Systematic review of epigenetic targets in acute myeloid leukemia

xlomafota13 shared this article with you from Inoreader Systematic review of epigenetic targets in acute myeloid leukemia Via American Journal of Blood Research Am J Blood Res. 2021 Oct 15;11(5):458-471. eCollection 2021. ABSTRACT Acute myeloid leukemia (AML), although genetically and morphologically distinct from other B and T cell ALL subtypes, has one of the most rapidly progressing course and worse outcomes. The current diagnostic classification of AML offers best curative intent, the outcomes are not usually those that are expected at the start of therapy. This is partly attributed to the complex mechanism of leukemogenesis and resistance to chemotherapy. The underlying genetic mechanism of resistance is as complex as is the disease etiopathogenesis. Recent advances in therapy of drug resistant AML highlight the role of epigenetic targets. New FDA approved targeted therapy has also provided some evidence at improving outcomes in clinical trials. This review provides a detailed review of FDA approved targets and ongoing clinical trials for targeting CRISPER, CAR-T and other intestinal moda lities for approach to epigenetictargets. However, this group of epigenetic targeted therapy needs more validation to prove its clinical efficacy. A systematic review of all published research on these targets, investigational agents and FDA approved targeted therapy summarizes this evidence. It also takes us through a brief review of mechanism of action and targets for therapy. PMID:34824880 | PMC:PMC8610793 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

An experience with 124 cases of fanconi anemia: clinical spectrum, hematological parameters and chromosomal breakage analysis

xlomafota13 shared this article with you from Inoreader An experience with 124 cases of fanconi anemia: clinical spectrum, hematological parameters and chromosomal breakage analysis Via American Journal of Blood Research Am J Blood Res. 2021 Oct 15;11(5):498-503. eCollection 2021. ABSTRACT BACKGROUND: Fanconi anemia is an inherited bone marrow failure syndrome characterized by somatic abnormalities and an increased predisposition to malignancies. OBJECTIVE: To determine the clinical spectrum and evaluate the hematological parameters as well as highlight diagnosis by chromosomal breakage analysis of Fanconi anemia patients. MATERIAL AND METHODS: A total of 124 patients were diagnosed as having Fanconi anemia from August 2014 to May 2020 at Armed Forces Institute of Pathology, Rawalpindi, Pakistan. Clinical details, somatic abnormalities, radiological findings, lab parameters and result of chromosomal breakage analysis were noted and analyzed. RESULTS: One hundred and twenty four (14.29%) were diagnosed as having Fanconi anemia (FA) on chromosomal breakage test. Median age was 09 years 06 months. Male to female ratio was 1.9:1. Six of t hese patients exhibited mosaicism and were classified as FA mosaic. Somatic abnormalities were detected in 74 (59.7%) patients; the most common being skeletal abnormalities and short stature. CONCLUSION: Chromosomal breakage analysis is a cost-effective method for diagnosis of Fanconi anemia. Early diagnosis is pertinent for proper treatment and long term prognosis. PMID:34824882 | PMC:PMC8610795 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Regulatory noncoding RNAs: potential biomarkers and therapeutic targets in acute myeloid leukemia

xlomafota13 shared this article with you from Inoreader Regulatory noncoding RNAs: potential biomarkers and therapeutic targets in acute myeloid leukemia Via American Journal of Blood Research Am J Blood Res. 2021 Oct 15;11(5):504-519. eCollection 2021. ABSTRACT The noncoding RNAs (ncRNA) comprise a substantial segment of the human transcriptome and have emerged as key elements of cellular homeostasis and disease pathogenesis. Dysregulation of these ncRNAs by alterations in the primary RNA motifs and/or aberrant expression levels is relevant in various diseases, especially cancer. The recent research advances indicate that ncRNAs regulate vital oncogenic processes, including hematopoietic cell differentiation, proliferation, apoptosis, migration, and angiogenesis. The ever-expanding role of ncRNAs in cancer progression and metastasis has sparked interest as potential diagnostic and prognostic biomarkers in acute myeloid leukemia. Moreover, advances in antisense oligonucleotide technologies and pharmacologic discoveries of small molecule inhibitors in targeting RNA structures and RNA-protein complexes have opened newer avenue s that may help develop the next generation anti-cancer therapeutics. In this review, we have discussed the role of ncRNA in acute myeloid leukemia and their utility as potential biomarkers and therapeutic targets. PMID:34824883 | PMC:PMC8610797 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Impact of G-CSF administration post-allogeneic hematopoietic stem-cell transplantation on outcomes: a systematic review and meta-analysis

