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Publisher: Smart Science and Technology LLC   (Total: 21 journals)   [Sort by number of followers]

Showing 1 - 21 of 21 Journals sorted alphabetically
Abdomen     Open Access  
Cancer Cell & Microenvironment     Open Access   (Followers: 8)
Cardiovascular Regenerative Medicine     Open Access  
Evidence-based Medicine & Public Health     Open Access   (Followers: 6)
Immunoendocrinology     Open Access   (Followers: 1)
Inflammation and Cell Signaling     Open Access   (Followers: 3)
Itch & Pain     Open Access   (Followers: 2)
J. of Advanced Nutrition and Human Metabolism     Open Access   (Followers: 14)
Macrophage     Open Access  
Molecular & Cellular Epilepsy     Open Access   (Followers: 2)
Musculoskeletal Regeneration     Open Access   (Followers: 2)
Neurotransmitter     Open Access  
Precision Medicine     Open Access   (Followers: 2)
Receptors & Clinical Investigation     Open Access   (Followers: 1)
RNA & Disease     Open Access   (Followers: 1)
Science Proceedings     Open Access   (Followers: 1)
Stem Cell and Translational Investigation     Open Access   (Followers: 2)
Stem Cell Epigenetics     Open Access   (Followers: 3)
Telomere and Telomerase     Open Access  
Therapeutic Targets for Neurological Diseases     Open Access   (Followers: 1)
Uterus & Ovary     Open Access  
Journal Cover Cancer Cell & Microenvironment
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   ISSN (Print) 2331-0928
   Published by Smart Science and Technology LLC Homepage  [21 journals]
  • Scaling up to study brca2: the zeppelin zebrafish mutant reveals a role
           for brca2 in embryonic development of kidney mesoderm

    • Authors: Bridgette E. Drummond, Rebecca Ann Wingert
      Abstract: Specialized renal epithelial cells known as podocytes are essential components of the filtering structures within the kidney that coordinate the process of removing waste from the bloodstream. Podocyte loss initiates many human kidney diseases as it triggers subsequent damage to the kidney, leading to progressive loss of function that culminates with end stage renal failure. Podocyte morphology, function and gene expression profiles are well conserved between zebrafish and humans, making the former a relevant model to study podocyte development and model kidney diseases. Recently, we reported that whole genome sequencing of the zeppelin (zep) zebrafish mutant, which exhibits podocyte abrogation, revealed that the causative lesion for this defect was a splicing mutation in the breast cancer 2, early onset (brca2) gene. This was a surprising and novel discovery, as previous research on brca2/BRCA2 in a number of vertebrate animal models had not implicated an explicit role for this gene in kidney mesoderm development. Interestingly, the abrogation of the podocyte lineage in zep mutants was also accompanied by the formation of a larger interrenal (IR) gland, which is analogous to the adrenal gland in mammals, and suggested a fate switch between the renal and interrenal mesodermal derivatives. Mirroring these findings, knockdown of brca2 also recapitulated the loss of podocytes and increased IR populace. In addition, brca2 overexpression was sufficient to partially rescue podocytes in zep mutants, and induced ectopic podocyte formation in wild-type embryos. Interestingly, immunofluorescence studies indicated that zep mutants had elevated P-h2A.X levels, suggesting that DNA repair is dysfunctional in these animals and contributes to the zep phenotype. Moving forward, this unique zebrafish mutant provides a new model to further explore how brca2 contributes to the development of tissues including the kidney mesoderm—roles which may have implications for renal diseases as well.
      PubDate: 2018-04-09
      Issue No: Vol. 5, No. 1 (2018)
       
