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1.
Medicine (Baltimore) ; 100(29): e26650, 2021 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-34398022

RESUMO

RATIONAL: Epidermal growth factor receptor (EGFR) 20 exon insertion is the second most common EGFR aberrations in non-small cell lung cancer (NSCLC). Despite some novel EGFR inhibitors, clinically obtainable management for this subset of patients remains an unmet need. there are no previous reports of upfront combination therapy with immunotherapy and chemotherapy for lung adenocarcinoma with brain metastasis harboring EGFR 20 insertion. PATIENT CONCERNS: A 56-year-old man who sought care for dry cough was diagnosed with lung adenocarcinoma with brain metastases indicating a poor prognosis. DIAGNOSIS: Next-generation sequencing of lung biopsied tissue revealed an EGFR exon 20 in-frame insertion (P772_H773insYNP+H773Y). INTERVENTIONS: The patient started treatment of pemetrexed and carboplatin plus programmed cell death-1 inhibitor sintilimab in November 2019. OUTCOMES: The patient achieved partial responses both intra- and extra-cranially. After 6 cycles of treatment, the patient accepted sintilimab plus pemetrexed every 3 weeks as maintenance therapy, which was well-tolerated without any toxicity and is still ongoing after 18 months since initiation of 1st-line treatment. LESSONS: This is the first case report of the clinical benefit of upfront immune checkpoint inhibitors (ICIs) plus chemotherapy for a brain metastatic NSCLC patient harboring EGFR exon 20 insertion mutation. Further study is needed to validate the predictor involved in responders to ICIs-based therapy with EGFR mutations.


Assuntos
Adenocarcinoma/terapia , Neoplasias Encefálicas/terapia , Neoplasias Pulmonares/terapia , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/secundário , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/secundário , Terapia Combinada , Receptores ErbB/genética , Humanos , Imunoterapia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Resultado do Tratamento
2.
Medicine (Baltimore) ; 100(31): e26439, 2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34397793

RESUMO

ABSTRACT: This study aimed to investigate the expression and clinical significance of aurora B kinase (AURKB) gene in lung adenocarcinoma (LUAD) by collecting relevant data in Oncomine database.Firstly, mRNA expression level of AURKB in LUAD was systematically analyzed using the ONCOMINE and the cancer genome atlas databases. Then, the association between AURKB expression and clinical parameters was investigated by UALCAN. The Kaplan-Meier Plotter was used to assess the prognostic significance of AURKB.Pooled analysis showed that AURKB was frequently up-regulated expression in LUAD. In addition, immunohistochemistry showed that AURKB was highly expressed in lung adenocarcinoma tissues, while it was weakly expressed in normal tissues. Subsequently, AURKB expression was identified to be negatively associated with Overall survival (P < 1e-16), post-progression survival (P = .017), first progression (P = 9.8e-09).This study confirms that increased expression of AURKB in LUAD is associated with poor prognosis, suggesting that AURKB might be used as a promising prognostic biomarker and novel therapeutic target for LUAD.


Assuntos
Adenocarcinoma/genética , Aurora Quinase B/genética , Neoplasias Pulmonares/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/secundário , Idoso , Aurora Quinase B/metabolismo , Biologia Computacional , Mineração de Dados , Bases de Dados Genéticas , Progressão da Doença , Feminino , Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , RNA Mensageiro/metabolismo , Taxa de Sobrevida , Regulação para Cima
3.
Int J Mol Sci ; 22(11)2021 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-34200314

