Researchers are looking into the potential development of natural compounds for anticancer therapy. Previous studies have postulated the cytotoxic effect of helichrysetin towards different cancer cell lines. In this study, we investigated the cytotoxic effect of helichrysetin, a naturally occurring chalcone on four selected cancer cell lines, A549, MCF-7, Ca Ski, and HT-29, and further elucidated its biochemical and molecular mechanisms in human lung adenocarcinoma, A549. Helichrysetin showed the highest cytotoxic activity against Ca Ski followed by A549. Changes in the nuclear morphology of A549 cells such as chromatin condensation and nuclear fragmentation were observed in cells treated with helichrysetin. Further evidence of apoptosis includes the externalization of phosphatidylserine and the collapse of mitochondrial membrane potential which are both early signs of apoptosis. These signs of apoptosis are related to cell cycle blockade at the S checkpoint which suggests that the alteration of the cell cycle contributes to the induction of apoptosis in A549. These results suggest that helichrysetin has great potentials for development as an anticancer agent.
Pulmonary epithelioid hemangioendothelioma is an uncommon lung malignancy of endothelial origin. Besides demonstrating unpredictable presentation features and prognosis, the paucity of established treatment guidelines remains a challenge in managing these patients. We present two patients. The first patient presented with chronic productive cough over 1-year duration. He was initially diagnosed and showed partial response to treatment for cardiac failure. A persistent right upper zone consolidation on chest radiograph prompted further investigations which revealed the diagnosis of pulmonary epithelioid hemangioendothelioma. The second patient presented with right-sided hemiparesis for 1-month duration. Initial computer tomography scan of the brain showed findings of distant metastatic foci. Subsequent investigations revealed pulmonary epithelioid hemangioendothelioma as the primary lesion. Both patients succumbed without any treatment due to rapid progression of the disease. We believe that pulmonary epithelioid hemangioendothelioma is undoubtedly rarely reported in south-east Asia region. In these two case reports, the patients were diagnosed in west and east Malaysia, respectively, in the same year (2015). Both cases highlight the increasing prevalence of pulmonary epithelioid hemangioendothelioma. We postulate that this could possibly be secondary to the advancement in diagnostic capabilities and improved healthcare facilities available in this region. Late presentation of pulmonary epithelioid hemangioendothelioma generally results in grave prognosis. Further investigations are required to elucidate the nature of progression and therapeutic options for patients with pulmonary epithelioid hemangioendothelioma.
Introduction: Specific mutations in the epidermal growth factor receptor (EGFR) characterize a subgroup of nonsmall
cell lung cancer (NSCLC) patients that may be highly responsive to receptor inhibitor therapy. 18F-FDG PET/CT
scans can map the glucose metabolism and treatment response of NSCLC. Therefore, we aimed to assess the pattern
of metabolic response and outcome of inoperable NSCLC treated with epidermal growth factor receptor (EGFR)
inhibitors, using 18F-FDG PET/CT scan. Methods: A retrospective study of inoperable NSCLC patients on EGFR
inhibitor treatment that were referred for wholebody18F-FDG PET/CT scans was conducted based on cases scanned
from January 2011 to June 2014. Comparison was made among serial attenuation-corrected fused PET/CT images for
all study patients throughout the course of their treatment. Comparison based on PERCIST criteria was categorized
into 4 levels ie. complete response (CMR), partial response (PMR), stable disease (SMD), progressive metabolic
disease (PMD). Results: Overall, there were 5 patients identified, mean age: 57.4 years old +/- 2.9 years; The median
survival time from initiation of EGFR inhibitor treatment to death was 17 months. Two patients showed initial partial
metabolic response (PMR), two had progressive metabolic disease (PMD) and one had complete metabolic response
(CMR) after the initiation of treatment. The patient with initial CMR had relapse and PMD 5 months later. Majority of
patients eventually succumbed to their illness. Conclusions: Wholebody18F-FDG PET/CT is able to assess metabolic
treatment response of NSCLC towards EGFR inhibitor treatment.
