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1.
IEEE Trans Vis Comput Graph ; 30(5): 2591-2601, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38437092

RESUMO

Autism Spectrum Disorder is a neurodevelopmental condition that can affect autonomy and independence. Our research explores the integration of Cross-Reality and Conversational Agents for Autistic persons to improve ability and confidence in everyday life situations. We combine two technologies of the Virtual-Real continuum. User experiences unfold from the simulation of tasks in VR to the execution of similar tasks supported by AR in the real world. A speech-based Conversational Agent is integrated with both VR and AR. It provides contextualized help, promotes generalization, and stimulates users to apply what they learned in the virtual space. The paper presents the approach and describes an empirical study involving 17 young Autistic persons.


Assuntos
Transtorno do Espectro Autista , Transtorno Autístico , Humanos , Gráficos por Computador , Aprendizagem , Poder Psicológico
2.
Bioengineering (Basel) ; 10(7)2023 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-37508821

RESUMO

Due to the increased use of common and non-invasive abdominal imaging techniques over the last few decades, the diagnosis of about 60% of renal tumors is incidental. Contrast-enhancing renal nodules on computed tomography are diagnosed as malignant tumors, which are often removed surgically without first performing a biopsy. Most kidney nodules are renal cell carcinoma (RCC) after surgical treatment, but a non-negligible rate of these nodules may be benign on final pathology; as a result, patients undergo unnecessary surgery with an associated significant morbidity. Our study aimed to identify a subgroup of patients with higher odds of harboring benign tumors, who would hence benefit from further diagnostic examinations (such as renal biopsy) or active surveillance. We performed a retrospective review of the medical data, including pathology results, of patients undergoing surgery for solid renal masses that were suspected to be RCCs (for a total sample of 307 patients). Owing to the widespread use of common and non-invasive imaging techniques, the incidental diagnosis of kidney tumors has become increasingly common. Considering that a non-negligible rate of these tumors is found to be benign after surgery at pathological examination, it is crucial to identify features that can correctly diagnose a mass as benign or not. According to our study results, female sex and tumor size ≤ 3 cm were independent predictors of benign disease. Contrary to that demonstrated by other authors, increasing patient age was also positively linked to a greater risk of malign pathology.

3.
Cells ; 12(10)2023 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-37408248

RESUMO

The F-Box and WD Repeat Domain Containing 7 (FBXW7) protein has been shown to regulate cellular growth and act as a tumor suppressor. This protein, also known as FBW7, hCDC4, SEL10 or hAGO, is encoded by the gene FBXW7. It is a crucial component of the Skp1-Cullin1-F-box (SCF) complex, which is a ubiquitin ligase. This complex aids in the degradation of many oncoproteins, such as cyclin E, c-JUN, c-MYC, NOTCH, and MCL1, via the ubiquitin-proteasome system (UPS). The FBXW7 gene is commonly mutated or deleted in numerous types of cancer, including gynecologic cancers (GCs). Such FBXW7 mutations are linked to a poor prognosis due to increased treatment resistance. Hence, detection of the FBXW7 mutation may possibly be an appropriate diagnostic and prognostic biomarker that plays a central role in determining suitable individualized management. Recent studies also suggest that, under specific circumstances, FBXW7 may act as an oncogene. There is mounting evidence indicating that the aberrant expression of FBXW7 is involved in the development of GCs. The aim of this review is to give an update on the role of FBXW7 as a potential biomarker and also as a therapeutic target for novel treatments, particularly in the management of GCs.


Assuntos
Proteínas F-Box , Neoplasias dos Genitais Femininos , Feminino , Humanos , Proteína 7 com Repetições F-Box-WD/genética , Proteína 7 com Repetições F-Box-WD/metabolismo , Proteínas F-Box/genética , Proteínas F-Box/metabolismo , Neoplasias dos Genitais Femininos/genética , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitinas/metabolismo
4.
Exp Ther Med ; 25(4): 173, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37006882