RESUMO

The influence of PVT1 and MALAT1 variants on colorectal cancer (CRC) susceptibility and their impact on PVT1/miRNA-186/epithelial-mesenchymal transition (EMT) and MALAT1/miRNA-101/EMT axes in CRC are unknown. We investigated the influence of PVT1 rs13255292 and MALAT1 rs3200401 on the risk of CRC and adenomatous polyps (AP), their impact on the long noncoding RNAs PVT1 and MALAT1 expression and their target miRNA-186, miRNA-101/E-cadherin pathways, along with their potential as early CRC biomarkers. Overall, 280 individuals were recruited: 140 patients with CRC, 40 patients with AP, and 100 healthy volunteers. Genotyping and serum expression profiles were assessed using qPCR. The EMT biomarker, E-cadherin, was measured by ELISA. rs3200401 was associated with increased CRC risk, whereas rs13255292 was protective. Serum PVT1 and MALAT1 were upregulated in CRC and AP patients versus healthy controls, whereas, miRNA-186, miRNA-101 and E-cadherin were downregulated in CRC versus non-CRC groups. MALAT1 showed superior diagnostic potential for CRC and predicted CRC risk among non-CRC groups in the multivariate logistic analysis. PVT1, MALAT1, miRNA-186 and miRNA-101 levels were correlated with E-cadherin, tumor stage, lymph node and distant metastasis. E-cadherin was lost in metastatic vs. non-metastatic CRC. rs3200401CC genotype carriers showed higher E-cadherin levels than CC + CT carriers. rs3200401 was correlated with lymph node status. For the first time, rs13255292 and rs3200401 are potential genetic CRC predisposition markers, with rs3200401 possibly impacting the EMT process. Serum PVT1, MALAT1, miRNA-186 and miRNA-101 are novel non-invasive diagnostic biomarkers that could improve the clinical outcome of CRC.


Assuntos
Adenocarcinoma/secundário , Neoplasias Colorretais/patologia , Transição Epitelial-Mesenquimal , MicroRNAs/genética , RNA Longo não Codificante/genética , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adulto , Idoso , Biomarcadores Tumorais/genética , Estudos de Casos e Controles , Proliferação de Células , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Feminino , Seguimentos , Regulação Neoplásica da Expressão Gênica , Genótipo , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Prognóstico , Transcriptoma , Células Tumorais Cultivadas , Adulto Jovem
4.
Int J Cancer ; 149(7): 1473-1482, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34109624

RESUMO

The purpose of our study was to investigate the safety, pharmacokinetics (PK), and initial antitumor efficacy of HC-1119 in patients with metastatic castration-resistant prostate cancer (mCRPC). Eligible mCRPC patients were included in our study (NCT03774056) with two parts. Part A was a dose escalation study in which patients received a dose escalation of HC-1119 (40, 80, 160 and 200 mg/day). Part B was a dose expansion study in which patients received HC-1119 at the dose of 80 and 160 mg. Safety assessment and pharmacokinetic samplings were performed for all patients at the given time points; preliminary tumor response was also assessed. Twenty-four patients were enrolled in part A and 19 patients in part B, respectively. HC-1119 was safe, well tolerated and no dose-limiting toxicity was observed. Fatigue was the most common treatment-related adverse event and no seizures were observed. At the dose levels of 40, 80 and 160 mg, the AUC and Cmax of HC-1119 in plasma increased almost dose-proportionally at the steady state in mCRPC patients. Maximum prostate-specific antigen (PSA) response rates (≥50% reduction from the baseline) in dose escalation and dose expansion cohorts were 77% and 75%, respectively; the overall disease control rate (22 patients available for imaging analysis) was 72.7%, with PR in 4 patients, SD in 12 patients and PD in 6 patients; the 2-year overall survival rate in patients from Part B was 56.8%. HC-1119 was safe, well tolerated and efficacious and HC-1119 at 80 mg/day is recommended for further studies.


Assuntos
Adenocarcinoma/tratamento farmacológico , Antineoplásicos/uso terapêutico , Benzamidas/uso terapêutico , Nitrilas/uso terapêutico , Feniltioidantoína/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Adenocarcinoma/secundário , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/farmacocinética , Benzamidas/farmacocinética , Seguimentos , Humanos , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Nitrilas/farmacocinética , Feniltioidantoína/farmacocinética , Prognóstico , Neoplasias da Próstata/patologia , Distribuição Tecidual
5.
Acta Cytol ; 65(4): 348-353, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34077933

