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1.
Medicine (Baltimore) ; 99(28): e20938, 2020 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-32664092

RESUMO

RATIONALE: Primary adrenal lymphoma (PAL) is an extremely rare and highly invasive malignant disease. Imaging examination usually shows bilateral adrenal involvement with large tumor masses and local infiltration. However, it is unclear how lymphoma dynamically develops into huge tumor masses in the adrenal glands. The overall survival rate of PAL is generally poor, and the underlying mechanism might be related to prooncogenic mutation but not fully elucidated. PATIENT CONCERNS: A 52-year-old woman complaining of a large mass in the left adrenal region for 1 month was admitted to our department. DIAGNOSIS: Computed tomography firstly showed a huge mass (8.9 × 7.5 cm) in the left adrenal gland and diffusely enlarged right adrenal gland. A month later, the mass in the left adrenal gland further enlarged (9.5x7.5 cm) with infiltration of the left renal artery and retroperitoneal lymphadenopathy, and the right adrenal gland rapidly progressed into a huge mass (8.0x4.7 cm). Additionally, her chest computed tomography revealed mediastinal and bilateral hilar lymphadenopathy. Then an adrenal biopsy confirmed the diagnosis of diffuse large B-cell lymphoma, nongerminal center B-cell type, stage IV by Ann Arbor staging system. Immunohistochemistry showed positivity for Ki-67 (approximately 90%), BCL2 (approximately 80%) and MYC (approximately 70%) double-expressor lymphoma. INTERVENTIONS: The patient's condition progressed rapidly, there was no opportunity to use pathology-based chemotherapy. Dexamethasone was given intravenously by thoracic and intraperitoneal injection; antibiotics and supporting treatment were also given. OUTCOMES: The patient's condition progressed rapidly, with the development of malignant chest and abdominal cavity fluid and lung infection, and eventually developed septic shock and respiratory failure. She responded poorly to treatment regimens, and eventually died 8 days after the diagnosis of PAL. LESSONS: PAL grows progressively throughout the adrenal glands, high Ki-67 positivity and BCL2/ MYC co-expression predict rapid progress and poor prognosis.


Assuntos
Neoplasias das Glândulas Suprarrenais/patologia , Linfoma Difuso de Grandes Células B/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica
2.
Bull Cancer ; 107(5S): S49-S55, 2020 Jun.
Artigo em Francês | MEDLINE | ID: mdl-32620207

RESUMO

Local and systemic immunotherapies are used for the management of bladder cancer in daily practice. BCG has been administered for almost 40 years in patients with non-muscle invasive bladder cancer (NMIBC). Despite its efficacy, disease progression is observed in nearly 30% of patients. Given the antitumor activity of immune checkpoint inhibitors in metastatic setting, these therapies are currently investigated in NMIBC. Pembrolizumab is now approved by the Food and Drug Administration (FDA) for the treatment of patients with BCG-unresponsive, high-risk, NMIBC with carcinoma in situ with or without papillary tumors who are ineligible for or have not elected to undergo cystectomy. Several phase 3 trials are ongoing to investigate the efficacy of PD(L)1 inhibitors combined with BCG such as ALBAN study in France.


Assuntos
Imunoterapia , Neoplasias da Bexiga Urinária/terapia , Adjuvantes Imunológicos/uso terapêutico , Administração Intravesical , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/uso terapêutico , Vacina BCG/uso terapêutico , Humanos , Invasividade Neoplásica , Nivolumabe/uso terapêutico , Neoplasias da Bexiga Urinária/patologia
3.
Bull Cancer ; 107(5S): eS1-eS7, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32620210

RESUMO

BACKGROUND: The standard treatment in first line of advanced or metastatic urothelial bladder cancer (MBC) is the association of Gemcitabine and Cisplatin (GC). Avelumab, an anti-PD-L1 agent, has recently demonstrated efficacy. The objective is to evaluate the combination of these 3 agents. METHODS: This phase II randomized open-label study, evaluated if GC-avelumab increases response rate and duration of response of patients in 1st line treatment for MBC compared to GC. Severe toxicities should not overlap and be acceptable. The two co-primary end points are the objective response rate and the incidence of severe toxicity after six cycles of treatment. The study will recruit 90 participants, randomized in two arms (1:2), GC (gemcitabine 1 000 mg/m2/j, J1,J8, Cisplatine 70 mg/m2, J1 = J21), and GC-avelumab (10 mg/Kg/3 semaines). Randomization will be stratified on Karnofsky status (≥ 80 % vs. < 80 %) and visceral vs non visceral metastases. The duration of the inclusion period is 24 months, with a duration of participation of each patient of 18 months and a total study duration of 42 months. DISCUSSION: If both efficacy and safety of the association of GC+avelumab are in the range of acceptable through this specific study design, this will support a subsequent randomized phase III study comparing both arms with an overall survival end-point. In addition, the evaluation of predictive parameters to be confirmed (e.g. the impact of tumor PD-L1 expression) or other immunological parameters, may support a selection of the population. NCT number : NCT03324282.


