Biobanking of human gut organoids for translational research

Perrone Francesca,Zilbauer Matthias 생화학분자생물학회 2021 Experimental and molecular medicine Vol.53 No.-

The development of human organoid culture models has led to unprecedented opportunities to generate self-organizing, three-dimensional miniature organs that closely mimic in vivo conditions. The ability to expand, culture, and bank such organoids now provide researchers with the opportunity to generate next-generation living biobanks, which will substantially contribute to translational research in a wide range of areas, including drug discovery and testing, regenerative medicine as well as the development of a personalized treatment approach. However, compared to traditional tissue repositories, the generation of a living organoid biobank requires a much higher level of coordination, additional resources, and scientific expertise. In this short review, we discuss the opportunities and challenges associated with the generation of a living organoid biobank. Focusing on human intestinal organoids, we highlight some of the key aspects that need to be considered and provide an outlook for future development in this exciting field.

REMARKS ON LEVI HARMONICITY OF CONTACT SEMI-RIEMANNIAN MANIFOLDS

Perrone, Domenico Korean Mathematical Society 2014 대한수학회지 Vol.51 No.5

In a recent paper [10] we introduced the notion of Levi harmonic map f from an almost contact semi-Riemannian manifold (M, ${\varphi}$, ${\xi}$, ${\eta}$, g) into a semi-Riemannian manifold $M^{\prime}$. In particular, we compute the tension field ${\tau}_H(f)$ for a CR map f between two almost contact semi-Riemannian manifolds satisfying the so-called ${\varphi}$-condition, where $H=Ker({\eta})$ is the Levi distribution. In the present paper we show that the condition (A) of Rawnsley [17] is related to the ${\varphi}$-condition. Then, we compute the tension field ${\tau}_H(f)$ for a CR map between two arbitrary almost contact semi-Riemannian manifolds, and we study the concept of Levi pluriharmonicity. Moreover, we study the harmonicity on quasicosymplectic manifolds.

Acute Promyelocytic Leukemia After Radium-223 Exposure for Prostate Cancer in a Chemotherapy-Naïve Patient

Perrone Salvatore,Ortu La Barbera Elettra,Ottone Tiziana,Capriata Marcello,Passucci Mauro,Filippi Luca,Bagni Oreste,Voso Maria Teresa,Cimino Giuseppe 대한핵의학회 2020 핵의학 분자영상 Vol.54 No.5

223Ra-dichloride is a bone-seeking targeted alpha (α)-emitting approved for bonemetastases in prostate cancer. Here, we report a case of therapy-related acute promyelocytic leukemia (t-APL) following administration of 223Ra, showing some evidence of a causative relationship. A patient with metastatic prostate cancer received therapy with 223Ra, with 6 injections of the radiopharmaceutical at a standard dose of 55 kBq/kg at 4-week intervals for a cumulative administered activity of 26.3MBq. PET/CT with 18F-methylcholine repeated 1 month after the conclusion of 223Ra was negative. After 8 months, he developed pancytopenia and we made a diagnosis of therapy-related acute promyelocytic leukemia (t-APL). We then studied the genomic locations of the breakpoints in the PML and RARA genes, which were at nucleotide positions 1708-09 of PML intron 3, respectively, outside the previously reported Topo II-associated hotspot region. t-APL was cured with all-trans-retinoic acid (ATRA) and arsenic trioxide. The type of PML/RARA rearrangement we identified, in absence of other myelotoxic treatments, is suggestive of a possible direct causal relationship with exposure to 223Ra and warrants further investigations.

