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Cancers, Volume 2, Issue 2 (June 2010) – 58 articles , Pages 209-1378

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579 KiB  
Review
The Nrf1 and Nrf2 Balance in Oxidative Stress Regulation and Androgen Signaling in Prostate Cancer Cells
by Michelle A. Schultz, Asim B. Abdel-Mageed and Debasis Mondal
Cancers 2010, 2(2), 1354-1378; https://doi.org/10.3390/cancers2021354 - 21 Jun 2010
Cited by 27 | Viewed by 15619
Abstract
Reactive oxygen species (ROS) signaling has recently sparked a surge of interest as being the molecular underpinning for cancer cell survival, but the precise mechanisms involved have not been completely elucidated. This review covers the possible roles of two ROS-induced transcription factors, Nrf1 [...] Read more.
Reactive oxygen species (ROS) signaling has recently sparked a surge of interest as being the molecular underpinning for cancer cell survival, but the precise mechanisms involved have not been completely elucidated. This review covers the possible roles of two ROS-induced transcription factors, Nrf1 and Nrf2, and the antioxidant proteins peroxiredoxin-1 (Prx-1) and Thioredoxin-1 (Txn-1) in modulating AR expression and signaling in aggressive prostate cancer (PCa) cells. In androgen independent (AI) C4-2B cells, in comparison to the parental androgen dependent (AD) LNCaP cells, we present evidence of high Nrf1 and Prx-1 expression and low Nrf2 expression in these aggressive PCa cells. Furthermore, in DHT treated C4-2B cells, increased expression of the p65 (active) isoform of Nrf1 correlated with enhanced AR transactivation. Our findings implicate a crucial balance of Nrf1 and Nrf2 signaling in regulating AR activity in AI-PCa cells. Here we will discuss how understanding the mechanisms by which oxidative stress may affect AR signaling may aid in developing novel therapies for AI-PCa. Full article
(This article belongs to the Special Issue Oxidative Stress and Cancer)
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269 KiB  
Review
Alterations of MicroRNAs in Solid Cancers and Their Prognostic Value
by Panagiota Chira, Katerina Vareli, Ioannis Sainis, Christos Papandreou and Evangelos Briasoulis
Cancers 2010, 2(2), 1328-1353; https://doi.org/10.3390/cancers2021328 - 14 Jun 2010
Cited by 17 | Viewed by 10951
Abstract
MicroRNAs (miRNAs) are evolutionarily conserved, naturally abundant, small, regulatory non-coding RNAs that inhibit gene expression at the post-transcriptional level in a sequence-specific manner. Each miRNA represses the protein expression of several coding genes in a manner proportional to the sequence complementarity with the [...] Read more.
MicroRNAs (miRNAs) are evolutionarily conserved, naturally abundant, small, regulatory non-coding RNAs that inhibit gene expression at the post-transcriptional level in a sequence-specific manner. Each miRNA represses the protein expression of several coding genes in a manner proportional to the sequence complementarity with the target transcripts. MicroRNAs play key regulatory roles in organismal development and homeostasis. They control fundamental biological processes, such as stem-cell regulation and cellular metabolism, proliferation, differentiation, stress resistance, and apoptosis. Differential miRNA expression is found in malignant tumors in comparison to normal tissue counterparts. This indicates that miRNA deregulation contributes to the initiation and progression of cancer. Currently, miRNA expression signatures are being rigorously investigated in various tumor types, with the aim of developing novel, efficient biomarkers that can improve clinical management of cancer patients. This review discusses deregulated miRNAs in solid tumors, and focuses on their emerging prognostic potential. Full article
(This article belongs to the Special Issue Biomarkers: Oncology Studies)
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353 KiB  
Review
Serum Biomarkers for Early Detection of Gynecologic Cancers
by Yutaka Ueda, Takayuki Enomoto, Toshihiro Kimura, Takashi Miyatake, Kiyoshi Yoshino, Masami Fujita and Tadashi Kimura
Cancers 2010, 2(2), 1312-1327; https://doi.org/10.3390/cancers2021312 - 14 Jun 2010
Cited by 258 | Viewed by 9607
Abstract
Ovarian, endometrial, and cervical cancers are three of the most common malignancies of the female reproductive organs. CA 125, historically the most reliable serum marker for ovarian cancer, is elevated in 50% of early-stage ovarian tumors. For endometrial cancers, there are no established [...] Read more.
Ovarian, endometrial, and cervical cancers are three of the most common malignancies of the female reproductive organs. CA 125, historically the most reliable serum marker for ovarian cancer, is elevated in 50% of early-stage ovarian tumors. For endometrial cancers, there are no established serum markers. SCC, which is the best studied serum marker for squamous cell carcinomas, has been unreliable; SCC is elevated in cervical squamous cell carcinomas ranging from 28–85% of the time. Recent proteomics-based analyses show great promise for the discovery of new and more useful biomarkers. In this review, we will discuss the currently utilized serum tumor markers for gynecologic cancers and the novel biomarkers that are now under investigation. Full article
402 KiB  
Review
Interfering with ROS Metabolism in Cancer Cells: The Potential Role of Quercetin
by Lara Gibellini, Marcello Pinti, Milena Nasi, Sara De Biasi, Erika Roat, Linda Bertoncelli and Andrea Cossarizza
Cancers 2010, 2(2), 1288-1311; https://doi.org/10.3390/cancers2021288 - 14 Jun 2010
Cited by 258 | Viewed by 22511
Abstract
A main feature of cancer cells, when compared to normal ones, is a persistent pro-oxidative state that leads to an intrinsic oxidative stress. Cancer cells have higher levels of reactive oxygen species (ROS) than normal cells, and ROS are, in turn, responsible for [...] Read more.