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma de Células de Transição/tratamento farmacológico , Cisplatino/administração & dosagem , Ensaios Clínicos Fase II como Assunto/métodos , Desoxicitidina/análogos & derivados , Estudos Multicêntricos como Assunto/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Carcinoma de Células de Transição/patologia , Desoxicitidina/administração & dosagem , Humanos , Invasividade Neoplásica , Estudos Prospectivos , Neoplasias da Bexiga Urinária/patologia
4.
Bull Cancer ; 107(5S): eS8-eS15, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32620213

RESUMO

BACKGROUND: Neoadjuvant cisplatin-based chemotherapy (NAC) is the standard of care in localized muscle-invasive bladder cancer (MIBC). However, 60-70% of patients have residual tumor after NAC. Based on the overall response rate observed in the metastatic setting, ddMVAC is the most commonly used NAC regimen in Europe. The emergence of immune checkpoint inhibitor (ICI) in the metastatic setting raises the question if the combination of chemo plus ICI could increase the pCR rate. METHODS/DESIGN: NEMIO is a French open-label randomized phase I/II trial assessing in the neoadjuvant setting the combination of ddMVAC plus durvalumab alone or with tremelimumab: 4 cycles of ddMVAC/2 weeks + 2 cycles of Durvalumab +/- Tremelimumab/4 weeks. Cystectomy is performed 4-8 weeks after the last dose of ddMVAC. Six pts will be included in each arm in a safety run-in cohort to evaluate the toxicity rate. Each arm will be expanded to a maximum of 60 pts. The primary endpoint of the safety run-in phase will be the rate of grade 3/4 treatment-related adverse events G3/4 TRAE. The primary endpoint of the phase II will be the pathological response rate and G 3/4 TRAE. Exploratory endpoints will include biomarkers of response and resistance to the combo. A total of 120 patients will be included in 15 French centers and we expect the recruitment to be completed in 2021. DISCUSSION: NEMIO trial will assess for the first time the tolerance and the efficacy of ddMVAC regimen associated with checkpoints inhibitors as neoadjuvant treatment in localized MIBC. NCT number: NCT03549715. Registered on June 8, 2018.


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma de Células de Transição/tratamento farmacológico , Ensaios Clínicos Fase II como Assunto/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células de Transição/patologia , Cisplatino/uso terapêutico , Doxorrubicina/uso terapêutico , Humanos , Metotrexato/uso terapêutico , Terapia Neoadjuvante , Invasividade Neoplásica , Resultado do Tratamento , Neoplasias da Bexiga Urinária/patologia , Vimblastina/uso terapêutico
5.
Anticancer Res ; 40(6): 3239-3246, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32487618

RESUMO

BACKGROUND/AIM: Non-structural maintenance of chromosomes condensin I complex subunit H (NCAPH) is implicated in correct chromosome condensation and segregation during mitosis. However, the functional role of NCAPH in the pathogenesis of non-small-cell lung cancer (NSCLC) remains unclear. The aim of this study was to elucidate the role of NCAPH in NSCLC cells. MATERIALS AND METHODS: A549 and H1299 NSCLC cells were transfected with small-interfering RNA (siRNA) against NCAPH. Subsequently, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, colony-formation assay and flow cytometry analysis were performed to reveal the role of NCAPH in NSCLC cells. In addition, migration and invasion assay were also performed. RESULTS: NCAPH knockdown inhibited cell proliferation, induced cell-cycle arrest at G2/M phase, and prevented colony formation, migration and invasion by NSCLC cells. CONCLUSION: NCAPH is involved in NSCLC progression and development, and may be a potential therapeutic target for NSCLC treatment.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Proteínas de Ciclo Celular/metabolismo , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Proteínas Nucleares/metabolismo , Células A549 , Carcinoma Pulmonar de Células não Pequenas/genética , Pontos de Checagem do Ciclo Celular/fisiologia , Proteínas de Ciclo Celular/biossíntese , Proteínas de Ciclo Celular/deficiência , Proteínas de Ciclo Celular/genética , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Técnicas de Silenciamento de Genes , Humanos , Neoplasias Pulmonares/genética , Invasividade Neoplásica , Proteínas Nucleares/biossíntese , Proteínas Nucleares/deficiência , Proteínas Nucleares/genética , RNA Interferente Pequeno/administração & dosagem , RNA Interferente Pequeno/genética , Transfecção , Regulação para Cima
6.
Anticancer Res ; 40(6): 3287-3296, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32487624

