15 results on '"Federica de Cicco"'
Search Results
2. Pathology Reporting in Neuroendocrine Neoplasms of the Digestive System: Everything You Always Wanted to Know but Were Too Afraid to Ask
- Author
-
Manuela Albertelli, Federica Grillo, Fabio Lo Calzo, Giulia Puliani, Carmen Rainone, Annamaria Anita Livia Colao, Antongiulio Faggiano, NIKE group, Barbara Altieri, Luigi Barrea, Filomena Bottiglieri, Severo Campione, Federica De Cicco, Sergio Di Molfetta, Alessandra Dicitore, Carlotta Dolci, Tiziana Feola, Giuseppe Fanciulli, Diego Ferone, Francesco Ferraù, Marco Gallo, Elisa Giannetta, Erika Grossrubatscher, Elia Guadagno, Valentina Guarnotta, Andrea M. Isidori, Andrea Lania, Andrea Lenzi, Pasquale Malandrino, Erika Messina, Roberta Modica, Giovanna Muscogiuri, Luca Pes, Genoveffa Pizza, Riccardo Pofi, Paola Razzore, Laura Rizza, Manila Rubino, Rosa Maria Ruggieri, Emilia Sbardella, Franz Sesti, Mary Anna Venneri, Giovanni Vitale, and Maria Chiara Zatelli
- Subjects
neuroendocrine neoplasms (NENs) ,neuroendocrine classification ,immunohistochemistry ,pathology ,morphology ,grade ,Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
During the 5th NIKE (Neuroendocrine tumors Innovation in Knowledge and Education) meeting, held in Naples, Italy, in May 2019, discussions centered on the understanding of pathology reports of gastroenetropancreactic neuroendocrine neoplasms. In particular, the main problem concerned the difficulty that clinicians experience in extrapolating relevant information from neuroendocrine tumor pathology reports. During the meeting, participants were asked to identify and rate issues which they have encountered, for which the input of an expert pathologist would have been appreciated. This article is a collection of the most rated questions and relative answers, focusing on three main topics: 1) morphology and classification; 2) Ki67 and grading; 3) immunohistochemistry. Patient management should be based on multidisciplinary decisions, taking into account clinical and pathology-related features with clear comprehension between all health care professionals. Indeed, pathologists require clinical details and laboratory findings when relevant, while clinicians require concise and standardized reports. In keeping with this last statement, the minimum requirements in pathology datasets are provided in this paper and should be a baseline for all neuroendocrine tumor professionals.
- Published
- 2021
- Full Text
- View/download PDF
3. Vitamin D deficiency and tumor aggressiveness in gastroenteropancreatic neuroendocrine tumors
- Author
-
Roberta Modica, Carolina Di Somma, Antongiulio Faggiano, Giovanna Muscogiuri, Luigi Barrea, Luisa Circelli, Filomena Bottiglieri, Barbara Altieri, Silvia Savastano, Annamaria Colao, Giovanni Savarese, Federica de Cicco, Altieri, B., Barrea, L., Modica, R., Bottiglieri, F., de Cicco, F., Muscogiuri, G., Circelli, L., Savarese, G., Di Somma, C., Savastano, S., Colao, A., and Faggiano, A.