RESUMO

The aim of the present study was to analyze incidence, histopathological features and clinical outcomes of patients undergoing radical cystoprostatectomy (RCP) for bladder cancer, in which incidental prostate cancer (PCa) was found. How these types of cancer impacted the patients' management and whether prostate-sparing cystectomy could be an option for these patients was determined. The current study retrospectively analyzed the data of a cohort of patients from 'Umberto I' Hospital of Nocera Inferiore who underwent RCP for bladder transitional cell carcinoma. Patients with a preoperative diagnosis or clinical suspicion of PCa were excluded. Patients affected by incidental PCa in the RCP specimens were identified, and then their demographic, histopathological and clinical outcome data were collected. Overall, it was revealed that of the 303 patients undergoing RCP for bladder cancer, 69 (22.7%) had incidental PCa, with a median age of 71.6 (age range, 54-89 years). In total, 23 (33.33%) of the 69 patients with incidental PCa were considered to have clinically significant prostate disease. In conclusion, it was relatively common to identify incidental PCa in RCP specimens but no preoperative predictive factors were identified that were able to determine 'non-aggressive' PCa status. Therefore, the present results demonstrate the need for a careful and complete prostate removal during RCP. Nevertheless, since organ-sparing surgeries are widely performed in young population, due to the impossibility of predicting aggressive prostate cancer, these patients require close monitoring through lifelong PSA surveillance, particularly focusing on the possible relapse of PCa after RCP.

5.
Front Immunol ; 14: 1129513, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36999042

RESUMO

Introduction: Despite increased attention on immunotherapy, primarily immune checkpoint blockade, as a therapeutic approach for mesothelioma (MMe), its efficacy and tolerability remain questioned. One potential explanation for different responses to immunotherapy is the gut and intratumor microbiota; however, these remain an underexplored facet of MMe. This article highlights the cancer intratumor microbiota as a novel potential prognostic indicator in MMe. Methods: TCGA data on 86 MMe patients from cBioPortal underwent bespoke analysis. Median overall survival was used to divide patients into "Low Survivors" and "High Survivors". Comparison of these groups generated Kaplan-Meier survival analysis, differentially expressed genes (DEGs), and identification of differentially abundant microbiome signatures. Decontamination analysis refined the list of signatures, which were validated as an independent prognostic indicator through multiple linear regression modelling and Cox proportional hazards modelling. Finally, functional annotation analysis on the list of DEGs was performed to link the data together. Results: 107 genera signatures were significantly associated with patient survival (positively or negatively), whilst clinical characteristic comparison between the two groups demonstrated that epithelioid histology was more common in "High Survivors" versus biphasic in "Low Survivors". Of the 107 genera, 27 had published articles related to cancer, whilst only one (Klebsiella) had MMe-related published articles. Functional annotation analysis of the DEGs between the two groups highlighted fatty acid metabolism as the most enriched term in "High Survivors", whilst for "Low Survivors" the enriched terms primarily related to cell cycle/division. Linking these ideas and findings together is that the microbiome influences, and is influenced by, lipid metabolism. Finally, to validate the independent prognostic value of the microbiome, multiple linear regression modelling as well as Cox proportional hazards modelling were employed, with both approaches demonstrating that the microbiome was a better prognostic indicator than patient age or stage of the cancer. Discussion: The findings presented herein, alongside the very limited literature from scoping searches to validate the genera, highlight the microbiome and microbiota as a potentially rich source of fundamental analysis and prognostic value. Further in vitro studies are needed to elucidate the molecular mechanisms and functional links that may lead to altered survival.


Assuntos
Mesotelioma Maligno , Mesotelioma , Microbiota , Humanos , Prognóstico , Mesotelioma/patologia
6.
Diseases ; 11(1)2023 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-36810541

RESUMO

In daily medical practice, an increasing number of kidney masses are being incidentally detected using common imaging techniques, owing to the improved diagnostic accuracy and increasingly frequent use of these techniques. As a consequence, the rate of detection of smaller lesions is increasing considerably. According to certain studies, following surgical treatment, up to 27% of small enhancing renal masses are identified as benign tumors at the final pathological examination. This high rate of benign tumors challenges the appropriateness of surgery for all suspicious lesions, given the morbidity associated with such an intervention. The objective of the present study was, therefore, to determine the incidence of benign tumors at partial nephrectomy (PN) for a solitary renal mass. To meet this end, a total of 195 patients who each underwent one PN for a solitary renal lesion with the intent to cure RCC were included in the final retrospective analysis. A benign neoplasm was identified in 30 of these patients. The age of the patients ranged from 29.9-79 years (average: 60.9 years). The tumor size range was 1.5-7 cm (average: 3 cm). All the operations were successful using the laparoscopic approach. The pathological results were renal oncocytoma in 26 cases, angiomyolipomas in two cases, and cysts in the remaining two cases. In conclusion, we have shown in our present series the incidence rate of benign tumors in patients who have been subjected to laparoscopic PN due to a suspected solitary renal mass. Based on these results, we advise that the patient should be counseled not only about the intra- and post-operative risks of nephron-sparing surgery but also about its dual therapeutic and diagnostic role. Therefore, the patients should be informed of the considerably high probability of a benign histological result.