RESUMO

BACKGROUND/AIM: Transforming growth factor ß1 (TGF-ß1) is an important epithelial-mesenchymal transition (EMT) activator that regulates the expression of E-cadherin and vimentin through Smad signalling. Tranilast is an anti-allergic drug that inhibits TGF-ß1, and is used in the treatment of keloids and hypertrophic scars. We investigated whether tranilast inhibits TGF-ß1-induced EMT and invasiveness in human non-small cell lung cancer cell lines. MATERIALS AND METHODS: We examined the effects of tranilast treatment on EMT markers, TGF-ß1/Smad signalling, and cell invasiveness in A549 and PC14 cells. Tumours from a mouse orthotopic lung cancer model with or without tranilast treatment were also immunohistochemically evaluated. RESULTS: Tranilast increased E-cadherin expression via Smad4 suppression and inhibited cell invasion in TGF-ß1-stimulated cells. Tranilast treatment of the in vivo mouse model reduced the pleural dissemination of cancer cells and suppressed vimentin and Smad4 expression. CONCLUSION: Tranilast inhibited TGF-ß1-induced EMT and cellular invasion/metastasis by suppressing Smad4 expression in cancer cells.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Neoplasias Pulmonares/genética , Proteína Smad4/genética , Fator de Crescimento Transformador beta1/efeitos dos fármacos , ortoaminobenzoatos/uso terapêutico , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Linhagem Celular Tumoral , Humanos , Neoplasias Pulmonares/patologia , Masculino , Camundongos , Camundongos Nus , Invasividade Neoplásica , Metástase Neoplásica , ortoaminobenzoatos/farmacologia
7.
Zhonghua Zhong Liu Za Zhi ; 42(6): 449-455, 2020 Jun 23.
Artigo em Chinês | MEDLINE | ID: mdl-32575939

RESUMO

Objective: To investigate the high resolution CT (HRCT) features of lung adenocarcinoma for differentiating synchronous multiple lung adenocarcinoma from lung adenocarcinoma with intrapulmonary metastasis. Methods: The clinical and imaging features of 131 lesions from 62 patients of synchronous multiple primary lung adenocarcinoma (primary group) and 67 lesions from 31 patients of lung adenocarcinoma with intrapulmonary metastases (metastasis group) were retrospectively analyzed. According to the types of lesion, including pure ground glass nodule (pGGN), mixed ground glass nodule (mGGN) and solid nodule (SN), the image feature matching types of patients were divided into 7 types. The differences of image feature matching types between the primary group and the metastasis group were compared. Multiple lesions in the lung of patients were classified into the main lesion and the concomitant lesions according to their size. The differences including the size of the main lesion and the concomitant lesion (long diameter of nodule, long diameter of solid component in nodule), whether it contains ground glass components in nodule, shape, lobulation, margin, spiculation, bubble-like lucency, pleural retraction and pleural attachment were recorded and analyzed. The differences of image features of main lesion and the concomitant lesion in the primary group and the metastasis group were compared. Results: The image feature matching types of pGGN + mGGN and mGGN + mGGN were more common in the primary group, and the ground glass component contained pGGN or mGGN was accounted for 62.9%(39/62). At least one lesion containing the ground glass component was accounted for 96.8% (60/62). There were two types in metastatic groups, mGGN+ SN and SN+ SN accounting for 6.5% (2/31) and 93.5% (29/31), respectively. There were significant differences in image feature matching types between the primary group and metastatic group (P<0.01). Univariate analysis of the main lesions between the two groups showed that the gender, smoking history, long diameter of the main lesion, long diameter of the solid component, the ground glass component and pleural attachment were statistically different (P<0.05). Further analysis by multivariate logistic regression showed that the male (OR=5.742, P=0.010), SN (OR=41.291, P<0.01) and pleural attachment (OR=9.288, P=0.001) were the three significant risk factors associated with the main lesions in metastasis group.The most common concomitant lesions in primary group were pGGN, containing the ground glass component. However, all of the concomitant lesions in the metastatic group were SN (P<0.01), showing round lesions with well-defined margin, attaching the pleura (P<0.05). Conclusions: The HRCT features of lung adenocarcinoma can differentiate synchronous multiple lung adenocarcinoma from lung adenocarcinoma with intrapulmonary metastasis. At least one lesion contains ground glass components (pGGN or mGGN) in synchronous multiple primary lung adenocarcinoma, while SN is more common in lung adenocarcinoma with lung metastasis. Lung cancer with intrapulmonary metastasis can be considered when the main lesion is SN with pleural attachment and the intrapulmonary accompanying lesion is also solid nodules without lobular, speculation and bubble-like lucency.


