Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 81
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Anticancer Res ; 40(1): 435-441, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31892598

RESUMO

AIM: The purpose of the Imadje study was to confirm the efficacy and safety of imatinib, following resection of kit-positive gastrointestinal stromal tumour (GIST), in the adjuvant setting in the Greek population. PATIENTS AND METHODS: A total of 34 adult patients already receiving imatinib were enrolled. Recurrence-free (RFS) and overall survival, as well as time to treatment failure and safety were assessed. RESULTS: Overall survival could not be estimated in the present study, as no death occurred. Overall, 91.2% of patients were recurrence-free at 36 months, while the median time to treatment failure was 35 months. No new or unexpected safety findings were observed. Mutation analysis in 14 patients showed that the most frequent mutations were located in KIT exon 11 (64.3%) and exon 9 (28.6%). Univariate analysis showed that only surgical resection with a margin classification of R0 was associated with better RFS. CONCLUSION: Adjuvant treatment with imatinib for 3 years in patients with intermediate to high risk of recurrence was proven to prolong RFS, while being well-tolerated and not exhibiting a negative impact on patient compliance with therapy.


Assuntos
Tumores do Estroma Gastrointestinal/tratamento farmacológico , Mesilato de Imatinib/uso terapêutico , Recidiva Local de Neoplasia/patologia , Análise Mutacional de DNA , Intervalo Livre de Doença , Feminino , Grécia , Humanos , Mesilato de Imatinib/efeitos adversos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
2.
Anticancer Res ; 40(1): 305-313, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31892581

RESUMO

BACKGROUND: Cancer-associated thrombosis (CAT), the second leading cause of death in patients with cancer can be treated with low molecular weight heparin (LMWH) according to guidelines. PATIENTS AND METHODS: A multicenter prospective observational study was carried out to record anti-thrombotic treatment practice, assess thrombosis recurrence and bleeding, and identify potential risk factors. Adult patients from 18 Oncology Departments throughout Greece were followed-up for 12 months. RESULTS: A total of 120 patients with CAT receiving anticoagulant treatment were enrolled (35% incidental); 85% were treated for more than 6 months, 95.8% were treated with tinzaparin and smaller percentages with other agents. Thrombosis recurred in three patients and there was minor bleeding in four patients. Bleeding was associated with high body mass index (>35 kg/m2), trauma history, renal insufficiency and bevacizumab use. CONCLUSION: Incidental thrombosis contributes significantly to CAT burden. Long-term use of LMWH seems to be effective and safe. Several risk factors associated with bleeding should be considered during anti-coagulation therapy planning.


Assuntos
Neoplasias/complicações , Trombose/etiologia , Trombose/terapia , Feminino , Hemorragia/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Fatores de Risco
3.
Microorganisms ; 7(9)2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31438593

RESUMO

Bacterial infections are frequent complications in cancer patients. Among them, those caused by multidrug-resistant (MDR) bacteria increase morbidity and mortality mainly because of limited therapeutic options. Current knowledge regarding MDR infections in patients with solid tumors is limited. We assessed the epidemiology and risk factors of increased mortality in these patients. In this retrospective five-year single cohort observational study, we included all oncological patients with MDR infections. Cancer-related parameters, comorbidities, prior use of antibiotics, previous surgical interventions and hospitalization, as well as the use of invasive procedures were investigated as potential risk factors causing adverse outcomes. Seventy-three patients with MDR infection were included: 37% with carbapenem-resistant Klebsiella pneumoniae, 24% with oxacillin-resistant Staphylococcus aureus (MRSA) and 21% with carbapenem-resistant Acinetobacter baumanni. Previous colonization with MDR bacteria was detected in 14% patients, while 20% of the patients presented MDR colonization or infection at ward admission. Mortality during the infection episode was 32%. Duration of hospitalization and CRP were statistically significant risk factors of mortality, whereas administration of guided antibiotics was a protective factor. Knowledge of local epidemiology of MDR bacteria can help physicians promptly identify cancer patients at risk of MDR infections and initiate timely effective empirical antibiotic treatment that can eventually improve the overall therapeutic management.

