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1.
Int J Mol Sci ; 24(15)2023 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-37569332

RESUMO

Circulating tumor cells (CTCs) and/or circulating tumor microemboli (CTM) from non-small cell lung cancer (NSCLC) patients may be a non-invasive tool for prognosis, acting as liquid biopsy. CTCs interact with platelets through the transforming growth factor-ß/transforming growth factor-ß receptor type 1 (TGF-ß/TGFßRI) forming clusters. CTCs also may express the Cluster of Differentiation 47 (CD47) protein, responsible for the inhibition of phagocytosis, the "don't eat me" signal to macrophages. OBJECTIVES: To isolate, quantify and analyze CTCs/CTMs from metastatic NSCLC patients, identify TGFßRI/CD47 expression in CTCs/CTMs, and correlate with progression-free survival (PFS). METHODS: Blood (10 mL) was collected at two time-points: T1 (before the beginning of any line of treatment; T2 (60 days after initial collection). CTCs were isolated using ISET®. Immunocytochemistry was conducted to evaluate TGFßRI/CD47 expression. RESULTS: 45 patients were evaluated. CTCs were observed in 82.2% of patients at T1 (median: 1 CTC/mL; range: 0.33-11.33 CTCs/mL) and 94.5% at T2 (median: 1.33 CTC/mL; 0.33-9.67). CTMs were observed in 24.5% of patients and significantly associated with poor PFS (10 months vs. 17 months for those without clusters; p = 0.05) and disease progression (p = 0.017). CTMs CD47+ resulted in poor PFS (p = 0.041). TGFßRI expression in CTCs/CTMs was not associated with PFS. CONCLUSION: In this study, we observed that CTC/CTM from NSCLC patients express the immune evasion markers TGFßRI/CD47. The presence of CTMs CD47+ is associated with poor PFS. This was the first study to investigate CD47 expression in CTCs/CTM of patients with NSCLC and its association with poor PFS.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Células Neoplásicas Circulantes , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Células Neoplásicas Circulantes/patologia , Antígeno CD47 , Neoplasias Pulmonares/metabolismo , Biomarcadores , Receptor do Fator de Crescimento Transformador beta Tipo I , Fatores de Crescimento Transformadores , Biomarcadores Tumorais/metabolismo
2.
Leuk Lymphoma ; 64(13): 2165-2177, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37647140

RESUMO

Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma subtype and dependent on angiogenesis (AG), whose main effectors are VEGFA and VEGFR2. Functional single nucleotide variants (SNVs) are described in VEGFA and KDR genes. However, it still unknown whether VEGFA - 2578C/A, -2489C/T, -1154G/A, -634G/C, -460C/T and KDR-604T/C, -271G/A, +1192G/A and +1719A/T SNVs act on DLBCL risk and angiogenic features. Genomic DNA from 168 DLBCL patients and 205 controls was used for SNV genotyping. Angiogenesis was immunohistochemically assessed in tumor biopsies, with reactions for VEGFA, VEGFR2, and CD34. VEGFA -1154GG genotype were associated with 1.6-fold higher DLBCL risk. KDR + 1192GG plus KDR + 1719 TT and KDR + 1192GG plus VEGFA - 2578CC combined genotypes are associated with 2.19- and 2.04-fold higher risks of DLBCL, respectively. VEGFA - 634GG or GC genotypes are associated with increased microvessel density and VEGFA levels. No relationship was observed between SNVs and cell-of-origin classification of DLBCL, but higher VEGFA and VEGFR2 were seen in non-germinal center tumors.


