Displaying publications 1 - 20 of 67 in total

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  1. Sulaiman AH, Musa R
    Curr Drug Targets, 2018;19(8):855.
    PMID: 29792134 DOI: 10.2174/138945011908180518113546
    Matched MeSH terms: Molecular Targeted Therapy*
  2. Abdullah B
    Biomed Imaging Interv J, 2006 Oct;2(4):e28.
    PMID: 21614327 MyJurnal DOI: 10.2349/biij.2.4.e28
    Predicting the future is a dangerous undertaking at best, and not meant for the faint-hearted. However, viewing the advances in molecular medicine, genomics and proteomics, it is easy to comprehend those who believe that molecular imaging methods will open up new vistas for medical imaging. The knock on effect will impact our capacity to diagnose and treat diseases. Anatomically detectable abnormalities, which have historically been the basis of the practice of radiology, will soon be replaced by molecular imaging methods that will reflect the under expression or over expression of certain genes which occur in almost every disease. Molecular imaging can then be resorted to so that early diagnosis and characterisation of disease can offer improved specificity. Given the growing importance of molecular medicine, imagers will find it profitable to educate themselves on molecular targeting, molecular therapeutics and the role of imaging in both areas.
    Matched MeSH terms: Molecular Targeted Therapy
  3. Hassan MZ, Osman H, Ali MA, Ahsan MJ
    Eur J Med Chem, 2016 Nov 10;123:236-255.
    PMID: 27484512 DOI: 10.1016/j.ejmech.2016.07.056
    Coumarins have received a considerable attention in the last three decades as a lead structures for the discovery of orally bioavailable non-peptidic antiviral agents. A lot of structurally diverse coumarins analogues were found to display remarkable array of affinity with the different molecular targets for antiviral agents and slight modifications around the central motif result in pronounced changes in its antiviral spectrum. This manuscript thoroughly reviews the design, discovery and structure-activity relationship studies of the coumarin analogues as antiviral agents focusing mainly on lead optimization and its development into clinical candidates.
    Matched MeSH terms: Molecular Targeted Therapy
  4. Norshidah H, Leow CH, Ezleen KE, Wahab HA, Vignesh R, Rasul A, et al.
    Front Cell Infect Microbiol, 2023;13:1061937.
    PMID: 36864886 DOI: 10.3389/fcimb.2023.1061937
    An increase in the occurrence of viral infectious diseases is a global concern for human health. According to a WHO report, dengue virus (DENV) is one of the most common viral diseases affecting approximately 400 million people annually, with worsening symptoms in nearly 1% of cases. Both academic and industrial researchers have conducted numerous studies on viral epidemiology, virus structure and function, source and route of infection, treatment targets, vaccines, and drugs. The development of CYD-TDV or Dengvaxia® vaccine has been a major milestone in dengue treatment. However, evidence has shown that vaccines have some drawbacks and limitations. Therefore, researchers are developing dengue antivirals to curb infections. DENV NS2B/NS3 protease is a DENV enzyme essential for replication and virus assembly, making it an interesting antiviral target. For faster hit and lead recognition of DENV targets, methods to screen large number of molecules at lower costs are essential. Similarly, an integrated and multidisciplinary approach involving in silico screening and confirmation of biological activity is required. In this review, we discuss recent strategies for searching for novel DENV NS2B/NS3 protease inhibitors from the in silico and in vitro perspectives, either by applying one of the approaches or by integrating both. Therefore, we hope that our review will encourage researchers to integrate the best strategies and encourage further developments in this area.
    Matched MeSH terms: Molecular Targeted Therapy
  5. Gandhi S, Mohamad Razif MF, Othman S, Chakraborty S, Nor Rashid N
    Mol Med Rep, 2023 Feb;27(2).