4.
Int J Oncol ; 54(2): 537-549, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30483772

RESUMO

Caveolin­1 (Cav­1) expression has been shown to be associated with tumor growth and resistance to chemotherapy in pancreatic cancer. The primary aim of this study was to explore the significance of Cav­1 expression in pancreatic cancer cells as compared to fibroblasts in relation to cancer cell proliferation and chemoresistance, both in vitro and in vivo, in an immunodeficient mouse model. We also aimed to evaluate the immunohistochemical expression of Cav­1 in the epithelial and stromal component of pancreatic cancer tissue specimens. The immunohistochemical staining of poorly differentiated tissue sections revealed a strong and weak Cav­1 expression in the epithelial tumor cells and stromal fibroblasts, respectively. Conversely, the well­differentiated areas were characterized by a weak epithelial Cav­1 expression. Cav­1 downregulation in cancer cells resulted in an increased proliferation in vitro; however, it had no effect on chemoresistance and growth gain in vivo. By contrast, the decreased expression of Cav­1 in fibroblasts resulted in a growth advantage and the chemoresistance of cancer cells when they were co­injected into immunodeficient mice to develop mixed fibroblast/cancer cell xenografts. On the whole, the findings of this study suggest that the downregulation of Cav­1 in fibroblasts is associated with an increased tumor proliferation rate in vivo and chemoresistance. Further studies are warranted to explore whether the targeting of Cav­1 in the stroma may represent a novel therapeutic approach in pancreatic cancer.


Assuntos
Caveolina 1/genética , Proliferação de Células/genética , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias Pancreáticas/tratamento farmacológico , Animais , Caveolina 1/antagonistas & inibidores , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Fibroblastos/metabolismo , Fibroblastos/patologia , Regulação Neoplásica da Expressão Gênica , Inativação Gênica , Humanos , Camundongos , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
5.
Pathol Oncol Res ; 25(1): 225-231, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29081034

RESUMO

To investigate the potential prognostic role of NFκB expression in primary high-grade non-muscle-invasive bladder cancer. Patients with primary high-grade non-muscle-invasive bladder cancer who received induction and maintenance BCG therapy were retrospectively included. Recurrence and progression were histologically proven. Intensity and extent of immunochemistry were assessed. The final evaluation of the NFκB staining was done by combining intensity and extent as ΄΄product΄΄ and expressing it as ΄΄low NFκΒ expression΄΄ or ΄΄high NFκB expression΄΄. Epidemiological, pathological, clinical parameters and NFκB expression were statistically analyzed for recurrence (REC), progression (PR), recurrence-free survival (RFS) and progression-free survival (PFS). NFκB is significantly associated with disease progression (p < 0,001 in univariate analysis and p = 0,001, Odds Ratio = 14,484, 95% Confidence Interval = 3187-65,821 in multivariate analysis), but not with recurrence. The median value of NFκB expression as ΄΄product΄΄ is significantly higher for the patients with progression in comparison to patients with recurrence only (p = 0,003) and patients without recurrence or progression (p = 0,001). Patients' age is significantly associated (p = 0,001 in univariate analysis and p = 0,003, Odds Ratio = 1273, 95% Confidence Interval = 1086-1492 in multivariate analysis) with disease recurrence. High NFκB expression in primary high-grade non-muscle-invasive bladder cancer, treated with postoperative intravesical BCG immunotherapy, could represent an unfavorable prognostic factor.


Assuntos
Biomarcadores Tumorais/metabolismo , NF-kappa B/metabolismo , Recidiva Local de Neoplasia/patologia , Neoplasias da Bexiga Urinária/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Feminino , Seguimentos , Humanos , Imunoterapia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Invasividade Neoplásica , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/metabolismo , Estudos Retrospectivos , Taxa de Sobrevida , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/metabolismo
6.
Urol Ann ; 10(4): 413-415, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30386097

RESUMO

Malignant transformation of teratoma develops in a small subset of testis cancer patients. Primitive neuroectodermal tumor represents a highly malignant component of testicular germ cell tumors. It is a rare clinical entity which is characterized by a high risk of disease progression and death. Surgical resection plus chemotherapy appears to be the therapy of choice.