Patients with symptomatic complex malignant pleural effusion (MPE) are frequently unfit for decortication and have a poorer prognosis. Septations can develop in MPE, which may lead to failure of complete drainage and pleural infection. Intrapleural fibrinolytic therapy (IPFT) is an alternative treatment. The use of IPFT in patients with anaemia and high risk for intrapleural bleeding is not well established. We report a successful drainage of complex haemoserous MPE with a single modified low-dose of intrapleural 5 mg of alteplase and 5 mg of dornase alfa in a patient with pre-existing anaemia with no significant risk of intrapleural bleeding.
Several randomized controlled trials (RCTs) evaluated the afatinib efficacy in patients with advanced non-small cell lung cancer (NSCLC) and recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). This review systemically outlined and meta-analyzed the afatinib efficacy in NSCLC and R/M HNSCC in terms of overall survival (OS) and progression-free survival (PFS) endpoints. Records were retrieved from PubMed, Web of Science, and ScienceDirect from 2011 to 2020. Eight afatinib RCTs were included and assessed for the risk of bias. In meta-analysis, overall pooled effect size (ES) of OS in afatinib group (AG) significantly improved in all RCTs and NSCLC-RCTs [hazard ratios (HRs): 0.89 (95% CI: 0.81-0.98, p = 0.02); I2 = 0%, p = 0.71/ 0.86 (95% CI: 0.76-0.97; p = 0.02); I2 = 0%, p = 0.50, respectively]. ES of PFS in AG significantly improved in all RCTs, NSCLC-RCTs, and HNSCC-RCTs [HRs: 0.75 (95% CI: 0.68-0.83; p < 0.00001); I2 = 26%, p = 0.24; 0.75 (95% CI: 0.66-0.84; p < 0.00001); I2 = 47%, p = 0.15/0.76 (95% CI: 0.65-88; p = 0.0004); I2 = 34%, p = 0.0004, respectively]. From a clinical viewpoint of severity, interstitial lung disease, dyspnea, pneumonia, acute renal failure, and renal injury were rarely incident adverse events in the afatinib group. In conclusion, first- and second-line afatinib monotherapy improved the survival of patients with NSCLC, while second-line afatinib monotherapy could be promising for R/M HNSCC. The prospective protocol is in PROSPERO (ID = CRD42020204547).
Chemotherapeutic agents used in treating certain cancer types operate in a non-selective manner tending to accumulate in normal, healthy tissue when high doses are used. To mitigate the toxicity effect resulting from this, there is an urgent need to develop active nano delivery systems capable of regulating optimal doses specifically to cancer cells without harming adjacent normal cells. Herein, we report a versatile nanoparticle - zeolitic imidazolate framework-8 (nZIF-8) - that is loaded with a chemotherapeutic agent (gemcitabine; GEM) and surface-functionalized with an autonomous homing system (Arg-Gly-Asp peptide ligand; RGD) via a straightforward, one-pot solvothermal reaction. Successful functionalization of the surface of nZIF-8 loaded GEM (GEM⊂nZIF-8) with RGD was proven by spectroscopic and electron microscopy techniques. This surface-functionalized nanoparticle (GEM⊂RGD@nZIF-8) exhibited enhanced uptake in human lung cancer cells (A549), compared with non-functionalized GEM⊂nZIF-8. The GEM⊂RGD@nZIF-8, experienced not only efficient uptake within A549, but also induced obvious cytotoxicity (75% at a concentration of 10 μg mL-1) and apoptosis (62%) after 48 h treatment when compared to the nanoparticle absent of the RGD homing system (GEM⊂nZIF-8). Most importantly, this surface-functionalized nanoparticle was more selective towards lung cancer cells (A549) than normal human lung fibroblast cells (MRC-5) with a selectivity index (SI) of 3.98. This work demonstrates a new one-pot strategy for realizing a surface-functionalized zeolitic imidazolate framework that actively targets cancer cells via an autonomous homing peptide system to deliver a chemotherapeutic payload effectively.