    PMID: 36633133 DOI: 10.3892/mmr.2023.12933
    The lack of specific and accurate therapeutic targets poses a challenge in the treatment of cervical cancer (CC). Global proteomics has the potential to characterize the underlying and intricate molecular mechanisms that drive the identification of therapeutic candidates for CC in an unbiased manner. The present study assessed human papillomavirus (HPV)‑induced proteomic alterations to identify key cancer hallmark pathways and protein‑protein interaction (PPI) networks, which offered the opportunity to evaluate the possibility of using these for targeted therapy in CC. Comparative proteomic profiling of HPV‑transfected (HPV16/18 E7), HPV‑transformed (CaSki and HeLa) and normal human keratinocyte (HaCaT) cells was performed using the liquid chromatography‑tandem mass spectrometry (LC‑MS/MS) technique. Both label‑free quantification and differential expression analysis were performed to assess differentially regulated proteins in HPV‑transformed and ‑transfected cells. The present study demonstrated that protein expression was upregulated in HPV‑transfected cells compared with in HPV‑transformed cells. This was probably due to the ectopic expression of E7 protein in the former cell type, in contrast to its constitutive expression in the latter cell type. Subsequent pathway visualization and network construction demonstrated that the upregulated proteins in HPV16/18 E7‑transfected cells were predominantly associated with a diverse array of cancer hallmarks, including the mTORC1 signaling pathway, MYC targets V1, hypoxia and glycolysis. Among the various proteins present in the cancer hallmark enrichment pathways, phosphoglycerate kinase 1 (PGK1) was present across all pathways. Therefore, PGK1 may be considered as a potential biomarker. PPI analysis demonstrated a direct interaction between p130 and polyubiquitin B, which may lead to the degradation of p130 via the ubiquitin‑proteasome proteolytic pathway. In summary, elucidation of the key signaling pathways in HPV16/18‑transfected and ‑transformed cells may aid in the design of novel therapeutic strategies for clinical application such as targeted therapy and immunotherapy against cervical cancer.
    Matched MeSH terms: Molecular Targeted Therapy
  6. Yeong CH, Cheng MH, Ng KH
    J Zhejiang Univ Sci B, 2014 Oct;15(10):845-63.
    PMID: 25294374 DOI: 10.1631/jzus.B1400131
    The potential use of radionuclides in therapy has been recognized for many decades. A number of radionuclides, such as iodine-131 ((131)I), phosphorous-32 ((32)P), strontium-90 ((90)Sr), and yttrium-90 ((90)Y), have been used successfully for the treatment of many benign and malignant disorders. Recently, the rapid growth of this branch of nuclear medicine has been stimulated by the introduction of a number of new radionuclides and radiopharmaceuticals for the treatment of metastatic bone pain and neuroendocrine and other malignant or non-malignant tumours. Today, the field of radionuclide therapy is enjoying an exciting phase and is poised for greater growth and development in the coming years. For example, in Asia, the high prevalence of thyroid and liver diseases has prompted many novel developments and clinical trials using targeted radionuclide therapy. This paper reviews the characteristics and clinical applications of the commonly available therapeutic radionuclides, as well as the problems and issues involved in translating novel radionuclides into clinical therapies.
    Matched MeSH terms: Molecular Targeted Therapy/trends*
  7. Abdullah JM, Mustafa Z, Ideris A
    Biomed Res Int, 2014;2014:386470.
    PMID: 25243137 DOI: 10.1155/2014/386470
    Glioblastoma multiforme (GBM), or grade IV glioma, is one of the most lethal forms of human brain cancer. Current bioscience has begun to depict more clearly the signalling pathways that are responsible for high-grade glioma initiation, migration, and invasion, opening the door for molecular-based targeted therapy. As such, the application of viruses such as Newcastle disease virus (NDV) as a novel biological bullet to specifically target aberrant signalling in GBM has brought new hope. The abnormal proliferation and aggressive invasion behaviour of GBM is reported to be associated with aberrant Rac1 protein signalling. NDV interacts with Rac1 upon viral entry, syncytium induction, and actin reorganization of the infected cell as part of the replication process. Ultimately, intracellular stress leads the infected glioma cell to undergo cell death. In this review, we describe the characteristics of malignant glioma and the aberrant genetics that drive its aggressive phenotype, and we focus on the use of oncolytic NDV in GBM-targeted therapy and the interaction of NDV in GBM signalling that leads to inhibition of GBM proliferation and invasion, and subsequently, cell death.
