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1.  Preclinical development and clinical use of perillyl alcohol for chemoprevention and cancer therapy 
American Journal of Cancer Research  2015;5(5):1580-1593.
Perillyl alcohol (POH) is a naturally occurring dietary monoterpene isolated from the essential oils of lavender, peppermint, and other plants. Medical interest in this compound was generated by research findings showing that POH was able to inhibit the growth of tumor cells in cell culture and exert cancer preventive and therapeutic activity in a variety of animal tumor models. Based on this promising preclinical work, POH was formulated in soft gelatine capsules and orally administered to cancer patients several times a day on a continuous basis. However, such clinical trials in humans yielded disappointing results, also because the large number of capsules that had to be swallowed caused hard-to-tolerate intestinal side effects, causing many patients to withdraw from treatment due to unrelenting nausea, fatigue, and vomiting. As a result, efforts to treat cancer patients with oral POH were abandoned and did not enter clinical practice. Intriguingly, clinical trials in Brazil have explored intranasal POH delivery as an alternative to circumvent the toxic limitations of oral administration. In these trials, patients with recurrent malignant gliomas were given comparatively small doses of POH via simple inhalation through the nose. Results from these studies show this type of long-term, daily chemotherapy to be well tolerated and effective. In this review, we will present the vicissitudes of POH’s evaluation as an anticancer agent, and its most recent success in therapy of patients with malignant brain tumors.
PMCID: PMC4497427  PMID: 26175929
Monoterpene; intranasal drug delivery; inhalation drug delivery; glioblastoma
2.  Polycomb protein family member CBX7 plays a critical role in cancer progression 
American Journal of Cancer Research  2015;5(5):1594-1601.
CBX7 is a polycomb protein that participates in the formation of polycomb repressive complex 1. Apart from few exceptions, CBX7 expression is lost in human malignant neoplasias and a clear correlation between its downregulated expression and a cancer aggressiveness and poor prognosis has been observed. These findings indicate a critical role of CBX7 in cancer progression. Consistently, CBX7 is able to differentially regulate crucial genes involved in cancer progression and in epithelial-mesenchymal transition, as osteopontin and E-cadherin. Recent evidences indicate a role of CBX7 also in the modulation of response to therapy. In conclusion, CBX7 represents an important prognostic factor, whose loss of expression in general indicates a bad prognosis and a progression towards a fully malignant phenotype.
PMCID: PMC4497428  PMID: 26175930
CBX7; cancer progression; polycomb group
3.  PI3K/Akt/mTOR signaling pathway in cancer stem cells: from basic research to clinical application 
American Journal of Cancer Research  2015;5(5):1602-1609.
Cancer stem cells (CSCs) are a subpopulation of tumor cells that possess unique self-renewal activity and mediate tumor initiation and propagation. The PI3K/Akt/mTOR signaling pathway can be considered as a master regulator for cancer. More and more recent studies have shown the links between PI3K/Akt/mTOR signaling pathway and CSC biology. Herein, we provide a comprehensive review on the role of signaling components upstream and downstream of PI3K/Akt/mTOR signaling in CSC. In addition, we also summarize various classes of small molecule inhibitors of PI3K/Akt/mTOR signaling pathway and their clinical potential in CSC. Overall, the current available data suggest that the PI3K/Akt/mTOR signaling pathway could be a promising target for development of CSC-target drugs.
PMCID: PMC4497429  PMID: 26175931
Cancer stem cells; PI3K/Akt/mTOR signaling pathway; self-renew; tumor initiation; rapamycin
4.  Homeostasis of redox status derived from glucose metabolic pathway could be the key to understanding the Warburg effect 
American Journal of Cancer Research  2015;5(4):1265-1280.