RESUMO

INTRODUCTION: Multiplex biomarker analysis of cytological body fluid specimens is often used to assist cytologists in distiguishing metastatic cancer cells from reactive mesothelial cells. However, evaluating biomarker expression visually may be challenging, especially when the cells of interest are scant. Deep-learning algorithms (DLAs) may be able to assist cytologists in analyzing multiple biomarker expression at the single cell level in the multiplex fluorescence imaging (MFI) setting. This preliminary study was performed to test the feasibility of using DLAs to identify immunofluorescence-stained metastatic adenocarcinoma cells in body fluid cytology samples. METHODS: A DLA was developed to analyze MFI-stained cells in body fluid cytological samples. A total of 41 pleural fluid samples, comprising of 20 positives and 21 negatives, were retrospectively collected. Multiplex immunofluorescence labeling for MOC31, BerEP4, and calretinin, were performed on cell block sections, and results were analyzed by manual analysis (manual MFI) and DLA analysis (MFI-DLA) independently. RESULTS: All cases with positive original cytological diagnoses showed positive results either by manual MFI or MFI-DLA, but 2 of the 14 (14.3%) original cytologically negative cases had rare cells with positive MOC31 and/or BerEP4 staining in addition to calretinin. Manual MFI analysis and MFI-DLA showed 100% concordance. CONCLUSION: MFI combined with DLA provides a potential tool to assist in cytological diagnosis of metastatic malignancy in body fluid samples. Larger studies are warranted to test the clinical validity of the approach.


Assuntos
Adenocarcinoma/química , Biomarcadores Tumorais/análise , Citodiagnóstico , Aprendizado Profundo , Diagnóstico por Computador , Imunofluorescência , Processamento de Imagem Assistida por Computador , Microscopia de Fluorescência , Derrame Pleural Maligno/química , Adenocarcinoma/secundário , Diagnóstico Diferencial , Estudos de Viabilidade , Humanos , Derrame Pleural Maligno/patologia , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Estudos Retrospectivos
6.
Ann Ital Chir ; 92: 141-148, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34031289

RESUMO

INTRODUCTION: Breast metastases although rare are challenging for diagnostic difficulties and management. Treatment differs according to morphological, immunophenotipycal and biologic features of the primary tumor and their general behaviour is extremely different compared to primary breast cancer. The most frequent primary tumors include melanoma, lymphomas, gynecological, pulmonary, head and neck, gastroenteric and urinary tract cancers. Patient's prognosis is poor being generally associated to disseminated systemic disease with limited survival despite the effects of systemic treatment. PATIENTS AND METHODS: We report the analysis of the diagnostic and therapeutic approach on the institutional experience of four cases of breast metastases originating from melanoma, pulmonary adenocarcinoma and differentiated thyroid carcinomas. CONCLUSIONS: The management of breast secondarisms requires focused diagnosis and evaluation in order to provide an adequate treatment with a multidisciplinary approach especially when the primary tumor is unknown. KEY WORDS: Breast metastases, Melanoma, Pulmonary, Thyroid.


Assuntos
Adenocarcinoma , Neoplasias da Mama , Neoplasias Pulmonares , Melanoma , Neoplasias Cutâneas , Neoplasias da Glândula Tireoide , Adenocarcinoma/diagnóstico , Adenocarcinoma/secundário , Adenocarcinoma/terapia , Adulto , Antineoplásicos/uso terapêutico , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/secundário , Neoplasias da Mama/terapia , Feminino , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Mastectomia Segmentar , Melanoma/diagnóstico , Melanoma/secundário , Melanoma/terapia , Metastasectomia , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/terapia , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/terapia , Tireoidectomia
7.
Theranostics ; 11(13): 6560-6572, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33995676

RESUMO

Rationale: Metastasis, the development of secondary malignant growth at a distance from a primary tumor, is the main cause of cancer-associated death. However, little is known about how metastatic cancer cells adapt to and colonize in the new organ environment. Here we sought to investigate the functional mechanism of cholesterol metabolic aberration in colorectal carcinoma (CRC) liver metastasis. Methods: The expression of cholesterol metabolism-related genes in primary colorectal tumors (PT) and paired liver metastases (LM) were examined by RT-PCR. The role of SREBP2-dependent cholesterol biosynthesis pathway in cell growth and CRC liver metastasis were determined by SREBP2 silencing in CRC cell lines and experimental metastasis models including, intra-splenic injection models and liver orthotropic injection model. Growth factors treatment and co-culture experiment were performed to reveal the mechanism underlying the up-regulation of SREBP2 in CRC liver metastases. The in vivo efficacy of inhibition of cholesterol biosynthesis pathway by betulin or simvastatin were evaluated in experimental metastasis models. Results: In the present study, we identify a colorectal cancer (CRC) liver metastasis-specific cholesterol metabolic pathway involving the activation of SREBP2-dependent cholesterol biosynthesis, which is required for the colonization and growth of metastatic CRC cells in the liver. Inhibiting this cholesterol biosynthesis pathway suppresses CRC liver metastasis. Mechanically, hepatocyte growth factor (HGF) from liver environment activates SREBP2-dependent cholesterol biosynthesis pathway by activating c-Met/PI3K/AKT/mTOR axis in CRC cells. Conclusion: Our findings support the notion that CRC liver metastases show a specific cholesterol metabolic aberration. Targeting this cholesterol biosynthesis pathway could be a promising treatment for CRC liver metastasis.


