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1.
World J Oncol ; 12(4): 104-110, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34349854

RESUMO

BACKGROUND: Metastatic colorectal cancer (mCRC) with wild type expression of RAS and RAF genes can be treated with anti-epidermal growth factor receptor (EGFR) monoclonal antibodies, such as cetuximab, in combination with chemotherapy. Skin toxicity represents the most serious and frequent side effect in these patients. Skin manifestations occur in approximately 80% of patients. In this study, we investigated the consequences on body image and quality of life (QoL) of patients with severe skin toxicity. METHODS: One hundred patients were enrolled with mCRC. All patients signed informed consent and completed questionnaires to assess QoL and body discomfort. Toxicity was assessed on Common Terminology Criteria for Adverse Events (CTCAEs). RESULTS: The greatest impact on QoL was represented by difficulties in managing skin rash-related side effects. Data showed a significant impact in psychological sphere and social relationships. CONCLUSIONS: Skin side effects, particularly rash, influence QoL and social relationships, compromising therapeutic compliance.

2.
Cell Death Dis ; 12(6): 558, 2021 05 29.
Artigo em Inglês | MEDLINE | ID: mdl-34052831

RESUMO

Epithelial ovarian cancer (EOC) is a highly heterogeneous disease with a high death rate mainly due to the metastatic spread. The expression of MDM4, a well-known p53-inhibitor, is positively associated with chemotherapy response and overall survival (OS) in EOC. However, the basis of this association remains elusive. We show that in vivo MDM4 reduces intraperitoneal dissemination of EOC cells, independently of p53 and an immune-competent background. By 2D and 3D assays, MDM4 impairs the early steps of the metastatic process. A 3D-bioprinting system, ad hoc developed by co-culturing EOC spheroids and endothelial cells, showed reduced dissemination and intravasation into vessel-like structures of MDM4-expressing cells. Consistent with these data, high MDM4 levels protect mice from ovarian cancer-related death and, importantly, correlate with increased 15 y OS probability in large data set analysis of 1656 patients. Proteomic analysis of EOC 3D-spheroids revealed decreased protein synthesis and mTOR signaling, upon MDM4 expression. Accordingly, MDM4 does not further inhibit cell migration when its activity towards mTOR is blocked by genetic or pharmacological approaches. Importantly, high levels of MDM4 reduced the efficacy of mTOR inhibitors in constraining cell migration. Overall, these data demonstrate that MDM4 impairs EOC metastatic process by inhibiting mTOR activity and suggest the usefulness of MDM4 assessment for the tailored application of mTOR-targeted therapy.


Assuntos
Proteínas de Ciclo Celular/metabolismo , Neoplasias Ovarianas/genética , Proteômica/métodos , Proteínas Proto-Oncogênicas/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Animais , Feminino , Humanos , Camundongos , Metástase Neoplásica , Neoplasias Ovarianas/mortalidade , Análise de Sobrevida
3.
Rheumatol Immunol Res ; 2(2): 113-119, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36465974

RESUMO

In order to evaluate the importance of pain in systemic sclerosis (SSc), the characteristics of pain reported by patients with SSc were analyzed and compared with the characteristics of pain reported by patients with primary Sjogren's syndrome (pSS). Pain was reported by 56 patients (80%) in a group of 70 patients with SSc and by 25 patients (78%) in a group of 32 patients with pSS. Pain severity was assessed by the Pain Rating Index (PRI) and the Present Pain Intensity (PPI) of the McGill Pain Questionnaire (MPQ) and by values obtained by a visual analog scale (VAS) indicating the intensity of pain felt in the moment of the examination and the intensity of pain felt in the week preceding the moment of the examination. No significant difference was detected in the comparison of mean values of pain indices between patients with SSc and patients with pSS and in the comparison among subgroups of patients with SSc. The data indicate that pain is a frequent and important cause of suffering in SSc as in other chronic diseases. The association of different methods may be especially useful to obtain a careful evaluation of pain in clinical research.