7.
J Transl Med ; 20(1): 593, 2022 12 13.
Artigo em Inglês | MEDLINE | ID: mdl-36514092

RESUMO

In this commentary, using existing clinical trial data and FDA approvals we propose that there is currently a critical need for an appropriate balancing between the financial impact of new cancer drugs and their actual benefit for patients. By adopting "pleural mesothelioma" as our clinical model we summarize the most relevant pertinent and available literature on this topic, and use an analysis of the reliability of the trials submitted for registration and/or recently published as a case in point to raise concerns with respect to appropriate trial design, biomarker based stratification and to highlight the ongoing need for balancing the benefit/cost ratio for both patients and healthcare providers.


Assuntos
Neoplasias Pulmonares , Mesotelioma Maligno , Mesotelioma , Neoplasias Pleurais , Humanos , Reprodutibilidade dos Testes , Mesotelioma/patologia , Neoplasias Pleurais/tratamento farmacológico , Neoplasias Pulmonares/patologia
8.
Mol Clin Oncol ; 17(2): 127, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35832470

RESUMO

The present study aimed to investigate the relationship between BMI and the prostate cancer (PCa) risk at biopsy in Italian men. Retrospective analyses of the clinical data of 2,372 consecutive men undergoing ultrasound-guided multicore (≥10) prostate biopsy transrectally between May 2010 and December 2018 were performed. BMIs were categorized, according to Western countries' classification of obesity, as follows: <18.5 kg/m2 (underweight), 18.5-24.99 kg/m2 (normal weight), 25-30 kg/m2 (overweight) and >30 kg/m2 (obese). The distribution of patients undergoing biopsy was compared with a model population from the official survey data. Patient characteristics and the relationships between characteristics were investigated using correlation analysis, ANOVA, Kruskal-Wallis and Dunn's tests. The present study estimated the influence on cancer incidence not only of BMI but also of other patient characteristics using multi-variable logistic modelling and compared, using the models, the expected outcomes for patients who differed only in BMI. From a sample of 2,372 men, the present study enrolled 1,079 men due to a lack of clinical data [such as prostate specific antigen (PSA) and BMI data] in the other patients undergoing prostate biopsy. Their distribution was significantly different from the model distribution with the probability of undergoing biopsy increasing with increasing BMI. The median age was 69.4 years. The median BMI was 26.4 kg/m2, while the median PSA level was 7.60 ng/ml. In total, the biopsies detected PCa in 320 men (29.7%) and high-grade PCa (HGPCa) in 218 men (20.2%). Upon applying the aforementioned Western countries' criteria for BMI categories, there were 4 (0.4%) underweight, 318 (29.5%) of normal weight, 546 (50.6%) overweight, and 211 (19.6%) obese patients. ANOVA/Kruskal-Wallis tests revealed that overweight and obese men were younger than the normal-weight men, while there was no statistical difference in their PSA values. Furthermore, 29.3% of normal-weight men, 29.5% of overweight men and 29.9% of obese men were diagnosed with PCa, while 19.5% of normal-weight men, 20.1% of overweight men and 21.8% of obese men were affected by severe cancer. BMI was found to be positively correlated with PCa risk and negatively correlated with both age and PSA level. Age and PSA level were both positively correlated with PCa risk, while digital rectal examination (DRE) outcome was strongly indicative of PCa discovery if the test outcome was positive. Logistics models attributed a positive coefficient to BMI when evaluated against both PCa risk and HGPCa risk. In patients having a negative DRE outcome who differed only in BMI, logistic regression showed a 60% increased risk of PCa diagnosis in obese patients compared with in normal-weight patients. This risk difference increased when other characteristics were less indicative of PCa (younger age/lower PSA), while it decreased when patient characteristics were more indicative (older age/higher PSA, positive DRE). In conclusion, the present study demonstrated that, in men with higher BMIs, the risk of PCa is higher. The relative difference in risk between low and high BMI is most pronounced in younger patients having a lower PSA level and a negative DRE outcome.

