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1.
J Magn Reson Imaging ; 57(1): 248-258, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35561019

RESUMO

BACKGROUND: Computational analysis of routinely acquired MRI has potential to improve the tumor chemoresistance prediction and to provide decision support in precision medicine, which may extend patient survival. Most radiomic analytical methods are compatible only with rectangular regions of interest (ROIs) and irregular tumor shape is therefore an important limitation. Furthermore, the currently used analytical methods are not directionally sensitive. PURPOSE: To implement a tumor analysis that is directionally sensitive and compatible with irregularly shaped ROIs. STUDY TYPE: Retrospective. SUBJECTS: A total of 54 patients with histopathologic diagnosis of primary osteosarcoma on tubular long bones and with prechemotherapy MRI. FIELD STRENGTH/SEQUENCE: A 1.5 T, T2-weighted-short-tau-inversion-recovery-fast-spin-echo. ASSESSMENT: A model to explore associations with osteosarcoma chemo-responsiveness included MRI data obtained before OsteoSa MAP neoadjuvant cytotoxic chemotherapy. Osteosarcoma morphology was analyzed in the MRI data by calculation of the nondirectional two-dimensional (2D) and directional and nondirectional one-dimensional (1D) Higuchi dimensions (Dh). MAP chemotherapy response was assessed by histopathological necrosis. STATISTICAL TESTS: The area under the receiver operating characteristic (ROC) curve (AUC) evaluated the association of the calculated features with the actual chemoresponsiveness, using tumor histopathological necrosis (95%) as the endpoint. Least absolute shrinkage and selection operator (LASSO) machine learning and multivariable regression were used for feature selection. Significance was set at <0.05. RESULTS: The nondirectional 1D Dh reached an AUC of 0.88 in association with the 95% tumor necrosis, while the directional 1D analysis along 180 radial lines significantly improved this association according to the Hanley/McNeil test, reaching an AUC of 0.95. The model defined by variable selection using LASSO reached an AUC of 0.98. The directional analysis showed an optimal predictive range between 90° and 97° and revealed structural osteosarcoma anisotropy manifested by its directionally dependent textural properties. DATA CONCLUSION: Directionally sensitive radiomics had superior predictive performance in comparison to the standard nondirectional image analysis algorithms with AUCs reaching 0.95 and full compatibility with irregularly shaped ROIs. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 1.


Assuntos
Imageamento por Ressonância Magnética , Neoplasias , Humanos , Estudos Retrospectivos , Imageamento por Ressonância Magnética/métodos , Espectroscopia de Ressonância Magnética , Necrose
2.
Radiol Case Rep ; 16(9): 2646-2650, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34345325

RESUMO

A distinctive feature of some angiosarcomas is that two or more atypical forms of pulmonary metastases may be detected concomitantly. In this case report, we present a 37-year-old man diagnosed with angiosarcoma of the neck, with extreme diversity of lung metastases on chest computed tomography (CT). We analyzed CT features of metastases and discussed possible reasons for their pleomorphism, as well as clinical implications of these findings.

3.
Clin Med Insights Case Rep ; 13: 1179547620972414, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33239933

RESUMO

Mondor's disease (MD), or superficial thrombophlebitis of the anterolateral thoracoabdominal wall, is a rare disease that presents with a palpable cord-like induration beneath the skin. It is a benign, self-limiting condition with probably underestimated significance due to the fact it may be a rare manifestation of an underlying breast carcinoma. It can also resemble breast malignancy and, if physician is not familiar with clinical features of MD, it may lead to unnecessary biopsy. The diagnosis is straightforward in most cases and it may be based on a thorough history and physical examination and it can be ultrasonographically confirmed. Raising awareness of this condition may facilitate recognition and diagnosing MD and eventually limit unnecessary diagnostic procedures.

