Cancer Biomarkers - Volume 8, issue 4-5

Authors: Bast, Jr., Robert C.

Article Type: Editorial

DOI: 10.3233/CBM-2011-0209

Citation: Cancer Biomarkers, vol. 8, no. 4-5, pp. 161-166, 2011

Authors: Nowosinska, Ewa | Avril, Stefanie | Murray, Iain | Szyszko, Teresa | Avril, Norbert

Article Type: Research Article

Abstract: In the clinical setting the vast majority of positron emission tomography (PET) procedures use the glucose analogue F-18 fluorodeoxyglucose (FDG) to visualize the increased glucose consumption of malignant lesions. Co-registered PET/CT has improved the diagnostic accuracy compared to either imaging procedure alone, particularly in ovarian cancer. FDG-PET/CT demonstrates primary malignant ovarian tumors; however, it is often unable to accurately differentiate between benign and malignant pelvic masses and to visualize borderline ovarian tumors. FDG-PET/CT has a suggested role for staging, by improving treatment planning in individual cases, but it is particularly helpful in the setting of disease recurrence when CA125 tumor …marker levels are rising and conventional imaging (CT or MR) is inconclusive or negative. The aim of this review is to demonstrate the value of FDG-PET-CT in diagnosis and management of patients with ovarian malignancies, outlining its advantages and limitations. Show more

Keywords: PET, FDG-PET, PET/CT, ovarian cancer, diagnosis, staging, treatment monitoring

DOI: 10.3233/CBM-2011-0219

Citation: Cancer Biomarkers, vol. 8, no. 4-5, pp. 167-175, 2011

Authors: Nolen, Brian M. | Lokshin, Anna E.

Article Type: Research Article

Abstract: The early detection of ovarian cancer represents a clinical objective with an enormous potential for a meaningful improvement in our ability to treat and cure afflicted patients. The magnitude of this potential is matched by the challenges associated with attaining it. In addition to the well noted aspects of ovarian cancer which have thus far precluded the development a effective screening strategies, recent work regarding the differential pathogenesis and origins of the various histological subtypes of epithelial ovarian cancer have further revealed the challenges ahead. These findings are reviewed here with a particular focus on reports describing the early development …of high-grade serous carcinomas, the most prevalent and aggressive disease subtype. The unique set of difficulties associated with the early detection of these tumors is discussed in depth. An update on findings stemming from several large randomized screening trials is provided. While the current state of ovarian cancer screening remains characterized by unmet needs, the ongoing evaluation of those needs is providing a strong basis for future advancement. This advancement will rely upon the refined application of currently available diagnostic tools based on lessons well learned. Show more

Keywords: Ovarian cancer, screening, CA-125, histology, biomarkers, early detection, clinical trials

DOI: 10.3233/CBM-2011-0210

Citation: Cancer Biomarkers, vol. 8, no. 4-5, pp. 177-186, 2011

Authors: Chatterjee, Madhumita | Tainsky, Michael A.

Article Type: Research Article

Abstract: Ovarian cancer (OVCA) has the highest mortality of all gynecologic cancers. The poor survival rate is due to the lack of diagnostic screening tests and high incidence of recurrence in OVCA patients resistant to chemotherapy that leads to a more aggressive form of the disease. Therefore, a search for biomarkers holds great promise not only for early detection of OVCA at presymptomatic stage and for monitoring the course of the disease during the first-line chemotherapy treatment but also for identifying those women whose disease is likely to recur. Research efforts have sought to unravel the complexity of the tumor specific …proteome by profiling immune responses generated against tumor associated antigens (TAAs) using multianalyte-based analytical discovery platforms readily adaptable to clinical diagnostic screening tests. The occurrence of tumor-specific autoantibodies directed to respective TAAs can be observed before the development of clinical symptoms. Evaluation of the level of tumor autoantibodies during the time of tumor debulking followed by first-line chemotherapy for the prediction of early recurrence as well as their correlation with other clinical parameters to evaluate their prognostic value has been conducted in various clinical studies. The anti-tumor immune response against OVCA is the ultimate key to the development of multiple immune-based therapeutic strategies that have been proposed and tested in different clinical trials that may have beneficial impact on the disease outcome in OVCA patients. Show more

Keywords: Ovarian cancer, humoral immune response, tumor autoantibodies, early detection, recurrence, immunotherapy

DOI: 10.3233/CBM-2011-0213

Citation: Cancer Biomarkers, vol. 8, no. 4-5, pp. 187-201, 2011

Authors: Balch, Curtis | Nephew, Kenneth P.

