scholarly journals Genetic variants in miR-146a, miR-149, miR-196a2, miR-499 and their influence on relative expression in lung cancers

2011 ◽  
Vol 49 (12) ◽  
Author(s):  
Serena Vinci ◽  
Stefania Gelmini ◽  
Nicola Pratesi ◽  
Simona Conti ◽  
Francesca Malentacchi ◽  
...  
Keyword(s):  
Small Cell Lung Carcinoma ◽  
Sequence Variants ◽  
Genotype Distribution ◽  
Nucleotide Polymorphisms ◽  
Cell Lung Carcinoma ◽  
Lung Cancers ◽  
Relative Expression ◽  
Normal Tissues ◽  
Mrna Targets ◽  
Paired Samples

AbstractThe presence of sequence variants in miRNA genes may influence their processing, expression and binding to target mRNAs. Since single miRNA can have a large number of potential mRNA targets, even minor variations in its expression can have influences on hundreds of putative mRNAs.Here, we evaluated 101 paired samples (cancer and normal tissues) from non-small cell lung carcinoma (NSCLC) patients to study the genotype distribution of single nucleotide polymorphisms (SNPs) inRelative expression ofOur results seem to demonstrate that sequence variants of

Production of Monoclonal Antibodies against a New Carcinoma-associated Marker in View of Developing a Serological Test

1990 ◽  
Vol 5 (3) ◽  
pp. 109-117 ◽  
Author(s):  
E. Tagliabue ◽  
F. Centis ◽  
A. Mastroianni ◽  
S. Martignone ◽  
S. Ménard ◽  
...  
Keyword(s):  
Lung Carcinoma ◽  
Serological Test ◽  
Small Cell Lung Carcinoma ◽  
Metastatic Breast ◽  
Cell Lung Carcinoma ◽  
Normal Tissues ◽  
Diagnostic Applications ◽  
Low Sensitivity ◽  
Nsclc Patients ◽  
And Control

By immunizing a mouse with human metastatic breast tumor cells from patient effusions and infiltrated lymph nodes, a monoclonal antibody (MLuC2), which identifies a new carcinoma-associated marker, was raised. The reactivity of this reagent was studied by immunohistochemistry on live and fixed cells from tumor cell lines and on frozen sections from surgical specimens. Besides reacting with 73% of breast carcinomas, MLuC2 also reacted with 93% of non-small cell lung carcinoma (NSCLC) and with a few normal tissues. The MLuC2-recognized molecule (CaMLuC2), whose MW was 90 KDa according to immunoblotting experiments, was found to be detectable in the serum and could therefore be of particular interest for serological diagnostic applications. Since the CaMLuC2 epitope was not polyexpressed on the bearing molecule, we produced a new generation of MAbs in order to define epitopes coexpressed with CaMLuC2 on the same 90 KDa molecule, and which are therefore suitable to develop a double-determinant immunoradiometric assay (DDIRMA) for the detection of this marker in the sera of lung carcinoma patients. Different analyses by immunohistochemistry, binding inhibition tests and DDIRMA, proved that the two new reagents developed, MLuC8 and MLuC9, recognize the same or closely related epitopes, which are however different from CaMLuC2, but which are all present on the same molecule. Preliminary immunoradiometric tests performed on sera from lung cancer and control patients showed a good specificity but a low sensitivity. In fact, only 42% of the 28 tested sera samples from NSCLC patients scored positive despite the fact that more than 90% of the NSCLC expressed the relevant antigen

Mammalian Target of Rapamycin (mTOR) Inhibition in Advanced Bronchial Carcinoids

2015 ◽  
Vol 11 (2) ◽  
pp. 100
Author(s):  
Nicola Fazio ◽  
Anna Maria Frezza ◽  
◽  
Keyword(s):  
Small Cell Lung Carcinoma ◽  
Mammalian Target Of Rapamycin ◽  
Distant Metastases ◽  
Large Cell ◽  
Somatostatin Analogues ◽  
Neuroendocrine Neoplasms ◽  
Mtor Inhibition ◽  
Cell Lung Carcinoma ◽  
Lung Cancers ◽  
Bronchial Carcinoids