- Subjects
Intestinal Neoplasm ,medicine.medical_specialty ,Prognosi ,Endocrinology, Diabetes and Metabolism ,Neuroendocrine tumors ,Gastroenterology ,vitamin D deficiency ,Somatostatin analog ,Endocrinology ,Neuroendocrine tumor ,Retrospective Studie ,Stomach Neoplasm ,Stomach Neoplasms ,Diabetes mellitus ,Internal medicine ,Intestinal Neoplasms ,medicine ,Vitamin D and neurology ,Humans ,Vitamin D ,Retrospective Studies ,Cross-Sectional Studie ,25(OH)D ,business.industry ,Incidence (epidemiology) ,Pancreatic Neoplasm ,Vitamin D Deficiency ,medicine.disease ,Primary tumor ,Pancreatic Neoplasms ,Neuroendocrine Tumors ,MEN1 ,Cross-Sectional Studies ,business ,Body mass index ,Progressive disease ,PTH ,Human - Abstract
Purpose: Data regarding vitamin D status in patients affected by gastroenteropancreatic (GEP) neuroendocrine tumor (NET) are limited and often showing contrasting results. The aim of the study was to evaluate the incidence of vitamin D deficiency (
- Published
- 2021
4. Quality of Life in Patients with Neuroendocrine Neoplasms: The Role of Severity, Clinical Heterogeneity, and Resilience
- Author
-
Pasquale Dolce, Annamaria Colao, Greta G Dipietrangelo, Nelson Mauro Maldonato, Benedetta Muzii, Federica de Cicco, Cristiano Scandurra, Elisa Giannetta, Andrea M. Isidori, Andrea Lenzi, Roberta Centello, Roberta Modica, Antongiulio Faggiano, Filomena Bottiglieri, Valentina Di Vito, Scandurra, Cristiano, Modica, Roberta, Maldonato, Nelson Mauro, Dolce, Pasquale, Dipietrangelo, Greta G, Centello, Roberta, Di Vito, Valentina, Bottiglieri, Filomena, de Cicco, Federica, Giannetta, Elisa, Isidori, Andrea M, Lenzi, Andrea, Muzii, Benedetta, Faggiano, Antongiulio, and Colao, Annamaria
- Subjects
Adult ,Male ,medicine.medical_specialty ,Constipation ,Endocrinology, Diabetes and Metabolism ,media_common.quotation_subject ,Clinical Biochemistry ,Social Interaction ,severity ,Context (language use) ,Severity of Illness Index ,Biochemistry ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Quality of life ,Internal medicine ,medicine ,Global health ,Humans ,In patient ,030212 general & internal medicine ,metastases ,resilience ,Aged ,media_common ,Biochemistry (medical) ,Middle Aged ,Resilience, Psychological ,Moderation ,Clinical trial ,Neuroendocrine Tumors ,Psychosocial Functioning ,Cross-Sectional Studies ,Biological Variation, Population ,Italy ,quality of life ,metastase ,030220 oncology & carcinogenesis ,Female ,Psychological resilience ,heterogeneity ,medicine.symptom ,neuroendocrine tumor - Abstract
Context Although health-related quality of life (HRQoL) is a fundamental outcome in oncological clinical trials, its evaluation in the neuroendocrine neoplasm (NEN) research field is still limited. Objectives This study assessed the role of clinical severity (ie, presence or absence of metastasis and lines of therapies) and heterogeneity (ie, primary site, types of therapy, biology, and surgery) of NEN in relation to HRQoL, as well as resilience as a moderator between clinical severity and HRQoL. Design Cross-sectional multicentric study. Setting Italian university hospitals. Patients A total of 99 Italian patients (53 men and 46 women) with NEN and ranged in age from 22–79 years old. Main Outcome Measure Severity and heterogeneity of NENs, HRQoL, and resilience. Results The presence of metastasis and a greater number of therapies affected the global health and some physical symptoms. Resilience was associated with global health, functional status, and some physical symptoms, and it moderated the impact of metastases on constipation and of the multiple therapies on diarrhea and financial problems. Patients with NEN in districts other than the gastroenteropancreatic system and those in follow-up perceived fewer physical symptoms than their counterparts. Patients with a sporadic NEN perceived their functional status, global health, and disease-related worries as better than those with a hereditary NEN. Patients who underwent surgery were lower in constipation than their counterparts. Conclusion These findings highlight the need to assess the relationships between the clinical severity and heterogeneity of NEN with HRQoL and the role of resilience in improving patients’ HRQoL.
- Published
- 2020
5. Case Report: Abdominal Lymph Node Metastases of Parathyroid Carcinoma: Diagnostic Workup, Molecular Diagnosis, and Clinical Management
- Author
-
Giuseppe Fanciulli, Sergio Di Molfetta, Andrea Dotto, Tullio Florio, Tiziana Feola, Annamaria Colao, Antongiulio Faggiano, NIKE Group, Manuela Albertelli, Barbara Altieri, Luigi Barrea, Filomena Bottiglieri, Severo Campione, Federica de Cicco, Alessandra Dicitore, Diego Ferone, Francesco Ferraù, Erika Grossrubatscher, Marco Gallo, Elisa Giannetta, Federica Grillo, Elia Guadagno, Valentina Guarnotta, Andrea M. Isidori, Andrea Lania, Andrea Lenzi, Fabio Lo Calzo, Pasquale Malandrino, Erika Messina, Roberta Modica, Giovanna Muscogiuri, Genoveffa Pizza, Riccardo Pofi, Giulia Puliani, Carmen Rainone, Paola Razzore, Laura Rizza, Manila Rubino, Rosa Maria Ruggieri, Emilia Sbardella, Franz Sesti, Mary Anna Venneri, Giovanni Vitale, Maria Chiara Zatelli, Fanciulli, G., Di Molfetta, S., Dotto, A., Florio, T., Feola, T., Colao, A., and Faggiano, A.
