Cancers, Vol. 10, Pages 101: Epigenetic Modifications as Biomarkers of Tumor Development, Therapy Response, and Recurrence across the Cancer Care Continuum

Cancers, Vol. 10, Pages 101: Epigenetic Modifications as Biomarkers of Tumor Development, Therapy Response, and Recurrence across the Cancer Care Continuum

Cancers doi: 10.3390/cancers10040101

Authors: Margaret Thomas Paola Marcato

Aberrant epigenetic modifications are an early event in carcinogenesis, with the epigenetic landscape continuing to change during tumor progression and metastasis—these observations suggest that specific epigenetic modifications could be used as diagnostic and prognostic biomarkers for many cancer types. DNA methylation, post-translational histone modifications, and non-coding RNAs are all dysregulated in cancer and are detectable to various degrees in liquid biopsies such as sputum, urine, stool, and blood. Here, we will focus on the application of liquid biopsies, as opposed to tissue biopsies, because of their potential as non-invasive diagnostic tools and possible use in monitoring therapy response and progression to metastatic disease. This includes a discussion of septin-9 (SEPT9) DNA hypermethylation for detecting colorectal cancer, which is by far the most developed epigenetic biomarker assay. Despite their potential as prognostic and diagnostic biomarkers, technical issues such as inconsistent methodology between studies, overall low yield of epigenetic material in samples, and the need for improved histone and non-coding RNA purification methods are limiting the use of epigenetic biomarkers. Once these technical limitations are overcome, epigenetic biomarkers could be used to monitor cancer development, disease progression, therapeutic response, and recurrence across the entire cancer care continuum.

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Cancers, Vol. 10, Pages 102: EBV+ and MSI Gastric Cancers Harbor High PD-L1/PD-1 Expression and High CD8+ Intratumoral Lymphocytes

Cancers, Vol. 10, Pages 102: EBV+ and MSI Gastric Cancers Harbor High PD-L1/PD-1 Expression and High CD8+ Intratumoral Lymphocytes

Cancers doi: 10.3390/cancers10040102

Authors: Simona De Rosa Nora Sahnane Maria Tibiletti Francesca Magnoli Alessandro Vanoli Fausto Sessa Anna Chiaravalli

Both EBV+ and MSI gastric cancers (GCs) have high lymphoid infiltration which is rare in MSS/EBV− cancers. PD-L1/PD-1 interaction leads to a down-regulated immune response and it is one of the most promising targets for gastric cancer immunotherapy. PD-L1/PD-1 and CD8 expression were immunohistochemically investigated in a series of 169 FFPE GCs, including 33 EBV+, 59 MSI and 77 MSS/EBV− cases. PD-L1 membrane immunoreactivity in more than 5% of tumor cells was present in 31/169 GCs and was associated with high levels of CD8 intraepithelial lymphocytes (TILs; p < 0.001). PD-L1+ cases were mainly poorly differentiated (71%), intestinal type (85%) and high lymphoid response (HLR; 90%) tumors. PD-L1 expression was only present in EBV⁺ (46%), MSI (24%) and rare MSS/EBV− (3%) GCs with high CD8+ TILs (p < 0.001). Despite being associated with a better prognosis both in the whole series (p < 0.05) and in the MSI subset, PD-L1 is not an independent prognostic factor. PD-L1 gene amplification was detected in 3/17 cases, including 2/7 EBV+ and 1/8 MSI GC. PD-1⁺ TILs were significantly higher in EBV⁺ than MSI and MSS/EBV− cases. PD-L1/PD-1 pathway is selectively activated in HLR GCs and could be considered an emerging therapeutic target, particularly for EBV and MSI GCs.

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GeneXpert MTB/RIF Outperforms Mycobacterial Culture in Detecting Mycobacterium tuberculosis from Salivary Sputum

GeneXpert MTB/RIF (Xpert) assay has been endorsed for the diagnosis of pulmonary TB due to its high sensitivity and specificity for culture positive TB. There is no doubt that Xpert could not be more sensitive than mycobacterial culture, while the positive rate of Xpert among sputum samples was higher than that of mycobacterial culture in our laboratory. We therefore carried out a prospective study to determine a potential explanation for this unexpected result regarding the clinical use of Xpert. Overall, a total of 558 patients meeting inclusion criteria were enrolled in final analysis between August 2017 and September 2017 in Beijing Chest Hospital. The overall positive rate of Xpert among sputum samples was 45.9% (256/558), which was significantly higher than that of liquid culture (33.4%, 184/558; ). The percentage of culture negative result in salivary sputum was significantly higher than that in mucoid sputum [odds ratio (OR): 5.04, 95% confidence interval (95% CI): 2.74–9.28; ]. In addition, the TB cases having previous treatment history had a higher proportion of culture negative result than new cases (OR: 4.26, 95% CI: 1.61–11.28; ). In conclusion, the results of this study demonstrate that Xpert outperforms mycobacterial culture in detecting MTB from salivary sputum. In addition, the previously treated patients are more likely to yield negative culture results. Our data will provide important hints to formulate an appropriate diagnostic algorithm for pulmonary tuberculosis based on the appearance of sputum samples.