4.
Popul Health Manag ; 24(2): 174-181, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33373536

RESUMO

Italy was one of the countries most affected by the number of people infected and dead during the first COVID-19 wave. The authors describe the rapid rollout of a population health clinical and organizational response in preparedness and capabilities to support the first wave of the COVID-19 pandemic in the Italian province of Modena. The authors review the processes, the challenges faced, and describe how excess demand for hospital services was successfully mitigated and thus overwhelming the healthcare services avoided the collapse of the local health care system. An analysis of bed occupancy in the region predicted during the first weeks of the epidemic. The SEIR model estimated the number of infected people under different containment measures. Community resources were mobilized to reduce provincial hospitals' burden of care. A population health approach, based on a radical reorganization of the workflow and emergency patient management, was implemented. The bed saturation of the Modena Healthcare Agency was measured by an ad hoc, newly implemented intensive care unit (ICU) bed occupancy and COVID-19 centralized governance dashboard. ICU bed occupancy increased by 114%, avoiding saturation of the Modena Healthcare Agency system. The Emilia-Romagna region achieved a higher rate of ICU bed availability at 2.15 ICU beds per 10,000 inhabitants as compared with community 1 ICU bed availability prior to the pandemic. Rapid and radical local reorganization of regional efforts helped inform the successful development and implementation of strategic choices within the hospital and the community to prevent the saturation of key facilities.


Assuntos
COVID-19/terapia , Controle de Doenças Transmissíveis/organização & administração , Número de Leitos em Hospital , Unidades de Terapia Intensiva/organização & administração , Saúde da População , Capacidade de Resposta ante Emergências/organização & administração , COVID-19/epidemiologia , Humanos , Itália
5.
Artigo em Inglês | MEDLINE | ID: mdl-32994802

RESUMO

BACKGROUND: TAS-102 is an oral monotherapy, combining trifluridine and tipiracil hydrochloride, indicated for the treatment of pretreated metastatic colorectal cancer (mCRC). The aim of this real-life study is to evaluate the efficacy and safety of TAS-102 in heavily pretreated elderly patients with mCRC whose disease has progressed with standard therapies. METHODS: In this retrospective observational study, we enrolled 50 elderly patients >70 years of age (median age 78 years) with a diagnosis of mCRC who were previously treated or were not considered candidates for treatment with other available therapies. Patients aged >70 years with advanced colorectal cancer and with an ECOG performance status of grade 0 (n=18) or grade 1 (n=32) were included. Overall survival and progression-free survival were the primary endpoints, whereas objective response rate, tolerability, and quality of life were the secondary endpoints. RESULTS: Treatment with TAS-102 appeared to be well tolerated and side effects were generally mild, achieving disease control and a benefit on quality of life. The median overall survival was 6.7 (95% CI 5.7-11.3) and the median progression-free survival was 2.1 months (95% CI 1.2-3.2), estimated using the Kaplan-Meier method. CONCLUSION: TAS-102 represents a manageable and effective therapeutic opportunity and appeared to be well tolerated with generally mild side effects in elderly patients with mCRC who were heavily pretreated with standard therapies.

6.
Cancers (Basel) ; 11(9)2019 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-31547268

RESUMO

Estrogen activity towards cancer-related pathways can impact therapeutic intervention. Recent omics data suggest possible crosstalk between estrogens/gender and MDM4, a key regulator of p53. Since MDM4 can either promote cell transformation or enhance DNA damage-sensitivity, we analysed in vivo impact of estrogens on both MDM4 activities. In Mdm4 transgenic mouse, Mdm4 accelerates the formation of fibrosarcoma and increases tumor sensitivity to cisplatin as well, thus confirming in vivo Mdm4 dual mode of action. Noteworthy, Mdm4 enhances chemo- and radio-sensitivity in male but not in female animals, whereas its tumor-promoting activity is not affected by mouse gender. Combination therapy of transgenic females with cisplatin and fulvestrant, a selective estrogen receptor degrader, was able to recover tumor cisplatin-sensitivity, demonstrating the relevance of estrogens in the observed sexual dimorphism. Molecularly, estrogen receptor-α alters intracellular localization of MDM4 by increasing its nuclear fraction correlated to decreased cell death, in a p53-independent manner. Importantly, MDM4 nuclear localization and intra-tumor estrogen availability correlate with decreased platinum-sensitivity and apoptosis and predicts poor disease-free survival in high-grade serous ovarian carcinoma. These data demonstrate estrogen ability to modulate chemo-sensitivity of MDM4-expressing tumors and to impinge on intracellular trafficking. They support potential usefulness of combination therapy involving anti-estrogenic drugs.