Assuntos
Predisposição Genética para Doença , Linfoma Difuso de Grandes Células B , Humanos , Polimorfismo de Nucleotídeo Único , Genótipo , Linfoma Difuso de Grandes Células B/genética , Nucleotídeos , Fator A de Crescimento do Endotélio Vascular/genética , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/genética
3.
Cancer Control ; 30: 10732748221149543, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36592369

RESUMO

INTRODUCTION: The role of primary prophylaxis (PP) with granulocyte colony-stimulating factor (G-CSF) for patients with metastatic pancreatic adenocarcinoma (MPA) treated with FOLFIRINOX is unknown. We aimed to compare the frequencies of grades 3 or 4 neutropenia (G3/4N) and febrile neutropenia (FN) and survival outcomes according to the use of PP. METHODS: This is a retrospective study. We included patients with pathologically confirmed MPA treated with FOLFIRINOX in first-line. Patients who received primary prophylaxis (PP group) were compared to patients who received secondary or no G-CSF (no-PP group). Overall survival (OS) and progression-free survival (PFS) were evaluated using the standard Cox proportional hazard model. To account for potential biases, we performed sensitivity analyses excluding patients who received secondary prophilaxis and treating G-CSF as a time-dependent covariate in extended Cox proportional hazard models. RESULTS: The study population consisted of 123 patients. PP was used by 75 patients (61.0%). G3/4 N occurred more frequently among patients without PP (10.7 vs 41.7%; P < .001). There was no difference in the frequency of FN between groups (5.3 vs 8.3%; P = .710). In multivariate analysis, PP was associated with a trend toward improved OS (HR = .66; 95% confidence interval [95% CI] .41 - 1.07; P = .094). In the multivariate model excluding patients with secondary prophylaxis (HR = .54; 95% CI 0.32 - .91; P = .022) and in the time-dependent model (HR = .47; 95% CI 0.28 - .80; P = .005), PP was associated with statistically superior OS. CONCLUSIONS: Despite the reduction in the frequency of G3/4N, the risk of FN among patients treated with FOLFIRINOX without G-CSF is too low to justify its use in a routine basis. However, given the potential of G-CSF to improve survival in this setting, further studies are warranted to assess its role during treatment with FOLFIRINOX for patients with MPA.


Assuntos
Adenocarcinoma , Neutropenia , Neoplasias Pancreáticas , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Estudos Retrospectivos , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/etiologia , Adenocarcinoma/tratamento farmacológico , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Neutropenia/tratamento farmacológico , Neutropenia/etiologia , Neutropenia/prevenção & controle , Neoplasias Pancreáticas
4.
Tumour Biol ; 43(1): 129-140, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34219681

RESUMO

OBJECTIVES: Single nucleotide variants (SNVs) in vascular endothelial growth factor A (VEGFA) and VEGFA receptor (KDR) genes confer different inherited abilities in angiogenesis (AG) pathway. We aimed in the present study to evaluate influence of six VEGFA and four KDR SNVs in clinical features and survival of diffuse large B-cell lymphoma (DLBCL) patients. METHODS: One hundred and sixty-eight DLBCL patients diagnosed between June 2009-September 2014 were enrolled in the study. Patients were homogeneously treated with R-CHOP. Genotypes were identified in genomic DNA by real-time polymerase chain reaction. RESULTS: Patients with VEGFA -634CC and +936CT or TT genotypes were at increased risk of showing grade III / IV toxicities and not achieving complete remission with treatment, and shorter event-free and overall survival were seen in patients with VEGFA -1154GA or AA genotype and VEGFA ATAGCC haplotype. CONCLUSION: Our data suggest that inherited abnormalities in AG's gene modulate clinical features and prognosis of DLBCL patients homogeneously treated with R-CHOP.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/genética , Linfoma Difuso de Grandes Células B/patologia , Neovascularização Patológica/patologia , Polimorfismo de Nucleotídeo Único , Fator A de Crescimento do Endotélio Vascular/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Seguimentos , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/genética , Masculino , Pessoa de Meia-Idade , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/genética , Prednisona/administração & dosagem , Prognóstico , Estudos Prospectivos , Rituximab/administração & dosagem , Taxa de Sobrevida , Vincristina/administração & dosagem
5.
Diagnostics (Basel) ; 11(3)2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33809053