Glucose metabolism in mitochondria through oxidative phosphorylation (OXPHOS) for generation of adenosine triphosphate (ATP) is vital for cell function. However, reactive oxygen species (ROS), a by-product from OXPHOS, is a major source of endogenously produced toxic stressors on the genome. In fact, ATP could be efficiently produced in a high throughput manner without ROS generation in cytosol through glycolysis, which could be a unique and critical metabolic pathway to prevent spontaneous mutation during DNA replication. Therefore glycolysis is dominant in robust proliferating cells. Indeed, aerobic glycolysis, or the Warburg effect, in normal proliferating cells is an example of homeostasis of redox status by transiently shifting metabolic flux from OXPHOS to glycolysis to avoid ROS generation during DNA synthesis and protect genome integrity. The process of maintaining redox homeostasis is driven by genome wide transcriptional clustering with mitochondrial retrograde signaling and coupled with the glucose metabolic pathway and cell division cycle. On the contrary, the Warburg effect in cancer cells is the results of the alteration of redox status from a reprogramed glucose metabolic pathway caused by the dysfunctional OXPHOS. Mutations in mitochondrial DNA (mtDNA) and nuclear DNA (nDNA) disrupt mitochondrial structural integrity, leading to reduced OXPHOS capacity, sustained glycolysis and excessive ROS leak, all of which are responsible for tumor initiation, progression and metastasis. A “plumbing model” is used to illustrate how redox status could be regulated through glucose metabolic pathway and provide a new insight into the understanding of the Warburg effect in both normal and cancer cells.
PMCID: PMC4473309  PMID: 26101696
Mitochondrial bioredox; glucose metabolic pathway; the Warburg effect; mitochondrial dynamics; glycolysis
5.  L-type amino acid transport and cancer: targeting the mTORC1 pathway to inhibit neoplasia 
American Journal of Cancer Research  2015;5(4):1281-1294.
The L-type amino acid transporter (LAT) family are Na+-independent transporters, which deliver neutral amino acids into cells. The four LATs, LAT1 (SLC7A5), LAT2 (SLC7A8), LAT3 (SLC43A1) and LAT4 (SLC43A2), are responsible for the majority of cellular leucine uptake. They show increased expression in many cancers, and are critical for control of protein translation and cell growth through the mTORC1 pathway. The increased transporter expression observed in cancers is regulated by transcriptional pathways such as hormone receptors, c-myc and nutrient starvation responses. We review the expression and function of the LAT family in cancer, as well as the recent development of specific inhibitors targeting LAT1 or LAT3. These LAT family inhibitors may be useful adjuvant therapeutics in multiple cancers.
PMCID: PMC4473310  PMID: 26101697
L-type amino acid; transport; cancer; mTORC1 pathway
6.  Tubal origin of ovarian endometriosis and clear cell and endometrioid carcinoma 
Current research has strongly proposed that contrary to prior beliefs, many ovarian epithelial cancers (OECs) do not, as their name suggests, originate in the ovaries. Recent findings regarding both high-grade and low-grade serous carcinomas has implicated the fallopian tube as a cell source for these OECs, but until now, there has been little insight into the cellular source for clear cell and endometrioid carcinomas. In this commentary review article, we aimed to discuss the new findings that support the possible contribution from the fallopian tube in clear cell and endometrioid carcinomas. Specifically, we have provided results that showcased ovarian surface epithelia (OSE) and ovarian epithelial inclusions (OEIs) as having mesothelial and tubal origins and have strongly recognized the secondary müllerian system and the ability for tubal epithelia to implant upon the ovarian surface as contributing to fallopian tube-derived OEIs (F-OEIs). We have provided initial indications of these F-OEIs and their relationship to endometriosis and then clear cell and endometrioid carcinomas and subsequently offer our new proposal of a probable tubal origin. This new proposal is a paradigm that drastically changes the understanding behind the origin of these OECs and has significant clinical implications in the near future.
PMCID: PMC4449423  PMID: 26045974
Fallopian tube; secondary müllerian system; endometriosis; clear cell carcinoma; endometrioid carcinoma
7.  Chemotherapy targeting cancer stem cells 
Conventional chemotherapy is the main treatment for cancer and benefits patients in the form of decreased relapse and metastasis and longer overall survival. However, as the target therapy drugs and delivery systems are not wholly precise, it also results in quite a few side effects, and is less efficient in many cancers due to the spared cancer stem cells, which are considered the reason for chemotherapy resistance, relapse, and metastasis. Conventional chemotherapy limitations and the cancer stem cell hypothesis inspired our search for a novel chemotherapy targeting cancer stem cells. In this review, we summarize cancer stem cell enrichment methods, the search for new efficient drugs, and the delivery of drugs targeting cancer stem cells. We also discuss cancer stem cell hierarchy complexity and the corresponding combination therapy for both cancer stem and non-stem cells. Learning from cancer stem cells may reveal novel strategies for chemotherapy in the future.
