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Targeting eosinophils in respiratory diseases: Biological axis, emerging therapeutics and treatment modalities

Lee LY, Hew GSY, Mehta M, Shukla SD, Satija S, Khurana N, et al.

Life Sci, 2021 Feb 15;267:118973.
PMID: 33400932 DOI: 10.1016/j.lfs.2020.118973

Eosinophils are bi-lobed, multi-functional innate immune cells with diverse cell surface receptors that regulate local immune and inflammatory responses. Several inflammatory and infectious diseases are triggered with their build up in the blood and tissues. The mobilization of eosinophils into the lungs is regulated by a cascade of processes guided by Th2 cytokine generating T-cells. Recruitment of eosinophils essentially leads to a characteristic immune response followed by airway hyperresponsiveness and remodeling, which are hallmarks of chronic respiratory diseases. By analysing the dynamic interactions of eosinophils with their extracellular environment, which also involve signaling molecules and tissues, various therapies have been invented and developed to target respiratory diseases. Having entered clinical testing, several eosinophil targeting therapeutic agents have shown much promise and have further bridged the gap between theory and practice. Moreover, researchers now have a clearer understanding of the roles and mechanisms of eosinophils. These factors have successfully assisted molecular biologists to block specific pathways in the growth, migration and activation of eosinophils. The primary purpose of this review is to provide an overview of the eosinophil biology with a special emphasis on potential pharmacotherapeutic targets. The review also summarizes promising eosinophil-targeting agents, along with their mechanisms and rationale for use, including those in developmental pipeline, in clinical trials, or approved for other respiratory disorders.

Matched MeSH terms: Lung/pathology
The great masquerade: Empyema thoracis as an unusual presentation of primary lung malignancy

Nyanti LE, Kho SS, Tie ST

Med J Malaysia, 2019 02;74(1):79-81.
PMID: 30846667

Primary lung malignancy presenting as empyema is rare, with a reported incidence of 0.3%. We report a case of a 60- year-old man presenting with unilateral pleural effusion; diagnostic thoracocentesis confirmed Salmonella empyema. Post-drainage, chest radiograph showed persisting right hemithorax opacity; subsequent computed tomography revealed a right lung mass with right upper lobe bronchus obliteration. Percutaneous biopsy confirmed advanced stage lung adenocarcinoma. We discuss the mechanism of post-obstructive pneumonia in lung cancerassociated empyema and the utility of bedside ultrasound in diagnosis of lung masses. Clinicians are alerted to the possibility of lung malignancy in elderly patients presenting with empyema.

Matched MeSH terms: Lung/pathology
Fulltext The Interplay between MicroRNAs and Cellular Components of Tumour Microenvironment (TME) on Non-Small-Cell Lung Cancer (NSCLC) Progression

Lee SS, Cheah YK

J Immunol Res, 2019;2019:3046379.
PMID: 30944831 DOI: 10.1155/2019/3046379

Cellular components of the tumour microenvironment (TME) are recognized to regulate the hallmarks of cancers including tumour proliferation, angiogenesis, invasion, and metastasis, as well as chemotherapeutic resistance. The linkage between miRNA, TME, and the development of the hallmarks of cancer makes miRNA-mediated regulation of TME a potential therapeutic strategy to complement current cancer therapies. Despite significant advances in cancer therapy, lung cancer remains the deadliest form of cancer among males in the world and has overtaken breast cancer as the most fatal cancer among females in more developed countries. Therefore, there is an urgent need to develop more effective treatments for NSCLC, which is the most common type of lung cancer. Hence, this review will focus on current literature pertaining to antitumour or protumourigenic effects elicited by nonmalignant stromal cells of TME in NSCLC through miRNA regulation as well as current status and future prospects of miRNAs as therapeutic agents or targets to regulate TME in NSCLC.

Matched MeSH terms: Carcinoma, Non-Small-Cell Lung/pathology*
Rutin loaded liquid crystalline nanoparticles inhibit non-small cell lung cancer proliferation and migration in vitro

Paudel KR, Wadhwa R, Tew XN, Lau NJX, Madheswaran T, Panneerselvam J, et al.