7.
J Neurooncol ; 134(2): 443-451, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28687923

RESUMO

Small molecules, mainly tyrosine kinase inhibitors, are currently used in various malignancies. Lapatinib, a dual inhibitor of EGFR/HER2 tyrosine kinases, has demonstrated effectiveness in brain metastases from HER2-overexpressing breast cancer. It also appears to sensitize EGFR-expressing cell lines to radiation. To evaluate the efficacy of lapatinib in combination with whole brain radiotherapy (WBRT) in patients with brain metastases from non-small cell lung cancer (NSCLC) and breast cancer, as assessed by volumetric analysis by MRI. 81 patients were treated with WBRT (30 Gy in ten fractions) in combination with lapatinib 1250 mg once daily, followed by lapatinib 1500 mg once daily for a total 6 weeks. 21 patients had primary breast cancer and 60 patients NSCLC. Pre- and post-treatment MRI scans in a compact disk for central volumetric assessment were available for 43 patients. 27 patients (62.8%) achieved partial response, 15 patients (34.9%) had stable disease and only one patient (2.3%) had disease progression. Response was not associated to EGFR protein expression. All 81 patients were assessed for safety. The large majority of the adverse events were mild. Eight deaths occurred, four of which were considered related to the study drugs but there were also other contributing factors. Nine cases of serious infections were observed in eight patients, but they were also receiving dexamethasone. Lapatinib in combination with WBRT in patients with brain metastases from breast cancer and NSCLC is a feasible approach that can be further studied in larger clinical trials.


Assuntos
Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/terapia , Neoplasias da Mama/patologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Quimiorradioterapia , Neoplasias Pulmonares/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Encéfalo/diagnóstico por imagem , Encéfalo/efeitos dos fármacos , Encéfalo/efeitos da radiação , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias da Mama/terapia , Carcinoma Pulmonar de Células não Pequenas/terapia , Quimiorradioterapia/efeitos adversos , Progressão da Doença , Feminino , Seguimentos , Humanos , Lapatinib , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Quinazolinas/efeitos adversos , Quinazolinas/uso terapêutico , Resultado do Tratamento
8.
World J Urol ; 35(3): 411-419, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27395374

RESUMO

PURPOSE: To identify prognostic molecular profiles in patients with mRCC treated with sunitinib, we performed immunohistochemical analysis for VEGF and PI3K/Akt/mTOR pathway components. METHODS: The immunohistochemical expression of VEGF, p85α, p110γ, PTEN, p-Akt, p-mTOR, p-4E-BP1 and p-p70S6K was studied in 79 patients with mRCC who received first-line treatment with sunitinib. Expression was correlated with clinicopathological features and survival. RESULTS: VEGF was highly expressed (median H-Score 150), while positivity for the markers of the PI3K/Akt/mTOR pathway was: p85α 43/66 (65 %), p110γ41/60 (68 %), PTEN 32/64 (50 %), p-Akt57/63 (90 %), p-mTOR48/64 (75 %), p-4E-BP1 58/64 (90 %) and p-p70S6K 60/65 (92 %). No single immunohistochemical marker was found to have prognostic significance. Instead, the combination of increased p-mTOR and low VEGF expression was adversely correlated with overall survival (OS) (3.2 vs. 16.9 months, P = 0.001). CONCLUSION: Immunohistochemistry for VEGF and p-mTOR proteins may discriminate patients refractory to first-line sunitinib with poor prognosis. Prospective validation of our findings is needed.


Assuntos
Carcinoma de Células Renais/metabolismo , Neoplasias Renais/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/secundário , Classe Ib de Fosfatidilinositol 3-Quinase/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Indóis/uso terapêutico , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , PTEN Fosfo-Hidrolase/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Fosfoproteínas/metabolismo , Prognóstico , Pirróis/uso terapêutico , Estudos Retrospectivos , Proteínas Quinases S6 Ribossômicas 70-kDa/metabolismo , Sunitinibe , Taxa de Sobrevida
9.
J Cancer Res Clin Oncol ; 142(10): 2141-58, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27530445