A main feature of cancer cells, when compared to normal ones, is a persistent pro-oxidative state that leads to an intrinsic oxidative stress. Cancer cells have higher levels of reactive oxygen species (ROS) than normal cells, and ROS are, in turn, responsible for the maintenance of the cancer phenotype. Persistent ROS stress may induce adaptive stress responses, enabling cancer cells to survive with high levels of ROS and maintain cellular viability. However, excessive ROS levels render cancer cells highly susceptible to quercetin, one of the main dietary flavonoids. Quercetin depletes intracellular glutathione and increases intracellular ROS to a level that can cause cell death. Full article
(This article belongs to the Special Issue Oxidative Stress and Cancer)
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5241 KiB  
Review
Exogenous Molecular Probes for Targeted Imaging in Cancer: Focus on Multi-modal Imaging
by Bishnu P. Joshi and Thomas D. Wang
Cancers 2010, 2(2), 1251-1287; https://doi.org/10.3390/cancers2021251 - 11 Jun 2010
Cited by 72 | Viewed by 17481
Abstract
Cancer is one of the major causes of mortality and morbidity in our healthcare system. Molecular imaging is an emerging methodology for the early detection of cancer, guidance of therapy, and monitoring of response. The development of new instruments and exogenous molecular probes [...] Read more.
Cancer is one of the major causes of mortality and morbidity in our healthcare system. Molecular imaging is an emerging methodology for the early detection of cancer, guidance of therapy, and monitoring of response. The development of new instruments and exogenous molecular probes that can be labeled for multi-modality imaging is critical to this process. Today, molecular imaging is at a crossroad, and new targeted imaging agents are expected to broadly expand our ability to detect and manage cancer. This integrated imaging strategy will permit clinicians to not only localize lesions within the body but also to manage their therapy by visualizing the expression and activity of specific molecules. This information is expected to have a major impact on drug development and understanding of basic cancer biology. At this time, a number of molecular probes have been developed by conjugating various labels to affinity ligands for targeting in different imaging modalities. This review will describe the current status of exogenous molecular probes for optical, scintigraphic, MRI and ultrasound imaging platforms. Furthermore, we will also shed light on how these techniques can be used synergistically in multi-modal platforms and how these techniques are being employed in current research. Full article
(This article belongs to the Special Issue Biomarkers: Oncology Studies)
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239 KiB  
Review
Circulating Tumor Cells, Enumeration and Beyond
by Jian-Mei Hou, Matthew Krebs, Tim Ward, Karen Morris, Robert Sloane, Fiona Blackhall and Caroline Dive
Cancers 2010, 2(2), 1236-1250; https://doi.org/10.3390/cancers2021236 - 09 Jun 2010
Cited by 207 | Viewed by 12505
Abstract
The detection and enumeration of circulating tumor cells (CTCs) has shown significant clinical utility with respect to prognosis in breast, colorectal and prostate cancers. Emerging studies show that CTCs can provide pharmacodynamic information to aid therapy decision making. CTCs as a ‘virtual and [...] Read more.
The detection and enumeration of circulating tumor cells (CTCs) has shown significant clinical utility with respect to prognosis in breast, colorectal and prostate cancers. Emerging studies show that CTCs can provide pharmacodynamic information to aid therapy decision making. CTCs as a ‘virtual and real-time biopsy’ have clear potential to facilitate exploration of tumor biology, and in particular, the process of metastasis. The challenge of profiling CTC molecular characteristics and generating CTC signatures using current technologies is that they enrich rather than purify CTCs from whole blood; we face the problem of looking for the proverbial ‘needle in the haystack’. This review summarizes the current methods for CTC detection and enumeration, focuses on molecular characterization of CTCs, unveils some aspects of CTC heterogeneity, describes attempts to purify CTCs and scans the horizon for approaches leading to comprehensive dissection of CTC biology. Full article
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193 KiB  
Review
Significance of Micrometastases: Circulating Tumor Cells and Disseminated Tumor Cells in Early Breast Cancer
by Catherine Oakman, Marta Pestrin, Silvia Bessi, Francesca Galardi and Angelo Di Leo
Cancers 2010, 2(2), 1221-1235; https://doi.org/10.3390/cancers2021221 - 08 Jun 2010
Cited by 16 | Viewed by 11454
Abstract
Adjuvant systemic therapy targets minimal residual disease. Our current clinical approach in the adjuvant setting is to presume, rather than confirm, the presence of minimal residual disease. Based on assessment of the primary tumor, we estimate an individual’s recurrence risk. Subsequent treatment decisions [...] Read more.
Adjuvant systemic therapy targets minimal residual disease. Our current clinical approach in the adjuvant setting is to presume, rather than confirm, the presence of minimal residual disease. Based on assessment of the primary tumor, we estimate an individual’s recurrence risk. Subsequent treatment decisions are based on characteristics of the primary tumor, with the presumption of consistent biology and treatment sensitivity between micrometastases and the primary lesion. An alternative approach is to identify micrometastatic disease. Detection of disseminated tumor cells (DTC) in the bone marrow and circulating tumor cells (CTC) from peripheral blood collection may offer quantification and biocharacterization of residual disease. This paper will review the prognostic and predictive potential of micrometastatic disease in early breast cancer. Full article
(This article belongs to the Special Issue Biomarkers: Oncology Studies)
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289 KiB  
Review
Inflammatory Genetic Markers of Prostate Cancer Risk
by Elizabeth A. Tindall, Vanessa M. Hayes and Desiree C. Petersen
Cancers 2010, 2(2), 1198-1220; https://doi.org/10.3390/cancers2021198 - 08 Jun 2010
Cited by 36 | Viewed by 13020
Abstract
Prostate cancer is the most common cancer in Western society males, with incidence rates predicted to rise with global aging. Etiology of prostate cancer is however poorly understood, while current diagnostic tools can be invasive (digital rectal exam or biopsy) and/or lack specificity [...] Read more.