    Matched MeSH terms: Molecular Targeted Therapy*
  8. Lim SH, Wu L, Kiew LV, Chung LY, Burgess K, Lee HB
    PLoS One, 2014;9(3):e82934.
    PMID: 24622277 DOI: 10.1371/journal.pone.0082934
    Reprogramming of energy metabolism is pivotal to cancer, so mitochondria are potential targets for anticancer therapy. A prior study has demonstrated the anti-proliferative activity of a new class of mitochondria-targeting rosamines. This present study describes in vitro cytotoxicity of second-generation rosamine analogs, their mode of action, and their in vivo efficacies in a tumor allografted mouse model. Here, we showed that these compounds exhibited potent cytotoxicity (average IC50<0.5 µM), inhibited Complex II and ATP synthase activities of the mitochondrial oxidative phosphorylation pathway and induced loss of mitochondrial transmembrane potential. A NCI-60 cell lines screen further indicated that rosamine analogs 4 and 5 exhibited potent antiproliferative effects with Log10GI50 = -7 (GI50 = 0.1 µM) and were more effective against a colorectal cancer sub-panel than other cell lines. Preliminary in vivo studies on 4T1 murine breast cancer-bearing female BALB/c mice indicated that treatment with analog 5 in a single dosing of 5 mg/kg or a schedule dosing of 3 mg/kg once every 2 days for 6 times (q2d×6) exhibited only minimal induction of tumor growth delay. Our results suggest that rosamine analogs may be further developed as mitochondrial targeting agents. Without a doubt proper strategies need to be devised to enhance tumor uptake of rosamines, i.e. by integration to carrier molecules for better therapeutic outcome.
    Matched MeSH terms: Molecular Targeted Therapy*
  9. Pandurangan AK, Esa NM
    Asian Pac J Cancer Prev, 2014;15(2):551-60.
    PMID: 24568457
    Colorectal cancer (CRC) is the third most common malignancy and fourth most common cause of cancer mortality worldwide. Untreated chronic inflammation in the intestine ranks among the top three high-risk conditions for colitis-associated colorectal cancer (CAC). Signal Transducer and Activator of Transcription 3 (STAT3) protein is a member of the STAT family of transcription factors often deregulated in CRC. In this review, we try to emphasize the critical role of STAT3 in CAC as well as the crosstalk of STAT3 with inflammatory cytokines, nuclear factor (NF)- κB, PI3K/Akt, Mammalian Target of Rapamycin (mTOR), Notch, Wnt/β-catenin and microRNA (MiR) pathways. STAT3 is considered as a primary drug target to treat CAC in humans and rodents. Also we updated the findings for inhibitors of STAT3 with regard to effeects on tumorigenesis. This review will hopefully provide insights on the use of STAT3 as a therapeutic target in CAC.
    Matched MeSH terms: Molecular Targeted Therapy*
  10. Jalil MA, Suwanpayak N, Kulsirirat K, Suttirak S, Ali J, Yupapin PP
    Int J Nanomedicine, 2011;6:2925-32.
    PMID: 22131837 DOI: 10.2147/IJN.S26266
    A novel nanomicro syringe system was proposed for drug storage and delivery using a PANDA ring resonator and atomic buffer. A PANDA ring is a modified optical add/drop filter, named after the well known Chinese bear. In principle, the molecule/drug is trapped by the force generated by different combinations of gradient fields and scattering photons within the PANDA ring. A nanomicro needle system can be formed by optical vortices in the liquid core waveguide which can be embedded on a chip, and can be used for long-term treatment. By using intense optical vortices, the required genes/molecules can be trapped and transported dynamically to the intended destinations via the nanomicro syringe, which is available for drug delivery to target tissues, in particular tumors. The advantage of the proposed system is that by confining the treatment area, the effect can be decreased. The use of different optical vortices for therapeutic efficiency is also discussed.
