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Citrus Fruits and their Bioactive Ingredients: Leading Four Horsemen from Front
Farooqi, Ammad Ahmad,Wang, Zhiqiang,Hasnain, Sidra,Attar, Rukset,Aslam, Ayesha,Mansoor, Qaisar,Ismail, Muhammad Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.6
Cancer is a multifaceted and genomically complex disease and rapidly accumulating high impact research is deepening our understanding related to the mechanisms underlying cancer development, progression and resistance to therapeutics. Increasingly it is being realized that genetic/epigenetic mutations, inactivation of tumor suppressor genes, overexpression of oncogenes, deregulation of intracellular signaling cascades and loss of apoptosis are some of the extensively studied aspects. Confluence of information suggested that rapidly developing resistance to therapeutics is adding another layer of complexity and overwhelmingly increasing preclinical studies are identifying different natural agents with efficacy and minimal off-target effects. We partition this multi-component review into citrus fruits and their bioactive ingredients mediating rebalancing of pro- and anti-apoptotic proteins to induce apoptosis in resistant cancer cells. We also discuss how oncogenic protein networks are targeted in cancer cells and how these findings may be verified in preclinical studies.
Recently Emerging Signaling Landscape of Ataxia-Telangiectasia Mutated (ATM) Kinase
Farooqi, Ammad Ahmad,Attar, Rukset,Arslan, Belkis Atasever,Romero, Mirna Azalea,ul Haq, Muhammad Fahim,Qadir, Muhammad Imran Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.16
Research over the years has progressively and sequentially provided near complete resolution of regulators of the DNA repair pathways which are so important for cancer prevention. Ataxia-telangiectasia mutated kinase (ATM), a high-molecular-weight PI3K-family kinase has emerged as a master regulator of DNA damage signaling and extensive cross-talk between ATM and downstream proteins forms an interlaced signaling network. There is rapidly growing scientific evidence emphasizing newly emerging paradigms in ATM biology. In this review, we provide latest information regarding how oxidative stress induced activation of ATM can be utilized as a therapeutic target in different cancer cell lines and in xenografted mice. Moreover, crosstalk between autophagy and ATM is also discussed with focus on how autophagy inhibition induces apoptosis in cancer cells.
Drugs from Marine Sources: Modulation of TRAIL Induced Apoptosis in Cancer Cells
Farooqi, Ammad Ahmad,Attar, Rukset,Gasparri, Maria Luisa Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.20
There have been overwhelming advances in molecular oncology and data obtained through high-throughput technologies have started to shed light on wide ranging molecular mechanisms that underpin cancer progression. Increasingly it is being realized that marine micro-organisms and the biodiversity of plankton are rich sources of various anticancer compounds. Marine derived compounds play major roles in inducing apoptosis in cancer cells. More importantly, various agents have been noted to enhance TRAIL induced apoptosis in cancer cells by functionalizing intrinsic and extrinsic pathways. In this commentary, a list of marine derived compounds reported to induce apoptosis is discussed.
miR-421, miR-155 and miR-650: Emerging Trends of Regulation of Cancer and Apoptosis
Farooqi, Ammad Ahmad,Qureshi, Muhammad Zahid,Coskunpinar, Ender,Naqvi, Syed Kamran-Ul-Hassan,Yaylim, Ilhan,Ismail, Muhammad Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.5
It is becoming progressively more understandable that between transcription and translation there lies another versatile regulator that quantitatively controls the expression of mRNAs. Identification of miRNAs as key regulators of wide ranging signaling cascades and modulators of different cell-type and context dependent activities attracted basic and clinical scientists to study modes and mechanisms in details. In line with this approach overwhelmingly increasing in vivo and in vitro studies are deepening our understanding regarding miR-421, mir-155 and miR-650 mediated regulation of cellular activities. We also attempt to provide an overview of long non coding RNAs.
The biological complexity of RKIP signaling in human cancers
Ammad Ahmad Farooqi,Yiwei Li,Fazlul H Sarkar 생화학분자생물학회 2015 Experimental and molecular medicine Vol.47 No.-
The Raf kinase inhibitory protein (RKIP) has been demonstrated to modulate different intracellular signaling pathways in cancers. Studies have shown that RKIP is frequently downregulated in cancers; therefore, attempts have been made to upregulate the expression of RKIP using natural and synthetic agents for the treatment of human malignancies. Moreover, various regulators such as specific proteins and microRNAs (miRNAs) that are involved in the regulation of RKIP expression have also been identified. RKIP mechanistically modulates the apoptotic regulators of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) signaling. Because of its critical role in human cancers, RKIP has drawn much research attention, and our understanding is expanding rapidly. Here, we summarize some of the biological complexities of RKIP regulation. However, we restrict our discussion to selected tumors by focusing on TRAIL, miRNAs and natural agents. Emerging evidence suggests a role for natural agents in RKIP regulation in cancer cells; therefore, naturally occurring agents may serve as cancer-targeting agents for cancer treatment. Although the literature suggests some advancement in our knowledge of RKIP biology, it is incomplete with regard to its preclinical and clinical efficacy; thus, further research is warranted. Furthermore, the mechanism by which chemotherapeutic drugs and novel compounds modulate RKIP and how nanotechnologically delivered RKIP can be therapeutically exploited remain to be determined.