Prostate cancer is the most common cancer in Western society males, with incidence rates predicted to rise with global aging. Etiology of prostate cancer is however poorly understood, while current diagnostic tools can be invasive (digital rectal exam or biopsy) and/or lack specificity for the disease (prostate-specific antigen (PSA) testing). Substantial histological, epidemiological and molecular genetic evidence indicates that inflammation is important in prostate cancer pathogenesis. In this review, we summarize the current status of inflammatory genetic markers influencing susceptibility to prostate cancer. The focus will be on inflammatory cytokines regulating T-helper cell and chemokine homeostasis, together with the Toll-like receptors as key players in the host innate immune system. Although association studies indicating a genetic basis for prostate cancer are presently limited mainly due to lack of replication, larger and more ethnically and clinically defined study populations may help elucidate the true contribution of inflammatory gene variants to prostate cancer risk. Full article
(This article belongs to the Special Issue Biomarkers: Oncology Studies)
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159 KiB  
Review
Outpatient Follow-up and Secondary Prevention for Melanoma Patients
by Ryan G. Gamble, Daniel Jensen, Andrea L. Suarez, Anne H. Hanson, Lauren McLaughlin, Jodi Duke and Robert P. Dellavalle
Cancers 2010, 2(2), 1178-1197; https://doi.org/10.3390/cancers2021178 - 07 Jun 2010
Cited by 2 | Viewed by 9831
Abstract
Health care providers and their patients jointly participate in melanoma prevention, surveillance, diagnosis, and treatment. This paper reviews screening and follow-up strategies for patients who have been diagnosed with melanoma, based on current available evidence, and focuses on methods to assess disease recurrence [...] Read more.
Health care providers and their patients jointly participate in melanoma prevention, surveillance, diagnosis, and treatment. This paper reviews screening and follow-up strategies for patients who have been diagnosed with melanoma, based on current available evidence, and focuses on methods to assess disease recurrence and second primary occurrence. Secondary prevention, including the roles of behavioral modification and chemoprevention are also reviewed. The role of follow-up dermatologist consultation, with focused physical examinations complemented by dermatoscopy, reflectance confocal microscopy, and/or full-body mapping is discussed. Furthermore, we address the inclusion of routine imaging and laboratory assessment as components of follow-up and monitoring of advanced stage melanoma. The role of physicians in addressing the psychosocial stresses associated with a diagnosis of melanoma is reviewed. Full article
(This article belongs to the Special Issue Current Concepts in the Diagnosis and Treatment of Cutaneous Melanoma)
767 KiB  
Article
Different Serotonergic Expression in Nevomelanocytic Tumors
by Clara Naimi-Akbar, Markus Ritter, Sasika Demel, Husameldin El-Nour, Mari-Anne Hedblad, Efrain C. Azmitia and Klas Nordlind
Cancers 2010, 2(2), 1166-1177; https://doi.org/10.3390/cancers2021166 - 07 Jun 2010
Cited by 37 | Viewed by 9722
Abstract
The neuromediator serotonin (5-hydroxytryptamine; 5-HT) has been proposed to play a role in tumor progression. Thus, the aim of the present investigation was to determine whether alterations in the serotonergic system occur in nevomelanocytic tumors. For this purpose, paraffin-embedded biopsies of superficial spreading [...] Read more.
The neuromediator serotonin (5-hydroxytryptamine; 5-HT) has been proposed to play a role in tumor progression. Thus, the aim of the present investigation was to determine whether alterations in the serotonergic system occur in nevomelanocytic tumors. For this purpose, paraffin-embedded biopsies of superficial spreading malignant melanoma (SSM), dysplastic compound nevi (DN) and benign compound nevi (BCN) were characterized with regard to their expression of 5-HT, the 5-HT1A and 5-HT2A receptors, and the serotonin transporter protein (SERT), by immunohistochemical analysis. Melanocytes in the region surrounding the tumor were found to express both the 5-HT1A and 5-HT2A receptors. Tumor cells that immunostained positively for the different serotonergic markers were observed in the suprabasal epidermis of DN tissue and, to an even greater extent, in the case of SSM. Furthermore, some of these latter cells expressed both 5-HT1AR and 5-HT2AR. The level of expression of 5-HT1AR at the junctional area was lower for SSM than for DN or BCN. As the degree of atypia increased, the intensity of tumor cell staining in the dermis for 5-HT1AR and SERT declined. Vessel immunoreactivity for 5-HT2A was more intense in SSM than in BCN tissue. Round-to-dendritic cells that expressed both SERT and 5-HT1AR were seen to infiltrate into the dermal region of the tumor, this infiltration being more evident in the case of DN and SSM. These latter cells were also tryptase-positive, indicating that they are mast cells. Thus, alterations in serotonergic system may be involved in nevomelanocytic tumors and mast cells may play an important role in this connection. Full article
(This article belongs to the Special Issue Current Concepts in the Diagnosis and Treatment of Cutaneous Melanoma)
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619 KiB  
Review
The Connection between the Presence of Melanoma and Changes in Fibre Diffraction Patterns
by Veronica J. James and Nigel Kirby
Cancers 2010, 2(2), 1155-1165; https://doi.org/10.3390/cancers2021155 - 04 Jun 2010
Cited by 16 | Viewed by 9063
Abstract
An accurate diagnosis of melanomas at an early stage correlates directly with a better prognosis. However the incidence of melanoma is still increasing along with the number of related deaths. Melanoma cells grow extremely fast, with the result that many patients present after [...] Read more.
