A t(2;3)(q12-13;p24-25) in follicular thyroid adenomas.

We report the cytogenetic analysis of five cases of follicular thyroid adenoma. In two of them, we observed an identical t(2;3)(q12-13;p24-25) as a unique chromosome change. A third case showed a hyperdiploid karyotype with trisomies of chromosomes 7 and 12. Two cases had a normal diploid karyotype. These changes could define subgroups of follicular adenomas endowed with different malignant potential.     

Expression of angiogenesis stimulators and inhibitors in human thyroid tumors and correlation with clinical pathological features

Experimental evidence has shown, both in vitro and in animal models, that neoplastic growth and subsequent metastasis formation depend on the tumor's ability to induce an angiogenic switch. This requires a change in the balance of angiogenic stimulators and inhibitors. To assess the potential role of angiogenesis factors in human thyroid tumor growth and spread, we analyzed their expression by semiquantitative RT-PCR and immunohistochemistry in normal thyroid tissues, benign lesions, and different thyroid carcinomas. Compared to normal tissues, in thyroid neoplasias we observed a consistent increase in vascular endothelial growth factor (VEGF), VEGF-C, and angiopoietin-2 and in their tyrosine kinase receptors KDR, Flt-4, and Tek. In particular, we report the overexpression of angiopoietin-2 and VEGF in thyroid tumor progression from a prevascular to a vascular phase. In fact, we found a strong association between tumor size and high levels of VEGF and angiopoietin-2. Furthermore, our results show an increased expression of VEGF-C in lymph node invasive thyroid tumors and, on the other hand, a decrease of thrombospondin-1, an angioinhibitory factor, in thyroid malignancies capable of hematic spread. These results suggest that, in human thyroid tumors, angiogenesis factors seem involved in neoplastic growth and aggressiveness. Moreover, our findings are in keeping with a recent hypothesis that in the presence of VEGF, angiopoietin-2 may collaborate at the front of invading vascular sprouts, serving as an initial angiogenic signal that accompanies tumor growth.     

P2x7 deficiency suppresses development of experimental autoimmune encephalomyelitis

Background  

The purinergic receptor P2x7 is expressed on myeloid cells as well as on CNS glial cells, and P2x7 activation has been shown to increase both glial and T-cell activation. These properties suggest a role in the development of autoimmune disease including multiple sclerosis.     

Is the alpha-beta ratio of prostate cancer really low? A prospective, non-randomized trial comparing standard and hyperfractionated conformal radiation therapy.

BACKGROUND AND PURPOSE: The objectives of the current study were to compare genito-urinary (GU) and gastro-intestinal (GI) toxicities as well as biochemical control (bRFS) in prostate cancer, utilizing conventional (2.0 Gy daily) (STD) or hyperfractionated (HFX) conformal irradiation (CRT). HFX (1.2 Gy BID) was chosen as a radiobiological method to try to reduce long term sequelae without compromising local control. PATIENTS AND METHODS: Three-hundred-and-seventy consecutive patients (pts) entered this prospective, non-randomized trial in the period January 1993-January 2003; 209 were treated with STD and 161 with HFX CRT. All were evaluable for acute toxicity analysis, 179 (STD) and 151 pts (HFX) being evaluable for late sequelae and bRFS analyses. Pt characteristics were not statistically different in the two groups. CRT consisted of a 4-field technique for prostate and/or pelvic nodes and a 5-field boost with rectal shielding. Median doses were 74 and 79.2 Gy for STD and HFX patients respectively, the latter dose being isoeffective for tumour control assuming alpha/beta=10 (EQD(2)=73.9 Gy). Median follow-up was 29.4 months (25.2 mos for STD; 37.7 mos for HFX; P<0.01). The two regimens were compared in terms of acute and late GU and GI toxicities and 5-year bRFS by univariate and multivariate analyses. RESULTS: Acute grade> or =2 GU toxicity was higher in the STD group (48.6% versus 37.3% in HFX, P=0.03), while no significant difference was found for acute GI toxicity. Late grade> or =2 GU and GI toxicities were lower in the HFX group (5-year actuarial rate: GU: 10.1% versus 20.3%, P=0.05; GI: 6.0% versus 10.6%, P=0.18). Five-year bRFS were 70% (+/-13.8%, 95% CI) and 82.6% (+/-7.2%) for STD and HFX, respectively (P=0.44); a trend favouring HFX was found in the subgroup of pts who did not receive hormonal therapy (5-year bRFS: 85.9%+/-12.4% versus 63.9%+/-23.8%, P=0.15). Multivariate analysis revealed only risk groups and age statistically related to bRFS but not fractionation regimen. Using the Nahum-Chapman TLCP model and prostate parameter set, which includes hypoxia, the TLCPs are approximately equal for the two regimens, whereas assuming alpha/beta=1.5 and no hypoxia we obtain 73% for the STD group but only 36% for the HFX group. CONCLUSIONS: As expected from radiobiological considerations, HFX reduces GI and GU late toxicities. Concerning early bRFS, our clinical findings suggest that HFX is no less effective than STD when delivering an isoeffective (alpha/beta=10) dose. Despite the relatively short follow-up, this result appears to be inconsistent with a low alpha/beta ratio for prostate cancer.     

