Displaying publications 1 - 20 of 308 in total

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  1. Tan D, Mohamad Salleh SA, Manan HA, Yahya N
    J Med Imaging Radiat Oncol, 2023 Aug;67(5):564-579.
    PMID: 37309680 DOI: 10.1111/1754-9485.13546
    INTRODUCTION: Delta-radiomics models are potentially able to improve the treatment assessment than single-time point features. The purpose of this study is to systematically synthesize the performance of delta-radiomics-based models for radiotherapy (RT)-induced toxicity.

    METHODS: A literature search was performed following the PRISMA guidelines. Systematic searches were performed in PubMed, Scopus, Cochrane and Embase databases in October 2022. Retrospective and prospective studies on the delta-radiomics model for RT-induced toxicity were included based on predefined PICOS criteria. A random-effect meta-analysis of AUC was performed on the performance of delta-radiomics models, and a comparison with non-delta radiomics models was included.

    RESULTS: Of the 563 articles retrieved, 13 selected studies of RT-treated patients on different types of cancer (HNC = 571, NPC = 186, NSCLC = 165, oesophagus = 106, prostate = 33, OPC = 21) were eligible for inclusion in the systematic review. Included studies show that morphological and dosimetric features may improve the predictive model performance for the selected toxicity. Four studies that reported both delta and non-delta radiomics features with AUC were included in the meta-analysis. The AUC random effects estimate for delta and non-delta radiomics models were 0.80 and 0.78 with heterogeneity, I2 of 73% and 27% respectively.

    CONCLUSION: Delta-radiomics-based models were found to be promising predictors of predefined end points. Future studies should consider using standardized methods and radiomics features and external validation to the reviewed delta-radiomics model.

    Matched MeSH terms: Lung Neoplasms*
  2. Goh JJ, Ong HT, Lee BS, Teoh HK
    Malays J Pathol, 2023 Aug;45(2):247-259.
    PMID: 37658534
    INTRODUCTION: Mesenchymal stromal cells (MSCs) are promising vehicles for cancer therapy due to their homing ability and potency to be genetically manipulated through either viral or non-viral methods. Interleukin-12 (IL-12) is one of the key immunomodulatory cytokines which has anti-tumour effect. However, systemic administration of the cytokine at therapeutic dosage can cause serious toxicity in the host system due to the high systemic level of interferon-γ (IFN-γ) induced.

    OBJECTIVES: This study aimed to investigate the in vitro growth inhibition of genetically engineered human umbilical cord-derived mesenchymal stromal cells (hUCMSC) expressing IL-12 on H1975 human lung adenocarcinoma cells.

    MATERIALS AND METHODS: Both adenoviral method and electroporation which used to generate hUCMSC-IL12 were compared. The method with better outcome was selected to generate hUCMSC-IL12 for the co-culture experiment with H1975 or MRC-5 cells. Characterisation of hUCMSC and hUCMSC-IL12 was performed.

    RESULTS: Adenoviral method showed superior results in transfection efficiency (63.6%), post-transfection cell viability (82.6%) and hIL-12 protein expression (1.2 x 107 pg/ml) and thus was selected for the downstream experiments. Subsequently, hUCMSC-IL12 showed significant inhibition effect on H1975 cells after 5 days of co-culture. No significant difference was observed for all other co-culture groups, indicating that the inhibition effect was because of hIL-12. Lastly, the integrity of hUCMSC-IL12 remained unaffected by the transduction through examination of their surface markers and differentiation properties.

    CONCLUSION: This study provided proof of concept that hUCMSC can be genetically engineered to express hIL-12 which exerts direct growth inhibition effect on human lung adenocarcinoma cells.