Article Type: Research Article

Abstract: The term “epigenetics” refers to DNA sequence-independent events that regulate gene expression, including DNA methylation, modifications to histone proteins, and microRNA-associated post-transcriptional control of protein translation. Epigenetic aberrations are now considered a defining characteristic of numerous human pathologies, including cancer. However, in contrast to DNA sequence mutations, many oncogenic epigenetic modifications are potentially reversible, with studies now showing numerous tumor cell types to possess remarkable phenotypic “plasticity,” strongly supporting possible reversion of their malignant status. The “epigenome” of one such malignancy, ovarian cancer, has now been studied in depth, with specific epigenetic alterations correlated with tumor initiation, progression, metastasis, and …therapy resistance. Ovarian cancer is the most lethal malignancy of the female reproductive tract, largely due to lack or diagnoses of early-stage disease and the eventual develoment of drug resistance; thus, reliable early detection biomarkers and alternative therapies are urgently needed. In this chapter, we discuss the epigenetics of ovarian cancer, including its likely role in the establishment of “cancer stem cells,” i.e., highly tumorigenic progenitor cells believed to be largely or solely responsible for the propagation of malignant, chemotherapy-resistant and metastatic disease. Improved understanding of these gene-regulatory phenomena could likely result in improved detection and survival of this highly destructive malignancy. Show more

DOI: 10.3233/CBM-2011-0214

Citation: Cancer Biomarkers, vol. 8, no. 4-5, pp. 203-221, 2011

Authors: Rodland, Karin D. | Maihle, Nita J.

Article Type: Research Article

Abstract: The stark difference in clinical outcome for patients with ovarian cancer diagnosed at early stages (95% survival at 5 years) versus late stages (27.6% survival at 5 years) has driven a decades-long quest for effective biomarkers that will enable earlier detection of ovarian cancer. Yet despite intense efforts, including the application of modern high throughput technologies including transcriptomics and proteomics, there has been little improvement in performance compared to the gold standard of quantifying serum CA125 immunoreactivity paired with transvaginal ultrasound. This review describes the strategies that have been used for identification of ovarian cancer biomarkers, including the recent introduction …of novel bioinformatic approaches. Results obtained using high throughput-based vs. biologically rational approaches for the discovery of diagnostic early detection biomarkers are compared and analyzed for functional enrichment. Show more

Keywords: Ovarian cancer, diagnostics, biomarkers, early detection, systems biology

DOI: 10.3233/CBM-2011-0216

Citation: Cancer Biomarkers, vol. 8, no. 4-5, pp. 223-230, 2011

Authors: Huang, Jie | Hu, Wei | Sood, Anil K.

Article Type: Research Article

Abstract: Epithelial ovarian cancer (EOC) remains the most lethal gynecological malignancy despite several~decades of progress in diagnosis and treatment. Taking advantage of the robust development of discovery and utility of prognostic biomarkers, clinicians and researchers are developing personalized and targeted treatment strategies. This review encompasses recently discovered biomarkers of ovarian cancer, the utility of published prognostic biomarkers for EOC (especially biomarkers related to angiogenesis and key signaling pathways), and their integration into clinical practice.