RESUMO

The discovery of predictive biomarkers in metastatic colorectal cancer (mCRC) is essential to improve clinical outcomes. Recent data suggest a potential role of circulating tumor cells (CTCs) as prognostic indicators. We conducted a follow-on analysis from a prospective study of consecutive patients with mCRC. CTC analysis was conducted at two timepoints: baseline (CTC1; before starting chemotherapy), and two months after starting treatment (CTC2). CTC isolation/quantification were completed by ISET® (Rarecells, France). CTC expressions of drug resistance-associated proteins were evaluated. Progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method. Seventy-five patients were enrolled from May 2012 to May 2014. A CTC1 cut-off of >1.5 CTCs/mL was associated with an inferior median OS compared to lower values. A difference of CTC2-CTC1 > 5.5 CTCs/mL was associated with a reduced median PFS. By multivariate analysis, CTC1 > 1.5 CTCs/mL was an independent prognostic factor for worse OS. Multi-drug resistance protein-1 (MRP-1) expression was associated with poor median OS. CTC baseline counts, kinetics, and MRP-1 expression were predictive of clinical outcomes. Larger studies are warranted to explore the potential clinical benefit of treating mCRC patients with targeted therapeutic regimens guided by CTC findings.

6.
Thorac Cancer ; 12(7): 1058-1066, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33586297

RESUMO

BACKGROUND: Due to the increasing number of trials with immune checkpoint inhibitors (ICIs) in the first-line therapy of non-small cell lung cancer (NSCLC) patients, we performed a systematic review and meta-analyses to investigate the difference between anti PD-1 and PD-L1 antibodies, used alone or in combination with chemotherapy, through adjusted indirect analysis to minimize the potential bias regarding overall survival (OS), progression-free survival (PFS), overall response rate (ORR) and grade 3-5 adverse events (AEs). METHODS: A systematic review of studies reporting clinical outcomes and toxicity associated with first-line therapy employing anti-PD1 or anti-PD-L1 antibodies alone, or in combination with chemotherapy, to treat metastatic, treatment-naïve NSCLC patients was performed. Primary outcomes were OS, PFS, ORR and grade 3-5 AEs. We used a random-effects model to generate pooled estimates for proportions. Meta-analyses using pooled risk ratios were performed for binary outcomes from comparative studies with the random effects model. RESULTS: A total of 13 eligible studies met our eligibility criteria, including 7673 patients. In the ICI-chemotherapy combination subgroup, we observed that anti-PD1 therapy was associated with better OS (p = 0.022) and PFS (p = 0.029) compared with anti-PD-L1 therapy. In the monotherapy subgroup, there was no statistical difference between the use of anti-PD-1 and anti-PD-L1 for OS and PFS. With regard to ORR and toxicity, in the ICI-chemotherapy combination subgroup, we observed a trend of better ORR (p = 0.12) with the use of anti-PD1 therapy and less frequent grade 3-5 AEs compared to the use of anti-PD-L1 therapy (p = 0.0302). In the monotherapy subgroup, there was no statistical difference between the use of anti-PD-1 and anti-PD-L1 regarding ORR and toxicity. CONCLUSIONS: Our study suggests that PD-1 drug plus chemotherapy is superior to anti-PD-L1 plus chemotherapy for NSCLC; nevertheless, as monotherapy, both strategies appear to be similar.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Inibidores de Checkpoint Imunológico/uso terapêutico , Imunoterapia/métodos , Neoplasias Pulmonares/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Inibidores de Checkpoint Imunológico/farmacologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Intervalo Livre de Progressão , Resultado do Tratamento
7.
Tumour Biol ; 41(9): 1010428319872092, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31486713

