Faizan Haider Khan

Bio: Faizan Haider Khan is an academic researcher from National University of Ireland, Galway. The author has contributed to research in topics: Cancer & Genotype. The author has an hindex of 11, co-authored 21 publications receiving 300 citations. Previous affiliations of Faizan Haider Khan include University of Oklahoma & Oklahoma State University–Stillwater.

The Role of Nitric Oxide in Cancer: Master Regulator or NOt?

Abstract: Nitric oxide (NO) is a key player in both the development and suppression of tumourigenesis depending on the source and concentration of NO. In this review, we discuss the mechanisms by which NO induces DNA damage, influences the DNA damage repair response, and subsequently modulates cell cycle arrest. In some circumstances, NO induces cell cycle arrest and apoptosis protecting against tumourigenesis. NO in other scenarios can cause a delay in cell cycle progression, allowing for aberrant DNA repair that promotes the accumulation of mutations and tumour heterogeneity. Within the tumour microenvironment, low to moderate levels of NO derived from tumour and endothelial cells can activate angiogenesis and epithelial-to-mesenchymal transition, promoting an aggressive phenotype. In contrast, high levels of NO derived from inducible nitric oxide synthase (iNOS) expressing M1 and Th1 polarised macrophages and lymphocytes may exert an anti-tumour effect protecting against cancer. It is important to note that the existing evidence on immunomodulation is mainly based on murine iNOS studies which produce higher fluxes of NO than human iNOS. Finally, we discuss different strategies to target NO related pathways therapeutically. Collectively, we present a picture of NO as a master regulator of cancer development and progression.

Acquired genetic alterations in tumor cells dictate the development of high-risk neuroblastoma and clinical outcomes

Abstract: Background Determining the driving factors and molecular flow-through that define the switch from favorable to aggressive high-risk disease is critical to the betterment of neuroblastoma cure.

Metastatic neuroblastoma cancer stem cells exhibit flexible plasticity and adaptive stemness signaling

Abstract: High-risk neuroblastoma (HR-NB) presenting with hematogenous metastasis is one of the most difficult cancers to cure. Patient survival is poor. Aggressive tumors contain populations of rapidly proliferating clonogens that exhibit stem cell properties, cancer stem cells (CSCs). Conceptually, CSCs that evade intensive multimodal therapy dictate tumor progression, relapse/recurrence, and poor clinical outcomes. Herein, we investigated the plasticity and stem-cell related molecular response of aggressive metastatic neuroblastoma cells that fit the CSC model. Well-characterized clones of metastatic site-derived aggressive cells (MSDACs) from a manifold of metastatic tumors of clinically translatable HR-NB were characterized for their CSC fit by examining epithelial-to-mesenchymal transition (EMT) (E-cadherin, N-Cadherin), survival (NFκB P65, p50, IκB and pIκB) and drug resistance (ABCG2) by immunoblotting; pluripotency maintenance (Nanog, SOX2) by immunofluorescence; and EMT and stemness related transcription of 93 genes by QPCR profiling. Plasticity of MSDACs under sequential alternation of culture conditions with serum and serum-free stem-cell conditions was assessed by clonal expansion (BrdU incorporation), tumorosphere formation (anchorage independent growth), EMT and stemness related transcriptome (QPCR profiling) and validated with MYC, SOX2, EGFR, NOTCH1 and CXCL2 immunoblotting. HR-NB MSDACs maintained in alternated culture conditions, serum-free stem cell medium to growth medium with serum and vice versa identified its flexible revocable plasticity characteristics. We observed signatures of stem cell-related molecular responses consistent with phenotypic conversions. Successive reintroduction to the favorable niche not only regained identical EMT, self-renewal capacity, pluripotency maintenance, and other stem cell-related signaling events, but also instigated additional events depicting aggressive adaptive plasticity. Together, these results demonstrated the flexible plasticity of HR-NB MSDACs that typically fit the CSC model, and further identified the intrinsic adaptiveness of the successive phenotype switching that clarifies the heterogeneity of HR-NB. Moreover, the continuous ongoing acquisition of stem cell-related molecular rearrangements may hold the key to the switch from favorable disease to HR-NB.

Pesticides: an update of human exposure and toxicity.

Abstract: Pesticides are a family of compounds which have brought many benefits to mankind in the agricultural, industrial, and health areas, but their toxicities in both humans and animals have always been a concern. Regardless of acute poisonings which are common for some classes of pesticides like organophosphoruses, the association of chronic and sub-lethal exposure to pesticides with a prevalence of some persistent diseases is going to be a phenomenon to which global attention has been attracted. In this review, incidence of various malignant, neurodegenerative, respiratory, reproductive, developmental, and metabolic diseases in relation to different routes of human exposure to pesticides such as occupational, environmental, residential, parental, maternal, and paternal has been systematically criticized in different categories of pesticide toxicities like carcinogenicity, neurotoxicity, pulmonotoxicity, reproductive toxicity, developmental toxicity, and metabolic toxicity. A huge body of evidence exists on the possible role of pesticide exposures in the elevated incidence of human diseases such as cancers, Alzheimer, Parkinson, amyotrophic lateral sclerosis, asthma, bronchitis, infertility, birth defects, attention deficit hyperactivity disorder, autism, diabetes, and obesity. Most of the disorders are induced by insecticides and herbicides most notably organophosphorus, organochlorines, phenoxyacetic acids, and triazine compounds.