Targeted delivery of chemotherapeutics through the respiratory system is a potential approach to improve drug accumulation in the lung tumor, while decreasing their negative side effects. However, elimination by the pulmonary clearance mechanisms, including the mucociliary transport system, and ingestion by the alveolar macrophages, rapid absorption into the blood, enzymatic degradation, and low control over the deposition rate and location remain the main complications for achieving an effective pulmonary drug delivery. Therefore, particle-based delivery systems have emerged to minimize pulmonary clearance mechanisms, enhance drug therapeutic efficacy, and control the release behavior. A successful implementation of a particle-based delivery system requires understanding the influential parameters in terms of drug carrier, inhalation technology, and health status of the patient's respiratory system. This review aims at investigating the parameters that significantly drive the clinical outcomes of various particle-based pulmonary delivery systems. This should aid clinicians in appropriate selection of a delivery system according to their clinical setting. It will also guide researchers in addressing the remaining challenges that need to be overcome to enhance the efficiency of current pulmonary delivery systems for aerosols.
Dermatomyositis is often presented as paraneoplastic syndrome. The diagnosis of dermatomyositis can prompt clinicians to further investigate the underlying cause, in particular malignancy. This case report illustrates the association of lung adenocarcinoma and dermatomyositis with antecedent presentation of cutaneous and musculoskeletal manifestations, one year prior to the diagnosis of carcinoma.
Epidermal growth factor receptor (EGFR)--tyrosine kinase inhibitors (TKI) like erlotinib and gefitinib have been approved as monotherapy for the treatment of patients with locally advanced or metastatic non small cell lung cancer (NSCLC) after failure of at least one prior chemotherapy regimen. The use of EGFR-TKI is associated with unique and dramatic dermatologic side effects. We report 2 patients with NSCLC developing a typical acneiform (papulo-pustular) eruption shortly after initiation of EGFR-TKI.
Nine phenolic compounds were identified and quantified in Artocarpus altilia fruit. One of the main compounds was quercetin, which is the major class of flavonoids has been identified and quantified in pulp part of A. altilis fruit of methanol extract. The aim of this study was to evaluate in vitro cytotoxic assay. Inhibitory concentration 50% concentration was determined using trypan blue exclusion assay. Apoptosis induction and cell cycle regulation were studied by flow cytometric analysis. The expression of apoptosis and cell cycle-related regulatory genes were assessed by RT-qPCR study of the methanol extract of pulp part on human lung carcinoma (A549) cell line. A significant increase of cells at G2/M phases was detected (P
Hepatocellular carcinoma (HCC) is an important cancer in Malaysia. This study aimed to determine the epidemiological characteristics and clinical presentations of patients in a multiracial population consisting of three major Asian races: Malays, Chinese and Indians.
Mesenchymal stem cells (MSCs) are emerging as vehicles for anti-tumor cytotherapy; however, investigation on its efficacy to target a specific cancer stem cell (CSC) population in non-small cell lung cancer (NSCLC) is lacking. Using assays to evaluate cell proliferation, apoptosis, and gene expression, we investigated the efficacy of MSCs expressing tumour necrosis factor (TNF)-related apoptosis inducing ligand (MSC-TRAIL) to target and destroy CD133+ (prominin-1 positive) NSCLC-derived CSCs. Characterization of TRAIL death receptor 5 (DR5) revealed that it was highly expressed in the CD133+ CSCs of both H460 and H2170 cell lines. The human MSC-TRAIL generated in the study maintained its multipotent characteristics, and caused significant tumor cell inhibition in NSCLC-derived CSCs in a co-culture. The MSC-TRAIL induced an increase in annexin V expression, an indicator of apoptosis in H460 and H2170 derived CD133+ CSCs. Through investigation of mitochondria membrane potential, we found that MSC-TRAIL was capable of inducing intrinsic apoptosis to the CSCs. Using pathway-specific gene expression profiling, we uncovered candidate genes such as NFKB1, BAG3, MCL1, GADD45A, and HRK in CD133+ CSCs, which, if targeted, might increase the sensitivity of NSCLC to MSC-TRAIL-mediated inhibition. As such, our findings add credibility to the utilization of MSC-TRAIL for the treatment of NSCLC through targeting of CD133+ CSCs.