    Matched MeSH terms: Lung Neoplasms*
  3. Rohilla S, Singh M, Priya S, Almalki WH, Haniffa SM, Subramaniyan V, et al.
    PMID: 36734949 DOI: 10.1615/JEnvironPatholToxicolOncol.2022042088
    Melatonin is a serotonin-derived pineal gland hormone with many biological functions like regulating the sleep-wake cycle, circadian rhythm, menstrual cycle, aging, immunity, and antioxidants. Melatonin synthesis and release are more pronounced during the night, whereas exposure to light decreases it. Evidence is mounting in favor of the therapeutic effects of melatonin in cancer prevention, treatment and delayed onset in various cancer subtypes. Melatonin exerts its anticancer effect through modification of its receptors such as melatonin 1 (MT1), melatonin 2 (MT2), and inhibition of cancer cell proliferation, epigenetic alterations (DNA methylation/demethylation, histone acetylation/deacetylation), metastasis, angiogenesis, altered cellular energetics, and immune evasion. Melatonin performs a significant function in immune modulation and enhances innate and cellular immunity. In addition, melatonin has a remarkable impact on epigenetic modulation of gene expression and alters the transcription of genes. As an adjuvant to cancer therapies, it acts by decreasing the side effects and boosting the therapeutic effects of chemotherapy. Since current treatments produce drug-induced unwanted toxicities and side effects, they require alternate therapies. A recent review article attempts to summarize the mechanistic perspective of melatonin in different cancer subtypes like skin cancer, breast cancer, hepatic cancer, renal cell cancer, non-small cell lung cancer (NSCLC), colon oral, neck, and head cancer. The various studies described in this review will give a firm basis for the future evolution of anticancer drugs.
    Matched MeSH terms: Lung Neoplasms*
  4. Kho SS, Chan SK, Ismail AM, Tie ST
    Diagn Cytopathol, 2022 Dec;50(12):583-585.
    PMID: 36135808 DOI: 10.1002/dc.25056
    Matched MeSH terms: Lung Neoplasms*
  5. 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: Lung Neoplasms/drug therapy; Lung Neoplasms/genetics; Lung Neoplasms/physiopathology*
  6. 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: Lung Neoplasms/chemically induced; Lung Neoplasms/physiopathology*
  7. Surien O, Ghazali AR, Masre SF
    Sci Rep, 2021 Jul 21;11(1):14862.
    PMID: 34290382 DOI: 10.1038/s41598-021-94508-7
    Cell proliferation and cell death abnormalities are strongly linked to the development of cancer, including lung cancer. The purpose of this study was to investigate the effect of pterostilbene on cell proliferation and cell death via cell cycle arrest during the transition from G1 to S phase and the p53 pathway. A total of 24 female Balb/C mice were randomly categorized into four groups (n = 6): N-nitroso-tris-chloroethyl urea (NTCU) induced SCC of the lungs, vehicle control, low dose of 10 mg/kg PS + NTCU (PS10), and high dose of 50 mg/kg PS + NTCU (PS50). At week 26, all lungs were harvested for immunohistochemistry and Western blotting analysis. Ki-67 expression is significantly lower, while caspase-3 expression is significantly higher in PS10 and PS50 as compared to the NTCU (p lung SCC as it has the ability to upregulate the p53/p21 pathway, causing cell cycle arrest.
    Matched MeSH terms: Lung Neoplasms/genetics*; Lung Neoplasms/pathology*
  8. Wan Mohd Tajuddin WNB, Abas F, Othman I, Naidu R
    Int J Mol Sci, 2021 Jul 10;22(14).
    PMID: 34299042 DOI: 10.3390/ijms22147424
    Diarylpentanoid (DAP), an analog that was structurally modified from a naturally occurring curcumin, has shown to enhance anticancer efficacy compared to its parent compound in various cancers. This study aims to determine the cytotoxicity, antiproliferative, and apoptotic activity of diarylpentanoid MS13 on two subtypes of non-small cell lung cancer (NSCLC) cells: squamous cell carcinoma (NCI-H520) and adenocarcinoma (NCI-H23). Gene expression analysis was performed using Nanostring PanCancer Pathways Panel to determine significant signaling pathways and targeted genes in these treated cells. Cytotoxicity screening revealed that MS13 exhibited greater inhibitory effect in NCI-H520 and NCI-H23 cells compared to curcumin. MS13 induced anti-proliferative activity in both cells in a dose- and time-dependent manner. Morphological analysis revealed that a significant number of MS13-treated cells exhibited apoptosis. A significant increase in caspase-3 activity and decrease in Bcl-2 protein concentration was noted in both MS13-treated cells in a time- and dose-dependent manner. A total of 77 and 47 differential expressed genes (DEGs) were regulated in MS13 treated-NCI-H520 and NCI-H23 cells, respectively. Among the DEGs, 22 were mutually expressed in both NCI-H520 and NCI-H23 cells in response to MS13 treatment. The top DEGs modulated by MS13 in NCI-H520-DUSP4, CDKN1A, GADD45G, NGFR, and EPHA2-and NCI-H23 cells-HGF, MET, COL5A2, MCM7, and GNG4-were highly associated with PI3K, cell cycle-apoptosis, and MAPK signaling pathways. In conclusion, MS13 may induce antiproliferation and apoptosis activity in squamous cell carcinoma and adenocarcinoma of NSCLC cells by modulating DEGs associated with PI3K-AKT, cell cycle-apoptosis, and MAPK pathways. Therefore, our present findings could provide an insight into the anticancer activity of MS13 and merits further investigation as a potential anticancer agent for NSCLC cancer therapy.
    Matched MeSH terms: Lung Neoplasms/metabolism; Lung Neoplasms/pathology*
  9. 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: Lung Neoplasms/drug therapy*; Lung Neoplasms/pathology
  10. Kho SS, Nyanti LE, Chai CS, Chan SK, Tie ST
    Clin Respir J, 2021 Jun;15(6):595-603.
    PMID: 33113256 DOI: 10.1111/crj.13297
    BACKGROUND: Although radial endobronchial ultrasound (rEBUS) is an important verification tool in guided bronchoscopy, a navigational route was not provided. Manual airway mapping allows the bronchoscopist to translate the bronchial branching in computed tomography (CT) into a comparable bronchoscopic road map. We aimed to explore the feasibility of this technique in navigating conventional rEBUS bronchoscopy in the localisation of peripheral pulmonary lesion by determining navigation success and diagnostic yield.