Verim, Aysegul,Turan, Saime,Farooqi, Ammad Ahmad,Kahraman, Ozlem Timirci,Tepe-Karaca, Cigdem,Yildiz, Yemliha,Naiboglu, Baris,Ozkan, Nazli Ezgi,Ergen, Arzu,Isitmangil, Gulbu Aydinoglu,Yaylim, Ilhan Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.24
The laryngeal squamous cell carcinoma (LSCC) is one of the most common malignant tumors occurring in the head and neck. Tumor necrosis factor related apoptosis induce ligand (TRAIL) and TRAIL-receptors (DR4, DR5, DcR1, DcR2) are known as important members of TRAIL-mediated biochemical signaling pathway. Associations between polymorphisms in these genes and clinicopathological characteristics of human laryngeal carcinoma are not well defined. This study therefore aimed to investigate a possible relationship among the TRAIL and TRAIL-DR4 polymorphisms and sTRAIL levels in the risk or progression of LSCC. A total of 99 patients with laryngeal cancer and 120 healthy subjects were enrolled in the study. DR4 C626G and TRAIL 1595 C/T genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis and sTRAIL levels were measured by ELISA. There were significant differences in the distribution of DR4 C626G genotypes and frequencies of the alleles between laryngeal cancer patients and controls (p<0.001) but not in TRAIL 1595 C/T. We found the increased frequency of the DR4 C626G homozygote CC genotype in patients than in controls (p<0.001). Haplotype analysis revealed that there was also a statistically significant relationship between TRAIL and TRAIL-DR4 polymorphisms and laryngeal cancer. Serum sTRAIL levels in the laryngeal patients with CC genotype who had advanced tumour stage were lower than those of patients with early tumor stage (p=0.014). Our findings suggest that DR4 C626G genotypes and sTRAIL levels might be associated with progression of laryngeal cancer in the Turkish population.
Anthocyanins: Targeting of Signaling Networks in Cancer Cells
Sehitoglu, Muserref Hilal,Farooqi, Ammad Ahmad,Qureshi, Muhammad Zahid,Butt, Ghazala,Aras, Aliye Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.5
It is becoming progressively more understandable that phytochemicals derived from edible plants have shown potential in modelling their interactions with their target proteins. Rapidly accumulating in-vitro and in- vivo evidence indicates that anthocyanins have anticancer activity in rodent models of cancer. More intriguingly, evaluation of bilberry anthocyanins as chemopreventive agents in twenty-five colorectal cancer patients has opened new window of opportunity in translating the findings from laboratory to clinic. Confluence of information suggests that anthocyanins treated cancer cells reveal up-regulation of tumor suppressor genes. There is a successive increase in the research-work in nutrigenomics and evidence has started to shed light on intracellular-signaling cascades as common molecular targets for anthocyanins. In this review we bring to l imelight how anthocyanins induced apoptosis in cancer cells via activation of extrinsic and intrinsic pathways.
Nogueira, Daniele Rubert,Rolim, Clarice M. Bueno,Farooqi, Ammad Ahmad Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.12
Nanotechnology is an emerging field with many promising applications in drug delivery systems. Because of outstanding developments in this field, rapidly increasing research is directed to the development of nanocarriers that may enhance the availability of drugs to the target sites. Substantial fraction of information has been added into the existing scientific literature focusing on the fact that nanoparticles usually generate reactive oxygen species to a greater extent than micro-sized particles. It is worth mentioning that oxidative stress regulates an array of cell signaling cascades that resulted in cancer cell damage. Accumulating experimental evidence over the years has shown that wide-ranging biological mechanisms are triggered by these NPs in cultured cells due to the unique properties of engineered nanoparticles. In this review, we have attempted to provide an overview of the signaling cascades that are activated by oxidative stress in cancer cells in response to different kinds of nanomaterials, including quantum dots, metallic and polymeric nanoparticles.
Ionizing Radiations Induce Apoptosis in TRAIL Resistant Cancer Cells: in vivo and in vitro Analysis
Silva, Marcela Fernandes,Khokhar, Abdur Rehman,Qureshi, Muhammad Zahid,Farooqi, Ammad Ahmad Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.5
Increasingly it is being realized that despite considerable advancements in therapeutic interventions related to treatment of cancer, satisfactory results are still difficult to achieve. Rapidly accumulating evidence has started to shed light on the fact that cancer cells escape from death via constitutive activation of pro-survival signaling cascades. Cell biology and genetics have extensively enhanced our current understanding of the molecular mechanisms that underlie loss of apoptosis in cancer cells. This review is focused on ionizing radiation mediated restoration of TRAIL mediated apoptosis as evidenced by cell culture and animal model studies. Moreover, we also bring to the limelight radiation induced expression of miRNAs and how miRNAs further control response of cancer cells to radiation.
TRAIL and Bortezomib: Killing Cancer with Two Stones
Qureshi, Muhammad Zahid,Romero, Mirna Azalea,Attar, Rukset,Javed, Zeeshan,Farooqi, Ammad Ahmad Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.4
Cancer genomics and proteomics have undergone considerable broadening in the past decades and increasingly it is being realized that solid/liquid phase microarrays and high-throughput resequencing have provided platforms to improve our existing knowledge of determinants of cancer development, progression and survival. Loss of apoptosis is a widely and deeply studied process and different approaches are being used to restore apoptosis in resistant cancer phenotype. Modulating the balance between pro-apoptotic and anti-apoptotic proteins is essential to induce apoptosis. It is becoming more understood that pharmacological inhibition of the proteasome might prove to be an effective option in improving TRAIL induced apoptosis in cancer cells. Keeping in view rapidly accumulating evidence of carcinogenesis, metastasis, resistance against wide ranging therapeutics and loss of apoptosis, better knowledge regarding tumor suppressors, oncogenes, pro-apoptotic and anti-apotptic proteins will be helpful in translating the findings from benchtop to bedside.