Biological response of cancer cells to radiation treatment.

Abstract: Cancer is a class of diseases characterized by uncontrolled cell growth and has the ability to spread or metastasize throughout the body. In recent years, remarkable progress has been made towards the understanding of proposed hallmarks of cancer development, care and treatment modalities. Radiation therapy or radiotherapy is an important and integral component of cancer management, mostly conferring a survival benefit. Radiation therapy destroys cancer by depositing high-energy radiation on the cancer tissues. Over the years, radiation therapy has been driven by constant technological advances and approximately 50% of all patients with localized malignant tumors are treated with radiation at some point in the course of their disease. In radiation oncology, research and development in the last three decades has led to considerable improvement in our understanding of the differential responses of normal and cancer cells. The biological effectiveness of radiation depends on the linear energy transfer (LET), total dose, number of fractions and radiosensitivity of the targeted cells or tissues. Radiation can either directly or indirectly (by producing free radicals) damages the genome of the cell. This has been challenged in recent years by a newly identified phenomenon known as radiation induced bystander effect (RIBE). In RIBE, the non-irradiated cells adjacent to or located far from the irradiated cells/tissues demonstrate similar responses to that of the directly irradiated cells. Understanding the cancer cell responses during the fractions or after the course of irradiation will lead to improvements in therapeutic efficacy and potentially, benefitting a significant proportion of cancer patients. In this review, the clinical implications of radiation induced direct and bystander effects on the cancer cell are discussed.

Relationships between tissue concentrations of polycyclic aromatic hydrocarbons and antioxidative responses of marine mussels, Perna viridis

Abstract: Local mussels, Perna viridis, were transplanted from a relatively clean site to various polluted sites in Hong Kong. After a 30-day field exposure, different antioxidant parameters including glutathione S transferase (GST), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), NADPH DT-diaphorase (DT-d), glutathione (GSH) and lipid peroxidation were quantified, and tissue concentrations of benzo[a]pyrene (B[a]P) as well as a total of five polycyclic aromatic hydrocarbons (PAHs) with potential carcinogenicity were determined for individual mussels. Results indicated that: (1) tissue concentrations of B[a]P and total PAHs from the same site were highly variable; (2) gill SOD, DT-d and lipid peroxidation showed no response to tissue pollutants: (3) the majority of the antioxidant parameters were induced by increasing tissue pollutant concentrations; and (4) amongst the various parameters, oxyradical scavenger GSH [ best correlated with tissue concentrations of pollutants.

Portrait of inflammatory response to ionizing radiation treatment

Abstract: Ionizing radiation (IR) activates both pro-and anti-proliferative signal pathways producing an imbalance in cell fate decision. IR is able to regulate several genes and factors involved in cell-cycle progression, survival and/or cell death, DNA repair and inflammation modulating an intracellular radiation-dependent response. Radiation therapy can modulate anti-tumour immune responses, modifying tumour and its microenvironment. In this review, we report how IR could stimulate inflammatory factors to affect cell fate via multiple pathways, describing their roles on gene expression regulation, fibrosis and invasive processes. Understanding the complex relationship between IR, inflammation and immune responses in cancer, opens up new avenues for radiation research and therapy in order to optimize and personalize radiation therapy treatment for each patient.

The role of tumor microenvironment in therapeutic resistance.

Abstract: // Beomseok Son 1,* , Sungmin Lee 1,* , HyeSook Youn 2,* , EunGi Kim 1 , Wanyeon Kim 3,4 and BuHyun Youn 1,4 1 Department of Integrated Biological Science, Pusan National University, Busan 46241, Republic of Korea 2 Department of Integrative Bioscience and Biotechnology, Sejong University, Seoul 05006, Republic of Korea 3 Integrative Graduate Program of Ship and Offshore Plant Technology for Ocean Energy Resource, Pusan National University, Busan 46241, Republic of Korea 4 Department of Biological Sciences, Pusan National University, Busan 46241, Republic of Korea * These authors have contributed equally to this work Correspondence to: BuHyun Youn, email: // Wanyeon Kim, email: // Keywords : tumor microenvironment, therapeutic resistance, myeloid cells, cancer-associated fibroblasts, mesenchymal stem cells Received : September 02, 2016 Accepted : December 01, 2016 Published : December 11, 2016 Abstract Cancer cells undergo unlimited progression and survival owing to activation of oncogenes. However, support of the tumor microenvironment is essential to the formation of clinically relevant tumors. Recent evidence indicates that the tumor microenvironment is a critical regulator of immune escape, progression, and distant metastasis of cancer. Moreover, the tumor microenvironment is known to be involved in acquired resistance of tumors to various therapies. Despite significant advances in chemotherapy and radiotherapy, occurrence of therapeutic resistance leads to reduced efficacy. This review highlights myeloid cells, cancer-associated fibroblasts, and mesenchymal stem cells consisting of the tumor microenvironment, as well as the relevant signaling pathways that eventually render cancer cells to be therapeutically resistant.