras p21 and JNKs: an ex vivo/in vitro exposure study in respiratory disease patients.

Zinc oxide (ZnO) nanoparticles are the mostly used engineered metal oxide nanoparticles in consumer products. This has increased the likelihood of human exposure to this engineered nanoparticle (ENPs) through different routes. At present, the majority of the studies concerning ZnO ENPs toxicity have been conducted using in vitro and in vivo systems. In this study, for the first time we assessed the effect of ZnO ENPs on the major cellular pathways in the lymphocytes of healthy individuals as well as in susceptible patients suffering from lung cancer, chronic obstructive pulmonary disease (COPD) and asthma. Using the differential expression analysis, we observed a significant (P < 0.05) dose-dependent (10, 20 and 40 µg/ml for 6h) increase in the expression of tumour suppressor protein p53 (40, 60 and 110%); Ras p21 (30, 52 and 80%); c-Jun N-terminal kinases; JNKs) (28, 47 and 78%) in lung cancer patient samples treated with ZnO ENPs compared to healthy controls. A similar trend was also seen in COPD patient samples where a significant (P < 0.05) dose-dependent increase in the expression of tumour suppressor protein p53 (26, 45 and 84%), Ras p21 (21, 40 and 77%), JNKs (17, 32 and 69%) was observed after 6h of ZnO ENPs treatment at the aforesaid concentrations. However, the increase in the expression profile of tested protein was not significant in the asthma patients as compared to controls. Our results reiterate the concern about the safety of ZnO ENPs in consumer products and suggest the need for a complete risk assessment of any new ENPs before its use.

Pulmonary embolism in Bradford, UK: role of end-tidal CO2 as a screening tool.

End-tidal CO2 (ETCO2) can represent dead space ventilation. The authors aimed to define the optimum ETCO2 to conclusively exclude a pulmonary embolic event. One hundred consecutive patients with suspected pulmonary embolisms (PEs) were enrolled over 6 months in 2012. Symptoms, demographic date, Wells' score, D-dimer levels and the gold standard computed tomography pulmonary angiogram (CTPA) results were collated for analysis. ETCO2 was measured within 24 hours of presentation in all 100 patients. Patient ages ranged from 18 years to 93 years. PE was diagnosed in 38% of cases. The average ETCO2 in patients with a positive CTPA was 3.35 kPa (range 2.4-4.2 kPa, SD 0.50). The average ETCO2 in patients without a PE was 4.41 kPa (range 1.3-6.6 kPa, SD 1.10). All patients positive for a PE obtained an ETCO2 <4.3 kPa (32.3 mmHg). This point (4.3 kPa) had a sensitivity and specificity (100% and 68% respectively), with a negative predictive value of 100% and positive predictive value of 66%. ETCO2 may reliably be used to screen and exclude patients with suspected PEs. If used in combination with D-dimer with clinical probability as a screening tool, CTPA will be required in only a minority of patients.

Effect of nanoparticles on human cells from healthy individuals and patients with respiratory diseases.

The effects of titanium dioxide (TiO2) nanoparticles in peripheral blood lymphocytes from patients with respiratory diseases (lung cancer, chronic obstructive pulmonary disease (COPD) and asthma) were compared with those in healthy individuals, to determine differences in sensitivity to nanochemical insult. The observations made show statistically significant concentration-dependent genotoxic effects of TiO2 in both respiratory patient and control groups in the Comet assay. An increase in the pattern of cytogenetic damage measured in the MN assay without statistical significance except when compared to the negative control of healthy individuals was also observed.

Varicosities of the valleculae: an unusual cause of hemoptysis?

Hemoptysis is a common respiratory symptom causing a great deal of anxiety. The cause is often apparent following a clinical history, upper-airway examination, bronchoscopy, and CT scanning of the thorax. We present a case of massive hemoptysis, the etiology of which was not readily apparent despite this conventional approach. Vallecular hemorrhage has been previously reported but is usually minor unless associated with surgical trauma, and can be readily missed if not aware of the possibility. We speculate about the etiology and mechanism for recurrent hemorrhage.