An accurate diagnosis of melanomas at an early stage correlates directly with a better prognosis. However the incidence of melanoma is still increasing along with the number of related deaths. Melanoma cells grow extremely fast, with the result that many patients present after metastasis has occurred, too late for effective treatment. This paper describes the changes in the fibre diffraction patterns of skin that indicate the presence of a melanoma. Identification of these changes would provide an alternative early low-cost, reliable diagnostic test which could be conducted on a regular basis in local radiology facilities using rotating anode X-ray generators or as a mass screening test using suitable small angle x-ray beam-lines at synchrotrons. Full article
(This article belongs to the Special Issue Current Concepts in the Diagnosis and Treatment of Cutaneous Melanoma)
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958 KiB  
Review
Markers for Detection of Prostate Cancer
by Raymond A. Clarke, Horst J. Schirra, James W. Catto, Martin F. Lavin and Robert A. Gardiner
Cancers 2010, 2(2), 1125-1154; https://doi.org/10.3390/cancers2021125 - 04 Jun 2010
Cited by 38 | Viewed by 12262
Abstract
Early detection of prostate cancer is problematic, not just because of uncertainly whether a diagnosis will benefit an individual patient, but also as a result of the imprecise and invasive nature of establishing a diagnosis by biopsy. Despite its low sensitivity and specificity [...] Read more.
Early detection of prostate cancer is problematic, not just because of uncertainly whether a diagnosis will benefit an individual patient, but also as a result of the imprecise and invasive nature of establishing a diagnosis by biopsy. Despite its low sensitivity and specificity for identifying patients harbouring prostate cancer, serum prostate specific antigen (PSA) has become established as the most reliable and widely-used diagnostic marker for this condition. In its wake, many other markers have been described and evaluated. This review focuses on the supporting evidence for the most prominent of these for detection and also for predicting outcome in prostate cancer. Full article
(This article belongs to the Special Issue Biomarkers: Oncology Studies)
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257 KiB  
Review
Serum Tumor Markers in Pancreatic Cancer—Recent Discoveries
by Felix Rückert, Christian Pilarsky and Robert Grützmann
Cancers 2010, 2(2), 1107-1124; https://doi.org/10.3390/cancers2021107 - 02 Jun 2010
Cited by 44 | Viewed by 13731
Abstract
The low prevalence of pancreatic cancer remains an obstacle to the development of effective screening tools in an asymptomatic population. However, development of effective serologic markers still offers the potential for improvement of diagnostic capabilities, especially for subpopulations of patients with high risk [...] Read more.
The low prevalence of pancreatic cancer remains an obstacle to the development of effective screening tools in an asymptomatic population. However, development of effective serologic markers still offers the potential for improvement of diagnostic capabilities, especially for subpopulations of patients with high risk for pancreatic cancer. The accurate identification of patients with pancreatic cancer and the exclusion of disease in those with benign disorders remain important goals. While clinical experience largely dismissed many candidate markers as useful markers of pancreatic cancer, CA19-9 continues to show promise. The present review highlights the development and the properties of different tumor markers in pancreatic cancer and their impact on the diagnostic and treatment of this aggressive disease. Full article
(This article belongs to the Special Issue Pancreatic Cancer)
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890 KiB  
Article
Studies on the Non-Protein Thiols of a Human Prostatic Cancer Cell Line: Glutathione Content
by Michael Gronow
Cancers 2010, 2(2), 1092-1106; https://doi.org/10.3390/cancers2021092 - 02 Jun 2010
Cited by 6 | Viewed by 8565
Abstract
The low molecular weight thiol (-SH) content of a human prostate carcinoma cell line (LNCap), important to the cellular resistance to drugs and irradiation, was investigated using three forms of thiol assay each utilizing different chemistries. The composition of the mixture was examined [...] Read more.
The low molecular weight thiol (-SH) content of a human prostate carcinoma cell line (LNCap), important to the cellular resistance to drugs and irradiation, was investigated using three forms of thiol assay each utilizing different chemistries. The composition of the mixture was examined by derivatization of the thiols with a three-fold excess of the Ellman reagent to give mixed aromatic disulfides. The components were isolated by chromatography on C18 reverse phase silica gel followed by DE52 anion exchange separation, and then analyzed by capillary electrophoresis against prepared standards. The glutathione adduct (GSSE) and an unknown disulfide (RSSE) were the major components isolated on DE52 together with two minor ones. However, from the absorbance at 325 nm, it was found that the GSSE isolated (1.5 ± 0.2 femtomoles/cell) could only account for 28.5 ± 4.3% of the total ASF thiols. It appeared that the bulk of the thiol material had not formed a stable mixed disulfide with Ellman’s reagent, and this was confirmed by 35S labeling of the cells. A large proportion of the 35S labeled components, obtained after reaction of the ASF thiols with the Ellman reagent, did not form mixed aromatic disulfides and could therefore not be identified by this labeling method. Full article
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252 KiB  
Review
Reinventing Diagnostics for Personalized Therapy in Oncology
by Diponkar Banerjee
Cancers 2010, 2(2), 1066-1091; https://doi.org/10.3390/cancers2021066 - 02 Jun 2010
Cited by 4 | Viewed by 11201
Abstract
Human cancers are still diagnosed and classified using the light microscope. The criteria are based upon morphologic observations by pathologists and tend to be subject to interobserver variation. In preoperative biopsies of non-small cell lung cancers, the diagnostic concordance, even amongst experienced pulmonary [...] Read more.
Human cancers are still diagnosed and classified using the light microscope. The criteria are based upon morphologic observations by pathologists and tend to be subject to interobserver variation. In preoperative biopsies of non-small cell lung cancers, the diagnostic concordance, even amongst experienced pulmonary pathologists, is no better than a coin-toss. Only 25% of cancer patients, on average, benefit from therapy as most therapies do not account for individual factors that influence response or outcome. Unsuccessful first line therapy costs Canada CAN$1.2 billion for the top 14 cancer types, and this extrapolates to $90 billion globally. The availability of accurate drug selection for personalized therapy could better allocate these precious resources to the right therapies. This wasteful situation is beginning to change with the completion of the human genome sequencing project and with the increasing availability of targeted therapies. Both factors are giving rise to attempts to correlate tumor characteristics and response to specific adjuvant and neoadjuvant therapies. Static cancer classification and grading systems need to be replaced by functional classification systems that not only account for intra- and inter- tumor heterogeneity, but which also allow for the selection of the correct chemotherapeutic compounds for the individual patient. In this review, the examples of lung and breast cancer are used to illustrate the issues to be addressed in the coming years, as well as the emerging technologies that have great promise in enabling personalized therapy. Full article
(This article belongs to the Special Issue Biomarkers: Oncology Studies)
484 KiB  
Review
Biomarkers for Basal-like Breast Cancer
by Jennifer R. Choo and Torsten O. Nielsen
Cancers 2010, 2(2), 1040-1065; https://doi.org/10.3390/cancers2021040 - 28 May 2010
Cited by 39 | Viewed by 11107
Abstract
Initially recognized through microarray-based gene expression profiling, basal-like breast cancer, for which we lack effective targeted therapies, is an aggressive form of carcinoma with a predilection for younger women. With some success, immunohistochemical studies have attempted to reproduce the expression profile classification of [...] Read more.