Life Sci, 2021 Jul 01;276:119436.
PMID: 33789146 DOI: 10.1016/j.lfs.2021.119436

Non-small cell lung cancer (NSCLC) is one of the major causes of cancer-related mortality globally. Despite the availability of therapeutic options, the improvement in patient survival is yet to be achieved. Recent advances in natural product (e.g., Rutin) research, therapeutic nanotechnology and especially the combination of both could aid in achieving significant improvements in the treatment or management of NSCLC. In this study, we explore the anti-cancer activity of Rutin-loaded liquid crystalline nanoparticles (LCNs) in an in vitro model where we have employed the A549 human lung epithelial carcinoma cell line. The anti-proliferative activity was determined by MTT and Trypan blue assays, whereas, the anti-migratory activity was evaluated by the scratch wound healing assay and a modified Boyden chamber assay. We also evaluated the anti-apoptotic activity by Annexin V-FITC staining, and the colony formation activity was studied using crystal violet staining. Here, we report that Rutin-LCNs showed promising anti-proliferative and anti-migratory activities. Furthermore, Rutin-LCNs also induced apoptosis in the A549 cells and inhibited colony formation. The findings warrant further detailed and in-depth anti-cancer mechanistic studies of Rutin-LCNs with a focus towards a potential therapeutic option for NSCLC. LCNs may help to enhance the solubility of Rutin used in the treatment of lung cancer and hence enhance the anticancer effect of Rutin.

Matched MeSH terms: Carcinoma, Non-Small-Cell Lung/pathology
Oestrogen actions contribute to female gender-specific risks in the development of lung carcinoma

Liau CS, Mogan P, Thomas W

J Steroid Biochem Mol Biol, 2021 04;208:105786.
PMID: 33189851 DOI: 10.1016/j.jsbmb.2020.105786

Lung cancer is increasing in incidence particularly among women, associated with a global change in smoking habits. Steroid hormones, particularly oestrogen exert an influence on tumour progression in tissues where their target receptor is expressed. Oestrogen receptor, particularly ERβ is highly expressed in the lung and becomes more highly expressed in lung carcinogenesis. Genes involved in the process of lung carcinoma progression and signalling cascades linked to invasion and angiogenesis are modulated by oestrogen receptors. This review intends to collate recently published evidence identifying a role for oestrogen in the initiation and progression of lung carcinoma and how these two processes are differentially affected by circulating oestrogens both in women and in men. Circulating oestrogens may be a significant risk factor in women's susceptibility to lung carcinoma and also provide an additional approach for more targeted therapy.

Matched MeSH terms: Lung/pathology
Aerosol-based airway epithelial cell delivery improves airway regeneration and repair

Kardia E, Ch'ng ES, Yahaya BH

J Tissue Eng Regen Med, 2018 02;12(2):e995-e1007.
PMID: 28105760 DOI: 10.1002/term.2421

Aerosol-based cell therapy has emerged as a novel and promising therapeutic strategy for treating lung diseases. The goal of this study was to determine the safety and efficacy of aerosol-based airway epithelial cell (AEC) delivery in the setting of acute lung injury induced by tracheal brushing in rabbit. Twenty-four hours following injury, exogenous rabbit AECs were labelled with bromodeoxyuridine and aerosolized using the MicroSprayer® Aerosolizer into the injured airway. Histopathological assessments of the injury in the trachea and lungs were quantitatively scored (1 and 5 days after cell delivery). The aerosol-based AEC delivery appeared to be a safe procedure, as cellular rejection and complications in the liver and spleen were not detected. Airway injury initiated by tracheal brushing resulted in disruption of the tracheal epithelium as well as morphological damage in the lungs that is consistent with acute lung injury. Lung injury scores were reduced following 5 days after AEC delivery (AEC-treated, 0.25 ± 0.06 vs. untreated, 0.53 ± 0.05, P lungs, following acute insults. These findings suggest that aerosol-based AEC delivery can be a valuable tool for future therapy to treat acute lung injury. Copyright © 2017 John Wiley & Sons, Ltd.