    METHODS: Retrospective review of consecutive rEBUS bronchoscopy performed with a 6.2 mm conventional bronchoscope navigated via manual bronchial branch reading technique over 18 months.

    RESULTS: Ninety-eight target lesions were included. Median lesion size was 2.67 cm (IQR 2.22-3.38) with 96.9% demonstrating positive CT bronchus sign. Majority (86.7%) of lesions were situated in between the third and fifth airway generations. Procedure was performed with endotracheal intubation in 43.9% and fluoroscopy in 72.4%. 98.9% of lesions were successfully navigated and verified by rEBUS following the pre-planned airway road map. Bidirectional guiding device was employed in 29.6% of cases. Clinical diagnosis was secured in 88.8% of cases, majority of which were malignant disease. The discrepancy between navigation success and diagnostic yield was 10.1%. Target PPL located within five airway generations was associated with better diagnostic yield (95.1% vs. 58.8%, P 

    Matched MeSH terms: Lung Neoplasms*
  11. Chong ZX, Ho WY, Yeap SK, Wang ML, Chien Y, Verusingam ND, et al.
    J Chin Med Assoc, 2021 Jun 01;84(6):563-576.
    PMID: 33883467 DOI: 10.1097/JCMA.0000000000000535
    Lung cancer is one of the most prevalent human cancers, and single-cell RNA sequencing (scRNA-seq) has been widely used to study human lung cancer at the cellular, genetic, and molecular level. Even though there are published reviews, which summarized the applications of scRNA-seq in human cancers like breast cancer, there is lack of a comprehensive review, which could effectively highlight the broad use of scRNA-seq in studying lung cancer. This review, therefore, was aimed to summarize the various applications of scRNA-seq in human lung cancer research based on the findings from different published in vitro, in vivo, and clinical studies. The review would first briefly outline the concept and principle of scRNA-seq, followed by the discussion on the applications of scRNA-seq in studying human lung cancer. Finally, the challenges faced when using scRNA-seq to study human lung cancer would be discussed, and the potential applications and challenges of scRNA-seq to facilitate the development of personalized cancer therapy in the future would be explored.
    Matched MeSH terms: Lung Neoplasms/drug therapy; Lung Neoplasms/genetics*
  12. Heng WS, Kruyt FAE, Cheah SC
    Int J Mol Sci, 2021 May 27;22(11).
    PMID: 34071790 DOI: 10.3390/ijms22115697
    Lung cancer is still one of the deadliest cancers, with over two million incidences annually. Prevention is regarded as the most efficient way to reduce both the incidence and death figures. Nevertheless, treatment should still be improved, particularly in addressing therapeutic resistance due to cancer stem cells-the assumed drivers of tumor initiation and progression. Phytochemicals in plant-based diets are thought to contribute substantially to lung cancer prevention and may be efficacious for targeting lung cancer stem cells. In this review, we collect recent literature on lung homeostasis, carcinogenesis, and phytochemicals studied in lung cancers. We provide a comprehensive overview of how normal lung tissue operates and relate it with lung carcinogenesis to redefine better targets for lung cancer stem cells. Nine well-studied phytochemical compounds, namely curcumin, resveratrol, quercetin, epigallocatechin-3-gallate, luteolin, sulforaphane, berberine, genistein, and capsaicin, are discussed in terms of their chemopreventive and anticancer mechanisms in lung cancer and potential use in the clinic. How the use of phytochemicals can be improved by structural manipulations, targeted delivery, concentration adjustments, and combinatorial treatments is also highlighted. We propose that lung carcinomas should be treated differently based on their respective cellular origins. Targeting quiescence-inducing, inflammation-dampening, or reactive oxygen species-balancing pathways appears particularly interesting.
    Matched MeSH terms: Lung Neoplasms/diagnosis; Lung Neoplasms/etiology*; Lung Neoplasms/metabolism*; Lung Neoplasms/therapy
