Oxygen is essential for aerobic life, and hypoxia has very severe consequences. Organisms need to overcome low oxygen levels to maintain biological functions during normal development and in disease states. The mechanism underlying the hypoxic response has been widely investigated in model animals such as Drosophila melanogaster and Caenorhabditis elegans. Hypoxia-inducible factor (HIF), a key gene product in the response to oxygen deprivation, is primarily regulated by prolyl hydroxylase domain enzymes (PHDs). However, recent findings have uncovered novel HIF-independent functions of PHDs. This review provides an overview of how invertebrates are able to sustain hypoxic damages, and highlights some recent discoveries in the regulation of cellular signalling by PHDs. Given that some core genes and major pathways are evolutionarily conserved, these research findings could provide insight into oxygen-sensitive signalling in mammals, and have biomedical implications for human diseases.
Four cycles of chemotherapy are required to assess responses of multiple myeloma (MM)
patients. We investigated whether circulating endothelial progenitor cells (cEPCs)
could be a biomarker for predicting patient response in the first cycle of
chemotherapy with bortezomib and dexamethasone, so patients might avoid ineffective
and costly treatments and reduce exposure to unwanted side effects. We measured cEPCs
and stromal cell-derived factor-1α (SDF-1α) in 46 MM patients in the first cycle of
treatment with bortezomib and dexamethasone, and investigated clinical relevance
based on patient response after four 21-day cycles. The mononuclear cell fraction was
analyzed for cEPC by FACS analysis, and SDF-1α was analyzed by ELISA. The study
population was divided into 3 groups according to the response to chemotherapy: good
responders (n=16), common responders (n=12), and non-responders (n=18). There were no
significant differences among these groups at baseline day 1 (P>0.05). cEPC levels
decreased slightly at day 21 (8.2±3.3 cEPCs/μL) vs day 1 (8.4±2.9
cEPCs/μL) in good responders (P>0.05). In contrast, cEPC levels increased
significantly in the other two groups (P<0.05). SDF-1α changes were closely
related to changes in cEPCs. These findings indicate that change in cEPCs at day 21
in the first cycle might be considered a noninvasive biomarker for predicting a later
response, and extent of change could help decide whether to continue this costly
chemotherapy. cEPCs and the SDF-1α/CXCR4 axis are potential therapeutic targets for
improved response and outcomes in MM patients.
We report the case of a father and son diagnosed with atypical chronic myeloid
leukemia (aCML). Both patients harbored SETBP1 mutations, which are
present in 24.3% of aCML patients. Moreover, both shared the variant encoding
p.Pro737His, but the aCML severity was greater in the son because of the presence of
two other missense mutations causing p.Asp868Asn and p.Ser885Arg alterations.
SETBP1 mutations may be associated with an adverse prognosis, so
their detection would help in the diagnosis of aCML and the determination of a
patient's prognosis.
Background: Diabetes mellitus (DM) is a common comorbidity in patients with lung cancer (LC). This study aimed to evaluate the prognostic value of DM comorbidity for LC patients with DM and to assess whether an optimal glycemic control improves survival. Method: A total of 4390 patients diagnosed with LC between 2012 and 2013 at Shanghai Chest Hospital were retrospectively reviewed, 491 patients with DM and 3899 without DM. The relationship between hemoglobin A1c (HbA1c) level and the overal survival (OS) was plotted by a smooth curve. LC patients with DM were subdivided into the well-controlled group (HbA1c < 7%, n¼438) and uncontrolled group (HbA1c 7%, n¼53). OS differences among patients without DM, with well-controlled DM, and uncontrolled DM were evaluated by multivariate Cox regression analysis with adjustment for stage, sex, age, histology, smoking history and EGFR mutation status. The survival benefit of wellcontrolled DM was compared across subgroups. Result: The median follow-up of the entire cohort was 35.8 months. DM patients (11.2%) had a significantly worse OS than nondiabetic patients [median (95% CI): 47.5 (39.0-56.1) vs. 73.6 (54.8-92.4) months, P<0.001]. The risk of mortality increased along with the elevation of HbA1c level. Uncontrolled DM patients tended to be male, elder, non-adenocarcinoma, with smoking history, wide-type EGFR mutations and advanced stage. Wellcontrolled DM patients had a worse OS [HR (95% CI): 2.3 (1.9-2.7), P<0.001] compared to nondiabetic patients without adjustment but a similar OS with adjustment for stage, sex, age, histology, smoking history and EGFR mutation status [HR (95% CI): 0.9 (0.8-1.1), P¼0.185]. Benefit of well-controlled DM was more obviously seen in patients with advanced stage (III-IV) [HR (95% CI): 0.8 (0.6-1.1), P¼0.130] or EGFR mutations [HR (95% CI): 1.2 (0.9-1.5), P¼0.262]. Conclusion: Elevated glycemic status negatively affected OS for patients with LC. LC patients with DM is recommended to have a glycemic control (HbA1c < 7%) especially for those with advanced stage and EGFR mutations.
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