Matched MeSH terms: Lung/pathology*
First case of schistosomiasis in Malaysia

Murugasu R, Por P

Southeast Asian J. Trop. Med. Public Health, 1973 Dec;4(4):519-23.
PMID: 4787654
Matched MeSH terms: Lung/pathology
Results of PROFILE 1029, a Phase III Comparison of First-Line Crizotinib versus Chemotherapy in East Asian Patients with ALK-Positive Advanced Non-Small Cell Lung Cancer

Wu YL, Lu S, Lu Y, Zhou J, Shi YK, Sriuranpong V, et al.

J Thorac Oncol, 2018 10;13(10):1539-1548.
PMID: 29966800 DOI: 10.1016/j.jtho.2018.06.012

INTRODUCTION: The phase III randomized PROFILE 1014 study demonstrated superiority of crizotinib to first-line chemotherapy in prolonging progression-free survival (PFS) in previously untreated patients with ALK receptor tyrosine kinase gene (ALK)-positive advanced nonsquamous NSCLC. This result was consistent with that in the smaller subset of East Asian patients in PROFILE 1014. The subsequent study reported here prospectively evaluated crizotinib in a larger East Asian patient population.
METHODS: In this open-label phase III study (PROFILE 1029), patients were randomized 1:1 to receive orally administered crizotinib 250 mg twice daily continuously (3-week cycles) or intravenously administered chemotherapy (pemetrexed 500 mg/m2, plus cisplatin 75 mg/m2, or carboplatin [at a dose to produce area under the concentration-time curve of 5-6 mg·min/mL]) every 3 weeks for a maximum of six cycles. PFS confirmed by independent radiology review was the primary end point.
RESULTS: Crizotinib significantly prolonged PFS (hazard ratio, 0.402; 95% confidence interval [CI]: 0.286-0.565; p < 0.001). The median PFS was 11.1 months with crizotinib and 6.8 months with chemotherapy. The objective response rate was 87.5% (95% CI: 79.6-93.2%) with crizotinib versus 45.6% (95% CI: 35.8-55.7%) with chemotherapy (p < 0.001). The most common adverse events were increased transaminase levels, diarrhea, and vision disorders with crizotinib and leukopenia, neutropenia, and anemia with chemotherapy. Significantly greater improvements from baseline in patient-reported outcomes were seen in crizotinib-treated versus chemotherapy-treated patients.
CONCLUSIONS: First-line crizotinib significantly improved PFS, objective response rate, and patient-reported outcomes compared with standard platinum-based chemotherapy in East Asian patients with ALK-positive advanced NSCLC, which is similar to the results from PROFILE 1014. The safety profiles of crizotinib and chemotherapy were consistent with those previously published.

Matched MeSH terms: Carcinoma, Non-Small-Cell Lung/pathology
Assessment of vaccination with gamma radiationattenuated infective Toxocara canis eggs on murine toxocariasis

Hafez EN, Awadallah FM, Ibrahim SA, Amin MM, El-Nawasera NZ

Trop Biomed, 2020 Mar 01;37(1):89-102.
PMID: 33612721

Toxocara canis is a major parasite that infects many animals with high risk of human infections. This study aims at assessing the immunization with gamma radiationattenuated infective stage on rats challenged with non-irradiated dose. Level of vaccine protection was evaluated in liver and lung regarding parasitological, histopathological, biochemical and molecular parameters. Fifty rats were enrolled in three groups: group A (10 rats) as normal control; group B (20 rats) subdivided into subgroup B1 (infected control) and subgroup B2 infected then challenged after 14 days with the same dose of infection (challenged infected control); and group C (20 rats) subdivided into subgroup C1 vaccinated with a dose of 800 gray (Gy) gamma-radiated infective eggs (vaccine control) and subgroup C2 vaccinated then challenged on 14th day with same number of infective eggs (vaccinated-challenged). Tissues were stained with Haematoxylin and Eosin (H and E) for histopathological studies. Biochemical studies through detection of nitric oxide (NO) and Caspase-3 were conducted. Extent of DNA damage by Comet assay was assessed. Vaccinated-challenged subgroup revealed a marked reduction in larvae in tissues with mild associated histological changes. In addition there was accompanied reduction of NO, Casepase-3 level and DNA damage compared to the control infected group. It could be concluded that vaccination of rats with a dose of 800Gy gamma radiation-attenuated infective stage improves immune response to challenge infection and drastically reduces the morbidity currently seen.