Laparoscopic vs. robotic-assisted laparoscopy in endometrial cancer staging: large retrospective single institution study

Emanuele Perrone,Ilaria Capasso,Tina Pasciuto,Alessandro Gioè,Salvatore Gueli Alletti,Stefano Restaino,Giovanni Scambia,Francesco Fanfani 대한부인종양학회 2021 Journal of Gynecologic Oncology Vol.32 No.3

Objective: The aim of this study is to analyze and draw the potential differences between therobotic-assisted surgery (RS) and the laparoscopy (LPS) in endometrial cancer staging. Methods: In this single-institution retrospective study we enrolled 1,221 consecutive clinicalstage I–III endometrial cancer patients undergone minimally invasive surgical staging. Wecompared patients treated by LPS and by RS, on the basis of perioperative and oncologicaloutcomes (disease-free survival [DFS] and overall survival [OS]). A sub-analysis of the high risk endometrial cancer population was performed in the 2 cohorts. Results: The 2 cohorts (766 treated by LPS and 455 by RS) were homogeneous in termsof perioperative and pathological data. We recorded differences in number of relapse/progression (11.7% in LPS vs. 7% in RS, p=0.008) and in number of deaths (9.8% in LPSvs. 4.8% in RS, p=0.002). Whereas, univariate and multivariate analyses according to DFSand OS confirmed that the surgical approach did not influence the DFS or the OS. In themultivariable analysis the association of the age and grading was significant for DFS and OS. In the sub-analysis of the 426 high risk EC patients (280 in LPS and 146 in RS) the univariateand the multivariate confirmed the influence of the age in DFS and OS, independently of theminimally invasive approach. Conclusions: In our large retrospective analysis, we confirmed that the RS and LPS havesimilar efficacy and safety for endometrial cancer staging also for the high-risk endometrialcancer patients.

REMARKS ON LEVI HARMONICITY OF CONTACT SEMI-RIEMANNIAN MANIFOLDS

Domenico Perrone 대한수학회 2014 대한수학회지 Vol.51 No.5

In a recent paper [10] we introduced the notion of Levi har- monic map f from an almost contact semi-Riemannian manifold (M,ϕ,ξ, η,g) into a semi-Riemannian manifold M ′ . In particular, we computed the tension field τ H (f) for a CR map f between two almost contact semi-Riemannian manifolds satisfying the so-called ϕ-condition, where H = Ker(η) is the Levi distribution. In the present paper we show that the condition (A) of Rawnsley [17] is related to the ϕ-condition. Then, we compute the tension field τ H (f) for a CR map between two arbitrary almost contact semi-Riemannian manifolds, and we study the concept of Levi pluriharmonicity. Moreover, we study the harmonicity on quasi- cosymplectic manifolds.

Steel nitriding optimization through multi-objective and FEM analysis

Cavaliere, Pasquale,Perrone, Angelo,Silvello, Alessio Society for Computational Design and Engineering 2016 Journal of computational design and engineering Vol.3 No.1

Steel nitriding is a thermo-chemical process leading to surface hardening and improvement in fatigue properties. The process is strongly influenced by many different variables such as steel composition, nitrogen potential, temperature, time, and quenching media. In the present study, the influence of such parameters affecting physic-chemical and mechanical properties of nitride steels was evaluated. The aim was to streamline the process by numerical-experimental analysis allowing defining the optimal conditions for the success of the process. Input parameters-output results correlations were calculated through the employment of a multi-objective optimization software, modeFRONTIER (Esteco). The mechanical and microstructural results belonging to the nitriding process, performed with different processing conditions for various steels, are presented. The data were employed to obtain the analytical equations describing nitriding behavior as a function of nitriding parameters and steel composition. The obtained model was validated, through control designs, and optimized by taking into account physical and processing conditions.

