Bartlett, AL; Leslie, ND; Gupta, A; Geller, JI. Acquired ornithine transcarbamylase deficiency in pediatric and adolescent patients with fibrolamellar hepatocellular carcinoma. Pediatric Blood and Cancer. 2018; 65(12):1510-1517.
Ornithine transcarbamylase deficiency (OTCD) disrupts the metabolic pathway responsible for converting nitrogenous waste to urea, allowing for excretion. When impaired, ammonia levels accumulate in the blood resulting in severe, sometimes life-threatening toxicities. Abnormalities of the urea cycle are often inherited, though there are some rarer acquired forms. We describe two cases of acquired OTCD in pediatric patients with fibrolamellar hepatocellular carcinoma (FL-HCC). We detail its presentation and management, explore potential underlying pathophysiology, and propose a practice change to optimize care of FL-HCC patients.
Hayashi, Y; Yokota, A; Harada, H; Huang, G. Hypoxiapseudohypoxia-mediated activation of hypoxia-inducible factor-1 in cancer. Cancer Science. 2019; 110(5):1010-1014.
Since the first identification of hypoxic cells in sections of carcinomas in the 1950s, hypoxia has been known as a central hallmark of cancer cells and their microenvironment. Indeed, hypoxia benefits cancer cells in their growth, survival, and metastasis. The historical discovery of hypoxia-inducible factor-1α (HIF1A) in the early 1990s had a great influence on the field as many phenomena in hypoxia could be explained by HIF1A. Oxygen-independent glycolysis is activated in cancer cells even in the normoxia condition, which is known as the Warburg effect. Accumulating evidence and recent advances in cancer metabolism research suggest that hypoxia-independent mechanisms for HIF signaling activation is a hallmark for cancer. Given the importance of HIF1A for cancer pathobiology, the pseudohypoxia concept could shed light on the longstanding mystery of the Warburg effect and accelerate better understanding of the diverse phenomena seen in a variety of cancers.
Aljeaid, D; Lombardo, RC; Witte, DP; Hopkin, RJ. A novel pathogenic variant in OFD1 results in X-linked Joubert syndrome with orofaciodigital features and pituitary aplasia. American Journal of Medical Genetics, Part A. 2019; 179(6):815-819.
Orofaciodigital syndrome type I and X-linked recessive Joubert syndrome are known ciliopathic disorders that are caused by pathogenic variants in OFD1 gene. Endocrine system involvement with these conditions is not well described. We present the first report of a newborn male with a novel hemizygous variant in OFD1 gene c.515T>C, (p.Leu172Pro) resulting in X-linked Joubert syndrome and orofaciodigital features with complete pituitary gland aplasia and subsequent severe hypoplasia of peripheral endocrine glands. This clinical report expands the phenotypic spectrum of endocrine system involvement in OFD1-related disorders and suggests that OFD1 gene may be related to pituitary gland development.
Li, B; Liu, J; Xu, Z; Qin, T; Shi, Z; Song, Z; Huang, H; Fang, L; Zhang, H; Pan, L; Hu, N; Qu, S; Zhang, Y; Huang, G; Xiao, Z. The usefulness of mutational data on prognosis of myelodysplastic syndromes alone or incorporated into the IPSS-R. British Journal of Haematology. 2018; 183(5).
The myelodysplastic syndromes (MDS) comprise a heterogeneous group of clonal haematopoietic neoplasms with a variable propensity to progress to acute myeloid leukaemia (AML). This emphasises the need to differentiate MDS patients as low or high risk for progression, so that therapy is tailored according to the risk group. Several prognostic models combining traditional morphological and clinical criteria have been developed as default staging systems to risk‐stratify patients with MDS, including the International Prognostic Scoring System (IPSS), the WHO classification‐based Prognostic Scoring System, the MD Anderson Prognostic Scoring System and the revised IPSS (IPSS‐R). The IPSS‐R, based on large international databases of more than 7000 patients and integrated detailed disease‐related and patient‐related factors, has been proved as an excellent predictor of MDS prognosis and is most commonly used.