Matched MeSH terms: Lung/pathology
Fulltext Small Cell Transformation and T790M Mutation as Coresistance Mechanisms for First-line Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitor (TKI) Therapy Failure

Shee-Chai C, Liam CK, Mun KS

J Thorac Oncol, 2017 10;12(10):e171-e173.
PMID: 28939153 DOI: 10.1016/j.jtho.2017.06.068
Matched MeSH terms: Carcinoma, Non-Small-Cell Lung/pathology
Fulltext Host-dependent molecular factors mediating SARS-CoV-2 infection to gain clinical insights for developing effective targeted therapy

Shafi G, Desai S, Srinivasan K, Ramesh A, Chaturvedi R, Uttarwar M

Mol Genet Genomics, 2021 May;296(3):501-511.
PMID: 33743061 DOI: 10.1007/s00438-021-01774-1

Coronavirus disease 2019 (COVID-19), a recent viral pandemic that first began in December 2019, in Hunan wildlife market, Wuhan, China. The infection is caused by a coronavirus, SARS-CoV-2 and clinically characterized by common symptoms including fever, dry cough, loss of taste/smell, myalgia and pneumonia in severe cases. With overwhelming spikes in infection and death, its pathogenesis yet remains elusive. Since the infection spread rapidly, its healthcare demands are overwhelming with uncontrollable emergencies. Although laboratory testing and analysis are developing at an enormous pace, the high momentum of severe cases demand more rapid strategies for initial screening and patient stratification. Several molecular biomarkers like C-reactive protein, interleukin-6 (IL6), eosinophils and cytokines, and artificial intelligence (AI) based screening approaches have been developed by various studies to assist this vast medical demand. This review is an attempt to collate the outcomes of such studies, thus highlighting the utility of AI in rapid screening of molecular markers along with chest X-rays and other COVID-19 symptoms to enable faster diagnosis and patient stratification. By doing so, we also found that molecular markers such as C-reactive protein, IL-6 eosinophils, etc. showed significant differences between severe and non-severe cases of COVID-19 patients. CT findings in the lungs also showed different patterns like lung consolidation significantly higher in patients with poor recovery and lung lesions and fibrosis being higher in patients with good recovery. Thus, from these evidences we perceive that an initial rapid screening using integrated AI approach could be a way forward in efficient patient stratification.

Matched MeSH terms: Lung/pathology
Fulltext Lung development, repair and cancer: A study on the role of MMP20 gene in adenocarcinoma

Mok PL, Anandasayanam ANK, Oscar David HM, Tong J, Farhana A, Khan MSA, et al.

PLoS One, 2021;16(4):e0250552.
PMID: 33914777 DOI: 10.1371/journal.pone.0250552

Multiple matrix metalloproteinases have significant roles in tissue organization during lung development, and repair. Imbalance of proteinases may lead to chronic inflammation, changes in tissue structure, and are also highly associated to cancer development. The role of MMP20 is not well studied in lung organogenesis, however, it was previously shown to be present at high level in lung adenocarcinoma. The current study aimed to identify the functional properties of MMP20 on cell proliferation and motility in a lung adenocarcinoma in vitro cell model, and relate the interaction of MMP20 with other molecular signalling pathways in the lung cells after gaining tumoral properties. In this study, two different single guide RNA (sgRNAs) that specifically targeted on MMP20 sites were transfected into human lung adenocarcinoma A549 cells by using CRISPR-Cas method. Following that, the changes of PI3-K, survivin, and MAP-K mRNA gene expression were determined by Real-Time Polymerase Chain Reaction (RT-PCR). The occurrence of cell death was also examined by Acridine Orange/Propidium Iodide double staining. Meanwhile, the motility of the transfected cells was evaluated by wound healing assay. All the data were compared with non-transfected cells as a control group. Our results demonstrated that the transfection of the individual sgRNAs significantly disrupted the proliferation of the A549 cell line through suppression in the gene expression of PI3-K, survivin, and MAP-K. When compared to non-transfected cells, both experimental cell groups showed reduction in the migration rate, as reflected by the wider gaps in the wound healing assay. The current study provided preliminary evidence that MMP20 could have regulatory role on stemness and proliferative genes in the lung tissues and affect the cell motility. It also supports the notion that targeting MMP20 could be a potential treatment mode for halting cancer progression.

