Investigating the genomic alteration improved the clinical outcome of aged patients with lung carcinoma

Background Lung carcinoma is a common geriatric disease. The development of genotype-targeted therapies greatly improved the management of lung carcinoma. However, the treatment for old patients can be more complex than that for young individuals. Results To investigate the benefits of genetic detection for older patients with lung carcinoma, we explored the genomic profiling of 258 patients with more than 55 years using a targeted next generation sequencing, and some of these patients were treated with targeted therapies based on the results of genomic detection. KRAS codon 61 mutations were found in 15.2% KRAS-mutated patients, which tend to be co-existing with other classical activating mutations other than codons 12/13. Acquired EGFR C797S mutations were identified in 2 cases and ERBB2 amplification was identified in 1 case. All these 3 cases developed resistance to EGFR tyrosine kinase inhibitors and showed expected results of their followed therapies. The median progression-free survival and median overall survival of patients treated with molecular targeted therapies were better than those of patients treated with chemoradiotherapy alone. Conclusions Our findings revealed the specific genomic profiles of patients older than 55 years with lung carcinoma and suggested that these old patients have been benefit from the genetic detection, which helped identify druggable mutations and distinguish resistance mechanisms.

Low-dose aspirin and incidence of lung carcinoma in patients with chronic obstructive pulmonary disease in Hong Kong: A cohort study

Background Evidence suggests that chronic obstructive pulmonary disease (COPD) is associated with a higher risk of lung carcinoma. Using a territory-wide clinical electronic medical records system, we investigated the association between low-dose aspirin use (≤160 mg) among patients with COPD and incidence of lung carcinoma and the corresponding risk of bleeding. Methods and findings This is a retrospective cohort study conducted utilizing Clinical Data Analysis Reporting System (CDARS), a territory-wide database developed by the Hong Kong Hospital Authority. Inverse probability of treatment weighting (IPTW) was used to balance baseline covariates between aspirin nonusers (35,049 patients) with new aspirin users (7,679 patients) among all eligible COPD patients from 2005 to 2018 attending any public hospitals. The median age of the cohort was 75.7 years (SD = 11.5), and 80.3% were male. Competing risk regression with Cox proportional hazards model were performed to estimate the subdistribution hazard ratio (SHR) of lung carcinoma with low-dose aspirin and the associated bleeding events. Of all eligible patients, 1,779 (4.2%, 1,526 and 253 among nonusers and users) were diagnosed with lung carcinoma over a median follow-up period of 2.6 years (interquartile range [IQR]: 1.4 to 4.8). Aspirin use was associated with a 25% lower risk of lung carcinoma (SHR = 0.75, 95% confidence interval [CI] 0.65 to 0.87, p = <0.001) and 26% decrease in lung carcinoma–related mortality (SHR = 0.74, 95% CI 0.64 to 0.86, p = <0.001). Subgroup analysis revealed that aspirin was beneficial for patients aged above or below 75 years, but was also beneficial among populations who were male, nondiabetic, and nonhypertensive. Aspirin use was not associated with an increased risk of upper gastrointestinal bleeding (UGIB) (SHR = 1.19, 95% CI 0.94 to 1.53, p = 0.16), but was associated with an increased risk of hemoptysis (SHR = 1.96, 95% CI 1.73 to 2.23, p < 0.001). The main limitations of the study were (i) that one group of patients may be more likely to seek additional medical attention, although this was partially mitigated by the use of propensity score analysis; and (ii) the observational nature of the study renders it unable to establish causality between aspirin use and lung carcinoma incidence. Conclusions In this study, we observed that low-dose aspirin use was associated with a lower risk of lung carcinoma and lung carcinoma–related mortality among COPD patients. While aspirin was not associated with an increased risk of UGIB, the risk of hemoptysis was elevated.

Evaluation of P40 and Napsin A in the Differential Diagnosis of Non Small Cell Bronchogenic Carcinoma on Small Lung Biopsies

BACKGROUND :- Lung cancer is the leading cause of cancer-related mortality over word wide, Although the pathological diagnosis of lung carcinoma is limited as only small specimen available for diagnosis.the availability of targeted therapies has created a need for precise subtyping of non-small cell lung carcinoma . Several recent studies have demonstrated that the use of Immunohistochemical markers can be helpful in differentiating lung squamous cell carcinoma (LSCC) from lung adenocarcinoma (LAC) not on surgically resected material but also on small biopsy samples and cytology. AIM (1) To classify the non small cell lung carcinoma into major categories like squamous cell carcinoma (LSCC) and adenocarcinoma (LAC) and other categories by applying immunohistochemicalmarker like p40 (truncated p63) and Napsin A (2) To analyse the sensitivity and specificity of p40 and Napsin A in light of histomorphology and/or other relevant immunohistochemical markers available, using appropriate statistical tests. Material and methods:- This study was a one and half year (18 months) prospective study from Jan 2017 to June 2018, conducted in department of pathology on patients attending the outpatient and inpatient department of TB and respiratory disease, a total of 210 bronchoscopic guided biopsies / transthoracic (CT/MRI /guided) small tissue biopsies from the patients suspected of lung malignancy were incorporated in the study. 20 corresponding resection specimens (wedge resection and lobectomy) were also included in the study for correlation of morphology and immunohistochemical findings on small biopsies. RESULTS:-In our study IHC for both p40 and napsin –A aided in subtyping of 71.9% cases of non small cell lung carcinoma and this diagnostic accuracy was found to be statistically significant with p-value < 0.05.,on statistical analysis we found that napsin-A had a sensitivity of 90% and specificity of 80%. Also, positive predictive value and negative predictive value were seen to be 88.0% and 81.8% respectively.