  • Cellular Homeostasis or Tumorigenesis: USP7 Playing the Double Agent

    • Authors: Mrinal Kanti Ghosh, Bhaskar Basu, Gouranga Saha, Shreyasee Ghatak Choudhury
      Abstract: The ubiquitin specific protease USP7/HAUSP is a major deubiquitinase that acts upon a wide spectrum of substrate proteins. Deubiquitination by USP7 generally leads to stabilization of substrates and their rescue from proteasomal degradation, but can also lead to alteration in their intracellular localization and activity. On the basis of its substrate proteins, USP7 has been shown to regulate processes involved in both the maintenance of homeostasis and the promotion of tumorigenesis. USP7, so far does not seem to be a dedicated regulator for either of these cellular phenomena, instead the relative abundance of a particular set of substrates over another being the factor that decides towards which phenomena it will be monopolized. The onset of cancer unfortunately creates an abundance of pro-oncogenic substrates, and this leads to a drastic monopolization of USP7 function towards the enhancement of further pro-oncogenic signaling.
      PubDate: 2018-02-05
      Issue No: Vol. 5, No. 1 (2018)
       
  • Role of Monoamine oxidase A (MAO-A) in cancer progression and metastasis

    • Authors: Ashish Bhattacharjee, Pritam Biswas, Sukhamoy Dhabal, Payel Das, Pradip Das, Surbhi Swaroop, Tuhina Prasad, Dhanalakshmi J, Indhumathi S
      Abstract: Monoamine oxidase A (MAO-A) is a flavoenzyme that catalyzes biogenic amines into the corresponding aldehydes by oxidative deamination. Although MAO-A is primarily associated with depression and antisocial behaviour, dysregulation of MAO-A has been associated with neurodegenerative diseases and cardiovascular disorders. Moreover, the contribution of MAO-A in the resolution of inflammation is well established. Recent reports reveal the unanticipated role of MAO-A in tumorigenesis. In this review we provide informations that MAO-A is involved in the progression and metastasis of many different cancer cells including prostate cancer, colorectal cancer, hepatocellular carcinoma and lung cancer. We further discuss the regulatory mechanisms that control tumorigenesis, progression and metastasis in these different type of cancer cells. Altogether these informations indicate that MAO-A can be a general therapeutic target in cancer treatment. 
      PubDate: 2018-02-05
      Issue No: Vol. 5, No. 1 (2018)
       
  • Research Highlight: Metastatic Malignant Thymoma to the Abdomen

    • Authors: Saju Joseph
      Abstract: Thymoma is a rare neoplasm of thymic epithetical cells that has the ability to spread by local extension. While metastases are most commonly confined to the pleura, pericardium and diaphragm, cases of abdominal metastases have been reported. In a recent publication [ref 7], we conducted a SEER database and literature review to identify cases of malignant thymoma (MT) and abdominal metastases, demonstrating an increasing overall incidence of MT with a significant male predominance. Additionally, we suggested routine screening for all MT patients as roughly 50% of abdominal metastasis cases presented as asymptomatic, as well as a multimodal treatment approach for those with metastatic MT to the abdomen. In this highlight, we briefly present the evidence for a rising rate of MT, review reported cases of abdominal metastasis, and emphasize the need for a multimodal treatment approach.  
      PubDate: 2018-01-29
      Issue No: Vol. 5, No. 1 (2018)
       
  • Cryptotanshinone suppresses cell proliferation and induces apoptosis in
           renal cell carcinoma as an STAT3 inhibitor

    • Authors: wei zhai
      Abstract: Cryptotanshinone (CPT) is a lipid-soluble constituent isolated from the root of Salvia Miltiorrhiza Bunge. Except the widely known antimicrobial, cardioprotection and antiinflammation effect, recent studies emphasize the potent anticancer activity of CPT in a wide variety of human cancers. Our previous study paid attention to the function of CPT against RCC. Results demonstrated that CPT could significantly suppress RCC formation in vitro and in vivo as a specific STAT3 inhibitor, indicating the potential therapeutic value of CPT against RCC.
      PubDate: 2017-12-11
      Issue No: Vol. 4, No. 4 (2017)
       