Matched MeSH terms: Lung/pathology
Respiratory health status of workers that exposed to welding fumes at Lumut shipyard

Ithnin A, Zubir A, Awang N, Mohamad Sulaiman NN

Pak J Biol Sci, 2019 Jan;22(3):143-147.
PMID: 30972984 DOI: 10.3923/pjbs.2019.143.147

BACKGROUND AND OBJECTIVE: Welding fume exposure has led to the respiratory problems among welders including cough, phlegm, chest illnesses, nausea and fatigue. Inadequate ventilation during welding works causes the situation to worsen. Welding fumes can cause a decrease in lung function among welders. Chronic exposure will lead to other health effects especially COPD (Chronic Obstructive Pulmonary Disease). The objective of this study is to determine the exposure of welding fumes (Cd, Fe, Pb and Zn) towards respiratory health including lung function test (FEV1, FVC, FEV1/FVC, PEFR) of workers in Lumut shipyard, Perak.

MATERIAL AND METHODS: This research study the relationship between exposures of welding fumes towards lung function test among workers in Lumut shipyard, Perak. Lung function test was measured by spirometry among 30 welders and 31 non-welders. The concentration welding fume exposure was measured using OSHA ID-121 method. Sociodemographic data, respiratory symptoms and smoking habit data was analyzed based on the ATS 1987 questionnaire.

RESULTS: The mean concentration for Pb in welding fumes was 2.752 mg m-3 which is above 0.5 mg m-3 PEL-TWA. The FEV1 and FVC readings showed significant different between welders and non-welders (p = 0.001). Cough and phlegm symptoms showed significant different between welders and non-welders (p = 0.001). Welders had higher prevalence in smoking habit than the non-welders. Chest illnesses symptom showed an association with the smoking habit (p = 0.01).

CONCLUSION: There is relationship between welding fumes exposure on lung function test of workers in Lumut shipyard. Pb in welding fumes has high concentration and exceeded PEL-TWA level. The FEV1 and FVC in welders are lower than non-welder due to the fumes exposure. Welders showed higher respiratory symptoms than non-welders. Smoking habit is a contributing factor towards respiratory problem.

Matched MeSH terms: Lung/pathology*
Fulltext The Nature of Exposure Drives Transmission of Nipah Viruses from Malaysia and Bangladesh in Ferrets

Clayton BA, Middleton D, Arkinstall R, Frazer L, Wang LF, Marsh GA

PLoS Negl Trop Dis, 2016 06;10(6):e0004775.
PMID: 27341030 DOI: 10.1371/journal.pntd.0004775

Person-to-person transmission is a key feature of human Nipah virus outbreaks in Bangladesh. In contrast, in an outbreak of Nipah virus in Malaysia, people acquired infections from pigs. It is not known whether this important epidemiological difference is driven primarily by differences between NiV Bangladesh (NiV-BD) and Malaysia (NiV-MY) at a virus level, or by environmental or host factors. In a time course study, ferrets were oronasally exposed to equivalent doses of NiV-BD or NiV-MY. More rapid onset of productive infection and higher levels of virus replication in respiratory tract tissues were seen for NiV-BD compared to NiV-MY, corroborating our previous report of increased oral shedding of NiV-BD in ferrets and suggesting a contributory mechanism for increased NiV-BD transmission between people compared to NiV-MY. However, we recognize that transmission occurs within a social and environmental framework that may have an important and differentiating role in NiV transmission rates. With this in mind, ferret-to-ferret transmission of NiV-BD and NiV-MY was assessed under differing viral exposure conditions. Transmission was not identified for either virus when naïve ferrets were cohoused with experimentally-infected animals. In contrast, all naïve ferrets developed acute infection following assisted and direct exposure to oronasal fluid from animals that were shedding either NiV-BD or NiV-MY. Our findings for ferrets indicate that, although NiV-BD may be shed at higher levels than NiV-MY, transmission risk may be equivalently low under exposure conditions provided by cohabitation alone. In contrast, active transfer of infected bodily fluids consistently results in transmission, regardless of the virus strain. These observations suggest that the risk of NiV transmission is underpinned by social and environmental factors, and will have practical implications for managing transmission risk during outbreaks of human disease.