RESUMO

Angiogenesis, induced by the vascular endothelial growth factor A through its ligation to the vascular endothelial growth receptor 2, has been described as a crucial point in high-grade glioma development. The aim of this study was to evaluate the influence of VEGFA-2578C/A, -2489C/T, -1154G/A, -634G/C, and -460C/T, and KDR-604T/C, -271G/A, +1192G/A, and +1719A/T single-nucleotide polymorphisms on risk and clinicopathological aspects of high-grade glioma. This case-control study enrolled 205 high-grade glioma patients and 205 controls. Individuals with VEGFA-2578 CC or CA, VEGFA-1154 GG, VEGFA-634 GC or CC, and VEGFA-460 CT or TT genotypes were under 2.56, 1.53, 1.54, and 1.84 increased risks of high-grade glioma, compared to others, respectively. And 1.61, 2.66, 2.52, 2.53, and 2.02 increased risks of high-grade glioma were seen in individuals with VEGFA-2578 CC plus VEGFA-1154 GG, VEGFA-2578 CC or CA plus VEGFA-634 GC or CC, VEGFA-2578 CC or CA plus VEGFA-460 CT or TT, VEGFA-1154 GG or GA plus VEGFA-634 GC or CC, and VEGFA 634 GC or CC plus VEGFA-460 CT or TT combined genotypes, respectively, when compared to others. The "CAGT" haplotype of KDR single-nucleotide polymorphisms was more common in patients with grade IV than in those with grade III tumors, and individuals carrying this haplotype were at 1.76 increased risk of developing grade IV tumors than others. We present, for the first time, preliminary evidence that VEGFA-2578C/A and VEGFA-1154G/A single-nucleotide polymorphisms increases high-grade glioma risk, and "CAGT" haplotype of the KDR gene alters high-grade glioma aggressiveness and risk of grade IV tumors in Brazil.


Assuntos
Glioma/genética , Haplótipos , Polimorfismo de Nucleotídeo Único , Fator A de Crescimento do Endotélio Vascular/genética , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Fatores de Risco , Adulto Jovem
8.
Rev Assoc Med Bras (1992) ; 65(2): 136-140, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30892435

RESUMO

We describe the case of a female patient, 52 years old, with dizziness and left motor incoordination for 2 weeks. Brain MRI magnetic resonance imaging) revealed a hyperintense lesion on T2-weighted images, without restricted diffusion, in the left middle cerebellar peduncle. Spectroscopy demonstrated peak of lipids and perfusion did not show any elevation in relative cerebral blood volume (rCBV). The patient underwent an open biopsy and resection, and the diagnosis of diffuse large B-cell lymphoma (DLBCL) was established. The patient received intravenous dexamethasone with symptoms remission, followed by four cycles of methotrexate plus cytarabine. After 3 months, the patient returned with decreased consciences level and a new MRI revealed a right superior frontal gyrus lesion with features suggesting a lymphomatous lesion. The patient died five days after her relapse.


Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Linfoma Difuso de Grandes Células B/diagnóstico por imagem , Neoplasias Encefálicas/tratamento farmacológico , Evolução Fatal , Feminino , Humanos , Imunocompetência , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Recidiva Local de Neoplasia
9.
Rev. Assoc. Med. Bras. (1992) ; 65(2): 136-140, Feb. 2019. graf
Artigo em Inglês | LILACS | ID: biblio-990325

RESUMO

SUMMARY We describe the case of a female patient, 52 years old, with dizziness and left motor incoordination for 2 weeks. Brain MRI magnetic resonance imaging) revealed a hyperintense lesion on T2-weighted images, without restricted diffusion, in the left middle cerebellar peduncle. Spectroscopy demonstrated peak of lipids and perfusion did not show any elevation in relative cerebral blood volume (rCBV). The patient underwent an open biopsy and resection, and the diagnosis of diffuse large B-cell lymphoma (DLBCL) was established. The patient received intravenous dexamethasone with symptoms remission, followed by four cycles of methotrexate plus cytarabine. After 3 months, the patient returned with decreased consciences level and a new MRI revealed a right superior frontal gyrus lesion with features suggesting a lymphomatous lesion. The patient died five days after her relapse.


