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Frontiers in Oncology

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https://www.readbyqxmd.com/read/28642839/the-mitochondrial-complex-i-ty-of-cancer
#1
REVIEW
Félix A Urra, Felipe Muñoz, Alenka Lovy, César Cárdenas
Recent evidence highlights that the cancer cell energy requirements vary greatly from normal cells and that cancer cells exhibit different metabolic phenotypes with variable participation of both glycolysis and oxidative phosphorylation. NADH-ubiquinone oxidoreductase (Complex I) is the largest complex of the mitochondrial electron transport chain and contributes about 40% of the proton motive force required for mitochondrial ATP synthesis. In addition, Complex I plays an essential role in biosynthesis and redox control during proliferation, resistance to cell death, and metastasis of cancer cells...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28634571/current-immunotherapeutic-strategies-to-enhance-oncolytic-virotherapy
#2
REVIEW
Daniel E Meyers, Amanda A Wang, Chandini M Thirukkumaran, Don G Morris
Oncolytic viruses (OV) represent a promising strategy to augment the spectrum of cancer therapeutics. For efficacy, they rely on two general mechanisms: tumor-specific infection/cell-killing, followed by subsequent activation of the host's adaptive immune response. Numerous OV genera have been utilized in clinical trials, ultimately culminating in the 2015 Food and Drug Administration approval of a genetically engineered herpes virus, Talminogene laherparepvec (T-VEC). It is generally accepted that OV as monotherapy have only modest clinical efficacy...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28626728/commentary-fasting-mimicking-diet-reduces-ho-1-to-promote-t-cell-mediated-tumor-cytotoxicity
#3
COMMENT
Giovanni Li Volti, Roberto Avola, Manlio Vinciguerra
No abstract text is available yet for this article.
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28626727/mast-cell-infiltration-in-human-brain-metastases-modulates-the-microenvironment-and-contributes-to-the-metastatic-potential
#4
Ananya Roy, Sylwia Libard, Holger Weishaupt, Ida Gustavsson, Lene Uhrbom, Göran Hesselager, Fredrik J Swartling, Fredrik Pontén, Irina Alafuzoff, Elena Tchougounova
Metastatic brain tumors continue to be a clinical problem, despite new therapeutic advances in cancer treatment. Brain metastases (BMs) are among the most common mass lesions in the brain that are resistant to chemotherapies, have a very poor prognosis, and currently lack any efficient diagnostic tests. Predictions estimate that about 40% of lung and breast cancer patients will develop BM. Despite this, very little is known about the immunological and genetic aberrations that drive tumorigenesis in BM. In this study, we demonstrate the infiltration of mast cells (MCs) in a large cohort of human BM samples with different tissues of origin for primary cancer...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28626726/cancer-stem-cells-in-oral-cavity-squamous-cell-carcinoma-a-review
#5
REVIEW
Ranui Baillie, Swee T Tan, Tinte Itinteang
Cancer stem cells (CSCs) have been identified in oral cavity squamous cell carcinoma (OCSCC). CSCs possess the ability for perpetual self-renewal and proliferation, producing downstream progenitor cells and cancer cells that drive tumor growth. Studies of many cancer types including OCSCC have identified CSCs using specific markers, but it is still unclear as to where in the stem cell hierarchy these markers fall. This is compounded further by the presence of multiple CSC subtypes within OCSCC, making investigation reliant on the use of multiple markers...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28620581/third-generation-tyrosine-kinase-inhibitors-targeting-epidermal-growth-factor-receptor-mutations-in-non-small-cell-lung-cancer
#6
REVIEW
Tristan A Barnes, Grainne M O'Kane, Mark David Vincent, Natasha B Leighl