Analysis of Histopathological Findings of Lung Carcinoma in Czech Black Coal Miners in Association with Coal Workers’ Pneumoconiosis

Coal miners with coal workers’ pneumoconiosis (CWP, J60 according to ICD-10) were previously found to have a significantly higher risk of lung carcinoma compared to the general male population. The presented study aimed to analyze the (i) incidence of lung carcinoma in miners, (ii) histopathological findings in cohorts with and without CWP, and (iii) effect of smoking cessation on the histopathological profile. Analyzed cohorts consisted of miners with (n = 3476) and without (n = 6687) CWP. Data on personal and working history obtained from the medical records were combined with information on lung cancer from the Czech Oncological Register and histopathological findings. Statistical analysis was performed using non-parametric tests and the incidence risk ratio at the significance level of 5%. In 1992–2015, 180 miners (2.7%) without CWP and 169 (4.9%) with CWP, respectively, were diagnosed with lung carcinoma. The risk of lung cancer in miners with CWP was 1.82 (95% CI: 1.48–2.25) times higher than in those without CWP. Squamous cell carcinoma (37%) was the most common histopathological type, followed by adenocarcinoma (22%) and small cell carcinoma (21%). A statistically significant difference between the cohorts (p = 0.003) was found in the histopathological subtypes, with the incidence of small cell carcinoma being 2 times higher in miners without CWP than in those with CWP. Only a few individuals with lung carcinoma were non-smokers. The incidence of small cell carcinoma, which is strongly associated with smoking, is significantly higher in miners without CWP. Smoking constitutes the most important risk factor for developing lung carcinoma even in that cohort. However, CWP remains a very important risk factor.

Serum deprivation enhanced ethanol-induced toxic responses in A549, lung carcinoma cells

Aim: The current study explores the toxic consequences of ethanol on human lung carcinoma cell, A549 in serum-deprived condition. Methodology: Human lung carcinoma cells, A549, were cultured in complete and serum-deprived medium for 6 hr. Subsequently, they were exposed to 50 mM and 100 mM concentrations of ethanol. Cytotoxicity studies linked with cell viability, oxidative stress, cell cycle arrest and micronuclei formation were performed using various toxicological parameters, namely MTT assay, DCFDA based ROS generation, cell cycle analysis and micronuclei formation assay. The cytotoxicity of ethanol in complete and serum deprived medium were compared at similar doses and time duration. Results: The metabolic viability assay demonstrated that 50 mM and 100 mM concentration of ethanol did not induce significant levels of cytotoxic alteration in A549 lung carcinoma cells in complete medium. However, in serum-deprived conditions, 50 mM and 100 mM ethanol concentration significantly altered cell viability. Further, exposure of 50 mM and 100 mM concentration of ethanol enhanced reactive oxygen species levels in A549 cells more significantly in serum-deprived conditions than in complete medium. In addition to cytotoxicity and oxidative stress, 50 mM and 100 mM ethanol also arrested the cells at G0 phase more significantly in serum deprived conditions compared to complete medium. Interpretation: Both 50 mM and 100 mM ethanol concentration enhanced the cell cytotoxicity and reactive oxygen species, cell cycle arrest and micronuclei formation more severely in serum-deprived medium than in complete medium (containing 10% FBS) under similar treatment conditions.

Synthesis of CEG-AgNPs as a Promising MMPs/COX-2/Bcl-2 Signaling Pathway Modulator in BaP-Induced Lung Carcinoma

Cucurbitacins are a class of highly oxidized tetracyclic triterpenoids. It’s hydrophobic properties and poor solubility in water, polymeric micellar systems exhibited improved antitumor efficacy because of a better solubilization and targeting after local and/or systemic administration. The aim of the present work was to evaluate the anticancer activity of CEG-AgNPs against benzo[a]pyren (BaP)-induced lung carcinoma. CEG-AgNPs was prepared, characterized and evaluated for its cytotoxic activity against A549 lung carcinoma cell line. Also, the anticancer activity of CEG-AgNPs (70.25 mg/kg) against BaP-induced lung carcinoma was evaluated in vivo, using 30 adult mice for 43 days. IC50 of CEG-AgNPs against A549 lung carcinoma cell line were approximately 94.47 μg/mL. Administration of BaP (50 mg/kg b.w.) to mice induced lung carcinoma with a significant increase in lung MMP-2, MMP-9, MMP-12, MDA, IL-6 and NF-κB as well as significant decreased in lung CAT, GPx and GSH level. Also, treatment with BaP produced significant increase in lung VEGF-C, COX-2 and Bcl-2 gene expression as compared to control group. Daily oral administration of CEG-AgNPs to mice treated with BaP showed a significant protection against-induced increase in lung MMP-2, MMP-9, MMP-12, MDA, IL-6 and NF-κB levels. The treatment also resulted in a significant increase in lung CAT, GPx and GSH level. In addition, the CEG-AgNPs could inhibit lung VEGF-C, COX-2 and Bcl-2 gene expression as compared to BaP treated mice. The histological and MRI examination showed that a significant normalization has been observed through in CEG-AgNPs treated mice. The biochemical, histological and MRI results showed that CEG-AgNPs have potent anticancer activity against BaP-induced lung carcinoma through modulating multiple cellular behaviours and signaling pathways leading to the suppression of adaptive immune responses.