7.
Oncology ; 97(6): 341-347, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31461721

RESUMO

BACKGROUND: Vinflunine is a microtubule inhibitor of the vinca alkaloid class approved for the treatment of urothelial bladder carcinoma after a platinum-containing regimen. METHODS: To evaluate the effectiveness of vinflunine, we enrolled 80 subjects with a histologically confirmed diagnosis of metastatic urothelial bladder carcinoma that had previously undergone chemotherapy with a platinum-containing regimen and had measurable lesions according to the Response Evaluation Criteria in Solid Tumors (RECIST). The patients (n = 80) received vinflunine (Javlor®) every 3 weeks at 320 mg/m2 via 20-min intravenous infusion. The endpoints were progression-free survival (PFS), objective response rate, overall survival (OS), and tolerability. The cumulative survival of the patients was analyzed using the Kaplan-Meier method. RESULTS: In this retrospective study, vinflunine treatment was well tolerated and resulted in a good level of disease control (complete response + partial response + stable disease >50%), with a manageable toxicity profile. The median PFS and OS were 3.2 and 6.8 months, respectively. A significant correlation between pain and PFS was also noted. The major hematologic adverse event was neutropenia, observed in 47% of the patients. The most common nonhematologic adverse events were constipation in 48% of the patients and fatigue in 26%. DISCUSSION: In this real-word non-randomized clinical trial setting, the data showed that vinflunine is an efficacious and safe therapeutic option for second-line treatment of patients with metastatic urothelial carcinoma of the bladder after a platinum-containing regimen.


Assuntos
Neoplasias da Bexiga Urinária/tratamento farmacológico , Vimblastina/análogos & derivados , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cisplatino/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estudos Retrospectivos , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/patologia , Vimblastina/efeitos adversos , Vimblastina/uso terapêutico
8.
Onco Targets Ther ; 12: 1621-1627, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30881017

RESUMO

OBJECTIVE: Metastatic breast cancer (MBC) is an incurable disease; the treatment of this disease prolongs survival, improving the quality of life (QoL) with a balance between efficacy and toxicity of the treatment. In recent years, treatment with nab-paclitaxel has improved the already known antitumor activity of conventional paclitaxel, in terms of increased efficacy and better tolerability. The aim of this study was to evaluate nab-paclitaxel in Italian patients with MBC. METHODS: We conducted a retrospective analysis of 90 patients with histologically confirmed diagnosis of MBC. To evaluate the efficacy of nab-paclitaxel, overall survival (OS), progression-free survival (PFS), and overall response rate were the primary endpoints, whereas carbohydrate antigen 15.3 (Ca15.3) reduction, QoL, and tolerability were secondary endpoints. RESULTS: The median OS was 10.4 months, the median PFS was 6.8 months. A considerable difference Ca15.3 before and after treatment was observed. Descriptive and regression analyses were done to examine the associations between Ca15.3 response and OS, demonstrating good correlation, revealing that Ca15.3 reduction is an important predictor of OS. CONCLUSION: Nab-paclitaxel is an effective and well-tolerated treatment of patients affected by MBC. The drug showed an improved tolerability profile. With all the limitations of the observational nature of our results, nab-paclitaxel has proven to be an effective and safe therapeutic option in patients with MBC.