4.
Clin Imaging ; 65: 119-123, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32446129

RESUMO

PURPOSE: Texture analysis (TA) parameters (variance of SI, mean of gradient, variance of gradient, kurtosis of SI, and entropy) in patients with invasive ductal carcinoma (IDC) contribute to objective assessment of neoadjuvant chemotherapy (NACT) activity. The objective was to assess TA parameters in early identification of non-responders (NR) in NACT, after the 2nd cycle of NACT. MATERIAL AND METHODS: Fifty patients (N = 50) were included in the retrospective analysis of baseline and MRI following the 2nd cycle of NACT. TA parameters were computed and correlated to the lesion size and DWI-ADC in NR (N1 = 25). Additional matched responders (R, N2 = 25) assessed for the same parameters, served as the control group. RESULTS: Tumor size and ADC did not change significantly in NR after the 2nd cycle of NACT (2.88 ± 0.38 vs. 2.76 ± 0.36 [cm], p = 0.131; 1.01 ± 0.14 vs. 1.05 ± 0.13 [mm2/s × 10-3], p = 0.363), but TA parameters changed significantly: variance of gradient (346.5 ± 12.6 vs. 355.6 ± 16.9, p = 0.01), kurtosis of SI (1.47 ± 0.09 vs. 1.54 ± 0.11, p = 0.02), entropy LH (60.39 ± 4.34 vs. 64.42 ± 3.05, p = 0.001) and entropy HL (61.02 ± 5.51 vs. 65.63 ± 3.63, p < 0.00001). TA parameters, particularly entropy (EN LH 64.42 ± 3.05 vs. 61.59 ± 1.76, p < 0.0001; EN HL 65.63 ± 3.63 vs. 62.89 ± 2.05, p < 0.0001), significantly differ between NR and R in early response assessment. CONCLUSION: Entropy, kurtosis of SI and variance of gradient tend to increase in NR. TA parameters significantly differ between NR and R after the 2nd cycle of NACT. TA parameters, related to morpho-functional parameters may contribute to early NR identification.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Carcinoma Ductal/diagnóstico por imagem , Terapia Neoadjuvante , Adulto , Idoso , Neoplasias da Mama/patologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Radiografia , Estudos Retrospectivos , Resultado do Tratamento
5.
Eur J Radiol ; 124: 108854, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32007817

RESUMO

PURPOSE: To assess relative apparent diffusion coefficient (rADC) and ADC in B3 and B5 lesions in premenopausal female patients, added to standard morpho-dynamic breast contrast-enhanced MRI. METHODS: 104 patients with histologically confirmed B3 (N1 = 52) and matched B5 lesions (N2 = 52), were examined on MRI (1.5 T, full diagnostic protocol, diffusion weighted imaging - b50, b850) in a retrospective analysis following the IRB approval: Atypical ductal hyperplasia (ADH, n1 = 20), Flat epithelial atypia (FEA, n2 = 11), Classic lobular neoplasia (CLN, n3 = 8), Papillary lesion (PL, n4 = 6) and Phyllodes tumor (PT, n5 = 7). rADC and ADC were computed for each lesion. The two-tailed Mann-Whitney U test was used for comparison with B5 lesions. RESULTS: Mean rADC value for B3 lesions, (N1 = 52): 0.81+/-0.08 mm2/s x 10-3 and B5 lesions, (N2 = 52): 0.58+/-0.07 mm2/s x 10-3 is statistically different (p < 0.00001). Mean rADC values [mm2/s x 10-3], per entity in B3 are: ADH, 0.82+/-0.06; FEA, 0.75+/-0.03; CLN, 0.73+/-0.03; PL, 0.94+/-0.02; PT 0.86+/-0.05. CONCLUSIONS: Although morpho-dynamic features of borderline and malignant lesions may overlap, the initial results in this research, suggest the highly significant difference in both ADC and rADC between B3 and B5 lesions. Larger trials are needed to confirm the initial data.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Meios de Contraste , Aumento da Imagem/métodos , Imageamento por Ressonância Magnética/métodos , Biópsia , Mama/diagnóstico por imagem , Mama/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos
7.
BMC Med Imaging ; 18(1): 54, 2018 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-30567503

RESUMO

BACKGROUND: This is the first reported case of a primary intraosseous angioleiomyoma and the second case of a primary leiomyoma of the rib, irrespective of age. Angioleiomyomas mostly occur in patients of advanced age, in any part of the body, particularly the lower extremities and present as painful, slow-growing nodules in the dermis, subcutaneous fat or deep fascia. Other localizations, especially bone, are considered extremely rare, as well as their occurrence in paediatric patients. CASE PRESENTATION: A 10-year-old girl was admitted to the orthopaedic surgery department for further assessment of a pain localized in the posterior part of the right hemithorax. After magnetic resonance imaging (MRI) and surgical biopsy, intraosseus angioleiomyoma of the fourth rib was diagnosed by histopathology examination. Atypical costal localization of this type of a benign tumour presents diagnostic difficulty, especially in children. The differential diagnoses included cartilaginous tumours, Ewing sarcoma, fibrous dysplasia, Langerhans cell histiocytosis, intraosseous haemangioma and metastatic tumours. We report a detailed diagnostic procedure including MRI, selective angiography and histopathologic examination. CONCLUSION: Diagnosis of intraosseous angioleiomyoma is difficult due to the extreme rarity of this tumour and absence of pathognomonic radiological signs. Although very rarely identified in bones and young age group, radiographers and reporting doctors should be aware of this possible angioleiomyoma presentation and supported by the provided detailed diagnostic information.