Assuntos
Adenocarcinoma/secundário , Colesterol/biossíntese , Neoplasias Colorretais/metabolismo , Neoplasias Hepáticas/secundário , Adenocarcinoma/metabolismo , Animais , Técnicas de Cocultura , Neoplasias Colorretais/patologia , Vetores Genéticos/farmacologia , Fator de Crescimento de Hepatócito/fisiologia , Humanos , Neoplasias Hepáticas/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Proteínas de Neoplasias/metabolismo , Especificidade de Órgãos , Proteínas Proto-Oncogênicas c-met/fisiologia , Interferência de RNA , RNA Interferente Pequeno/genética , Distribuição Aleatória , Transdução de Sinais , Sinvastatina/uso terapêutico , Proteína de Ligação a Elemento Regulador de Esterol 2/metabolismo , Serina-Treonina Quinases TOR/fisiologia , Ensaio Tumoral de Célula-Tronco
8.
Int J Mol Sci ; 22(9)2021 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-33946818

RESUMO

Since 2010, several treatment options have been available for men with metastatic castration-resistant prostate cancer (mCRPC), including immunotherapeutic agents, although the clinical benefit of these agents remains inconclusive in unselected mCRPC patients. In recent years, however, immunotherapy has re-emerged as a promising therapeutic option to stimulate antitumor immunity, particularly with the use of immune checkpoint inhibitors (ICIs), such as PD-1/PD-L1 and CTLA-4 inhibitors. There is increasing evidence that ICIs may be especially beneficial in specific subgroups of patients with high PD-L1 tumor expression, high tumor mutational burden, or tumors with high microsatellite instability/mismatch repair deficiency. If we are to improve the efficacy of ICIs, it is crucial to have a better understanding of the mechanisms of resistance to ICIs and to identify predictive biomarkers to determine which patients are most likely to benefit. This review focuses on the current status of ICIs for the treatment of mCRPC (either as monotherapy or in combination with other drugs), mechanisms of resistance, potential predictive biomarkers, and future challenges in the management of mCRPC.


Assuntos
Adenocarcinoma/secundário , Antineoplásicos Imunológicos/uso terapêutico , Antígeno B7-H1/antagonistas & inibidores , Inibidores de Checkpoint Imunológico/uso terapêutico , Imunoterapia/métodos , Neoplasias de Próstata Resistentes à Castração/terapia , Adenocarcinoma/terapia , Antineoplásicos Imunológicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores , Ensaios Clínicos como Assunto , Reparo do DNA/genética , Resistencia a Medicamentos Antineoplásicos , Previsões , Humanos , Inibidores de Checkpoint Imunológico/administração & dosagem , Masculino , Proteínas de Membrana Transportadoras/efeitos dos fármacos , Estudos Multicêntricos como Assunto , Proteínas de Neoplasias/antagonistas & inibidores , Compostos Organoplatínicos/administração & dosagem , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Medicina de Precisão/métodos , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Taxoides/administração & dosagem
9.
JSLS ; 25(1)2021.
Artigo em Inglês | MEDLINE | ID: mdl-33879998

RESUMO

Background: Minimally invasive oncologic surgery has become the standard of care in many gynecologic cancers. While laparoscopic surgery provides many benefits to patients, such as faster recovery, there are unique challenges associated with minimally invasive techniques. Port-site metastasis is a rare complication after laparoscopic oncologic surgery in management of gynecologic malignancies. Methods: We present the case of a 44-year-old female with isolated port-site recurrence following laparoscopic radical hysterectomy with node-negative, clinical stage IB1 cervical adenocarcinoma. In addition, we provide an updated review of the literature on management and oncologic outcomes of port-site metastasis. Conclusion: Port-site metastasis prevention necessitates a better understanding of underlying risk factors and pathophysiology in order to optimize outcomes. Future studies are needed on risk-reducing strategies and standardization of management for port-site metastasis.


