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A review on epidermal growth factor receptor's role in breast and non-small cell lung cancer

Subramaniyan V, Fuloria S, Gupta G, Kumar DH, Sekar M, Sathasivam KV, et al.

Chem Biol Interact, 2022 Jan 05;351:109735.
PMID: 34742684 DOI: 10.1016/j.cbi.2021.109735

Epithelial growth factor receptor (EGFR) is a cell surface transmembrane receptor that mediates the tyrosine signaling pathway to carry the extracellular messages inside the cell and thereby alter the function of nucleus. This leads to the generation of various protein products to up or downregulate the cellular function. It is encoded by cell erythroblastosis virus oncogene B1, so called C-erb B1/ERBB2/HER-2 gene that acts as a proto-oncogene. It belongs to the HER-2 receptor-family in breast cancer and responds best with anti-Herceptin therapy (anti-tyrosine kinase monoclonal antibody). HER-2 positive breast cancer patient exhibits worse prognosis without Herceptin therapy. Similar incidence and prognosis are reported in other epithelial neoplasms like EGFR + lung non-small cell carcinoma and glioblastoma (grade IV brain glial tumor). Present study highlights the role and connectivity of EGF with various cancers via signaling pathways, cell surface receptors mechanism, macromolecules, mitochondrial genes and neoplasm. Present study describes the EGFR associated gene expression profiling (in breast cancer and NSCLC), relation between mitrochondrial genes and carcinoma, and several in vitro and in vivo models to screen the synergistic effect of various combination treatments. According to this study, although clinical studies including targeted treatments, immunotherapies, radiotherapy, TKi-EGFR combined targeted therapy have been carried out to investigate the synergism of combination therapy; however still there is a gap to apply the scenarios of experimental and clinical studies for further developments. This review will give an idea about the transition from experimental to most advanced clinical studies with different combination drug strategies to treat cancer.

Matched MeSH terms: Carcinoma, Non-Small-Cell Lung/physiopathology*
Fulltext Relationship between pulmonary function and degree of spinal deformity, location of apical vertebrae and age among adolescent idiopathic scoliosis patients

Johari J, Sharifudin MA, Ab Rahman A, Omar AS, Abdullah AT, Nor S, et al.

Singapore Med J, 2016 Jan;57(1):33-8.
PMID: 26831315 DOI: 10.11622/smedj.2016009

This retrospective review aimed to examine the relationship between preoperative pulmonary function and the Cobb angle, location of apical vertebrae and age in adolescent idiopathic scoliosis (AIS). To our knowledge, there have been no detailed analyses of preoperative pulmonary function in relation to these three factors in AIS.

Matched MeSH terms: Lung/physiopathology*
Fulltext NTCU induced pre-malignant and malignant stages of lung squamous cell carcinoma in mice model

Zakaria MA, Rajab NF, Chua EW, Selvarajah GT, Masre SF

Sci Rep, 2021 Nov 18;11(1):22500.
PMID: 34795360 DOI: 10.1038/s41598-021-01988-8

Mice have served as an excellent model to understand the etiology of lung cancer for years. However, data regarding dual-stage carcinogenesis of lung squamous cell carcinoma (SCC) remain elusive. Therefore, we aim to develop pre-malignant (PM) and malignant (M) lung SCC in vivo using N-nitroso-tris-chloroethylurea (NTCU). BALB/C mice were allotted into two main groups; PM and M groups which received treatment for 15 and 30 weeks, respectively. Then, the mice in each main group were allotted into three groups; control, vehicle, and cancer (n = 6), which received normal saline, 70% acetone, and 0.04 M NTCU by skin painting, respectively. Histopathologically, we discovered a mix of hyperplasia, metaplasia, and dysplasia lesions in the PM group and intracellular bridge; an SCC feature in the M group. The M group was positive for cytokeratin 5/6 protein which confirmed the lung SCC subtype. We also found significantly higher (P lung SCC in mice model at appropriate weeks and the vehicle group was suggested to be adequate as control group for future research.

Matched MeSH terms: Carcinoma, Non-Small-Cell Lung/physiopathology*
Predicting the risk of exacerbation in patients with chronic obstructive pulmonary disease using home telehealth measurement data

Mohktar MS, Redmond SJ, Antoniades NC, Rochford PD, Pretto JJ, Basilakis J, et al.