xlomafota13 shared this article with you from Inoreader Impact of G-CSF administration post-allogeneic hematopoietic stem-cell transplantation on outcomes: a systematic review and meta-analysis Via American Journal of Blood Research Am J Blood Res. 2021 Oct 15;11(5):544-563. eCollection 2021. ABSTRACT Granulocyte colony-stimulating factors (G-CSFs) have been used post hematopoietic stem cell transplant (HSCT) for earlier neutrophil engraftment. The use of G-CSFs, and their effect on other post-HSCT outcomes remains debatable. In this systematic review and meta-analysis, we searched PubMed, Embase, Cochrane library, Google Scholar, and IndMed using a predefined search strategy. We included randomized controlled trials (RCTs) and non-randomized studies (NRSs) reporting data on G-CSF administration post-HSCT, published in the English language from their inception until Jan 31, 2021. The primary outcome of this systematic review and meta-analysis was to evaluate the time to neutrophil engraftment (NE). The secondary outcomes were probability of NE, time to platelet engraftment (PE), the incidence of graft-versus-host disease (GVHD), duration of hospital stay (HS), and overall survival (OS). The review is registered with PROSPERO (CRD42020206989). Fourteen studies were extracted (n=9850), of which five were RCTs, and nine were NRSs. As per Egger's test, publication bias was not present for any outcome. After meta-analysis, we found that the duration of NE favouring G-CSF arm from RCTs was -0.94 days (SMD) [(95% CI: -1.38, -0.51); I2=35%], and from NRSs -1.2 days (SMD) [(95% CI: -1.43, -0.96); I2=74%]. For the outcome of GVHD, the relative risks (RR) of incidence for chronic GVHD and overall GVHD were not significant for the RCTs, and these were 1.11 (RR) [(95% CI: 1.00, 1.22); I2=43%] and 1.10 (RR) [(95% CI: 1.03, 1.18); I2=48%], respectively for NRSs. There was no difference in the incidence of GVHD (acute or chronic) in both arms. No significant difference was found between the two arms for the outcomes of PE, HS, and OS. For NE, there was a marginal benefit of around one day with the use of G-CSF. Th e use of G-CSF did not alter time to PE, the incidence of GVHD, HS, and OS in both arms. PMID:34824887 | PMC:PMC8610798 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Intensity‐modulated proton radiation therapy as a radical treatment modality for nasopharyngeal carcinoma in China: A cost‐effectiveness analysis

xlomafota13 shared this article with you from Inoreader Intensity‐modulated proton radiation therapy as a radical treatment modality for nasopharyngeal carcinoma in China: A cost‐effectiveness analysis Via Head & Neck Abstract Background Compared to conventional intensity-modulated photon radiation therapy (IMRT), intensity-modulated proton radiation therapy (IMPT) has potential to reduce irradiation-induced late toxicities while maintaining excellent tumor control in patients with nasopharyngeal carcinoma (NPC). However, the relevant cost-effectiveness remains controversial. Methods A Markov decision tree analysis was performed under the assumption that IMPT offered normal tissue complication probability reduction (NTCP reduction) in long-term dysphagia, xerostomia, and hearing loss, compared to IMRT. Base-case evaluation was performed on T2N2M0 NPC of median age (43 years old). A Chinese societal willingness-to-pay threshold (33558 US dollars [$])/quality-adjusted life-year [QALY]) was adopted. Results For patients at median age and having NTCP reduction of 10%, 20%, 30%, 40%, 50%, and 60%, their incremental cost-effectiveness ratios were $102684.0/QALY, $43161.2/QALY, $24134.7/QALY, $13991.6/QALY, $8259.8/QALY, and $4436.1/QALY, respectively; IMPT should provide an NTCP reduction of ≥24% to be considered cost-effective. Conclusions IMPT has potential to be cost-effective for average Chinese NPC patients and should be validated clinically. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

The Insula: A Stimulating Island of the Brain

xlomafota13 shared this article with you from Inoreader The Insula: A Stimulating Island of the Brain Via cortical auditory Brain Sci. 2021 Nov 19;11(11):1533. doi: 10.3390/brainsci11111533. ABSTRACT Direct cortical stimulation (DCS) in epilepsy surgery patients has a long history of functional brain mapping and seizure triggering. Here, we review its findings when applied to the insula in order to map the insular functions, evaluate its local and distant connections, and trigger seizures. Clinical responses to insular DCS are frequent and diverse, showing a partial segregation with spatial overlap, including a posterior somatosensory, auditory, and vestibular part, a central olfactory-gustatory region, and an anterior visceral and cognitive-emotional portion. The study of cortico-cortical evoked potentials (CCEPs) has shown that the anterior (resp. posterior) insula has a higher connectivity rate with itself than with the posterior (resp. anterior) insula, and that both the anterior and posterior insula are closely connected, notably between the homologous insula r subdivisions. All insular gyri show extensive and complex ipsilateral and contralateral extra-insular connections, more anteriorly for the anterior insula and more posteriorly for the posterior insula. As a rule, CCEPs propagate first and with a higher probability around the insular DCS site, then to the homologous region, and later to more distal regions with fast cortico-cortical axonal conduction delays. Seizures elicited by insular DCS have rarely been specifically studied, but their rate does not seem to differ from those of other DCS studies. They are mainly provoked from the insular seizure onset zone but can also be triggered by stimulating intra- and extra-insular early propagation zones. Overall, in line with the neuroimaging studies, insular DCS studies converge on the view that the insula is a multimodal functional hub with a fast propagation of information, whose organization helps understand where insular seizures start and how they propagate. PMID:34827532 | DOI:10.3390/brainsci11111533 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Audiovestibular Symptoms in Patients With Idiopathic Hypertrophic Pachymeningitis: Systematic Literature Review

xlomafota13 shared this article with you from Inoreader Audiovestibular Symptoms in Patients With Idiopathic Hypertrophic Pachymeningitis: Systematic Literature Review Via Acta Otorrinolaringologica English Publication date: November–December 2021 Source: Acta Otorrinolaringologica (English Edition), Volume 72, Issue 6 Author(s): Eugenia López-Simón, Patricia Corriols-Noval, Nathalia Castillo-Ledesma, Minerva Rodríguez-Martín, Carmelo Morales-Angulo View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.