Bioactive compounds from the medicinal plant, Eurycoma longifolia Jack have been shown to promote anti-proliferative effects on various cancer cell lines. Here we examined the effects of purified eurycomanone, a quassinoid found in Eurycoma longifolia Jack extract, on the expression of selected genes of the A549 lung cancer cells. Eurycomanone inhibited A549 lung cancer cell proliferation in a dose-dependent manner at concentrations ranging from 5 to 20 μg/ml. The concentration that inhibited 50% of cell growth (GI(50)) was 5.1 μg/ml. The anti-proliferative effects were not fully reversible following the removal of eurycomanone, in which 30% of cell inhibition still remained (p<0.0001, T-test). At 8 μg/ml (GI(70)), eurycomanone suppressed anchorage-independent growth of A549 cells by >25% (p<0.05, T-test, n=8) as determined using soft agar colony formation assay. Cisplatin, a chemotherapy drug used for the treatment of non small cell lung cancer on the other hand, inhibited A549 cells proliferation at concentrations ranging from 0.2 μg/ml to 15 μg/ml with a GI(50) of 0.58 μg/ml. The treatment with eurycomanone reduced the abundance expression of the lung cancer markers, heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1, p53 tumor suppressor protein and other cancer-associated genes including prohibitin (PHB), annexin 1 (ANX1) and endoplasmic reticulum protein 28 (ERp28) but not the house keeping genes. The mRNA expressions of all genes with the exception of PHB were significantly downregulated, 72 h after treatment (p<0.05, T-test, n=9). These findings suggest that eurycomanone at viable therapeutic concentrations of 5-20 μg/ml exhibited significant anti-proliferative and anti-clonogenic cell growth effects on A549 lung cancer cells. The treatment also resulted in suppression of the lung cancer cell tumor markers and several known cancer cell growth-associated genes.
Radon gas has been known as one of the main factors that cause breathing complications which lead to lung cancer, second only after smoking habit. As one of the most commonly found Naturally Occurring Radioactive Materials (NORM), its contribution to background radiation is immense, and its contributors, Uranium and Thorium are widely available on Earth and have been in existence for such a long time with long half-lives. Indoor radon exposure contributed by building materials worsens the effects. The probability of inhaling radon-polluted air and being surrounded by it in any buildings is very high. This research is focused on the detection of radon emanation rate from various building materials which are commonly being used in Malaysia. Throughout this research, common building materials used in constructions in Malaysia were collected and indoor radon exposure from each material was measured individually using Tight Chamber Method coupled to a Continuous Radon Monitor, CRM 1029. It has been shown that sand brick is the biggest contributor to indoor radon compared to other samples such as sand, soil, black cement, white cement, and clay brick. From the results, materials which have high radon emanation could be reconsidered as building materials and mitigation action can be chosen, suitable to its application.
Two hundred and ninety-three bronchoscopies were done for 285 patients (78% males, 22% females) at Hospital University Sains Malaysia between 1984 and 1988. The mean age was 56.4 years (range 13 to 90 years). 70.2% of patients underwent bronchoscopies to confirm or exclude the diagnosis of carcinoma of the bronchus, out of which 58% were confirmed to have bronchial carcinoma. 77% of the 98 patients with visible endobronchial tumours had biopsy specimens diagnostic of malignancy. Brushing and washing cytology increased the positive yield to 92%. The commonest histological type of bronchial carcinoma identified was squamous cell carcinoma (48.1%), followed by small cell carcinoma (27.1%), anaplastic/undifferentiated carcinoma (12.9%), adenocarcinoma (9.4%) and large cell carcinoma (2.4%). Bronchoscopy for the investigation of haemoptysis identified the commonest cause as 'bronchitis'. There were no complications noted in our series. Notable differences of our experience compared to that of the western series were the high percentage of bronchoscopy done for infective respiratory disorders and the younger age of our patients.
A patient with nasopharyngeal carcinoma developed clubbing and hypertrophic osteoarthropathy 6 months before radiological detection of secondary deposits in the lung. Another patient with nasopharyngeal carcinoma developed digital clubbing and hypertrophic osteoarthropathy 6 months after the discovery of lung metastases. Development of a paraneoplastic syndrome in the form of hypertrophic osteoarthropathy and digital clubbing is very rare. This manifestation of nasopharyngeal cancers is presented, with a short review of its biology and pathogenesis.
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).
Three cases of progressive dyspnoea in young female adults due to pulmonary lymphangitic carcinomatosis are reported. The underlying primary neoplasm was gastric carcinoma in all 3 cases. The diagnosis was not suspected in 2 patients because of their young age.