9.
Onco Targets Ther ; 11: 3059-3063, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29872317

RESUMO

BACKGROUND: In many clinical trials designed to assess the efficacy of anticancer treatments, overall survival (OS) is often used as a primary endpoint despite its several points of weakness. METHODS: This study evaluated the role of progression-free survival (PFS) in the first three lines of treatment as a potential surrogate endpoint of OS in patients with metastatic colorectal cancer (MCRC). One hundred and twenty patients with MCRC were enrolled in this study. The median PFS of the first-, second-, and third-lines of treatment and the OS were evaluated. The correlation between the time to progression and the OS was analyzed. The median PFS of the three lines of treatment were 8.5, 5, and 3 months, respectively. RESULTS: The median OS was 32.4 months. A modest correlation was found between the PFS to the first-line treatment with Folfox-avastin and OS. Similar data were obtained with the second-line treatment. However, no correlation was found between the PFS and OS during the third-line treatment. The regression analysis revealed that PFS is predictive of OS. CONCLUSION: In brief, the PFS of the first- and second-lines of treatment could be a good candidate as a surrogate endpoint of OS in patients with MCRC.

10.
Drug Des Devel Ther ; 12: 1769-1775, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29950811

RESUMO

PURPOSE: Pancreatic carcinoma is the neoplasia with the major mortality, and main standard treatments in this cancer increase survival but do not lead to complete recovery of the patient. The aim of this study was to evaluate the efficacy of Abraxane® (nab-paclitaxel) in Italian patients with metastatic pancreatic cancer (MPC). PATIENTS AND METHODS: We conducted a retrospective analysis of 80 patients. Overall survival (OS) was the primary end point for evaluating the efficacy of nab-paclitaxel in combination with gemcitabine treatment, while carbohydrate antigen 19-9 (CA 19-9) reduction, safety, progression-free survival (PFS), overall response rate and reduction in pain were secondary end points. RESULTS: The median OS was 8 months, and the median PFS was 5 months. A considerable difference in CA 19-9 before and after treatment was observed. Descriptive and correlation analyses were done to examine the relationship between CA 19-9 response and OS. Linear regression analysis between OS and CA 19-9 response revealed that CA 19-9 is an important predictor of OS, showing a positive correlation. CONCLUSION: Nab-paclitaxel is a well-tolerated and effective treatment for patients affected by MPC. The drug showed an improved tolerability profile, significant pain relief and an increase in survival rate.


Assuntos
Adenocarcinoma/tratamento farmacológico , Paclitaxel Ligado a Albumina/uso terapêutico , Albuminas/uso terapêutico , Antineoplásicos/uso terapêutico , Paclitaxel/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Adenocarcinoma/sangue , Adenocarcinoma/mortalidade , Adenocarcinoma/secundário , Idoso , Paclitaxel Ligado a Albumina/efeitos adversos , Albuminas/efeitos adversos , Antineoplásicos/efeitos adversos , Antígeno CA-19-9/sangue , Intervalo Livre de Doença , Feminino , Humanos , Itália , Estimativa de Kaplan-Meier , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Paclitaxel/efeitos adversos , Dor/prevenção & controle , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
11.
Oncology ; 94(3): 161-166, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29241166

RESUMO

BACKGROUND/AIM: Prostate cancer frequently causes bone metastases and skeletal events that impair quality of life (QoL) and survival. The alpha emitter radium-223 is a new drug that improves treatment in men with castration-resistant prostate cancer (CRPC) and bone metastases. Our aim was to evaluate the effectiveness of radium-223. SUBJECTS AND METHODS: In this retrospective study we enrolled 48 subjects. Pain reduction, alkaline phosphatase (ALP), time to first symptomatic skeletal event, and QoL were the variables we evaluated. RESULTS: Radium-223 was well tolerated, with a manageable toxicity profile and a modest objective response rate. A considerable difference in serum ALP levels before and after treatment was observed, with a significant correlation between pain relief and QoL, which showed a value of R2 to 0.44 with a slope of 1.50 (p = 0.0021). CONCLUSIONS: Radium-223 showed a clinical benefit, with a reduction in pain symptoms in 58% of patients. Radium-223 was shown to be an effective and well-tolerated therapeutic option in patients with metastatic CRPC progressing after docetaxel plus prednisone treatment.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/secundário , Neoplasias de Próstata Resistentes à Castração/patologia , Radioisótopos/uso terapêutico , Rádio (Elemento)/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Docetaxel , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Prednisona/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Qualidade de Vida , Estudos Retrospectivos , Taxoides/uso terapêutico
12.
Oncology ; 93(6): 354-358, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28873372