COVID‐19 and heart failure: from infection to inflammation and angiotensin II stimulation. Searching for evidence from a new disease

Patients with cardiovascular disease and, namely, heart failure are more susceptible to coronavirus disease 2019 (COVID‐19) and have a more severe clinical course once infected. Heart failure and myocardial damage, shown by increased troponin plasma levels, occur in at least 10% of patients hospitalized for COVID‐19 with higher percentages, 25% to 35% or more, when patients critically ill or with concomitant cardiac disease are considered. Myocardial injury may be elicited by multiple mechanisms, including those occurring with all severe infections, such as fever, tachycardia, adrenergic stimulation, as well as those caused by an exaggerated inflammatory response, endotheliitis and, in some cases, myocarditis that have been shown in patients with COVID‐19. A key role may be that of the renin–angiotensin–aldosterone system. Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infects human cells binding to angiotensin‐converting enzyme 2 (ACE2), an enzyme responsible for the cleavage of angiotensin II into angiotensin 1–7, which has vasodilating and anti‐inflammatory effects. Virus‐mediated down‐regulation of ACE2 may increase angiotensin II stimulation and contribute to the deleterious hyper‐inflammatory reaction of COVID‐19. On the other hand, ACE2 may be up‐regulated in patients with cardiac disease and treated with ACE inhibitors or angiotensin receptor blockers. ACE2 up‐regulation may increase the susceptibility to COVID‐19 but may be also protective vs. angiotensin II‐mediated vasoconstriction and inflammatory activation. Recent data show the lack of untoward effects of ACE inhibitors or angiotensin receptor blockers for COVID‐19 infection and severity. Prospective trials are needed to ascertain whether these drugs may have protective effects.     

Angiotensin-(1-12): A Chymase-Mediated Cellular Angiotensin II Substrate

Historically, primary hypertension (HTN) has been prevalent typically in adults. Recent data however, suggests an increasing number of children diagnosed with primary HTN, mainly in the setting of obesity. One of the factors considered in the etiology of HTN is the autonomous nervous system, namely its dysregulation. In the past, the sympathetic nervous system (SNS) was regarded as a system engaged mostly in buffering major acute changes in blood pressure (BP), in response to physical and emotional stressors. Recent evidence suggests that the SNS plays a much broader role in the regulation of BP, including the development and maintenance of sustained HTN by a chronically elevated central sympathetic tone in adults and children with central/visceral obesity. Consequently, attempts have been made to reduce the SNS hyperactivity, in order to intervene early in the course of the disease and prevent HTN-related complications later in life.     

The homopolymerization of 2,3-dimethyl-1,3-butadiene and the copolymerization of 1,3-butadiene/2,3-dimethyl-1,3-butadiene using the catalyst system AlEt2Cl-Co(acac)2. A structural investigation of the products

The homopolymerization of 2,3-dimethyl-1,3-butadiene with the catalyst system AlEt₂Cl-Co(acac)₂ affords polymers consisting of about 81% cis-1,4-units and 19% 1,2-units. The copolymerization of 1,3-butadiene/2,3-dimethyl-1,3-butadiene using the same system is of the ideal type and the composition of the copolymers is practically identical with that of the monomer mixture. The structure of the copolymers depends on their composition. The butadiene units, which are more than 95% cis-1,4 in the homopolymer, become partially 1,2 in the copolymers; their amount increases with increasing dimethylbutadiene content. Conversely, the fraction of dimethylbutadiene units with 1,2-structure decreases in the copolymers with increasing butadiene content. In the copolymers containing more than 50% of butadiene, the dimethylbutadiene units are practically all cis-1,4. The analysis of sequence distribution shows that the 1,2-butadiene units in the copolymers are not randomly distributed but are mostly adjacent to dimethylbutadiene units. The results obtained with dimethylbutadiene are compared with those reported for the homopolymerization of isoprene and the copolymerization of isoprene/butadiene using the same catalyst system.