Assuntos
Adenocarcinoma de Pulmão/diagnóstico por imagem , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Nódulos Pulmonares Múltiplos/diagnóstico por imagem , Nódulos Pulmonares Múltiplos/patologia , Neoplasias Primárias Múltiplas/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Adenocarcinoma , Humanos , Pulmão/diagnóstico por imagem , Pulmão/patologia , Masculino , Invasividade Neoplásica , Interpretação de Imagem Radiográfica Assistida por Computador , Estudos Retrospectivos
8.
Am J Med Sci ; 359(6): 365-371, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32498943

RESUMO

BACKGROUND: It has been reported that miR-294 is highly expressed in hepatocellular carcinoma (HCC) tissues and cells. However, the potential role of miR-294 in the pathogenesis of HCC remains unclear. This study aimed to explore the role of miR-294 in HCC and the potential mechanism involved in this process. MATERIALS AND METHODS: Reverse transcription polymerase chain reaction was performed to determine the expression of miR-294 in HCC tissues and cell lines. Following the overexpression or knockdown of miR-294, the proliferation, migration, and invasion abilities of cells were determined using Cell Counting Kit-8 (CCK-8), wound healing and transwell assays, respectively. The phosphorylation of JNK and ERK was determined through western blotting. Furthermore, HCC cells were treated with JNK inhibitor SP600125 or ERK inhibitor U0126 and transfected with miR-294 mimics or negative control. Subsequently, the phosphorylation of JNK and ERK was evaluated and the proliferation, migration and invasion abilities of HCC cells were also determined. RESULTS: The expression of miR-294 was significantly increased in HCC tissues and cell lines. Following the overexpression of miR-294, proliferation, migration, and invasion were promoted in the SSMC-7721 cell line, and the phosphorylation of JNK and ERK was increased, while silencing of miR-294 led to the opposite result. Use of the JNK or ERK inhibitor to treat SSMC-7721 cells transfected with miR-294 mimics decreased the phosphorylation of JNK and ERK and inhibited the proliferation, migration and invasion abilities of cells. CONCLUSIONS: miR-294 is important for the development of HCC in terms of the biological activities of cells, and may be a novel therapeutic target for HCC.


Assuntos
Carcinoma Hepatocelular/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Neoplasias Hepáticas/metabolismo , MAP Quinase Quinase 4/metabolismo , Sistema de Sinalização das MAP Quinases , MicroRNAs/metabolismo , Idoso , Antracenos/farmacologia , Butadienos/farmacologia , Carcinoma Hepatocelular/genética , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Feminino , Regulação Neoplásica da Expressão Gênica , Células Hep G2 , Humanos , Neoplasias Hepáticas/genética , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Invasividade Neoplásica , Nitrilos/farmacologia , Fosforilação , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transfecção , Regulação para Cima
10.
Medicine (Baltimore) ; 99(26): e20594, 2020 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-32590735

RESUMO

The recently published 8th edition of the tumor node and metastasis Classification of Lung Cancer proposes using the maximum dimension of the solid component of a ground glass nodule (GGN) for the T categorization. However, few studies have investigated the collection of this information when using mediastinal window settings. In this study, we evaluated tumor measurement data obtained from computed tomography (CT) scans when using mediastinal window settings.This study included 202 selected patients with persistent, partly solid GGNs detected on thin-slice CT after surgical treatment between 2004 and 2013. We compared the differences in tumor diameters measured by 2 different radiologists using a repeated-measures analysis of variance. We divided the patients into 2 groups based on the clinical T stage (T1a+T1b vs T1c) and estimated the probability of overall survival (OS) and disease-free survival (DFS) using Kaplan-Meier curves.The study included 94 male and 108 female patients. The inter-reviewer differences between tumor diameters were significantly smaller when the consolidation to maximum tumor diameter ratio was ≤0.5. The 2 clinical groups classified by clinical T stage differed significantly with respect to DFS when using the mediastinal window settings. However, no significant differences in OS or DFS were observed when using the lung window setting.Our study yielded 2 major findings. First, the diameters of GGNs could be measured more accurately using the mediastinal window setting. Second, measurements obtained using the mediastinal window setting more clearly depicted the effect of clinical T stage on DFS.


