The occurrence of prion protein in surgically resected pancreatic adenocarcinoma

Background: Among the several new targets for the comprehension of the biology of pancreatic ductal adenocarcinoma (PDAC), Prion proteins (PrPc) deserve particular mention, since they share a marked neurotropism. Actually, PrPc could have also a role in tumorigenesis, as recently demonstrated. However, only few in vitro studies in cell cultures showed the occurrence of PrPc in PDAC cells. We aim to evaluate the presence of PrPc in vivo in PDAC tissues as a potential new biomarker. Methods: Samples from tumors of 23 patients undergone pancreatic resections from July 2018 to May 2020 at our institution were collected and analyzed. Immunohistochemistry and western blotting of PDAC tissues were compared with control tissues. Immunohistochemistry was used also to evaluate the localization of PrPc and of CD155, a tumoral stem-cell marker. Results: All cases were moderately differentiated PDAC, with perineural invasion (PNI) in 19/23 cases (83%). According to western-blot analysis, PrPc was markedly expressed in PDAC tissues (273.5 ± 44.63 OD) respect to controls (100 ± 28.35 OD, p = 0.0018). Immunohistochemistry confirmed these findings, with higher linear staining of PrPc in PDAC ducts (127.145 ± 7.56 μm vs 75.21 ± 5.01 μm, p < 0.0001). PrPc and CD155 exactly overlapped in ductal tumoral cells, highlighting the possible relationship of PrPc with cancer stemness. Finally, PrPc expression related with cancer stage and there was a potential correspondence with PNI. Conclusions: Our work provides evidence for increased levels of PrPc in PDAC. This might contribute to cancer aggressiveness and provides a potentially new biomarker. Work is in progress to decipher clinical implications

Providing management options to control corn mouse (Calomys musculinus) reservoir populations using a cohort structured model

Fil: Piacenza, M. F. Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires; Argentina.Fil: Gomez, M. D. Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, ArgentinaFil: Simone, I. Grupo de Investigación en Ecología de Poblaciones, Facultad de Ciencias Exactas, Físico-Químicas y Naturales, Universidad Nacional de Río Cuarto, Córdoba; Argentina.Fil: Lamfri, Mario. Instituto Gulich, Comisión Nacional de Actividades Espaciales, Centro Espacial Teófilo Tabanera, Falda del Cañete, Córdoba; Argentina.Fil: Scavuzzo, C. M. Instituto Gulich, Comisión Nacional de Actividades Espaciales, Centro Espacial Teófilo Tabanera, Falda del Cañete, Córdoba; Argentina.Fil: Calderón, Gladys. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Virales Humanas; Argentina.Fil: Polop, Jaime J. Grupo de Investigación en Ecología de Poblaciones, Facultad de Ciencias Exactas, Físico-Químicas y Naturales, Universidad Nacional de Río Cuarto, Córdoba; Argentina.We evaluate several management options for Calomys musculinus populations through the formulation and validation of a cohort structured model. Initially, a basic model was constructed and validated using field population data. Next, the model was altered to allow us to evaluate different management options. In general, basic model results were in agreement with field data, demonstrating that this model would be useful in describing aspects of corn mouse population dynamics. Restricting control measures to when mouse numbers reach high levels would be inadequate, because population numbers tend to increase in size after some years. In contrast, reducing vegetation cover in spring was more effective in reducing field population abundances. Despite some limitations, the model could be useful for evaluating the relationships between population dynamics and some biotic or physical environmental variables, and thus ensure more efficient use of resources in integrated pest management

Przestrzenne i czasowe zmiany jakości wody w eutroficznym jeziorze ze sztucznym napowietrzaniem

In this work we present novel results concerning water quality changes in an eutrophic water body connected with an artificial aeration system installed in it. Sixty one in-situ and laboratory measurements of biogeochemical variables were recorded monthly between October 2008 and June 2011 to evaluate temporal and spatial changes in San Roque reservoir (Argentina). t-Student mean difference tests, carried out over the whole period, showed with 95% confidence that a monitoring point located at the centre of the water body is representative of the chemical behaviour of the reservoir. Thermal stratification was observed in all sampling sites in the summer, but the frequency of these episodes was markedly lower in bubbling zones. Mean chlorophyll-a concentrations were 58.9 μg∙dm–3 and 117.0 μg∙dm–3 in the absence and in the presence of thermocline respectively. According to the t-Student test, this difference was significant, with p < 0.001. Phosphate release from sediments was corroborated under hypoxia conditions. ANOVA one way analysis did not show significant spatial differences for any variable. Mean normalize spatial index (MENSI) was developed to compare data from different regions affected by high temporal variability. It proved to be useful to quantify spatial differences. Structure analysis of temporal series was used to scrutinize both chemical and spatial association successfully. Three chemically different zones were determined in the reservoir. This study demonstrated that spatial comparisons by means of marginal statistics may not be an adequate method when high temporal variation is present. In such a case, temporal structure analysis has to be considered.W pracy przedstawiono oryginalne wyniki dotyczące zmian jakości wody w eutroficznym zbiorniku wodnym związanych z zainstalowanym tam systemem sztucznego napowietrzania. Od października 2008 do czerwca 2011 r. dokonywano co miesiąc in situ i w laboratorium 61 pomiarów parametrów biogeochemicznych aby ocenić czasowe i przestrzenne zmiany w zbiorniku San Roque (Argentyna). Testy t-Studenta prowadzone dla całego okresu badawczego wykazały z 95-procentowym poziomem ufności, że stanowisko monitoringu zlokalizowane w centrum zbiornika wodnego jest reprezentatywne dla właściwości chemicznych całego zbiornika. Stratyfikację termiczną obserwowano latem we wszystkich stanowiskach badawczych, ale częstość wystąpień tych epizodów była znacząco mniejsza w strefie napowietrzania. Średnie stężenie chlorofilu a wynosiło 58,9 μg∙dm–3 i 117,0 μg∙dm–3 odpowiednio w warunkach braku i w warunkach występowaniu termokliny. Różnica wg testu t-Studenta była statystycznie istotna, gdy p < 0,001. Stwierdzono uwalnianie fosforanów z osadów w warunkach deficytu tlenowego. Jednoczynnikowa analiza ANOVA nie wykazała istotnego zróżnicowania przestrzennego żadnego z mierzonych parametrów. Utworzono średni znormalizowany indeks przestrzenny (MENSI) do porównania danych cechujących się dużą zmiennością czasową pochodzących z różnych regionów. Indeks okazał się użyteczny do ilościowego przedstawienia różnic przestrzennych. Przeprowadzono analizę struktury szeregów czasowych, aby przeanalizować powiązanie cech chemicznych ze zmiennością przestrzenną. Wyodrębniono trzy chemicznie odmienne strefy zbiornika. Badania wykazały, że analiza przestrzenna za pomocą statystyki jednoczynnikowej może nie być odpowiednią metodą w warunkach dużej zmienności czasowej. W takim przypadku należy rozważyć analizę struktury czasowej

