Sunday, January 29, 2023

Role of non‐coding RNAs with emphasis on long non‐coding RNAs as cervical cancer biomarkers

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Abstract

Cervical cancer is a significant public health problem in developing countries, as most cases present at an advanced stage. This review aimed to analyze the role of non-coding RNAs as diagnostic and prognostic biomarkers in cervical cancers. Published studies on specific microRNA signatures in body fluids and cervical cancer tissues are highly heterogeneous, and there are no validated assays. The precision of the various immune-associated lncRNA signatures should be assessed in clinical samples. Even though lncRNAs are tissue and cancer-specific, safe and appropriate methods for delivery to tumor tissues, toxicities and side effects are to be explored. Few studies have evaluated deregulated lncRNA expression levels with clinicopathological factors in a limited number of clinical samples. Prospective studies assessing the diagnostic and prognostic roles of circulating lncRNAs and P-Element-induced wimpy testis interacting PIWI RNAs (Piwil RNAs) in cervical ca ncer cases are essential. For the clinical application of lnc-RNA-based biomarkers, comprehensive research is needed as the impact of non-coding transcripts on molecular pathways is complex. The standardization and validation of deregulated ncRNAs in non-invasive samples of cervical cancer cases are needed.

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Novel Murine Glioblastoma Models That Reflect the Immunotherapy Resistance Profile of Human Disease

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Abstract
Background
The lack of murine glioblastoma models that mimic the immunobiology of human disease has impeded basic and translational immunology research. We therefore developed murine glioblastoma stem cell lines derived from Nestin-CreERT2QkL/L; Trp53L/L; PtenL/L (QPP) mice driven by clinically relevant genetic mutations common in human glioblastoma. This study aims to determine the immune sensitivities of these QPP lines in immunocompetent hosts and underlying mechanisms.
Methods
The differential responsiveness of QPP lines was assessed in the brain and flank in untreat ed, anti-PD-1, or anti-CTLA-4 treated mice. The impact of genomic landscape on responsiveness of each tumor was measured through whole exome sequencing. The immune microenvironments of sensitive (QPP7) versus resistant (QPP8) lines were compared in the brain using flow cytometry. Drivers of flank sensitivity versus brain resistance were also measured for QPP8.
Results
QPP lines are syngeneic to C57BL/6J mice and demonstrate varied sensitivities to T cell immune checkpoint blockade ranging from curative responses to complete resistance. Infiltrating tumor immune analysis of QPP8 reveals improved T cell fitness and augmented effector to suppressor ratios when implanted subcutaneously (sensitive), which are absent upon implantation in the brain (resistant). Upregulation of PD-L1 across the myeloid stroma acts to establish this state of immune privilege in the brain. In contrast, QPP7 responds to checkpoint immunotherapy even in the brain likely resulting from its elevated neoa ntigen burden.
Conclusions
These syngeneic QPP models of glioblastoma demonstrate clinically-relevant profiles of immunotherapeutic sensitivity and potential utility for both mechanistic discovery and evaluation of immune therapies.
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Immunological efficacy of pneumococcal vaccination including the 13-valent pneumococcal vaccine in adult patients with sickle-cell disease: results of the randomized DREVAC controlled trial

alexandrossfakianakis shared this article with you from Inoreader
Abstract
Background
Patients with sickle-cell disease (SCD) are at high risk for invasive pneumococcal diseases. The immunological efficacy of 13-valent conjugate pneumococcal vaccine (PCV13) followed by a 23-valent polysaccharide vaccine (PPSV23) is poorly documented in adults with SCD.
Methods
This was a randomized open-labelled phase 2 study of the immunogenicity of PCV13 at week (W)0, followed by PPSV23 at W4, compared to PPSV23 alone at W4 in adult patients with SCD. The proportion of responders (four-fold increase of serotype-specific IgG antibodies) to at least 10-shared serotypes was assessed at W8. Secondary endpoints were: i) geometrical mean titers (GMTs), ii) responders to 0-1, 2-5, 6-9, and 10-12 serotypes, iii) pneumococcal opsonophagocytic (OPA) activity, and iv) response durability at W24 and W96.
Results
In total, 128 patients were randomized in the PCV13/PPSV23 (n=63) or PPSV23-alone groups (n=65). At W8, 24.5 6% and 8.20% of patients from the PCV13/PPSV23 and PPSV23 groups, respectively, reached the primary endpoint (p=0.016). These numbers were 36.2% and 8.7% for OPA responders (p=0.002). A combined PCV13/PPSV23 strategy improved the breadth of responses to 0-1, 2-5, 6-9, and 10-12 serotypes with 15.8%, 35%, 24.6%, and 24.6% versus 52.5%, 31%, 8%, and 8% in the PPSV23 group. At W96, GMTs were significantly higher in the PCV13/PPSV23 than in the PPSV23 alone group for five serotypes (4, 14, 19A, 19F, 23F).
Conclusions
A PCV13/PPSV23 regimen improved the breadth and magnitude of antibody responses against a large range of pneumococcal serotypes in adults with SCD. The sustainability of the immune response requires recall strategies.Clinical Trial Registration: NCT02274415
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68Ga-DOTA.SA.FAPI as a Potential, Noninvasive Diagnostic Probe for Recurrent and Metastatic Adrenocortical Carcinoma: A Head-to-Head Comparison With: 18: F-FDG