Sensitizing mutations in the epidermal growth factor receptor (EGFR) predict response to EGFR tyrosine kinase inhibitors (TKIs) and both first- and second-generation TKIs are available as first-line treatment options in patients with advanced EGFR-mutant non-small cell lung cancer. Eventual resistance develops with multiple mechanisms identifiable both upon repeat biopsy and in plasma circulating tumor DNA. The T790M gatekeeper mutation is responsible for almost 60% of cases. A number of third-generation TKIs are in clinical development, and osimertinib has been approved by the US Food and Drug Administration for the treatment of patients with EGFR T790M mutant lung cancer after failure of initial EGFR kinase therapy...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28620580/the-human-nadph-oxidase-nox4-regulates-cytoskeletal-organization-in-two-cancer-cell-lines-hepg2-and-sh-sy5y
#7
Simon Auer, Mark Rinnerthaler, Johannes Bischof, Maria Karolin Streubel, Hannelore Breitenbach-Koller, Roland Geisberger, Elmar Aigner, Janne Cadamuro, Klaus Richter, Mentor Sopjani, Elisabeth Haschke-Becher, Thomas Klaus Felder, Michael Breitenbach
NADPH oxidases of human cells are not only functional in defense against invading microorganisms and for oxidative reactions needed for specialized biosynthetic pathways but also during the past few years have been established as signaling modules. It has been shown that human Nox4 is expressed in most somatic cell types and produces hydrogen peroxide, which signals to remodel the actin cytoskeleton. This correlates well with the function of Yno1, the only NADPH oxidase of yeast cells. Using two established tumor cell lines, which are derived from hepatic and neuroblastoma tumors, respectively, we are showing here that in both tumor models Nox4 is expressed in the ER (like the yeast NADPH oxidase), where according to published literature, it produces hydrogen peroxide...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28620579/delineation-of-the-prostate-bed-the-invisible-target-is-still-an-issue
#8
Igor Latorzeff, Paul Sargos, Geneviève Loos, Stéphane Supiot, Stéphane Guerif, Christian Carrie
For pathological high-risk prostate cancer, adjuvant irradiation has shown a survival benefit. Phase III studies have highlighted that half men would face biochemical relapse and would be candidate for radiotherapy at adjuvant or salvage times. Despite at least four published international contouring guidelines from different collaborative groups, discrepancies remain for volumes, delineation, and margins to be considered in order to optimize radiotherapy planning. This article from "Groupe d'Etude des Tumeurs UroGénitales (GETUG)" members will focus on controversies to help clinicians to create best volume delineation for adjuvant or salvage post prostatectomy radiotherapy...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28620578/surgical-management-of-advanced-and-metastatic-renal-cell-carcinoma-a-multidisciplinary-approach
#9
REVIEW
Brian M Shinder, Kevin Rhee, Douglas Farrell, Nicholas J Farber, Mark N Stein, Thomas L Jang, Eric A Singer
The past decade has seen a rapid proliferation in the number and types of systemic therapies available for renal cell carcinoma. However, surgery remains an integral component of the therapeutic armamentarium for advanced and metastatic kidney cancer. Cytoreductive surgery followed by adjuvant cytokine-based immunotherapy (predominantly high-dose interleukin 2) has largely given way to systemic-targeted therapies. Metastasectomy also has a role in carefully selected patients. Additionally, neoadjuvant systemic therapy may increase the feasibility of resecting the primary tumor, which may be beneficial for patients with locally advanced or metastatic disease...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28611940/involvement-of-chromatin-remodeling-genes-and-the-rho-gtpases-rhob-and-cdc42-in-ovarian-clear-cell-carcinoma
#10
Nicolai Skovbjerg Arildsen, Jenny-Maria Jönsson, Katarina Bartuma, Anna Ebbesson, Sofia Westbom-Fremer, Anna Måsbäck, Susanne Malander, Mef Nilbert, Ingrid A Hedenfalk
OBJECTIVE: Ovarian clear cell carcinomas (OCCCs) constitute a rare ovarian cancer subtype with distinct clinical features, but may nonetheless be difficult to distinguish morphologically from other subtypes. There is limited knowledge of genetic events driving OCCC tumorigenesis beyond ARID1A, which is reportedly mutated in 30-50% of OCCCs. We aimed to further characterize OCCCs by combined global transcriptional profiling and targeted deep sequencing of a panel of well-established cancer genes...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28611939/selective-targeting-of-the-l858r-mutation-egfr-in-non-small-cell-lung-cancer-a-mechanism-for-advancing-targeted-chemotherapy