RESUMO

PURPOSE: Bortezomib (BTZ) is used for the treatment of multiple myeloma (MM). However, a significant proportion of patients may be refractory to the drug. This study aimed to investigate whether the endothelin (ET-1) axis may act as an escape mechanism to treatment with bortezomib in MM cells. METHODS: NCI-H929 and RPMI-8226 (human MM cell lines) were cultured with or without ET-1, BTZ, and inhibitors of the endothelin receptors. ET-1 levels were determined by ELISA, while the protein levels of its receptors and of the PI3K and MAPK pathways' components by western blot. Effects of ET-1 on cell proliferation were studied by MTT and on the ubiquitin proteasome pathway by assessing the chymotryptic activity of the 20S proteasome in cell lysates. RESULTS: Endothelin receptors A and B (ETAR and ETBR, respectively) were found to be expressed in both cell lines, with the RPMI-8226 cells that are considered resistant to BTZ, expressing higher levels of ETBR and in addition secreting ET-1. Treatment of the NCI-H929 cells with ET-1 increased proliferation, while co-incubation of these cells with ET-1 and BTZ decreased BTZ efficacy with concomitant upregulation of 20S proteasomal activity. Si-RNA silencing or chemical blockade of ETBR abrogated the protective effects of ET-1. Finally, data suggest that the predominant signaling pathway involved in ET-1/ETBR-induced BTZ resistance in MM cells may be the MAPK pathway. CONCLUSION: Our data suggest a possible role of the ET-1/ETBR axis in regulating the sensitivity of MM cells to BTZ. Thus, combining bortezomib with strategies to target the ET-1 axis could prove to be a novel promising therapeutic approach in MM.


Assuntos
Bortezomib/farmacologia , Endotelina-1/metabolismo , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/metabolismo , Receptor de Endotelina B/metabolismo , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos , Antagonistas do Receptor de Endotelina A/farmacologia , Endotelina-1/farmacologia , Humanos , Sistema de Sinalização das MAP Quinases , Mieloma Múltiplo/enzimologia , Peptídeos Cíclicos/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , Receptor de Endotelina A/metabolismo , Ubiquitina/metabolismo
10.
J Hepatol ; 65(6): 1140-1147, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27469901

RESUMO

BACKGROUND & AIMS: GIDEON (Global Investigation of therapeutic DEcisions in hepatocellular carcinoma and Of its treatment with sorafeNib) is a prospective, observational registry study evaluating the safety of sorafenib and treatment practices in hepatocellular carcinoma patients. This large global database allowed for assessment of the use and tolerability of sorafenib in patients with liver dysfunction. METHODS: Baseline characteristics and medical/treatment history were collected in patients for whom a decision to treat with sorafenib had been made. Adverse event, dosing, and outcomes data were collected during follow-up. RESULTS: In the overall safety population (n=3202), 1968 patients (61%) had Child-Pugh A status and 666 (21%) had Child-Pugh B. The majority of Child-Pugh A (72%) and Child-Pugh B (70%) patients received an initial sorafenib dose of 800mg, consistent with the label, and dose reduction rates were 40% and 29%, respectively. The type and incidence of adverse events were generally consistent across Child-Pugh subgroups. The incidence of drug-related adverse events leading to discontinuation was similar between Child-Pugh A and Child-Pugh B patients (17% and 21%). In the intent-to-treat population (n=3213), median overall survival (months [95% confidence interval]) was longer in Child-Pugh A patients (13.6 [12.8-14.7]) compared with Child-Pugh B patients (5.2 [4.6-6.3]). CONCLUSIONS: In clinical practice, the safety profile of sorafenib appeared to be consistent across Child-Pugh A and Child-Pugh B patients. Findings suggest sorafenib may be safely used in some Child-Pugh B patients and indicate the importance of careful patient evaluation when making treatment decisions. LAY SUMMARY: The GIDEON (Global Investigation of therapeutic DEcisions in hepatocellular carcinoma and Of its treatment with sorafeNib) study is a large prospective registry of patients with liver cancer who were treated with sorafenib. The aims were to evaluate the safety and tolerability of sorafenib among those in which the liver was not functioning properly. The study showed that the safety profile of sorafenib was consistent across patients with preserved liver function and those in which the liver was not functioning properly, and therefore, suggesting that sorafenib may be a valid treatment for some patients with liver impairment.


