Background Activated mutations in NOTCH1 are drivers of T-cell type acute lymphoblastic leukemia/lymphoma. The gamma-secretase inhibitor (GSI), which suppresses the function of NOTCH1, is expected to ...be a molecular-targeted agent. NOTCH1 is also expressed in other malignant neoplasms. We aimed to determine the function of NOTCH1 expression and the effects of GSI on adult T-cell leukemia/lymphoma (ATL) caused by long-term human T-cell leukemia virus type I (HTLV-1) infection. Methods We analyzed the expression of NOTCH1 in six ATL- and HTLV-1-infected cell lines and investigated the influence of activated NOTCH1 (i.e., the cleaved form of NOTCH1) together with GSI on cell proliferation. Results Activated NOTCH1 found in ATL- and HTLV-1-infected cell lines was undetectable after incubation with GSI, regardless of Tax expression (HTLV-1-coded protein). Whole-exome sequencing revealed that activated NOTCH1 mutations were undetectable in six ATL- and HTLV-1-infected cell lines, regardless of abundant NOTCH1 expression. Moreover, GSI did not suppress the growth of ATL cell lines. Conclusions These findings suggested that NOTCH1 protein is constitutively activated but is likely a passenger during NOTCH1-mutation-negative ATL cell proliferation. Keywords: NOTCH1, Adult T-cell leukemia/lymphoma, gamma-Secretase inhibitor, Molecular pathogenesis
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objective
This study was designed to evaluate the diagnostic accuracy of magnetic resonance imaging (MRI) for lateral pelvic lymph-node metastasis.
Patients
Eighty-four patients with primary lower ...rectal cancer were examined by MRI and subsequently underwent radical surgery with lateral pelvic lymph-node dissection, without preoperative treatment. Lateral lymph-node metastases were assessed preoperatively by MRI, and the results were compared with the histopathological findings. The criterion for lateral lymph-node metastasis was any recognizable lymph node in the pelvic wall, regardless of diameter.
Result
Lateral pelvic lymph-node metastasis was diagnosed on preoperative MRI in 16 patients (19.9 %). The overall patient-based sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of MRI were 75, 69.1, 36.4, 92.2, and 70.2 %, respectively. When a cut-off value of 10 mm was used for diagnosis, the corresponding values were 43.8, 98.5, 87.5, 88.1, and 88.1 %, respectively. The mean diameter of metastatic nodes (14.7 mm) was significantly larger than that of negative nodes (5.7 mm;
P
< 0.01).
Conclusion
MRI is an effective technique for predicting lateral pelvic node involvement and thus may facilitate preoperative decision-making in rectal cancer treatment. A cut-off value of 10 mm is useful for avoiding unnecessary lateral lymph-node dissection.
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EMUNI, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UL, UM, UPUK, VKSCE, ZAGLJ
The magnetic skyrmion is a nanoscale topological object characterized by the winding of magnetic moments, appearing in magnetic materials with broken inversion symmetry. Because of its low current ...threshold for driving the skyrmion motion, they have been intensely studied toward novel storage applications by using electron-beam, X-ray, and visible light microscopies. Here, we demonstrate another imaging method for skyrmions by using spin-caloritronic phenomena, that is, the spin Seebeck and anomalous Nernst effects, as a probe of magnetic texture. We scanned a focused heating spot on a Hall-cross shaped MgO/CoFeB/Ta/W multilayer film and mapped the magnitude as well as the direction of the resultant thermoelectric current due to the spin-caloritronic phenomena. Our experimental and calculation reveal that the characteristic patterns in the thermoelectric signal distribution reflect the skyrmions' magnetic texture. The thermoelectric microscopy will be a complementary and useful imaging technique for the development of skyrmion devices owing to the unique symmetry of the spin-caloritronic phenomena.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Purpose
We conducted a prospective study to evaluate the efficacy and safety of postoperative enoxaparin for the prevention of venous thromboembolism (VTE) after laparoscopic surgery for colorectal ...cancer (LAC) in Japanese patients.