Assuntos
Angiomioma/diagnóstico por imagem , Angiomioma/patologia , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/patologia , Imageamento por Ressonância Magnética/métodos , Costelas/diagnóstico por imagem , Costelas/patologia , Angiomioma/cirurgia , Biópsia , Neoplasias Ósseas/cirurgia , Criança , Diagnóstico Diferencial , Feminino , Humanos , Costelas/cirurgia
8.
Cell Oncol (Dordr) ; 41(4): 409-426, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29790111

RESUMO

PURPOSE: Anaplastic thyroid carcinoma (ATC) is an aggressive, chemo-resistant malignancy. Chemo-resistance is often associated with changes in activity of the RAS/MAPK/ERK and PI3K/AKT/mTOR pathways and/or a high expression of ATP binding cassette (ABC) transporters, such as P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP). To assess the therapeutic efficacy in ATC of a combination of the dual mTOR kinase inhibitor vistusertib (AZD2014) and paclitaxel (PTX), we generated a new cell line (Rho-) via the selection of human thyroid carcinoma 8505C cells that exhibit a low accumulation of rhodamine 123, which serves as a P-gp and BCRP substrate. METHODS: Immunohistochemistry was used for P-gp and BCRP expression analyses in primary ATC patient samples. Spheroid formation and immunodeficient NSG mice were used for performing in vitro and in vivo tumorigenicity assays, respectively. MTT, flow-cytometry, fluorescent microscopy, cell death and proliferation assays, as well as migration, invasion and gelatin degradation assays, were used to assess the potential of AZD2014 to enhance the effects of PTX. ATC xenografts in SCID mice were used for evaluating in vivo treatment efficacies. RESULTS: Rho- cells were found to be 10-fold more resistant to PTX than 8505C cells and, in addition, to be more tumorigenic. We also found that AZD2014 sensitized Rho- cells to PTX by inhibiting proliferation and by inducing autophagy. The combined use of AZD2014 and PTX efficiently inhibited in vitro ATC cell migration and invasion. Subsequent in vivo xenograft studies indicated that the AZD2014 and PTX combination effectively suppressed ATC tumor growth. CONCLUSIONS: Our data support results from recent phase I clinical trials using combinations of AZD2014 and PTX for the treatment of solid tumors. Such combinations may also be employed for the design of novel targeted ATC treatment strategies.


Assuntos
Morfolinas/uso terapêutico , Paclitaxel/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Carcinoma Anaplásico da Tireoide/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Animais , Apoptose/efeitos dos fármacos , Benzamidas , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos , Feminino , Citometria de Fluxo , Humanos , Imuno-Histoquímica , Masculino , Camundongos , Camundongos SCID , Pessoa de Meia-Idade , Pirimidinas , Ensaios Antitumorais Modelo de Xenoenxerto
9.
Forensic Sci Med Pathol ; 14(3): 406-409, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29644530

RESUMO

Pseudoaneurysms arise from a disruption of arterial wall continuity and are most commonly related to a penetrating trauma, an arterial wall inflammation or iatrogenic causes. They differ from real aneurysms due to a lack of one or more layers of the arterial wall. The frequency of peripheral artery pseudoaneurysms in the upper extremities is less than in the lower extremities and its most common cause is a gunshot or a stab wound. The risk of a rupture is higher than in true aneurysms due to a lack of wall layers, therefore requiring surgical treatment in most cases. Here we describe an unusual case of an 8-year-old girl who presented to the emergency department complaining of swelling and pain in her left distal forearm. One month before admission she experienced a penetrating trauma in the same area due to a self inflicted stab wound. After clinical and duplex ultrasonography evaluation the tumefaction proved to be a posttraumatic pseudoaneurysm of the left radial artery.


