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2.
Hum Vaccin Immunother ; 19(1): 2176083, 2023 12 31.
Article in English | MEDLINE | ID: mdl-36794338

ABSTRACT

To address vaccine hesitancy, specific self-rated tools have been developed to assess vaccine literacy (VL) related to COVID-19, including additional variables, such as beliefs, behavior, and willingness to be vaccinated. To explore the recent literature a search was performed selecting articles published between January 2020 and October 2022: 26 papers were identified using these tools in the context of COVID-19. Descriptive analysis showed that the levels of VL observed in the studies were generally in agreement, with functional VL score often lower than the interactive-critical dimension, as if the latter was stimulated by the COVID-19-related infodemic. Factors associated with VL included vaccination status, age, educational level, and, possibly, gender. Effective communication based on VL when promoting vaccination is critical to sustaining immunization against COVID-19 and other communicable diseases. The VL scales developed to date have shown good consistency. However, further research is needed to improve these tools and develop new ones.


Subject(s)
COVID-19 Vaccines , COVID-19 , Humans , Literacy , COVID-19/prevention & control , Educational Status , Vaccination
3.
Curr Issues Mol Biol ; 44(8): 3364-3377, 2022 Jul 27.
Article in English | MEDLINE | ID: mdl-36005128

ABSTRACT

Helix aspersa is a species of land snail belonging to the Helicidae family, widespread in the Mediterranean and continental area up to Northern Europe. In some areas it is appreciated as a food, but is mostly considered a parasite of gardens and cultivated fields. The mucus of Helix aspersa has found multiple applications in the cosmetic and health fields. In the present study, we investigated for the first time the angiogenetic properties of purified extracts from Helix aspersa using a transgenic zebrafish line Tg (kdrl:EGFP). The angiogenesis induced by purified snail extracts was demonstrated by their capability to increase the three well-established parameters of angiogenesis: generation of intersegmental vessels, modeling of caudal venous plexus, and formation of sub-intestinal venous plexus. The effects appeared to be mediated by the vascular endothelial growth factor (VEGF) pathway, being prevented by pretreatment of embryos with the selective VEGF receptor antagonist SU5416, and supported by the increased VEGF mRNA levels found in snail-extract-treated embryos. Insufficient vascular supply is underlined by low VEGF signaling, primarily because of its indispensable role in preventing capillary loss. Our findings might have a pharmacological impact by counteracting VEGF hypofunction and promoting angiogenesis to maintain adequate microvascular and vascular density in normal and suffering tissues and organs.

4.
Aging Clin Exp Res ; 33(10): 2899-2907, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34319512

ABSTRACT

BACKGROUND: Policies to combat the COVID-19 pandemic have disrupted the screening, diagnosis, treatment, and monitoring of noncommunicable (NCD) patients while affecting NCD prevention and risk factor control. AIMS: To discuss how the first wave of the COVID-19 pandemic affected the health management of NCD patients, identify which aspects should be carried forward into future NCD management, and propose collaborative efforts among public-private institutions to effectively shape NCD care models. METHODS: The NCD Partnership, a collaboration between Upjohn and the European Innovation Partnership on Active and Healthy Ageing, held a virtual Advisory Board in July 2020 with multiple stakeholders; healthcare professionals (HCPs), policymakers, researchers, patient and informal carer advocacy groups, patient empowerment organizations, and industry experts. RESULTS: The Advisory Board identified barriers to NCD care during the COVID-19 pandemic in four areas: lack of NCD management guidelines; disruption to integrated care and shift from hospital-based NCD care to more community and primary level care; infodemics and a lack of reliable health information for patients and HCPs on how to manage NCDs; lack of availability, training, standardization, and regulation of digital health tools. CONCLUSIONS: Multistakeholder partnerships can promote swift changes to NCD prevention and patient care. Intra- and inter-communication between all stakeholders should be facilitated involving all players in the development of clinical guidelines and digital health tools, health and social care restructuring, and patient support in the short-, medium- and long-term future. A comprehensive response to NCDs should be delivered to improve patient outcomes by providing strategic, scientific, and economic support.


Subject(s)
COVID-19 , Noncommunicable Diseases , Caregivers , Humans , Noncommunicable Diseases/epidemiology , Noncommunicable Diseases/prevention & control , Pandemics/prevention & control , SARS-CoV-2
5.
Vaccines (Basel) ; 9(3)2021 Mar 17.
Article in English | MEDLINE | ID: mdl-33802873

ABSTRACT

Rapid online surveys are an important tool for tracking the public's knowledge and perceptions during infectious disease outbreaks. In June 2020, during the early phases of COVID-19 vaccines development, we conducted a survey in 885 Italian adults that aimed at assessing their attitudes and opinions about vaccination, in addition to their vaccine literacy levels (i.e., skills in finding, understanding, and using information about vaccines). In January 2021, the same questionnaire was administered to a similar population (n = 160). Interactive vaccine literacy was significantly higher in January 2021 than in June 2020 (mean score 3.38 vs. 3.27 respectively, p = 0.0021). The percentage of participants willing to be vaccinated against COVID-19 assessed by either-or questions, was equally high in both surveys (>90%), which is quite reassuring, although metrics based on categorical scales cannot identify hesitant subjects.