Keywords: Biomarkers, ovarian carcinoma, prognosis

DOI: 10.3233/CBM-2011-0212

Citation: Cancer Biomarkers, vol. 8, no. 4-5, pp. 231-251, 2011

Authors: Li, Chunsheng | Sasaroli, Dimitra | Chen, Xiang | Hu, Jia | Sandaltzopoulos, Raphael | Omidi, Yadolah | Coukos, George

Article Type: Research Article

Abstract: Tumor vasculature varies significantly from its normal counterpart and displays unique markers. Recent technological advancements including immunohistochemistry laser-capture microdissection (immuno-LCM), genome-wide high-throughput screening, and proteomics have uncovered a vast array of vascular bed-specific markers that may provide a platform for discovery of new therapeutics directed against various malignancies. However, an essential step in the translation of these markers to clinical application will be the identification of those biomarkers with the highest diagnostic and therapeutic potential. The aim of the current review is to provide a synopsis of recent advancements in the identification of tumor vasculature biomarkers.

DOI: 10.3233/CBM-2011-0217

Citation: Cancer Biomarkers, vol. 8, no. 4-5, pp. 253-271, 2011

Authors: Abbott, Karen L.

Article Type: Research Article

Abstract: Glycosylation is undeniably the most complex posttranslational modification. Glycan structures found on proteins and lipids are diverse, often changing in different tissues from normal physiologic conditions to diseases such as cancer. Glycomics encompasses the study of glycans along with the proteins and lipids to which they are attached. In this review we will discuss the glycomics of ovarian cancer from the pre- mass spectrometry era to current discoveries and finally to future potential clinical applications of research based on glycomic discoveries.

DOI: 10.3233/CBM-2011-0218

Citation: Cancer Biomarkers, vol. 8, no. 4-5, pp. 273-280, 2011

Authors: Roberson, Carolyn D. | Atay, Safinur | Gercel-Taylor, Cicek | Taylor, Douglas D.

Article Type: Research Article

Abstract: Tumor cells release membranous structures, defined as microvesicles or exosomes, consisting of an array of macromolecules derived from the originating cells, including proteins, lipids, and RNA. The expression of antigenic molecules recognizable by T cells originally suggested a role for these vesicles as a cell-free antigen source for anti-cancer vaccines; however, evidence demonstrates that tumor exosomes can exert a broad array of detrimental effects on the immune system – ranging from apoptosis of activated cytotoxic T cells to impairment of monocyte differentiation into dendritic cells, to induction of myeloid-suppressive cells. Immunosuppressive exosomes of tumor origin can be found in neoplastic …lesions and biologic fluids from cancer patients, implying a potential role of these pathways in in vivo tumor progression and systemic paraneoplastic syndromes. Through the expression of molecules involved in angiogenesis promotion, stromal remodeling, signaling pathway activation through growth factor/receptor transfer, chemoresistance, and intercellular genetic exchange, tumor exosomes could represent a central mediator of the tumor microenvironment. Their release by tumor cells may represent the future for targeting therapeutic interventions and for development of multiplexed diagnostic biomarkers. Show more

Keywords: Exosomes, cancer, biomarkers, biogenesis, intercellular communication

DOI: 10.3233/CBM-2011-0211

Citation: Cancer Biomarkers, vol. 8, no. 4-5, pp. 281-291, 2011

Authors: Ramirez, Arturo B. | Lampe, Paul D.

Article Type: Research Article

Abstract: Here we demonstrate the utility of high-density antibody microarrays for ovarian cancer biomarker discovery. This report describes the technology and how it can be optimized for hypothesis-generating and testing experiments. Our previous results validated the high density antibody array technology platform, the current work expands on it utilizing a second generation array that we tested with a larger set of ovarian case and control serum samples. We then describe our strategies and methods for result validation, including Western immunoblots to confirm antibody specificity. By comparing and combining the current results with our previous study, we solidified the case that the …markers found could be used for ovarian cancer diagnosis using this technology. These results set the stage for further validation of these potential biomarkers and the use of this technology in future biomarker discovery studies. Show more

Keywords: Ovarian cancer, antibody microarray, biomarkers

DOI: 10.3233/CBM-2011-0215

Citation: Cancer Biomarkers, vol. 8, no. 4-5, pp. 293-307, 2011