9.
J Surg Case Rep ; 2022(6): rjac127, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35692301

RESUMO

Pneumothorax is a rare complication in laparoscopic renal surgery. However, due to the increasing renal pathologies managed by laparoscopic technique, this infrequent complication is a potential risk. We investigated the incidence rate of this complication in our experience of laparoscopic renal surgery, taking into account the laparoscopic approach, the type of intervention, the character of the pathology (neoplastic or other), the site of the intervention, as well as the localization of the lesion (in case of malignant pathology). About 384 laparoscopic nephrectomies were reviewed at our institution, with a total of four cases (1.04%) of diaphragmatic injury. Diaphragmatic repair was always carried out by intracorporeal suturing, with no complications. Repair of diaphragmatic injuries should always be attempted with intracorporeal suture since this is a safe and effective technique. Then, although in the retroperitoneal approach pneumothorax is more likely, our experience has shown that transperitoneal access is not free from this complication.

10.
Cancers (Basel) ; 14(11)2022 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-35681689

RESUMO

Overweight and obesity constitute the most impactful lifestyle-dependent risk factors for cancer and have been tightly linked to a higher number of tumor-related deaths nowadays. The excessive accumulation of energy can lead to an imbalance in the level of essential cellular biomolecules that may result in inflammation and cell-cycle dysregulation. Nutritional strategies and phytochemicals are gaining interest in the management of obesity-related cancers, with several ongoing and completed clinical studies that support their effectiveness. At the same time, cyclin-dependent kinases (CDKs) are becoming an important target in breast and ovarian cancer treatment, with various FDA-approved CDK4/6 inhibitors that have recently received more attention for their potential role in diet-induced obesity (DIO). Here we provide an overview of the most recent studies involving nutraceuticals and other dietary strategies affecting cell-cycle pathways, which might impact the management of breast and ovarian cancers, as well as the repurposing of already commercialized chemotherapeutic options to treat DIO.

11.
Int J Mol Sci ; 23(9)2022 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-35563557

RESUMO

Cervical cancer (CC) is the fourth most common type of gynecological malignancy affecting females worldwide. Most CC cases are linked to infection with high-risk human papillomaviruses (HPV). There has been a significant decrease in the incidence and death rate of CC due to effective cervical Pap smear screening and administration of vaccines. However, this is not equally available throughout different societies. The prognosis of patients with advanced or recurrent CC is particularly poor, with a one-year relative survival rate of a maximum of 20%. Increasing evidence suggests that cancer stem cells (CSCs) may play an important role in CC tumorigenesis, metastasis, relapse, and chemo/radio-resistance, thus representing potential targets for a better therapeutic outcome. CSCs are a small subpopulation of tumor cells with self-renewing ability, which can differentiate into heterogeneous tumor cell types, thus creating a progeny of cells constituting the bulk of tumors. Since cervical CSCs (CCSC) are difficult to identify, this has led to the search for different markers (e.g., ABCG2, ITGA6 (CD49f), PROM1 (CD133), KRT17 (CK17), MSI1, POU5F1 (OCT4), and SOX2). Promising therapeutic strategies targeting CSC-signaling pathways and the CSC niche are currently under development. Here, we provide an overview of CC and CCSCs, describing the phenotypes of CCSCs and the potential of targeting CCSCs in the management of CC.