- Subjects
Oncology ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Immune checkpoint inhibitors ,immune checkpoint inhibitor ,Ipilimumab ,Pembrolizumab ,Diseases of the endocrine glands. Clinical endocrinology ,immune checkpoint inhibitors ,Antineoplastic Agents, Immunological ,Endocrinology ,Internal medicine ,medicine ,antineoplastic agents ,Humans ,ipilimumab ,Lymph node ,nivolumab ,business.industry ,General Commentary ,Lymph Node ,Lymphatic Metastasi ,parathyroid carcinoma ,medicine.disease ,RC648-665 ,immunological ,medicine.anatomical_structure ,Parathyroid Neoplasms ,Parathyroid carcinoma ,Lymphatic Metastasis ,pembrolizumab ,Lymph Nodes ,Nivolumab ,business ,humans ,lymph nodes ,lymphatic metastasis ,antineoplastic agents, immunological ,parathyroid neoplasms ,medicine.drug ,Human - Published
- 2021
6. Carcinoma a cellule di Merkel: gestione clinica e controversie
- Author
-
Marco Gallo, Valentina Guarnotta, Annamaria Colao, Antongiulio Faggiano, Manila Rubino, and Federica de Cicco
- Subjects
Gynecology ,medicine.medical_specialty ,business.industry ,Medicine ,business - Abstract
Il carcinoma a cellule di Merkel e una rara e aggressiva neoplasia neuroendocrina cutanea, piu frequente tra gli anziani con carnagione chiara e/o immunodepressi. I fattori di rischio sono l’esposizione ai raggi UV e l’infezione da un poliomavirus. Di recente, alcuni inibitori del checkpoint immunitario hanno mostrato ottimi risultati nel trattamento delle forme avanzate/metastatiche, modificandone l’algoritmo terapeutico, ma molti aspetti gestionali e terapeutici restano ancora controversi.
- Published
- 2019
7. Advances in the Management of Medullary Thyroid Carcinoma: Focus on Peptide Receptor Radionuclide Therapy
- Author
-
Erika, Grossrubatscher, Giuseppe, Fanciulli, Luca, Pes, Franz, Sesti, Carlotta, Dolci, Federica, de Cicco, Annamaria, Colao, Antongiulio, Faggiano, and Nike Group
- Subjects
Oncology ,medicine.medical_specialty ,Peptide receptor ,Medullary cavity ,endocrine system diseases ,lcsh:Medicine ,Review ,030218 nuclear medicine & medical imaging ,Thyroid carcinoma ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medullary thyroid carcinoma ,medicine ,Effective treatment ,peptide receptor radionuclide therapy ,Low toxicity ,somatostatin analogues ,neuroendocrine neoplasm ,business.industry ,lcsh:R ,General Medicine ,Clinical trial ,Somatostatin ,030220 oncology & carcinogenesis ,Radionuclide therapy ,business - Abstract
Effective treatment options in advanced/progressive/metastatic medullary thyroid carcinoma (MTC) are currently limited. As in other neuroendocrine neoplasms (NENs), peptide receptor radionuclide therapy (PRRT) has been used as a therapeutic option in MTC. To date, however, there are no published reviews dealing with PRRT approaches. We performed an in-depth narrative review on the studies published in this field and collected information on registered clinical trials related to this topic. We identified 19 published studies, collectively involving more than 200 patients with MTC, and four registered clinical trials. Most cases of MTC were treated with PRRT with somatostatin analogues (SSAs) radiolabelled with 90 yttrium (90Y) and 177 lutetium (177Lu). These radiopharmaceuticals show efficacy in the treatment of patients with MTC, with a favourable radiological response (stable disease, partial response or complete response) in more than 60% of cases, coupled with low toxicity. As MTC specifically also expresses cholecystokinin receptors (CCK2Rs), PRRT with this target has also been tried, and some randomised trials are ongoing. Overall, PRRT seems to have an effective role and might be considered in the therapeutic strategy of advanced/progressive/metastatic MTC.