Artif Intell Med, 2015 Jan;63(1):51-9.
PMID: 25704112 DOI: 10.1016/j.artmed.2014.12.003

BACKGROUND: The use of telehealth technologies to remotely monitor patients suffering chronic diseases may enable preemptive treatment of worsening health conditions before a significant deterioration in the subject's health status occurs, requiring hospital admission.
OBJECTIVE: The objective of this study was to develop and validate a classification algorithm for the early identification of patients, with a background of chronic obstructive pulmonary disease (COPD), who appear to be at high risk of an imminent exacerbation event. The algorithm attempts to predict the patient's condition one day in advance, based on a comparison of their current physiological measurements against the distribution of their measurements over the previous month.
METHOD: The proposed algorithm, which uses a classification and regression tree (CART), has been validated using telehealth measurement data recorded from patients with moderate/severe COPD living at home. The data were collected from February 2007 to January 2008, using a telehealth home monitoring unit.
RESULTS: The CART algorithm can classify home telehealth measurement data into either a 'low risk' or 'high risk' category with 71.8% accuracy, 80.4% specificity and 61.1% sensitivity. The algorithm was able to detect a 'high risk' condition one day prior to patients actually being observed as having a worsening in their COPD condition, as defined by symptom and medication records.
CONCLUSION: The CART analyses have shown that features extracted from three types of physiological measurements; forced expiratory volume in 1s (FEV1), arterial oxygen saturation (SPO2) and weight have the most predictive power in stratifying the patients condition. This CART algorithm for early detection could trigger the initiation of timely treatment, thereby potentially reducing exacerbation severity and recovery time and improving the patient's health. This study highlights the potential usefulness of automated analysis of home telehealth data in the early detection of exacerbation events among COPD patients.

Matched MeSH terms: Lung/physiopathology
Fulltext Does the duration of smoking cessation have an impact on hospital admission and health-related quality of life amongst COPD patients?

Abu Hassan H, Abd Aziz N, Hassan Y, Hassan F

Int J Chron Obstruct Pulmon Dis, 2014;9:493-8.
PMID: 24868154 DOI: 10.2147/COPD.S56637

BACKGROUND: Lack of awareness among ex-smokers on the benefits of sustaining smoking cessation may be the main cause of their smoking relapse. This study explored health-related quality of life (HRQoL) and hospital admission amongst chronic obstructive pulmonary disease (COPD) patients according to the duration of smoking cessation.
MATERIALS AND METHODS: This study recruited COPD patients from a chest clinic who agreed to participate in a medication therapy-adherence program from January to June 2013. They were interviewed during their visits to obtain information regarding their smoking history and HRQoL. They were divided into three groups according to smoking status (sustained quitters, quit ≥5 years; quitters, quit <5 years; and smokers, smoking at least one cigarette/day). The effects of the duration of cessation on HRQoL and hospital admission were analyzed using a multinomial logistic model.
RESULTS: A total of 117 participants with moderate COPD met the inclusion criteria, who were comprised of 41 sustained quitters, 40 quitters, and 36 smokers. Several features were similar across the groups. Most of them were married elderly men (aged >64 years) with low-to-middle level of education, who smoked more than 33 cigarettes per day and had high levels of adherence to the medication regimen. The results showed that sustained quitters were less likely to have respiratory symptoms (cough, phlegm and dyspnea) than smokers (odds ratio 0.02, confidence interval 0-0.12; P<0.001). The hospital admission rate per year was increased in quitters compared to smokers (odds ratio 4.5, confidence interval 1.91-10.59; P<0.005).
CONCLUSION: A longer duration of quitting smoking will increase the benefits to COPD patients, even if they experience increased episodic respiratory symptoms in the early period of the cessation. Thus, the findings of this study show the benefits of early smoking cessation.
KEYWORDS: HRQoL; chronic obstructive pulmonary disease (COPD); hospital admission and hospital stay
Study site: Chest Clinic, Hospital Melaka, Malaysia

Matched MeSH terms: Lung/physiopathology*
Pulmonary tuberculosis presenting as community-acquired pneumonia

Liam CK, Pang YK, Poosparajah S

Respirology, 2006 Nov;11(6):786-92.
PMID: 17052309

The aims of this study were to investigate the frequency of Mycobacterium tuberculosis as a cause of community-acquired pneumonia (CAP) requiring hospitalization in Malaysia, and to define the clinical features of pulmonary tuberculosis (PTB) that distinguish it from non-TB CAP.

