Phosphorylation Alters the Properties of Pol : Implications for Translesion Synthesis and Cancer Etiology

2018 ◽  
Author(s):  
Chandana Peddu ◽  
Sufang Zhang ◽  
Hong Zhao ◽  
Ernest Y.C. Lee ◽  
Marietta Y.W.T. Lee ◽  
...  
2019 ◽  
Vol 0 (1) ◽  
pp. 7-17
Author(s):  
V. O. Palamarchuk ◽  
O. A. Tovkai ◽  
V. V. Voitenko ◽  
O. V. Mazur ◽  
O. P. Nechay

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Angel T. Chan ◽  
William Dinsfriend ◽  
Jiwon Kim ◽  
Brian Yum ◽  
Razia Sultana ◽  
...  

Abstract Background Late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) is widely used to identify cardiac neoplasms, for which diagnosis is predicated on enhancement stemming from lesion vascularity: Impact of contrast-enhancement pattern on clinical outcomes is unknown. The objective of this study was to determine whether cardiac metastasis (CMET) enhancement pattern on LGE-CMR impacts prognosis, with focus on heterogeneous lesion enhancement as a marker of tumor avascularity. Methods Advanced (stage IV) systemic cancer patients with and without CMET matched (1:1) by cancer etiology underwent a standardized CMR protocol. CMET was identified via established LGE-CMR criteria based on lesion enhancement; enhancement pattern was further classified as heterogeneous (enhancing and non-enhancing components) or diffuse and assessed via quantitative (contrast-to-noise ratio (CNR); signal-to-noise ratio (SNR)) analyses. Embolic events and mortality were tested in relation to lesion location and contrast-enhancement pattern. Results 224 patients were studied, including 112 patients with CMET and unaffected (CMET -) controls matched for systemic cancer etiology/stage. CMET enhancement pattern varied (53% heterogeneous, 47% diffuse). Quantitative analyses were consistent with lesion classification; CNR was higher and SNR lower in heterogeneously enhancing CMET (p < 0.001)—paralleled by larger size based on linear dimensions (p < 0.05). Contrast-enhancement pattern did not vary based on lesion location (p = NS). Embolic events were similar between patients with diffuse and heterogeneous lesions (p = NS) but varied by location: Patients with right-sided lesions had threefold more pulmonary emboli (20% vs. 6%, p = 0.02); those with left-sided lesions had lower rates equivalent to controls (4% vs. 5%, p = 1.00). Mortality was higher among patients with CMET (hazard ratio [HR] = 1.64 [CI 1.17–2.29], p = 0.004) compared to controls, but varied by contrast-enhancement pattern: Diffusely enhancing CMET had equivalent mortality to controls (p = 0.21) whereas prognosis was worse with heterogeneous CMET (p = 0.005) and more strongly predicted by heterogeneous enhancement (HR = 1.97 [CI 1.23–3.15], p = 0.005) than lesion size (HR = 1.11 per 10 cm [CI 0.53–2.33], p = 0.79). Conclusions Contrast-enhancement pattern and location of CMET on CMR impacts prognosis. Embolic events vary by CMET location, with likelihood of PE greatest with right-sided lesions. Heterogeneous enhancement—a marker of tumor avascularity on LGE-CMR—is a novel marker of increased mortality risk.


2021 ◽  
Vol 11 (2) ◽  
pp. 88
Author(s):  
Nithya Subrahmanyam ◽  
Hamidreza Ghandehari

The extracellular matrix (ECM) plays an active role in cell life through a tightly controlled reciprocal relationship maintained by several fibrous proteins, enzymes, receptors, and other components. It is also highly involved in cancer progression. Because of its role in cancer etiology, the ECM holds opportunities for cancer therapy on several fronts. There are targets in the tumor-associated ECM at the level of signaling molecules, enzyme expression, protein structure, receptor interactions, and others. In particular, the ECM is implicated in invasiveness of tumors through its signaling interactions with cells. By capitalizing on the biology of the tumor microenvironment and the opportunities it presents for intervention, the ECM has been investigated as a therapeutic target, to facilitate drug delivery, and as a prognostic or diagnostic marker for tumor progression and therapeutic intervention. This review summarizes the tumor ECM biology as it relates to drug delivery with emphasis on design parameters targeting the ECM.


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