PMCID: PMC4449424  PMID: 26045975
Side effects; biomarkers; drug delivery system; multifunctional carrier; cancer hierarchy
8.  Pancreatic cancer stem cells 
Studies are emerging in support of the cancer stem cells (CSCs) theory which considers that a tiny subset of cancer cells is exclusively responsible for the initiation and malignant behavior of a cancer. This cell population, also termed CSCs, possesses the capacity both to self-renew, producing progeny that have the identical tumorigenic potential, and to differentiate into the bulk of cancer cells, helping serve the formation of the tumor entities, which, altogether, build the hierarchically organized structure of a cancer. In this review, we try to articulate the complicated signaling pathways regulating the retention of the characteristics of pancreatic CSCs, and in the wake of which, we seek to offer insights into the CSCs-relevant targeted therapeutics which are, in the meantime, confronted with bigger challenges than ever.
PMCID: PMC4449425  PMID: 26045976
Pancreatic cancer; cancer stem cells; signaling pathway; microRNA; CSC-targeted therapeutic
9.  Long non-coding RNAs in gastric cancer: versatile mechanisms and potential for clinical translation 
Gastric cancer (GC) remains a serious threat to many people, representing the second leading cause of cancer-related death worldwide. The lack of early diagnostic biomarkers, effective prognostic indicators and therapeutic targets all account for the poor prognosis of GC. Therefore, the identification of novel molecular biomarkers for early diagnosis, therapeutic response, and prognosis are urgently needed. High-throughput sequencing has identified a large number of transcribed long non-coding RNAs (lncRNAs) throughout the human genome. Accumulating evidence demonstrates that these lncRNAs play multiple roles in regulating gene expression at the transcriptional, post-transcriptional, and epigenetic levels. Aberrant expression of lncRNAs occurs in various pathological processes, including GC. Many dysregulated lncRNAs in GC have been significantly associated with a larger tumor size, higher degree of tumor invasion, lymph node and distant metastasis, and poorer survival outcome. In this review, we will provide an overview of the pathogenesis of GC, the characteristics and regulatory functions of lncRNAs, and the versatile mechanisms of lncRNAs in GC development, as well as evaluate the translational potential of lncRNAs as novel diagnostic and prognostic biomarkers and therapeutic targets in GC.
PMCID: PMC4449426  PMID: 26045977
Gastric cancer; lncRNA; diagnosis; prognosis; therapy; biomarker
10.  Homeostasis of redox status derived from glucose metabolic pathway could be the key to understanding the Warburg effect 
Glucose metabolism in mitochondria through oxidative phosphorylation (OXPHOS) for generation of adenosine triphosphate (ATP) is vital for cell function. However, reactive oxygen species (ROS), a by-product from OXPHOS, is a major source of endogenously produced toxic stressors on the genome. In fact, ATP could be efficiently produced in a high throughput manner without ROS generation in cytosol through glycolysis, which could be a unique and critical metabolic pathway to prevent spontaneous mutation during DNA replication. Therefore glycolysis is dominant in robust proliferating cells. Indeed, aerobic glycolysis, or the Warburg effect, in normal proliferating cells is an example of homeostasis of redox status by transiently shifting metabolic flux from OXPHOS to glycolysis to avoid ROS generation during DNA synthesis and protect genome integrity. The process of maintaining redox homeostasis is driven by genome wide transcriptional clustering with mitochondrial retrograde signaling and coupled with the glucose metabolic pathway and cell division cycle. On the contrary, the Warburg effect in cancer cells is the results of the alteration of redox status from a reprogramed glucose metabolic pathway caused by the dysfunctional OXPHOS. Mutations in mitochondrial DNA (mtDNA) and nuclear DNA (nDNA) disrupt mitochondrial structural integrity, leading to reduced OXPHOS capacity, sustained glycolysis and excessive ROS leak, all of which are responsible for tumor initiation, progression and metastasis. A “plumbing model” is used to illustrate how redox status could be regulated through glucose metabolic pathway and provide a new insight into the understanding of the Warburg effect in both normal and cancer cells.