RESUMO Descrevemos o caso de uma paciente do sexo feminino, de 52 anos, apresentando história de tontura e perda da coordenação motora do lado esquerdo há duas semanas. A RM (ressonância magnética) de crânio revelou uma lesão hiperintensa nas imagens ponderadas em T2, sem restrição à difusão, localizada no pedúnculo cerebelar médio esquerdo. A espectroscopia demonstrou pico de lipídeos, sem elevação do volume sanguíneo cerebral relativo (rCBV) à perfusão. A paciente foi submetida à biópsia a céu aberto, estabelecendo o diagnóstico de linfoma difuso de grandes células B (DLBCL). Houve remissão dos sintomas após o início do tratamento com dexametasona endovenosa, seguida de quatro ciclos de metotrexato associado à citarabina. Após três meses, a paciente retornou apresentando rebaixamento do nível de consciência, e a RM de crânio revelou uma nova lesão de origem linfomatosa no giro frontal superior direito. A paciente faleceu após cinco dias.


Assuntos
Humanos , Feminino , Neoplasias Encefálicas/diagnóstico por imagem , Linfoma Difuso de Grandes Células B/diagnóstico por imagem , Neoplasias Encefálicas/tratamento farmacológico , Imageamento por Ressonância Magnética , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Evolução Fatal , Imunocompetência , Pessoa de Meia-Idade , Recidiva Local de Neoplasia
10.
Int J Gynecol Cancer ; 28(7): 1251-1257, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30142123

RESUMO

OBJECTIVE: The aim of this study was to analyze and compare the clinicopathologic features and prognosis of clear cell ovarian carcinoma (CCOC) and endometrioid ovarian carcinoma (EOC) associated or not with endometriosis. METHODS: This was a reconstituted cohort study from a single-institution Brazilian cancer center approved under review board no. 68150617.7.0000.5404 with 50 patients with CCOC and EOC diagnosed between 1995 and 2016, followed up until 2017. Clinicopathologic characteristics and survival outcomes were analyzed. RESULT(S): There were 23 women (46%) with CCOC and 27 with EOC (54%); 80% of those women had histologic confirmation of endometriosis; 42% were nulliparous, and 42% were premenopausal; and cancer antigen 125 was elevated in both International Federation of Gynecology and Obstetrics stages I-II disease (mean, 614.7 Ui/mL; range, 3-6030 Ui/mL) or International Federation of Gynecology and Obstetrics stages III-IV disease (mean, 2361.2 Ui/mL; range, 8-12771 Ui/mL). Women with EOC were 7 years younger than those with CCOC. When associated with endometriosis, CCOCs were more likely diagnosed at earlier stages. Endometrioid ovarian carcinoma and CCOC at initial stage and EOC at advanced stage share similar good prognosis. Univariate analysis showed that CCOC not associated with endometriosis has worse overall survival (OS). However, multivariate analysis showed that only abnormally elevated levels of cancer antigen 125 and advanced stage at diagnosis were significantly associated with reduced progression-free survival. Tumor stage remains the only prognostic factor for OS. CONCLUSIONS: The presence of coexisting endometriosis did not change the prognosis of EOC but was associated with better OS in patients with CCOC. Patients with CCOC and EOC at initial stages and EOC at advanced stages have a good prognosis; however, CCOC at advanced stages had a sooner recurrence and shorter OS.