Assuntos
Niacinamida/análogos & derivados , Compostos de Fenilureia/uso terapêutico , Antineoplásicos , Carcinoma Hepatocelular , Criança , Humanos , Neoplasias Hepáticas , Niacinamida/uso terapêutico , Estudos Prospectivos , Sistema de Registros , Sorafenibe
11.
Breast Cancer Res Treat ; 158(2): 307-21, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27369359

RESUMO

The purpose of this study is to investigate whether the outcome of breast cancer (BC) patients treated with adjuvant chemotherapy is affected by co-mutated TP53 and PIK3CA according to stromal tumor-infiltrating lymphocytes (TILs). Paraffin tumors of all clinical subtypes from 1661 patients with operable breast cancer who were treated within 4 adjuvant trials with anthracycline-taxanes chemotherapy were informative for TP53 and PIK3CA mutation status (semiconductor sequencing genotyping) and for stromal TILs density. Disease-free survival (DFS) was examined. TP53 mutations were associated with higher (p < 0.001) and PIK3CA with lower (p = 0.004) TILs in an ER /PgR-specific manner (p < 0.001). Mutations did not affect the favorable DFS of patients with lymphocyte-predominant (LP) BC. Within non-LPBC, PIK3CA-only mutations conferred best, while TP53-PIK3CA co-mutations (6 % of all tumors) conferred worst DFS (HR 0.59; 95 % CI 0.44-0.79; p = 0.001 for PIK3CA-only). TP53-only mutations were unfavorable in patients with lower TILs, while patients with lower TILs performed worse if their tumors carried TP53-only mutations (interaction p = 0.046). Multivariate analysis revealed favorable PIK3CA-only mutations in non-LPBC (HR 0.64; 95 % CI 0.47-0.88; p = 0.007), and unfavorable TP53 mutations in ER/PgRpos/HER2neg (HR 1.55; 95 % CI 1.07-2.24; p = 0.021). Mutations did not interact with TILs in non-LP triple-negative and HER2-positive patients. TP53 and PIK3CA mutations appear to have diverse effects on the outcome of early BC patients, according to whether these genes are co-mutated or not, and for TP53 according to TILs density and ER/PgR-status. These findings need to be considered when evaluating the effect of these two most frequently mutated genes in the context of large clinical trials.


Assuntos
Antraciclinas/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Classe I de Fosfatidilinositol 3-Quinases/genética , Linfócitos do Interstício Tumoral/patologia , Mutação , Taxoides/uso terapêutico , Proteína Supressora de Tumor p53/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Antraciclinas/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/genética , Quimioterapia Adjuvante , Intervalo Livre de Doença , Feminino , Humanos , Linfócitos do Interstício Tumoral/efeitos dos fármacos , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos , Análise de Sobrevida , Taxoides/farmacologia , Adulto Jovem
12.
Oncotarget ; 7(22): 32731-53, 2016 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-27129168

RESUMO

BACKGROUND: We investigated the impact of PIK3CA and TP53 mutations and p53 protein status on the outcome of patients who had been treated with adjuvant anthracycline-taxane chemotherapy within clinical trials in the pre- and post-trastuzumab era. RESULTS: TP53 and PIK3CA mutations were found in 380 (21.5%) and 458 (25.9%) cases, respectively, including 104 (5.9%) co-mutated tumors; p53 immunopositivity was observed in 848 tumors (53.5%). TP53 mutations (p < 0.001) and p53 protein positivity (p = 0.001) were more frequent in HER2-positive and triple negative (TNBC) tumors, while PIK3CA mutations were more frequent in Luminal A/B tumors (p < 0.001). TP53 mutation status and p53 protein expression but not PIK3CA mutation status interacted with trastuzumab treatment for disease-free survival; patients with tumors bearing TP53 mutations or immunopositive for p53 protein fared better when treated with trastuzumab, while among patients treated with trastuzumab those with the above characteristics fared best (interaction p = 0.017 for mutations; p = 0.015 for IHC). Upon multivariate analysis the above interactions remained significant in HER2-positive patients; in the entire cohort, TP53 mutations were unfavorable in patients with Luminal A/B (p = 0.003) and TNBC (p = 0.025); p53 immunopositivity was strongly favorable in patients treated with trastuzumab (p = 0.009). MATERIALS AND METHODS: TP53 and PIK3CA mutation status was examined in 1766 paraffin tumor DNA samples with informative semiconductor sequencing results. Among these, 1585 cases were also informative for p53 protein status assessed by immunohistochemistry (IHC; 10% positivity cut-off). CONCLUSIONS: TP53 mutations confer unfavorable prognosis in patients with Luminal A/B and TNBC tumors, while p53 immunopositivity may predict for trastuzumab benefit in the adjuvant setting.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Biomarcadores Tumorais/genética , Análise Mutacional de DNA , Imuno-Histoquímica , Mutação , Trastuzumab/uso terapêutico , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Proteína Supressora de Tumor p53/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Quimioterapia Adjuvante , Distribuição de Qui-Quadrado , Classe I de Fosfatidilinositol 3-Quinases/análise , Classe I de Fosfatidilinositol 3-Quinases/genética , Ensaios Clínicos como Assunto , Progressão da Doença , Intervalo Livre de Doença , Feminino , Predisposição Genética para Doença , Grécia , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Análise Multivariada , Seleção de Pacientes , Fenótipo , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Neoplasias de Mama Triplo Negativas/química , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia , Proteína Supressora de Tumor p53/análise , Adulto Jovem
13.
Clin Colorectal Cancer ; 15(2): 116-27, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-27032873