Assuntos
Falso Aneurisma/diagnóstico por imagem , Artéria Radial/diagnóstico por imagem , Artéria Radial/lesões , Ferimentos Perfurantes/complicações , Falso Aneurisma/etiologia , Criança , Feminino , Humanos , Comportamento Autodestrutivo/complicações , Ultrassonografia Doppler
10.
Radiol Oncol ; 51(2): 130-136, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28740447

RESUMO

BACKGROUND: We aimed to analyse the morphokinetic features of breast fibrocystic changes (nonproliferative lesions, proliferative lesions without atypia and proliferative lesions with atypia) presenting as a non-mass enhancement (NME)in dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) examination. PATIENTS AND METHODS: Forty-six patients with histologically proven fibrocystic changes (FCCs) were retrospectively reviewed, according to Breast Imaging Reporting and Data System (BI-RADS) lexicon. Prior to DCE-MRI examination, a unilateral breast lesion suspicious of malignancy was detected clinically, on mammography or breast ultrasonography. RESULTS: The predominant features of FCCs presenting as NME in DCE-MRI examination were: unilateral regional or diffuse distribution (in 35 patients or 76.1%), heterogeneous or clumped internal pattern of enhancement (in 36 patients or 78.3%), plateau time-intensity curve (in 25 patients or 54.3%), moderate or fast wash-in (in 31 patients or 67.4%).Nonproliferative lesions were found in 11 patients (24%), proliferative lesions without atypia in 29 patients (63%) and lesions with atypia in six patients (13%), without statistically significant difference of morphokinetic features, except of the association of clustered microcysts with proliferative dysplasia without atypia. CONCLUSIONS: FCCs presenting as NME in DCE-MRI examination have several morphokinetic features suspicious of malignancy, therefore requiring biopsy (BI-RADS 4). Nonproliferative lesions, proliferative lesions without atypia and proliferative lesions with atypia predominantly share the same predefined DCE-MRI morphokinetic features.

11.
Cell Oncol (Dordr) ; 40(1): 47-62, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27822706

RESUMO

BACKGROUND: Current high lung cancer mortality rates are mainly due to the occurrence of metastases and therapeutic resistance. Therefore, simultaneous targeting of these processes may be a valid approach for the treatment of this type of cancer. Here, we assessed relationships between CXC chemokine receptor type 4 (CXCR4) and focal adhesion kinase (FAK) gene expression levels and expression levels of the drug resistance-related genes ABCB1 and ABCC1, and tested the potential of CXCR4 and FAK inhibitors to reverse doxorubicin (DOX) resistance and to decrease the invasive capacity of non-small cell lung carcinoma (NSCLC) cells. METHODS: qRT-PCR was used for gene expression analyses in primary lung tissue samples obtained from 30 NSCLC patients and the human NSCLC-derived cell lines NCI-H460, NCI-H460/R and COR-L23. MTT, flow cytometry, cell death and ß-galactosidase activity assays were used to assess the in vitro impact of CXCR4 and FAK inhibitors on DOX sensitivity. In addition, invasion and gelatin degradation assays were used to assess the in vitro impact of the respective inhibitors on metastasis-related processes in combination with DOX treatment. RESULTS: We found that ABCB1 over-expression was significantly associated with CXCR4 and FAK over-expression, whereas ABCC1 over-expression was associated with increased FAK expression. We also found that CXCR4 and FAK inhibitors strongly synergized with DOX in reducing cell viability, arresting the cell cycle in the S or G2/M phases and inducing senescence. Additionally, we found that DOX enhanced the anti-invasive potential of CXCR4 and FAK inhibitors by reducing gelatin degradation and invasion. CONCLUSIONS: From our data we conclude that targeting of CXCR4 and FAK may overcome ABCB1 and ABCC1-dependent DOX resistance in NSCLC cells and that simultaneous treatment of these cells with DOX may potentiate the anti-invasive effects of CXCR4 and FAK inhibitors.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Resistencia a Medicamentos Antineoplásicos/genética , Quinase 1 de Adesão Focal/antagonistas & inibidores , Neoplasias Pulmonares/patologia , Receptores CXCR4/antagonistas & inibidores , Subfamília B de Transportador de Cassetes de Ligação de ATP/biossíntese , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Aminopiridinas/farmacologia , Benzilaminas/farmacologia , Western Blotting , Carcinoma Pulmonar de Células não Pequenas/genética , Doxorrubicina/uso terapêutico , Quinase 1 de Adesão Focal/genética , Perfilação da Expressão Gênica , Humanos , Neoplasias Pulmonares/genética , Proteínas Associadas à Resistência a Múltiplos Medicamentos/biossíntese , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Invasividade Neoplásica/genética , Quinolonas/farmacologia , Reação em Cadeia da Polimerase em Tempo Real , Receptores CXCR4/genética , Sulfonas/farmacologia , Transcriptoma
12.
Vojnosanit Pregl ; 73(3): 239-45, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27295907