Assuntos
Adenocarcinoma de Pulmão/diagnóstico por imagem , Neoplasias Pulmonares/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Adenocarcinoma de Pulmão/mortalidade , Adenocarcinoma de Pulmão/patologia , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Invasividade Neoplásica , Estudos Retrospectivos
11.
Medicine (Baltimore) ; 99(26): e20644, 2020 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-32590739

RESUMO

The present study aimed to investigate the correlation between ultrasonographic features, basic fibroblast growth factor (bFGF), and the local invasiveness of papillary thyroid carcinoma (PTC).A total of 350 samples of thyroid nodules were collected. Routine ultrasonography was performed before the operation and routine pathological diagnosis and bFGF detection were performed after the operation.'These 350 samples of thyroid nodules included 90 samples of nodular goiter, 36 samples of focal thyroiditis, and 224 samples of PTC. A total of 326 thyroid nodules were examined for bFGF. The results revealed that the difference in the expression of bFGF between the benign and malignant groups was statistically significant (P < .05) and the difference in the positive expression of bFGF between the invasive and non-invasive PTC groups was statistically significant (P < .05).Whether the shape of PTC is regular or not and whether there is micro-calcification in PTC and other ultrasonographic features, the size and location of the lesions and the age of the patient help make a preliminary prediction of local invasiveness before the operation. Postoperative detection of bFGF is helpful for further risk assessments of PTC.


Assuntos
Fator 2 de Crescimento de Fibroblastos/metabolismo , Câncer Papilífero da Tireoide/diagnóstico por imagem , Câncer Papilífero da Tireoide/metabolismo , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/metabolismo , Adulto , Fatores Etários , Idoso , Biomarcadores Tumorais/metabolismo , Feminino , Bócio/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estudos Prospectivos , Câncer Papilífero da Tireoide/patologia , Neoplasias da Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/metabolismo , Tireoidite/metabolismo , Ultrassonografia , Adulto Jovem
12.
Anticancer Res ; 40(6): 3031-3037, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32487596

RESUMO

Perineural invasion (PNI) is detected in 7.0-35.1% of cervical carcinomas. This histological finding correlates with cervical invasion, lymph-vascular space invasion (LVSI), tumor size, positive resection margins, parametrial invasion, node metastases and advanced stage. Some authors have reported that PNI has no prognostic relevance, others have found that PNI is related to disease-free survival or overall survival (OS) at univariate analysis, and others have observed that it is an independent poor prognostic factor for OS. The evaluation of PNI status should be included in the decision-making process for planning adjuvant treatment. PNI has been found in 7.6-52.4% of vulvar carcinomas. This feature, which is strongly associated with depth of invasion, LVSI, tumor size, advanced stage and nodal involvement, is an independent prognostic variable for the risk of recurrence and death in most series. PNI should be evaluated routinely in histopathology reports of vulvar carcinoma and could help clinicians to tailor adjuvant treatment.


Assuntos
Quimioterapia Adjuvante/métodos , Invasividade Neoplásica/patologia , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/cirurgia , Neoplasias Vulvares/tratamento farmacológico , Neoplasias Vulvares/cirurgia , Feminino , Humanos , Prognóstico , Neoplasias do Colo do Útero/complicações , Neoplasias do Colo do Útero/patologia , Neoplasias Vulvares/complicações , Neoplasias Vulvares/patologia
13.
Anticancer Res ; 40(6): 3081-3089, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32487602

RESUMO

BACKGROUND: Grade I meningiomas are generally benign and non-invasive whereas Grade II (atypical) and Grade III (malignant) meningiomas tend to be invasive with a high risk of recurrence. SPARC, secreted protein, acidic and rich in cysteine, is a multifunctional glycoprotein which has been proposed to be a potential diagnostic marker of invasive meningiomas. There has been increased reporting of atypical meningiomas since the current World Health Organization (WHO) included brain invasion as a grading criterion for classification of these particular meningiomas. MATERIALS AND METHODS: The aim of this study was to re-evaluate any correlation between immunohistochemical expression of SPARC in 34 meningiomas of various grades using the current classification (2016). We had previously classified these cases using the 2002 WHO criteria. RESULTS: There is no correlation between expression of SPARC and invasion in different grades of meningioma. CONCLUSION: SPARC does not appear to be a good predictor of invasion in meningiomas.


Assuntos
Neoplasias Meníngeas/metabolismo , Meningioma/metabolismo , Osteonectina/biossíntese , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Imuno-Histoquímica , Masculino , Neoplasias Meníngeas/patologia , Meningioma/patologia , Pessoa de Meia-Idade , Gradação de Tumores , Invasividade Neoplásica , Osteonectina/metabolismo , Adulto Jovem
14.
Anticancer Res ; 40(6): 3119-3128, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32487606