6.
Proc Natl Acad Sci U S A ; 118(15)2021 04 13.
Article in English | MEDLINE | ID: mdl-33876771

ABSTRACT

Uterine leiomyosarcomas (uLMS) are aggressive tumors arising from the smooth muscle layer of the uterus. We analyzed 83 uLMS sample genetics, including 56 from Yale and 27 from The Cancer Genome Atlas (TCGA). Among them, a total of 55 Yale samples including two patient-derived xenografts (PDXs) and 27 TCGA samples have whole-exome sequencing (WES) data; 10 Yale and 27 TCGA samples have RNA-sequencing (RNA-Seq) data; and 11 Yale and 10 TCGA samples have whole-genome sequencing (WGS) data. We found recurrent somatic mutations in TP53, MED12, and PTEN genes. Top somatic mutated genes included TP53, ATRX, PTEN, and MEN1 genes. Somatic copy number variation (CNV) analysis identified 8 copy-number gains, including 5p15.33 (TERT), 8q24.21 (C-MYC), and 17p11.2 (MYOCD, MAP2K4) amplifications and 29 copy-number losses. Fusions involving tumor suppressors or oncogenes were deetected, with most fusions disrupting RB1, TP53, and ATRX/DAXX, and one fusion (ACTG2-ALK) being potentially targetable. WGS results demonstrated that 76% (16 of 21) of the samples harbored chromoplexy and/or chromothripsis. Clinically actionable mutational signatures of homologous-recombination DNA-repair deficiency (HRD) and microsatellite instability (MSI) were identified in 25% (12 of 48) and 2% (1 of 48) of fresh frozen uLMS, respectively. Finally, we found olaparib (PARPi; P = 0.002), GS-626510 (C-MYC/BETi; P < 0.000001 and P = 0.0005), and copanlisib (PIK3CAi; P = 0.0001) monotherapy to significantly inhibit uLMS-PDXs harboring derangements in C-MYC and PTEN/PIK3CA/AKT genes (LEY11) and/or HRD signatures (LEY16) compared to vehicle-treated mice. These findings define the genetic landscape of uLMS and suggest that a subset of uLMS may benefit from existing PARP-, PIK3CA-, and C-MYC/BET-targeted drugs.


Subject(s)
Genotype , Leiomyosarcoma/genetics , Mutation , Oncogene Fusion , Uterine Neoplasms/genetics , Animals , Antineoplastic Agents/therapeutic use , Female , Humans , Leiomyosarcoma/drug therapy , Metabolic Networks and Pathways , Mice , Mice, Inbred C57BL , Molecular Targeted Therapy/methods , Phthalazines/administration & dosage , Phthalazines/therapeutic use , Piperazines/administration & dosage , Piperazines/therapeutic use , Pyrimidines/administration & dosage , Pyrimidines/therapeutic use , Quinazolines/administration & dosage , Quinazolines/therapeutic use , Uterine Neoplasms/drug therapy
7.
Hum Vaccin Immunother ; 17(5): 1304-1312, 2021 05 04.
Article in English | MEDLINE | ID: mdl-33118868

ABSTRACT

The COVID-19 infodemic can be countered by scientific evidence, clear and consistent communication, and improved health literacy of both individuals in need of information and those providing it. A rapid online survey was carried out to evaluate vaccine literacy (VL) skills in the general population and perceptions about COVID-19 vaccine candidates, along with behavior and beliefs about current vaccinations. Observed VL levels were consistent with previous observations - where comparable self-reported tools were administered face-to-face and by paper-and-pencil - the mean functional score being = 2.92, while the interactive-critical score was = 3.27, out of a maximum of 4. Perceptions regarding future COVID-19 vaccines, along with beliefs about vaccination, were mostly positive and significantly associated with functional and interactive-critical VL scales. Despite limitations, the study confirms that surveys via the web are a suitable method to evaluate and track attitudes during infectious disease outbreaks and assess health literacy skills about vaccination, which can be useful to adapt medical communication strategies, for a better understanding of the value of immunization.