RESUMO

BACKGROUND/AIM: Not only that ultrasound makes the difference between cystic and solid changes in breast tissue, as it was the case at the beginning of its use, but it also makes the differential diagnosis in terms of benign-malignant. The aim of this study was to assess the role of sonography in the diagnosis of palpable breast masses according to the American College of Radiology Ultrasonographic Breast Imaging Reporting and Data System (BI-RADS) and to correlate the BI-RADS 4 and BI-RADS 5 category with pathohistological findings. METHODS: A retrospective study was conducted with the breast sonograms of 30 women presented with palpable breast masses found to be mammography category BI-RADS 0 and ultrasonographic BI-RADS categories 4 and 5. The sonographic categories were correlated with pathohistological findings. RESULTS: Surgical biopsy in 30 masses revealed: malignancy (56.7%), fibroadenoma (26.7%), fibrocystic dysplasia with/without atypia (10/6), lipoma (3.3%) and intramammary lymph node (3.3%). Correlation between BI-RADS categories and pathohistological findings was found (P < 0.05). All BI-RADS 5 masses were malignant, while in BI-RADS 4A category fibroadenomas dominated. A total of 53.8% of all benign lesions were found in women 49 years of age or younger as compared with 35.3% of all malignancies in this group (p < 0.05). CONCLUSION: Ultrasonography BI-RADS improved classification of breast masses. The ultrasound BI-RADS 4 (A, B, C) and BI-RADS 5 lesions should be worked-up with biopsy.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Carcinoma Ductal de Mama/diagnóstico por imagem , Carcinoma Intraductal não Infiltrante/diagnóstico por imagem , Carcinoma Lobular/diagnóstico por imagem , Fibroadenoma/diagnóstico por imagem , Doença da Mama Fibrocística/diagnóstico por imagem , Lipoma/diagnóstico por imagem , Linfonodos/diagnóstico por imagem , Adulto , Idoso , Biópsia , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Carcinoma Intraductal não Infiltrante/patologia , Carcinoma Lobular/patologia , Estudos de Coortes , Diagnóstico Diferencial , Feminino , Fibroadenoma/patologia , Doença da Mama Fibrocística/patologia , Humanos , Lipoma/patologia , Linfonodos/patologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Ultrassonografia Mamária
13.
Iran J Radiol ; 13(1): e12991, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27110328

RESUMO

Inflammatory myofibroblastic tumor (IMT) is an aggressive benign mass that may arise from various tissues and organs with a great variability of histological and clinical appearances. Due to variable and nonspecific imaging findings, diagnosis of IMT is not obtained before surgery. The aim of this paper is to present CT and MRI findings during four-year follow-up of complete, spontaneous regression of IMT of the uterus. The diagnosis was made by histology and immunohistochemistry analysis of the open excisional biopsy specimen. At that time, the organ of origin was not specified. After analysis of the follow-up imaging findings and the mode of tumor regression, the uterus was proclaimed as the probable site of origin. IMT of the uterus is extremely rare and has been reported in ten cases up to now. The gradual, complete regression of uterine IMT documented by CT and MRI may contribute to understanding of its nature.