Assuntos
Neoplasias Abdominais/secundário , Adenocarcinoma/cirurgia , Histerectomia/efeitos adversos , Laparoscopia/efeitos adversos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Neoplasias do Colo do Útero/cirurgia , Neoplasias Abdominais/diagnóstico , Neoplasias Abdominais/terapia , Parede Abdominal , Adenocarcinoma/secundário , Adulto , Feminino , Humanos , Inoculação de Neoplasia , Neoplasias do Colo do Útero/patologia
10.
Cancer Radiother ; 25(5): 480-483, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33896682

RESUMO

Penile metastasization is an uncommon condition, mostly derived from primitive advanced abdominal cancers, with disabling symptoms. Palliative treatment, in reason of poor prognosis patients, is frequently surgical with destructive management. We report two cases of penile metastasis, from primitive prostatic adenocarcinoma and primitive urothelial carcinoma, effectively managed with radiation treatment at our institution. A three-dimensional conformal radiation therapy with 42Gy to the planning target volume in 14 fractions was delivered. Radiation treatment was safely delivered, with low toxicity profile and achieved adequate symptoms control without compromising genitourinary functions. Radiation therapy should be considered in management of rare penile metastases.


Assuntos
Adenocarcinoma/radioterapia , Carcinoma de Células de Transição/radioterapia , Neoplasias Penianas/radioterapia , Radioterapia Conformacional , Adenocarcinoma/patologia , Adenocarcinoma/secundário , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células de Transição/patologia , Carcinoma de Células de Transição/secundário , Humanos , Masculino , Neoplasias Penianas/secundário , Neoplasias da Próstata/patologia , Neoplasias da Bexiga Urinária/patologia
12.
Acta Cytol ; 65(3): 242-249, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33827073

RESUMO

BACKGROUND: The diagnosis of atypical cases in the effusion cytology sample often poses a challenge to the cytologists. AIMS AND OBJECTIVES: We evaluated the diagnostic role of MOC31 in the metastatic adenocarcinoma in effusion fluid. MATERIALS AND METHODS: The cytological examination and MOC31 immunostaining in the cell block sections were carried out in 64 cases of serous effusion. A total of 23 cases showed atypical cytology, out of which suspicious for malignancy (SFM) and atypia of undetermined significance (AUS) were 19 and 4 cases, respectively. In these cases, we also performed calretinin immunostaining. The cytological features, results of MOC31 immunostaining, and follow-up data were correlated to find out the sensitivity and specificity of MOC31 immunostaining in the diagnosis of metastatic adenocarcinoma. RESULT: The sensitivity and specificity of MOC31 were 100%. MOC31 detected all the cases of metastatic adenocarcinoma. MOC31 showed strong positivity in 19 cases of SFM. All these cases had a malignant outcome in histopathology or follow-up data. In AUS cases, MOC31 immunostaining was negative with a benign outcome. In all the atypical but malignant cases calretinin stain showed diffuse cytoplasmic and nuclear positivity. In contrast, MOC31 showed strong membranous positivity and occasionally cytoplasmic positivity. CONCLUSION: MOC31 is an excellent marker of metastatic adenocarcinoma in the serous effusion. The membranous positivity of MOC31 and negative calretinin immuno-staining are helpful in atypical cytological cases to avoid the diagnostic dilemma. The MOC31 positivity is significantly useful in discrete atypical cells which are more challenging to recognize.


Assuntos
Adenocarcinoma/imunologia , Anticorpos Monoclonais , Líquido Ascítico/imunologia , Biomarcadores Tumorais/análise , Molécula de Adesão da Célula Epitelial/análise , Imuno-Histoquímica , Derrame Pericárdico/imunologia , Derrame Pleural/imunologia , Adenocarcinoma/secundário , Adulto , Idoso , Líquido Ascítico/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Derrame Pericárdico/patologia , Derrame Pleural/patologia , Valor Preditivo dos Testes , Estudos Retrospectivos
13.
Am J Surg ; 222(3): 529-535, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33750573

RESUMO

BACKGROUND: Mucinous adenocarcinoma represents a distinct histological subtype of colorectal cancer. To date there has been limited data available for patients with colorectal cancer liver metastases (CRCLM) derived from mucinous adenocarcinoma. This systematic review and meta-analysis aims to provide data on the clinicopathological and survival outcomes of this cohort. METHODS: Databases were searched for studies comparing clinicopathological and survival outcomes between patients with mucinous CRCLM and CRCLM from adenocarcinoma not otherwise specified who underwent liver resection. A random-effects model was used for analysis. RESULTS: Eight studies describing 9157 patients were included. Mucinous CRCLM were positively associated with colon tumors (OR 1⋅64, P = 0⋅01), T3/T4 tumors (OR 1⋅58, P = 0⋅02), node positive tumors (OR 1⋅55, P = 0⋅005). The review also identified a trend towards worse overall survival in patients with mucinous CRCLM. CONCLUSIONS: Despite the distinct clinicopathological characteristics and impaired long term outcomes of mucinous CRCLM, resection should remain the gold standard where possible.