PMCID: PMC4449427  PMID: 26045978
Mitochondrial bioredox; glucose metabolic pathway; the Warburg effect; mitochondrial dynamics; glycolysis
11.  TGF-β signaling and its targeting for glioma treatment 
Transforming growth factor-beta (TGF-β) is a pleiotropic cytokine, secreted by a variety of cells including immune cells, tumor cells, and stromal cells. TGF-β signaling is dysregulated in cancer patients, and this aberrant signaling at least in part contributes to initiation and progression of many cancers including glioma. The dysregulated signaling components provide molecular targets for the treatment of glioma. In this article, we review TGF-β signaling and its targeting in glioma.
PMCID: PMC4449428  PMID: 26045979
TGF-β; TGF-β signaling; glioma; gliomagenesis; glioma treatment
12.  Circular RNAs in cancer: novel insights into origins, properties, functions and implications 
Circular RNAs (circRNAs) are a large class of RNAs that, unlike linear RNAs, form covalently closed continuous loops and have recently shown huge capabilities as gene regulators in mammals. These circRNAs mainly arise from exons or introns, and are differentially generated by back splicing or lariat introns. Interestingly, they are found to be enormously abundant, evolutionally conserved and relatively stable in cytoplasm. These features confer numerous potential functions to circRNAs, such as acting as microRNA (miRNA) sponges, binding to RNA-associated proteins to form RNA-protein complexes and then regulating gene transcription. Importantly, circRNAs associate with cancer-related miRNAs and the circRNA-miRNA axes are involved in cancer-related pathways. Some synthetic circRNAs have shown the remarkable anti-cancer effects. Though circRNAs are ancient molecules, the huge therapeutic potentials of circRNAs are recently being discovered from the laboratory to the clinic. Here, we review the current understanding of the roles of circRNAs in cancers and the potential implications of circRNAs in cancer targeted therapy.
PMCID: PMC4396047  PMID: 25973291
Circular RNA; microRNA sponge; anti-cancer; targeted therapy
13.  MYC-xing it up with PIK3CA mutation and resistance to PI3K inhibitors: summit of two giants in breast cancers 
Approximately 35% of breast cancers exhibit PIK3CA activating mutation. Since PIK3CA hotspot mutation is the most frequently mutated gene in human breast cancers and primarily overlaps in HER2+ as well as ER+ breast cancers, the subset of patients bearing PIK3CA activating mutation does not get fullest benefit from either anti-HER2 or anti-hormonal agents. Literature also suggests that these patients may have chemotherapy resistance. Indeed, multiple clinical trials are currently evaluating the efficacy of over 30 drugs targeting different nodal points in the PI3K-AKT-mTOR pathway in breast and other cancers. However, to date, responses of solid tumors to PI3K pathway inhibitor monotherapy remains modest with an accompanied rapid emergences of drug resistance. MYC elevation represents one of the potential modes of actions by which breast tumors develop resistance to the PI3K pathway-specific targeted therapies. As products of oncogenes, both MYC and PIK3CA are well-established onco-proteins which contribute to breast oncogenesis. However, their similarities out number their dissimilarities in the context of their specific oncogenic cellular signals. In this review we will describe the specific cellular signals initiated following alteration in the MYC gene and PIK3CA gene in breast cancers. We will interrogate how MYC gene alterations influence the action of PI3K pathway targeted drugs in the context of PIK3CA mutation towards the development PI3K inhibitor induced drug-resistance in breast cancers.