  13. Ullah A, Leong SW, Wang J, Wu Q, Ghauri MA, Sarwar A, et al.
    Cell Death Dis, 2021 05 14;12(5):490.
    PMID: 33990544 DOI: 10.1038/s41419-021-03771-z
    Lung cancer (LC) is one of the leading causes of cancer-related death. As one of the key features of tumor microenvironment, hypoxia conditions are associated with poor prognosis in LC patients. Upregulation of hypoxic-induced factor-1α (HIF-1α) leads to the activation of various factors that contribute to the increased drug resistance, proliferation, and migration of tumor cells. Apurinic/apyrimidinic endonuclease-1 (APEX1) is a multi-functional protein that regulates several transcription factors, including HIF-1α, that contribute to tumor growth, oxidative stress responses, and DNA damage. In this study, we explored the mechanisms underlying cell responses to hypoxia and modulation of APEX1, which regulate HIF-1α and downstream pathways. We found that hypoxia-induced APEX1/HIF-1α pathways regulate several key cellular functions, including reactive oxygen species (ROS) production, carbonic anhydrase 9 (CA9)-mediated intracellular pH, migration, and angiogenesis. Cephalomannine (CPM), a natural compound, exerted inhibitory effects in hypoxic LC cells via the inhibition of APEX1/HIF-1α interaction in vitro and in vivo. CPM can significantly inhibit cell viability, ROS production, intracellular pH, and migration in hypoxic LC cells as well as angiogenesis of HUVECs under hypoxia through the inhibition of APEX1/HIF-1α interaction. Taken together, CPM could be considered as a promising compound for LC treatment.
    Matched MeSH terms: Lung Neoplasms/genetics*; Lung Neoplasms/pathology
  14. Azizi MIHN, Othman I, Naidu R
    Cancers (Basel), 2021 Apr 05;13(7).
    PMID: 33916349 DOI: 10.3390/cancers13071716
    MicroRNAs (miRNAs) are short-strand non-coding RNAs that are responsible for post-transcriptional regulation of many biological processes. Their differential expression is important in supporting tumorigenesis by causing dysregulation in normal biological functions including cell proliferation, apoptosis, metastasis and invasion and cellular metabolism. Cellular metabolic processes are a tightly regulated mechanism. However, cancer cells have adapted features to circumvent these regulations, recognizing metabolic reprogramming as an important hallmark of cancer. The miRNA expression profile may differ between localized lung cancers, advanced lung cancers and solid tumors, which lead to a varying extent of metabolic deregulation. Emerging evidence has shown the relationship between the differential expression of miRNAs with lung cancer metabolic reprogramming in perpetuating tumorigenesis. This review provides an insight into the role of different miRNAs in lung cancer metabolic reprogramming by targeting key enzymes, transporter proteins or regulatory components alongside metabolic signaling pathways. These discussions would allow a deeper understanding of the importance of miRNAs in tumor progression therefore providing new avenues for diagnostic, therapeutic and disease management applications.
    Matched MeSH terms: Lung Neoplasms
  15. 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 Neoplasms/blood*; Lung Neoplasms/epidemiology; Lung Neoplasms/pathology
  16. Kho SS, Ho YF, Chan SK, Tie ST
    Lancet, 2021 03 13;397(10278):e8.
    PMID: 33714391 DOI: 10.1016/S0140-6736(21)00200-2
    Matched MeSH terms: Lung Neoplasms/diagnosis*
  17. Baraya YS, Yankuzo HM, Wong KK, Yaacob NS
    J Ethnopharmacol, 2021 Mar 01;267:113522.
    PMID: 33127562 DOI: 10.1016/j.jep.2020.113522
    ETHNOPHARMACOLOGICAL RELEVANCE: Locally known as 'pecah batu', 'bayam karang', 'keci beling' or 'batu jin', the Malaysian medicinal herb, Strobilanthes crispus (S. crispus), is traditionally used by the local communities as alternative or adjuvant remedy for cancer and other ailments and to boost the immune system. S. crispus has demonstrated multiple anticancer therapeutic potential in vitro and in vivo. A pharmacologically active fraction of S. crispus has been identified and termed as F3. Major constituents profiled in F3 include lutein and β-sitosterol.