RESUMO

Despite significant advances in the management of colorectal cancer (CRC) the identification of new prognostic biomarkers continues to be a challenge. Since its initial discovery, the role of the Hedgehog (Hh) signaling pathway in carcinogenesis has been extensively studied. We herein review and comment on the prognostic significance of the Hh signaling pathway in CRC. The differential expression of Hh pathway components between malignant and nonmalignant conditions as well as correlation of Hh activation markers with various clinicopathological parameters and the effect on disease-free survival, overall survival, and disease recurrence in patients with CRC is summarized and discussed. According to the studies reviewed herein the activation of the Hh pathway seems to be correlated with adverse clinicopathological features and worse survival. However, to date study results show significant variability with regard to the effect on outcomes. Such results need to be interpreted carefully and emphasize the need for further well designed studies to characterize the actual influence of the Hh pathway in CRC prognosis.


Assuntos
Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Proteínas Hedgehog/metabolismo , Transdução de Sinais/fisiologia , Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/mortalidade , Humanos , Prognóstico
14.
Liver Int ; 36(8): 1196-205, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-26901163

RESUMO

BACKGROUND & AIMS: Treatment approaches for hepatocellular carcinoma (HCC) vary across countries, but these differences and their potential impact on outcomes have not been comprehensively assessed. Data from the multinational GIDEON (Global Investigation of therapeutic DEcisions in HCC and Of its treatment with sorafeNib) registry evaluated differences in patient characteristics, practice patterns and outcomes in HCC across geographical regions in patients who received sorafenib. METHODS: GIDEON is a non-randomised, observational registry study conducted in 39 countries across five global regions. HCC patients in whom a decision to treat with sorafenib was made in clinical practice and according to local practices were included. RESULTS: 3202 patients were evaluable for safety analysis: Asia-Pacific (n = 928), Japan (n = 508), Europe (n = 1113), USA (n = 563) and Latin America (n = 90). Patients in Japan had earlier-stage disease at initial diagnosis compared with patients in other regions (Barcelona Clinic Liver Cancer stage A; 43.7% vs 9.1-24.3%). Use of locoregional therapies before sorafenib, including transarterial chemoembolisation, was more common in Japan (84.4%) and Asia-Pacific (67.2%) compared with the USA (49.4%) and Europe (43.5%). Treatment patterns with respect to sorafenib also differed, with a shorter duration of treatment reported in the USA and Asia-Pacific. Time from initial diagnosis to death was longer in Japan compared with other regions (median, 79.6 months vs 14.8-25.0 months). CONCLUSIONS: Data from GIDEON highlight regional variations in the management of HCC and patient outcomes. Greater standardisation of management may help optimise outcomes for HCC patients.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/terapia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/terapia , Niacinamida/análogos & derivados , Compostos de Fenilureia/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Quimioembolização Terapêutica , Gerenciamento Clínico , Detecção Precoce de Câncer , Europa (Continente) , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Niacinamida/efeitos adversos , Niacinamida/uso terapêutico , Ilhas do Pacífico , Compostos de Fenilureia/efeitos adversos , Sistema de Registros , Sorafenibe , Adulto Jovem
15.
Radiology ; 279(2): 630-40, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26744927

