Vascular endothelial growth factor receptor-1 mRNA overexpression in peripheral blood as a useful prognostic marker in breast cancer

INTRODUCTION: Identification of useful markers associated with poor prognosis in breast cancer patients is critically needed. We previously showed that expression of vascular endothelial growth factor receptor-1 mRNA in peripheral blood may be useful to predict distant metastasis in gastric cancer patients. However, expression of vascular endothelial growth factor receptor-1 mRNA in peripheral blood of breast cancer patients has not yet been studied. METHODS: Real-time reverse transcriptase-PCR was used to analyze vascular endothelial growth factor receptor-1 mRNA expression status with respect to various clinical parameters in 515 patients with breast cancer and 25 controls. RESULTS: Expression of vascular endothelial growth factor receptor-1 mRNA in peripheral blood was higher in breast cancer patients than in controls. Increased vascular endothelial growth factor receptor-1 mRNA expression was associated with large tumor size, lymph node metastasis and clinical stage. Patients with high vascular endothelial growth factor receptor-1 mRNA expression also experienced a poorer survival rate than those with low expression levels, including those patients with triple-negative type and luminal-HER2(-) type disease. CONCLUSIONS: Expression of vascular endothelial growth factor receptor-1 mRNA in peripheral blood may be useful for prediction of poor prognosis in breast cancer, especially in patients with triple-negative type and luminal-HER2(-) type disease

Redox-sensitive transient receptor potential channels in oxygen sensing and adaptation

Regulation of ion channels is central to the mechanisms that underlie immediate acute physiological responses to changes in the availability of molecular oxygen (O2). A group of cation-permeable channels that are formed by transient receptor potential (TRP) proteins have been characterized as exquisite sensors of redox reactive species and as efficient actuators of electric/ionic signals in vivo. In this review, we first discuss how redox-sensitive TRP channels such as TRPA1 have recently emerged as sensors of the relatively inert oxidant O2. With regard to the physiological significance of O2 sensor TRP channels, vagal TRPA1 channels are mainly discussed with respect to their role in respiratory regulation in comparison with canonical pathways in glomus cells of the carotid body, which is a well-established O2-sensing organ. TRPM7 channels are discussed regarding hypoxia-sensing function in ischemic cell death. Also, ubiquitous expression of TRPA1 and TRPM7 together with their physiological relevance in the body is examined. Finally, based upon these studies on TRP channels, we propose a hypothesis of “O2 remodeling.” The hypothesis is that cells detect deviation of O2 availability from appropriate levels via sensors and adjust local O2 environments in vivo by controlling supply and consumption of O2 via pathways comprising cellular signals and transcription factors downstream of sensors, which consequently optimize physiological functions. This new insight into O2 adaptation through ion channels, particularly TRPs, may foster a paradigm shift in our understanding in the biological significance of O2

Association of depressive symptomatology and dry-mouth feeling in relation to state of taking medicine in citizens from their 40s to 70s selected randomly from two cities in Hokkaido, Japan

Background: Troponin I (TnI) are highly specific to the myocardium, and measurement of the plasma TnI levels has been widely used to evaluate myocardial damage. This study was performed to ascertain the pathologic or perioperative variables that are significantly associated with the plasma cardiac TnI level. We also intended to provide reference range of TnI elevation after uncomplicated pediatric open heart surgery.Methods: One hundred fifty-one patients undergoing repair of atrial septal defects (ASDs) (n = 61), ventricular septal defects (VSDs) (n = 71), tetralogy of Fallot (TOF) (n = 14), or complete atrioventricular septal defects (CAVSDs) (n = 5) were included. The plasma TnI level was measured prior to surgery, on days 1 and 7 postoperatively. We analyzed the relationship between the TnI level and pathology, cardiopulmonary bypass, and other perioperative actors.Results: All patients underwent uncomplicated surgery and postoperative course. With all pathologies, the plasma TnI level peaked on postoperative day 1 and rapidly declined. The TnI level on postoperative day 1 was higher in VSD than ASD, and there was a further rise in TOF and CAVSD but no significant difference between them. The TnI level on postoperative day 1 was strongly correlated with the operative time, cardiopulmonary bypass time, and aortic cross-clamp (ACC) time. Multiple linear regression analysis showed that the operative time, ACC time, lowest rectal temperature, TOF lesion, and inotropic support period could influence the TnI level.Conclusions: Elevation of plasma TnI after pediatric open heart surgery for various congenital heart diseases is mainly associated with the condition of cardiopulmonary bypass (operative and ACC times) and is not affected with surgical procedures expect for ventricular muscle resection during repair of TOF. Level of TnI elevation confirmed in the study could provide reference range in uncomplicated open heart surgery for each four pathologies. (298 words