RESUMO

BACKGROUND/AIM: Myoferlin (MYOF) has emerged as an oncogenic protein in various human cancer types. This study was conducted to investigate comprehensively the expression and functional properties of MYOF in clear-cell renal-cell carcinoma (ccRCC) with respect to its value as diagnostic biomarker and therapeutic target. MATERIALS AND METHODS: mRNA and protein expression of MYOF were assessed by quantitative polymerase chain reaction and immunohistochemistry. siRNA-mediated knockdown of MYOF was performed in the RCC cell line ACHN followed by proliferation, migration and invasion assays. RESULTS: MYOF mRNA and protein expression were significantly up-regulated in ccRCC. Higher mRNA levels were measured in advanced tumors. MYOF protein expression was increased in tumors with higher histological grades, and those with positive lymph node and surgical margin status. MYOF knockdown led to reduction of migration and invasion in ACHN cells, whereas expression of angiogenesis-associated genes tyrosine-protein kinase receptor-2 (TIE2), angiopoietin 2 (ANG2) and caveolin-1 (CAV1) was up-regulated following knockdown. CONCLUSION: MYOF may serve as a diagnostic biomarker of tumor progression and a potential therapeutic target in ccRCC.


Assuntos
Proteínas de Ligação ao Cálcio/metabolismo , Carcinoma de Células Renais/genética , Neoplasias Renais/genética , Proteínas de Membrana/metabolismo , Proteínas Musculares/metabolismo , Carcinoma de Células Renais/patologia , Movimento Celular , Feminino , Humanos , Neoplasias Renais/patologia , Masculino , Invasividade Neoplásica
15.
Medicine (Baltimore) ; 99(22): e20615, 2020 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-32481476

RESUMO

The aim of the study was to evaluate the potential role of circulating tumor cell (CTC) detection in the surgical assessment of renal cell carcinoma (RCC) patients with thrombi.Nine patients diagnosed with renal mass and thrombi were enrolled from June 2018 to January 2019. Blood samples were collected for CTC detection using SE-iFISH assay. CD45, DAPI, programmed death ligand 1, and fluorescence in situ hybridization with the centromere of chromosome 8 (CEP8) were immune-stained for analysis. Patient demographics, clinical features, pathological characteristics, and CTC detection results were extracted for analysis.Seven of 9 patients (77.8%) had 12 detectable CTCs, 5 of which were with CEP8-positive signal ≥5 and the others were CEP8-positive signal = 3. All 3 patients (100%) with IVC invasion had detectable CTCs, whereas CTCs were detected in 4 of 6 patients (66.7%) without IVC invasion. CEP8 analysis revealed that CTCs in IVC invasion patients were all of CEP8-positive signal ≥5 status, whereas only half of the CTCs in patients without IVC invasion were of CEP8-positive signal ≥5 pattern.In conclusion, both CTC subtype and total CTC number may serve as a marker for predicting inferior vena cava invasion in RCC patients.


Assuntos
Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , Invasividade Neoplásica/patologia , Células Neoplásicas Circulantes/patologia , Trombose/patologia , Veia Cava Inferior/patologia , Adulto , Idoso , Biomarcadores Tumorais/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
16.
Braz J Med Biol Res ; 53(7): e9029, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32520206

RESUMO

This study examined the expression and potential mechanism of microRNA (miRNA)-424-5p in nasopharyngeal carcinoma (NPC). NPC tissues were collected from 40 patients who were enrolled in the study, and skin samples were collected from 26 healthy subjects during plastic surgery as controls. We performed various in vitro assays using miR-424-5p to examine its function in primary NPC-1 cells. Bioinformatics was employed to analyze potential target genes and signaling pathways of miR-424-5p. We found that miR-424-5p expression in NPC tissues is downregulated and negatively correlated with lymph node metastasis and clinical staging. Expression of miR-424-5p in NPC cells was also downregulated, and transfection with miR-424-5p mimics inhibited proliferation, migration, and invasion of NPC-1 cells. Bioinformatics identified the AKT3 gene as a potential target of miR-424-5p and dual luciferase assays confirmed this finding. Upregulation of AKT3 expression rescued the inhibitory effect of miR-424-5p on the proliferation, migration, and invasion. Our results suggest that miR-424-5p inhibited the proliferation, migration, and invasion of NPC cells by decreasing AKT3 expression.


