Search results for "Rare Disease"
showing 10 items of 154 documents
CRISPR-Cas9 screen reveals a MYCN-amplified neuroblastoma dependency on EZH2.
2018
Pharmacologically difficult targets, such as MYC transcription factors, represent a major challenge in cancer therapy. For the childhood cancer neuroblastoma, amplification of the oncogene MYCN is associated with high-risk disease and poor prognosis. Here, we deployed genome-scale CRISPR-Cas9 screening of MYCN-amplified neuroblastoma and found a preferential dependency on genes encoding the polycomb repressive complex 2 (PRC2) components EZH2, EED, and SUZ12. Genetic and pharmacological suppression of EZH2 inhibited neuroblastoma growth in vitro and in vivo. Moreover, compared with neuroblastomas without MYCN amplification, MYCN-amplified neuroblastomas expressed higher levels of EZH2. ChIP…
“Puffy hand syndrome”
2016
Resume La toxicomanie intraveineuse est responsable de nombreuses complications notamment cutanees et infectieuses. Il existe un syndrome rarement observe en rhumatologie se traduisant par des « grosses mains » : le puffy hand syndrome. Nous en rapportons deux cas rencontres en consultation de rhumatologie chez deux patients toxicomanes. Il s’agit d’un œdeme des mains, bilateral, indolore, ne prenant pas le godet, survenant chez un de nos patients pendant l’intoxication par heroine, et chez l’autre 2 ans apres avoir arrete ses injections. Chez nos deux patients les bilans complementaires (biologiques, radiologiques, echographiques) etaient sans particularite, ce qui a permis dans le context…
Isolated osteoblastoma of the cuboid bone: A case report and review of the literature
2020
Osteoblastoma is a relatively rare, benign, bone-forming tumor, commonly observed in the second and third decades of life. Spine and the long tubular bones are the most common sites of involvement. Osteoblastoma is infrequently seen in other sites, including the bones of hand and foot. A rare case of a 35-year-old man that presented an osteoblastoma of the cuboid bone is reported. The patient was treated with surgical resection and grafting. After the intervention, the patient recovered with no clinical and radiological evidence of recurrence after one year of follow-up. Several cases of osteoblastoma-like variant of osteosarcoma of the cuboid have been previously reported, but, to our know…
Truncating mutations in the last exon of NOTCH2 cause a rare skeletal disorder with osteoporosis.
2010
Hajdu-Cheney syndrome is a rare autosomal dominant skeletal disorder with facial anomalies, osteoporosis and acro-osteolysis. We sequenced the exomes of six unrelated individuals with this syndrome and identified heterozygous nonsense and frameshift mutations in NOTCH2 in five of them. All mutations cluster to the last coding exon of the gene, suggesting that the mutant mRNA products escape nonsense-mediated decay and that the resulting truncated NOTCH2 proteins act in a gain-of-function manner.
Associations of ofatumumab exposure and treatment outcomes in patients with untreated CLL receiving chemoimmunotherapy
2016
Relationships between patient characteristics, ofatumumab pharmacokinetics, and treatment outcomes were investigated in this phase 2 trial of ofatumumab plus fludarabine and cyclophosphamide (FC) in untreated chronic lymphocytic leukemia. Patients were randomized 1:1 to receive 500 or 1000 mg ofatumumab (Cycle 1; 300 mg) plus FC every 4 weeks for six cycles. Median C(max) and C(trough) values were similar at Cycle 1 regardless of the ultimate clinical outcome. At later doses, these values were higher for patients with complete response (CR) than for other patients. Higher C(max) and C(trough) values at Cycles 3 and 6 were significantly associated with an increased likelihood of CR, whereas …
The Challenges of the European Anorectal Malformations-Net Registry
2015
Item does not contain fulltext Anorectal malformations (ARM) have a low prevalence, patients need specialized surgical care, and in many cases, patients born with ARM even need life-long aftercare. Due to its low prevalence most patients are still treated in low-volume pediatric surgical centers without any adequate monitoring of the outcome. Data on prevalence, comparison of different surgical techniques, and prospective outcome measurements are still scarce and difficult to interpret. In 2010, a consortium was founded (ARM-Net consortium) including several European pediatric surgical centers to collaborate more in research and share knowledge on ARM. One of the structures started by the c…
The genomic landscape of the Ewing Sarcoma family of tumors reveals recurrent STAG2 mutation.
2014
The Ewing sarcoma family of tumors (EFT) is a group of highly malignant small round blue cell tumors occurring in children and young adults. We report here the largest genomic survey to date of 101 EFT (65 tumors and 36 cell lines). Using a combination of whole genome sequencing and targeted sequencing approaches, we discover that EFT has a very low mutational burden (0.15 mutations/Mb) but frequent deleterious mutations in the cohesin complex subunit STAG2 (21.5% tumors, 44.4% cell lines), homozygous deletion of CDKN2A (13.8% and 50%) and mutations of TP53 (6.2% and 71.9%). We additionally note an increased prevalence of the BRCA2 K3326X polymorphism in EFT patient samples (7.3%) compared …
A Modification of Stone's Test for Trend for Binary Outcome
1998
STONE (1988) suggested the first isotonic regression estimator as a tool for drawing inferences on possibly increased cancer case counts among several subregions around a putative source. He assumed the case counts to be Poisson distributed and therefore introduced a rare disease assumption into his approach. However, when analyzing cross sectional data one would rather refer to prevalence estimates among these subregions around a point risk source (for example the origin of chemical fallout). Therefore we applied antitonic regression estimation in Binomial distributions to derive a test statistic and a p value to test for a possible trend in the observed prevalence data around the putative…
Fluorescent in situ hybridization (FISH): A useful diagnostic tool for childhood conjunctival melanoma
2021
Introduction: Conjunctival melanoma is extremely rare in children and has low rates of resolution. Definitive histopathological diagnosis based exclusively on microscopic findings is sometimes difficult. Thus, early diagnosis and adequate treatment are essential to improve clinical outcomes. Clinical case: We present the first case in which the fluorescent in situ hybridization (FISH) diagnostic technique was applied to a 10-year-old boy initially suspected of having amelanotic nevi in his right eye. Based on the 65% of tumor cells with 11q13 (CCND1) copy number gain and 33% with 6p25 (RREB1) gain as measured by the FISH analysis, and on supporting histopathological findings, the diagnosis …
Langerhans cell histiocytosis with oral manifestations: a rare and unusual case report
2012
Langerhans cell histiocytosis (LCH), is a rare, proliferative disorder in which the accumulation of pathologic Langerhans cells leads to local tissue infiltration and destruction. We present a case of a 32 years old, completely edentulous female patient who presented with erythema of hard palate, maxillary alveolar mucosa and mucosa over the distobuccal part of mandibular alveolar ridge with foci of ulcerations. Histopathologic features were suggestive of LCH which was confirmed by immunohistochemistry which was CD1a positive, confirmatory for LCH. Bone scan revealed multiple bone involvement. At this stage, disease had already progressed to multisystem involvement with endocrinal abnormali…