Methods
The subjects of this multicenter, open-label randomized-controlled trial were 121 patients who underwent LAC between September 2015 and May 2017. The patients were randomly allocated to receive intermittent pneumatic compression (IPC) with enoxaparin (20 mg, twice daily), started 24–36 h after surgery and continued until discharge (Enoxaparin group;
n
= 61), or IPC alone (IPC group;
n
= 60). The primary endpoint was the incidence of VTE on day 28 after surgery. The safety outcome was the incidence of any bleeding during treatment and follow-up.
Results
The incidence of VTE on day 28 after surgery was 12.3% (7/57 patients) in the enoxaparin group and 11.9% (7/59 patients) in the IPC group ((
p
= 1.00). One of the 57 patients (1.8%) in the enoxaparin group and none in the IPC group experienced a bleeding event.
Conclusions
It may be unnecessary to give enoxaparin to all Japanese patients for the prevention of VTE after LAC.
The UMIN Clinical Trials Registry number was UMIN000018633.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Social signals play powerful roles in shaping self-oriented reward valuation and decision making. These signals activate social and valuation/decision areas, but the core computation for their ...integration into the self-oriented decision machinery remains unclear. Here, we study how a fundamental social signal, social value (others' reward value), is converted into self-oriented decision making in the human brain. Using behavioral analysis, modeling, and neuroimaging, we show three-stage processing of social value conversion from the offer to the effective value and then to the final decision value. First, a value of others' bonus on offer, called offered value, was encoded uniquely in the right temporoparietal junction (rTPJ) and also in the left dorsolateral prefrontal cortex (ldlPFC), which is commonly activated by offered self-bonus value. The effective value, an intermediate value representing the effective influence of the offer on the decision, was represented in the right anterior insula (rAI), and the final decision value was encoded in the medial prefrontal cortex (mPFC). Second, using psychophysiological interaction and dynamic causal modeling analyses, we demonstrated three-stage feedforward processing from the rTPJ and ldPFC to the rAI and then from rAI to the mPFC. Further, we showed that these characteristics of social conversion underlie distinct sociobehavioral phenotypes. We demonstrate that the variability in the conversion underlies the difference between prosocial and selfish subjects, as seen from the differential strength of the rAI and ldlPFC coupling to the mPFC responses, respectively. Together, these findings identified fundamental neural computation processes for social value conversion underlying complex social decision making behaviors.
In daily life, we make decisions based on self-interest, but also in consideration for others' status. These social influences modulate valuation and decision signals in the brain, suggesting a fundamental process called value conversion that translates social information into self-referenced decisions. However, little is known about the conversion process and its underlying brain mechanisms. We investigated value conversion using human fMRI with computational modeling and found three essential stages in a progressive brain circuit from social to empathic and decision areas. Interestingly, the brain mechanism of conversion differed between prosocial and individualistic subjects. These findings reveal how the brain processes and merges social information into the elemental flow of self-interested decision making.
It has been reported that the epidermal growth factor receptor (EGFR) expression is associated with the extracellular matrix metalloproteinase inducer (EMMPRIN) in some solid tumors; however, the ...relationship of EMMPRIN with EGFR in head and neck cancers is not fully understood. To determine the relationship between EMMPRIN and EGFR in head and neck squamous cell carcinoma (HNSCC), HNSCC cells were stimulated with epidermal growth factor (EGF), a ligand of EGFR. EMMPRIN expression in HNSCC cells was upregulated by EGF. In addition, EGF stimulation induced HNSCC cell invasion and MMP-9 expression. This increase in invasion and MMP-9 expression was abrogated by downmodulation of EMMPRIN. Furthermore, to determine the effects of combined EMMPRIN and EGFR targeting in HNSCC, HNSCC cells were treated with an EMMPRIN function-blocking antibody and the EGFR inhibitor AG1478. This combined treatment resulted in greater inhibition of HNSCC cell proliferation and migration compared with the individual agents alone. These results suggest that EMMPRIN mediates EGFR-induced tumorigenicity and that combined targeting of EMMPRIN and EGFR may be an efficacious treatment approach.
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