Clinical and Experimental Projects on Chemotherapy of Bladder Tumours

Our clinical and experimental experience with chemotherapy of bladder tumours is reviewed. The routes of drug administrations, drug dosages and combinations, are presented. Adjuvant radiotherapy and chemoprophylaxis of certain tumours are discussed.S. Afr. Med. J., 48, 631 (1974

Clinical and experimental projects on chemotherapy of bladder tumours

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Neuroprotective effects of human amniotic fluid stem cells-derived secretome in an ischemia/reperfusion model

Stem cells offer the basis for the promotion of robust new therapeutic approaches for a variety of human disorders. There are still many limitations to be overcome before clinical therapeutic application, including a better understanding of the mechanism by which stem cell therapies may lead to enhanced recovery. In vitro investigations are necessary to dissect the mechanisms involved and to support the potential development in stem cell-based therapies. In spite of growing interest in human amniotic fluid stem cells, not much is known about the characteristics of their secretome and regarding the potential neuroprotective mechanism in different pathologies, including stroke. To get more insight on amniotic fluid cells therapeutic potential, signal transduction pathways activated by human amniotic fluid stem cells (hAFSCs)-derived secretome in a stroke in vitro model (ischemia/reperfusion [I/R] model) were investigated by Western blot. Moreover, miRNA expression in the exosomal fraction of the conditioned medium was analyzed. hAFSCs-derived secretome was able to activate pro-survival and anti-apoptotic pathways. MicroRNA analysis in the exosomal component revealed a panel of 16 overexpressed miRNAs involved in the regulation of coherent signaling pathways. In particular, the pathways of relevance in ischemia/reperfusion, such as neurotrophin signaling, and those related to neuroprotection and neuronal cell death, were analyzed. The results obtained strongly point toward the neuroprotective effects of the hAFSCs-conditioned medium in the in vitro stroke model here analyzed. This can be achieved by the modulation and activation of pro-survival processes, at least in part, due to the activity of secreted miRNAs

Monitoring of Land Subsidence in Ravenna Municipality Using Integrated SAR - GPS Techniques: Description and First Results

The Emilia Romagna Region (N-E Italy) and in particular the Adriatic Sea coastline of Ravenna, is affected by a noticeable subsidence that started in the 1950s, when the exploitation of on and off-shore methane reservoirs began, along with the pumping of groundwater for industrial uses. In such area the current subsidence rate, even if lower than in the past, reaches the -2 cm/y. Over the years, local Authorities have monitored this phenomenon with different techniques: spirit levelling, GPS surveys and, more recently, Differential Interferometric Synthetic Aperture Radar (DInSAR) techniques, confirming the critical situation of land subsidence risk. In this work, we present the comparison between the results obtained with DInSAR and GPS techniques applied to the study of the land subsidence in the Ravenna territory. With regard to the DInSAR, the Small Baseline Subset (SBAS) and the Coherent Pixel Technique (CPT) techniques have been used. Different SAR datasets have been exploited: ERS-1/2, ENVISAT, TerraSAR-X and Sentinel-1. Some GPS campaigns have been also carried out in a subsidence prone area. 3D vertices have been selected very close to existing persistent scatterers in order to link the GPS measurement results to the SAR ones. GPS data were processed into the International reference system and the comparisons between the coordinates, for the first 6 months of the monitoring, provided results with the same trend of the DInSAR data, even if inside the precision of the method

Surgical Treatment of Spinal Meningiomas in the Elderly (≥75 Years): Which Factors Affect the Neurological Outcome? An International Multicentric Study of 72 Cases