#11
Rohan Arora, Venkat Krishnan
Lung cancer remains one of today's most deadly and intractable cancers. Non-small cell lung cancer (NSCLC) accounts for roughly 85% of lung cancers, with an extremely poor survival rate. To ensure patient comfort and survival, the development of a selective therapy is imperative. However, lung cancer does not display surface proteins associated uniquely with tumor cells; thus, it is very difficult to develop a tumor-specific drug. Current techniques that target overexpression of proteins or inhibit growth pathways are either non-specific or prone to rapid drug resistance...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28603694/estrogen-effects-on-the-mammary-gland-in-early-and-late-life-and-breast-cancer-risk
#12
REVIEW
Genevieve Victoria Dall, Kara Louise Britt
A woman has an increased risk of breast cancer if her lifelong estrogen exposure is increased due to an early menarche, a late menopause, and/or an absence of childbearing. For decades, it was presumed that the number of years of exposure drove the increased risk, however, recent epidemiological data have shown that early life exposure (young menarche) has a more significant effect on cancer risk than late menopause. Thus, rather than the overall exposure it seems that the timing of hormone exposure plays a major role in defining breast cancer risk...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28603693/cancer-untethering-mitochondria-from-the-endoplasmic-reticulum
#13
REVIEW
Maria Sol Herrera-Cruz, Thomas Simmen
Following the discovery of the mitochondria-associated membrane (MAM) as a hub for lipid metabolism in 1990 and its description as one of the first examples for membrane contact sites at the turn of the century, the past decade has seen the emergence of this structure as a potential regulator of cancer growth and metabolism. The mechanistic basis for this hypothesis is that the MAM accommodates flux of Ca(2+) from the endoplasmic reticulum (ER) to mitochondria. This flux then determines mitochondrial ATP production, known to be low in many tumors as part of the Warburg effect...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28596941/highly-specific-and-effective-targeting-of-egfrviii-positive-tumors-with-tandab-antibodies
#14
Kristina Ellwanger, Uwe Reusch, Ivica Fucek, Stefan Knackmuss, Michael Weichel, Thorsten Gantke, Vera Molkenthin, Eugene A Zhukovsky, Michael Tesar, Martin Treder
To harness the cytotoxic capacity of immune cells for the treatment of solid tumors, we developed tetravalent, bispecific tandem diabody (TandAb) antibodies that recognize EGFRvIII, the deletion variant III of the epidermal growth factor receptor (EGFR), and CD3 on T-cells, thereby directing immune cells to eliminate EGFRvIII-positive tumor cells. Using phage display, we identified scFv antibodies selectively binding to EGFRvIII. These highly EGFRvIII-specific, fully human scFv were substantially improved by affinity maturation, achieving KDs in the picomolar range, and were used to construct a set of bispecific EGFRvIII-targeting TandAbs with a broad range of binding and cytotoxic properties...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28596940/histone-deacetylase-inhibitor-treatment-increases-the-expression-of-the-plasma-membrane-ca-2-pump-pmca4b-and-inhibits-the-migration-of-melanoma-cells-independent-of-erk
#15
Luca Hegedüs, Rita Padányi, Judit Molnár, Katalin Pászty, Karolina Varga, István Kenessey, Eszter Sárközy, Matthias Wolf, Michael Grusch, Zoltán Hegyi, László Homolya, Clemens Aigner, Tamás Garay, Balázs Hegedüs, József Tímár, Enikö Kállay, Ágnes Enyedi
Several new therapeutic options emerged recently to treat metastatic melanoma; however, the high frequency of intrinsic and acquired resistance among patients shows a need for new therapeutic options. Previously, we identified the plasma membrane Ca(2+) ATPase 4b (PMCA4b) as a metastasis suppressor in BRAF-mutant melanomas and found that mutant BRAF inhibition increased the expression of the pump, which then inhibited the migratory and metastatic capability of the cells. Earlier it was also demonstrated that histone deacetylase inhibitors (HDACis) upregulated PMCA4b expression in gastric, colon, and breast cancer cells...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28596939/undifferentiated-pleomorphic-sarcoma-and-the-importance-of-considering-the-oncogenic-and-immune-suppressant-role-of-the-human-t-cell-lymphotropic-virus-type-1-a-case-report