Bronchial carcinoids (BCs), comprising typical (TC) and atypical (AC) carcinoids, account for 1–2 % of all lung cancers and approximately 20–30 % of all neuroendocrine neoplasms (NENs). They represent the low- and intermediate-grade lung NENs, whereas small cell lung carcinoma (SCLC) and large cell neuroendocrine carcinoma (LCNEC) represent the high-grade entities. While the prognosis of BCs is favourable at early stages, it is poor when distant metastases are present. Unfortunately, there is a lack of therapeutic options as well as limited data to support the use of standard therapies and sequences of treatments. Some chemotherapeutic regimens have been reported to be active, but their efficacy has not been validated so far. Somatostatin analogues (SSAs) as single agents can be an option for very slow-growing disease, but their role in combination with other therapies has not been established. Among the new targeted agents, data from clinical trials showed that everolimus is a promising one.

scholarly journals Histopathological subtypes of lung cancer presented at a tertiary care cancer hospital in Kerala: a cross sectional study

2020 ◽  
Vol 8 (1) ◽  
pp. 11
Author(s):  
Sourabh Radhakrishnan ◽  
Sreeja Raju ◽  
Jamuna Angel Joy ◽  
Sanjana Ramakrishnan
Keyword(s):  
Lung Cancer ◽  
Lung Carcinoma ◽  
Clinical Presentation ◽  
Small Cell Lung Carcinoma ◽  
Small Cell ◽  
Histological Subtype ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma ◽  
Lung Cancers ◽  
Significant Difference

Background: Lung cancer is one of the commonest cancers causes high rate of mortality worldwide. An increasing incidence of lung cancer and the pathological profile varies among gender and geographical regions. The present study was aimed to assess the pattern of histological subtypes of lung cancer and their distribution with age and gender.Methods: Histologically proven primary lung cancers were selected from the cancer registry. Distribution of subtypes of lung cancer in various age and gender was collected. The major clinical presentation among the non-small cell lung carcinoma (NSCLC) and small cell lung carcinoma (SCLC) were also analysed. The data were statistically analysed.Results: A total of 155 cases of lung cancers were analysed. Adenocarcinoma of lung was the most common subtype followed by squamous cell carcinoma and SCLC. Majority were males with age of presentation from 23 to 93 years. Age of presentation in the female group was 23-75 years. Significant difference was found between cancer numbers in male and female patients (p=0.0001). Statistically significant difference was found among the distribution of smokers and non-smokers in the NSCLC and SCLC patients (p=0.046). Most of the NSCLC and SCLC patients were presented with dyspnea and coughing.Conclusions: Lung cancers were commonly seen in males and smokers. The most common histological subtype in males and females was adenocarcinoma. The diagnosis of histological subtype at the onset of clinical presentation of suspected cases of lung cancer is required to start the therapeutic regimen at the earliest to increase the longevity of patients.

Rapid Arc-SBRT: Non-invasive immune adjuvant for advanced stage Non-Small Cell Lung Carcinoma

2021 ◽  
Vol 21 ◽  
Author(s):  
Arun Chairmadurai ◽  
Sandeep K. Jain ◽  
Aklank Jain ◽  
Hridayesh Prakash
Keyword(s):  
Lung Carcinoma ◽  
Early Stage ◽  
Small Cell Lung Carcinoma ◽  
Small Cell ◽  
Advanced Stage ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma ◽  
Normal Tissues ◽  
Metastatic Lesions ◽  
Immune Adjuvant

: In conjunction with Radio-chemotherapy, pulmonary resection is recommended for early-stage Non-small-cell lung carcinoma but not for advanced-stage NSCLC patients with having high-grade metastatic lesions. In these cases, Rapid Arc-Stereotactic body radiotherapy (Ra-SBRT) technique offers a therapeutic advantage by delivering focal irradiation to metastatic lung lesions and reduces the bystander toxicity to normal tissues. We have previously demonstrated that Ra-SBRT ablates metastatic lesions and induces tumor immune rejection of metastatic tumors by promoting in situ programming of M2 TAM towards M1-TAM and infiltration of Siglec-8+ Eosinophils. Most interestingly, Ra SBRT has very low abscopal impact and spares normal tissues, which are the significant limitations with conventional radiotherapy. In view of this and Immune adjuvant potential of Ra SBRT, it promotes normalization of aberrant vasculature and inhibits the metastatic potential of NSCLC lesions. In view of this we here propose that Ra-SBRT indeed represents an immunogenic approach for the effective management of advanced-stage NSCLC.