alexandrossfakianakis shared this article with you from Inoreader
imageMetastatic or recurrent adrenocortical carcinoma (ACC) is a potentially fatal malignancy, which poses major challenges in disease management owing to lack of effective systemic therapies. The drastically reduced survival rates require prompt identification of selective molecules for development of targeted therapeutics. We evaluated the squaric acid containing FAPI derivative, DOTA.SA.FAPI (FAPI), as a potential diagnostic probe in 2 cases of histopathologically proven metastatic and recurrent ACC. Both patients underwent 18F-FDG and 68Ga-FAPI PET/CT scans for comparative analysis. 68Ga-DOTA.SA.FAPI emerged as an excellen t diagnostic agent for ACC and performed similar to 18F-FDG.
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Clinical Impact of SPECT/CT in Evaluation of Abdominothoracic Fistula

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imageAbdominothoracic fistula is rarely observed but can be life-threatening. Pleuroperitoneal communication, known to occur in 1.6% of all patients who undergo continuous ambulatory peritoneal dialysis, is an uncommon but well-recognized complication. The most common symptoms are dyspnea and right-sided pleural effusion. A biliopleural fistula is well-described as a complication of radiofrequency ablation and transcatheter arterial chemoembolization of hepatic lesions. It is important to diagnose the cause of pleural effusion early for proper treatment because if the abdominothoracic fistula effusion amount is not large, appro priate diagnosis may be difficult. Here, we introduce 2 cases showing the usefulness of SPECT/CT in evaluating pleuroperitoneal and biliopleural fistulas.
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18F-THK5351 PET Can Evaluate Tumor Extension in Intravascular Large B-Cell Lymphoma: Comparison With: 11: C-Methionine PET and: 18: F-FDG PET

alexandrossfakianakis shared this article with you from Inoreader
imageA 79-year-old man presenting with gait disturbance and cognitive decline was diagnosed with intravascular large B-cell lymphoma (IVLBCL) by random skin biopsy. Some IVLBCL lesions were identified by PET examinations using 11C-methionine, 18F-FDG, and 18F-THK5351. 11C-methionine and 18F-FDG uptake, which likely reflects the presence of the lymphoma cells themselves, increased clearly in the left putamen but weakly in the left deep white matter. 18F-THK5351 uptake increased in all lesions, likely reflecting perivascular astrogliosis caused by IVLBCL. Hence, 18F-THK5351 PET can evaluate tumor extension in IVLBCL lesions wh ere 11C-methionine and 18F-FDG PET may fail in its visualization.
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Bone Scan With Pulmonary Uptake in Scleroderma

alexandrossfakianakis shared this article with you from Inoreader
imageWe present a 61-year-old woman with a history of scleroderma and suspicion of osteomyelitis in her left wrist. She underwent a 3-phase bone scan for evaluation of osteomyelitis. Incidentally, the scan showed bilateral pulmonary MDP uptake, especially in lower lobes, which was proven to be due to the nonfibrotic form of nonspecific interstitial pneumonia.
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Interesting Findings in 68Ga-FAPI-46 PET/CT Imaging in a Patient With Glioblastoma Multiforme

alexandrossfakianakis shared this article with you from Inoreader
imageA 55-year-old disabled man with glioblastoma multiforme was referred to us for fibroblast activation protein inhibitor (FAPI) PET/CT imaging. 68Ga-DOTA-FAPI-46 scan revealed uptake in the primary tumor and unexpected uptakes in soft tissue, especially in periarticular regions. These latter foci were compatible with calcifications on the CT. One in the breast was compatible with fibrotic tissue, but 2 other foci, in the rectus abdominis and gallbladder wall, could not be correlated with the CT findings. In Neurogenic heterotopic ossification, hypoxia-associated oxidative stress results in the metaplastic transformation of fi broblasts. Abnormal differentiation of fibroblasts in neurogenic heterotopic ossification before ossification could explain radiolabeled FAPI avidity in the mentioned areas.
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Transmission of Mpox: A narrative review of environmental, viral, host and population factors in relation to the 2022 international outbreak