Matched MeSH terms: Lung/physiopathology
Fulltext VitalQPlus: a potential screening tool for early diagnosis of COPD

Sui CF, Ming LC, Neoh CF, Ibrahim B

Int J Chron Obstruct Pulmon Dis, 2015;10:1613-22.
PMID: 26316735 DOI: 10.2147/COPD.S84618

Background: This study utilized a validated combination of a COPD Population Screener
(COPD-PS) questionnaire and a handheld spirometric device as a screening tool for patients at high risk of COPD, such as smokers. The study aimed to investigate and pilot the feasibility and application of this combined assessment, which we termed the “VitalQPlus”, as a screening tool for the early detection of COPD, especially in primary care settings.
Methods: This was a cross-sectional study screening potentially undiagnosed COPD patients using a validated five-item COPD-PS questionnaire together with a handheld spirometric device. Patients were recruited from selected Malaysian government primary care health centers.
Results: Of the total of 83 final participants, only 24.1% (20/83) were recruited from Perak and Penang (peninsular Malaysia) compared to 75.9% (63/83) from Sabah (Borneo region). Our dual assessment approach identified 8.4% of the surveyed patients as having potentially undiagnosed COPD. When only the Vitalograph COPD-6 screening tool was used, 15.8% of patients were detected with a forced expiratory volume in 1 second/forced expiratory volume in 6 seconds (FEV1/FEV6) ratio at <0.75, while 35.9% of patients were detected with the COPD-PS questionnaire. These findings suggested that this dual assessment approach has a greater chance of identifying potentially undiagnosed COPD patients compared to the Vitalograph COPD-6 or COPD-PS questionnaire when used alone. Our findings show that patients with more symptoms (scores of >=5) yielded twice the percentage of outcomes of FEV1/FEV6 <0.75 compared to patients with fewer COPD symptoms (scores <5).
Conclusion: With the availability of a simple screening questionnaire and the COPD-6, there is an opportunity easily to make patients more aware of their lung symptoms and to encourage the provision of early treatment. The proposed dual assessment approach, which we termed the VitalQPlus, may play a profound role in the early diagnosis of COPD, which is crucial in improving the clinical management of the disease.
Keywords: spirometry, pulmonary function test, chronic obstructive pulmonary disease,
airway obstruction

Matched MeSH terms: Lung/physiopathology*
Fulltext Clinical phenotypes of COPD and health-related quality of life: a cross-sectional study

Chai CS, Liam CK, Pang YK, Ng DL, Tan SB, Wong TS, et al.

Int J Chron Obstruct Pulmon Dis, 2019 03 01;14:565-573.
PMID: 30880946 DOI: 10.2147/COPD.S196109

Introduction: The Spanish COPD guideline (GesEPOC) classifies COPD into four clinical phenotypes based on the exacerbation frequency and dominant clinical manifestations. In this study, we compared the disease-specific health-related quality of life (HRQoL) of patients with different clinical phenotypes.
Methods: This was a cross-sectional study of patients with COPD attending the respiratory medicine clinic of University of Malaya Medical Centre from 1 June 2017 to 31 May 2018. Disease-specific HRQoL was assessed by using the COPD Assessment Test (CAT) and St George's Respiratory Questionnaire for COPD (SGRQ-c).
Results: Of 189 patients, 28.6% were of non-exacerbator phenotype (NON-AE), 18.5% were of exacerbator with emphysema phenotype (AE NON-CB), 39.7% were of exacerbator with chronic bronchitis phenotype (AE CB), and 13.2% had asthma-COPD overlap syndrome phenotype (ACOS). The total CAT and SGRQ-c scores were significantly different between the clinical phenotypes (P<0.001). Patients who were AE CB had significantly higher total CAT score than those with ACOS (P=0.033), AE NON-CB (P=0.001), and NON-AE (P<0.001). Concerning SGRQ-c, patients who were AE CB also had a significantly higher total score than those with AE NON-CB (P=0.001) and NON-AE (P<0.001). However, the total SGRQ-c score of AE CB patients was only marginally higher than those who had ACOS (P=0.187). There was a significant difference in the score of each CAT item (except CAT 7) and SGRQ-c components between clinical phenotypes, with AE CB patients recording the highest score in each of them.
Conclusion: Patients who were AE CB had significantly poorer HRQoL than other clinical phenotypes and recorded the worst score in each of the CAT items and SGRQ-c components. Therefore, AE CB patients may warrant a different treatment approach that focuses on the exacerbation and chronic bronchitis components.

Matched MeSH terms: Lung/physiopathology*
Fulltext Pulmonary function in symptom-free asthmatics

Yaacob I, Mohammad M

Singapore Med J, 1993 Dec;34(6):522-3.
PMID: 8153715

Seventy-five adult asthmatic patients with clinical remission underwent spirometry. Only 8.3% of the subjects demonstrated normal spirometry. The others had reduced vital capacity (VC), forced vital capacity (FVC), forced expiratory volume in one second (FEV1), maximum mid-expiratory flow rate (MMF) and peak flow rate (PEFR). This study demonstrates that asthma can cause irreversible airflow obstruction and there is a poor relationship between symptoms in asthmatics and their respiratory function test results.
Study site: Chest clinic, Hospital Universiti Sains Malaysia (HUSM), Kelantan, Malaysia

Matched MeSH terms: Lung/physiopathology*