RESUMO

BACKGROUND/AIM: A clinical trial demonstrated that treatment with oral multikinase regorafenib improved overall survival (OS), progression-free survival (PFS), and disease control [García-Alfonso et al.: J Clin Transl Oncol 2016;18:1072-1081; Bertocchi et al.: J Chemother 2017;29:102-105]. In this study, we aimed to evaluate its effectiveness in Italian patients with hormone-refractory metastatic castration-resistant prostate cancer (mCRPC) progressing after chemotherapy with docetaxel plus prednisone. MATERIALS AND METHODS: 60 patients were enrolled. OS has been assessed as the primary endpoint while PFS, quality of life, safety, and response rate represented secondary endpoints. RESULTS: A modest tolerability was observed in our group showing a manageable toxicity profile and a modest objective response rate. It was associated with stable disease. A significant correlation between quality of life and OS was also noticed. CONCLUSIONS: Regorafenib has been proven to be an effective and well-tolerated therapeutic option in patients with mCRPC progressing after docetaxel plus prednisone treatment.


Assuntos
Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Compostos de Fenilureia/efeitos adversos , Compostos de Fenilureia/uso terapêutico , Piridinas/efeitos adversos , Piridinas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Intervalo Livre de Doença , Docetaxel , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Qualidade de Vida , Estudos Retrospectivos , Taxoides/administração & dosagem , Resultado do Tratamento
13.
Anticancer Drugs ; 28(9): 1047-1052, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28857768

RESUMO

The aim of this study was to evaluate abiraterone's efficacy in Italian patients affected with metastatic prostate cancer progressing after treatment with docetaxel. We conducted a retrospective analysis of 60 patients. Prostate-specific antigen (PSA) reduction in serum was the primary endpoint for evaluating the efficacy of abiraterone in combination with prednisone treatment, whereas reduced pain, safety, progression-free survival, response rate, and overall survival (OS) were secondary endpoints. A significant correlation was noticed between PSA response and OS. Further, the Index Bravais-Pearson (r) correlation allowed us to observe a significant negative interdependence between PSA response and reduction in pain of 0.57 (95% confidence interval: -0.30 to 0.80) (P=0.005). Meanwhile, regression analysis revealed that PSA levels are predictive of OS. There was a positive correlation with OS, which showed a value of R to 0.50 with a slope of 1.44 (P=0.0021). Abiraterone is a well-tolerated and effective treatment modality for patients affected with metastatic castration-resistant prostate cancer. The drug has a better tolerability profile, gives significant pain relief, and increases the survival rate.


Assuntos
Androstenos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Androstenos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Docetaxel , Humanos , Calicreínas/sangue , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Antígeno Prostático Específico/sangue , Neoplasias de Próstata Resistentes à Castração/sangue , Neoplasias de Próstata Resistentes à Castração/patologia , Estudos Retrospectivos , Taxoides/uso terapêutico
14.
Anticancer Res ; 37(9): 5187-5192, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28870953