Subject(s)
COVID-19 Vaccines , COVID-19 , Health Knowledge, Attitudes, Practice , Health Literacy/statistics & numerical data , Internet , Surveys and Questionnaires , Vaccination , Adolescent , Adult , Aged , Female , Humans , Italy , Male , Middle Aged , SARS-CoV-2 , Young Adult
8.
Proc Natl Acad Sci U S A ; 116(45): 22730-22736, 2019 11 05.
Article in English | MEDLINE | ID: mdl-31624127

ABSTRACT

The prognosis of advanced/recurrent cervical cancer patients remains poor. We analyzed 54 fresh-frozen and 15 primary cervical cancer cell lines, along with matched-normal DNA, by whole-exome sequencing (WES), most of which harboring Human-Papillomavirus-type-16/18. We found recurrent somatic missense mutations in 22 genes (including PIK3CA, ERBB2, and GNAS) and a widespread APOBEC cytidine deaminase mutagenesis pattern (TCW motif) in both adenocarcinoma (ACC) and squamous cell carcinomas (SCCs). Somatic copy number variants (CNVs) identified 12 copy number gains and 40 losses, occurring more often than expected by chance, with the most frequent events in pathways similar to those found from analysis of single nucleotide variants (SNVs), including the ERBB2/PI3K/AKT/mTOR, apoptosis, chromatin remodeling, and cell cycle. To validate specific SNVs as targets, we took advantage of primary cervical tumor cell lines and xenografts to preclinically evaluate the activity of pan-HER (afatinib and neratinib) and PIK3CA (copanlisib) inhibitors, alone and in combination, against tumors harboring alterations in the ERBB2/PI3K/AKT/mTOR pathway (71%). Tumors harboring ERBB2 (5.8%) domain mutations were significantly more sensitive to single agents afatinib or neratinib when compared to wild-type tumors in preclinical in vitro and in vivo models (P = 0.001). In contrast, pan-HER and PIK3CA inhibitors demonstrated limited in vitro activity and were only transiently effective in controlling in vivo growth of PIK3CA-mutated cervical cancer xenografts. Importantly, combinations of copanlisib and neratinib were highly synergistic, inducing long-lasting regression of tumors harboring alterations in the ERBB2/PI3K/AKT/mTOR pathway. These findings define the genetic landscape of cervical cancer, suggesting that a large subset of cervical tumors might benefit from existing ERBB2/PIK3CA/AKT/mTOR-targeted drugs.


Subject(s)
Class I Phosphatidylinositol 3-Kinases/genetics , Exome Sequencing , Mutation , Receptor, ErbB-2/genetics , Uterine Cervical Neoplasms/genetics , Uterine Cervical Neoplasms/therapy , Animals , Cell Line, Tumor , Combined Modality Therapy , DNA Copy Number Variations , Female , Heterografts , Humans , Polymorphism, Single Nucleotide , Uterine Cervical Neoplasms/pathology
9.
Proc Natl Acad Sci U S A ; 116(2): 619-624, 2019 01 08.
Article in English | MEDLINE | ID: mdl-30584090

ABSTRACT

Ovarian cancer remains the most lethal gynecologic malignancy. We analyzed the mutational landscape of 64 primary, 41 metastatic, and 17 recurrent fresh-frozen tumors from 77 patients along with matched normal DNA, by whole-exome sequencing (WES). We also sequenced 13 pairs of synchronous bilateral ovarian cancer (SBOC) to evaluate the evolutionary history. Lastly, to search for therapeutic targets, we evaluated the activity of the Bromodomain and Extra-Terminal motif (BET) inhibitor GS-626510 on primary tumors and xenografts harboring c-MYC amplifications. In line with previous studies, the large majority of germline and somatic mutations were found in BRCA1/2 (21%) and TP53 (86%) genes, respectively. Among mutations in known cancer driver genes, 77% were transmitted from primary tumors to metastatic tumors, and 80% from primary to recurrent tumors, indicating that driver mutations are commonly retained during ovarian cancer evolution. Importantly, the number, mutation spectra, and signatures in matched primary-metastatic tumors were extremely similar, suggesting transcoelomic metastases as an early dissemination process using preexisting metastatic ability rather than an evolution model. Similarly, comparison of SBOC showed extensive sharing of somatic mutations, unequivocally indicating a common ancestry in all cases. Among the 17 patients with matched tumors, four patients gained PIK3CA amplifications and two patients gained c-MYC amplifications in the recurrent tumors, with no loss of amplification or gain of deletions. Primary cell lines and xenografts derived from chemotherapy-resistant tumors demonstrated sensitivity to JQ1 and GS-626510 (P = 0.01), suggesting that oral BET inhibitors represent a class of personalized therapeutics in patients harboring recurrent/chemotherapy-resistant disease.