14.
Tumour Biol ; 36(11): 8773-80, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26055143

RESUMO

Cyclin D1 is one of the major cellular oncogenes, overexpressed in number of human cancers, including non-small cell lung carcinoma (NSCLC). However, it does not exert tumorigenic activity by itself, but rather cooperates with other altered oncogenes and tumor suppressors. Therefore, in the present study, we have examined mutual role of cyclin D1, KRAS, and PTEN alterations in the pathogenesis of NSCLC and their potential to serve as multiple molecular markers for this disease. CCND1 gene amplification and gene expression were analyzed in relation to mutational status of KRAS gene as well as to PTEN alterations (loss of heterozygosity and promoter hypermethylation) in NSCLC patient samples. Moreover, the effect of these co-alterations on patient survival was examined. Amplified CCND1 gene was exclusively associated with increased gene expression. Statistical analyses also revealed significant association between CCND1 overexpression and KRAS mutations in the whole group and in the groups of patients with adenocarcinoma, grade 1/2, and stage I/II. In addition, CCND1 overexpression was significantly related to PTEN promoter hypermethylation in the whole group and in the group of patients with squamous cell carcinoma and lymph node invasion. These joint alterations also significantly shortened patients' survival and were shown to be an independent factor for adverse prognosis. Overall results point that cyclin D1 expression cooperates with KRAS and PTEN alterations in pathogenesis of NSCLC, and they could serve as potential multiple molecular markers for specific subgroups of NSCLC patients as well as prognostic markers for this type of cancer.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Ciclina D1/genética , PTEN Fosfo-Hidrolase/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Biomarcadores Tumorais/biossíntese , Carcinoma Pulmonar de Células não Pequenas/patologia , Ciclina D1/biossíntese , Metilação de DNA/genética , Intervalo Livre de Doença , Amplificação de Genes , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Perda de Heterozigosidade/genética , Mutação , PTEN Fosfo-Hidrolase/biossíntese , Prognóstico , Proteínas Proto-Oncogênicas p21(ras)/biossíntese
15.
Exp Mol Pathol ; 98(1): 27-32, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25449334

RESUMO

Lung cancer is the most common cause of neoplasia-related death worldwide. Accounting for approximately 80% of all lung carcinomas, the non-small cell lung carcinoma (NSCLC) is the most common clinical form with its two predominant histological types, adenocarcinoma (ADC) and squamous cell carcinoma (SCC). Although surgical resection is the most favorable treatment for patients with NSCLC, relapse is still high, so neoadjuvant chemotherapy (NAC) is an accepted treatment modality. In this study we examined whether some of the key molecules associated with the RAS/RAF/MEK/ERK and PI3K/AKT/mTOR signaling pathways could have predictive and prognostic value for the NAC application. To that end we examined the expression status of PTEN, pAKT, pERK and loss of heterozygosity (LOH) of PTEN in two groups of NSCLC patients, those who received and those who did not receive NAC. LOH PTEN and low pERK expression is shown to be correlated with the longest survival of patients with SCC and ADC, respectively, who received NAC. These results point that the application of NAC is beneficial in the NSCLC patients with specific molecular alterations which could further help to improve constant search for the druggable molecular targets used in personalized therapy.


Assuntos
Adenocarcinoma/mortalidade , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma de Células Escamosas/mortalidade , Neoplasias Pulmonares/mortalidade , Terapia Neoadjuvante , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Feminino , Seguimentos , Regulação Neoplásica da Expressão Gênica , Humanos , Técnicas Imunoenzimáticas , Perda de Heterozigosidade , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Invasividade Neoplásica , Estadiamento de Neoplasias , PTEN Fosfo-Hidrolase/genética , Fosfatidilinositol 3-Quinases/metabolismo , Reação em Cadeia da Polimerase , Prognóstico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Taxa de Sobrevida , Serina-Treonina Quinases TOR/metabolismo
16.
Transl Res ; 164(5): 411-23, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25016932

RESUMO

Anaplastic thyroid carcinoma (ATC) is a rare, but aggressive and chemoresistant tumor with dismal prognosis. Most ATCs harbor mutations that activate RAS/MAPK/ERK and PI3K/AKT/mTOR pathways. Therefore, we investigated and correlated the expression of phosphatase and tensin homolog, pERK, and pAKT proteins as well as mutations of BRAF, RAS, and p53 genes in samples of patients with ATC. Furthermore, we evaluated the potential of inhibition of these pathways on chemosensitization of ATC using 2 thyroid carcinoma cell lines (FRO and SW1736). Our results revealed a negative correlation between the activity of RAS-MAPK-ERK and PI3K-AKT-mTOR pathways in samples of patients. To be specific, the PI3K-AKT-mTOR pathway was suppressed in patients with activated NRAS or high pERK expression. In vitro results suggest that the inhibition of either RAS-MAPK-ERK or PI3K-AKT-mTOR components may confer sensitivity of thyroid cancer cells to classic chemotherapeutics. This may form a basis for the development of novel genetic-based therapeutic approach for this cancer type.