RESUMO

BACKGROUND/AIM: To evaluate the role of densitometric criterion using the Choi Criteria in the assessment of the response to antiangiogenic treatments of metastatic colorectal cancer (mCRC) compared to the RECIST criteria. PATIENTS AND METHODS: Fifty-four patients (mean age=50.6 years) affected by advanced colorectal cancer and with hepatic and possibly peritoneal and pulmonary metastases, that can be treated with bevacizumab, were prospectively evaluated by computerized tomography (CT) scan. Metastases were also evaluated by CT in one-dimensional form according to RECIST. RESULTS: Results show that in 58% of analyzed cases, stable disease according to RECIST coincided with stable disease according to the CHOI criteria, whereas in 42% of analyzed cases disease progression according to RECIST corresponded to stable disease or even partial response according to CHOI criteria. CONCLUSION: By using the densitometric criterion with CHOI criteria, the evaluation of the response to antiangiogenic treatment of mCRC is partially different compared to RECIST criteria.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Densitometria/métodos , Neoplasias Hepáticas/secundário , Neoplasias Colorretais/diagnóstico por imagem , Demografia , Feminino , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada Multidetectores , Resultado do Tratamento
15.
Nat Commun ; 8(1): 293, 2017 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-28819097

RESUMO

The brain cytoplasmic (BC1) RNA is a non-coding RNA (ncRNA) involved in neuronal translational control. Absence of BC1 is associated with altered glutamatergic transmission and maladaptive behavior. Here, we show that pyramidal neurons in the barrel cortex of BC1 knock out (KO) mice display larger excitatory postsynaptic currents and increased spontaneous activity in vivo. Furthermore, BC1 KO mice have enlarged spine heads and postsynaptic densities and increased synaptic levels of glutamate receptors and PSD-95. Of note, BC1 KO mice show aberrant structural plasticity in response to whisker deprivation, impaired texture novel object recognition and altered social behavior. Thus, our study highlights a role for BC1 RNA in experience-dependent plasticity and learning in the mammalian adult neocortex, and provides insight into the function of brain ncRNAs regulating synaptic transmission, plasticity and behavior, with potential relevance in the context of intellectual disabilities and psychiatric disorders.Brain cytoplasmic (BC1) RNA is a non-coding RNA that has been implicated in translational regulation, seizure, and anxiety. Here, the authors show that in the cortex, BC1 RNA is required for sensory deprivation-induced structural plasticity of dendritic spines, as well as for correct sensory learning and social behaviors.


Assuntos
Aprendizagem/fisiologia , Neocórtex/fisiologia , Plasticidade Neuronal/fisiologia , Células Piramidais/fisiologia , RNA Citoplasmático Pequeno/genética , Animais , Sequência de Bases , Células Cultivadas , Espinhas Dendríticas/metabolismo , Espinhas Dendríticas/fisiologia , Potenciais Pós-Sinápticos Excitadores/genética , Potenciais Pós-Sinápticos Excitadores/fisiologia , Hibridização in Situ Fluorescente , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Microscopia Eletrônica , Neocórtex/citologia , Neocórtex/metabolismo , Plasticidade Neuronal/genética , Células Piramidais/metabolismo , Células Piramidais/ultraestrutura , Privação Sensorial/fisiologia , Homologia de Sequência do Ácido Nucleico , Comportamento Social , Transmissão Sináptica/genética , Transmissão Sináptica/fisiologia , Vibrissas/metabolismo , Vibrissas/fisiologia
16.
Anticancer Res ; 37(3): 1475-1480, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28314320

RESUMO

BACKGROUND/AIM: To evaluate the effectiveness of enzalutamide in Italian patients with hormone-refractory metastatic castration-resistant prostate cancer, progressing after chemotherapy with docetaxel plus prednisone. PATIENTS AND METHODS: A total of 60 patients were enrolled. Reduction in serum prostate-specific antigen (PSA) was assessed as the primary endpoint, while reduction in pain, safety, progression-free survival and overall survival represented secondary endpoints. RESULTS: Enzalutamide was well tolerated, with a manageable toxicity profile and a modest objective response rate. A considerable difference in serum levels of PSA before and after treatment was observed. A significant correlation between PSA response and overall survival was also noted. The regression analysis revealed PSA level to be predictive of overall survival. CONCLUSION: Enzalutamide was shown to be an effective and well-tolerated therapeutic option in patients with metastatic castration-resistant prostate cancer progressing after docetaxel plus prednisone treatment.


