Development of a Brønsted Acid-Promoted Arene–Ynamide Cyclization toward the Total Syntheses of Marinoquinolines A and C and Aplidiopsamine A

A Brønsted acid-promoted arene–ynamide cyclization has been developed to construct the 3<i>H</i>-pyrrolo­[2,3-<i>c</i>]­quinolines. This reaction consists of the generation of a highly reactive keteniminium intermediate from arene–ynamide activated by a Brønsted acid and electrophilic aromatic substitution reaction to give arene-fused quinolines in high yields. This methodology enabled facile access to marinoquinolines A and C and aplidiopsamine A

EMMPRIN Promotes Angiogenesis, Proliferation, Invasion and Resistance to Sunitinib in Renal Cell Carcinoma, and Its Level Predicts Patient Outcome

<div><p>Purpose</p><p>Extracellular matrix metalloproteinase inducer (EMMPRIN) has been reported to play crucial roles, including in angiogenesis, in several carcinomas. However, the correlation between EMMPRIN levels and angiogenesis expression profile has not been reported, and the role of EMMPRIN in renal cell carcinoma (RCC) is unclear. In the present study, we evaluated the association of EMMPRIN with angiogenesis, its value in prognosis, and its roles in RCC.</p> <p>Experimental Design</p><p>EMMPRIN expression was examined in 50 RCC patients treated with radical nephrectomy. Angiogenesis, proliferation, and invasion activity were evaluated using EMMPRIN knockdown RCC cell lines. The size of EMMPRIN-overexpressing xenografts was measured and the degree of angiogenesis was quantified. EMMPRIN expression was evaluated in RCC patients who received sunitinib therapy and in sunitinib-resistant cells. Further, the relation between EMMPRIN expression and sensitivity to sunitinib was examined.</p> <p>Results</p><p>EMMPRIN score was significantly associated with clinicopathological parameters in RCC patients, as well as being significantly correlated with microvessel area (MVA) in immature vessels and with prognosis. Down-regulation of EMMPRIN by siRNA led to decreased VEGF and bFGF expression, cell proliferation, and invasive potential. EMMPRIN over-expressing xenografts showed accelerated growth and MVA of immature vessels. EMMPRIN expression was significantly increased in patients who received sunitinib therapy as well as in sunitinib-resistant 786-O cells (786-suni). EMMPRIN-overexpressing RCC cells were resistant to sunitinib.</p> <p>Conclusion</p><p>Our findings indicate that high expression of EMMPRIN in RCC plays important roles in tumor progression and sunitinib resistance. Therefore, EMMPRIN could be a novel target for the treatment of RCC.</p> </div

EMMPRIN was associated with the MVA of immature vessels and prognosis in RCC patients.

<div><p>(A) EMMPRIN staining pattern (left: weak, score 0; middle: moderate, score 1; right: strong, score 2) (× 200).</p> <p>(B) Effect of EMMPRIN expression level on overall survival (OS) and progression free survival (PFS) rates in RCC patients.</p> <p>(C) The correlation between EMMPRIN score and MVA of immature vessels in RCC patients.</p></div

EMMPRIN levels in sunitinib-resistant RCC.

<div><p>(A) Characterization of sunitinib resistant 786-O. Cell survival of 786-O and 786-Suni cells exposed to sunitinib for 72 h.</p> <p>(B) EMMPRIN protein expression in 786-O and 786-Suni cells.</p> <p>(C) Anti-proliferative effects of sunitinib on Caki-1 mock transformants and Caki-1 EMMPRIN transformants.</p> <p>(D) EMMPRIN staining in 2 bilateral RCC patients (left: pre sunitinib treatment, right: post sunitinib treatment) (×200).</p></div

Transient siRNA knockdown of EMMPRIN decreased the expression of soluble VEGF and intracellular bFGF proteins.

<div><p>(A) Downregulation of EMMPRIN by siRNA in 786-O and OUR10 cells showed a remarkable decrease of EMMPRIN protein relative to normal or siControl 786-O cells.</p> <p>(B) CBA showed siRNA EMMPRIN decreased soluble VEGF protein expression and intracellular bFGF protein expression in RCC cells for 786-O compared with a 786-O siControl, and for OUR10 compared with an OUR10 siControl. *p: < 0.05.</p></div

Table_1_A short decision time for transcatheter embolization can better associate mortality in patients with pelvic fracture: a retrospective study.docx

BackgroundEarly use of hemostasis strategies, transcatheter arterial embolization (TAE) is critical in cases of pelvic injury because of the risk of hemorrhagic shock and other fatal injuries. We investigated the influence of delays in TAE administration on mortality.MethodsPatients admitted to the Advanced Critical Care Center at Gifu University with pelvic injury between January 2008 and December 2019, and who underwent acute TAE, were retrospectively enrolled. The time from when the doctor decided to administer TAE to the start of TAE (needling time) was defined as “decision-TAE time.”ResultsWe included 158 patients, of whom 23 patients died. The median decision-TAE time was 59.5 min. Kaplan–Meier curves for overall survival were compared between patients with decision-TAE time above and below the median cutoff value; survival was significantly better for patients with values below the median cutoff value (p = 0.020). Multivariable Cox proportional hazards regression analysis revealed that the longer the decision-TAE time, the higher the risk of mortality (p = 0.031). TAE duration modified the association between decision-TAE time and overall survival (p = 0.109), as shorter TAE duration (procedure time) was associated with the best survival rate (p for interaction = 0.109).ConclusionDecision-TAE time may play a key role in establishing resuscitation procedures in patients with pelvic fracture, and efforts to shorten this time should be pursued.</p