Subject(s)
Antineoplastic Agents/pharmacology , Azepines/pharmacology , Mutation , Neoplasm Recurrence, Local , Proteins , Proto-Oncogene Proteins c-myc , Triazoles/pharmacology , Animals , BRCA1 Protein/genetics , BRCA1 Protein/metabolism , BRCA2 Protein/genetics , BRCA2 Protein/metabolism , Cell Line, Tumor , Class I Phosphatidylinositol 3-Kinases/genetics , Class I Phosphatidylinositol 3-Kinases/metabolism , Female , Humans , Mice , Neoplasm Metastasis , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/genetics , Neoplasm Recurrence, Local/metabolism , Ovarian Neoplasms , Proteins/antagonists & inhibitors , Proteins/genetics , Proteins/metabolism , Proto-Oncogene Proteins c-myc/genetics , Proto-Oncogene Proteins c-myc/metabolism , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/metabolism , Xenograft Model Antitumor Assays
10.
Adv Nutr ; 8(4): 532-545, 2017 Jul.
Article in English | MEDLINE | ID: mdl-28710141

ABSTRACT

A large body of evidence supports the notion that incorrect or insufficient nutrition contributes to disease development. A pivotal goal is thus to understand what exactly is appropriate and what is inappropriate in food ingestion and the consequent nutritional status and health. The effective application of these concepts requires the translation of scientific information into practical approaches that have a tangible and measurable impact at both individual and population levels. The agenda for the future is expected to support available methodology in nutrition research to personalize guideline recommendations, properly grading the quality of the available evidence, promoting adherence to the well-established evidence hierarchy in nutrition, and enhancing strategies for appropriate vetting and transparent reporting that will solidify the recommendations for health promotion. The final goal is to build a constructive coalition among scientists, policy makers, and communication professionals for sustainable health and nutritional policies. Currently, a strong rationale and available data support a personalized dietary approach according to personal variables, including sex and age, circulating metabolic biomarkers, food quality and intake frequency, lifestyle variables such as physical activity, and environmental variables including one's microbiome profile. There is a strong and urgent need to develop a successful commitment among all the stakeholders to define novel and sustainable approaches toward the management of the health value of nutrition at individual and population levels. Moving forward requires adherence to well-established principles of evidence evaluation as well as identification of effective tools to obtain better quality evidence. Much remains to be done in the near future.


Subject(s)
Diet, Healthy/standards , Health Promotion/legislation & jurisprudence , Health Promotion/standards , Nutrition Policy/legislation & jurisprudence , Databases, Factual , Humans , Life Style , Nutritional Status
11.
Br J Cancer ; 117(4): 494-502, 2017 Aug 08.
Article in English | MEDLINE | ID: mdl-28664915

ABSTRACT

BACKGROUND: The biological mechanisms underlying early- and advanced-stage epithelial ovarian cancers (EOCs) are still poorly understood. This study explored kinase-driven metabolic signalling in early and advanced EOCs, and its role in tumour progression and response to carboplatin-paclitaxel treatment. METHODS: Tumour epithelia were isolated from two independent sets of primary EOC (n=72 and 30 for the discovery and the validation sets, respectively) via laser capture microdissection. Reverse phase protein microarrays were used to broadly profile the kinase-driven metabolic signalling of EOC with particular emphasis on the LBK1-AMPK and AKT-mTOR axes. Signalling activation was compared between early and advanced lesions, and carboplatin-paclitaxel-sensitive and -resistant tumours. RESULTS: Advanced EOCs were characterised by a heterogeneous kinase-driven metabolic signature and decreased phosphorylation of the AMPK-AKT-mTOR axis compared to early EOC (P<0.05 for AMPKα T172, AMPKα1 S485, AMPKß1 S108, AKT S473 and T308, mTOR S2448, p70S6 S371, 4EBP1 S65, GSK-3 α/ß S21/9, FOXO1 T24/FOXO3 T32, and FOXO1 S256). Advanced tumours with low relative activation of the metabolic signature and increased FOXO1 T24/FOXO3 T32 phosphorylation (P=0.041) were associated with carboplatin-paclitaxel resistance. CONCLUSIONS: If validated in a larger cohort of patients, the decreased AMPK-AKT-mTOR activation and phosphorylation of FOXO1 T24/FOXO3 T32 may help identify carboplatin-paclitaxel-resistant EOC patients.


Subject(s)
AMP-Activated Protein Kinases/metabolism , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Neoplasms, Glandular and Epithelial/drug therapy , Neoplasms, Glandular and Epithelial/metabolism , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction , TOR Serine-Threonine Kinases/metabolism , Adult , Aged , Aged, 80 and over , Carboplatin/administration & dosage , Carcinoma, Ovarian Epithelial , Chemotherapy, Adjuvant , Disease Progression , Drug Resistance, Neoplasm , Epithelium/metabolism , Female , Forkhead Box Protein O1/metabolism , Forkhead Box Protein O3/metabolism , Humans , Middle Aged , Neoplasm Staging , Neoplasms, Glandular and Epithelial/pathology , Neoplasms, Glandular and Epithelial/surgery , Ovarian Neoplasms/pathology , Ovarian Neoplasms/surgery , Paclitaxel/administration & dosage , Phosphorylation , Protein Array Analysis , Young Adult
12.
J Exp Clin Cancer Res ; 36(1): 63, 2017 05 08.
Article in English | MEDLINE | ID: mdl-28482906