Assuntos
Endometriose/complicações , Neoplasias Ovarianas/complicações , Adenocarcinoma de Células Claras/complicações , Adenocarcinoma de Células Claras/patologia , Carcinoma Endometrioide/complicações , Carcinoma Endometrioide/patologia , Estudos de Coortes , Endometriose/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Neoplasias Ovarianas/patologia , Prognóstico
11.
Oncotarget ; 9(22): 15818-15827, 2018 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-29662608

RESUMO

OBJECTIVE: To evaluate the diagnostic and prognostic value of the immunohistochemical expression of WT1, p53 and p16 in low- (LGSOCs) and high-grade serous ovarian carcinomas (HGSOCs). RESULTS: HGSOC had a significantly higher proportion of advanced stage disease, higher CA125 levels, higher proportion of post-surgery residual disease and higher recurrence or disease progression. WT1 was expressed in 71.4% of LGSOCs and in 57.1% of HGSOCs (p = 0.32). Focal and/or complete absence of p53 expression with negative p16 expression was found in 90.5% of LGSOCs, in contrast to the 88.1% of HGSOCs with diffuse or complete absence of p53 expression with positive p16 expression (<0.001). The IHC p53/p16 index and the morphological classification were closely matched (k = 0.68). In the univariate analysis, FIGO stage, post-surgery residual disease and histological grade were significantly associated with progression-free survival (PFS) and overall survival (OS). The IHC p53/p16 index was associated only with PFS. WT1 was not associated with PFS or OS. According to the multivariate analysis, advanced FIGO stage and presence of post-surgery residual disease remained independent prognostic factors for worst PFS, however these features had only a trend association with OS. METHODS: 21 LGSOC and 85 HGSOC stage I-IV cases were included. The morphological classification was assessed according to the World Health Organization (WHO) criteria. Immunohistochemistry (IHC) was performed in tissue microarray slides. IHC p53/p16 index was compared with the morphological classification. CONCLUSIONS: The IHC p53/p16 index was a good marker for the differentiation of LGSOC and HGSOC, but the morphologic classification showed a better association with survival. FIGO stage and post-surgery residual disease remained the only independent prognostic factors for survival.

12.
Int J Gynecol Cancer ; 28(3): 437-447, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29465506

RESUMO

OBJECTIVE: The purpose of this study was to compare the immunohistochemical expression of BRCA1, Ki67, and ß-catenin in women with low-grade (LGSOC) and high-grade serous ovarian carcinomas (HGSOC) and their relationship with clinicopathological features, response to platinum-based chemotherapy, and survival. METHODS: For this study, 21 LGSOC and 85 HGSOC stage I to IV cases, diagnosed and treated from 1996 to 2013 and followed-up until December 2016, were included. BRCA1, Ki67, and ß-catenin expression was assessed using tissue microarray-based immunohistochemistry. RESULTS: Women with HGSOC were significantly more likely to have advanced-stage disease (P < 0.001), higher CA125 levels (P < 0.001), postsurgery residual disease (P < 0.01), and higher rates of disease progression and recurrence (P = 0.001). The percentage of women with HGSOC whose tumors expressed Ki67 was significantly higher compared with women with LGSOC (P < 0.001). The expression of BRCA1 and ß-catenin did not differ between LGSOC and HGSOC (P = 0.12 and P = 1.00, respectively). The clinicopathological features and the response to platinum-based chemotherapy did not differ according to the BRCA1, Ki67, and ß-catenin expression in either group. In HGSOC, only International Federation of Gynecology and Obstetrics stage was independently associated with poor survival (PFS and OS). CONCLUSIONS: Ki67 expression was significantly higher in HGSOC. BRCA1 and ß-catenin expression did not differ between LGSOC and HGSOC samples. BRCA1, Ki67, and ß-catenin expression was neither related to clinicopathological features, response to platinum-based chemotherapy, nor survival. Only International Federation of Gynecology and Obstetrics stage remained associated with poor survival in women with HGSOC.