- Published
- 2020
8. From microbiota toward gastro-enteropancreatic neuroendocrine neoplasms: Are we on the highway to hell?
- Author
-
Giulia Puliani, Andrea Lania, Fabio Lo Calzo, Valentina Guarnotta, Giuseppe Fanciulli, Alessandra Dicitore, Carmen Rainone, Annamaria Colao, Genoveffa Pizza, Manila Rubino, Giovanni Vitale, Severo Campione, Francesco Ferraù, Maria Chiara Zatelli, Mary Anna Venneri, Emilia Sbardella, Diego Ferone, Marco Gallo, Riccardo Pofi, Roberta Modica, Luigi Barrea, Erika Grossrubatscher, Federica Grillo, Antongiulio Faggiano, Franz Sesti, Rosa Maria Ruggieri, Barbara Altieri, Erika Messina, Luca Pes, P. Razzore, Nike, Andrea M. Isidori, Sergio Di Molfetta, Pasquale Malandrino, Andrea Lenzi, Manuela Albertelli, Tiziana Feola, Laura Rizza, Giovanna Muscogiuri, Federica de Cicco, Filomena Bottiglieri, Elia Guadagno, Elisa Giannetta, Vitale G, Dicitore A, Barrea L, Sbardella E, Razzore P, Campione S, Faggiano A, Colao A, NIKE, Albertelli M, Altieri B, Bottiglieri F, De Cicco F, Di Molfetta S, Fanciulli G, Feola T, Ferone D, Ferraù F, Gallo M, Giannetta E, Grillo F, Grossrubatscher E, Guadagno E, Guarnotta V, Isidori AM, Lania A, Lenzi A, Calzo FL, Malandrino P, Messina E, Modica R, Muscogiuri G, Pes L, Pizza G, Pofi R, Puliani G, Rainone C, Rizza L, Rubino M, Ruggieri RM, Sesti F, Venneri MA, Zatelli MC., Vitale, G., Dicitore, A., Barrea, L., Sbardella, E., Razzore, P., Campione, S., Faggiano, A., Colao, A., Albertelli, M., Altieri, B., Bottiglieri, F., De Cicco, F., Di Molfetta, S., Fanciulli, G., Feola, T., Ferone, D., Ferrau, F., Gallo, M., Giannetta, E., Grillo, F., Grossrubatscher, E., Guadagno, E., Guarnotta, V., Isidori, A. M., Lania, A., Lenzi, A., Calzo, F. L., Malandrino, P., Messina, E., Modica, R., Muscogiuri, G., Pes, L., Pizza, G., Pofi, R., Puliani, G., Rainone, C., Rizza, L., Rubino, M., Ruggieri, R. M., Sesti, F., Venneri, M. A., and Zatelli, M. C.
- Subjects
Endocrinology, Diabetes and Metabolism ,Tumor microenvironment ,Biology ,Gut flora ,Neuroendocrine tumors ,medicine.disease_cause ,digestive system ,Article ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Immune system ,Neuroendocrine tumor ,Gastro ,medicine ,Humans ,Cytokine ,030304 developmental biology ,Gastrointestinal Neoplasms ,Inflammation ,0303 health sciences ,Microbiota ,digestive, oral, and skin physiology ,medicine.disease ,biology.organism_classification ,Cytokines ,Gastrointestinal Microbiome ,030220 oncology & carcinogenesis ,Immunology ,Dysbiosis ,Carcinogenesis ,Drug metabolism - Abstract
Gut microbiota is represented by different microorganisms that colonize the intestinal tract, mostly the large intestine, such as bacteria, fungi, archaea and viruses. The gut microbial balance has a key role in several functions. It modulates the host’s metabolism, maintains the gut barrier integrity, participates in the xenobiotics and drug metabolism, and acts as protection against gastro-intestinal pathogens through the host’s immune system modulation. The impaired gut microbiota, called dysbiosis, may be the result of an imbalance in this equilibrium and is linked with different diseases, including cancer. While most of the studies have focused on the association between microbiota and gastrointestinal adenocarcinomas, very little is known about gastroenteropancreatic (GEP) neuroendocrine neoplasms (NENs). In this review, we provide an overview concerning the complex interplay between gut microbiota and GEP NENs, focusing on the potential role in tumorigenesis and progression in these tumors.