scholarly journals Exploring the prognostic value of SCARF1 in non-small cell lung cancers

2021 ◽  
Author(s):  
Daniel A. Patten ◽  
Shishir Shetty
Keyword(s):  
Endothelial Cells ◽  
Prognostic Value ◽  
Therapeutic Potential ◽  
Small Cell Lung Carcinoma ◽  
Lung Squamous Cell Carcinoma ◽  
Small Cell ◽  
The Cancer Genome Atlas ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma ◽  
Lung Cancers

AbstractScavenger receptor class F member 1 (SCARF1) has previously been shown to be highly expressed within the human liver, hold prognostic value in hepatocellular carcinoma and mediate the specific recruitment of leukocytes to liver sinusoidal endothelial cells; however, to date, the liver remains the only major organ in which SCARF1 has been explored in any detail. Here, we utilised publically-available RNA-sequencing data from The Cancer Genome Atlas (TGCA) to identify the lungs as a site of significant SCARF1 expression and attribute the majority of its expression to endothelial cell populations. Next, we show that SCARF1 expression is significantly reduced in two histologically distinct types of non-small cell lung carcinoma cancers (NSCLCs), lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), compared to non-tumoural tissues. Interestingly, loss of SCARF1 expression was associated with aggressive tumour biology in LUAD tissues, but not in LUSC. Furthermore, increased SCARF1 expression was highly prognostic of better overall survival in LUAD tumour tissues, but this was again in contrast to LUSC tumours, in which SCARF1 held no prognostic value. Finally, we showed that SCARF1 is widely expressed in tumour endothelial cells of non-small cell lung cancers and that its total expression in LUAD tumour tissues correlated with immune score and CD4+ T cell infiltration. This study represents the first detailed exploration of SCARF1 expression in normal and diseased human lung tissues and further highlights the prognostic value and therapeutic potential of SCARF1 in immunologically active cancers.

Are sarcomatoid lung cancers resistant tumors to conventional chemotherapy?

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e19036-e19036
Author(s):  
Marie Wislez ◽  
Thibault Vieira ◽  
Mony Ung ◽  
Martine Antoine ◽  
Isabelle Monnet ◽  
...  
Keyword(s):  
Small Cell Lung Carcinoma ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Cell Lung Carcinoma ◽  
Free Survival ◽  
Lung Cancers ◽  
Risk Of Death ◽  
Best Response ◽  
Early Progression ◽  
Stage Iv Disease

e19036 Background: Pulmonary sarcomatoid carcinomas (SC) account for about 0.4% of non-small cell lung carcinoma. These tumors have a poor prognosis due to high aggressiveness and maybe chemotherapy (CT) resistance. Methods: From 1995 to 2012, all consecutive patients with SC from 7 French hospitals and who underwent a 1st-line chemotherapy were included. Clinical characteristics and effect of CT (best response by RECIST 1.1 and progression-free survival [PFS]) as well as overall survival (OS) were collected. Results: Ninety-seven patients were included. Mean age was 62±1 years, 70% were men, 84% smokers, 84% symptomatic, 25% had a stage III and 75% a stage IV disease. At 1st-line, 73% received a platinum-based CT and 27% received a non-platinum-based CT. Progression (PR), stable disease (SD) and response (RR) rates were 69, 14.5 and 16.5%, respectively. For patients with platinum-based CT, PR, SD and RR rates were 69, 11 and 20%, respectively. RR rate was higher for platinum- than for non-platinum-based CT (p=0.018). Median PFS and OS were 2.0 mo [1.8 ; 2.3] and 6.7 mo [5.1 ; 8.2], respectively. No statistical difference in PFS (p=0.264) and OS (p=0.096) was observed between platinum and non-platinum based CT. In multivariate analysis, factors associated with better OS were disease control (HR=0.36 [0.21;0.59]), platinum-based CT (HR=0.92 [0.85;0.99]) and tobacco status (HR=0.92 [0.85 ; 0.99]). Conclusions: Two-thirds of patients with SC had early progression during 1st-line CT. Platinum-based regimen increased response rate for a few and was an independent factor for better OS with a 8% decreased risk of death. Overall, SC appear to be chemoresistant suggesting that new therapeutic strategies based on a better knowledge of its carcinogenesis should be tested for these patients.