Assuntos
MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Carcinoma Anaplásico da Tireoide/metabolismo , Neoplasias da Glândula Tireoide/metabolismo , Proteínas ras/metabolismo , Idoso , Idoso de 80 Anos ou mais , Oxirredutases do Álcool , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos , MAP Quinases Reguladas por Sinal Extracelular/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismo , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo , Carcinoma Anaplásico da Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/tratamento farmacológico , Proteína Supressora de Tumor p53
17.
Eur J Radiol ; 83(8): 1363-7, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24894697

RESUMO

OBJECTIVES: The aim of this study was to contribute to the standardization of the numeric positive enhancement integral (PEI) values in breast parenchyma, ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) and to evaluate the significance of the difference in PEI values between IDC and parenchyma, DCIS and parenchyma and IDC and DCIS. MATERIALS AND METHODS: In the prospective trial, we analyzed the dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) of 60 consecutive patients with histologically confirmed unilateral DCIS (n=30) and IDC (n=30) and defined the PEI values (range; mean ± SD) for the lesions and the breast parenchyma. Tumor-to-non-tumor (T/NT) ratios were calculated for DCIS and IDC and compared. PEI color maps (PEICM) were created. The differences in PEI values between IDC and parenchyma and between DCIS and parenchyma were tested according to t-test. Analysis of variance (ANOVA) was used to test the differences between the mean PEI values of parenchyma, DCIS and IDC. RESULTS: IDC showed highly statistically different PEI numeric values compared to breast parenchyma (748.7 ± 32.2 vs. 74.6 ± 17.0; p<0.0001). The same applied to the differences in the group of patients with DCIS (428.0 ± 25.0 vs. 66.0 ± 10.6; p<0.0001). The difference between IDC, DCIS and parenchyma were also considered highly statistically significant (p<0.0001) and so were the T/NT ratios for IDC and DCIS (10.1 ± 2.4 vs. 6.6 ± 1.4; p<0.0001). CONCLUSIONS: PEI numeric values may contribute to differentiation between invasive and in situ breast carcinoma.


Assuntos
Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Carcinoma Intraductal não Infiltrante/patologia , Imageamento por Ressonância Magnética/métodos , Meios de Contraste , Feminino , Gadolínio DTPA , Humanos , Aumento da Imagem/métodos , Mamografia , Pessoa de Meia-Idade , Estudos Prospectivos
18.
Int J Clin Exp Pathol ; 7(4): 1826-33, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24817989

RESUMO

Multiple cancers represent 2.42% of all human cancers and are mainly double or triple cancers. Many possible causes of multiple malignancies have been reported such as genetic alterations, exposure to anti-cancer chemotherapy, radiotherapy, immunosuppressive therapy and reduced immunologic response. We report a female patient with multiple sclerosis and quadruple cancers of different embryological origin. Patient was diagnosed with stage III (T3, N1a, MO) medullary thyroid carcinoma (MTC), multicentric micropapillary thyroid carcinoma, scapular and lumbar melanomas (Clark II, Breslow II), and lobular invasive breast carcinoma (T1a, NO, MO). All tumors present in our patient except micropapillary thyroid carcinomas were investigated for gene alterations known to have a key role in cancer promotion and progression. Tumor samples were screened for the p16 alterations (loss of heterozygosity and homozygous deletions), loss of heterozygosity of PTEN, p53 alterations (mutational status and loss of heterozygosity) and mutational status of RET, HRAS and KRAS. Each type of tumor investigated had specific pattern of analyzed genetic alterations. The most prominent genetic changes were mutual alterations in PTEN and p53 tumor suppressors present in breast cancer and two melanomas. These co-alterations could be crucial for promoting development of multiple malignancies. Moreover the insertion in 4(th) codon of HRAS gene was common for all tumor types investigated. It represents frameshift mutation introducing stop codon at position 5 which prevents synthesis of a full-length protein. Since the inactivated RAS enhances sensitivity to tamoxifen and radiotherapy this genetic alteration could be considered as a good prognostic factor for this patient.


Assuntos
Azatioprina/uso terapêutico , Neoplasias Ósseas/genética , Neoplasias da Mama/genética , Imunossupressores/uso terapêutico , Esclerose Múltipla/complicações , Esclerose Múltipla/tratamento farmacológico , Mutação/genética , Neoplasias da Glândula Tireoide/genética , Adulto , Azatioprina/efeitos adversos , Neoplasias Ósseas/terapia , Neoplasias da Mama/terapia , Carcinoma Ductal de Mama/genética , Carcinoma Ductal de Mama/terapia , Carcinoma Medular/genética , Carcinoma Medular/terapia , Carcinoma Papilar/genética , Carcinoma Papilar/terapia , Terapia Combinada , Inibidor p16 de Quinase Dependente de Ciclina , Feminino , Humanos , Imunossupressores/efeitos adversos , Melanoma/genética , Melanoma/terapia , Proteínas de Neoplasias/genética , PTEN Fosfo-Hidrolase/genética , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas c-ret/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Neoplasias da Glândula Tireoide/terapia , Proteína Supressora de Tumor p53/genética , Proteínas ras/genética
19.
Diagn Interv Radiol ; 19(6): 463-70, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24047722