A Possible Pathogenic Linkage Among Headache, Migraine, and Nocturnal Enuresis in Children

Pietro Ferrara,Livia Dell’Aquila,Giacomo Perrone,Giulia Spina,Francesco Miconi,Valentina Rapaccini,Ester Del Vescovo,Vincenzo Di Lazzaro,Alberto Verrotti 대한배뇨장애요실금학회 2016 International Neurourology Journal Vol.20 No.4

Purpose: This study aims to evaluate the prevalence of headaches and migraine in children with nocturnal enuresis (NE) and to improve knowledge on these conditions. In particular, for this purpose, a possible pathogenic relationship linking both conditions and the impact of headaches and migraine on NE persistence was evaluated. Methods: Researchers enrolled 123 children with NE, aged between 5 and 15 years, referred to the Service of Pediatrics, Campus Bio-Medico University Hospital of Rome between January 2014 and January 2015. Parents of all children enrolled in the study were invited to complete a self-reported questionnaire. The study protocol was approved by the Human Research Ethics Committee of Campus-Bio-Medico University. The NE group data was compared with the data of a control group (107 children). Results: Of the eligible patients, 7.8% suffer from headaches/migraine (mean age, 9.63 years; interquartile range [IQR], 3.5 years) and 47.1% have a family history of headaches (mean age, 8.46 years; IQR, 3.75 years). Of the 8 patients with headaches, all are male, 3 have tension-type headaches (2 of them have maternal family history) and 5 have migraine (3 of them have maternal family history). Of the 35.3% with a migraine family history (mean age, 8.36 years; IQR, 3.5 years), 22 are male, and 14 are female. Three of these patients have migraine. A total of 92.2% suffer from NE but not from headaches (mean age, 8.43 years; IQR, 3 years). Of these patients, 33 are female (35.1%), and 61 are male (64.9%). In the control group, 4.7% (5 out of 107) of the children suffer from headaches, and of these, 4 are affected by nonmigraine headaches and 1 by migraine. Conclusions: In conclusion, according to the hypothesis, NE and headaches/migraine could be linked by several similarities.

Synthesis and Evaluation of Tricarbonyl ^99m Tc-Labeled 2-(4-Chloro)phenyl-imidazo[1,2- <i>a</i> ]pyridine Analogs as Novel SPECT Imaging Radiotracer for TSPO-Rich Cancer

Choi, Ji Young,Iacobazzi, Rosa Maria,Perrone, Mara,Margiotta, Nicola,Cutrignelli, Annalisa,Jung, Jae Ho,Park, Do Dam,Moon, Byung Seok,Denora, Nunzio,Kim, Sang Eun,Lee, Byung Chul MDPI 2016 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol.17 No.7

<P>The 18-kDa translocator protein (TSPO) levels are associated with brain, breast, and prostate cancer progression and have emerged as viable targets for cancer therapy and imaging. In order to develop highly selective and active ligands with a high affinity for TSPO, imidazopyridine-based TSPO ligand (CB256, <B>3</B>) was prepared as the precursor. <SUP>99m</SUP>Tc- and Re-CB256 (<B>1</B> and <B>2</B>, respectively) were synthesized in high radiochemical yield (74.5% ± 6.4%, decay-corrected, <I>n</I> = 5) and chemical yield (65.6%) by the incorporation of the [<SUP>99m</SUP>Tc(CO)<SUB>3</SUB>(H<SUB>2</SUB>O)<SUB>3</SUB>]<SUP>+</SUP> and (NEt<SUB>4</SUB>)<SUB>2</SUB>[Re(CO)<SUB>3</SUB>Br<SUB>3</SUB>] followed by HPLC separation. Radio-ligand <B>1</B> was shown to be stable (>99%) when incubated in human serum for 4 h at 37 °C with a relatively low lipophilicity (log<I>D</I> = 2.15 ± 0.02). The rhenium-185 and -187 complex <B>2</B> exhibited a moderate affinity (<I>K</I><SUB>i</SUB> = 159.3 ± 8.7 nM) for TSPO, whereas its cytotoxicity evaluated on TSPO-rich tumor cell lines was lower than that observed for the precursor. In vitro uptake studies of <B>1</B> in C6 and U87-MG cells for 60 min was found to be 9.84% ± 0.17% and 7.87% ± 0.23% ID, respectively. Our results indicated that <SUP>99m</SUP>Tc-CB256 can be considered as a potential new TSPO-rich cancer SPECT imaging agent and provides the foundation for further in vivo evaluation.</P>