  • Photoinduced antitumor and antimicrobial effects of nanomaterials

    • Authors: Huining Bai, Lily Li, Zhen Ji, Cong Wang, Weijia Wen
      Abstract: The photoinduced effects of nanomaterials encompass several incredibly hot research topics, including the photoelectric, photothermal (PT) and photochemical effects. The PT effect arises from the synergistic effect between light irradiation and heat diffusion and has potential uses in cancer therapy and antimicrobial materials. Meanwhile, the photo-Fenton (PF) reaction is a typical photochemical reaction that has become an important method for combating environmental waste and organisms. Here, the development of the PT effect and PF reaction of nanoparticles (NPs) has been reviewed. Considerable attention has been paid to the tremendous wide range of nanomaterial types, such as oxide/sulfide, carbon-based NPs and metallic NPs, that can provide a photoheat or photochemical response and for determining the optimal dose for each material. The main focus of this review is the development and physicochemical mechanisms of each classical compound type as well as the application of photoresponsive nanomaterials in therapy and disinfection.
      PubDate: 2017-10-30
      DOI: 10.14800/ccm.1606
      Issue No: Vol. 4, No. 4 (2017)
       
  • Protein synthesis inhibition enhances Paraptotic death induced by
           inhibition of Cyclophilins in Glioblastoma Cells

    • Authors: Lin Wang, Justin H Gundelach, Richard J Bram
      Abstract: Treatment of cancer is frequently unsuccessful related to the loss of apoptotic signaling in malignant cells. This is a particular problem for high-grade gliomas, such as Glioblastoma Multiforme (GBM), which are almost universally fatal within a year or so of diagnosis. Novel therapies that capitalize on non-apoptotic cell death pathways may yield more effective outcomes, if their underlying mechanisms can be more completely deciphered. In a recent publication (ref 10), the mechanisms by which cellular cyclophilins support GBM cell survival have been identified. Inhibition of cyclophilins activated paraptosis, which relied on a combination of endoplasmic reticulum (ER) stress and transient activation of autophagy. An important aspect of this effect was the relative rates of cap-dependent versus cap-independent protein synthesis, which were differentially modulated by protein synthesis inhibitors or mTOR inhibition. Although cycloheximide has previously been characterized as an inhibitor of paraptosis, in the case of cyclophilin inhibition, it appears to significantly enhance stress-related paraptosis and cell death. This work reveals an important role for cap-independent protein translation and autophagy in the ability of GBM cells to resist non-apoptotic death, and adds to our understanding of the events that underlie paraptosis.
      PubDate: 2017-10-02
      DOI: 10.14800/ccm.1601
      Issue No: Vol. 4, No. 3 (2017)
       
  • Roles of alternative splicing in the pathogenesis of lung cancer

    • Authors: Hongyan Liu, Lianlian Li, Xiaoyu Zhang, Dayong Cui
      Abstract: Alternative splicing contributes to the vast complexity of mRNA transcripts and protein isoforms. It has been estimated that the majority of protein-coding genes are subject to alternative splicing in humans. Alternative splicing plays a critical role in physiological processes and cell development programs, and dysregulation of alternative splicing is often associated with pathologic conditions such as cancer. Indeed, the abnormal splicing is frequently found in lung cancer, which produces various isoforms of proteins with properties that may have different function and therefore even diverse effects on cancer progression. In this highlight, we summarize the evidence supporting the functional role of alternative splicing in lung cancer, discuss the regulation of alternative splicing, and highlight the relevance of splicing variation on lung cancer therapy.
      PubDate: 2017-09-18
      DOI: 10.14800/ccm.1596
      Issue No: Vol. 4, No. 3 (2017)
       
  • Cytidine Deaminase as a Molecular Target in Cancer: An Insight

    • Authors: Debasish Bandyopadhyay, Claudia A Almaraz
      Abstract: Cancer is one of the leading causes of death globally. Although more than 400 varieties of cancer have been reported, based on cell lines, still the actual reason of all types of cancer is not very clear. Several internal and external factors have been identified and the study is ongoing. Up to now about 73 proteins have been identified that play major role in different phases of cancer including cellular mutation, formation, invasion, angiogenesis, and metastasis. Cytidine deaminase is one of the important proteins that is responsible for various types of cancer that includes, but are not limited to, gastric, liver, biliary tract, bladder, breast, pancreatic ductal adenocarcinoma (PDAC) and so on. Two excellent inhibitors of cytidine deaminase are commercially available. A brief overview is presented in this advanced review. Any omission is completely unintentional. 
      PubDate: 2017-08-21
      DOI: 10.14800/ccm.1584
      Issue No: Vol. 4, No. 3 (2017)
       