ABSTRACT

BACKGROUND: Epithelial ovarian cancer (EOC) is a spectrum of different diseases, which makes their treatment a challenge. Forkhead box M1 (FOXM1) is an oncogene aberrantly expressed in many solid cancers including serous EOC, but its role in non-serous EOCs remains undefined. We examined FOXM1 expression and its correlation to prognosis across the three major EOC subtypes, and its role in tumorigenesis and chemo-resistance in vitro. METHODS: Gene signatures were generated by microarray for 14 clear-cell and 26 endometrioid EOCs, and 15 normal endometrium snap-frozen biopsies. Validation of FOXM1 expression was performed by RT-qPCR and immunohistochemistry in the same samples and additionally in 50 high-grade serous EOCs and in their most adequate normal controls (10 luminal fallopian tube and 20 ovarian surface epithelial brushings). Correlations of FOXM1 expression to clinic-pathological parameters and patients' prognosis were evaluated by Kaplan-Meier and Cox proportional-hazards analyses. OVCAR-3 and two novel deeply characterized EOC cell lines (EOC-CC1 and OSPC2, with clear-cell and serous subtype, respectively) were employed for in vitro studies. Effects of FOXM1 inhibition by transient siRNA transfection were evaluated on cell-proliferation, cell-cycle, colony formation, invasion, and response to conventional first- and second-line anticancer agents, and to the PARP-inhibitor olaparib. Gene signatures of FOXM1-silenced cell lines were generated by microarray and confirmed by RT-qPCR. RESULTS: A significant FOXM1 mRNA up-regulation was found in EOCs compared to normal controls. FOXM1 protein overexpression significantly correlated to serous histology (p = 0.001) and advanced FIGO stage (p = 0.004). Multivariate analyses confirmed FOXM1 protein overexpression as an independent indicator of worse disease specific survival in non-serous EOCs, and of shorter time to progression in platinum-resistant cases. FOXM1 downregulation in EOC cell lines inhibited cell growth and clonogenicity, and promoted the cytotoxic effects of platinum compounds, doxorubicin hydrochloride and olaparib. Upon FOXM1 knock-down in EOC-CC1 and OSPC2 cells, microarray and RT-qPCR analyses revealed the deregulation of several common and other unique subtype-specific FOXM1 putative targets involved in cell cycle, metastasis, DNA repair and drug response. CONCLUSIONS: FOXM1 is up-regulated in all three major EOCs subtypes, and is a prognostic biomarker and a potential combinatorial therapeutic target in platinum resistant disease, irrespective of tumor histology.


Subject(s)
Drug Resistance, Neoplasm/genetics , Forkhead Box Protein M1/genetics , Gene Expression Regulation, Neoplastic , Neoplasms, Glandular and Epithelial/genetics , Neoplasms, Glandular and Epithelial/mortality , Ovarian Neoplasms/genetics , Ovarian Neoplasms/mortality , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biomarkers, Tumor , Carcinoma, Ovarian Epithelial , Cell Line, Tumor , Cell Movement , Cell Proliferation , Cell Transformation, Neoplastic/genetics , Cystadenocarcinoma, Serous/genetics , DNA Repair , Disease Progression , Female , Gene Expression Profiling , Gene Knockdown Techniques , Humans , Kaplan-Meier Estimate , Middle Aged , Neoplasm Grading , Neoplasm Metastasis , Neoplasm Staging , Neoplasms, Glandular and Epithelial/drug therapy , Neoplasms, Glandular and Epithelial/pathology , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/pathology , Prognosis , Protein Isoforms , RNA, Small Interfering/genetics
13.
BMC Cancer ; 17(1): 366, 2017 05 25.
Article in English | MEDLINE | ID: mdl-28545541

ABSTRACT

BACKGROUND: The existence of cancer stem cells (CSCs) within a tumor bulk has been demonstrated for many solid tumors including epithelial ovarian carcinoma (EOC). CSCs have been associated to tumor invasion, metastasis and development of chemoresistant recurrences. In this context, we aim to characterize EOC CSCs from the molecular point of view in order to identify potential biomarkers associated with chemoresistance. METHODS: We isolated a population of cells with stem-like characteristics (OVA-BS4 spheroids) from a primary human EOC cell line under selective conditions. OVA-BS4 spheroids were characterized for drug response by cytotoxicity assays and their molecular profile was investigated by microarray and RT-qPCR. Finally, we performed a gene expression study in a cohort of 74 high-grade serous EOC (HGSOC) patients by RT-qPCR. RESULTS: Spheroids exhibited properties of self-renewal and a pronounced expression of well-known stem cell genes. Moreover, they demonstrated greater resistance towards several anticancer drugs compared to parent cell line, consistent with their higher ABCG2 gene expression. From microarray studies MAL (T-cell differentiation protein) emerged as the most up-regulated gene in spheroids, compared to parent cell line. In HGSOC patients, MAL was significantly overexpressed in platinum-resistant compared to platinum-sensitive patients and resulted as an independent prognostic marker of survival. CONCLUSIONS: This investigation provides an important contribution to the identification of molecular markers of ovarian CSCs and chemoresistance. Successful translation of molecular findings would lead to a better comprehension of the mechanisms triggering chemoresistant recurrences, to the individuation of novel therapeutic targets and to the personalization of treatment regimens.