Assuntos
Adenocarcinoma/tratamento farmacológico , Feniltioidantoína/análogos & derivados , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias da Próstata/tratamento farmacológico , Adenocarcinoma/mortalidade , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Benzamidas , Docetaxel , Resistencia a Medicamentos Antineoplásicos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Nitrilas , Feniltioidantoína/uso terapêutico , Prednisona/administração & dosagem , Estudos Prospectivos , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/mortalidade , Neoplasias de Próstata Resistentes à Castração/mortalidade , Análise de Regressão , Taxoides/administração & dosagem , Resultado do Tratamento
17.
Oncology ; 92(6): 325-334, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28259891

RESUMO

OBJECTIVE: This study aimed to understand how psychological variables and attachment styles can contribute to improve effective and functional adjustment to the disease and promote better psychological well-being. METHODS: A total of 176 participants (88 couples) took part in this research. One member of each couple attended surgery centers at the Oncology Department of the University Hospital of Palermo. Each participant had filled in 5 questionnaires assessing the variables couple relationships, quality of life, anxiety, depression, and psychosocial adjustment to illness. RESULTS: Significant correlations were found among the observed variables. Levels of anxiety and the attachment styles of couples influence adjustment to tumor disease and negatively affect the quality of conjugal relationships. Moreover, the results highlighted the correlation between levels of anxiety and depression in patients and in their respective partners. Finally, we found a correlation between the level of psychological distress of the patient and the level of marital satisfaction perceived by the partner: the latter is lower in couples where the oncological patient has high levels of distress. CONCLUSIONS: The results suggest that psychological variables and attachment styles of cancer patients and their partners may be important factors affecting adjustment in multiple domains.


Assuntos
Adaptação Psicológica , Neoplasias/psicologia , Apego ao Objeto , Cônjuges/psicologia , Ansiedade/complicações , Estudos Transversais , Depressão/complicações , Progressão da Doença , Feminino , Humanos , Itália/epidemiologia , Masculino , Adesão à Medicação/psicologia , Pessoa de Meia-Idade , Neoplasias/complicações , Neoplasias/terapia , Qualidade de Vida , Estresse Psicológico/complicações , Inquéritos e Questionários , Assistência Terminal/psicologia
18.
Oncology ; 92(2): 94-100, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-27960186

RESUMO

PURPOSE: The present study aims to evaluate the efficacy of cabazitaxel in combination with prednisone treatment in Italian patients affected by hormone-refractory metastatic castration-resistant prostate cancer (mCRPC) previously treated with docetaxel plus prednisone. METHODS: Thirty patients with mCRPC were enrolled between June 2013 and January 2016 (the last follow-up was in January 2016). Cabazitaxel was used according to the summary of product characteristics and administered at a dose of 25 mg/m2 every 3 weeks plus oral prednisone at a dose of 5-mg tablets twice a day continuously. The reduction in serum prostate-specific antigen (PSA) was the primary endpoint while reducing pain, safety, progression-free survival, response rate and overall survival (OS) were secondary endpoints. RESULTS: Cabazitaxel was well tolerated, showing a manageable toxicity profile, associated with a modest objective response rate and a good reduction in PSA levels. Only 12 patients (40%) had a partial response, 10 patients (33%) showed stabilization of disease and 8 (27%) experienced disease progression. The median OS was 14.8 months (95% CI: 11.6-19.8). The linear regression analysis revealed that PSA response was an important predictor of OS, showing a positive correlation with OS (ß = 0.377, p < 0.01). CONCLUSIONS: Three-week treatment with cabazitaxel was found to be valid and was a well-tolerated treatment option for patients with mCRPC after a first-line docetaxel treatment.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Taxoides/uso terapêutico , Idoso , Progressão da Doença , Docetaxel , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Neoplasias de Próstata Resistentes à Castração/patologia
19.
Expert Opin Ther Pat ; 26(12): 1417-1429, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27603098

