Enhancement of Drug Dissolution of Erlotinib Tablets by Micronization Technique Using Pharmaceutical Experimental Design

Lung cancer is the second most frequent cancer and among the top cause of death worldwide. Chemotherapy is the main therapeutic option for non-small-cell lung cancer (NSCLC), which accounts for the majority of all lung malignancies. The aim of the current work was to develop a tablet formulation having increased drug release profile to improve the bioavailability in order to reduce the dose of the drug. In this present study, Erlotinib tablet was prepared using micronization technique which showed increase drug release profile. Film-coated tablets containing Erlotinib hydrochloride (150 mg) were prepared by dry granulation technique and coated using Opadry ready-mix. Tablets were characterized for Hardness, Friability, Potency and Drug release profile. Drug release was checked in 0.1 N HCL containing 0.5 % SLS and biorelevant dissolution media up to 60 minutes. Tablets of the selected batch were subjected to dissolution in biorelevant media and compare with reference product. The improvement in the drug release was observed in the biorelevant media in comparison with reference product. The in-vitrodissolution data demonstrated the potential of micronization technology to prepare tablets with improved bioavailability of the drug.

Prevalence and outcome of extra-cardiac findings in patients referred for cardiac computed tomography angiography

Background Cardiac computed tomography angiography (CCTA) includes several extra-cardiac structures. A variety of abnormalities may be clinically important and, in some cases, explain the patient's symptoms. The incidence of extra cardiac findings (ECFs) on CCTA examination ranges between 7% and 56%, with the true prevalence likely affected by patient selection. Methods Cardiac CT scans with suspected coronary disease were prospectively and independently reviewed by a radiologist for the presence of ECFs. Data was collected from a prospectively collated database of all patients who underwent a CCTA scans between June 2011 and October 2015. Patients were followed up for one year after incidental findings were made. Results A total of 635 patients had a CCTA scan during the study period. Of these 325 (51.2%) were male, mean age was 66 [22–88] years, with a mean BMI of 27 [17–56]. Extra-cardiac findings were reported in 126 (19.8%) of these 62 (49%) were classified as clinically important and had further imaging and follow-up. The most common abnormalities were pulmonary nodules 61 (46.8%), Hiatus hernia 15 (12%), lymphadenopathy 12 (10%) and liver cysts 10 (8%), Figure 1a. Malignant tumours were identified in 2 (1.6%) patients and one (0.8%) had both aortic root dilatation and type B aortic dissection. Conclusion Non-cardiac abnormalities in patients undergoing CCTA provides useful information e.g. early diagnosis of lung malignancies and other life threatening conditions in up to 40% of patients. FUNDunding Acknowledgement Type of funding sources: None.

CYTO-HISTOLOGICAL CORRELATION OF BRONCHIAL BRUSH AND BRONCHIAL BIOPSY IN LUNG MALIGNANCIES

BACKGROUND:Lung cancer is one of the most common cancer and cause of cancer related deaths in about 29% of males and 26% of females all over the world. Fiberoptic bronchoscopy has an excellent result in diagnosis of lung cancer when combined with brushing cytology and biopsy. The Aim of the study is to correlate AIM: cytological and histological ndings in diagnosing lung carcinomas. This study was done in Department of Pathology, Government General MATERIALS AND METHODS: and Chest Hospital, Erragada, Hyderabad, Telangana from June 2018 to May 2020. 240 clinically suspected cases of lung malignancies underwent both bronchial brush and bronchial biopsy and were included in this study.RESULTS: Out of 240 cases, malignancy was conrmed in 194 cases by histopathology of bronchial biopsy, in which 152 cases were well correlated with brush cytology. Bronchial brush cytology showed sensitivity of 78.35% , specicity of 100% and accuracy of 82.5%. Bronchial biopsy has better detection rate t CONCLUSION han bronchial brush cytology in this study. However combination of brush cytology and biopsy can be considered as the best procedures for the diagnosis of lung malignancies.

High-Throughput Screen of Natural Compounds and Biomarkers for NSCLC Treatment by Differential Expression and Weighted Gene Coexpression Network Analysis (WGCNA)

Lung cancer is known as the leading cause which presents the highest fatality rate worldwide; non-small-cell lung cancer (NSCLC) is the most prevalent type of lung carcinoma with high severity and affects 80% of patients with lung malignancies. Up to now, the general treatment for NSCLC includes surgery, chemotherapy, and radiotherapy; however, some therapeutic drugs and approaches could cause side effects and weaken the immune system. The combination of conventional therapies and traditional Chinese medicine (TCM) significantly improves treatment efficacy in lung cancer. Therefore, it is necessary to investigate the chemical composition and underlying antitumor mechanisms of TCM, so as to get a better understanding of the potential natural ingredient for lung cancer treatment. In this study, we selected 78 TCM to treat NSCLC cell line (A549) and obtained 92 transcriptome data; differential expression and WGCNA were applied to screen the potential natural ingredient and target genes. The sample which was treated with A. pierreana generated the most significant DEG set, including 6130 DEGs, 2479 upregulated, and 3651 downregulated. KEGG pathway analyses found that four pathways (MAPK, NF-kappa B, p53, and TGF-beta signaling pathway) were significantly enriched; 16 genes were significantly regulated in these four pathways. Interestingly, some of them such as EGFR, DUSP4, IL1R1, IL1B, MDM2, CDKNIA, and IDs have been used as the target biomarkers for cancer diagnosis and therapy. In addition, classified samples into 14 groups based on their pharmaceutical effects, WGCNA was used to identify 27 modules. Among them, green and darkgrey were the most relevant modules. Eight genes in the green module and four in darkgrey were identified as hub genes. In conclusion, we screened out three new TCM (B. fruticose, A. pierreana, and S. scandens) that have the potential to develop natural anticancer drugs and obtained the therapeutic targets for NSCLC therapy. Our study provides unique insights to screen the natural components for NSCLC therapy using high-throughput transcriptome analysis.