Assuntos
Proteína BRCA1/biossíntese , Cistadenocarcinoma Seroso/tratamento farmacológico , Cistadenocarcinoma Seroso/imunologia , Antígeno Ki-67/biossíntese , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/imunologia , beta Catenina/biossíntese , Proteína BRCA1/imunologia , Carboplatina/administração & dosagem , Diferenciação Celular/fisiologia , Estudos de Coortes , Ciclofosfamida/administração & dosagem , Cistadenocarcinoma Seroso/patologia , Feminino , Humanos , Imuno-Histoquímica , Antígeno Ki-67/imunologia , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Neoplasias Ovarianas/patologia , Paclitaxel/administração & dosagem , Prognóstico , Estudos Retrospectivos , beta Catenina/imunologia
13.
Future Oncol ; 13(5): 409-414, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27780361

RESUMO

AIM: Since VEGF polymorphisms were associated with variable protein production, we analyzed herein their roles in outcome of epithelial ovarian cancer (EOC) patients. METHODS: Genotypes of 85 patients with primary EOC were identified in DNA by real-time PCR. Progression-free survival and overall survival were analyzed using Kaplan-Meier method, univariate Cox model and bootstrap resampling study. RESULTS: At 60 months of follow-up, progression-free survival was shorter in patients with VEGF c.-2578 CC genotype compared with others (52.7 vs 82.2%; p = 0.04). Those patients had 2.15 more chance of presenting disease progression than others (p = 0.04); bootstrap study validated the result (p = 0.03). CONCLUSION: Our data suggest that VEGF c.-2578C>A polymorphism acts as a prognostic factor in EOC.


Assuntos
Neoplasias Epiteliais e Glandulares/genética , Neoplasias Epiteliais e Glandulares/mortalidade , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/mortalidade , Polimorfismo de Nucleotídeo Único , Fator A de Crescimento do Endotélio Vascular/genética , Alelos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Epitelial do Ovário , Feminino , Seguimentos , Genótipo , Humanos , Estimativa de Kaplan-Meier , Desequilíbrio de Ligação , Estadiamento de Neoplasias , Neoplasias Epiteliais e Glandulares/tratamento farmacológico , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Avaliação de Resultados da Assistência ao Paciente , Prognóstico
14.
Med Oncol ; 33(10): 112, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27586145

RESUMO

This study aimed to evaluate whether GSTM1 and GSTT1 (presents or nulls), GSTP1 c.313A>G and NQO2 c.-102A>C polymorphisms, involved in xenobiotic detoxification pathways, alter outcomes of epithelial ovarian cancer (EOC) patients. DNA from 84 EOC patients diagnosed at the University of Campinas Academic Hospital from January 1995 and July 2007 was analyzed by polymerase chain reaction and restriction fragment length polymorphism assays. The prognostic impact of genotypes of polymorphisms on progression-free survival and overall survival (OS) of EOC patients was examined using the Kaplan-Meier probability estimates and univariate and multivariate Cox proportional hazard ratio (HR) regression analyses. The significant results of Cox analyses were validated using a bootstrap resampling study (1000 replications). At 60 months of follow-up, lower OS was seen in patients with GSTT1 null genotype (50.0 vs. 76.7 %, P = 0.02) compared with the other genotype (Kaplan-Meier estimate). This outcome remained the same in univariate Cox analysis (HR 2.22, P = 0.02). After multivariate Cox analysis, patients with GSTT1 null (HR 2.11, P = 0.04, P bootstrap = 0.04) and NQO2 AA (HR 2.13, P = 0.03, P bootstrap = 0.04) genotypes were under greater risks of progressing to death when compared with those with others genotypes. Our data suggest, for the first time, that inherited abnormalities in xenobiotic detoxification pathway related to GSTT1 and NQO2 c.-102A>C polymorphisms act as independent prognostic factors for OS of EOC patients.


