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1.
Mol Cell Biochem ; 476(1): 165-174, 2021 Jan.
Article in English | MEDLINE | ID: mdl-32840738

ABSTRACT

Colorectal cancer (CRC) is the third most common cancer diagnosed worldwide making it a serious global challenge. CRC progression results from dysregulated cytoplasmic transcription factors, including signal transducer and activator of transcription (STAT) proteins that are involved in JAK-STAT pathway. The STAT proteins contain a conserved SH2 domain that facilitates the initiation of STAT activation via binding to tyrosine motifs followed by STAT dimerization. The STAT proteins include STAT1, STAT2 and STAT3 which all facilitate therapeutic targets for many drugs, since they are associated with pathogenesis in various cancers such as CRC. Genistein is an efficient chemopreventive phytochemical drug against CRC. The current investigation presents a computational study performed to investigate the molecular interaction between STAT1, STAT2 and STAT3 proteins with genistein. The molecular dynamic simulation was conducted for STAT2 protein. The studies from molecular docking revealed that the interaction of STAT proteins and genistein is predicted to be effective with better binding energies. Furthermore, targeting STAT3 could be an efficient therapeutic target and understanding the interaction between STAT3 and genistein can help to contribute to a better inhibition process for CRC progression. Treatment with genistein led to significant suppression of cell proliferation and STAT3 protein expression in both CRC (HCT 116 and HT-29) cell lines. This further provides development of efficient STAT inhibitors with better potency and bioavailability.


Subject(s)
Colorectal Neoplasms/metabolism , STAT1 Transcription Factor/metabolism , STAT2 Transcription Factor/metabolism , STAT3 Transcription Factor/metabolism , Binding Sites , Cell Proliferation , Colorectal Neoplasms/genetics , Computational Biology , Genistein/pharmacology , HCT116 Cells , HT29 Cells , Humans , Inflammation , Magnetic Resonance Spectroscopy , Molecular Docking Simulation , Mutagenesis, Site-Directed , Protein Domains , Protein Processing, Post-Translational , STAT1 Transcription Factor/genetics , STAT2 Transcription Factor/genetics , STAT3 Transcription Factor/genetics , Signal Transduction
2.
Crit Rev Oncol Hematol ; 151: 102968, 2020 Jul.
Article in English | MEDLINE | ID: mdl-32416345

ABSTRACT

Hepatocellular carcinoma (HCC) is the fifth most prevalent malignancy worldwide. Despite advances in imaging techniques, early diagnosis and management remain very poor. The early diagnosis of HCC requires diagnostic and imaging technologies with high sensitivity and precise quantification ability and with no tissue penetration limit. Nanotechnology-based cancer imaging is a rapidly emerging research area with significant applications in the diagnosis and treatment of cancer, which we review here with application to HCC. Furthermore, we discuss the combination of functional nanotheranostics and magnetic resonance imaging (MRI) for targeted delivery of phytochemical therapeutics, chemotherapeutic drugs, RNAi-based therapeutics, and vaccinations. Finally, this review presents the importance of MRI biomarkers for monitoring HCC treatment response. The use of advanced nanotheranostics as MRI contrast agents for imaging, diagnosis and drug delivery may enhance HCC management and provide a new area of research in tumor imaging technology.


Subject(s)
Carcinoma, Hepatocellular/diagnosis , Carcinoma, Hepatocellular/therapy , Liver Neoplasms/diagnosis , Liver Neoplasms/therapy , Polymers/chemistry , Antineoplastic Agents/administration & dosage , Drug Carriers , Humans , Magnetic Resonance Imaging , Nanotechnology
3.
Curr Drug Metab ; 20(13): 1033-1038, 2019.
Article in English | MEDLINE | ID: mdl-31902354

ABSTRACT

BACKGROUND: Cervical Cancer (CC) is the most common leading cancer in women globally. This is considered to be the type of cancer that is restricted to women. Any women in the reproductive age range can develop CC. However, women between the ages of 25 and 39 are at a higher risk. OBJECTIVE: In comparison with developed countries, the screening and awareness of CC in developing countries are significantly low. Infection with Human papillomavirus (HPV) is the main cause of CC, especially HPV-16 and HPV-18. Other than HPV, there are other factors that can contribute to CC, such as Human simplex virus (HSV) infection and immunocompromised patients with HIV. CONCLUSION: Cervical cancer can be detected by molecular techniques such as (1) PCR, (2) visual acetic acid method, (3) DNA Hybrid II test, (4) liquid-based cytology, (5) Pap-Smear techniques, and (6) colposcopy techniques. Early detection of CC is very much needed; cryotherapy or LEEP (Loop electro surgical excision procedure) can be conducted during the pre-invasive stage of CC. Some metabolic changes in the human body such as fluctuating levels of insulin and triglycerides and increased activity of adiponectin may lead to CC. These contributing factors, such as adipokines, can be used as biomarkers for CC detection.


Subject(s)
Adiponectin/metabolism , Uterine Cervical Neoplasms/metabolism , Adiponectin/chemistry , Animals , Female , Humans
4.
Crit Rev Oncol Hematol ; 127: 50-55, 2018 Jul.
Article in English | MEDLINE | ID: mdl-29891111

ABSTRACT

Lipoxygenases (LOXs) are dioxygenases that catalyze the peroxidation of linoleic acid (LA) or arachidonic acid (AA), in the presence of molecular oxygen. The existence of inflammatory component in the tumor microenvironment intimately links the LOXs to gastrointestinal (GI) cancer progression. Amongst the six-different human LOX-isoforms, 5-LOX is the most vital enzyme for leukotriene (LT) biosynthesis, which is the main inflammation intermediaries. As recent investigations have shown the association of 5-LOX with tumor metastasis, there has also been significant progress in discovering the function of 5-LOX pathway in GI cancer. Studies on GI cancer cells using the pharmacological drugs targeting 5-LOX pathway have shown antiproliferative and proapoptotic effects. Pharmacogenetic discoveries in other diseases have revealed strong heritable basis for the leukotriene pathway, which helps in exploring the mechanistic source of genetic alteration within the leukotriene pathway and offer insights into GI cancer pathogenesis and future prospects for treatment and prevention. This review recapitulates the current research status of 5-LOX activity in GI malignancies.


Subject(s)
Arachidonate 5-Lipoxygenase/physiology , Gastrointestinal Neoplasms/etiology , Gastrointestinal Neoplasms/pathology , Lipid Metabolism/physiology , Animals , Disease Progression , Gastrointestinal Neoplasms/metabolism , Humans , Isoenzymes/physiology , Lipoxygenase/physiology
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