scholarly journals BRAF in Lung Cancers: Analysis of Patient Cases Reveals Recurrent BRAF Mutations, Fusions, Kinase Duplications, and Concurrent Alterations

2018 ◽  
pp. 1-15 ◽  
Author(s):  
Yuri Sheikine ◽  
Dean Pavlick ◽  
Samuel J. Klempner ◽  
Sally E. Trabucco ◽  
Jon H. Chung ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Carcinoma ◽  
Small Cell ◽  
Braf V600e ◽  
Small Cell Lung ◽  
Braf Mutations ◽  
Data Set ◽  
Cell Lung Carcinoma ◽  
Lung Cancers ◽  
Small Series

Purpose Dabrafenib and trametinib are approved for the management of advanced non–small-cell lung cancers (NSCLCs) that harbor BRAF V600E mutations. Small series and pan-cancer analyses have identified non-V600 alterations as therapeutic targets. We sought to examine a large genomic data set to comprehensively characterize non-V600 B RAF alterations in lung cancer. Patients and Methods A total of 23,396 patients with lung cancer provided data to assay with comprehensive genomic profiling. Data were reviewed for predicted pathogenic BRAF base substitutions, short insertions and deletions, copy number changes, and rearrangements. Results Adenocarcinomas represented 65% of the occurrences; NSCLC not otherwise specified (NOS), 15%; squamous cell carcinoma, 12%; and small-cell lung carcinoma, 5%. BRAF was altered in 4.5% (1,048 of 23,396) of all tumors; 37.4% (n = 397) were BRAF V600E, 38% were BRAF non-V600E activating mutations, and 18% were BRAF inactivating. Rearrangements were observed at a frequency of 4.3% and consisted of N-terminal deletions (NTDs; 0.75%), kinase domain duplications (KDDs; 0.75%), and BRAF fusions (2.8%). The fusions involved three recurrent fusion partners: ARMC10, DOCK4, and TRIM24. BRAF V600E was associated with co-occurrence of SETD2 alterations, but other BRAF alterations were not and were instead associated with CDKN2A, TP53, and STK11 alterations ( P < .05). Potential mechanisms of acquired resistance to BRAF V600E inhibition are demonstrated. Conclusion This series characterized the frequent occurrence (4.4%) of BRAF alterations in lung cancers. Recurrent BRAF alterations in NSCLC adenocarcinoma are comparable to the frequency of other NSCLC oncogenic drivers, such as ALK, and exceed that of ROS1 or RET. This work supports a broad profiling approach in lung cancers and suggests that non-V600E BR AF alterations represent a subgroup of lung cancers in which targeted therapy should be considered.

scholarly journals TTF-1/p63-Positive Poorly Differentiated NSCLC: A Histogenetic Hypothesis from the Basal Reserve Cell of the Terminal Respiratory Unit

Diagnostics ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 25
Author(s):  
Daniela Cabibi ◽  
Sandro Bellavia ◽  
Antonino Giulio Giannone ◽  
Nadia Barraco ◽  
Calogero Cipolla ◽  
...  
Keyword(s):  
Mutational Analysis ◽  
Small Cell Lung Carcinoma ◽  
Alveolar Epithelium ◽  
Small Cell ◽  
Specific Marker ◽  
Basal Cells ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma ◽  
Lung Cancers ◽  
Poorly Differentiated

TTF-1 is expressed in the alveolar epithelium and in the basal cells of distal terminal bronchioles. It is considered the most sensitive and specific marker to define the adenocarcinoma arising from the terminal respiratory unit (TRU). TTF-1, CK7, CK5/6, p63 and p40 are useful for typifying the majority of non-small-cell lung cancers, with TTF and CK7 being typically expressed in adenocarcinomas and the latter three being expressed in squamous cell carcinoma. As tumors with coexpression of both TTF-1 and p63 in the same cells are rare, we describe different cases that coexpress them, suggesting a histogenetic hypothesis of their origin. We report 10 cases of poorly differentiated non-small-cell lung carcinoma (PD-NSCLC). Immunohistochemistry was performed by using TTF-1, p63, p40 (ΔNp63), CK5/6 and CK7. EGFR and BRAF gene mutational analysis was performed by using real-time PCR. All the cases showed coexpression of p63 and TTF-1. Six of them showing CK7+ and CK5/6− immunostaining were diagnosed as “TTF-1+ p63+ adenocarcinoma”. The other cases of PD-NSCLC, despite the positivity for CK5/6, were diagnosed as “adenocarcinoma, solid variant”, in keeping with the presence of TTF-1 expression and p40 negativity. A “wild type” genotype of EGFR was evidenced in all cases. TTF1 stained positively the alveolar epithelium and the basal reserve cells of TRU, with the latter also being positive for p63. The coexpression of p63 and TTF-1 could suggest the origin from the basal reserve cells of TRU and represent the capability to differentiate towards different histogenetic lines. More aggressive clinical and morphological features could characterize these “basal-type tumors” like those in the better known “basal-like” cancer of the breast.