alexandrossfakianakis shared this article with you from Inoreader

Abstract

Monkeypox virus (mpox) has spread globally. Emerging studies have now provided evidence regarding mpox transmission, that can inform rational evidence-based polices and reduce misinformation on this topic. We aimed to review the evidence on transmission of the virus. Real-world studies have isolated viable virus from high touch surfaces for as long as 15 days. Strong evidence suggests that current circulating monkeypox has evolved from previous outbreaks outside of Africa, but it is yet unknown whether these mutations may lead to an inherently increased infectivity of the virus. Strong evidence also suggests that the main route of current mkeypox transmission is sexual; through either close contact or directly, with detection of culturable virus in saliva, nasopharynx and sperm for prolonged periods and the presence of rashes mainly in genital areas. The milder clinical presentations and potential presence of presymptomatic transmission in the current circulating variant compared to previous clades, as well as the dominance of spread amongst men who have sex with men (MSMs) suggests that mpox has a developed distinct clinical phenotype that has increased its transmissibility. Increased public awareness of mpox transmission modalities may lead to earliar detection of the spillover of new cases into other groups.

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Molecular evolution of the human monkeypox virus

alexandrossfakianakis shared this article with you from Inoreader

ABSTRACT

Background

Recently, in 2022, new cases of human monkeypox virus (hMPXV) occurred in Europe and North America. The first case was reported in Europe in May 2022, and subsequently, more than 50,000 new cases were confirmed in 100 countries. Currently, the classification of hMPXV according to the nextstrain occurs in five big clades (1A, A.1, A.2, A.1.1, and B.1).

Aims

According to the resurgence of smallpox-like disease caused by hMPXV and the spread of the virus to the European and American continents, in the present study, we review and summarize the molecular evolution of the hMPXV, determining the molecular evolution of the main clades.

Methods

A total of 442 hMPXV whole-genome sequences (WGS) with available information from the country and sampling date (between October 2017 and 2022), were obtained and evaluated using the Bayesian method.

Results

The clade B.1 which is currently circulating was the most frequent (n=415; 93.9%). The other clades presented the following frequencies: 1A (n=13; 2.9%), A.1 (n=10; 2.3%), A.2 (n=3; 0.7%) and A.1.1 (n=1; 0.2%) The overall nucleotide divergence of hMPXV was 5,590e-5. The 1A clade was detected between 2017 and 2020. A.1 was observed, and between 2019 and 2022 some A.2 sequences were detected. In 2022, the great predominance of B.1 was observed. The common ancestor of the hMPXV belongs to the clade 1A and the time to the Most Recent Common Ancestor (tMRCA) was 2017-04-04 (Highest Posterior Density 95% (HPD95%): 2017-03-09; 2017-08-04) on the West African continent. The tMRCA of A.1 was 2018-05-21 (HPD95%: 2018-05-20; 2018-07-04) with divergence of 6.885e-5 substitutions per site per year (ssy). This clade was of West African origin but was eventually detected in European countries. Also, A.2 was detected with sequences of North America and showed tMRCA of 2019-07-15 (HPD95%: 2018-11- 18; 2020-02-24). A.1.1 showed tMRCA from 2021-06-05 (HPD95%: 2021-06-05; 2021-11-26) and this clade was detected in North America and was the precursor for the globally spreading B.1 which tMRCA was 2022-04-26 (HPD95%: 2022-02-27; 2022-04-26). hMPXV has been spread from West Africa to the United Kingdom, Israel, Singapore, the USA, Canada, Portugal, Spain, Ireland, France, Belgium, the Netherlands, Switzerland, Germany, Italy, Slovenia, Austria, the Republic Czech, Sweden, and Finland. hMPXV also reached countries such as Brazil, Mexico, Australia, and Taiwan.

Conclusion

The common ancestor of the hMPXV belongs to the clade 1A with origin in the West African continent. Clade B.1 was responsible for the recent widespread worldwide. Immunization to prevent the spread of hMPXV is not yet available to the public, future studies should focus on the development of effective vaccines to contain the spread of this virus.

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