Distinct pancreatic and neuronal Lung Carcinoid molecular subtypes revealed by integrative omic analysis

Lung Carcinoids (L-CDs) are uncommon low-grade neuroendocrine tumours that are only recently becoming characterised at the molecular level. Notably data on the molecular events that precipitate altered gene expression programmes are very limited. Here we have identified two discrete L-CD subtypes from transcriptomic and whole-genome DNA methylation data, and comprehensively defined their molecular profiles using Whole-Exome Sequencing (WES) and Single Nucleotide Polymorphism (SNP) genotyping. Subtype (Group) 1 features upregulation of neuronal markers (L-CD-NeU) and is characterised by focal spindle cell morphology, peripheral location (71%), high mutational load (P=3.4x10-4), recurrent copy number alterations and is enriched for Atypical Lung Carcinoids. Group 2 (L-CD-PanC) are centrally located and feature upregulation of pancreatic and metabolic pathway genes concordant with promoter hypomethylation of beta cell and genes related to insulin secretion (P<1x10-6). L-CD-NeU tumours harbour mutations in chromatin remodelling and in SWI/SNF complex members, while L-CD-PanC tumours show aflatoxin mutational signatures and significant DNA methylation loss genome-wide, particularly enriched in repetitive elements (P<2.2 x 10-16). Our findings provide novel insights into the distinct mechanisms of epigenetic dysregulation in these lung malignancies, potentially opening new avenues for biomarker selection and treatment in L-CD patients.

Development of thymic tumor in [LSL:KrasG12D; Pdx1-CRE] mice, an adverse effect associated with accelerated pancreatic carcinogenesis

Pancreatic Ductal AdenoCarcinoma (PDAC) represents about 90% of pancreatic cancers. It is one of the most aggressive cancer, with a 5-year survival rate below 10% due to late diagnosis and poor therapeutic efficiency. This bad prognosis thus encourages intense research in order to better understand PDAC pathogenesis and molecular basis leading to the development of innovative therapeutic strategies. This research frequently involves the KC (LSL:KrasG12D;Pdx1-CRE) genetically engineered mouse model, which leads to pancreatic cancer predisposition. However, as frequently encountered in animal models, the KC mouse model also exhibits biases. Herein, we report a new adverse effect of KrasG12D mutation in KC mouse model. In our hands, 10% of KC mice developed clinical signs reaching pre-defined end-points between 100- and 150-days post-parturition, and associated with large thymic mass development. Histological and genetic analyses of this massive thymus enabled us (1) to characterize it as a highly proliferative thymic lymphoma and (2) to detect the unexpected recombination of the Lox-STOP-Lox cassette upstream KrasG12D allele and subsequent KRASG12D protein expression in all cells composing thymic masses. Finally, we highlighted that development of such thymic tumor was associated with accelerated pancreatic carcinogenesis, immune compartment disorganization, and in some cases, lung malignancies.

Can Interstitial Lung Disease Be A Para-Neoplastic Syndrome?

Interstitial lung diseases (ILD) are a group of conditions with varied etiology, clinical presentation, management, outcome and complications. Although studies have described lung cancer as a sequel of ILD, the association of ILD with non-lung malignancies or ILD presenting as a paraneoplastic syndrome of an underlying occult malignancy deserves further study. In this case series, we describe eight patients with an ILD and an associated neoplasm and discuss the different questions raised by this association.

Pulmonary sequestration with Aspergillus infection presenting as massive hemoptysis and hemothorax with highly elevated carcinoembryonic antigen in pleural effusion that mimics advanced lung malignancy

Background Pulmonary sequestration (PS) associated with massive hemoptysis, hemothorax, and elevated tumor markers or even lung malignancy has been reported in several studies. These clinical features combined with lung lesions on chest imaging are sometimes hard to differentiate from lung malignancies and often complicate the diagnostic procedure. Case presentation A 45-year-old man with PS presented with massive hemoptysis, hemothorax, and extremely elevated carcinoembryonic antigen (CEA) in pleural effusion was initially misdiagnosed with advanced lung carcinoma, but was ultimately diagnosed with PS with Aspergillus infection. Conclusions PS is rarely concurrent with lung cancer; most of the time, it is misdiagnosed as a malignancy, especially when presenting with a fungal infection, which could remarkably elevate CEA in pleural effusion.