Subject(s)
Antineoplastic Agents/therapeutic use , Biomarkers, Tumor , Drug Resistance, Neoplasm , Gene Expression Regulation, Neoplastic , Myelin and Lymphocyte-Associated Proteolipid Proteins/genetics , Neoplasms, Cystic, Mucinous, and Serous/drug therapy , Ovarian Neoplasms/drug therapy , ATP Binding Cassette Transporter, Subfamily G, Member 2/genetics , Adult , Aged , Aged, 80 and over , Antineoplastic Agents/pharmacology , Disease Progression , Female , Humans , Middle Aged , Neoplasm Proteins/genetics , Neoplasms, Cystic, Mucinous, and Serous/metabolism , Neoplasms, Cystic, Mucinous, and Serous/mortality , Neoplasms, Cystic, Mucinous, and Serous/surgery , Neoplastic Stem Cells , Ovarian Neoplasms/metabolism , Ovarian Neoplasms/mortality , Ovarian Neoplasms/surgery , Prognosis , Up-Regulation
14.
Audiol Neurootol ; 21 Suppl 1: 3-9, 2016.
Article in English | MEDLINE | ID: mdl-27806351

ABSTRACT

Cognitive impairment and dementia are characterized by a progressive and devastating reduction in most cognitive abilities, functional independence, and social relationships. Dementia represents a substantial financial burden on society, one that is comparable to the financial burden of heart disease and cancer. Due to its insidious onset, cognitive impairment can be clinically silent for several years; therefore, diagnosis occurs late in the disease process, and treatment becomes almost useless. The identification of predictors of dementia may help identify the pathophysiological mechanisms underlying the disease and lead to the development of a more effective medical diagnosis and therapy, and thus an early treatment. Review of the literature suggests that in those individuals with less cognitive impairment (normal/predementia group), hearing loss has an association with language comprehension, and when cognitive impairment increases (moderate or severe dementia group), the contributing effect of hearing loss as a cognitive ability-impairing factor also increases. Greater understanding of the links between hearing impairment and cognition may have important implications for the screening and diagnosis of cognitive decline in older people with hearing impairment.


Subject(s)
Aging , Cognitive Dysfunction/epidemiology , Dementia/epidemiology , Hearing Loss/epidemiology , Cognition , Cognitive Dysfunction/complications , Cognitive Dysfunction/psychology , Comorbidity , Dementia/complications , Dementia/psychology , Hearing Loss/complications , Hearing Loss/psychology , Humans
15.
Proc Natl Acad Sci U S A ; 113(43): 12238-12243, 2016 10 25.
Article in English | MEDLINE | ID: mdl-27791010

ABSTRACT

Carcinosarcomas (CSs) of the uterus and ovary are highly aggressive neoplasms containing both carcinomatous and sarcomatous elements. We analyzed the mutational landscape of 68 uterine and ovarian CSs by whole-exome sequencing. We also performed multiregion whole-exome sequencing comprising two carcinoma and sarcoma samples from six tumors to resolve their evolutionary histories. The results demonstrated that carcinomatous and sarcomatous elements derive from a common precursor having mutations typical of carcinomas. In addition to mutations in cancer genes previously identified in uterine and ovarian carcinomas such as TP53, PIK3CA, PPP2R1A, KRAS, PTEN, CHD4, and BCOR, we found an excess of mutations in genes encoding histone H2A and H2B, as well as significant amplification of the segment of chromosome 6p harboring the histone gene cluster containing these genes. We also found frequent deletions of the genes TP53 and MBD3 (a member with CHD4 of the nucleosome remodeling deacetylase complex) and frequent amplification of chromosome segments containing the genes PIK3CA, TERT, and MYC Stable transgenic expression of H2A and H2B in a uterine serous carcinoma cell line demonstrated that mutant, but not wild-type, histones increased expression of markers of epithelial-mesenchymal transition (EMT) as well as tumor migratory and invasive properties, suggesting a role in sarcomatous transformation. Comparison of the phylogenetic relationships of carcinomatous and sarcomatous elements of the same tumors demonstrated separate lineages leading to these two components. These findings define the genetic landscape of CSs and suggest therapeutic targets for these highly aggressive neoplasms.