  • Progress in Isolation and Enrichment of Cancer Stem Cells

    • Authors: chanchan zhu
      Abstract: Cancer stem cells (CSC) are a group of cells capable of self-renewal and can proliferate into a heterogeneous bulk with cancer progeny population. This is the exactly primary reason for metastasis and recurrence of tumors. Strategies for studying cancer’s targeted therapy and biological property mainly include its isolation and enrichment. In the coming era it will also be the focus of significant value. We will summarize the current strategies used for isolation and enrichment of CSC, including serum-free suspension culture、feeder cell layers、immunoselection based on cell surface markers、side population cells、resistance to radiation treatment and chemotherapy、combined utilization of various strategies and a three dimension (3D) in vitro model in this review.
      PubDate: 2017-08-07
      DOI: 10.14800/ccm.1575
      Issue No: Vol. 4, No. 3 (2017)
       
  • Trichosanthin induces anti-cancer effects by increasing the penetration of
           Granzyme B into tumor cells

    • Authors: Yinxin Zhu, Dan Ye, Jing Shen, zhangang Xiao
      Abstract: Trichosanthin (TCS), known as a plant toxin, is applied as a midterm abortifacient in clinics, and currently reported to exhibit other biological and pharmaceutical effects such as anti-tumor, anti-HIV, and. Immunoregulation. TCS was found out to firmly inactivate the ribosomes of the eukaryotic cell, but this finding was far enough to explain its various biological and pharmaceutical effects. Our previous studies focused on exploring novel TCS binding proteins, as to reveal new mechanisms in mammalian cells. And we found out that TCS and cation-independent mannose-6-phosphate receptor (CI-MPR) competitively bind to Golgi-localized, γ-ear containing and Arf-binding proteins (GGA), which finally increased the cell permeability of Granzyme B and promoted the cytotoxic T lymphocyte-mediated tumor cell apoptosis.
      PubDate: 2017-07-31
      DOI: 10.14800/ccm.1576
      Issue No: Vol. 4, No. 3 (2017)
       
  • Brain derived neutrophic factor (BDNF) coordinates lymphovascular
           metastasis through a fibroblast-governed paracrine axis in the tumor
           microenvironment

    • Authors: Tilahun Jiffar, Turker Yilmaz, Junegoo Lee, Yair Miller, Lei Feng, Adel El-Naggar, Michael Kupferman
      Abstract: It has long been known that the tumor microenvironment contributes to the proliferation and survival of neoplasms through the constant interaction with the stromal and immune compartments. In this investigation, we explored the role of cancer associated fibroblasts (CAFs) in the regulation of the tumor microenvironment in head and neck squamous cell carcinoma (HNSCC) though a complex intercellular BDNF-TrkB signaling system. Our studies show that conditioned media derived from patient-derived CAFs promoted HNSCC cell proliferation, in vitro cell migration, cell invasion and chemotherapy resistance, compared to normal fibroblasts.. Furthermore, examination of the in vivo impact of CAF pathophysiology in the tumor microenvironment in animal xenograft models revealed  that HNSCC cell lines in combination with CAFs promoted  tumor growth and increased incidence of lymphovascular metastasis as compared to injection of tumor cells or CAF cells alone. Using pharmacological and genetic alterations, we mechanistically demonstrate the critical importance of BDNF-TrkB signaling in the tumor microenvironment . These investigations further support the rationale for BDNF/TRKB targeted therapy against in the treatment of HNSCC.
      PubDate: 2017-07-10
      DOI: 10.14800/ccm.1566
      Issue No: Vol. 4, No. 2 (2017)
       