RESUMO

PURPOSE: To evaluate transarterial chemoembolization (TACE) use prior to and concomitantly with sorafenib in patients with unresectable hepatocellular carcinoma (HCC) across different global regions. MATERIALS AND METHODS: GIDEON is an observational registry study of more than 3000 HCC patients. Patients with histologically, cytologically, or radiographically diagnosed HCC, and for whom a decision had been made to treat with sorafenib, were eligible. Patients were enrolled into the registry from 39 countries beginning in January 2009, with the last patient follow-up in April 2012. Detailed data on treatment history, treatment patterns, adverse events, and outcomes were collected. All treatment decisions were at the discretion of the treating physicians. Documented approval from local ethics committees was obtained, and all patients provided signed informed consent. Descriptive statistics, including minimum, median, and maximum, were calculated for metric data, and frequency tables for categorical data. Kaplan-Meier estimates with 95% confidence intervals were calculated for survival end points. RESULTS: A total of 3202 patients were eligible for safety analysis, of whom 2631 (82.2%) were male. Median age was 62 years (range, 15-98 years). A total of 1511 (47.2%) patients underwent TACE prior to sorafenib; 325 (10.1%) underwent TACE concomitantly. TACE prior to sorafenib was more common in Japan and Asia-Pacific compared with all other regions (362 [71.3%] and 560 [60.3%] vs 12-209 [13.3%-37.1%]). Adverse events were reported in 2732 (85.3%) patients overall, with no notable differences in the incidence of adverse events, regardless of TACE treatment history. Overall survival was 12.7 months in prior-TACE patients, 9.2 months in non-prior-TACE patients, 21.6 months in concomitant-TACE patients, and 9.7 months in non-concomitant-TACE patients. CONCLUSION: Global variation exists in TACE use in sorafenib-treated HCC patients. The combination of TACE with sorafenib appears to be a well-tolerated and viable therapeutic approach.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/métodos , Neoplasias Hepáticas/terapia , Niacinamida/análogos & derivados , Compostos de Fenilureia/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Niacinamida/uso terapêutico , Sorafenibe , Taxa de Sobrevida , Resultado do Tratamento
16.
Future Oncol ; 11(18): 2553-62, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26158398

RESUMO

AIMS: To evaluate sorafenib dosing and safety in the Global Investigation of therapeutic GIDEON study's European subpopulation. PATIENTS & METHODS: Patient demographics, disease characteristics and treatment history were recorded at enrollment; dose, adverse events and efficacy were recorded at follow-up. RESULTS: Of 1113 evaluable patients, 82% started on 800 mg/day sorafenib; patients starting on 400 mg/day were slightly older, had baseline characteristics indicative of greater disease progression and higher adverse events incidences (96 vs 88%). Treatment duration (18.0 vs 13.0 weeks) and median overall survival (12.1 vs 9.4 months) were longer in patients receiving 800 mg/day. CONCLUSION: Imbalances in independent predictive factors may have led to longer survival in patients receiving 800 mg/day sorafenib; nonetheless, results suggest that the majority can start on this dose.


Assuntos
Antineoplásicos/administração & dosagem , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Niacinamida/análogos & derivados , Compostos de Fenilureia/administração & dosagem , Inibidores de Proteínas Quinases/administração & dosagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Carcinoma Hepatocelular/etiologia , Feminino , Humanos , Neoplasias Hepáticas/etiologia , Masculino , Pessoa de Meia-Idade , Niacinamida/administração & dosagem , Niacinamida/efeitos adversos , Compostos de Fenilureia/efeitos adversos , Inibidores de Proteínas Quinases/efeitos adversos , Sorafenibe , Resultado do Tratamento , Adulto Jovem
17.
Arch Med Sci ; 11(2): 307-10, 2015 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-25995745