Subject(s)
Histones/genetics , Ovarian Neoplasms/genetics , Tumor Suppressor Protein p53/genetics , Uterine Neoplasms/genetics , Aged , Aged, 80 and over , Carcinosarcoma/genetics , Carcinosarcoma/pathology , Class I Phosphatidylinositol 3-Kinases/genetics , DNA-Binding Proteins/genetics , Epithelial-Mesenchymal Transition/genetics , Female , Gene Expression Regulation, Neoplastic , Humans , Middle Aged , Mutation , Ovarian Neoplasms/pathology , PTEN Phosphohydrolase/genetics , Telomerase/genetics , Uterine Neoplasms/pathology
16.
Oncol Lett ; 12(4): 2493-2500, 2016 Oct.
Article in English | MEDLINE | ID: mdl-27698818

ABSTRACT

Innovative therapies in cervical cancer (CC) remain a priority. Recent data indicate that human immunodeficiency virus (HIV)-protease inhibitors used in highly active antiretroviral therapy can exert direct antitumor activities also in HIV-free preclinical and clinical models. The aim of the present study was to evaluate the antineoplastic effects of various HIV-protease inhibitors (indinavir, ritonavir and saquinavir) on primary and established CC cell lines. Two CC cell lines established in our laboratory and four commercially available CC cell lines were treated with indinavir, ritonavir and saquinavir at different concentrations and for different times. Proliferation, clonogenicity and radiosensitivity were evaluated by crystal violet staining. Proteasomal activities were assessed using a cell-based assay and immunoblotting. Cell cycle was analyzed by propidium iodide staining and flow cytometric analysis. Invasion was tested with Matrigel chambers. A t-test for paired samples was used for statistical analysis. In all cell lines, saquinavir was more effective than ritonavir in reducing cell proliferation and inhibiting proteasomal activities (P≤0.05). Conversely, indinavir exerted a negligible effect. The saquinavir concentrations required to modulate the proteasome activities were higher than those observed to be effective in inhibiting cell proliferation. In HeLa cells, saquinavir was strongly effective in inhibiting cell invasion and clonogenicity (P≤0.05) at concentrations much lower than those required to perturb proteasomal activities. Saquinavir did not contribute to increase the sensitivity of HeLa cells to X-rays. In conclusion, the present results demonstrate that saquinavir is able to significantly reduce cell proliferation, cell invasion and clonogenicity in a proteasome-independent manner in in vitro models of CC, and suggest that saquinavir could be a promising CC therapeutic agent.

17.
Drugs Aging ; 33(9): 629-37, 2016 09.
Article in English | MEDLINE | ID: mdl-27444182

ABSTRACT

Poor adherence to treatment regimens has long been recognized as a substantial roadblock to achieving better outcomes for patients. Non-adherence to medications affects the quality and length of life and has been associated with negative health outcomes and increasing healthcare costs. The problem of non-adherence is particularly troublesome in older patients who are affected by multiple chronic diseases and for this reason receive multiple treatments. To date, no single intervention strategy has been shown to be effective in improving adherence across all patients, conditions, and settings. Between September and October 2014, a group of experts in geriatrics, pharmacology, epidemiology, and public health applied a modified RAND appropriateness method to reach a consensus on the possible best interventions to improve adherence in older individuals. Seven interventions were identified, classified based on their target (patient, therapy, and public health/society): (1) Comprehensive Geriatric Assessment, (2) patient (and caregiver) education to improve patient empowerment, (3) optimization of treatment, (4) use of adherence aids, (5) physician and other healthcare professionals' education, (6) adherence assessment, (7) facilitating access to medicine by service integration. For each intervention, experts assessed (a) target population, (b) health professionals potentially involved in the intervention, (c) strategies/instruments needed for implementation, and (d) time of the intervention. Interventions that target adherence must combine different approaches targeting the complex aspects of older adults in a holistic approach. Tackling non-adherence, with its complexity, requires a multi-stakeholder patient-centred approach acting in a defined framework of interactions in which the different players may provide different services but are integrated with one another.


Subject(s)
Aging , Consensus , Drug Therapy/methods , Geriatric Assessment , Medication Adherence/statistics & numerical data , Patient-Centered Care , Aged , Aged, 80 and over , Aging/psychology , Drug Therapy/standards , Drug Therapy/statistics & numerical data , Drug Therapy/trends , Education, Professional/organization & administration , Health Personnel/education , Humans , Italy , Middle Aged , Patient Education as Topic/organization & administration , Patient-Centered Care/methods , Patient-Centered Care/standards , Patient-Centered Care/trends
18.
Clinicoecon Outcomes Res ; 8: 253-65, 2016.
Article in English | MEDLINE | ID: mdl-27358570

ABSTRACT

Computerized health care databases have been widely described as an excellent opportunity for research. The availability of "big data" has brought about a wave of innovation in projects when conducting health services research. Most of the available secondary data sources are restricted to the geographical scope of a given country and present heterogeneous structure and content. Under the umbrella of the European Innovation Partnership on Active and Healthy Ageing, collaborative work conducted by the partners of the group on "adherence to prescription and medical plans" identified the use of observational and large-population databases to monitor medication-taking behavior in the elderly. This article describes the methodology used to gather the information from available databases among the Adherence Action Group partners with the aim of improving data sharing on a European level. A total of six databases belonging to three different European countries (Spain, Republic of Ireland, and Italy) were included in the analysis. Preliminary results suggest that there are some similarities. However, these results should be applied in different contexts and European countries, supporting the idea that large European studies should be designed in order to get the most of already available databases.