  • The regulation of Snail: On the Ubiquitin Edge

    • Authors: Qian Yu, Binhua Peter Zhou, yadi Wu
      Abstract: Metastasis accounts for a majority of cancer death. One key feature during metastasis is epithelial-mesenchymal transition (EMT), which is regulated by transcription factors such as Snail and Twist. In non-malignant cells, Snail has a short half-life and is degraded via ubiquitination, but its stability is increased in cancer cell. However, the mechanism by which Snail escapes ubiquitination and degradation remains unknown. Recently, we found that Dub3 is a deubiquinase of Snail. Most importantly, we determined that Dub3 responded to extracellular signals such as IL-6, and that the resultant signaling prevented Snail degradation, and promoted cancer growth, invasion, and migration. In this highlight, we present a concise picture of how the transcription factor Snail is regulated by ubiquitination in cancer cells, the role of Dub3 in this process, and its potential use as a treatment target.
      PubDate: 2017-07-03
      DOI: 10.14800/ccm.1567
      Issue No: Vol. 4, No. 2 (2017)
       
  • Emerging role of SHARPIN in hepatocellular carcinoma progression

    • Authors: Yasuo Tanaka, Ryosuke Tateishi, Kazuhiko Koike
      Abstract: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide and the leading cause of cancer-related death, especially in less economically developed regions. Despite recent progress in the diagnosis and therapy of HCC, the long-term survival rate of HCC patients is unacceptably low, in part due to the frequent development of vascular invasion or distant metastasis. The cellular functions of shank-associated RH domain-interacting protein (SHARPIN, also known as SIPL1) include the regulation of inflammation, apoptosis, immune signaling, and cell motility. SHARPIN is up-regulated in various types of cancers including HCC and has been implicated in the genesis and progression of malignant tumors, but its exact role in tumorigenesis is largely unknown. Here we present evidence supporting a role for SHARPIN in HCC invasion and progression. We also discuss the potential of SHARPIN and related genes as therapeutic targets for this currently incurable cancer.
      PubDate: 2017-05-24
      DOI: 10.14800/ccm.1540
      Issue No: Vol. 4, No. 2 (2017)
       
  • Inhibition of nucleo-cytoplasmic shuttling through XPO1/CRM1: A unique
           therapeutic approach for treatment of haematological and solid
           malignancies

    • Authors: Sneha S, Nagare R. P, Bindhya Sadhanandhan, Ramesh Shankar, Sidhanth Suresh, Trivadi S Ganesan, Manoj Garg
      Abstract: Cancer is the one of leading cause of morbidity and mortality worldwide. Regulated nucleo-cytoplasmic shuttling is very crucial for maintaining cellular homeostasis. Emerging evidence suggests that deregulation of the nucleo-cytoplasmic transport plays an important role in abnormal cellular growth, cell cycle, apoptosis, tumor progression, drug resistance. Exportin-1/XPO1 (also called as chromosome region maintenance 1/ CRM1) belongs to karyopherin-β superfamily and is the main mediator of nuclear export in several cell types.  The XPO1/CRM1 protein is overexpressed in liposarcoma, Ewing sarcoma, ovarian carcinoma, pancreatic cancer, hepatocellular carcinoma, lung cancer, osteosarcoma, gastric carcinoma, melanoma, glioma, acute myeloid leukemia, acute lymphocytic leukemia, chronic myeloid/lymphoid leukemia as well as multiple myeloma. Hot spot mutations are also observed in many cancers. Higher levels of XPO1/CRM1 are associated with poor prognosis, resistance to chemotherapy and recurrence in a large number of human malignancies. There are growing evidences that provided the foundation that inhibition of nuclear export by inhibiting nuclear export receptor (XPO1) might be a potential targeted therapeutic approach for the treatment of human cancers in the clinic. In the present review, we will discuss the role of XPO1 in cancers and potential of selective inhibitors of nuclear export (XPO1 inhibitors) to restore the normal function of tumor suppressor and growth regulatory proteins by blocking their export. Selinexor (KPT-330) is an orally available, highly potent and is being tested in human phase I/II clinical trials in both haematological and solid malignancies.
      PubDate: 2017-03-13
      DOI: 10.14800/ccm.1516
      Issue No: Vol. 4, No. 1 (2017)
       