    Matched MeSH terms: Molecular Targeted Therapy/instrumentation*
  11. Warrier S, Marimuthu R, Sekhar S, Bhuvanalakshmi G, Arfuso F, Das AK, et al.
    Int J Biochem Cell Biol, 2016 06;75:104-11.
    PMID: 27063405 DOI: 10.1016/j.biocel.2016.04.002
    The extracellular ligand, Wnt, and its receptors are involved in sign al transduction and play an important role in axis formation and neural development. In neurodegenerative disorders such as Alzheimer's disease (AD), a decrease of the intracellular Wnt effector, β-catenin, has been linked to amyloid-β-peptide-induced neurotoxicity. Despite this knowledge, targeting Wnt inhibitors as potential biomarkers has not been explored, and harnessing Wnt activators as therapeutic candidates remains largely not investigated. A wide acting family of Wnt mediators, secreted frizzled-related proteins (sFRPs), has not been probed so far as molecular indicators of disease occurrence and progression of Alzheimer's. Unlike the effect of the Dickkopf (DKK) family of Wnt antagonists on AD, the sFRP molecules have a more pleiotropic impact on the Wnt signaling cascade and probably have a far-reaching involvement in neurodegeneration. The role of sFRPs has been poorly described in AD, and in this review, we analyze the present status of the role of sFRPs on neurodegeneration, their likely involvement, and potential implications in treatment modalities of AD. This information would provide valuable clues for the development of potential therapeutic targets for aberrant neurodegenerative disorders.
    Matched MeSH terms: Molecular Targeted Therapy/methods*
  12. Sabetian S, Shamsir MS
    BMC Syst Biol, 2015;9:37.
    PMID: 26187737 DOI: 10.1186/s12918-015-0186-7
    Sperm-egg interaction defect is a significant cause of in-vitro fertilization failure for infertile cases. Numerous molecular interactions in the form of protein-protein interactions mediate the sperm-egg membrane interaction process. Recent studies have demonstrated that in addition to experimental techniques, computational methods, namely protein interaction network approach, can address protein-protein interactions between human sperm and egg. Up to now, no drugs have been detected to treat sperm-egg interaction disorder, and the initial step in drug discovery research is finding out essential proteins or drug targets for a biological process. The main purpose of this study is to identify putative drug targets for human sperm-egg interaction deficiency and consider if the detected essential proteins are targets for any known drugs using protein-protein interaction network and ingenuity pathway analysis.
    Matched MeSH terms: Molecular Targeted Therapy*
  13. Paudel YN, Angelopoulou E, Piperi C, Othman I, Aamir K, Shaikh MF
    Cells, 2020 02 07;9(2).
    PMID: 32046119 DOI: 10.3390/cells9020383
    Alzheimer's disease (AD) is a devastating neurodegenerative disorder and a leading cause of dementia, with accumulation of amyloid-beta (Aβ) and neurofibrillary tangles (NFTs) as defining pathological features. AD presents a serious global health concern with no cure to date, reflecting the complexity of its pathogenesis. Recent evidence indicates that neuroinflammation serves as the link between amyloid deposition, Tau pathology, and neurodegeneration. The high mobility group box 1 (HMGB1) protein, an initiator and activator of neuroinflammatory responses, has been involved in the pathogenesis of neurodegenerative diseases, including AD. HMGB1 is a typical damage-associated molecular pattern (DAMP) protein that exerts its biological activity mainly through binding to the receptor for advanced glycation end products (RAGE) and toll-like receptor 4 (TLR4). RAGE and TLR4 are key components of the innate immune system that both bind to HMGB1. Targeting of HMGB1, RAGE, and TLR4 in experimental AD models has demonstrated beneficial effects in halting AD progression by suppressing neuroinflammation, reducing Aβ load and production, improving spatial learning, and inhibiting microglial stimulation. Herein, we discuss the contribution of HMGB1 and its receptor signaling in neuroinflammation and AD pathogenesis, providing evidence of its beneficial effects upon therapeutic targeting.
    Matched MeSH terms: Molecular Targeted Therapy*
  14. Wong KK
    Cell Oncol (Dordr), 2020 Oct;43(5):779-792.