19.
BMC Public Health ; 16: 200, 2016 Feb 29.
Article in English | MEDLINE | ID: mdl-26927226

ABSTRACT

BACKGROUND: We carried out a study to evaluate the prevalence of Chlamydia trachomatis and Neisseria gonorrhoeae genital infections in school-based adolescents in Northern Italy. METHODS: Systematic screening for C. trachomatis and N. gonorrhoeae genital infection was performed in 13th grade students in the province of Brescia, an industrialized area in Northern Italy. Student filled in a questionnaire on sexual behaviour and provided a urine sample for microbiological testing. RESULTS: A total of 2,718 students (mean age: 18.4 years; 59.1% females) provided complete data (62.2% of those eligible). Overall 2,059 students (75.8%) were sexually active (i.e. had had at least one partner), and the mean age at sexual debut was 16.1 years (SD: 1.4). Only 27.5% of the sexually active students reported regular condom use during the previous 6 months, with higher frequency in males than in females (33.8% vs 24.2%). No case of N. gonorrhoeae infection was detected, while C. trachomatis was found in 36 adolescents, with a prevalence of 1.7% (95% CI: 1.2-2.4) among sexually active students, and no statistical difference between females and males (1.9 and 1.4%, respectively). Inconsistent condom use (odds ratio, OR = 5.5) and having had more than one sexual partner during the previous 6 months (OR = 6.8) were associated with an increased risk of Chlamydia infection at multivariate analysis. CONCLUSION: The prevalence of C. trachomatis infection among sexually active adolescents in Northern Italy was low, despite a high proportion of students who engage in risky sexual behaviour. No cases of N. gonorrhoeae infection were identified.


Subject(s)
Chlamydia Infections/epidemiology , Chlamydia trachomatis/isolation & purification , Gonorrhea/epidemiology , Neisseria gonorrhoeae/isolation & purification , Adolescent , Condoms/statistics & numerical data , Female , Humans , Italy/epidemiology , Male , Mass Screening , Multivariate Analysis , Prevalence , Risk Factors , Risk-Taking , Schools , Sexual Behavior/psychology , Sexual Behavior/statistics & numerical data , Sexual Partners , Students/psychology , Students/statistics & numerical data , Surveys and Questionnaires
20.
Intern Emerg Med ; 11(5): 677-85, 2016 Aug.
Article in English | MEDLINE | ID: mdl-26843198

ABSTRACT

Antiplatelet drugs, statins, angiotensinogen-converting enzyme inhibitors or angiotensin-II receptor blockers, and ß-blockers improve survival following myocardial infarction (MI). However, in old age they are under-prescribed, and their effectiveness in combination regimens is unproven. The aim of the study was to evaluate prescription of recommended cardiovascular drug classes and impact of a combination regimen on long-term mortality and hospitalizations. Records of 65+ years MI survivors, discharged from hospitals in four Local Health Units in Italy, were selected from administrative databases and analyzed. All-cause mortality and cardiovascular re-hospitalization in 12 months were compared across participants prescribed 0, 1, 2, 3, or 4 recommended drug classes. Out of 2626 participants (56 % men, 25 % aged 85+ years), 42 % were prescribed all, 14 % none of the recommended drug classes. The prescription rate decreased with advancing age. At all ages, mortality decreased with increasing number of drug classes prescribed: in participants aged 85+ years, adjusted hazard ratios (95 % confidence interval) for death were 0.74 (0.47-1.17), 0.52 (0.33-0.82), 0.30 (1.19-0.48), and 0.33 (0.20-0.53) for 1, 2, 3, and 4 classes prescribed, compared with none. The risk of cardiovascular re-hospitalizations decreased with an increasing number of drug classes prescribed through the age of 84 years. After MI, a combination regimen of recommended drug classes prevents long-term mortality at any age, and cardiovascular re-hospitalizations through the age of 84. Enhancing compliance with treatment guidelines may reduce the burden of mortality and hospitalizations in older MI survivors.


Subject(s)
Evidence-Based Medicine/methods , Myocardial Infarction/drug therapy , Patient Outcome Assessment , Adrenergic beta-Antagonists/pharmacology , Adrenergic beta-Antagonists/therapeutic use , Aged , Aged, 80 and over , Angiotensin II Type 2 Receptor Blockers/pharmacology , Angiotensin II Type 2 Receptor Blockers/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Cohort Studies , Evidence-Based Medicine/standards , Female , Humans , Italy/epidemiology , Male , Myocardial Infarction/epidemiology , Myocardial Infarction/mortality , Platelet Aggregation Inhibitors/pharmacology , Platelet Aggregation Inhibitors/therapeutic use , Regression Analysis
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