(1) Background: With the increasing life expectancy in the Western world, an increasing number of old patients presents with spinal meningioma. Considering the benign nature of these tumors, the functional outcome remains of great importance, since more people reach old age in general conditions of well-being and satisfactory autonomy. (2) Methods: We conducted an international multicenter retrospective study to investigate demographic, clinical and radiological data in a population of elderly patients (≥75 years of age) undergoing surgery for SM from January 2000 to December 2020 in four European referral centers. The aim was to identify prognostic and predictive factors for a good postoperative functional outcome. (3) Results: 72 patients were included in the study. Complete tumor resection (Simpson I or II) was achieved in 67 (95.7%) cases. Intraoperative complications were reported in 7 (9.9%) patients while postoperative complications were found in 12 (16.7%). An excellent general postoperative status (McCormick I and II) was achieved in 65.3%. Overall, surgical resection had a good impact on patients’ functional outcome (86.1% either showing an improvement or maintaining a good preoperative status). Uni- and multivariate analyses found that both age and preoperative modified McCormick independently correlated with relative outcome (coeff = −0.058, p = 0.0251; coeff = 0.597, p < 0.0001) and with postoperative status (coeff = 0.058, p = 0.02507; coeff = 0.402, p = 0.00027), respectively. (4) Conclusions: Age and preoperative modified McCormick were found to be independent prognostic factors. Nevertheless, advanced age (≥75), per se, did not seem to contraindicate surgery, even in those with severe preoperative neurological deficits. The functional results sustain the need for surgical resection of SM in the elderly

Anthracycline-Free Neoadjuvant Treatment in Patients with HER2-Positive Breast Cancer: Real-Life Use of Pertuzumab, Trastuzumab and Taxanes Association with an Exploratory Analysis of PIK3CA Mutational Status

HER2 is considered one of the most traditional prognostic and predictive biomarkers in breast cancer. Literature data confirmed that the addition of pertuzumab to a standard neoadjuvant chemotherapy backbone (either with or without anthracyclines), in patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (EBC), leads to a higher pathological complete response (pCR) rate, which is known to correlate with a better prognosis. In this retrospective analysis, 47 consecutive patients with HER2-positive EBC received sequential anthracyclines and taxanes plus trastuzumab (ATH) or pertuzumab, trastuzumab and docetaxel (THP). Despite the limited sample size, this monocentric experience highlights the efficacy (in terms of pCR) and safety of THP in the neoadjuvant setting of HER2-positive EBC as an anthracycline-free approach. Given the role of PIK3CA as a prognostic and therapeutic target in breast cancer, tumors were also analyzed to assess the PIK3CA mutational status. Thirty-eight out of forty-seven patients were evaluated, and PIK3CA variants were identified in 21% of tumor samples: overall, one mutation was detected in exon 4 (2.6%), two in exon 9 (5.3%) and four in exon 20 (10.5%). Of note, one sample showed concurrent mutations in exons 9 (codon 545) and 20 (codon 1047). Among patients reaching pCR (n = 13), 38.5% were PIK3CA mutants; on the other hand, among those lacking pCR (n = 25), just 12% showed PIK3CA variants. Regarding THP-treated mutant patients (n = 5), 80% reached pCR (three hormone-receptor-negative, one hormone-receptor-positive). Interestingly, the only patient not achieving pCR had a tumor with two co-occurring PIK3CA mutations. In conclusion, this study provides new evidence about the efficacy and good safety profile of THP, compared to the ATH regimen, as an anthracycline-free neoadjuvant treatment of HER2-positive EBC. Further studies on larger/multicentric cohorts are planned for more in-depth analysis to confirm our molecular and clinical results