Initially recognized through microarray-based gene expression profiling, basal-like breast cancer, for which we lack effective targeted therapies, is an aggressive form of carcinoma with a predilection for younger women. With some success, immunohistochemical studies have attempted to reproduce the expression profile classification of breast cancer through identification of subtype-specific biomarkers. This review aims to present an in depth summary and analysis of the current status of basal-like breast cancer biomarker research. While a number of biomarkers show promise for future clinical application, the next logical step is a comprehensive investigation of all biomarkers against a gene expression profile gold standard for breast cancer subtype assignment. Full article
(This article belongs to the Special Issue Biomarkers: Oncology Studies)
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343 KiB  
Review
Blood-Based Biomarkers for the Optimization of Anti-Angiogenic Therapies
by Cristina Rabascio and Francesco Bertolini
Cancers 2010, 2(2), 1027-1039; https://doi.org/10.3390/cancers2021027 - 28 May 2010
Cited by 63 | Viewed by 8646
Abstract
The dependence of tumor growth and metastasis on blood vessels makes tumor angiogenesis a rational target for therapy. Strategies have been pursued to inhibit neovascularization and to destroy existing tumor vessels, or both. These include direct targeting of endothelial cells, and indirect targeting [...] Read more.
The dependence of tumor growth and metastasis on blood vessels makes tumor angiogenesis a rational target for therapy. Strategies have been pursued to inhibit neovascularization and to destroy existing tumor vessels, or both. These include direct targeting of endothelial cells, and indirect targeting by inhibiting the release of proangiogenic growth factors by cancer or stromal cells. Many patients benefit from antiangiogenic therapies; thus, development of noninvasive biomarkers of disease response and relapse is a crucial objective to aid in their management. A number of non-invasive tools are described with their potential benefits and limitations. We review currently available candidate biomarkers of anti-angiogenic agent effect. Including these markers into clinical trials may provide insight into appropriate dosing for desired biological effects, appropriate timing of additional therapy, and prediction of individual response. This has important consequences for the clinical use of angiogenesis inhibitors and for drug discovery, not only for optimizing the treatment of cancer, but possibly also for developing therapeutic approaches for various other diseases. Full article
(This article belongs to the Special Issue Biomarkers: Oncology Studies)
216 KiB  
Review
Molecular Mechanisms Involved in the Antitumor Activity of Cannabinoids on Gliomas: Role for Oxidative Stress
by Paola Massi, Marta Valenti, Marta Solinas and Daniela Parolaro
Cancers 2010, 2(2), 1013-1026; https://doi.org/10.3390/cancers2021013 - 26 May 2010
Cited by 83 | Viewed by 12242
Abstract
Cannabinoids, the active components of Cannabis sativa, have been shown to exert antiproliferative and proapoptotic effects on a wide spectrum of tumor cells and tissues. Of interest, cannabinoids have displayed great potency in reducing the growth of glioma tumors, one of the [...] Read more.
Cannabinoids, the active components of Cannabis sativa, have been shown to exert antiproliferative and proapoptotic effects on a wide spectrum of tumor cells and tissues. Of interest, cannabinoids have displayed great potency in reducing the growth of glioma tumors, one of the most aggressive CNS tumors, either in vitro or in animal experimental models curbing the growth of xenografts generated by subcutaneous or intrathecal injection of glioma cells in immune-deficient mice. Cannabinoids appear to be selective antitumoral agents as they kill glioma cells without affecting the viability of non-transformed cells. This review will summarize the anti-cancer properties that cannabinoids exert on gliomas and discuss their potential action mechanisms that appear complex, involving modulation of multiple key cell signaling pathways and induction of oxidative stress in glioma cells. Full article
(This article belongs to the Special Issue Oxidative Stress and Cancer)
285 KiB  
Review
Wnt and Related Signaling Pathways in Melanomagenesis
by Jesse J. Keller, Randall T. Moon and Andy J. Chien
Cancers 2010, 2(2), 1000-1012; https://doi.org/10.3390/cancers2021000 - 26 May 2010
Cited by 8 | Viewed by 8121
Abstract
Given the pivotal roles of morphogen pathways including Wnt, Notch, Hedgehog, and BMP pathways in the development of the neural crest lineage, it is not surprising that these signaling networks have also been implicated in the biology of malignant melanoma. Understanding the mechanisms [...] Read more.
Given the pivotal roles of morphogen pathways including Wnt, Notch, Hedgehog, and BMP pathways in the development of the neural crest lineage, it is not surprising that these signaling networks have also been implicated in the biology of malignant melanoma. Understanding the mechanisms by which these pathways can alter cell fate and other biological properties in tumor cells will be essential for determining whether the therapeutic targeting of these pathways has a potential role in melanoma treatment. This review highlights some of the recent findings with regards to how morphogen signaling may regulate melanoma cell biology. Full article
(This article belongs to the Special Issue Current Concepts in the Diagnosis and Treatment of Cutaneous Melanoma)
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Review
Prognostic Significance of Melanoma Differentiation and Trans-Differentiation
by Nityanand Maddodi and Vijayasaradhi Setaluri
Cancers 2010, 2(2), 989-999; https://doi.org/10.3390/cancers2020989 - 26 May 2010
Cited by 9 | Viewed by 8040
Abstract
Cutaneous malignant melanomas share a number of molecular attributes such as limitless replicative potential that define capabilities acquired by most malignancies. Accordingly, much effort has been focused on evaluating and validating protein markers related to these capabilities to function as melanoma prognostic markers. [...] Read more.