    PMID: 32504382 DOI: 10.1007/s13402-020-00526-4
    BACKGROUND: Pancreatic cancer or pancreatic ductal adenocarcinoma (PDAC) is one of the most devastating cancer types with a 5-year survival rate of only 9%. PDAC is one of the leading causes of cancer-related deaths in both genders. Epigenetic alterations may lead to the suppression of tumor suppressor genes, and DNA methylation is a predominant epigenetic modification. DNA methyltransferase 1 (DNMT1) is required for maintaining patterns of DNA methylation during cellular replication. Accumulating evidence has implicated the oncogenic roles of DNMT1 in various malignancies including PDACs.

    CONCLUSIONS: Herein, the expression profiles, oncogenic roles, regulators and inhibitors of DNMT1 in PDACs are presented and discussed. DNMT1 is overexpressed in PDAC cases compared with non-cancerous pancreatic ducts, and its expression gradually increases from pre-neoplastic lesions to PDACs. DNMT1 plays oncogenic roles in suppressing PDAC cell differentiation and in promoting their proliferation, migration and invasion, as well as in induction of the self-renewal capacity of PDAC cancer stem cells. These effects are achieved via promoter hypermethylation of tumor suppressor genes, including cyclin-dependent kinase inhibitors (e.g., p14, p15, p16, p21 and p27), suppressors of epithelial-mesenchymal transition (e.g., E-cadherin) and tumor suppressor miRNAs (e.g., miR-148a, miR-152 and miR-17-92 cluster). Pre-clinical investigations have shown the potency of novel non-nucleoside DNMT1 inhibitors against PDAC cells. Finally, phase I/II clinical trials of DNMT1 inhibitors (azacitidine, decitabine and guadecitabine) in PDAC patients are currently underway, where these inhibitors have the potential to sensitize PDACs to chemotherapy and immune checkpoint blockade therapy.

    Matched MeSH terms: Molecular Targeted Therapy*
  15. Lee YT, Tan YJ, Oon CE
    Eur J Pharmacol, 2018 Sep 05;834:188-196.
    PMID: 30031797 DOI: 10.1016/j.ejphar.2018.07.034
    Molecular targeted therapies are revolutionized therapeutics which interfere with specific molecules to block cancer growth, progression, and metastasis. Many molecular targeted therapies approved by the Food and Drug Administration (FDA), have demonstrated remarkable clinical success in the treatment of a myriad of cancer types including breast, leukemia, colorectal, lung, and ovarian cancers. This review provides an update on the different types of molecular targeted therapies used in the treatment of cancer, focusing on the fundamentals of molecular targeted therapy, its mode of action in cancer treatment, as well as its advantages and limitations.
    Matched MeSH terms: Molecular Targeted Therapy/methods*
  16. Prasher P, Sharma M, Mehta M, Paudel KR, Satija S, Chellappan DK, et al.
    Chem Biol Interact, 2020 Jul 01;325:109125.
    PMID: 32376238 DOI: 10.1016/j.cbi.2020.109125
    The apparent predicament of the representative chemotherapy for managing respiratory distress calls for an obligatory deliberation for identifying the pharmaceuticals that effectively counter the contemporary intricacies associated with target disease. Multiple, complex regulatory pathways manifest chronic pulmonary disorders, which require chemotherapeutics that produce composite inhibitory effect. The cost effective natural product based molecules hold a high fervor to meet the prospects posed by current respiratory-distress therapy by sparing the tedious drug design and development archetypes, present a robust standing for the possible replacement of the fading practice of poly-pharmacology, and ensure the subversion of a potential disease relapse. This study summarizes the experimental evidences on natural products moieties and their components that illustrates therapeutic efficacy on respiratory disorders.
    Matched MeSH terms: Molecular Targeted Therapy/methods*
  17. Ong SB, Kalkhoran SB, Cabrera-Fuentes HA, Hausenloy DJ
    Eur J Pharmacol, 2015 Sep 15;763(Pt A):104-14.