SPANX-B and SPANX-C (Xq27 region) gene dosage analysis in Down's syndrome subjects with undescended testes

Down’s syndrome (DS) is one of the most common numer- ical chromosomal aberrations, usually caused by trisomy of chromosome 21, and is frequently complicated with congen- ital heart defects, duodenal obs truction and other conditions including undescended testis (UDT) (Fonkalsrud 1970). The incidence of undescended testes in DS was reported to be 6.52% (Chew and Hutson 2004) while the incidence of UDT in the first year is approximately 0.2%–0.8% in the nor- mal population (Benson et al . 1991; Ichiyanagi et al . 1998). Rapley et al . (2000) provided evidence for a testicular germ- cell tumours (TGCT) predisposition locus at Xq27; the au- thors obtained an hlod score of 4.7 from families with at least one bilateral case, corresponding to a genome-wide signifi- cance level of P = 0 . 034. The proportion of families with undescended testis linked to this locus was 74%. SPANX (sperm protein associated with the nucleus in the X chro- mosome) gene family maps in the same chromosomal region and seven highly homologous genes belonging to this fam- ily have been described ( SPANX-A1, SPANX-A2, SPANX-B1, SPANX-B2, SPANX-C, SPANX-D and SPANX-E ) according to the human genome database build 36.2. These genes, made up of two exons separated by a small intron of ≈ 650 bp, are expressed in sperm cells (Westbrook et al . 2000) and in many tumours (Wang et al . 2003; Zendman et al . 2003; Westbrook et al . 2004). Moreover, expression of SPANX genes has been demonstrated in TGCT (Salemi et al . 2006). The function of SPANX gene-encoded proteins is currently unknown, and it is also not known if all the members or some of them are normally expressed in the testis (West- brook et al . 2000). Evidence suggests that CTp11 ,which is 100% homologous to SPANX-C , is expressed in tumours such as melanoma (Zendman et al . 2003), and SPANX-B in myeloma and other haematological malignancies (Wang et al . 2003; Zendman et al . 2003). SPANX-C mRNA was found expressed in normal tissues and in embryonal carcinomas of the testis (Salemi et al . 2006). Further, it is very di ffi cult to design primers adequate for gene-specific PCR amplification within the SPANX locus. For this reason, we decided to fo- cus our study on SPANX-C and SPANX-B genes. The aim of this study is to evaluate the genetic variability of SPANX-B and SPANX-C in D.UDT (Down’s syndrom patients a ff ected by undescended testis) compared with D (Down’s syndrom patients without undescended testis) and Nm (normal popu- lation)

Combination of Lenvatinib and Pembrolizumab as Salvage Treatment for Paucicellular Variant of Anaplastic Thyroid Cancer: A Case Report

Anaplastic thyroid cancer (ATC) is a rare but aggressive thyroid cancer, responsible for about 50% of all thyroid cancer-related deaths. During the last two decades, the development of a multimodal personalized approach resulted in an increased survival. Here, we present an unusual case of a 54-year old woman with a paucicellular metastatic ATC, a rare variant of ATC, who was treated with a combination of surgery, radiation therapy and cytotoxic chemotherapy. More than two years later, when the disease was rapidly growing, a combination of lenvatinib and pembrolizumab induced a partial tumor response of lung metastasis that persisted over 18 months. Paucicellular ATC may initially show a less aggressive behavior compared to other histological ATC variants. However, over the time, its clinical course can rapidly progress like common ATC. The combination of lenvatinib and pembrolizumab was effective as a salvage therapy for a long period of time

Nuova architettura per l’Università Bocconi, Roberto Collovà

Progetto di concorso per l'ampliamento dell'università Bocconi, Milano 200