Assuntos
Regulação Neoplásica da Expressão Gênica , MicroRNAs/metabolismo , Carcinoma Nasofaríngeo/metabolismo , Neoplasias Nasofaríngeas/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Adulto , Idoso , Animais , Western Blotting , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Feminino , Humanos , Masculino , Camundongos , MicroRNAs/genética , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/genética , Invasividade Neoplásica , Proteínas Proto-Oncogênicas c-akt/genética , Reação em Cadeia da Polimerase em Tempo Real , Transdução de Sinais
17.
Medicine (Baltimore) ; 99(21): e20238, 2020 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-32481300

RESUMO

OBJECTS: The present study aimed to identify the clinicopathological characteristics of colorectal cancer (CRC) with invasive micropapillary components (IMPCs) and the relationship between different amounts of micropapillary components and lymph node metastasis. METHODS: A cohort of 363 patients with CRC who underwent surgical treatment in the Second Affiliated Hospital of Zhejiang University School of Medicine between January 2013 and December 2016 were retrospectively reviewed. We compared the clinicopathological characteristics, including survival outcomes and immunohistochemical profiles (EMA, MUC1, MLH1, MSH2, MSH6, and PMS2), between CRC with IMPCs and those with conventional adenocarcinoma (named non-IMPCs in this study). Logistic regression was used to identify the association between IMPCs and lymph node invasion. A multivariate analysis was performed using the Cox proportional hazard model to evaluate significant survival predictors. RESULTS: Among 363 patients, 76 cases had IMPCs, including 22 cases with a lower proportion of IMPCs (≤5%, IMPCs-L) and 54 cases with a higher proportion (>5%, IMPCs-H). Compared to the non-IMPC group, the IMPC group (including both IMPC-L and IMPC-H) had a lower degree of tumor differentiation (P = .000), a higher N-classification (P = .000), more venous invasion (P = .019), more perineural invasion (P = .025) and a later tumor node metastasis (TNM) stage (P = .000). Only tumor differentiation (P = .031) and tumor size (P = .022) were different between IMPCs-L and IMPCs-H. EMA/MUC1 enhanced the characteristic inside-out staining pattern of IMPCs, whereas non-IMPCs showed luminal staining patterns. The percentage of mismatch repair deficiency (dMMR) in the non-IMPC group was much higher than that in the IMPC group (14.7% vs 4.7%). The overall survival time of patients with IMPCs was significantly less than that of patients with non-IMPCs (P = .002), then that of IMPCs-H was lower than that of IMPCs-L (P = .030). Logistic regression revealed that patients with IMPCs were associated with lymph metastasis, regardless of the proportion of IMPCs. Multivariate analysis demonstrated both IMPCs-L and IMPCs-H as negative prognostic factors. CONCLUSIONS: IMPCs are significantly associated with lymph node metastasis and poor outcome, and even a minor component (≤5%) may render significant information and should therefore be part of the pathology report.


Assuntos
Neoplasias Colorretais/secundário , Neoplasias Colorretais/cirurgia , Linfonodos/patologia , Metástase Linfática/patologia , Adenocarcinoma/patologia , Idoso , Biomarcadores Tumorais/metabolismo , Neoplasias Encefálicas/epidemiologia , Estudos de Casos e Controles , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias/métodos , Síndromes Neoplásicas Hereditárias/epidemiologia , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida
18.
Zhonghua Zhong Liu Za Zhi ; 42(5): 383-390, 2020 May 23.
Artigo em Chinês | MEDLINE | ID: mdl-32482027

RESUMO

Objective: To examine the expression of T-box5 (TBX5) in colorectal cancer tissues and its clinical significance, and explore the effects of TBX5 on the invasion and metastasis of colorectal cancer cells and its mechanism. Methods: The expressions of TBX5 in cancer and adjacent normal tissues were tested by immunohistochemistry (IHC), and the relationship between TBX5 and clinicopathological features and prognosis of colorectal cancer was analyzed. Real-time quantitative PCR (RT-qPCR) and western blot were used to detect the expressions of TBX5 in different colorectal cancer cell lines. TBX5 overexpression plasmid was constructed and transfected into human colorectal cancer cell line HT-29, and cell counting kit-8 (CCK-8) was used to detect the activities of transfection HT-29 cells. Cell scratch test and Transwell assay were used to detect the migration and invasion abilities of cells, while RT-qPCR and western blot were used to detect the mRNA and protein expressions of PCNA, p21, p16, p27, MMP-2, MMP-7 and TIMP-1. Results: The positive rate of TBX5 protein in colorectal cancer tissues was 24.44% (22/90), significantly lower than 65.56% of adjacent normal tissues (P<0.001). The expression of TBX5 was significantly related to lymph node metastasis, depth of invasion and nerve invasion (P<0.05). The survival period of 22 patients with positive TBX5 expression was (60.2±2.4) months, better than (44.3±2.8) months of 68 patients with negative TBX5 expression (P<0.05). Among human colon cancer cell lines of HT29, SW620, SW480, LOVO and HCT116, the expression of TBX5 in HT29 cells was the weakest. After transfection, the expression of TBX5 in transfection group was significantly higher than those in control group and blank group (P=0.043 and P<0.001). Cell viability in transfection group was significantly lower than those in control group and blank group (both P<0.001). The ratio of cells in G(0)/G(1) phase was increased (P=0.009), while in G(2)/M phase was decreased (P<0.001). Cells' abilities of migration and invasion in transfection group were also significantly decreased (both P<0.001). Overexpression of TBX5 downregulated the expressions of PCNA, MMP-2 and MMP-7, while upregulated the expressions of p21, p16, p27 (P<0.05 for all). TBX5 had marginal effect on the expression of TIMP-1 (P>0.05). Conclusions: Downregulation of TBX5 is a marker of poor prognosis in patients with colorectal cancer. TBX5 may inhibit the progression of colorectal cancer by inhibiting proliferation, invasion and metastasis related genes.