Assuntos
Glutationa Transferase/genética , Neoplasias Epiteliais e Glandulares/enzimologia , Neoplasias Epiteliais e Glandulares/genética , Neoplasias Ovarianas/enzimologia , Neoplasias Ovarianas/genética , Quinona Redutases/genética , Adulto , Idoso , Carcinoma Epitelial do Ovário , Feminino , Glutationa S-Transferase pi , Humanos , Inativação Metabólica/genética , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Ovarianas/patologia , Polimorfismo de Nucleotídeo Único , Xenobióticos/farmacocinética , Adulto Jovem
18.
Ann Hematol ; 93(8): 1363-9, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24687381

RESUMO

Angiogenesis has been highlighted as a critical component in the progression of multiple myeloma (MM), and vascular endothelial growth factor (VEGF) as well as its type 2 receptor (VEGFR2) are thought to play a major role in the process. Single nucleotide polymorphisms (SNPs) have been described in VEGF and VEGFR2 genes, with quantitative or qualitative changes in encoded VEGF and VEGFR2. The roles of VEGF -2578C/A, -1154G/A, and -634G/C as well as VEGFR2 -604T/C and +1192G/A SNPs in the risk and manifestations of MM are still unknown; therefore, this study aimed to clarify this issue. DNA from 192 patients and 209 controls were analyzed by real-time polymerase chain reaction for identification of genotypes. The frequencies of VEGF -2578CC, VEGF -2578CC plus VEGF -634GG, and VEGF -2578CC plus VEGF -1154GG plus VEGF -634GG genotypes were higher in patients than in controls. Carriers of the respective genotypes had a 1.89-, a 5.52-, and a 4.91-fold increased risk for MM than others. VEGF -2578CC plus VEGFR2 +1192GG, VEGF -2578CC plus VEGF -634GG plus VEGFR2 +1192GG, and VEGF -1154GG plus VEGF -634GG plus VEGFR2 -604TT combined genotypes were more common in patients than in controls. Carriers of the respective genotypes had a 2.56-, a 10.97-, and a 14.10-fold increased risk for MM than others. An excess of VEGFR2 -604TT genotype was also seen in patients with stage II or III tumors when compared with those with stage I tumors. Our data suggest, for the first time, that inherited abnormalities in VEGF and VEGFR2 pathways influence the risk and aggressiveness of MM.


Assuntos
Mieloma Múltiplo/genética , Proteínas de Neoplasias/genética , Polimorfismo de Nucleotídeo Único , Fator A de Crescimento do Endotélio Vascular/genética , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/genética , Regiões 5' não Traduzidas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/patologia , Invasividade Neoplásica/genética , Proteínas de Neoplasias/fisiologia , Estadiamento de Neoplasias , Neovascularização Patológica/genética , Neovascularização Patológica/fisiopatologia , Regiões Promotoras Genéticas/genética , Fator A de Crescimento do Endotélio Vascular/fisiologia , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/fisiologia
19.
Int J Clin Exp Med ; 7(2): 456-60, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24600506

RESUMO

Diffuse large B-cell lymphoma (DLBCL) presented as a primary dural lesion is an extremely rare entity, which may be misdiagnosed as meningioma. Patients with symptomatic meningioma are usually treated with tumor resection. The five previously described cases of intracranial dural DLBCL were treated with surgery followed by chemotherapy and/or radiotherapy, with a favorable outcome, but with potential sequels. We reported the first case of DLBCL, presented as a primary dural lesion, successfully treated with chemotherapy only in a 52-year-old woman presented in October 2011 with rapidly progressive headaches, nausea and vomiting. Magnetic resonance imaging of the brain and head computed tomography showed a lesion en plaque in the right parieto-occipital region, tracking the dura matter, and osteolytic lesions. The patient underwent an open tumor biopsy, and the diagnosis of DLBCL was established. The patient received dexamethasone, cisplatin and cytarabine (DHAP) followed by methotrexate plus cytarabine, and obtained a durable complete response. Thus, intracranial dural DLBCL must be considered in differential diagnosis of meningeal lesions, particularly when a rapid progression of symptoms and osteolytic lesions are present, because an early diagnosis and rapid initiation of treatment, even though with chemotherapy, is associated with favorable outcome.

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