Rat adipose tissues were shown to exhibit a high level of autotaxin having lysophospholipase D activity. Previously, we reported that an elevated level of lysophosphatidic acid (LPA) in rat plasma was due to a decreased lysophosphatidylcholine concentration, increased plasma lysophospholipase D activity, and decreased lipid phosphate phosphatase activity toward LPA in adrenalectomized (ADL) rats. We hypothesized that the profiles of LPA, its precursor lysophospholipids (LPLs), and parent phospholipids (PLs) also may be altered in adipose tissues of ADL rats. To examine this possibility, we determined the tissue levels of molecular species of PLs and LPLs, including LPA, by LC-tandem MS. The levels of six LPLs in rat brown adipose tissue (BAT) were increased in ADL rats. In rat epididymal white adipose tissue (EpiWAT), the levels of LPLs except for LPA were increased. In rat inguinal WAT, the level of phosphatidylglycerol was increased. These results suggest that tissue levels of LPLs were upregulated by adrenal hormones in BAT and EpiWAT by different mechanisms.

Carboplatin (CBDCA) dosing is commonly determined using the Calvert formula, with creatinine clearance (Ccr) estimated by the Cockcroft–Gault formula. In Japan, where serum creatinine (sCr) is usually measured enzymatically, unadjusted Ccr may overestimate glomerular filtration rate and lead to CBDCA overdosing. We retrospectively compared treatment exposure, hematologic toxicity, and exploratory oncologic outcomes in patients with endometrial cancer who received postoperative paclitaxel plus CBDCA therapy. Patients were grouped according to whether CBDCA dosing was based on the conventional Cockcroft–Gault formula (CG group) or on adjusted Ccr calculated by adding 0.2 mg/dL to sCr (adjusted group). The incidence of Grade ≥3 neutropenia was significantly lower in the adjusted group than in the CG group. The 5-year progression-free survival (PFS) rate was numerically lower in the adjusted group than in the CG group, although no statistically significant difference was observed between the groups. Because the number of PFS events was limited, the effect of adjusted Ccr-based dosing on oncologic outcomes remains uncertain. These findings suggest that adjusted Ccr-based dosing may reduce hematologic toxicity in routine clinical practice. However, given the limited number of PFS events and the wide uncertainty in survival estimates, further studies are needed to clarify its impact on oncologic outcomes.

Platelet-activating factor (PAF) is known to induce smooth muscle contraction; however, its mechanisms in urinary bladder smooth muscle (UBSM) remain unclear. We investigated the involvement of Orai1 in PAF-induced contraction in guinea pig UBSM. PAF (10⁻⁶ M)-induced contraction was markedly inhibited by the Orai1 inhibitor Synta66 (10⁻⁵ M) and the L-type voltage-dependent Ca²⁺ channel (VDCC) inhibitor verapamil (10⁻⁵ M). Similarly, under Ca²⁺-free conditions with store depletion induced by cyclopiazonic acid (3 × 10⁻⁵ M), Ca²⁺-induced contraction was suppressed by Synta66 and verapamil. In contrast, Synta66 only partially inhibited contractions induced by acetylcholine (10⁻⁵ M) and α,β-methylene ATP (3 × 10⁻⁶ M), and it had no effect on high-potassium chloride (80 mM)-induced contraction. Inhibition of Na⁺/Ca²⁺ exchanger 1 (NCX1), transient receptor potential canonical (TRPC) 1/4/5 channels, or anoctamin 1 (ANO1) did not significantly affect PAF-induced contraction. These findings suggest that Orai1 contributes to PAF-induced contraction in association with VDCC-dependent mechanisms, whereas NCX1, TRPC1/4/5 channels, and ANO1 play limited roles under these conditions.

The transcription factor c-Myc is frequently upregulated in human cancers through multiple mechanisms, including chromosomal translocation and gene amplification. Since the human TRIB1 gene is located on chromosome 8q24 in close proximity to the MYC oncogene, the MYC and TRIB1 genes may be co-amplified in a large percentage of human cancers. We herein demonstrate molecular crosstalk between TRB1 and c-Myc. Bioinformatic analyses reveal a positive correlation between MYC and TRIB1 expression across multiple cancer types. In prostate cancer cells, the knockdown of c-Myc reduces TRB1 expression. Mechanistically, c-Myc directly binds to the proximal promoter region of the TRIB1 gene and activates its transcription. Conversely, the depletion of TRB1 decreases c-Myc levels and affects the expression of c-Myc target genes. These results indicate that TRB1 contributes to the oncogenic functions of c-Myc and suggest the potential of the TRB1–c-Myc axis as a therapeutic target for cancer treatment.