Assuntos
Neoplasias do Colo do Útero , Transformação Celular Neoplásica/metabolismo , Feminino , Humanos , Recidiva Local de Neoplasia/patologia , Células-Tronco Neoplásicas/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Proteínas de Ligação a RNA/metabolismo , Transdução de Sinais , Neoplasias do Colo do Útero/patologia
12.
J Thorac Oncol ; 17(7): 873-889, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35462085

RESUMO

The most common malignancies that develop in carriers of BAP1 germline mutations include diffuse malignant mesothelioma, uveal and cutaneous melanoma, renal cell carcinoma, and less frequently, breast cancer, several types of skin carcinomas, and other tumor types. Mesotheliomas in these patients are significantly less aggressive, and patients require a multidisciplinary approach that involves genetic counseling, medical genetics, pathology, surgical, medical, and radiation oncology expertise. Some BAP1 carriers have asymptomatic mesothelioma that can be followed by close clinical observation without apparent adverse outcomes: they may survive many years without therapy. Others may grow aggressively but very often respond to therapy. Detecting BAP1 germline mutations has, therefore, substantial medical, social, and economic impact. Close monitoring of these patients and their relatives is expected to result in prolonged life expectancy, improved quality of life, and being cost-effective. The co-authors of this paper are those who have published the vast majority of cases of mesothelioma occurring in patients carrying inactivating germline BAP1 mutations and who have studied the families affected by the BAP1 cancer syndrome for many years. This paper reports our experience. It is intended to be a source of information for all physicians who care for patients carrying germline BAP1 mutations. We discuss the clinical presentation, diagnostic and treatment challenges, and our recommendations of how to best care for these patients and their family members, including the potential economic and psychosocial impact.


Assuntos
Neoplasias Pulmonares , Melanoma , Mesotelioma Maligno , Mesotelioma , Neoplasias Cutâneas , Predisposição Genética para Doença , Mutação em Linhagem Germinativa , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/cirurgia , Melanoma/genética , Mesotelioma/diagnóstico , Mesotelioma/genética , Mesotelioma/cirurgia , Qualidade de Vida , Neoplasias Cutâneas/genética , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo , Ubiquitina Tiolesterase/genética , Ubiquitina Tiolesterase/metabolismo
13.
JAMA Netw Open ; 5(3): e221490, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-35262715

RESUMO

Importance: Some recently proposed frontline therapies for malignant pleural mesothelioma (MPM) are very costly, yet their impact on quality of life and overall survival of these patients remains arguable. Given the high social toll of this aggressive occupational cancer, it is paramount to establish the real clinical benefit of these treatments. Objective: To directly compare and analyze the statistical robustness of the 3 randomized clinical trials (RCTs) of frontline therapies recommended for MPM since 2003. Design, Setting, and Participants: This comparative effectiveness study assessed the following phase 3 RCTs: the Mesothelioma Cisplatin Pemetrexed Study (MPS) of cisplatin plus pemetrexed vs cisplatin; the Mesothelioma Avastin Cisplatin Pemetrexed Study (MAPS) of cisplatin plus pemetrexed plus bevacizumab vs cisplatin plus pemetrexed; and the CheckMate743 (CM743) study of nivolumab plus ipilimumab vs cisplatin plus pemetrexed. Data collection dates for the RCTs ranged from April 1999 to April 2018. Data for this study were analyzed from February to October 2021. Main Outcomes and Measures: Patient selection criteria, superiority of the intervention groups, survival-inferred fragility index, and censoring patterns in each RCT. Results: A total of 1501 patients were included in the analysis (1170 men [77.9%]; range of median age for treatment groups, 60 [IQR, 19-84] to 69 [IQR, 65-75] years). A virtual comparison of overall survival in MAPS vs the CM743 study showed no statistically significant difference (hazard ratio [HR], 0.97 [95% CI, 0.79-1.20]; P = .79), and the survival-inferred fragility index in the intention-to-treat (ITT) populations was as low as 0.22% of the total sample size in MPS, -0.45% of the total sample size in MAPS, and 0.99% of the total sample size in the CM743 trial. Moreover, reverse restricted mean survival time (RMST) analysis of overall survival using RMST-difference (RMST-D) demonstrated differential censoring in the ITT population of the CM743 trial favoring the control group (0.56 [95% CI, 0.18-0.94]; P = .004) and in the nonepithelioid group (reverse RMST-D, 0.90 [95% CI, 0.001-1.79]; P = .048). Conclusions and Relevance: This comparative effectiveness study found no survival benefit in the CM743 trial over MAPS, despite the inclusion of patients with worse prognosis in the latter trial. Moreover, the statistical conclusions of all the examined trials were shown to be extremely fragile, and the findings of differential censoring in the CM743 trial and in the ITT nonepithelial subset raised additional areas of concern. These findings suggest that selection criteria, fragility, and censoring patterns may affect the original conclusions drawn for the respective trials, casting a shadow on the real benefit. This model of analysis lays a rigorous groundwork extendable to trials of all cancer treatments before their registration.