  • Bystander effects of nitric oxide in anti-tumor photodynamic therapy

    • Authors: Albert Girotti, Jerzy Bazak, Jonathan M Fahey, Katarzyna Wawak, Witold Korytowski
      Abstract: Ionizing radiation of specifically targeted cells in a given population is known to elicit pro-death or pro-survival responses in non-targeted bystander cells, which often make no physical contact with the targeted ones. We have recently demonstrated a similar phenomenon for non-ionizing photodynamic therapy (PDT), showing that prostate cancer cells subjected to targeted photodynamic stress stimulated growth and migration of non-stressed, non-contacting bystander cells. Diffusible nitric oxide (NO) generated by stress-upregulated inducible nitric oxide synthase (iNOS) was shown to play a dominant role in these responses. Moreover, target-derived NO stimulated iNOS/NO induction in bystanders, suggesting a NO-mediated feed-forward field effect driven by targeted cells surviving the photodynamic challenge. In this research highlight, we will review these findings and discuss their potential negative implications on clinical PDT outcomes and how these might be mitigated through pharmacologic use of select iNOS inhibitors.
      PubDate: 2017-02-27
      DOI: 10.14800/ccm.1511
      Issue No: Vol. 4, No. 1 (2017)
       
  • A double-edged sword - the role of human ADAM17 in NK cell activity

    • Authors: Pinchas Tsukerman, Dominik Schmiedel, Ofer Mandelboim
      Abstract: ADAM17 is a pleiotropic sheddase that regulates the activity of diverse membrane-anchored proteins by proteolytic cleavage. Also, many immune functions depend on ADAM17 activity, for instance CD16 and TNFα, two key effector molecules of Natural Killer cells, are cleaved by this enzyme. Whereas CD16 is shed from the surface and therefore its activity is terminated by ADAM17, TNFα requires shedding to be soluble and fulfil its effector functions. Due to these antagonistic effects on immune system activity, clinical benefits of ADAM17 inhibition for the treatment of cancer patients are hard to predict.Recently, we reported of a patient with a very rare genetic deficiency of ADAM17 leading to a complete loss of ADAM17 protein. We characterized the patients’ PBMCs for cytokine secretion in response to LPS stimulation, as well as for antibody-dependent cellular cytotoxicity (ADCC) effector functions and IFNγ release following engagement of CD16.In this short review, we highlight these recent findings and discuss putative consequences for the clinical use of inhibitors for ADAM17.  
      PubDate: 2017-02-06
      DOI: 10.14800/ccm.1495
      Issue No: Vol. 4, No. 1 (2017)
       
  • Tumor Treating Field Therapy in non-MGMT-Methylated Newly Diagnosed
           Glioblastoma: Is there a Role for Temozolomide?

    • Authors: H. Ian Robins
      Abstract: A Research Highlight of a recently published paper: “The effects of tumor treating fields (and temozolomide in MGMT expressing and non-expressing patient-derived glioblastoma cells” (. J. Clin Neurosci In Press 2016, http://dx.doi.org/10.1016/j.jocn.2016.10.042) is presented. Introductory background on alternating tumor treating field (TTFields) therapy, an FDA approved therapy for newly diagnosed glioblastoma, is reviewed in the context of standard temozolomide (TMZ) chemotherapy. The highlighted paper evaluated the potential interactions of TMZ and TTFields in vitro, as this could not be readily accomplished clinically. The authors reported a clinical model using 2 different sets of patient-derived GBM stem-like cells (GSCs) including MGMT-expressing (TMZ resistant) GSC and non-MGMT-expressing (TMZ sensitive) GSC. The results demonstrated no interactions, and the inability of TTFields to overcome TMZ resistance. The significant clinical implications of these results, and the rationale for exploring other innovative treatment strategies in combination with TTFields are discussed. 
      PubDate: 2017-01-30
      DOI: 10.14800/ccm.1502
      Issue No: Vol. 4, No. 1 (2017)
       
