Activity

A significant part of them, belonging to molecular chaperones, were common partners for CYP5A1 and CYP8A1, while other proteins were unique with the tissue-dependent distribution. New aspects of CYP5A1 and CYP8A1 interactomics and hetero-complex formation with different protein partners, including cytochrome P450s are discussed.

To investigate the clinicopathological features and outcomes of targeted therapy in patients with recurrence of renal cell carcinoma in <5years or ≥5years after the surgical treatment for renal cell carcinoma.

Patients with metastatic renal cell carcinoma treated with targeted therapy in a multicenter database were retrospectively characterized according to time from surgery to recurrence. Early recurrence was defined as recurrence within 5years after surgery, and late recurrence was defined as occurring ≥5years after surgery. SP600125 The propensity scores for recurrence status were calculated, and patients with late recurrence were matched to patients with early recurrence at a 13 ratio. The oncological outcomes of targeted therapy in both groups were compared.

Among 716 patients, 512 (71.5%) experienced early recurrence and 204 (28.5%) experienced late recurrence. The patients with late recurrence presented with younger age at surgery, lower tumor stages and Fuhrman grade, and fewer sarcomatoid features and lymphovascular invasion (all P<0.005). All differences in clinicopathological characteristics before targeted therapy disappeared after matching. Patients with late recurrence had significantly longer median overall survival (56months vs 36months; P<0.0001) and median first-line progression-free survival (12months vs 8months; P=0.031). The early recurrence status was a significantly worse predictor for overall survival and first-line progression-free survival (hazard ratio 1.30, P=0.007; and hazard ratio 1.76, P<0.001, respectively).

Late recurrence might have prognostic value in terms of oncological outcomes in metastatic renal cell carcinoma treated with targeted therapy.

Late recurrence might have prognostic value in terms of oncological outcomes in metastatic renal cell carcinoma treated with targeted therapy.Acute promyelocytic leukemia (APL), a subtype of acute myeloid leukemia characterized with a translocation between promyelocytic leukemia gene (PML) on chromosome 15 and retinoic acid receptor alpha gene (RARα) on chromosome 17. Transcription of this fusion gene results in PML/RARα fusion protein blocking expression of critical genes involved in differentiation of myeloid cells through interaction with RAR element. PML/RARα fusion protein prevents normal function of PML and RARα as well as inhibiting apoptosis. Arsenic trioxide (ATO) is an important agent for the treatment of relapsed and newly diagnosed APL. ATO induces apoptosis, autophagy, and partial cellular differentiation as well as inhibiting cell growth and angiogenesis. Recognition of signaling pathways and molecular mechanisms induced by ATO can be effective for discovering novel treatment strategies to target leukemia cells. Also, it can be developed for the treatment of a variety of cancer cells. This review provides a perspective on anticancerous effects of ATO on APL and leukemia cells.

A computer simulation model has demonstrated that atrial fibrillation (AF) driver can be attached to heterogeneous fibrosis assessed by late gadolinium enhancement magnetic resonance imaging (LGE-MRI). However, it has not been well elucidated in patients with persistent AF. The aim of this study was to investigate whether radiofrequency (RF) applications in the fragmented LGE area (FLA) could terminate AF or convert it to atrial tachycardia (AT) and improve the rhythm outcome.

A total of 31 consecutive persistent AF patients with FLAs were enrolled (FLA ablation group, mean age 69 ± 8 years, mean left atrial diameter 42 ± 6 mm). A favorable response was defined as direct AF termination or AT conversion during RF applications at the FLA. The rhythm outcome was compared between the FLA ablation group and FLA burden-matched pulmonary vein isolation (PVI) group.

Favorable responses were found in 15 (48%) of 31 patients in the FLA group (AF termination in seven, AT conversion in eight patients), but not in the PVI group. AF recurrence at 12 months follow-up was significantly less in the FLA ablation group than in the PVI group (4 [13%] vs. 12 [39%] of 31 patients, log-rank p = .023). In patients with a favorable response, AT recurred in 1 (7%) of 15 patients, but AF did not.

FLA ablation could terminate AF or convert it to AT in half of the patients. No AF recurrence was documented in patients with a favorable response.

FLA ablation could terminate AF or convert it to AT in half of the patients. No AF recurrence was documented in patients with a favorable response.

Blunted cyclic variation of heart rate (CVHR), measured as a decrease in CVHR amplitude (Acv), predicts mortality risk after acute myocardial infarction (AMI). However, Acv also can be reduced in mild sleep apnea with mild O

desaturation. We investigated whether Acv’s predictive power for post-AMI mortality could be improved by considering the effect of sleep apnea severity.

In 24-hr ECG in 265,291 participants of the Allostatic State Mapping by Ambulatory ECG Repository project, sleep apnea severity was estimated by the frequency of CVHR (Fcv) measured by an automated algorithm for auto-correlated wave detection by adaptive threshold (ACAT). The distribution of Acv on the Acv-Fcv relation map was modeled by percentile regression, and a function converting Acv into percentile value was developed. In the retrospective cohort of the Enhancing Recovery in Coronary Heart Disease (ENRICHD) study, consisting of 673 survivors and 44 non-survivors after AMI, the mortality predictive power of percentile Acv calculated by the function was compared with that of unadjusted Acv.

Among the ALLSTAR ECG data, low Acv values appeared more likely when Fcv was low. The logistic regression analysis for mortality in the ENRICHD cohort showed c-statistics of 0.667 (SE, 0.041), 0.817 (0.035), and 0.843 (0.030) for Fcv, unadjusted Acv, and the percentile Acv, respectively. Compared with unadjusted Acv, the percentile Acv showed a significant net reclassification improvement of 0.90 (95% CI, 0.51-1.42).

The predictive power of Acv for post-AMI mortality is improved by considering its relation to sleep apnea severity estimated by Fcv.

The predictive power of Acv for post-AMI mortality is improved by considering its relation to sleep apnea severity estimated by Fcv.