Polymerization of propadiene by some η-allylic derivatives of rhodium(III)

An investigation has been carried out on the polymerization of propadiene (allene) by several η-allylic derivatives of rhodium(III). Polymers of a high structural regularity were obtained, along with liquid oligomers, at ca. 70°C. The results are compared with those obtained using complexes of rhodium(I) as catalysts. The catalytic cycle is interpreted on the basis of the formation of a complex of rhodium(III) in the initiation and of a complex of rhodium(I) in the termination.     

Stereospecific polymerization of cis,cis-1,4-dideuterio-1,3-butadiene to trans-1,4 or cis-1,4 polymers

cis,cis-1,4-Dideuterio-1,3-butadiene ( 1 ) was polymerized by various catalyst systems {Al(C₂H₅)₃? VCl₃, Al(C₂H₅)₂ Cl? VO(acac)₂, Al(C₂H₅)₃? TiI₄, Al(C₂H₅)₂ Cl? Co(acac)₂, (π-allyl)NiOCOCl₃, (π-allyl)NiI} to polymers having a trans-1,4 or a cis-1,4 structure. Degradative oxidation of the polymers gave a mixture of racemic and meso 2,3-dideuteriosuccinic acid ( 2 ), in a ratio dependent on the particular catalyst used. The polymers obtained with the catalyst systems Al(C₂H₅)₃? VCl₃ and Al(C₂H₅)₂Cl? Co(acac)₂ gave oxidation products with a high percentage of the racemic form of 2 (85–92%), which is indicative of a threo structure of the polymers. IR examination of the polymers obtained by the cobalt or vanadium system showed them to possess a regular structure (presence of the so-called regularity bands). The results are interpreted on the basis of a cis-addition of the monomer. The factors that determine the stereospecificity in the polymerization of 1 are discussed and possible schemes for the formation of the stereoregular polymers are examined.     

Association of the Careggi Collateral Score with 3-month modified Rankin Scale score after thrombectomy for stroke with occlusion of the middle cerebral artery

Background

The Careggi Collateral Score (CCS) (qualitative–quantitative evaluation) was developed from a single-centre cohort as an angiographic score to describe both the extension and effectiveness of the pial collateral circulation in stroke patients with occlusion of the anterior circulation. We aimed to examine the association between CCS (quantitative evaluation) and 3-month modified Rankin Scale (mRS) score in a large multi-center cohort of patients receiving thrombectomy for stroke with occlusion of middle cerebral artery (MCA).

Methods

We conducted a study on prospectively collected data from 1284 patients enrolled in the Italian Registry of Endovascular Treatment in Acute Stroke. According to the extension of the retrograde reperfusion in the cortical anterior cerebral artery (ACA)-MCA territories, CCS ranges from 0 (absence of retrograde filling) to 4 (visualization of collaterals until the alar segment of the MCA).

Results

Using CCS of 4 as reference, CCS grades were associated in the direction of unfavourable outcome on 3-month mRS shift (0 to 6); significant difference was found between CCS of 0 and CCS of 1 and between CCS of 3 and CCS of 4. CCS ≥ 3 was the optimal cut-off for predicting 3-month excellent outcome, while CCS ≥ 1 was the optimal cut-off for predicting 3-month survival. CCS of 0 and CCS < 3 were associated in the direction of unfavourable recanalization on TICI shift (0 to 3) compared with CCS ≥ 1 and CCS ≥ 3, respectively. Compared with CCS ≥ 3 as reference, CCS of 0 and CCS 1 to 2 were associated in the direction of unfavourable recanalization on TICI shift. There was no evidence of heterogeneity of effects of successful recanalization and procedure time ≤ 60 min on 3-month mRS shift across CCS categories.

Conclusion

The CCS could provide a future advantage for improving the prognosis in patients receiving thrombectomy for stroke with M1 or M1–M2 segment of the MCA occlusion.

     

uPAR Controls Vasculogenic Mimicry Ability Expressed by Drug-Resistant Melanoma Cells

Malignant melanoma is a highly aggressive skin cancer characterized by an elevated grade of tumor cell plasticity. Such plasticity allows adaptation of melanoma cells to different hostile conditions and guarantees tumor survival and disease progression, including aggressive features such as drug resistance. Indeed, almost 50% of melanoma rapidly develop resistance to the BRAF^V600E inhibitor vemurafenib, with fast tumor dissemination, a devastating consequence for patients’ outcomes. Vasculogenic mimicry (VM), the ability of cancer cells to organize themselves in perfused vascular-like channels, might sustain tumor spread by providing vemurafenib-resistant cancer cells with supplementary ways to enter into circulation and disseminate. Thus, this research aims to determine if vemurafenib resistance goes with the acquisition of VM ability by aggressive melanoma cells, and identify a driving molecule for both vemurafenib resistance and VM. We used two independent experimental models of drug-resistant melanoma cells, the first one represented by a chronic adaptation of melanoma cells to extracellular acidosis, known to drive a particularly aggressive and vemurafenib-resistant phenotype, the second one generated with chronic vemurafenib exposure. By performing in vitro tube formation assay and evaluating the expression levels of the VM markers EphA2 and VE-cadherin by Western blotting and flow cytometer analyses, we demonstrated that vemurafenib-resistant cells obtained by both models are characterized by an increased ability to perform VM. Moreover, by exploiting the CRISPR-Cas9 technique and using the urokinase plasminogen activator receptor (uPAR) inhibitor M25, we identified uPAR as a driver of VM expressed by vemurafenib-resistant melanoma cells. Thus, uPAR targeting may be successfully leveraged as a new complementary therapy to inhibit VM in drug-resistant melanoma patients, to counteract the rapid progression and dissemination of the disease.Key words: Drug resistance, Vasculogenic mimicry, Extracellular acidosis, Melanoma, Urokinase plasminogen activator receptor (uPAR)     