Assuntos
Adenocarcinoma Mucinoso , Neoplasias do Colo , Hepatectomia , Neoplasias Hepáticas/mortalidade , Neoplasias Retais , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adenocarcinoma/secundário , Adenocarcinoma/cirurgia , Adenocarcinoma Mucinoso/mortalidade , Adenocarcinoma Mucinoso/patologia , Adenocarcinoma Mucinoso/secundário , Adenocarcinoma Mucinoso/cirurgia , Fatores Etários , Neoplasias do Colo/mortalidade , Neoplasias do Colo/patologia , Neoplasias do Colo/secundário , Neoplasias do Colo/cirurgia , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Bases de Dados Factuais , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Masculino , Neoplasias Retais/mortalidade , Neoplasias Retais/patologia , Neoplasias Retais/secundário , Neoplasias Retais/cirurgia , Fatores Sexuais
14.
J Surg Oncol ; 123(8): 1764-1772, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33765336

RESUMO

OBJECTIVES: To evaluate the relationship between stathmin expression and clinical outcome in colorectal cancer (CRC). BACKGROUND: Stathmin is a phosphoprotein involved in the regulation of microtubule dynamics and integration of intracellular signaling pathways. Stathmin has been implicated in the tumorigenesis of several cancers and is a potential therapeutic target. METHODS: Stathmin expression was evaluated in 25 metastatic CRC (mCRC) patients by immunohistochemistry (IHC). Ki67 IHC and TUNEL assay were also evaluated in mCRC for cell proliferation and apoptosis. RESULTS: High expression of stathmin was correlated with CRC metastasis (p = .0084), and significantly worse overall survival (OS) in CRC patients (p = .036). There was a significant increase in cell proliferation and a decrease in apoptosis in liver metastasis compared with CRC primary tumors as determined by Ki67 IHC and TUNEL assay (p < .0001). We also observed a significant positive correlation between stathmin level and cell proliferation in both CRC primary tumor and liver metastasis (p = .0429 to 0.0451; r = .4236 to .4288). CONCLUSION: Stathmin expression correlated with worse patient prognosis in mCRC patients and positively correlated with increased cell proliferation. Together, our findings indicate stathmin as a novel potential marker for increased risk of CRC-specific mortality and identify stathmin as an attractive therapeutic target for the treatment of mCRC.


Assuntos
Adenocarcinoma/metabolismo , Adenocarcinoma/secundário , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Estatmina/metabolismo , Adenocarcinoma/mortalidade , Idoso , Neoplasias Colorretais/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Prognóstico , Taxa de Sobrevida
15.
Gynecol Oncol ; 161(2): 414-421, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33771396

RESUMO

OBJECTIVE: The current coronavirus pandemic caused a significant decrease in cancer-related encounters resulting in a delay in treatment of cancer patients. The objective of this study was to examine the survival effect of delay in starting concurrent chemo-radiotherapy (CCRT) in women with locally-advanced cervical cancer. METHODS: This is a retrospective observational study querying the National Cancer Database from 2004 to 2016. Women with stage IB2-IVA squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma of the uterine cervix who received definitive CCRT with known wait-time for CCRT initiation after cancer diagnosis were eligible (N=13,617). Cox proportional hazard regression model with restricted cubic spline transformation was fitted to assess the association between CCRT wait-time and all-cause mortality in multivariable analysis. RESULTS: The median wait-time to start CCRT was 6 (IQR 4-8) weeks. In a multivariable analysis, older age, non-Hispanic black and Hispanic ethnicity, recent year of diagnosis, Medicaid and uninsured status, medical comorbidities, and absence of nodal metastasis were associated with longer CCRT wait-time (P<.05). Women with aggressive tumor factors (poorer differentiation, large tumor size, nodal metastasis, and higher cancer stage) were more likely to have a short CCRT wait-time (P<.05). After controlling for the measured covariates, CCRT wait-time of 6.1-9.8 weeks was not associated with increased risk of all-cause mortality compared to a wait-time of 6 weeks. Similar association was observed when the cohort was stratified by histology, cancer stage, tumor size, or brachytherapy use. CONCLUSION: An implication of this study for the current coronavirus pandemic is that in the absence of aggressive tumor factors, a short period of wait-time to start definitive CCRT may not be associated with increased risk of mortality in women with locally-advanced cervical cancer.