Assuntos
Mesotelioma Maligno , Mesotelioma , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cisplatino/uso terapêutico , Feminino , Humanos , Masculino , Mesotelioma/tratamento farmacológico , Mesotelioma Maligno/tratamento farmacológico , Pessoa de Meia-Idade , Pemetrexede/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Adulto Jovem
15.
Viruses ; 13(12)2021 12 08.
Artigo em Inglês | MEDLINE | ID: mdl-34960727

RESUMO

Malignant mesothelioma (MM) is an aggressive asbestos-related cancer, against which no curative modalities exist. Oncolytic virotherapy is a promising therapeutic approach, for which MM is an ideal candidate; indeed, the pleural location provides direct access for the intra-tumoral injection of oncolytic viruses (OVs). Some non-human OVs offer advantages over human OVs, including the non-pathogenicity in humans and the absence of pre-existing immunity. We previously showed that caprine herpesvirus 1 (CpHV-1), a non-pathogenic virus for humans, can kill different human cancer cell lines. Here, we assessed CpHV-1 effects on MM (NCI-H28, MSTO, NCI-H2052) and non-tumor mesothelial (MET-5A) cells. We found that CpHV-1 reduced cell viability and clonogenic potential in all MM cell lines without affecting non-tumor cells, in which, indeed, we did not detect intracellular viral DNA after treatment. In particular, CpHV-1 induced MM cell apoptosis and accumulation in G0/G1 or S cell cycle phases. Moreover, CpHV-1 strongly synergized with cisplatin, the drug currently used in MM chemotherapy, and this agent combination did not affect normal mesothelial cells. Although further studies are required to elucidate the mechanisms underlying the selective CpHV-1 action on MM cells, our data suggest that the CpHV-1-cisplatin combination could be a feasible strategy against MM.


Assuntos
Antineoplásicos/farmacologia , Apoptose , Cisplatino/farmacologia , Mesotelioma Maligno/terapia , Terapia Viral Oncolítica , Vírus Oncolíticos/fisiologia , Varicellovirus/fisiologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Terapia Combinada , Humanos , Mesotelioma Maligno/tratamento farmacológico , Mesotelioma Maligno/fisiopatologia , Mesotelioma Maligno/virologia , Vírus Oncolíticos/genética , Varicellovirus/genética
16.
Cancers (Basel) ; 13(19)2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34638509

RESUMO

The members of the retinoblastoma (RB) protein family, RB1/p105, retinoblastoma-like (RBL)1/p107 and RBL2/p130 are critical modulators of the cell cycle and their dysregulation has been associated with tumor initiation and progression. The activity of RB proteins is regulated by numerous pathways including oncogenic signaling, but the molecular mechanisms of these functional interactions are not fully defined. We previously demonstrated that RBL2/p130 is a direct target of AKT and it is a key mediator of the apoptotic process induced by AKT inhibition. Here we demonstrated that RBL1/p107 levels are only minorly modulated by the AKT signaling pathway. In contrast, we discovered that RBL1/p107 levels are regulated by multiple pathways linked directly or indirectly to Ca2+-dependent signaling. Inhibition of the multifunctional calcium/calmodulin-dependent kinases (CaMKs) significantly reduced RBL1/p107 expression levels and phosphorylation, increased RBL1/p107 nuclear localization and led to cell cycle arrest in G0/G1. Targeting the Ca2+-dependent endopeptidase calpain stabilized RBL1/p107 levels and counteracted the reduction of RBL1/p107 levels associated with CaMKs inhibition. Thus, these novel observations suggest a complex regulation of RBL1/p107 expression involving different components of signaling pathways controlled by Ca2+ levels, including CaMKs and calpain, pointing out a significant difference with the mechanisms modulating the close family member RBL2/p130.

