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Liquid Biopsies for Pancreatic Cancer: A Step Towards Early Detection
Published in Surinder K. Batra, Moorthy P. Ponnusamy, Gene Regulation and Therapeutics for Cancer, 2021
Joseph Carmicheal, Rahat Jahan, Koelina Ganguly, Ashu Shah, Sukhwinder Kaur
Recently, blood-based liquid biopsies have become a highly investigated means by which PC may be detected. By using blood as the biopsy specimen, the risk to the patient is drastically reduced. Further, when the biopsy is not limited to a single solid tissue sample, tumor heterogeneity can be taken into account as well as various physiological responses to the tumor can be measured, thereby taking into account the overall gestalt of the disease. Myriad of molecules and particles have been studied in the attempt to find a PC specific liquid biopsy based biomarker including various glycoproteins [1] and miRNA [2]. While these modalities show great promise, no current biomarker is sufficient as of yet for accurate diagnosis. Novel emerging technologies and markers are required if this disease is to be detected at a curable stage. While not exhaustive, this chapter aims to elucidate some of the most promising molecules and methods that are currently being investigated including circulating cell-free tumor DNA (ctDNA), metabolomics, and exosomes.
The Molecular Genetics OF DNA Methylation in Colorectal Cancer
Published in Leonard H. Augenlicht, Cell and Molecular Biology of Colon Cancer, 2019
Two phenomena became apparent from this larger study. First, there is substantial heterogeneity of the hypomethylation patterns, no matter how one addresses that question. There is heterogeneity in the methylation pattern of a given gene from patient to patient and also from tumor to tumor for a given gene, when there are multiple lesions from the same patient. For example, one patient with two cancers and two polyps showed differences in methylation from gene to gene, and from site to site for a given gene.28 We also sampled multiple times from a given tumor, and at this level of dissection, we were unable to discern any difference in the methylation pattern. Therefore, we conclude that heterogeneity is a relatively early event in the development of a given neoplastic lesion or that there is intermingling of cells within that lesion. Tumor heterogeneity is a substantial problem in human cancer. Most solid tumors are capable of escaping a given chemotherapeutic or radiation protocol, as subpopulations of cells are resistant to that agent. This is the first demonstration at the genomic level of DNA heterogeneity in tumors, and it is intriguing to speculate that this may underlie at least part of the tumor heterogeneity seen at the phenotypic level.
Radiomics analysis for gynecologic cancers
Published in Ruijiang Li, Lei Xing, Sandy Napel, Daniel L. Rubin, Radiomics and Radiogenomics, 2019
Radiomics analysis is the process of extracting high-dimensional quantitative characterize of imaging heterogeneity within cancers. Many solid cancers exhibit widespread genomic tumor heterogeneity within and between cancers [1], and increased heterogeneity has been implicated to be associated with worse outcomes including in ovarian cancers [2]. Unlike biopsy-based quantification of heterogeneity that computes a static measurement of the tumor state at one time, radiomics analysis is non-invasive and therefore can be used to quantify and trace the evolution of image-based tumor heterogeneity over time. Furthermore, biopsy-based quantification of tumor heterogeneity only examines a small portion of the tumor while radiomics biomarkers can non-invasively quantify the tumor heterogeneity over the whole tumor extent. Whereas morphologic heterogeneity within cancers is subjectively described in radiological reports [3,4], radiomic analysis can produce potentially limitless number of quantitative imaging biomarkers that are distinct from subjective assessment and add to clinical decision-making [5]. Radiomics analysis has shown feasibility in characterization of disease aggressiveness and outcomes [6–8], as well as in predicting outcomes to treatment in a variety of cancers [9].
Prognostic role and immune infiltration characteristics of EI24 in multiple cancer types
Published in Expert Review of Molecular Diagnostics, 2023
Wanli Yang, Wei Zhou, Xinhui Zhao, Lili Duan, Liaoran Niu, Yujie Zhang, Yiding Li, Xiaoqian Wang, Junfeng Chen, Aqiang Fan, Qibin Xie, Jinqiang Liu, Yu Han, Daiming Fan, Liu Hong
In the present study, we found that EI24 was expressed at low levels in KIRP, KIPAN, WT, ACC, and KICH, whereas GBM, BMLGG, LGG, UCEC, BRCA, LUAD, ESCA, STES, COAD, COADREAD, PRAD, STAD, HNSC, LUSC, BLCA, THCA, OV, PAAD, TGCT, ALL, and LAML showed high EI24 mRNA expression levels. These results are consistent with those of previous studies on PAAD [19], LUAD [51], and skin cancer [20]. However, studies have also found that EI24 expression is downregulated in several cancers and functions as a tumor suppressor [17,18,52]. Tumor heterogeneity may account for this phenomenon and requires further validation. Moreover, survival analysis showed a correlation between high EI24 expression and poor overall survival in different cancers, including GBMLGG, LGG, LAML, BRCA, HNSC, SKCM, MESO, PAAD, and ACC. These findings indicate that EI24 may serve as a diagnostic and prognostic biomarker for cancers. Interestingly, our results revealed a discrepancy between the mRNA and protein levels of EI24 in COAD. This discrepancy may have been caused by post-translational modifications, epigenetic modifications, or other modulations. The mechanism by which the EI24 protein is downregulated in COAD samples remains to be elucidated.
HIF-1α affects sensitivity of murine squamous cell carcinoma to boron neutron capture therapy with BPA
Published in International Journal of Radiation Biology, 2021
Yu Sanada, Takushi Takata, Hiroki Tanaka, Yoshinori Sakurai, Tsubasa Watanabe, Minoru Suzuki, Shin-ichiro Masunaga
Tumor heterogeneity (existence of tumor cells that display distinct phenotypes) is well described in solid tumors, and is considered to influence response to cancer therapy (Fisher et al. 2013). SCC VII and SCC VII Hif-1α-deficient tumor tissues appeared to contain similar amounts of BPA (Figure 4(A)). However, the biological effects of BNCR may be dependent on the intracellular concentration and localization of the 10B-carrier due to the short range of α particles and 7Li ions. Since a hypoxic environment exists in solid tumor tissues (e.g. due to an abnormal vasculature), SLC7A5 protein expression may have been down-regulated and BPA uptake inhibited in intra-tumor hypoxic regions, which may partly explain the differences observed in cell survival between SCC VII and SCC VII Hif-1α-deficient cells from BPA-administered mice (Figure 4(B)).
CAR T cells and checkpoint inhibition for the treatment of glioblastoma
Published in Expert Opinion on Biological Therapy, 2020
Steven H. Shen, Karolina Woroniecka, Andrew B. Barbour, Peter E. Fecci, Luis Sanchez-Perez, John H. Sampson
While tumor heterogeneity is not as prominent among hematological cancers, solid malignancies are characterized by both intertumoral and intratumoral heterogeneity. The heterogeneous expression of tumor antigens severely limits the impact of strategies targeting one or a few antigens in solid tumors and has been shown to mitigate tumor escape following CAR T cell therapy. Approaches aimed at enhancing the endogenous T cell activity directed at the tumor, such as checkpoint blockade, may help to scale the barriers erected by tumor heterogeneity. Meanwhile, in the case of GBM, the concomitant presence of a highly immunosuppressive tumor microenvironment provides significant challenges even if a ubiquitously expressed strong tumor antigen is afforded. In particular, tumor-imposed T cell exhaustion has proved to be a challenge for CAR T cells specifically and likewise limits the efficacy of checkpoint blockade therapies. Therefore, strategies to counter exhaustion may license efficacy for both treatment platforms.