    AIM OF THE STUDY: In this study, the effects of F3, lutein and β-sitosterol on tumor development and metastasis were investigated in 4T1-induced mouse mammary carcinoma model.

    MATERIALS AND METHODS: Tumor-bearing mice were fed with F3 (100 mg/kg/day), lutein (50 mg/kg/day) and β-sitosterol (50 mg/kg/day) for 30 days (n = 5 each group). Tumor physical growth parameters, animal body weight and development of secondary tumors were investigated. The safety profile of F3 was assessed using hematological and histomorphological changes on the major organs in normal control mice (NM).

    RESULTS: Our findings revealed significant reduction of physical tumor growth parameters in all tumor-bearing mice treated with F3 (TM-F3), lutein (TM-L) or β-sitosterol (TM-β) as compared with the untreated group (TM). Statistically significant reduction in body weight was observed in TM compared to the NM or treated (TM-F3, TM-L and TM-β) groups. Histomorphological examination of tissue sections from the F3-treated group showed normal features of the vital organs (i.e., liver, kidneys, lungs and spleen) which were similar to those of NM. Administration of F3 to NM mice (NM-F3) did not cause significant changes in full blood count values.

    CONCLUSION: F3 significantly reduced the total tumor burden and prevented secondary tumor development in metastatic breast cancer without significant toxicities in 4T1-induced mouse mammary carcinoma model. The current study provides further support for therapeutic development of F3 with further pharmacokinetics studies.

    Matched MeSH terms: Lung Neoplasms/blood; Lung Neoplasms/prevention & control*; Lung Neoplasms/secondary
  18. Sachdev Manjit Singh B, Wan SA, Cheong YK, Chuah SL, Teh CL, Jobli AT
    J Med Case Rep, 2021 Feb 23;15(1):94.
    PMID: 33618728 DOI: 10.1186/s13256-020-02642-z
    BACKGROUND: Arthritis is rarely reported as a paraneoplastic manifestation of occult malignancy. We report herein two cases of paraneoplastic arthritis due to occult malignancy. CASE 1: The patient was a 65-year-old woman of asian descent who was a former smoker with a history of spine surgery performed for L4/L5 degenerative disc disease. She presented with a 1-month history of oligoarthritis affecting both ankle joints and early morning stiffness of about 3 hours. Laboratory tests were positive for antinuclear antibody at a titer of 1:320 (speckled) but negative for rheumatoid factor. She was treated for seronegative spondyloarthritis and started on prednisolone without much improvement. A routine chest radiograph incidentally revealed a right lung mass which was found to be adenocarcinoma of the lung. She was treated with gefitinib and her arthritis resolved. CASE 2: The patient was a 64-year-old woman of asian descent, nonsmoker, who presented with a chief complaint of asymmetrical polyarthritis involving her right wrist, second and third metacarpophalangeal joints, and first to fifth proximal interphalangeal joints. She was treated for seronegative rheumatoid arthritis (RA) and started on sulfasalazine, with poor clinical response. Six months later, she developed abdominal pain which was diagnosed as ovarian carcinoma by laparotomy. Her arthritis resolved following treatment of her malignancy with chemotherapy.

    CONCLUSION: In summary, paraneoplastic arthritis usually presents in an atypical manner and responds poorly to disease-modifying antirheumatic drugs. Accordingly, we recommend screening for occult malignancy in patients presenting with atypical arthritis.

    Matched MeSH terms: Lung Neoplasms/diagnosis; Lung Neoplasms/drug therapy
  19. Kamal NAMA, Abdulmalek E, Fakurazi S, Cordova KE, Abdul Rahman MB
    Dalton Trans, 2021 Feb 23;50(7):2375-2386.
    PMID: 33555001 DOI: 10.1039/d1dt00116g
    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.
    Matched MeSH terms: Lung Neoplasms/drug therapy*
  20. Abdul Satar N, Ismail MN, Yahaya BH
    Molecules, 2021 Feb 18;26(4).
    PMID: 33670440 DOI: 10.3390/molecules26041056
    Cancer stem cells (CSCs) represent a small subpopulation within a tumour. These cells possess stem cell-like properties but also initiate resistance to cytotoxic agents, which contributes to cancer relapse. Natural compounds such as curcumin that contain high amounts of polyphenols can have a chemosensitivity effect that sensitises CSCs to cytotoxic agents such as cisplatin. This study was designed to investigate the efficacy of curcumin as a chemo-sensitiser in CSCs subpopulation of non-small cell lung cancer (NSCLC) using the lung cancer adenocarcinoma human alveolar basal epithelial cells A549 and H2170. The ability of curcumin to sensitise lung CSCs to cisplatin was determined by evaluating stemness characteristics, including proliferation activity, colony formation, and spheroid formation of cells treated with curcumin alone, cisplatin alone, or the combination of both at 24, 48, and 72 h. The mRNA level of genes involved in stemness was analysed using quantitative real-time polymerase chain reaction. Liquid chromatography-mass spectrometry was used to evaluate the effect of curcumin on the CSC niche. A combined treatment of A549 subpopulations with curcumin reduced cellular proliferation activity at all time points. Curcumin significantly (p < 0.001) suppressed colonies formation by 50% and shrank the spheroids in CSC subpopulations, indicating inhibition of their self-renewal capability. This effect also was manifested by the down-regulation of SOX2, NANOG, and KLF4. Curcumin also regulated the niche of CSCs by inhibiting chemoresistance proteins, aldehyde dehydrogenase, metastasis, angiogenesis, and proliferation of cancer-related proteins. These results show the potential of using curcumin as a therapeutic approach for targeting CSC subpopulations in non-small cell lung cancer.
    Matched MeSH terms: Lung Neoplasms/drug therapy; Lung Neoplasms/genetics; Lung Neoplasms/pathology*
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