17.
Infect Agent Cancer ; 16(1): 62, 2021 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-34717691

RESUMO

SARS-CoV-2 infection can impact the physical, cognitive, mental health of patients, especially in those recovered in intensive care units. Moreover, it was proved that the effects of the virus may persist for weeks or months. The term long-COVID or post-COVID syndrome is commonly used for indicating a variety of physical and psychological symptoms that continue after the resolution of the acute phase. This narrative review is aimed at providing an updated overview of the impact of physical, cognitive, and psychological health disorders in COVID-19 survivors, by summarizing the data already published in literature in the last year. Studies cited were found through PubMed searches. We also presented an overview of the post-COVID-19 health consequences on three important aspects: nutritional status, neurological disorders, and physical health. Moreover, to activate a correct health planning policy, a multidisciplinary approach for addressing the post- COVID-19 issue, has been proposed. Finally, the involvement of health professionals is necessary even after the pandemic, to reduce expected post-pandemic psychosocial responses and mental health disorders.

18.
Int J Mol Sci ; 22(15)2021 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-34360598

RESUMO

Gynecological cancers (GCs) are currently among the major threats to female health. Moreover, there are different histologic subtypes of these cancers, which are defined as 'rare' due to an annual incidence of <6 per 100,000 women. The majority of these tend to be associated with a poor prognosis. Long non-coding RNAs (lncRNAs) play a critical role in the normal development of organisms as well as in tumorigenesis. LncRNAs can be classified into tumor suppressor genes or oncogenes, depending on their function within the cellular context and the signaling pathways in which they are involved. These regulatory RNAs are potential therapeutic targets for cancer due to their tissue and tumor specificity. However, there still needs to be a deeper understanding of the mechanisms by which lncRNAs are involved in the regulation of numerous biological functions in humans, both in normal health and disease. The lncRNA Mortal Obligate RNA Transcript (MORT; alias ZNF667-AS1) has been identified as a tumor-related lncRNA. ZNF667-AS1 gene, located in the human chromosome region 19q13.43, has been shown to be silenced by DNA hypermethylation in several cancers. In this review, we report on the biological functions of ZNF667-AS1 from recent studies and describe the regulatory functions of ZNF667-AS1 in human disease, including cancer. Furthermore, we discuss the emerging insights into the potential role of ZNF667-AS1 as a biomarker and novel therapeutic target in cancer, including GCs (ovarian, cervical, and endometrial cancers).


Assuntos
Neoplasias dos Genitais Femininos/patologia , RNA Longo não Codificante/genética , Animais , Feminino , Neoplasias dos Genitais Femininos/genética , Humanos
19.
Int J Mol Sci ; 22(12)2021 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-34204445

RESUMO

Choriocarcinoma (CC), a subtype of trophoblastic disease, is a rare and highly aggressive neoplasm. There are two main CC subtypes: gestational and non-gestational, (so called when it develops as a component of a germ cell tumor or is related to a somatic mutation of a poorly differentiated carcinoma), each with very diverse biological activity. A therapeutic approach is highly effective in patients with early-stage CC. The advanced stage of the disease also has a good prognosis with around 95% of patients cured following chemotherapy. However, advancements in diagnosis and treatment are always needed to improve outcomes for patients with CC. Long non-coding (lnc) RNAs are non-coding transcripts that are longer than 200 nucleotides. LncRNAs can act as oncogenes or tumor suppressor genes. Deregulation of their expression has a key role in tumor development, angiogenesis, differentiation, migration, apoptosis, and proliferation. Furthermore, detection of cancer-associated lncRNAs in body fluids, such as blood, saliva, and urine of cancer patients, is emerging as a novel method for cancer diagnosis. Although there is evidence for the potential role of lncRNAs in a number of cancers of the female genital tract, their role in CC is poorly understood. This review summarizes the current knowledge of lncRNAs in gestational CC and how this may be applied to future therapeutic strategies in the treatment of this rare cancer.


Assuntos
Coriocarcinoma/genética , Suscetibilidade a Doenças , Regulação Neoplásica da Expressão Gênica , RNA Longo não Codificante/genética , Neoplasias Uterinas/genética , Biomarcadores Tumorais , Coriocarcinoma/diagnóstico , Coriocarcinoma/metabolismo , Feminino , Humanos , Técnicas de Diagnóstico Molecular , Terapia de Alvo Molecular , Gradação de Tumores , Estadiamento de Neoplasias , Gravidez , Neoplasias Uterinas/diagnóstico , Neoplasias Uterinas/metabolismo
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