RESUMO

PURPOSE: We aimed to prospectively assess the role of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in the evaluation of predictive factors for breast conservative surgery during neoadjuvant chemotherapy. MATERIALS AND METHODS: Sixty-six patients were evaluated before the first treatment cycle, after the second cycle, and upon the completion of neoadjuvant chemotherapy according to largest tumor diameter, tumor volume, postcontrast enhancement, and tumor regression pattern. The patients were divided into responders (pathologic complete and near complete response) and nonresponders. Each subgroup was re-evaluated according to morphokinetic criteria for identification of candidates for breast conservative surgery. RESULTS: In responders (n=27), the lesion size upon the completion of neoadjuvant chemotherapy was significantly smaller compared to nonresponders (1.5 ± 0.6 vs. 3.2 ± 0.9 cm; P < 0.001), as was the volume (1.2 vs. 11.0 cm(3); P < 0.001). The measured lesion size did not differ from the histologic size (1.5 ± 0.6 vs. 1.2 ± 0.6 cm; P = 0.09) and had a high correlation (r=0.93). In responders, the following parameters were significantly different before and after neoadjuvant chemotherapy: size (3.6 ± 1.4 to 1.5 ± 0.6 cm; P < 0.001), volume (17.6 to 1.2 cm(3); P < 0.001), predominant concentric regression, plateau and continuous time-intensity curves (P < 0.001). DCE-MRI has the sensitivity of 87% and the accuracy of 77% to identify candidates for breast conservative surgery. CONCLUSION: Selected morphokinetic DCE-MRI parameters may contribute to the multidisciplinary decision when considering the selection of candidates for breast conservative surgery.


Assuntos
Neoplasias da Mama/patologia , Imageamento por Ressonância Magnética , Mastectomia Segmentar , Seleção de Pacientes , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/tratamento farmacológico , Carcinoma Ductal de Mama/patologia , Carcinoma Ductal de Mama/cirurgia , Carcinoma Lobular/tratamento farmacológico , Carcinoma Lobular/patologia , Carcinoma Lobular/cirurgia , Meios de Contraste , Feminino , Seguimentos , Humanos , Imageamento Tridimensional , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estudos Prospectivos
20.
Iran J Radiol ; 10(2): 99-102, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24046788

RESUMO

BACKGROUND: Adequate diagnosis of ductal carcinoma in situ (DCIS) could lead to efficacious treatment. Due to the fact that DCIS lesions can progress to invasive carcinomas and that the sensitivity of the standard examination - mammography - is between 70 and 80%, use of a more sensitive diagnostic tool was needed. In detection of DCIS, contrast-enhanced magnetic resonance imaging (CE-MRI) has the sensitivity up to 96%. OBJECTIVES: Morphological features and kinetic parameters were evaluated to define the most regular morphological, kinetic and morpho-kinetic patterns on MRI assessment of breast ductal carcinoma in situ (DCIS). PATIENTS AND METHODS: We retrospectively assessed eighteen patients with 23 histologically confirmed lesions (mean age, 52.4 ± 10.5 years). All patients were clinically and mammographically examined prior to MRI examination. RESULTS: DCIS appeared most frequently as non-mass-like lesions (12 lesions, 52.17%). The differences in the frequency of lesion types were statistically significant (P<0.05). The following morphological patterns were detected: A: no specific morphologic features, B: linear/branching enhancement, C: focal mass-like enhancement, D: segmental enhancement, E: segmental enhancement in triangular shape, F: diffuse enhancement, G: regional heterogeneous enhancement in one quadrant not conforming to duct distribution and H: dotted or granular type of enhancement with patchy distribution. The difference in the frequency of the proposed patterns was statistically significant (P<0.05). There were eight lesions with mass enhancement, and six with segmental lesions: regional and triangular. There was no statistically significant difference in the frequency of enhancement curve types (P>0.05). There was no significant difference in the frequency of morpho-kinetic patterns. CONCLUSION: Non-mass-like lesions, lesions with focal or segmental distribution, with a "plateau" enhancement curve type were the most frequent findings of DCIS lesions on MRI.

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