Cutaneous malignant melanomas share a number of molecular attributes such as limitless replicative potential that define capabilities acquired by most malignancies. Accordingly, much effort has been focused on evaluating and validating protein markers related to these capabilities to function as melanoma prognostic markers. However, a few studies have also highlighted the prognostic value of markers that define melanocytic differentiation and the plasticity of melanoma cells to trans-differentiate along several other cellular pathways. Here, we provide a comprehensive review and evaluation of the prognostic significance of melanocyte-lineage markers such as MITF and melanogenic proteins, as well as markers of vascular epithelial and neuronal differentiation. Full article
(This article belongs to the Special Issue Current Concepts in the Diagnosis and Treatment of Cutaneous Melanoma)
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Review
VEGF and Pleiotrophin Modulate the Immune Profile of Breast Cancer
by Kristi D. Lynn, Christina L. Roland and Rolf A. Brekken
Cancers 2010, 2(2), 970-988; https://doi.org/10.3390/cancers2020970 - 26 May 2010
Cited by 20 | Viewed by 9616
Abstract
Angiogenesis, the sprouting of the existing vascular network to form new vessels, is required for the growth of solid tumors. For this reason, the primary stimulant of angiogenesis, vascular endothelial growth factor-A (VEGF), is an attractive target for tumor therapy. In fact, there [...] Read more.
Angiogenesis, the sprouting of the existing vascular network to form new vessels, is required for the growth of solid tumors. For this reason, the primary stimulant of angiogenesis, vascular endothelial growth factor-A (VEGF), is an attractive target for tumor therapy. In fact, there are currently numerous anti-VEGF therapies in clinical development for the treatment of various cancers, including breast cancer. VEGF signals through two primary VEGF receptors, VEGFR1 and VEGFR2. VEGFR2 is the primary angiogenic receptor, and VEGFR1 has been implicated in macrophage chemotaxis and tumor cell survival and invasion. It has only been appreciated recently that the VEGFRs are expressed not only on endothelial cells and tumor cells but also on many host immune cells. Therefore, to better understand the effects of anti-VEGF therapy it is important to consider the effects of VEGF on all cells in the tumor microenvironment, including immune cells. Bevacizumab (Avastin®, Genetech), which binds VEGF and inhibits interaction with VEGFR1 and VEGFR2, was approved for the treatment of metastatic HER2/NEU-negative breast cancer in 2008, however, the majority of human mammary tumors are either innately resistant or will acquire resistance to anti-VEGF therapy. This suggests that these tumors activate alternate angiogenesis pathways. Pleiotrophin (PTN) is an important angiogenic cytokine in breast cancer and is expressed at high levels in approximately 60% of human breast tumors. PTN functions as an angiogenic factor and promotes remodeling of the tumor microenvironment as well as epithelial-mesenchymal transition (EMT). In addition, PTN can have profound effects on macrophage phenotype. The present review focuses on the functions of VEGF and PTN on immune cell infiltration and function in breast cancer. Furthermore, we will discuss how anti-VEGF therapy modulates the immune cell profile. Full article
(This article belongs to the Special Issue Breast Cancer)
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Review
Systemic Therapy of Non-Resectable Metastatic Melanoma
by Azadeh Orouji, Sergij Goerdt and Jochen Utikal
Cancers 2010, 2(2), 955-969; https://doi.org/10.3390/cancers2020955 - 26 May 2010
Cited by 8 | Viewed by 9013
Abstract
In advanced metastatic melanoma (non-resectable stage III/IV), the prognosis still remains poor, with median survival times between six and twelve months. Systemic therapeutic approaches for metastatic melanoma include chemotherapy, immunotherapy, immunochemotherapy, small molecules and targeted therapy. In this review, we will focus on [...] Read more.
In advanced metastatic melanoma (non-resectable stage III/IV), the prognosis still remains poor, with median survival times between six and twelve months. Systemic therapeutic approaches for metastatic melanoma include chemotherapy, immunotherapy, immunochemotherapy, small molecules and targeted therapy. In this review, we will focus on the various treatment modalities as well as new agents used for targeted therapy. Full article
(This article belongs to the Special Issue Current Concepts in the Diagnosis and Treatment of Cutaneous Melanoma)
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Review
Predictive and Prognostic Protein Biomarkers in Epithelial Ovarian Cancer: Recommendation for Future Studies
by Cécile Le Page, David G. Huntsman, Diane M. Provencher and Anne-Marie Mes-Masson
Cancers 2010, 2(2), 913-954; https://doi.org/10.3390/cancers2020913 - 26 May 2010
Cited by 28 | Viewed by 12397
Abstract
Epithelial ovarian cancer is the most lethal gynecological malignancy. Due to its lack of symptoms, this disease is diagnosed at an advanced stage when the cancer has already spread to secondary sites. While initial rates of response to first treatment is >80%, the [...] Read more.