    PMID: 25987420 DOI: 10.1016/j.ejphar.2015.04.056
    The past decade has witnessed a number of exciting developments in the field of mitochondrial dynamics - a phenomenon in which changes in mitochondrial shape and movement impact on cellular physiology and pathology. By undergoing fusion and fission, mitochondria are able to change their morphology between elongated interconnected networks and discrete fragmented structures, respectively. The cardiac mitochondria, in particular, have garnered much interest due to their unique spatial arrangement in the adult cardiomyocyte, and the multiple roles they play in cell death and survival. In this article, we review the role of the mitochondrial fusion and fission proteins as novel therapeutic targets for treating cardiovascular disease.
    Matched MeSH terms: Molecular Targeted Therapy/methods*
  18. Lee JJ, Saiful Yazan L, Che Abdullah CA
    Int J Nanomedicine, 2017;12:2373-2384.
    PMID: 28392694 DOI: 10.2147/IJN.S127329
    Breast cancer is the most common malignancy worldwide, especially among women, with substantial after-treatment effects. The survival rates of breast cancer have decreased over the years even with the existence of various therapeutic strategies, specifically, chemotherapy. Clinical drugs administered for breast cancer appear to be non-targeting to specific cancer sites leading to severe side effects and potentially harming healthy cells instead of just killing cancer cells. This leads to the need for designing a targeted drug delivery system. Nanomaterials, both organic and inorganic, are potential drug nanocarriers with the ability of targeting, imaging and tracking. Various types of nanomaterials have been actively researched together with their drug conjugate. In this review, we focus on selected nanomaterials, namely solid-lipid, liposomal, polymeric, magnetic nanoparticles, quantum dots, and carbon nanotubes and their drug conjugates, for breast cancer studies. Their advantages, disadvantages and previously conducted studies were highlighted.
    Matched MeSH terms: Molecular Targeted Therapy*
  19. Patmanathan SN, Johnson SP, Lai SL, Panja Bernam S, Lopes V, Wei W, et al.
    Sci Rep, 2016 05 10;6:25650.
    PMID: 27160553 DOI: 10.1038/srep25650
    Oral squamous cell carcinoma (OSCC) is a lethal disease with a 5-year mortality rate of around 50%. Molecular targeted therapies are not in routine use and novel therapeutic targets are required. Our previous microarray data indicated sphingosine 1-phosphate (S1P) metabolism and signalling was deregulated in OSCC. In this study, we have investigated the contribution of S1P signalling to the pathogenesis of OSCC. We show that the expression of the two major enzymes that regulate S1P levels were altered in OSCC: SPHK1 was significantly upregulated in OSCC tissues compared to normal oral mucosa and low levels of SGPL1 mRNA correlated with a worse overall survival. In in vitro studies, S1P enhanced the migration/invasion of OSCC cells and attenuated cisplatin-induced death. We also demonstrate that S1P receptor expression is deregulated in primary OSCCs and that S1PR2 is over-expressed in a subset of tumours, which in part mediates S1P-induced migration of OSCC cells. Lastly, we demonstrate that FTY720 induced significantly more apoptosis in OSCC cells compared to non-malignant cells and that FTY720 acted synergistically with cisplatin to induce cell death. Taken together, our data show that S1P signalling promotes tumour aggressiveness in OSCC and identify S1P signalling as a potential therapeutic target.
    Matched MeSH terms: Molecular Targeted Therapy
  20. Fatemian T, Chowdhury EH
    Curr Cancer Drug Targets, 2014;14(7):599-609.
    PMID: 25308718
    Malfunctions in membrane transporters or disruptions in signaling cascades induce resistance to chemotherapy in cancer cells resulting in treatment failure. To adjust the genetic alterations leading to these cellular protective measures, dissection and verification of the contributing routes would be required. In justification of knockdown of the key genes, RNA interference provides a reliable probing tool, enabling exploration of phenotypic manifestation of targeted genes. Investigation of the non-transporter targets, predominantly oncogenes and tumor suppressor genes, by means of small interfering RNA with the aim to re-sensitize cancer cells to therapeutics will be discussed in this review.
    Matched MeSH terms: Molecular Targeted Therapy*
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