Melatonin’s Effect on the Efficacy of Desmopressin in the Treatment of Enuresis

Pietro Ferrara,Annamaria Sbordone,Costanza Cutrona,Francesca Ianniello,Chiara Guadagno,Giacomo Perrone,Antonio Chiaretti,Alberto Verrotti,Vincenzo Di Lazzaro 대한배뇨장애요실금학회 2016 International Neurourology Journal Vol.20 No.3

Purpose: This study aims to evaluate and compare the efficacy of exogenous melatonin associated with desmopressin (dDAVP) and dietary recommendations. Methods: A total of 189 patients were enrolled from the Service of Pediatrics, Campus Bio-Medico University Hospital of Rome, from January 2013 to June 2015. Of the 189 original patients, 153 children, aged between 5 and 14 years (mean age, 8.7 years) were included in the study. After clinical evaluation and a 3-month period of observation without treatment, children were assigned to receive treatment in one of 3 groups: group 1, dDAVP at a dose of 120 mcg a day (Minirin); group 2, dDAVP at a dose of 120 mcg and dietary recommendations; or group 3, dDAVP at a dose of 120 mcg, dietary recommendations, and melatonin at a dose of 1 mg a day (Melamil plus). Each patient was treated for 3 months. Results: After the 3 months of therapy, a desiderable response was achieved in 30 of 51 patients (58.82%) treated with dDAVP, 35 of 53 patients (66.04%) treated with dDAVP and dietary recommendations, and 35 of 49 patients (71.43%) treated with dDAVP, dietary recommendations, and melatonin. Conclusions: Although not statistically significant, the results show that the association between dDAVP treatment with dietary recommendations and melatonin could be considered a safe and effective treatment of NE. Considering that the statistically insignificant results might be due to the small sample size, the study will be continued to increase the number of subjects.

Fertility-sparing treatment for intramucous, moderately differentiated, endometrioid endometrial cancer: a Gynecologic Cancer Inter-Group (GCIG) study

Francesca Falcone,Umberto Leone Roberti Maggiore,Violante Di Donato,Anna Myriam Perrone,Luigi Frigerio,Giuseppe Bifulco,Stephan Polterauer,Paolo Casadio,Gennaro Cormio,Valeria Masciullo,Mario Malzoni 대한부인종양학회 2020 Journal of Gynecologic Oncology Vol.31 No.5

Objective: ‘The Endometrial Cancer Conservative Treatment (E.C.Co.). A multicentre archive’is a worldwide project endorsed by the Gynecologic Cancer Inter-Group, aimed at registeringconservatively treated endometrial cancer (EC) patients. This paper reports the oncologicaland reproductive outcomes of intramucous, G2, endometrioid EC patients from this archive. Methods: Twenty-three patients (Stage IA, G2, endometrioid EC) were enrolled betweenJanuary 2004 and March 2019. Primary and secondary endpoints were, respectively, completeregression (CR) and recurrence rates, and pregnancy and live birth rates. Results: A median follow-up of 35 months (9–148) was achieved. Hysteroscopic resection(HR) plus progestin was adopted in 74% (17/23) of cases. Seventeen patients showed CR(median time to CR, 6 months; 3-13). Among the 6 non-responders, one showed persistenceand 5 progressed, all submitted to definitive surgery, with an unfavorauble outcome in one. The recurrence rate was 41.1%. Ten (58.8%) complete responders attempted to conceive, ofwhom 3 achieved at least one pregnancy with a live-birth. Two out of the 11 candidate patientsunderwent definitive surgery, while the remaining 9 have so far refused. To date, 22 patientsshow no evidence of disease, and one is still alive with disease. Conclusions: Fertility-sparing treatment seems to be feasible even in G2 EC, although cautionshould be kept considering the potential pathological undergrading or non-endometrioid histology misdiagnosis. The low rate of attempt to conceive and of compliance to definitivesurgery underline the need for a ‘global’ counselling extended to the follow-up period.