Assuntos
Neoplasias do Colo/genética , Neoplasias Colorretais/genética , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Neoplasias do Colo/patologia , Neoplasias Colorretais/patologia , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Invasividade Neoplásica , Reação em Cadeia da Polimerase em Tempo Real
19.
Life Sci ; 255: 117858, 2020 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-32497635

RESUMO

At present, cervical cancer is the fourth leading cause of cancer among women worldwide with no effective treatment options. In this study we aimed to evaluate the efficacy of hypericin (HYP) encapsulated on Pluronic® P123 (HYP/P123) photodynamic therapy (PDT) in a comprehensive panel of human cervical cancer-derived cell lines, including HeLa (HPV 18-positive), SiHa (HPV 16-positive), CaSki (HPV 16 and 18-positive), and C33A (HPV-negative), compared to a nontumorigenic human epithelial cell line (HaCaT). Were investigated: (i) cell cytotoxicity and phototoxicity, cellular uptake and subcellular distribution; (ii) cell death pathway and cellular oxidative stress; (iii) migration and invasion. Our results showed that HYP/P123 micelles had effective and selective time- and dose-dependent phototoxic effects on cervical cancer cells but not in HaCaT. Moreover, HYP/P123 micelles accumulated in endoplasmic reticulum, mitochondria and lysosomes, resulting in photodynamic cell death mainly by necrosis. HYP/P123 induced cellular oxidative stress mainly via type II mechanism of PDT and inhibited cancer cell migration and invasion mainly via MMP-2 inhibition. Taken together, our results indicate a potentially useful role of HYP/P123 micelles as a platform for HYP delivery to more specifically and effectively treat cervical cancers through PDT, suggesting they are worthy for in vivo preclinical evaluations.


Assuntos
Antineoplásicos/administração & dosagem , Nanopartículas , Perileno/análogos & derivados , Fotoquimioterapia/métodos , Neoplasias do Colo do Útero/tratamento farmacológico , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Sistemas de Liberação de Medicamentos , Feminino , Células HeLa , Humanos , Micelas , Invasividade Neoplásica , Estresse Oxidativo/efeitos dos fármacos , Perileno/administração & dosagem , Perileno/farmacologia , Poloxaleno/química , Fatores de Tempo , Neoplasias do Colo do Útero/patologia
20.
Arch Endocrinol Metab ; 64(3): 251-256, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32555991

RESUMO

OBJECTIVE: We aimed to evaluate the impact of minimal extrathyroidal extension (mETE) alone on the risk of recurrence of papillary thyroid carcinoma (PTC). The impact of other factors, including multifocality, age, tumor size, and stimulated thyroglobulin (sTg) values was also assessed. SUBJECTS AND METHODS: We retrospectively analyzed 1,108 PTC patients from a medical institution, who presented tumors ≤ 4 cm without any adverse characteristics other than mETE. Patients were classified according to their response to initial treatment 12 to 24 months after surgery as proposed by the 2015 American Thyroid Association (ATA) guideline. Statistical analysis was performed using multivariate logistic regression and receiver operating characteristic (ROC) curve. RESULTS: In the multivariate logistic regression analysis, mETE did not have an impact on the response to initial treatment (p = 0.44), similar to multifocality, age, and tumor size. Initial Tg value was the only variable associated with a poor response (p < 0.01, odds ratio = 1.303, 95% confidence interval 1.25-1.36). The ROC analysis revealed that Tg was significant (area under curve = 0.8750); the cutoff value of sTg as a predictor of poor response was 10 ng/mL (sensitivity = 72.2%, specificity = 98.5%). CONCLUSION: For low-risk PTC presenting mETE as the only aggressive feature, the initial sTg value is essential to identify patients who may have a poor response after initial treatment and benefit from further treatment. Arch Endocrinol Metab. 2020;64(3):251-6.


Assuntos
Câncer Papilífero da Tireoide/patologia , Neoplasias da Glândula Tireoide/patologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Distribuição Aleatória , Estudos Retrospectivos , Câncer Papilífero da Tireoide/cirurgia , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia , Carga Tumoral , Adulto Jovem
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