- Published
- 2020
9. Lanreotide Therapy vs Active Surveillance in MEN1-Related Pancreatic Neuroendocrine Tumors2 Centimeters
- Author
-
Luigi Camera, Giuseppe Badalamenti, Federica de Cicco, Franz Sesti, Annamaria Colao, Antongiulio Faggiano, Vincenzo Napolitano, Fialomena Bottiglieri, Roberta Modica, Andrea M. Isidori, Barbara Altieri, Fabio Lo Calzo, Faggiano A., Modica R., Lo Calzo F., Camera L., Napolitano V., Altieri B., De Cicco F., Bottiglieri F., Sesti F., Badalamenti G., Isidori A.M., Colao A., Faggiano, A, Modica, R., Lo Calzo, F., Camera, L., Napolitano, V., Altieri, B., De Cicco, F, Bottiglieri, F., Sesti, F., Badalamenti, G., Isidori, A. M., and Colao, A.
- Subjects
Male ,Endocrinology, Diabetes and Metabolism ,Clinical Biochemistry ,Neuroendocrine tumors ,Lanreotide ,Biochemistry ,Gastroenterology ,chemistry.chemical_compound ,Endocrinology ,active surveillance, lanreotide, MEN1, pancreatic neuroendocrine tumors, somatostatin analogues ,Prospective Studies ,Prospective cohort study ,Multiple endocrine neoplasia ,somatostatin analogues ,Middle Aged ,Prognosis ,Tumor Burden ,Neuroendocrine Tumors ,Somatostatin ,MEN1 ,Disease Progression ,Female ,lanreotide ,Adult ,medicine.medical_specialty ,Antineoplastic Agents ,pancreatic neuroendocrine tumor ,Peptides, Cyclic ,Young Adult ,Internal medicine ,medicine ,Multiple Endocrine Neoplasia Type 1 ,Humans ,Watchful Waiting ,Aged ,Centimeter ,pancreatic neuroendocrine tumors ,business.industry ,Biochemistry (medical) ,active surveillance ,medicine.disease ,Pancreatic Neoplasms ,chemistry ,Tumor progression ,Case-Control Studies ,business ,Follow-Up Studies - Abstract
Purpose Pancreatic neuroendocrine tumors (pNETs) are frequent in multiple endocrine neoplasia type 1 (MEN1) syndrome. They are usually not surgically treated unless larger than 1 to 2 cm or a growth rate > 0.5 cm per year. Somatostatin analogues represent one of the main therapeutic options in pNETs, but they have never been prospectively investigated in MEN1-related pNETs. The aim of this study was to prospectively evaluate the effectiveness of lanreotide in patients with MEN1-related pNETs < 2 cm. Methods MEN1 patients with 1 or more pNETs < 2 cm of maximal diameter were considered. Study design was prospective observational, comparing patients treated with lanreotide autogel 120 mg every 28 days (LAN group) and patients in active surveillance, not receiving any therapy (AS group). Results Forty-two patients were enrolled: 23 in LAN and 19 in AS group. Median follow-up was 73 months. Initial imaging identified a total of 91 pNETs. The median progression-free survival was significantly longer in the LAN than in the AS group (median not reached vs 40 months, P < 0.001). In the LAN group, 4 patients had an objective tumor response, 15 patients had stable disease, while 4 had tumor progression. In the AS group, 13 patients had pNET progression, while 6 were stable. Conclusions This is the first prospective study evaluating the efficacy of somatostatin analogues in MEN1-related pNETs. These findings highlight that lanreotide autogel is effective as antiproliferative therapy in MEN1-related pNETs < 2cm, suggesting the utility of somatostatin analogues to arrest the development of tumor lesions as well as to delay or avoid pancreatic surgery.