PMCID: PMC4300701  PMID: 25628917
Breast tumors; MYC; PIK3CA; PI3K inhibitors; resistance
14.  MicroRNA regulation and therapeutic targeting of survivin in cancer 
Survivin, the smallest member of IAP (inhibitor of apoptosis) family, is a dual functional protein acting as a critical apoptosis inhibitor and key cell cycle regulator. Survivin is usually expressed in embryonic tissues during development and undetectable in most terminally differentiated tissues. Numerous studies demonstrate that survivin is selectively upregulated in almost all types of human malignancies and its overexpression positively correlates with poor prognosis, tumor recurrence, and therapeutic resistance. This differential expression of survivin in tumors and normal tissues draws a great interest to develop survivin-targeted therapy for cancer treatment. Nonetheless, the molecular mechanisms controlling survivin expression in malignant tumor cells have not been fully understood. While aberrant activation of receptor tyrosine kinases (RTKs) and the downstream signaling, such as PI-3K/Akt, MEK/MAPK, mTOR, and STAT pathways, have frequently been shown to upregulate survivin, recent data suggest that a class of noncoding RNAs, microRNAs (miRNAs) also play an important role in survivin dysregulation in human cancers. Here, we focus on survivin expression-regulated by specific miRNAs binding to the 3’-UTR of survivin mRNA, and summarize the latest advances on survivin-targeted therapy in clinical trials and the therapeutic potential of survivin-targeting miRNAs in cancer.
PMCID: PMC4300714  PMID: 25628918
Survivin; miRNA; targeted therapy; cancer
15.  Anticancer activity of essential oils and their chemical components - a review 
Essential oils are widely used in pharmaceutical, sanitary, cosmetic, agriculture and food industries for their bactericidal, virucidal, fungicidal, antiparasitical and insecticidal properties. Their anticancer activity is well documented. Over a hundred essential oils from more than twenty plant families have been tested on more than twenty types of cancers in last past ten years. This review is focused on the activity of essential oils and their components on various types of cancers. For some of them the mechanisms involved in their anticancer activities have been carried out.
PMCID: PMC4266698  PMID: 25520854
Essential oils; anticancer activity; chemical composition
16.  Redundant kinase activation and resistance of EGFR-tyrosine kinase inhibitors 
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have shown dramatic effects against that tumors harboring EGFR activating mutations in the EGFR intracytoplasmic tyrosine kinase domain and resulted in cell apoptosis. Unfortunately, a number of patients ultimately developed resistance by multiple mechanisms. Thus, elucidation of the mechanism of resistance to EGFR-TKIs can provide strategies for blocking or reversing the situation. Recent studies suggested that redundant kinase activation plays pivotal roles in escaping from the effects of EGFR-TKIs. Herein, we aimed to characterize several molecular events involved in the resistance to EGFR-TKIs mediated by redundant kinase activation.
PMCID: PMC4266699  PMID: 25520855
EGFR; redundant kinase activation; resistance to EGFR-TKIs
17.  EGFR-TKI resistance in NSCLC patients: mechanisms and strategies 
The epidermal growth factor receptor (EGFR) is a kind of receptor tyrosine kinase (RTK) that plays a critical role in the initiation and development of malignant tumors via modulating downstream signaling pathways. In non-small cell lung cancer (NSCLC), the activating mutations located in the tyrosine kinase domains of EGFR have been demonstrated in multiple researches as the “Achilles’ heel” of this deadly disease since they could be well-targeted by epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). However, it’s still too early to celebrate since the first-generation EGFR-TKIs such as gefitinib and erlotinib have only achieved limited clinical benefits and acquired resistance to this kind of drugs occurred inevitably in almost all the NSCLC patients. In order to make the most of EGFR-TKIs and develop more effective regimens for the NSCLC patients, researchers majoring in different aspects start a battle against EGFR-TKI resistance. Challenging as it is, we still progress stably and step firmly toward the final victory. This review will summarize the major mechanisms of acquired resistance to EGFR-TKIs, and then discuss the development of rationally designed molecular target drugs in accordance with each mechanism, in the hope of shedding light on the great achievements we have obtained and tough obstacles we have to overcome in the battle against this deadly disease.