Epithelial ovarian cancer is the most lethal gynecological malignancy. Due to its lack of symptoms, this disease is diagnosed at an advanced stage when the cancer has already spread to secondary sites. While initial rates of response to first treatment is >80%, the overall survival rate of patients is extremely low, mainly due to development of drug resistance. To date, there are no reliable clinical factors that can properly stratify patients for suitable chemotherapy strategies. Clinical parameters such as disease stage, tumor grade and residual disease, although helpful in the management of patients after their initial surgery to establish the first line of treatment, are not efficient enough. Accordingly, reliable markers that are independent and complementary to clinical parameters are needed for a better management of these patients. For several years, efforts to identify prognostic factors have focused on molecular markers, with a large number having been investigated. This review aims to present a summary of the recent advances in the identification of molecular biomarkers in ovarian cancer patient tissues, as well as an overview of the need and importance of molecular markers for personalized medicine in ovarian cancer. Full article
(This article belongs to the Special Issue Biomarkers: Oncology Studies)
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Review
The Evolution of Biomarkers in Thyroid Cancer—From Mass Screening to a Personalized Biosignature
by Raymon H. Grogan, Elliot J. Mitmaker and Orlo H. Clark
Cancers 2010, 2(2), 885-912; https://doi.org/10.3390/cancers2020885 - 20 May 2010
Cited by 213 | Viewed by 15330
Abstract
Thyroid cancer is the most common malignancy of the endocrine system. The diagnosis of thyroid nodules, made by neck examination and ultrasonography, is a common event occurring in over 50% of the patient population over the age of 50. Yet, only 5% of [...] Read more.
Thyroid cancer is the most common malignancy of the endocrine system. The diagnosis of thyroid nodules, made by neck examination and ultrasonography, is a common event occurring in over 50% of the patient population over the age of 50. Yet, only 5% of these patients will be diagnosed with cancer. Fine needle aspiration biopsy is the gold standard for diagnosing thyroid nodules. However, 10–15% of these biopsies are inconclusive, ultimately requiring a diagnostic thyroid lobectomy. Consequently, research in thyroid biomarkers has become an area of active interest. In the 40 years since calcitonin was first described as the biomarker for medullary thyroid cancer, new biomarkers in thyroid cancer have been discovered. Advances in genomic and proteomic technologies have defined many of these novel thyroid biomarkers. The purpose of this article is to provide a comprehensive literature review of how these biomarkers have evolved from simple screening tests into a complex array of multiple markers to help predict the malignant potential and genetic signature of thyroid neoplasms. Full article
(This article belongs to the Special Issue Biomarkers: Oncology Studies)
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Review
Role of Oxidative Stress in Stem, Cancer, and Cancer Stem Cells
by Ahmed Abdal Dayem, Hye-Yeon Choi, Jung-Hyun Kim and Ssang-Goo Cho
Cancers 2010, 2(2), 859-884; https://doi.org/10.3390/cancers2020859 - 17 May 2010
Cited by 173 | Viewed by 34333
Abstract
The term ‘‘oxidative stress” refers to a cell’s state characterized by excessive production of reactive oxygen species (ROS) and oxidative stress is one of the most important regulatory mechanisms for stem, cancer, and cancer stem cells. The concept of cancer stem cells arose [...] Read more.
The term ‘‘oxidative stress” refers to a cell’s state characterized by excessive production of reactive oxygen species (ROS) and oxidative stress is one of the most important regulatory mechanisms for stem, cancer, and cancer stem cells. The concept of cancer stem cells arose from observations of similarities between the self-renewal mechanism of stem cells and that of cancer stem cells, but compared to normal stem cells, they are believed to have no control over the cell number. ROS have been implicated in diverse processes in various cancers, and generally the increase of ROS in cancer cells is known to play an important role in the initiation and progression of cancer. Additionally, ROS have been considered as the most significant mutagens in stem cells; when elevated, blocking self-renewal and at the same time, serving as a signal stimulating stem cell differentiation. Several signaling pathways enhanced by oxidative stress are suggested to have important roles in tumorigenesis of cancer or cancer stem cells and the self-renewal ability of stem or cancer stem cells. It is now well established that mitochondria play a prominent role in apoptosis and increasing evidence supports that apoptosis and autophagy are physiological phenomena closely linked with oxidative stress. This review elucidates the effect and the mechanism of the oxidative stress on the regulation of stem, cancer, and cancer stem cells and focuses on the cell signaling cascades stimulated by oxidative stress and their mechanism in cancer stem cell formation, as very little is known about the redox status in cancer stem cells. Moreover, we explain the link between ROS and both of apoptosis and autophagy and the impact on cancer development and treatment. Better understanding of this intricate link may shed light on mechanisms that lead to better modes of cancer treatment. Full article
(This article belongs to the Special Issue Oxidative Stress and Cancer)
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Review
Platelet Proteome and Tumor Dormancy: Can Platelets Content Serve as Predictive Biomarkers for Exit of Tumors from Dormancy?
by Nava Almog and Giannoula Lakka Klement
Cancers 2010, 2(2), 842-858; https://doi.org/10.3390/cancers2020842 - 11 May 2010
Cited by 66 | Viewed by 10181
Abstract
Although tumor dormancy is highly prevalent, the underling mechanisms are still mostly unknown. It is unclear which lesions will progress and become a disseminated cancer, and which will remain dormant and asymptomatic. Yet, an improved ability to predict progression would open the possibility [...] Read more.
Although tumor dormancy is highly prevalent, the underling mechanisms are still mostly unknown. It is unclear which lesions will progress and become a disseminated cancer, and which will remain dormant and asymptomatic. Yet, an improved ability to predict progression would open the possibility of timely treatment and improvement in outcomes. We have recently described the ability of platelets to selectively uptake angiogenesis regulators very early in tumor growth, and proposed their use as an early marker of malignancy. In this review we will summarize current knowledge about these processes and will discuss the possibility of using platelet content to predict presence of occult tumors. Full article
(This article belongs to the Special Issue Biomarkers: Oncology Studies)
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Review
Surgery of Primary Melanomas
by Piotr Rutkowski, Marcin Zdzienicki, Zbigniew I. Nowecki and Alexander C. J. Van Akkooi
Cancers 2010, 2(2), 824-841; https://doi.org/10.3390/cancers2020824 - 11 May 2010
Cited by 45 | Viewed by 18521
Abstract
Surgery remains the mainstay of melanoma therapy, regardless of the tumor site. Only the early diagnosis combined with proper surgical therapy currently gives patients affected by this malignancy the chance for a full cure. The main goal of surgical therapy is to provide [...] Read more.