- Published
- 2019
10. Vitamin D deficiency is a predictor marker of tumor aggressiveness in sporadic and MEN1-related well-differentiated, low-grade GEP-NET
- Author
-
Carolina Di Somma, Antongiulio Faggiano, Filomena Bottiglieri, Barbara Altieri, Annamaria Colao, Roberta Modica, Giovanni Savarese, Federica de Cicco, Silvia Savastano, Luigi Barrea, and Luisa Circelli
- Subjects
Cancer research ,medicine ,MEN1 ,Biology ,medicine.disease ,vitamin D deficiency ,Well differentiated - Published
- 2019
11. Fattori genetici ed epigenetici dei tumori neuroendocrini (NET)
- Author
-
Antongiulio Faggiano, Annamaria Colao, and Federica de Cicco
- Subjects
Gynecology ,medicine.medical_specialty ,business.industry ,medicine ,business - Published
- 2017
12. Penetranza e correlazioni genotipo-fenotipo del feocromocitoma e paraganglioma SDHB-correlato
- Author
-
Annamaria Colao, Antongiulio Faggiano, and Federica de Cicco
- Subjects
Gynecology ,medicine.medical_specialty ,business.industry ,medicine ,business - Published
- 2017
13. Tendenza all’aumento dell’incidenza dei tumori neuroendocrini a basso e alto grado
- Author
-
Annamaria Colao, Federica de Cicco, and Antongiulio Faggiano
- Subjects
business.industry ,Medicine ,business ,Humanities - Published
- 2017
14. Evaluation of the in vitro and in vivo antiangiogenic effects of denosumab and zoledronic acid
- Author
-
Gabriella, Misso, Manuela, Porru, Stoppacciaro, Antonella, Maria, Castellano, Federica De Cicco, Carlo, Leonetti, Daniele, Santini, Michele, Caraglia, Santini, Daniele, Misso, Gabriella, Porru, M, Stoppacciaro, A, Castellano, M, De Cicco, F, Leonetti, C, Santini, D, and Caraglia, Michele
- Subjects
Pathology ,Cancer Research ,Angiogenesis ,Angiogenesis Inhibitors ,Humanized antibody ,Neovascularization ,Mice ,zoledronic acid ,angiogenesis ,huvec ,Mice, Inbred BALB C ,biology ,Bone Density Conservation Agents ,Diphosphonates ,Neovascularization, Pathologic ,Imidazoles ,denosumab ,breast cancer ,acid 10.4161/cbt.22274 ,anticancer ,rankl ,zoledronic ,Angiogenesi ,Denosumab ,Diphosphonate ,Oncology ,RANKL ,Molecular Medicine ,Female ,medicine.symptom ,Breast Neoplasm ,medicine.drug ,Angiogenesis Inhibitor ,Human ,Research Paper ,medicine.medical_specialty ,Bone Density Conservation Agent ,Xenograft Model Antitumor Assay ,Cell Survival ,Human Umbilical Vein Endothelial Cell ,Mice, Nude ,Bone Neoplasms ,Breast Neoplasms ,Bone Neoplasm ,Antibodies, Monoclonal, Humanized ,In vivo ,Cell Line, Tumor ,medicine ,Human Umbilical Vein Endothelial Cells ,Animals ,Humans ,Imidazole ,Pharmacology ,Matrigel ,business.industry ,Animal ,RANK Ligand ,Xenograft Model Antitumor Assays ,In vitro ,Cancer research ,biology.protein ,business ,Neoplasm Transplantation - Abstract
""Denosumab (Dmab) and zoledronic acid (ZOL) are antiresorptive agents, with different mechanisms of action, that are indicated for delaying the onset of skeletal-related events in patients with bone metastases from solid tumors. Clinical and preclinical data suggest that ZOL may have also anti-angiogenic activity; however, the effects of Dmab (a fully humanized antibody against the receptor activator of nuclear factor kappa B ligand) on angiogenesis are largely unknown. The objective of this study was to compare the potential anti-angiogenic activity of Dmab with that of ZOL in preclinical models. Dmab (0.31 to 160 µM) had no effect on the viability of human MDA-MB-436 and CG5 breast cancer cells or human umbilical vein endothelial cells (HUVECs) and no effect on tubule formation or invasion of HUVECs. In contrast, ZOL (0.31 to 160 µM) decreased the viability of breast cancer and HUVECs in a time- and concentration-dependent manner, and also inhibited HUVEC tubule formation and invasion. In vivo, ZOL (100 µg\\\/kg s.c. twice weekly for 6 weeks) inhibited angiogenesis in Matrigel plugs and inhibited the growth and neo-angiogenesis of CG5 xenografts in athymic nude mice. In contrast, Dmab (100 µg\\\/kg s.c. twice weekly for 6 weeks) had no effect on Matrigel vascularization or xenograft growth in this model. These findings support the potential antiangiogenic and anticancer activity of ZOL in vitro and in vivo, and further suggest that Dmab does not have antiangiogenic activity. Additional studies are needed to elucidate