Matched MeSH terms: Lung/pathology
Fulltext Protective effect of a lipid-based preparation from Mycobacterium smegmatis in a murine model of progressive pulmonary tuberculosis

García Mde L, Borrero R, Lanio ME, Tirado Y, Alvarez N, Puig A, et al.

Biomed Res Int, 2014;2014:273129.
PMID: 25548767 DOI: 10.1155/2014/273129

A more effective vaccine against tuberculosis (TB) is urgently needed. Based on its high genetic homology with Mycobacterium tuberculosis (Mtb), the nonpathogenic mycobacteria, Mycobacterium smegmatis (Ms), could be an attractive source of potential antigens to be included in such a vaccine. We evaluated the capability of lipid-based preparations obtained from Ms to provide a protective response in Balb/c mice after challenge with Mtb H37Rv strain. The intratracheal model of progressive pulmonary TB was used to assess the level of protection in terms of bacterial load as well as the pathological changes in the lungs of immunized Balb/c mice following challenge with Mtb. Mice immunized with the lipid-based preparation from Ms either adjuvanted with Alum (LMs-AL) or nonadjuvanted (LMs) showed significant reductions in bacterial load (P < 0.01) compared to the negative control group (animals immunized with phosphate buffered saline (PBS)). Both lipid formulations showed the same level of protection as Bacille Calmette and Guerin (BCG). Regarding the pathologic changes in the lungs, mice immunized with both lipid formulations showed less pneumonic area when compared with the PBS group (P < 0.01) and showed similar results compared with the BCG group. These findings suggest the potential of LMs as a promising vaccine candidate against TB.

Matched MeSH terms: Lung/pathology
Fulltext Lung cancer staging now and in the future

Liam CK, Andarini S, Lee P, Ho JC, Chau NQ, Tscheikuna J

Respirology, 2015 May;20(4):526-34.
PMID: 25682805 DOI: 10.1111/resp.12489

For a long time lung cancer was associated with a fatalistic approach by healthcare professionals. In recent years, advances in imaging, improved diagnostic techniques and more effective treatment modalities are reasons for optimism. Accurate lung cancer staging is vitally important because treatment options and prognosis differ significantly by stage. The staging algorithm should include a contrast computed tomography (CT) of the chest and the upper abdomen including adrenals, positron emission tomography/CT for staging the mediastinum and to rule out extrathoracic metastasis in patients considered for surgical resection, endosonography-guided needle sampling procedure replacing mediastinoscopy for near complete mediastinal staging, and brain imaging as clinically indicated. Applicability of evidence-based guidelines for staging of lung cancer depends on the available expertise and level of resources and is directly impacted by financial issues. Considering the diversity of healthcare infrastructure and economic performance of Asian countries, optimal and cost-effective use of staging methods appropriate to the available resources is prudent. The pulmonologist plays a central role in the multidisciplinary approach to lung cancer diagnosis, staging and management. Regional respiratory societies such as the Asian Pacific Society of Respirology should work with national respiratory societies to strive for uniform standards of care. For developing countries, a minimum set of care standards should be formulated. Cost-effective delivery of optimal care for lung cancer patients, including staging within the various healthcare systems, should be encouraged and most importantly, tobacco control implementation should receive an absolute priority status in all countries in Asia.

Matched MeSH terms: Carcinoma, Non-Small-Cell Lung/pathology
Fulltext Panduratin A, a possible inhibitor in metastasized A549 cells through inhibition of NF-kappa B translocation and chemoinvasion

Cheah SC, Lai SL, Lee ST, Hadi AH, Mustafa MR

Molecules, 2013 Jul 24;18(8):8764-78.
PMID: 23887718 DOI: 10.3390/molecules18088764