RESUMO

INTRODUCTION: Restoration of the p53 tumor suppressor function is an attractive anticancer strategy. Despite the development of several therapeutics targeting the two main p53 negative regulators, MDM2 and MDM4, no one has yet reached clinical application. In the past, several efforts have been employed to develop more specific and efficient compounds that can improve and/or overcome some of the features related to small molecule compounds (SMC). Peptides and peptidomimetics are emerging as attractive molecules given their increased selectivity, reduced toxicity and reduced tendency to develop tumor-resistance compared to SMC. Area covered: This article reviews publications and patents (publicly available up to April 2016) for peptides and derivatives aimed to reactivate the oncosuppressive function of p53, with a particular focus on inhibitors of MDM2/MDM4. Emphasis is placed on the efficacy of these compounds compared to the p53-reactivating small molecules developed so far. Expert opinion: A number of promising peptides for p53 reactivation in cancer therapy have been developed. These compounds appear to possess improved features compared to SMC, especially for their ability to simultaneously target the MDM2/MDM4 inhibitors, and their increased specificity.


Assuntos
Antineoplásicos/farmacologia , Peptídeos/uso terapêutico , Peptidomiméticos/uso terapêutico , Animais , Antineoplásicos/uso terapêutico , Proteínas de Ciclo Celular , Desenho de Fármacos , Humanos , Neoplasias/tratamento farmacológico , Proteínas Nucleares/antagonistas & inibidores , Patentes como Assunto , Peptídeos/farmacologia , Peptidomiméticos/farmacologia , Proteínas Proto-Oncogênicas/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-mdm2/antagonistas & inibidores , Proteína Supressora de Tumor p53/metabolismo
20.
Radiol Med ; 121(10): 763-8, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27334010

RESUMO

OBJECTIVE: Every patient could feel anxious when he waits in a radiological department to undergo diagnostic exams. The aim of our study is to evaluate the impact of the radiological exams on patient anxiety. MATERIALS AND METHODS: We evaluated 343 patients (mean age 54.83 years) who underwent different types of diagnostic exams in the Department of Diagnostic Imaging at our Hospital from April 2013 to August 2014. We administered to patients the State and Trait Anxiety Inventory Test, which detected with high sensitivity both state anxiety and trait anxiety. A team of clinical psychologists and radiologists evaluated the scores obtained. RESULTS: 83 out of 343 patients were excluded because refused to file the questionnaire. 31 % of the patients were submitted to MR, 18 % to breast imaging, 10 % to X-ray, 22 % Computer Tomography and 19 % to ultrasound, as previously described. 41 % of patients were submitted to the examination because of an oncologic disease, while 59 % because of non-oncological disease. Therefore, it was found that high levels of anxiety were present in most (about 91 %) of the patients and the scores varied according to the imaging examination and to the examination's reason: anxiety level was higher in non-oncological patients (54 %) and in patients waiting to undergo to MRI exams (29 %). CONCLUSION: Our data suggest that the diagnostic exams are stressful events for the patient, also in non-oncological patients. So, it is important to adequate the radiological staff to receive the patient, to inform him and perform exams with emotive involvement with a targeted education. Also, further studies are needed to evaluate the anxiety level and the quality of the images, because the anxiety can result in a somatic disorder with hyperactivity of the autonomic nervous system which may affect the patient's physical examination, causing problems in the evaluation of radiological images making to non-cooperative patient. MRI imaging is the examination that more of all led to an anxious state of patients but the main stressor is not related to the type of diagnostic examination, but to the uncertainty of the diagnosis, therapy and prognosis.


Assuntos
Ansiedade/etiologia , Diagnóstico por Imagem/psicologia , Neoplasias/diagnóstico por imagem , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Qualidade de Vida , Apoio Social , Inquéritos e Questionários
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