China
Africa
Explore chapters and articles related to this topic
Werner Syndrome
Published in Dongyou Liu, Handbook of Tumor Syndromes, 2020
Differential diagnoses for Werner syndrome include atypical Werner syndrome (early age of onset at early 20s or earlier, faster rate of progression; normal WRN proteins, heterozygous pathogenic missense variants in LMNA in 15% of cases), mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome (MDPL; progeroid features, lipodystrophy, characteristic facial features, sensorineural hearing loss; absence of ocular cataracts), mandibulo-acral dysplasia (MAD; short stature, type A lipodystrophy, loss of fat in the extremities but accumulation of fat in the neck and trunk, thin, hyperpigmented skin, partial alopecia, prominent eyes, convex nasal ridge, tooth loss, micrognathia, retrognathia, and short fingers; biallelic pathogenic variants in LMNA, and zinc metalloproteinase ZMPSTE24), Hutchinson−Gilford progeria syndrome (HGPS, progeria of childhood; accelerated aging, profound failure to thrive during the first year, characteristic facies, partial alopecia progressing to total alopecia, loss of subcutaneous fat, progressive joint contractures, bone changes, abnormal tightness and/or small soft outpouchings of the skin over the abdomen and upper thighs during the second to third year; severe atherosclerosis; death due to cardiac or cerebrovascular disease between age 6 and 20 years; average life span of approximately 14.6 years; autosomal dominant disorder due to LMNA pathogenic variant c.1824C>T), early-onset type 2 diabetes with secondary complications (mimicking some features of Werner syndrome), myotonic dystrophy type 1 or myotonic dystrophy type 2 (young adult-onset cataracts, muscle wasting in adults), scleroderma, mixed connective tissue disorders, and lipodystrophy (similar skin features), Charcot−Marie−tooth hereditary neuropathy or familial leg ulcers of juvenile onset (distal atrophy and skin ulcerations in the absence of other manifestations characteristic of Werner syndrome), Rothmund−Thomson syndrome (RTS; autosomal recessive disorder due to pathogenic variants in RECQL4), BLM (increased sister chromatid exchange; autosomal recessive disorder due to pathogenic variants in BLM), Li−Fraumeni syndrome (multiple cancers, absence of juvenile-onset cataracts, autosomal dominant disorder due to pathogenic variants in TP53), Flynn−Aird syndrome (cataracts, skin atrophy and ulceration; neurologic abnormalities), brachiooculofacial syndrome (premature graying in adults; strabismus, coloboma, and microphthalmia; dysmorphic facial features; autosomal dominant disorder due to TFAP2A pathogenic variants), SHORT syndrome (short stature, hyperextensibility, hernia, ocular depression, Rieger anomaly, and teething delay; progeria-like facies and lipodystrophy, type 2 diabetes mellitus, cataracts and glaucoma; autosomal dominant disorder due to pathogenic variants in PIK3R1 [1,18,19].
Understanding host responses to equine encephalitis virus infection: implications for therapeutic development
Published in Expert Review of Anti-infective Therapy, 2022
Kylene Kehn-Hall, Steven B. Bradfute
A recent VEEV nsP3 interactome study identified 160 putative host interacting proteins, including eukaryotic initiation factor 2 subunit 2 (eIF2S2) and transcription factor AP-2 alpha (TFAP2A) which were validated for their importance in VEEV production through siRNA studies [83]. eIF2S2 was found to facilitate VEEV genomic RNA translation, but not translation of the subgenomic RNA [83]. Citalopram HBr and Z-VEID-FMK, inhibitors of TFAP2A, and Tomatidine, a small molecule inhibitor of eIF2S2, decreased VEEV production by >10 fold. Citalopram HBr, Z-VEID-FMK, and Tomatidine also suppressed EEEV replication.
Epigenetic biomarkers in colorectal cancer: premises and prospects
Published in Biomarkers, 2018
Mozhdeh Zamani, Seyed Vahid Hosseini, Pooneh Mokarram
Current chemotherapy drugs are suboptimal due to innate or acquired resistance and modest efficacy. In order to overcome these limitations and maximize the overall success of treatment with these chemotherapeutic agents, predictive biomarkers are required to identify low or high likelihoods of a response to specific drugs in patients (Okugawa et al.2015). A number of genes with aberrant methylation status have been suggested to apply as potential predictive biomarkers in CRC patients under treatment with different chemotherapeutic regimens. It has been demonstrated that hypermethylation of TFAP2A (Ebert et al.2012) and miR-148a (Takahashi et al.2012) results in resistance to 5-FU based chemotherapy and poor overall survival. Hypermethylated SRBC leads to resistance to Oxaliplatin-based chemotherapy (Moutinho et al.2014). MGMT hypermethylation also correlates with dacarbazine treatment benefit and non-recurrence after treatment with oral fluoropyrimidines (Nagasaka et al.2003, Amatu et al.2013). As mentioned in Table 1, in the most recent study, Pfütze et al. proposed that HYAL2 hypomethylation correlates with 5-FU treatment benefit (Pfütze et al.2015). It has also been reported that MGMT hypermethylation leads to better response to alkylating agents (Barault et al.2015) and decreased PKCΒ expression as frequent methylation induces no response to enzastaurin (a PKCΒ inhibitor) (Szmida et al.2015). Although Scartozzi et al. (2011) have demonstrated a significant association between EGFR methylation and resistance to Cetuximab-based chemotherapy in CRC patients, conversely, in a recent study by Chiadini et al. (2015) revealed that EGFR methylation leads to an improved response and overall survival rate in patients treated with Cetuximab-based chemotherapy. Further investigations are needed to verify the applicability of these new proposed markers. Most of the conducted studies related to potential biomarkers are retrospective. Therefore, to deal with challenges of clinical application of these biomarkers, prospective cohort studies and randomized control trials are inevitable to confirm new diagnostic, prognostic and predictive biomarkers for CRC. For this purpose, it is challenging to find large numbers of well-defined patients cohorts. Follow-up studies should also be performed after the discovery phase to eliminate the gap between discovery and clinical translation. Technical challenges are limited due to the emergence of new techniques such as high throughput sequencing and bead arrays. Furthermore, highly sensitive and reproducible techniques like pyrosequencing and methyl light are able to design clinical assays (Lam et al.2016).