  • EMERGING CYTOKINE NETWORKS IN OSTEOSARCOMA

    • Authors: Luís Carlos Lopes Júnior, Denise Sayuri Calheiros da Silveira, Anderson Vulczak, Jéssica Cristina dos Santos, Luciana Chain Veronez, Andressa Fisch, Milena Flória-Santos, Regina Aparecida Garcia Lima, Gabriela Pereira-da-Silva
      Abstract: Osteosarcoma is the most prevalent primary bone cancer. Although it has a global impact of approximately 1 to 3 cases/million a year, its etiopathophysiology is still unknown. Moreover, the immune response to its development is very individual as well as variable. Particular emphasis has been placed on the study of the immunoregulatory role of cytokines in osteosarcoma. In this scenario, newly identified cytokine networks have emerged. A deep understanding on the complex interplay of cytokines in osteosarcoma may have prognostic importance. In this review, we seek to highlight the classic roles of cytokines in osteosarcoma, to describe the role of new players in the emerging cytokine networks, and to discuss the therapeutic targets that encompass the complexity and implications of this network.Key words: Cytokines, Immunology, Osteosarcoma.
      PubDate: 2017-01-24
      DOI: 10.14800/ccm.1510
      Issue No: Vol. 4, No. 1 (2017)
       
  • Many are better than one - Next Generation Multi-Variate Biomarkers for
           Precision Oncology

    • Authors: Jinyan Du, Daniel C Kirouac, Birgit Schoeberl
      Abstract: Existing companion diagnostics have helped to match drug treatments to patients. However, they are largely restricted to single-molecule, single-time-point measurements, which cannot capture the full dynamic complexity of cancer biology.  The development of multivariate and even dynamic biomarkers for diagnostic assays could allow more patients to benefit from improved drug regimens.  Here we describe our work which provides a case study of multivariate biomarkers where we integrated experimental data generated using multivariate profiling technologies with a variety of computational modeling and simulations methods to identify such biomarkers and make clinical predictions on their therapeutic utility.  We believe this approach of integrating multivariate profiling technologies and computational models, and iterating between experimental discovery and model predictions, will be required to develop the next generation of multivariate diagnostics and realize the promise of precision medicine.
      PubDate: 2017-01-09
      DOI: 10.14800/ccm.1484
      Issue No: Vol. 3, No. 4 (2017)
       
  • Dendritic Cell Targeting Vaccine for HPV-Associated Cancer

    • Authors: Wenjie Yin, Dorothee Duluc, HyeMee Joo, SangKon Oh
      Abstract: Dendritic cells (DCs) are major antigen presenting cells that can efficiently prime and activate cellular immune responses. Delivering antigens to in vivo DCs has thus been considered as a promising strategy that could allow us to mount T cell-mediated therapeutic immunity against cancers in patients. Successful development of such types of cancer vaccines that can target in vivo DCs, however, requires a series of outstanding questions that need to be addressed. These include the proper selection of which DC surface receptors, specific DC subsets and DC activators that can further enhance the efficacy of vaccines by promoting effector T cell infiltration and retention in tumors and their actions against tumors. Supplementing these areas of research with additional strategies that can counteract tumor immune evasion mechanisms is also expected to enhance the efficacy of such therapeutic vaccines against cancers. After more than a decade of study, we have concluded that antigen targeting to DCs via CD40 to evoke cellular responses is more efficient than targeting antigens to the same types of DCs via eleven other DC surface receptors tested. In recent work, we have further demonstrated that a prototype vaccine (anti-CD40-HPV16.E6/7, a recombinant fusion protein of anti-human CD40 and HPV16.E6/7 protein) for HPV16-associated cancers can efficiently activate HPV16.E6/7-specific T cells, particularly CD8+ T cells, from the blood of HPV16+ head-and-neck cancer patients. Moreover, anti-CD40-HPV16.E6/7 plus poly(I:C) can mount potent therapeutic immunity against TC-1 tumor expressing HPV16.E6/7 protein in human CD40 transgenic mice. In this manuscript, we thus highlight our recent findings for the development of novel CD40 targeting immunotherapeutic vaccines for HPV16-associated malignancies. In addition, we further discuss several of key questions that still remain to be addressed for enhancing therapeutic immunity elicited by our prototype vaccine against HPV16-associated malignancies.
      PubDate: 2017-01-02
      DOI: 10.14800/ccm.1482
      Issue No: Vol. 3, No. 4 (2017)
       
  • Manuscript Preparation and Proofreading Guidelines

    • Authors: Editorial Office
      Abstract: More information can be found at Author Guidelines.
      DOI: 10.14800/ccm.1156
      Issue No: Vol. 3, No. 1
       
 
 
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