#16
Sergio Lupo, Carolina Berini, Camila Cánepa, Eduardo Santini Araujo, Mirna Biglione
INTRODUCTION: Soft-tissue sarcomas account for 0.7% of all malignant tumors, with an incidence rate of 3 per 100,000 persons/year. The undifferentiated pleomorphic sarcoma (UPS) with giant cells, a high grade tumor of soft tissue, is very unusual, especially in young adults before the age of 40. Human T-cell lymphotropic virus type 1 (HTLV-1) is a human retrovirus, classified as group 1 human carcinogens by The International Agency for Research on Cancer, that causes an aggressive malignancy known as adult T-cell lymphoma/leukemia and a progressive chronic inflammatory neurological disease named HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP)...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28589085/immune-system-friend-or-foe-of-oncolytic-virotherapy
#17
REVIEW
Anna C Filley, Mahua Dey
Oncolytic viruses (OVs) are an emerging class of targeted anticancer therapies designed to selectively infect, replicate in, and lyse malignant cells without causing harm to normal, healthy tissues. In addition to direct oncolytic activity, OVs have shown dual promise as immunotherapeutic agents. The presence of viral infection and subsequently generated immunogenic tumor cell death trigger innate and adaptive immune responses that mediate further tumor destruction. However, antiviral immune responses can intrinsically limit OV infection, spread, and overall therapeutic efficacy...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28589084/calreticulin-in-essential-thrombocythemia-stressing-out-the-megakaryocyte-nucleus
#18
Francisco Jose Iborra, Petros Papadopoulos
Calreticulin (CALR) is a multifaceted protein primarily involved in intracellular protein control processes. The identification of CALR mutations in essential thrombocythemia (ET) and primary myelofibrosis that are mutually exclusive with the JAK2 V617F mutation has stirred an intensive research interest about the molecular functions of CALR and its mutants in myeloproliferative neoplasms (MPNs) and its diagnostic/prognostic value. The recently characterized protein-protein interaction of CALR mutants and MPL receptor has advanced our knowledge on the functional role of CALR mutants in thrombocythemia but it has also uncovered limitations of the current established research models...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28589083/the-concerted-action-of-mitochondrial-dynamics-and-positioning-new-characters-in-cancer-onset-and-progression
#19
REVIEW
Diana Pendin, Riccardo Filadi, Paola Pizzo
Mitochondria are dynamic organelles whose morphology and activity are extremely variable, depending on the metabolic state of the cell. In particular, their shape and movements within the cell are finely regulated by an increasing number of proteins, which take part in the process of mitochondrial fission/fusion and connect the organelles to the cytoskeleton. As to their activities, mitochondria are considered to be at the crossroad between cell life and death since, on the one hand, they are essential in ATP production and in multiple metabolic pathways but, on the other, they are involved in the intrinsic apoptotic cascade, triggered by different stress conditions...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28589082/genetically-engineered-vaccinia-viruses-as-agents-for-cancer-treatment-imaging-and-transgene-delivery
#20
REVIEW
Dana Haddad
Despite advances in technology, the formidable challenge of treating cancer, especially if advanced, still remains with no significant improvement in survival rates, even with the most common forms of cancer. Oncolytic viral therapies have shown great promise for the treatment of various cancers, with the possible advantages of stronger treatment efficacy compared to conventional therapy due to higher tumor selectivity, and less toxicity. They are able to preferentially and selectively propagate in cancer cells, consequently destroying tumor tissue mainly via cell lysis, while leaving non-cancerous tissues unharmed...
2017: Frontiers in Oncology
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