幻肢和余剩幻肢研究的历史性回顾及新病例报告(英文)

大脑通常决定人类对其周围环境的感受。幻肢是接受过截肢手术的人所产生的一种幻觉,他们总感觉失去的肢体仍存在于躯干上。揭开幻肢的成因已成为神经病学领域的一个研究热点。此外,一些病人中风后会感觉到除正常存在的双臂和双腿之外,还存在额外的肢体。这种复杂的、意识和知觉上的偏差称为余剩幻肢。本文主要就幻肢和余剩幻肢的病因及对其认识的历史性发展作一综述,并报告一例余剩幻肢患者 。     

Endothelial progenitor cell-dependent angiogenesis requires localization of the full-length form of uPAR in caveolae

Endothelial urokinase-type plasminogen activator receptor (uPAR) is thought to provide a regulatory mechanism in angiogenesis. Here we studied the proangiogenic role of uPAR in endothelial colony-forming cells (ECFCs), a cell population identified in human umbilical blood that embodies all of the properties of an endothelial progenitor cell matched with a high proliferative rate. By using caveolae-disrupting agents and by caveolin-1 silencing, we have shown that the angiogenic properties of ECFCs depend on caveolae integrity and on the presence of full-length uPAR in such specialized membrane invaginations. Inhibition of uPAR expression by antisense oligonucleotides promoted caveolae disruption, suggesting that uPAR is an inducer of caveolae organization. Vascular endothelial growth factor (VEGF) promoted accumulation of uPAR in ECFC caveolae in its undegraded form. We also demonstrated that VEGF-dependent ERK phosphorylation required integrity of caveolae as well as caveolar uPAR expression. VEGF activity depends on inhibition of ECFC MMP12 production, which results in impairment of MMP12-dependent uPAR truncation. Further, MMP12 overexpression in ECFC inhibited vascularization in vitro and in vivo. Our data suggest that intratumor homing of ECFCs suitably engineered to overexpress MMP12 could have the chance to control uPAR-dependent activities required for tumor angiogenesis and malignant cells spreading.     

The inhibition of lung colonization of B16-F10 melanoma cells in EFA-deficient animals is related to enhanced apoptosis and reduced angiogenesis

Previous studies conducted in our laboratory showed that the reproduction of spontaneous and experimental metastases was reduced in host animals deprived of essential fatty acids (EFA). In the present study, we have explored the possibility whether apoptosis, proliferation, and angiogenesis might be involved in the antimetastatic effect of EFA deficiency. To this aim, in pulmonary colonies developed from B16-F10 cells in EFA-deficient animals or in animals fed a 5% corn oil diet, we performed an immunohistochemical analysis of bcl-2/bax proteins, PCNA, and VEGF and von Willebrand Factor (vWF), typical markers of apoptosis, proliferation, and angiogenesis, respectively. Apoptosis was also evaluated by detecting DNA fragments in metastatic cells. We found that the reduction of pulmonary colonies grown in EFA-deficient animals was associated with a high expression of apoptotic activity as revealed by the presence of apoptotic nuclei and a high immunoreactivity for bax. Cell proliferation seemed not to be influenced by EFA deficiency in view of the observation that PCNA was highly expressed in pulmonary colonies of control as well as EFA-deficient animals. Pulmonary colonies developed in EFA- deficient animals showed a lower expression of VEGF and a decreased microvessel density, indicating that a reduced angiogenesis contributes to the antimetastatic effects of EFA deficiency. Our analysis of the results invokes the possibility that a relationship between angiogenesis and apoptosis may account for the diminution of the development of experimental metastases in the lungs of EFA-deficient animals.     

Structural studies on 1,4-cis-poly(2-methyl-1,3-pentadiene) synthesized with Nd catalysts

(E)-2-Methyl-1,3-pentadiene was polymerized with the AlEt₂Cl-Nd(OCOC₇H₁₅)₃-Al(iBu)₃ system to a polymer consisting of 98–99% 1,4-cis-structure. The crude polymer was fractionated by successive extractions with boiling diethyl ether, heptane and toluene. Examination of the soluble fractions and of the residue to toluene extraction by NMR, X-ray and DSC techniques indicated that the crude polymer consists of macromolecules differing in stereoregularity. Evidence is reported that the crystalline residue after the toluene extraction has a 1,4-cis-isotactic structure. The existence of two different crystalline phases is shown and the respective cell parameters have been determined. α-Phase: a = 10,74, b = 13,04, c = 7,87 Å (?120°C), space group Pbca, Z = 8, D_c = 1,00 g · cm^?3. β-phase: a = 9,30, b = 7,73, c = 7,90 Å (25°C), space group P2₁2₁2₁Z = 4, D_c = 0,96 g · cm^?3.     

Polymerization of 1,3-dienes with methylaluminoxanetriacetylacetonatovanadium

Various 1,3-dienes (1,3-butadiene, isoprene, 2-ethyl-1,3-butadiene, (E)- and (Z)-1,3-pentadiene, (E)-2-methyl-1,3-pentadiene) were polymerized with the soluble catalyst system methylaluminoxane/V (acac)₃ (acac: acetylacetonato). Butadiene and (Z)-1,3-pentadiene gave trans-1,4 polymers, at low and room temperature. Isoprene, 2-ethyl-1,3-butadiene and (E)-2-methyl-1,3-pentadiene gave trans-1,4-polymers at low temperature (< ?20°C), but polymers of mixed cis/trans structure at room temperature. (E)-1,3-pentadiene gave polymers of mixed 1,2/trans-1,4 structure either at low or room temperature. An interpretation of the results is reported.