the potential anticancer activity of Dmab."" Denosumab (Dmab) and zoledronic acid (ZOL) are antiresorptive agents, with different mechanisms of action, that are indicated for delaying the onset of skeletal-related events in patients with bone metastases from solid tumors. Clinical and preclinical data suggest that ZOL may have also anti-angiogenic activity; however, the effects of Dmab (a fully humanized antibody against the receptor activator of nuclear factor kappa B ligand) on angiogenesis are largely unknown. The objective of this study was to compare the potential anti-angiogenic activity of Dmab with that of ZOL in preclinical models. Dmab (0.31 to 160 μM) had no effect on the viability of human MDA-MB-436 and CG5 breast cancer cells or human umbilical vein endothelial cells (HUVECs) and no effect on tubule formation or invasion of HUVECs. In contrast, ZOL (0.31 to 160 μM) decreased the viability of breast cancer and HUVECs in a time- and concentration-dependent manner and also inhibited HUVEC tubule formation and invasion. In vivo, ZOL (20 μg/mouse three times a week for three consecutive weeks) inhibited angiogenesis in Matrigel plugs and inhibited the growth and neo-angiogenesis of CG5 xenografts in athymic nude mice. In contrast, Dmab (10 mg/kg twice a week for four consecutive weeks) had no effect on Matrigel vascularization or xenograft growth in this model. These findings support the potential antiangiogenic and anticancer activity of ZOL in vitro and in vivo and further suggest that Dmab does not have antiangiogenic activity. Additional studies are needed to elucidate the potential anticancer activity of Dmab. © 2012 Landes Bioscience.
- Published
- 2012
15. On and off-target effects of telomere uncapping G-quadruplex selective ligands based on pentacyclic acridinium salts
- Author
-
Erica Salvati, Chiara Cingolani, Annamaria Biroccio, Sara Iachettini, Mark S. Searle, Rupesh Nanjunda, Thomas P. Garner, Marc Geoffery Hummersone, Carlo Leonetti, Pasquale Zizza, Mark Frigerio, Ian Hutchinson, Federica De Cicco, Carmen D'Angelo, David Wilson, Angela Maria Rizzo, Malcolm F. G. Stevens, Maurizio D'Incalci, Manoj Munde, and Manuela Porru
- Subjects
Cancer Research ,Telomerase ,Anti-cancer therapy ,Guinea Pigs ,Biology ,G-quadruplex ,Ligands ,chemistry.chemical_compound ,Animals ,Humans ,Uncapping ,Cells, Cultured ,Cell Proliferation ,Telomere-binding protein ,Research ,Promoter ,Telomere targeting agents ,Telomere ,Small molecule ,G-Quadruplexes ,Oncology ,Biochemistry ,chemistry ,Acridines ,DNA - Abstract
Quadruplexes DNA are present in telomeric DNA as well as in several cancer-related gene promoters and hence affect gene expression and subsequent biological processes. The conformations of G4 provide selective recognition sites for small molecules and thus these structures have become important drug-design targets for cancer treatment. The DNA G-quadruplex binding pentacyclic acridinium salt RHPS4 (1) has many pharmacological attributes of an ideal telomere-targeting agent but has undesirable off-target liabilities. Notably a cardiovascular effect was evident in a guinea pig model, manifested by a marked and sustained increase in QTcB interval. In accordance with this, significant interaction with the human recombinant β2 adrenergic receptor, and M1, M2 and M3 muscarinic receptors was observed, together with a high inhibition of the hERG tail current tested in a patch clamp assay. Two related pentacyclic structures, the acetylamines (2) and (3), both show a modest interaction with β2 adrenergic receptor, and do not significatively inhibit the hERG tail current while demonstrating potent telomere on-target properties comparing closely with 1. Of the two isomers, the 2-acetyl-aminopentacycle (2) more closely mimics the overall biological profile of 1 and this information will be used to guide further synthetic efforts to identify novel variants of this chemotype, to maximize on-target and minimize off-target activities. Consequently, the improvement of toxicological profile of these compounds could therefore lead to the obtainment of suitable molecules for clinical development offering new pharmacological strategies in cancer treatment.
- Published
- 2013
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.