RESUMO

INTRODUCTION: Maximizing responses of malignant gliomas is hampered by resistance to temozolomide (TMZ). Increasing efficacy but not toxicity is a key issue when testing drug combinations. The antimyeloma agent bortezomib (BZ) has shown promising results in vitro and is currently being tested in glioblastoma (GBM) patients. In this study we investigate whether reduction of TMZ dosage is feasible without compromising the antitumor effect of TMZ-BZ combination. MATERIAL AND METHODS: U87 GBM cells were treated with increasing doses of TMZ (1, 10, 100, 1000 µM), BZ (0.001, 0.01, 0.1, 1) and the combination during a 48-hour period, and apoptotic or/and necrotic cell death was evaluated by flow cytometry. RESULTS: Bortezomib alone at a dose as low as 0.001 µM markedly induced cell death, particularly late apoptosis, to a level which was comparable with high TMZ dosage. For combination treatments, the dose of 0.1 µM BZ, which was more potent than the maximal dose of TMZ (1000 µM), was chosen to be added to increasing TMZ concentrations. The combination of 0.1 BZ µM BZ with low doses of TMZ (1, 10 µM) further increased the cell death rate in an additive manner, at levels higher than those induced by high doses of TMZ monotherapy (100, 1000 µM). CONCLUSIONS: Efficacy of TMZ-BZ combination is feasible with low doses of TMZ in vitro.

19.
Front Oncol ; 5: 6, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25699233

RESUMO

Neuroendocrine prostate carcinoma, either co-present with the local adenocarcinoma disease or as a result of transdifferentiation later in time, was described as one major process of emerging resistance to androgen deprivation therapies, and at the clinical level it is consistent with the development of rapidly progressive visceral disease, often in the absence of elevated serum prostate-specific antigen level. Until present, platinum-based chemotherapy has been the only treatment modality, able to produce a fair amount of responses but of short duration. Recently, several efforts for molecular characterization of this lethal phenotype have resulted in identification of novel signaling factors involved in microenvironment interactions, mitosis, and neural reprograming as potential therapeutic targets. Ongoing clinical testing of specific inhibitors of these targets, for example, Aurora kinase A inhibitors, in carefully selected patients and exploitation of expression changes of the target before and after manipulation is anticipated to increase the existing data and facilitate therapeutic decision making at this late stage of the disease when hormonal manipulations, even with the newest androgen-directed therapies are no longer feasible.

20.
Tumour Biol ; 36(6): 4699-705, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25627007

RESUMO

Endothelin-1 (ET-1) is a multifunctional peptide exerting its effects via receptors A and B. ET-1 and its receptors, endothelin axis (ET axis), play a promoting role in cancer biology. Alterations of proteins of ET axis have been detected in non-metastatic muscle-invasive bladder cancer (NMMIBC). The objective of this study is to investigate the potential role of ET-1 tumor expression as a biomarker of prognosis, compared to other prognostic parameters (epidemiologic and pathologic), in NMMIBC. We prospectively included 40 consecutive, primary, high-grade NMMIBC patients. Tumor specimens after initial transurethral resection were stained immunohistochemically for ET-1. The ET-1 evaluation of expression was based on staining intensity (SI) of ET-1. SI was classified according to an arbitrary four-tiered scale (negative = 0, mild = 1, moderate = 2, strong = 3). Epidemiologic and pathologic parameters were analyzed, using univariate and multivariate statistics, for disease progression, progression-free survival (PFS), and overall survival (OS). ET-1 overexpression (SI = 3) was the unique parameter which associated significantly, both in univariate (log-rank test, p = 0.033) and multivariate (Cox regression analysis, p = 0.045, HR = 4.849, 95 % CI: 1.039-22.624) analysis, with an increased hazard ratio of progression. ET-1 overexpression (SI = 3) was also the unique parameter which associated, marginally significantly in univariate analysis (log-rank test, p = 0.056) and highly significantly in multivariate analysis (Cox regression analysis, p = 0.005, HR = 7.001, 95 % CI: 1.782-27.501), with an increased hazard ratio of death. Overexpression of ET-1 may be a potential biomarker of unfavorable prognosis in NMMIBC patients.


Assuntos
Biomarcadores Tumorais/biossíntese , Endotelina-1/biossíntese , Neoplasias Musculares/genética , Neoplasias da Bexiga Urinária/genética , Adulto , Idoso , Biomarcadores Tumorais/genética , Intervalo Livre de Doença , Endotelina-1/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Neoplasias Musculares/patologia , Músculos/patologia , Invasividade Neoplásica/genética , Prognóstico , Neoplasias da Bexiga Urinária/patologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA