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Intrinsic capabilities of Leptospermum javanicum in inducing apoptosis and suppressing the metastatic potential of human lung carcinoma cells

Navanesan S, Abdul Wahab N, Manickam S, Cheow YL, Sim KS

Chem Biol Interact, 2017 Aug 01;273:37-47.
PMID: 28578903 DOI: 10.1016/j.cbi.2017.05.022

The active isolate of LF1 in Leptospermum javanicum was further looked into its capabilities in provoking an apoptotic reaction and suppressing the metastasis process in treated non-small lung cancer cells. LF1 underwent isolation and purification to yield a white powder which was identified as Betulinic acid (BA) via NMR, LCMS and IR spectroscopy. The isolate, BA, which produced an encouraging cytotoxic effect against non-small lung cancer cells (A549 and NCI-H1299) through the MTT assay, was further assessed with TUNEL, Sub-G1 population quantification, acridine orange/ethidium bromide staining as well as activated caspase-3 detection. The results pointed towards the induction of apoptosis as a result of increasing doses of BA, regardless of the p53 status in both cell lines. Treatment with BA also prevented an effective attachment of the invasive A549 cells onto a new culture surface in addition to diminishing the migratory potential of treated cells across a porous membrane. Further investigation through the ELISA detection and gelatin zymography showed an adverse effect to production of matrix metalloproteinase-2 (MMP-2) while the levels of matrix metalloproteinase-9 (MMP-9) were not negatively affected. The findings from this study validate the potential of L. javanicum as a potential anti-cancer treatment as stated in our previous study. The isolate, BA not only showed a capacity in inducing apoptotic cell death in non-small lung cancer cells, but managed to distort the ability of the cancer cells in effectively undergoing the metastasis process.

Matched MeSH terms: Lung Neoplasms/drug therapy; Lung Neoplasms/pathology*
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: Lung Neoplasms/drug therapy; Lung Neoplasms/genetics; Lung Neoplasms/physiopathology*
Non-small cell lung cancer in very young and very old Malaysian patients

Liam CK, Lim KH, Wong CM

Chest, 2002 Jan;121(1):309-10.
PMID: 11796481
Matched MeSH terms: Lung Neoplasms/epidemiology*; Lung Neoplasms/pathology
Biochemical synthesis of silver nanoprticles using filamentous fungi Penicillium decumbens (MTCC-2494) and its efficacy against A-549 lung cancer cell line

Majeed S, Abdullah MS, Dash GK, Ansari MT, Nanda A

Chin J Nat Med, 2016 Aug;14(8):615-20.
PMID: 27608951 DOI: 10.1016/S1875-5364(16)30072-3

Biosynthesis of silver and other metallic nanoparticles is one of the emerging research area in the field of science and technology due to their potentiality, especially in the field of nano-biotechnology and biomedical sciences in order to develop nanomedicine. In our present study, Penicillium decumbens (MTCC-2494) was brought from Institute of Microbial Technology (IMTECH) Chandigarh and employed for extracellular biological synthesis of silver nanoparticles. Ag-NPs formation was appeared with a dark brown color inside the conical flask. Characterization of Ag-NPs were done by UV-Spectrophotometric analysis which showed absorption peak at 430 nm determines the presence of nanoparticles, Fourier transform infrared (FT-IR) spectroscopic analysis, showed amines and amides are the possible proteins involved in the stabilization of nanoparticles as capping agent. Atomic force Microscopy (AFM) confirmed the particle are spherical, size was around 30 to 60 nm and also the roughness of nanoparticles. Field emission scanning electron microscopy (FE-SEM) showed the topology of the nanoparticles and were spherical in shape. The biosynthesis process was found fast, ecofriendly and cost effective. Nano-silver particle was found to have a broad antimicrobial activity and also it showed good enhancement of antimicrobial activity of Carbenicillin, Piperacillin, Cefixime, Amoxicillin, Ofloxacin and Sparfloxacin in a synergistic mode. These Ag-NPs showed good anti-cancer activity at 80 μg·mL(-1)upon 24 hours of incubation and toxicity increases upon 48 hours of incubation against A-549 human lung cancer cell line and the synergistic formulation of the antibiotic with the synthesized nanoparticles was found more effective against the pathogenic bacteria studied.

Matched MeSH terms: Lung Neoplasms/drug therapy
Fulltext Tissue and Plasma EGFR Mutation Analysis in the FLAURA Trial: Osimertinib versus Comparator EGFR Tyrosine Kinase Inhibitor as First-Line Treatment in Patients with EGFR-Mutated Advanced Non-Small Cell Lung Cancer

Gray JE, Okamoto I, Sriuranpong V, Vansteenkiste J, Imamura F, Lee JS, et al.

Clin Cancer Res, 2019 Nov 15;25(22):6644-6652.
PMID: 31439584 DOI: 10.1158/1078-0432.CCR-19-1126

PURPOSE: To assess the utility of the cobas EGFR Mutation Test, with tissue and plasma, for first-line osimertinib therapy for patients with EGFR-mutated (EGFRm; Ex19del and/or L858R) advanced or metastatic non-small cell lung cancer (NSCLC) from the FLAURA study (NCT02296125).
EXPERIMENTAL DESIGN: Tumor tissue EGFRm status was determined at screening using the central cobas tissue test or a local tissue test. Baseline circulating tumor (ct)DNA EGFRm status was retrospectively determined with the central cobas plasma test.
RESULTS: Of 994 patients screened, 556 were randomized (289 and 267 with central and local EGFR test results, respectively) and 438 failed screening. Of those randomized from local EGFR test results, 217 patients had available central test results; 211/217 (97%) were retrospectively confirmed EGFRm positive by central cobas tissue test. Using reference central cobas tissue test results, positive percent agreements with cobas plasma test results for Ex19del and L858R detection were 79% [95% confidence interval (CI), 74-84] and 68% (95% CI, 61-75), respectively. Progression-free survival (PFS) superiority with osimertinib over comparator EGFR-TKI remained consistent irrespective of randomization route (central/local EGFRm-positive tissue test). In both treatment arms, PFS was prolonged in plasma ctDNA EGFRm-negative (23.5 and 15.0 months) versus -positive patients (15.2 and 9.7 months).
CONCLUSIONS: Our results support utility of cobas tissue and plasma testing to aid selection of patients with EGFRm advanced NSCLC for first-line osimertinib treatment. Lack of EGFRm detection in plasma was associated with prolonged PFS versus patients plasma EGFRm positive, potentially due to patients having lower tumor burden.

Matched MeSH terms: Lung Neoplasms/diagnosis; Lung Neoplasms/drug therapy*; Lung Neoplasms/genetics*; Lung Neoplasms/metabolism
Adaptation of international guidelines for metastatic colorectal cancer: an asian consensus

Cheng AL, Li J, Vaid AK, Ma BB, Teh C, Ahn JB, et al.

Clin Colorectal Cancer, 2014 Sep;13(3):145-55.
PMID: 25209093 DOI: 10.1016/j.clcc.2014.06.004

Colorectal cancer (CRC) is among the most common cancers worldwide, but marked epidemiological differences exist between Asian and non-Asian populations. Hence, a consensus meeting was held in Hong Kong in December 2012 to develop Asia-specific guidelines for the management of metastatic CRC (mCRC). A multidisciplinary expert panel, consisting of 23 participants from 10 Asian and 2 European countries, discussed current guidelines for colon or rectal cancer and developed recommendations for adapting these guidelines to Asian clinical practice. Participants agreed that mCRC management in Asia largely follows international guidelines, but they proposed a number of recommendations based on regional 'real-world' experience. In general, participants agreed that 5-fluorouracil (5-FU) infusion regimens in doublets can be substituted with UFT (capecitabine, tegafur-uracil) and S1 (tegafur, 5-chloro-2,4-dihydroxypyridine and oxonic acid), and that the monoclonal antibodies cetuximab and panitumumab are recommended for KRAS wild type tumors. For KRAS mutant tumors, bevacizumab is the preferred biological therapy. FOLFOX (folinic acid, 5-FU, and oxaliplatin) is preferred for initial therapy in Asian patients. The management of mCRC is evolving, and it must be emphasized that the recommendations presented here reflect current treatment practices and thus might change as more data become available.

Matched MeSH terms: Lung Neoplasms/genetics; Lung Neoplasms/secondary; Lung Neoplasms/therapy*
Fulltext Diagnosis of Lung Cancer by Fractal Analysis of Damaged DNA

Namazi H, Kiminezhadmalaie M

Comput Math Methods Med, 2015;2015:242695.
PMID: 26539245 DOI: 10.1155/2015/242695

Cancer starts when cells in a part of the body start to grow out of control. In fact cells become cancer cells because of DNA damage. A DNA walk of a genome represents how the frequency of each nucleotide of a pairing nucleotide couple changes locally. In this research in order to study the cancer genes, DNA walk plots of genomes of patients with lung cancer were generated using a program written in MATLAB language. The data so obtained was checked for fractal property by computing the fractal dimension using a program written in MATLAB. Also, the correlation of damaged DNA was studied using the Hurst exponent measure. We have found that the damaged DNA sequences are exhibiting higher degree of fractality and less correlation compared with normal DNA sequences. So we confirmed this method can be used for early detection of lung cancer. The method introduced in this research not only is useful for diagnosis of lung cancer but also can be applied for detection and growth analysis of different types of cancers.

Matched MeSH terms: Lung Neoplasms/diagnosis*; Lung Neoplasms/genetics
Fulltext Dermatomyositis Anteceding Lung Adenocarcinoma

Lim JL, Yusof NS, Md Tarekh NA, Abdul Rahman R

Cureus, 2020 Nov 19;12(11):e11580.
PMID: 33364104 DOI: 10.7759/cureus.11580

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.

Matched MeSH terms: Lung Neoplasms
The Emerging Role of the Hippo Pathway in Lung Cancers: Clinical Implications

Teoh SL, Das S

Curr Drug Targets, 2017 Nov 30;18(16):1880-1892.
PMID: 27628948 DOI: 10.2174/1389450117666160907153338

BACKGROUND: The incidence of lung cancers has increased globally. Increased exposure to tobacco, passive smoking, less consumption of vegetables and fruits and occupational exposure to asbestos, arsenic and chromium are the main risk factors. The pathophysiology of lung cancer is complex and not well understood. Various microRNAs, genes and pathways are associated with lung cancers. The genes involved in lung cancers produce proteins involved in cell growth, differentiation, different cell cycles, apoptosis, immune modulation, tumor spread and progression. The Hippo pathway (also known as the Salvador-Warts-Hippo pathway) is the latest emerging concept in cancers. The Hippo pathway plays an important role in controlling the size of the tissue and organ by virtue of its action on cell proliferation and apoptosis.
OBJECTIVE: In the present review, we highlight the mammalian Hippo pathway, role of its core members, its upstream regulators, downstream effectors and the resistance cases in lung cancers.
RESULTS: Specific interaction of Mer with cell surface hyaluronan receptor CD44 is vital in cell contact inhibition, thereby activating Hippo pathway. Both transcription co-activators YAP and TAZ (also known as WWTR1, being homologs of Drosophila Yki) are important regulators of proliferation and apoptosis, and serve as major downstream effectors of the Hippo pathway. Mutation of NF2, the upstream regulator of Hippo pathway is linked to the cancers.
CONCLUSION: Targeting YAP and TAZ may be important for future drug delivery and treatment.

Matched MeSH terms: Lung Neoplasms/drug therapy; Lung Neoplasms/genetics; Lung Neoplasms/metabolism*
The anti-idiotype vaccines for immunotherapy

Bhattacharya-Chatterjee M, Chatterjee SK, Foon KA

Curr. Opin. Mol. Ther., 2001 Feb;3(1):63-9.
PMID: 11249733

Certain anti-idiotypic antibodies that bind to the antigen-combining sites of antibodies can effectively mimic the three-dimensional structures and functions of the external antigens and can be used as surrogate antigens for active specific immunotherapy. Extensive studies in animal models have demonstrated the efficacy of these vaccines for triggering the immune system to induce specific and protective immunity against bacterial, viral and parasitic infections as well as tumors. Several monoclonal anti-idiotype antibodies that mimic distinct human tumor-associated antigens have been developed and characterized. Encouraging results have been obtained in recent clinical trials using these anti-idiotype antibodies as vaccines. In this article, we will review the current literature and discuss the potential of this novel therapeutic approach for various human cancers.

Matched MeSH terms: Lung Neoplasms/therapy
Advancing of Cellular Signaling Pathways in Respiratory Diseases Using Nanocarrier Based Drug Delivery Systems

Mehta M, Dhanjal DS, Satija S, Wadhwa R, Paudel KR, Chellappan DK, et al.

Curr Pharm Des, 2020;26(42):5380-5392.
PMID: 33198611 DOI: 10.2174/1381612826999201116161143

Cell Signaling pathways form an integral part of our existence that allows the cells to comprehend a stimulus and respond back. Such reactions to external cues from the environment are required and are essential to regulate the normal functioning of our body. Abnormalities in the system arise when there are errors developed in these signals, resulting in a complication or a disease. Presently, respiratory diseases contribute to being the third leading cause of morbidity worldwide. According to the current statistics, over 339 million people are asthmatic, 65 million are suffering from COPD, 2.3 million are lung cancer patients and 10 million are tuberculosis patients. This toll of statistics with chronic respiratory diseases leaves a heavy burden on society and the nation's annual health expenditure. Hence, a better understanding of the processes governing these cellular pathways will enable us to treat and manage these deadly respiratory diseases effectively. Moreover, it is important to comprehend the synergy and interplay of the cellular signaling pathways in respiratory diseases, which will enable us to explore and develop suitable strategies for targeted drug delivery. This review, in particular, focuses on the major respiratory diseases and further provides an in-depth discussion on the various cell signaling pathways that are involved in the pathophysiology of respiratory diseases. Moreover, the review also analyses the defining concepts about advanced nano-drug delivery systems involving various nanocarriers and propose newer prospects to minimize the current challenges faced by researchers and formulation scientists.

Matched MeSH terms: Lung Neoplasms*
Surface peptide functionalization of zeolitic imidazolate framework-8 for autonomous homing and enhanced delivery of chemotherapeutic agent to lung tumor cells

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*
Intrathyroidal oxyphilic parathyroid carcinoma: A potential diagnostic caveat in cytology?

Wong YP, Sharifah NA, Tan GC, Gill AJ, Ali SZ

Diagn Cytopathol, 2016 May 26.
PMID: 27229757 DOI: 10.1002/dc.23493

Oxyphilic (oncocytic) parathyroid lesions are very uncommon and their cytological features are rarely described. Due to the similarities in anatomical location and indistinguishable cytomorphological features, these lesions are easily confused with neoplastic and non-neoplastic thyroid lesions on fine needle aspiration (FNA). The diagnosis becomes more challenging in cases of unusual intrathyroidal location of the parathyroid lesions in the absence of clinical evidence of hyperparathyroidism, which simulate thyroid nodules clinically. We describe a case of intrathyroidal oxyphilic parathyroid carcinoma in a 66-year-old female, who presented with a dominant left "thyroid" nodule. FNA smears were cellular, comprising predominantly of oxyphilic cells arranged in papillary-like architecture with occasional nuclear grooves, which was mistaken for oncocytic variant of papillary carcinoma of the thyroid. The histological diagnosis of oxyphilic parathyroid "adenoma" was made following total thyroidectomy. The tumor, unfortunately, recurred 7 years later with associated multiple lung metastases. When dealing with thyroid lesions comprising predominantly of oncocytic cells, one should consider oxyphilic parathyroid neoplasms as one of the differential diagnosis. In difficult equivocal cases, a panel of immunocytochemical stains (PTH, GATA3, TTF-1, PAX8, and thyroglobulin) can be helpful. In addition, a combination of valuable clinical, radiological, and laboratory data, including serum calcium and parathyroid hormone levels are key to arriving at an accurate cytological diagnosis. Diagn. Cytopathol. 2016. © 2016 Wiley Periodicals, Inc.

Matched MeSH terms: Lung Neoplasms
Tissue-clot-coagulum cell block in EBUS/TBNA specimen adequacy: A real world experience

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*
Advances and challenges in developing andrographolide and its analogues as cancer therapeutic agents

Soo HL, Quah SY, Sulaiman I, Sagineedu SR, Lim JCW, Stanslas J

Drug Discov Today, 2019 09;24(9):1890-1898.
PMID: 31154065 DOI: 10.1016/j.drudis.2019.05.017

Andrographolide (AGP), a naturally occurring bioactive compound, has been investigated as a lead compound in cancer drug development. Its multidimensional therapeutic effects have raised interest among medicinal chemists, which has led to extensive structural modification of the compound, resulting in analogues with improved pharmacological and pharmaceutical properties. Nevertheless, the analogues with the improved properties need to be rigorously studied to identify drug-like lead compounds. We scrutinised articles published from 2012 to 2018, to objectively provide opinions on the mechanisms of action of AGP and its analogues, as well as their potential as viable anticancer drugs. Preclinical and clinical data, along with the extensive medicinal chemistry efforts, indicate the compounds are potential anticancer agents with specific value in treating recalcitrant cancers such as pancreatic and lung cancers.

Matched MeSH terms: Lung Neoplasms
Metastatic hepatocellular carcinoma presenting as a sphenoid sinus mass and meningeal carcinomatosis

Hashim H, Rahmat K, Abdul Aziz YF, Chandran PA

Ear Nose Throat J, 2014 Jun;93(6):E20-3.
PMID: 24932824

We report the case of a 30-year-old woman who was referred to us for evaluation of a 2-week history of fever, headache, vomiting, bilateral ptosis, and blurred vision. Imaging obtained by the referring institution had identified a sphenoid sinus mass and diffuse meningeal infiltration, which was thought to represent an infective process. We subsequently identified the mass as a metastatic hepatocellular carcinoma (HCC). The patient was placed under palliative care, and she died 1 month later. Metastases to the sphenoid sinus from any primary source are very rare, and they are generally not considered in the radiologic differential diagnosis. HCC is known to metastasize to the lung, lymph nodes, and musculoskeletal system; again, reported cases of metastasis to the sphenoid sinus are rare. Indeed, our review of the English-language literature found only 6 previously reported cases of sinonasal metastasis of a primary HCC. A diagnosis of a sinonasal metastasis is more difficult in a patient who has no previous diagnosis of a primary malignancy. In presenting this case, our aim is to remind readers of this possibility.

Matched MeSH terms: Lung Neoplasms/radiography; Lung Neoplasms/secondary*
Particulate matter air pollution components and risk for lung cancer

Raaschou-Nielsen O, Beelen R, Wang M, Hoek G, Andersen ZJ, Hoffmann B, et al.

Environ Int, 2016 Feb;87:66-73.
PMID: 26641521 DOI: 10.1016/j.envint.2015.11.007

Particulate matter (PM) air pollution is a human lung carcinogen; however, the components responsible have not been identified. We assessed the associations between PM components and lung cancer incidence.

Matched MeSH terms: Lung Neoplasms
Fulltext Association of carcinogenic polycyclic aromatic hydrocarbon emissions and smoking with lung cancer mortality rates on a global scale

Motorykin O, Matzke MM, Waters KM, Massey Simonich SL

Environ Sci Technol, 2013 Apr 2;47(7):3410-6.
PMID: 23472838 DOI: 10.1021/es305295d

The objective of this research was to investigate the relationship between lung cancer mortality rates, carcinogenic polycyclic aromatic hydrocarbon (PAH) emissions, and smoking on a global scale, as well as for different socioeconomic country groups. The estimated lung cancer deaths per 100,000 people (ED100000) and age standardized lung cancer death rate per 100,000 people (ASDR100000) in 2004 were regressed on PAH emissions in benzo[a]pyrene equivalence (BaPeq), smoking prevalence, cigarette price, gross domestic product per capita, percentage of people with diabetes, and average body mass index using simple and multiple linear regression for 136 countries. Using stepwise multiple linear regression, a statistically significant positive linear relationship was found between loge(ED100000) and loge(BaPeq) emissions for high (p-value <0.01) and for the combination of upper-middle and high (p-value <0.05) socioeconomic country groups. A similar relationship was found between loge(ASDR100000) and loge(BaPeq) emissions for the combination of upper-middle and high (p-value <0.01) socioeconomic country groups. Conversely, for loge(ED100000) and loge(ASDR100000), smoking prevalence was the only significant independent variable in the low socioeconomic country group (p-value <0.001). These results suggest that reducing BaPeq emissions in the U.S., Canada, Australia, France, Germany, Brazil, South Africa, Poland, Mexico, and Malaysia could reduce ED100000, while reducing smoking prevalence in Democratic People's Republic of Korea, Nepal, Mongolia, Cambodia, and Bangladesh could significantly reduce the ED100000 and ASDR100000.

Matched MeSH terms: Lung Neoplasms/mortality*
Novel lung adenocarcinoma and nuclear factor-kappa B (NF-κB) inhibitors: synthesis and evaluation of lantadene congeners

Suthar SK, Boon HL, Sharma M

Eur J Med Chem, 2014 Mar 3;74:135-44.
PMID: 24457265 DOI: 10.1016/j.ejmech.2013.12.052

The C-3, C-17 and C-22 congeners of pentacyclic triterpenoids reduced lantadene A (3), B (4) and 22β-hydroxyoleanolic acid (5) were synthesized and were tested in vitro for their NF-κB and IKKβ inhibitory potencies and cytotoxicity against A549 lung cancer cells. The lead congeners 12 and 13 showed IC50 of 0.56 and 0.42 μmol, respectively against TNF-α induced activation of NF-κB. The congeners 12 and 13 exhibited inhibition of IKKβ in a single-digit micromolar dose and at the same time, 12 and 13 showed marked cytotoxicity against A549 lung cancer cells with IC50 of 0.12 and 0.08 μmol, respectively. The lead ester congeners were stable in the acidic pH, while hydrolyzed readily in the human blood plasma to release the active parent moieties.

Matched MeSH terms: Lung Neoplasms/metabolism; Lung Neoplasms/pathology*
In vivo antitumour properties of tribenzyltin carboxylates in a 4T1 murine metastatic mammary tumour model: Enhanced efficacy by PLGA nanoparticles

Anasamy T, Chee CF, Kiew LV, Chung LY

Eur J Pharm Sci, 2020 Jan 15;142:105140.
PMID: 31704345 DOI: 10.1016/j.ejps.2019.105140

This study reports the in vivo performance of two tribenzyltin carboxylate complexes, tri(4-fluorobenzyl)tin[(N,N-diisopropylcarbamothioyl)sulfanyl]acetate (C1) and tribenzyltin isonicotinate (C9), in their native form as well as in a poly(lactic-co-glycolic acid) (PLGA)-based nanoformulation, to assess their potential to be translated into clinically useful agents. In a 4T1 murine metastatic mammary tumour model, single intravenous administration of C1 (2.7 mg/kg) and C9 (2.1 mg/kg; 2.1 mg/kg C9 is equivalent to 2.7 mg/kg C1) induced greater tumour growth delay than cisplatin and doxorubicin at equivalent doses, while a double-dose regimen demonstrated a much greater tumour growth delay than the single-dose treated groups. To improve the efficacy of the complexes in vivo, C1 and C9 were further integrated into PLGA nanoparticles to yield nanosized PLGA-C1 (183.7 ± 0.8 nm) and PLGA-C9 (163.2 ± 1.2 nm), respectively. Single intravenous administration of PLGA-C1 (2.7 mg C1 equivalent/kg) and PLGA-C9 (2.1 mg C9 equivalent/kg) induced greater tumour growth delay (33% reduction in the area under curve compared to that of free C1 and C9). Multiple-dose administration of PLGA-C1 (5.4 mg C1 equivalent/kg) and PLGA-C9 (4.2 mg C9 equivalent/kg) induced tumour growth suppression at the end of the study (21.7 and 34.6% reduction relative to the size on day 1 for the double-dose regimen; 73.5 and 79.0% reduction relative to the size on day 1 for the triple-dose regimen, respectively). Such tumour growth suppression was not observed in mice receiving multiple-dose regimens of free C1 and C9. Histopathological analysis revealed that metastasis to the lung and liver was inhibited in mice receiving PLGA-C1 and PLGA-C9. The current study has demonstrated the improved in vivo antitumour efficacies of C1 and C9 compared with conventional chemotherapy drugs and the enhancement of the efficacies of these agents via a robust PLGA-based nanoformulation and multiple-drug administration approach.

Matched MeSH terms: Lung Neoplasms/drug therapy

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