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Mandibular Flexure and Peri-Implant Bone Stress Distribution on an Implant-Supported Fixed Full-Arch Mandibular Prosthesis: 3D Finite Element Analysis

Purpose. The purpose of this study was to evaluate and compare the effect of three mandibular full-arch superstructures on the peri-implant bone stress distribution during mandibular flexure caused by mid-opening (27 mm) and protrusion mandibular movements. Materials and Methods. Three-dimensional finite element models were created simulating six osseointegrated implants in the jawbone. One model simulated a 1-piece framework and the other simulated 2-piece and 3-piece frameworks. Muscle forces with definite direction and magnitude were exerted over areas of attachment to simulate multiple force vectors of masticatory muscles during mandibular protrusion and opening. Results. During the movement of 27.5 mm jaw opening, the 1-piece and 3-piece superstructures showed the lowest values of bone stress around the mesial implants, gradually increasing towards the distal position. During the protrusion movement, bone stress increased compared to opening for any implant situation and for a divided or undivided framework. The 3-piece framework showed the highest values of peri-implant bone stress, regardless of the implant situation. Conclusions. The undivided framework provides the best biomechanical environment during mandibular protrusion and opening. Protrusion movement increases the peri-implant bone stress. The most mesial implants have the lowest biomechanical risk.

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Hypoparathyroidism Causing Seizures: When Epilepsy Does Not Fit

A 24-year-old man presented to the Chris Hani Baragwanath Academic Hospital emergency department with recurrent seizures having previously been diagnosed with epilepsy from age 14. The biochemical investigations and brain imaging were suggestive of seizures secondary to hypocalcemia, and a diagnosis of idiopathic hypoparathyroidism was confirmed. After calcium and vitamin D replacement, the patient recovered well and is seizure free, and off antiepileptic therapy. This case highlights the occurrence of brain calcinosis in idiopathic hypoparathyroidism; the occurrence of acute symptomatic seizures due to provoking factors other than epilepsy; and the importance, in the correct clinical setting, of considering alternative, and sometimes treatable, causes of seizures other than epilepsy.

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Relationship between High Temperature and Formation of Chalkiness and Their Effects on Quality of Rice

Occurrence of chalkiness in rice is attributed to genetic and environmental factors, especially high temperature (HT). The HT induces heat stress, which in turn compromises many grain qualities, especially transparency. Chalkiness in rice is commonly studied together with other quality traits such as amylose content, gel consistency, and protein storage. In addition to the fundamental QTLs, some other QTLs have been identified which accelerate chalkiness occurrence under HT condition. In this review, some of the relatively stable chalkiness, amylose content, and gel consistency related QTLs have been presented well. Genetically, HT effect on chalkiness is explained by the location of certain chalkiness gene in the vicinity of high-temperature-responsive genes. With regard to stable QTL distribution and availability of potential material resources, there is still feasibility to find out novel stable QTLs related to chalkiness under HT condition. A better understanding of those achievements is essential to develop new rice varieties with a reduced chalky grain percentage. Therefore, we propose the pyramiding of relatively stable and nonallelic QTLs controlling low chalkiness endosperm into adaptable rice varieties as pragmatic approach to mitigate HT effect.

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Biomaterial Scaffolds in Regenerative Therapy of the Central Nervous System

The central nervous system (CNS) is the most important section of the nervous system as it regulates the function of various organs. Injury to the CNS causes impairment of neurological functions in corresponding sites and further leads to long-term patient disability. CNS regeneration is difficult because of its poor response to treatment and, to date, no effective therapies have been found to rectify CNS injuries. Biomaterial scaffolds have been applied with promising results in regeneration medicine. They also show great potential in CNS regeneration for tissue repair and functional recovery. Biomaterial scaffolds are applied in CNS regeneration predominantly as hydrogels and biodegradable scaffolds. They can act as cellular supportive scaffolds to facilitate cell infiltration and proliferation. They can also be combined with cell therapy to repair CNS injury. This review discusses the categories and progression of the biomaterial scaffolds that are applied in CNS regeneration.

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