In the present study, we investigated the effects of panduratin A (PA), isolated from Boesenbergia rotunda, on apoptosis and chemoinvasion in A549 human non-small cell lung cancer cells. Activation of the executioner procaspase-3 by PA was found to be dose-dependent. Caspase-3 activity was significantly elevated at the 5 µg/mL level of PA treatment and progressed to a maximal level. However, no significant elevated level was detected on procaspase-8. These findings suggest that PA activated caspase-3 but not caspase-8. Numerous nuclei of PA treated A549 cells stained brightly by anti-cleaved PARP antibody through High Content Screening. This result further confirmed that PA induced apoptotic cell death was mediated through activation of caspase-3 and eventually led to PARP cleavage. Treatment of A549 cells with PA resulted in a strong inhibition of NF-κB activation, which was consistent with a decrease in nuclear levels of NF-κB/p65 and NF-κB/p50 and the elevation of p53 and p21. Besides that, we also showed that PA significantly inhibited the invasion of A549 cells in a dose-dependent manner through reducing the secretion of MMP-2 of A549 cells gelatin zymography assay. Our findings not only provide the effects of PA, but may also be important in the design of therapeutic protocols that involve targeting of either p53 or NF-κB.

Matched MeSH terms: Carcinoma, Non-Small-Cell Lung/pathology
Fulltext Recombinant measles virus vaccine expressing the Nipah virus glycoprotein protects against lethal Nipah virus challenge

Yoneda M, Georges-Courbot MC, Ikeda F, Ishii M, Nagata N, Jacquot F, et al.

PLoS One, 2013;8(3):e58414.
PMID: 23516477 DOI: 10.1371/journal.pone.0058414

Nipah virus (NiV) is a member of the genus Henipavirus, which emerged in Malaysia in 1998. In pigs, infection resulted in a predominantly non-lethal respiratory disease; however, infection in humans resulted in over 100 deaths. Nipah virus has continued to re-emerge in Bangladesh and India, and person-to-person transmission appeared in the outbreak. Although a number of NiV vaccine studies have been reported, there are currently no vaccines or treatments licensed for human use. In this study, we have developed a recombinant measles virus (rMV) vaccine expressing NiV envelope glycoproteins (rMV-HL-G and rMV-Ed-G). Vaccinated hamsters were completely protected against NiV challenge, while the mortality of unvaccinated control hamsters was 90%. We trialed our vaccine in a non-human primate model, African green monkeys. Upon intraperitoneal infection with NiV, monkeys showed several clinical signs of disease including severe depression, reduced ability to move and decreased food ingestion and died at 7 days post infection (dpi). Intranasal and oral inoculation induced similar clinical illness in monkeys, evident around 9 dpi, and resulted in a moribund stage around 14 dpi. Two monkeys immunized subcutaneously with rMV-Ed-G showed no clinical illness prior to euthanasia after challenge with NiV. Viral RNA was not detected in any organ samples collected from vaccinated monkeys, and no pathological changes were found upon histopathological examination. From our findings, we propose that rMV-NiV-G is an appropriate NiV vaccine candidate for use in humans.

Matched MeSH terms: Lung/pathology
Fulltext Triple primary cancers of the larynx, lung and thyroid presenting in one patient

Iqbal FR, Sani A, Gendeh BS, Aireen I

Med J Malaysia, 2008 Dec;63(5):417-8.
PMID: 19803306 MyJurnal

Patients with multiple malignant primary tumours are often described, based on their chronology of presentation, as simultaneous, synchronous or metachronous tumours. Lung malignancies presenting in association with head and neck tumours are well documented while there have been small series of thyroid synchronous cancers presenting with laryngeal lesions in literature. No cases, to our knowledge, have been reported in literature of a single patient with all three laryngeal, lung and thyroid malignancies. We report one such case of a 71-year-old Chinese man who had undergone a total laryngectomy for a recurrent cancer of the larynx only to be found to have tumours of the lung and thyroid in the post-operative period and he eventually died of post-operative complications. We also discuss screening for lung and thyroid malignancies in patients with head and neck squamous cell carcinoma (SCC).

Matched MeSH terms: Lung/pathology
Pathogenesis and vertical transmission of a transplacental rat cytomegalovirus

Loh HS, Mohd-Lila MA, Abdul-Rahman SO, Kiew LJ

Virol J, 2006;3:42.
PMID: 16737550

Cytomegalovirus (CMV) congenital infection is the major viral cause of well-documented birth defects in human. Because CMV is species-specific, the main obstacle to developing animal models for congenital infection is the difference in placental architecture, which preludes virus transmission across the placenta. The rat placenta, resembling histologically to that of human, could therefore facilitate the study of CMV congenital infection in human.

Matched MeSH terms: Lung/pathology

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