scholarly journals Bone morphogenetic protein-9 promotes the proliferation of non-small cell lung cancer cells by activating PI3K/Akt and Smad1/5 pathways

RSC Advances ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 7214-7220
Author(s):  
Xiaodong Hou ◽  
Yuanbo Peng ◽  
Jianhua Liu ◽  
Qixiang Zhong ◽  
Zhenglun Yu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Lung Carcinoma ◽  
Small Cell Lung Carcinoma ◽  
Small Cell ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma ◽  
Lung Cancers ◽  
Morphogenetic Protein ◽  
Bone Morphogenetic Protein 9

Non-small-cell lung carcinoma (NSCLC) is any type of epithelial lung cancer other than small cell lung carcinoma (SCLC), which accounts for about 85% of all lung cancers.

scholarly journals SAT-303 3D Mapping of the Human Growth Hormone Locus Identifies Putative Regulatory Hubs for Genes Involved in Cellular Signalling and Cancer-Related Pathways

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Lekha Jain ◽  
Tayaza Fadason ◽  
William Schierding ◽  
Mark Hedley Vickers ◽  
Justin M O’Sullivan ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Small Cell Lung Carcinoma ◽  
Normal Growth ◽  
Regulatory Elements ◽  
Signalling Pathways ◽  
Nucleotide Polymorphisms ◽  
Specific Expression ◽  
Cell Lung Carcinoma ◽  
Cellular Signalling ◽  
A Genome

Abstract Growth hormone (GH) is a peptide hormone predominantly produced in the pituitary that is crucial for normal growth and metabolism. Downstream effects of GH are mediated through binding to the GH receptor (GHR) and consequent activation of key signalling cascades including JAK-STAT, MAPK, PI3K-Akt and mTOR. The GH locus is comprised of five evolutionarily related genes under the control of an upstream locus control region which coordinates tissue-specific expression of these genes in the pituitary and placenta (1). Compromised GH signalling and genetic variation in these genes has been implicated in various disorders including cancer. We hypothesised that polymorphisms which occur within the GH locus have the potential to impact on disease phenotypes by altering or disrupting gene regulation. We used the CoDeS3D (Contextualize Developmental SNPs using 3D Information) algorithm to analyse 529 common single nucleotide polymorphisms (SNPs) across the locus. This algorithm identifies colocalised Hi-C and eQTL associations to determine which SNPs are associated with a change in gene expression at loci that physically interact within the nucleus. We identified 181 common SNPs that interacted with 292 eGenes in 48 different tissues. 145 eGenes were regulated in trans. We performed pathway enrichment of identified eGenes and found these to be enriched in GH/GHR-related downstream cellular signalling pathways including MAPK, PI3K-Akt-mTOR, and ErbB signalling. Enrichment was also observed in the Wnt and Hippo signalling pathways. There was also a significant representation of these eGenes in pathways associated with hepatocellular, colorectal, breast and non-small cell lung carcinoma. 33 eQTL SNPs identified in our study were found to be of regulatory importance in a genome-wide Survey of Regulatory Elements (SuRE) reporter screen (2). In addition, 7 eQTL SNPs were located in known enhancer regions. Our data suggests that regions within the GH locus form regulatory hubs for multiple genes in cis and trans (intra and inter-chromosomal), many of which are involved in mediating GH function in normal and pathogenic states. Reference: (1) Tsai et al. Nucleic Acids Res 2016, 44, 10, 4651 (2) van Arensbergen et al. Nat Genet 2019, 51, 7, 1160.

Sign in / Sign up

Export Citation Format

Share Document