Novel P53 mutations detected by FAMA in colorectal cancers

Background: The aim of the study was to identify p53 gene mutations by FAMA (fluorescence-assisted mismatch analysis) in colorectal cancers. Patients and methods: Analytical scanning of the p53 gene (exons 5\u20139) was performed in colon cancer samples from 44 consecutive patients by FAMA. FAMA is a semiautomatic scanning approach based on the chemical cleavage of the mismatch in fluorescently labeled heteroduplex DNA, obtained from the combination of a normal and a mutated allele. FAMA has already shown optimal levels of diagnostic accuracy and sensitivity in detecting gene mutations (nucleotide substitutions, insertions/deletions) both at the germline and somatic level. The peculiar feature of FAMA is its ability to detect and localize mutations, by a redundant pattern of signals due to fluorescent DNA fragments generated by chemical cleavage. Moreover, previous data have demonstrated that normal contaminating DNA from stromal cells in the sample does not affect the sensitivity of the procedure, leading to the identification of the mutation even when the ratio mutant/normal allele is 10%. Results: Eighteen mutations (12 missense, one nonsense, two deletions, three nucleotide substitutions at the level of the splice-junctions) and two polymorphisms were detected by FAMA in 17 patients (39%) and then confirmed by automated sequence analysis. Six of 18 mutations (33%) were not previously reported for colon cancer samples and two of 18 lesions (11%) were identified as novel p53 mutations. Conclusions: Analytical scanning of the p53 gene by FAMA in DNA from colon cancer samples provides a sensitive, accurate and specific diagnostic procedure for routine clinical application

Diagnostic accuracy of ultrasound dilution access blood flow measurement in detecting stenosis and predicting thrombosis in native forearm arteriovenous fistulae for hemodialysis.

BACKGROUND: Vascular access surveillance by ultrasound dilution blood flow rate (Qa) measurement is widely recommended; however, optimal criteria for detecting stenosis and predicting thrombosis in arteriovenous fistulae (AVFs) are still not clearly defined. METHODS: In a blinded trial, we evaluated the accuracy of single Qa measurement, Qa adjusted for mean arterial pressure (Qa/MAP), and decrease in Qa over time (dQa) in detecting stenosis and predicting thrombosis in an unselected population of 120 hemodialysis subjects with native forearm AVFs (91 AVFs, located at the wrist; 29 AVFs, located at the midforearm). All AVFs underwent fistulography, which identified greater than 50% stenosis in 54 cases. RESULTS: Receiver operating characteristic curve analysis showed that dQa, Qa, and Qa/MAP have a high stenosis discriminative ability with similar areas under the curve (AUCs), ie, 0.961 +/- 0.025, 0.946 +/- 0.021, and 0.912 +/- 0.032, respectively. In the population as a whole, optimal thresholds for stenosis were Qa less than 750 mL/min alone and in combination with dQa greater than 25% (efficiency, 90%); however, the best threshold depended on anastomotic site; it was Qa less than 750 mL/min for an AVF at the wrist and Qa less than 1,000 mL/min for an AVF in the midforearm. Qa was the best predictor of incipient thrombosis (AUC, 0.981 +/- 0.013) with an optimal threshold at less than 300 mL/min (efficiency, 94%). Pooled intra-assay and interassay variation coefficients were 8.2% for MAP, 7.9% for Qa, and 11.2% for Qa/MAP. CONCLUSION: Our study shows that ultrasound dilution Qa measurement is a reproducible and highly accurate tool for detecting stenosis and predicting thrombosis in forearm AVFs. Neither Qa/MAP nor dQa improve the diagnostic performance of Qa alone, although its combination with dQa increases the test's sensitivity for stenosis

Approximate Controllability for Linear Stochastic Differential Equations in Infinite Dimensions

The objective of the paper is to investigate the approximate controllability property of a linear stochastic control system with values in a separable real Hilbert space. In a first step we prove the existence and uniqueness for the solution of the dual linear backward stochastic differential equation. This equation has the particularity that in addition to an unbounded operator acting on the Y-component of the solution there is still another one acting on the Z-component. With the help of this dual equation we then deduce the duality between approximate controllability and observability. Finally, under the assumption that the unbounded operator acting on the state process of the forward equation is an infinitesimal generator of an exponentially stable semigroup, we show that the generalized Hautus test provides a necessary condition for the approximate controllability. The paper generalizes former results by Buckdahn, Quincampoix and Tessitore (2006) and Goreac (2007) from the finite dimensional to the infinite dimensional case.Comment: 31 pages, submitted to AM