PMCID: PMC4163608  PMID: 25232485
Non-small cell lung cancer; epithelial growth factor receptor; tyrosine kinase inhibitors; drug resistance; molecular targeted therapy
18.  A review of management strategies of malignant gliomas in the elderly population 
Glioblastoma Multiforme (GBM) is the most frequent primary malignant brain tumor in adults. It is an aggressive primary brain neoplasm, associated with a poor prognosis and median survival of less than 1 year. Approximately 50% of patients diagnosed with malignant gliomas in the United States are over the age of 65. Advancing age and poor performance status are two variables that have found to negatively affect prognosis. When compared to younger patients, not only is the treatment of elderly patients associated with decreased efficacy but also greater toxicity. As a result, elderly patients often receive less aggressive treatment and are excluded from clinical trials. There are many challenges in the treatment of elderly patients with GBM including increased surgical morbidity and mortality as well as increased toxicity to radiation and chemotherapy. As such, the optimal therapy remains unclear and controversial for the elderly malignant glioma population.
PMCID: PMC4163609  PMID: 25232486
High grade glioma; GBM; MGMT; malignant astrocytoma; elderly patients
19.  Role of SOX family of transcription factors in central nervous system tumors 
SOX genes are developmental regulators with functions in the instruction of cell fate and maintenance of progenitor’s identity during embryogenesis. They play additional roles during tissue homeostasis and regeneration in adults particularly in the Central Nervous System (CNS). In the last years a growing number of evidences has shown that mutations and dysfunction of SOX factors are implicated in several human diseases, including a variety of cancers. In this review, we will summarize the current knowledge about SOX family in CNS tumors and their role in the origin and maintenance of the subpopulation of cancer stem cells in these tumors.
PMCID: PMC4106650  PMID: 25057435
SOX; CNS tumors; glioblastoma; glioma stem cell; cell of origin; oncogenic SOX2; therapy target
20.  S100 protein family in human cancer 
S100 protein family has been implicated in multiple stages of tumorigenesis and progression. Among the S100 genes, 22 are clustered at chromosome locus 1q21, a region frequently rearranged in cancers. S100 protein possesses a wide range of intracellular and extracellular functions such as regulation of calcium homeostasis, cell proliferation, apoptosis, cell invasion and motility, cytoskeleton interactions, protein phosphorylation, regulation of transcriptional factors, autoimmunity, chemotaxis, inflammation and pluripotency. Many lines of evidence suggest that altered expression of S100 proteins was associated with tumor progression and prognosis. Therefore, S100 proteins might also represent potential tumor biomarkers and therapeutic targets. In this review, we summarize the evidence connecting S100 protein family and cancer and discuss the mechanisms by which S100 exerts its diverse functions.
PMCID: PMC3960449  PMID: 24660101
S100 proteins; proliferation; apoptosis; invasion; migration; pluripotency; biomarker
21.  Beyond laser microdissection technology: follow the yellow brick road for cancer research 
Normal biological tissues harbour different populations of cells with intricate spacial distribution patterns resulting in heterogeneity of their overall cellular composition. Laser microdissection involving direct viewing and expertise by a pathologist, enables access to defined cell populations or specific region on any type of tissue sample, thus selecting near-pure populations of targeted cells. It opens the way for molecular methods directed towards well-defined populations, and provides also a powerful tool in studies focused on a limited number of cells. Laser microdissection has wide applications in oncology (diagnosis and research), cellular and molecular biology, biochemistry and forensics for tissue selection, but other areas have been gradually opened up to these new methodological approaches, such as cell cultures and cytogenetics. In clinical oncology trials, molecular profiling of microdissected samples can yield global “omics” information which, together, with the morphological analysis of cells, can provide the basis for diagnosis, prognosis and patient-tailored treatments. This remarkable technology has brought new insights in the understanding of DNA, RNA, and the biological functions and regulation of proteins to identify molecular disease signatures. We review herein the different applications of laser microdissection in a variety of fields, and we particularly focus attention on the pre-analytical steps that are crucial to successfully perform molecular-level investigations.