Association of depressive symptomatology and dry-mouth feeling in relation to state of taking medicine in citizens from their 40s to 70s selected randomly from two cities in Hokkaido, Japan

Background: Troponin I (TnI) are highly specific to the myocardium, and measurement of the plasma TnI levels has been widely used to evaluate myocardial damage. This study was performed to ascertain the pathologic or perioperative variables that are significantly associated with the plasma cardiac TnI level. We also intended to provide reference range of TnI elevation after uncomplicated pediatric open heart surgery.Methods: One hundred fifty-one patients undergoing repair of atrial septal defects (ASDs) (n = 61), ventricular septal defects (VSDs) (n = 71), tetralogy of Fallot (TOF) (n = 14), or complete atrioventricular septal defects (CAVSDs) (n = 5) were included. The plasma TnI level was measured prior to surgery, on days 1 and 7 postoperatively. We analyzed the relationship between the TnI level and pathology, cardiopulmonary bypass, and other perioperative actors.Results: All patients underwent uncomplicated surgery and postoperative course. With all pathologies, the plasma TnI level peaked on postoperative day 1 and rapidly declined. The TnI level on postoperative day 1 was higher in VSD than ASD, and there was a further rise in TOF and CAVSD but no significant difference between them. The TnI level on postoperative day 1 was strongly correlated with the operative time, cardiopulmonary bypass time, and aortic cross-clamp (ACC) time. Multiple linear regression analysis showed that the operative time, ACC time, lowest rectal temperature, TOF lesion, and inotropic support period could influence the TnI level.Conclusions: Elevation of plasma TnI after pediatric open heart surgery for various congenital heart diseases is mainly associated with the condition of cardiopulmonary bypass (operative and ACC times) and is not affected with surgical procedures expect for ventricular muscle resection during repair of TOF. Level of TnI elevation confirmed in the study could provide reference range in uncomplicated open heart surgery for each four pathologies. (298 words

Osteoclasts adapt to physioxia perturbation through DNA demethylation

Oxygen plays an important role in diverse biological processes. However, since quantitation of the partial pressure of cellular oxygen in vivo is challenging, the extent of oxygen perturbation in situ and its cellular response remains underexplored. Using two-photon phosphorescence lifetime imaging microscopy, we determine the physiological range of oxygen tension in osteoclasts of live mice. We find that oxygen tension ranges from 17.4 to 36.4 mmHg, under hypoxic and normoxic conditions, respectively. Physiological normoxia thus corresponds to 5% and hypoxia to 2% oxygen in osteoclasts. Hypoxia in this range severely limits osteoclastogenesis, independent of energy metabolism and hypoxia-inducible factor activity. We observe that hypoxia decreases ten-eleven translocation (TET) activity. Tet2/3 cooperatively induces Prdm1 expression via oxygen-dependent DNA demethylation, which in turn activates NFATc1 required for osteoclastogenesis. Taken together, our results reveal that TET enzymes, acting as functional oxygen sensors, regulate osteoclastogenesis within the physiological range of oxygen tension, thus opening new avenues for research on in vivo response to oxygen perturbation.Nishikawa K., Seno S., Yoshihara T., et al. Osteoclasts adapt to physioxia perturbation through DNA demethylation. EMBO Reports 22, e53035 (2021); https://doi.org/10.15252/embr.202153035