Surgery remains the mainstay of melanoma therapy, regardless of the tumor site. Only the early diagnosis combined with proper surgical therapy currently gives patients affected by this malignancy the chance for a full cure. The main goal of surgical therapy is to provide the local control of the disease and to secure long-term survival of the patient without reasonable functional and esthetic impairment. The recommended method of biopsy—excisional biopsy, as an initial diagnostic and, to some extent, therapeutic procedure—is performed under local anesthesia as an elliptical incision with visual clear margins of 1–3 mm and with some mm of subcutaneous tissue. The extent of radical excision of the primary tumor (or scar after excisional biopsy) is based on the histopathologic characteristics of the primary tumor and usually consists of 1–2 cm margins with primary closure. The philosophy behind conducted randomized clinical trials has been to find the most conservative surgical approach that is able to guarantee the same results as more demolitive treatment. This has been the background of the trials designed to define the correct margins of excision around a primary cutaneous melanoma. Much less definition can be dedicated to the surgical management of patients with non-cutaneous melanomas. Full article
(This article belongs to the Special Issue Current Concepts in the Diagnosis and Treatment of Cutaneous Melanoma)
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Review
An Overview of Biomarkers and Molecular Signatures in HCC
by Seon-Hee Yim and Yeun-Jun Chung
Cancers 2010, 2(2), 809-823; https://doi.org/10.3390/cancers2020809 - 07 May 2010
Cited by 28 | Viewed by 11797
Abstract
Hepatocellular carcinoma (HCC) is the third most common cause of cancer mortality worldwide. Although most HCCs seem to originate from the accumulation of genetic abnormalities induced by various risk factors, underlying mechanisms of hepatocarcinogenesis remain unclear. Long-term survival of HCC patients is also [...] Read more.
Hepatocellular carcinoma (HCC) is the third most common cause of cancer mortality worldwide. Although most HCCs seem to originate from the accumulation of genetic abnormalities induced by various risk factors, underlying mechanisms of hepatocarcinogenesis remain unclear. Long-term survival of HCC patients is also poor, partly due to HCC recurrence. Although serum alpha-fetoprotein (AFP) level is a useful marker for the detection and monitoring of HCC, AFP levels may remain normal in the patients even with advanced HCC. To identify useful biomarkers for HCC, many studies have been conducted on molecular events such as genetic and epigenetic alterations, and gene expression. This review summarizes recent studies of potential molecular markers for diagnosis and monitoring metastasis or recurrence of HCC. Full article
(This article belongs to the Special Issue Biomarkers: Oncology Studies)
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Article
Cytokines and Growth Factors Expressed by Human Cutaneous Melanoma
by Elias G. Elias, Joanne H. Hasskamp and Bhuvnesh K. Sharma
Cancers 2010, 2(2), 794-808; https://doi.org/10.3390/cancers2020794 - 07 May 2010
Cited by 53 | Viewed by 11425
Abstract
Cytokines and growth factors have biologic effects that could stimulate tumor growth, invasion and angiogenesis. The incidence of 24 factors was investigated in 25 cultured human melanoma cell lines and in 62 fixed tissues at different stages of the disease. Over 80% of [...] Read more.
Cytokines and growth factors have biologic effects that could stimulate tumor growth, invasion and angiogenesis. The incidence of 24 factors was investigated in 25 cultured human melanoma cell lines and in 62 fixed tissues at different stages of the disease. Over 80% of the human melanoma cell lines expressed TGF-β, IL-8, IL-6, VEGF, PDGF-AA and OPN. Significantly higher TGF-β, IGF-1 and IL-15 were determined in primary lesions compared to distant metastases by immunohistochemistry. Illustrating the complexity of the milieu of the tumor microenvironment, some of these factors may have to be considered in targeted therapy. Full article
(This article belongs to the Special Issue Current Concepts in the Diagnosis and Treatment of Cutaneous Melanoma)
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Review
In Situ Conversion of Melanoma Lesions into Autologous Vaccine by Intratumoral Injections of α-gal Glycolipids
by Uri Galili, Mark R. Albertini, Paul M. Sondel, Kim Wigglesworth, Mary Sullivan and Giles F. Whalen
Cancers 2010, 2(2), 773-793; https://doi.org/10.3390/cancers2020773 - 04 May 2010
Cited by 67 | Viewed by 13563
Abstract
Autologous melanoma associated antigens (MAA) on murine melanoma cells can elicit a protective anti-tumor immune response following a variety of vaccine strategies. Most require effective uptake by antigen presenting cells (APC). APC transport and process internalized MAA for activation of anti-tumor T cells. [...] Read more.
Autologous melanoma associated antigens (MAA) on murine melanoma cells can elicit a protective anti-tumor immune response following a variety of vaccine strategies. Most require effective uptake by antigen presenting cells (APC). APC transport and process internalized MAA for activation of anti-tumor T cells. One potential problem with clinical melanoma vaccines against autologous tumors may be that often tumor cells do not express surface markers that label them for uptake by APC. Effective uptake of melanoma cells by APC might be achieved by exploiting the natural anti-Gal antibody which constitutes ~1% of immunoglobulins in humans. This approach has been developed in a syngeneic mouse model using mice capable of producing anti-Gal. Anti-Gal binds specifically to α-gal epitopes (Galα1-3Galα1-4GlcNAc-R). Injection of glycolipids carrying α-gal epitopes (α-gal glycolipids) into melanoma lesions results in glycolipid insertion into melanoma cell membranes, expression of α-gal epitopes on the tumor cells and binding of anti-Gal to these epitopes. Interaction between the Fc portions of bound anti-Gal and Fcγ receptors on APC induces effective uptake of tumor cells by APC. The resulting anti-MAA immune response can be potent enough to destroy distant micrometastases. A clinical trial is now open testing effects of intratumoral α-gal glycolipid injections in melanoma patients. Full article
(This article belongs to the Special Issue Current Concepts in the Diagnosis and Treatment of Cutaneous Melanoma)
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