PMCID: PMC3902229  PMID: 24482735
Laser microdissection; histopathology; quality control; snap-freezing; DNA; RNA; proteomics; in situ cellular and molecular analyses
22.  NFκB function and regulation in cutaneous T-cell lymphoma 
The nuclear accumulation and transcriptional activity of NFκB are constitutively increased in cutaneous T-cell lymphoma (CTCL) cells, and are responsible for their increased survival and proliferation. However, in addition to the anti-apoptotic and pro-inflammatory genes, NFκB induces expression of immunosuppressive genes, such as IL-10 and TGFβ, which inhibit the immune responses and are characteristic for the advanced stages of CTCL. While the mechanisms regulating NFκB-dependent transcription of anti-apoptotic and pro-inflammatory genes have been studied extensively, very little is known about the NFκB regulation of immunosuppressive genes. The specificity of NFκB-regulated responses is determined by the subunit composition of NFκB complexes recruited to the individual promoters, post-translational modifications of NFκB proteins, as well as by their interactions with other transcriptional factors and regulators. In this review, we discuss the mechanisms regulating the transcription of NFκB-dependent anti-apoptotic, pro-inflammatory and immunosuppressive genes in CTCL cells, as potential targets for CTCL therapies.
PMCID: PMC3816964  PMID: 24224122
Apoptosis; bortezomib; cutaneous T cell lymphoma; IκBα; IL-10; immunosuppression; NFκB; proteasome inhibition; TGFβ
23.  Nuclear transcription factor Y and its roles in cellular processes related to human disease 
Nuclear transcription factor Y (NF-Y) is an example of a transcriptional regulation factor in eukaryotes consisting of three different subunits, NF-YA, NF-YB and NF-YC, which are all necessary for formation of NF-Y complexes and binding to CCAAT boxes in promoters of its target genes. Highly conserved between human and Drosophila, NF-Y regulates transcription of various genes related to the cell cycle and various human diseases. Drosophila models have been widely used as tools for studying genetics and developmental biology and more recently for analyzing the functions of human disease genes, including those responsible for developmental and neurological disorders, cancer, cardiovascular disease and metabolic and storage diseases, as well as genes required for function of the visual, auditory and immune systems. In this review, in vivo findings from Drosophila models relevant to the roles of NF-Y in various human diseases are summarized. Recent studies have demonstrated novel contributions of dNF-Y to apoptosis and apoptosis-induced proliferation, and in photoreceptor cell differentiation during the development of the Drosophila compound eye.
PMCID: PMC3744014  PMID: 23977444
Transcription factors; NF-Y; NF-YB; apoptosis; Drosophila model
24.  BLT2 is a pro-tumorigenic mediator during cancer progression and a therapeutic target for anti-cancer drug development 
Cancer is a leading cause of death worldwide and has been linked to inflammation. Leukotriene B4 (LTB4) is synthesized from arachidonic acid via the 5-lipoxygenase pathway and is a potent chemoattractant for inflammatory cells. LTB4 was recently shown to be associated with the pathogenesis of inflammatory diseases, including cancer. Of the two known LTB4 receptors, BLT1 and BLT2, the biological roles of the low-affinity LTB4 receptor 2, BLT2, have only recently been elucidated. This review focuses on recent discoveries regarding BLT2 and its roles in cancer progression and the downstream signaling mechanisms of the BLT2-linked signaling cascade in cancer cells. We believe that these findings will facilitate the development of new cancer treatments.
PMCID: PMC3744015  PMID: 23977445
Leukotriene B4 receptor 2 (BLT2); leukotriene B4; NADPH oxidase; reactive oxygen species; nuclear factor-kB; cancer progression
25.  Mouse models for colorectal cancer 
Colorectal cancer (CRC) is the third leading cause of cancer-related death in the United States, with the number of affected people increasing. There are many risk factors that increase CRC risk, including family or personal history of CRC, smoking, consumption of red meat, obesity, and alcohol consumption. Conversely, increased screening, maintaining healthy body weight, not smoking, and limiting intake of red meat are all associated with reduced CRC morbidity and mortality. Mouse models of CRC were first used in 1928 and have played an important role in understanding CRC biology and treatment and have long been instrumental in clarifying the pathobiology of CRC formation and inhibition. This review focuses on advancements in modeling CRC in mice.
PMCID: PMC3696531  PMID: 23841024
Colorectal cancer; human; mouse models; tumorigenesis; Apc; FAP; HNPCC; stem cells

Results 1-25 (95)