Assuntos
Adenocarcinoma/terapia , COVID-19 , Carcinoma Adenoescamoso/terapia , Carcinoma de Células Escamosas/terapia , Tempo para o Tratamento , Neoplasias do Colo do Útero/terapia , Adenocarcinoma/secundário , Adulto , Afro-Americanos/estatística & dados numéricos , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , COVID-19/epidemiologia , Carcinoma Adenoescamoso/secundário , Carcinoma de Células Escamosas/secundário , Quimiorradioterapia , Feminino , Hispano-Americanos/estatística & dados numéricos , Humanos , Metástase Linfática , Medicaid/estatística & dados numéricos , Pessoas sem Cobertura de Seguro de Saúde/estatística & dados numéricos , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Fatores Raciais , Estudos Retrospectivos , SARS-CoV-2 , Taxa de Sobrevida , Carga Tumoral , Estados Unidos , Neoplasias do Colo do Útero/patologia
17.
Ann R Coll Surg Engl ; 103(4): e116-e119, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33682446

RESUMO

We report a 48-year-old fit and healthy woman who was incidentally diagnosed to have adenocarcinoma of gallbladder after laparoscopic cholecystectomy. Subsequent imaging showed no evidence of regional or distant spread. She was scheduled for elective laparotomy and resection of gallbladder bed, but during laparotomy frozen section analysis of an incidentally discovered peritoneal deposit confirmed metastasis, so the procedure was abandoned. Thereafter, she received cisplatin and gemcitabine chemotherapy. However, surveillance computed tomography incidentally noted a urinary bladder mass which had not been present before. Transurethral resection of the bladder lesion revealed moderately differentiated adenocarcinoma of urinary bladder. The appearance and immunoprofile of the lesion confirmed metastasis from the primary gallbladder cancer, which has not been documented in the literature to the best of our knowledge. Her disease progressed and she is being challenged with gemcitabine and carboplatin as second-line palliative chemotherapy. She is still alive two years after the initial diagnosis.


Assuntos
Adenocarcinoma/secundário , Neoplasias da Vesícula Biliar/patologia , Neoplasias da Bexiga Urinária/secundário , Adenocarcinoma/diagnóstico , Feminino , Neoplasias da Vesícula Biliar/diagnóstico , Humanos , Achados Incidentais , Pessoa de Meia-Idade , Neoplasias da Bexiga Urinária/diagnóstico
18.
Cell Death Dis ; 12(2): 224, 2021 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-33637680

RESUMO

Colorectal cancer (CRC) is one of the most common cancers around the world and endangers human health seriously. Liver metastasis is an important factor affecting the long-term prognosis of CRC and the specific mechanism of CRLM (colorectal cancer with liver metastasis) is not fully understood. LZTS1 has been found dysregulated in many cancers, especially in CRC. Theories suggested that hypermethylation of the promoter regions of LZTS1 was responsible for LZTS1 abnormal expression in multiple malignant tumors. Although the role of LZTS1 in CRC cell proliferation has been reported, its role in CRLM remains unclear. Numerous studies reported Long non-coding RNA (lncRNA) could regulate the gene expression level by regulating gene methylation status in many tumors. However, whether there were lncRNAs could change the methylation status of LZTS1 or not in CRLM was unknown. In this study, we aimed to investigate whether there are lncRNAs can regulate the expression of LZTS1 through affecting DNA methylation in CRLM. We found that upregulated Lnc-LALC in CRC was negatively correlated with LZTS1 expression, and Lnc-LALC could regulate LZTS1 expression in both mRNA and protein level in our study. Functionally, Lnc-LALC enhanced the CRC cells metastasis ability in vitro and vivo through inhibiting the expression of LZTS1. Furthermore, the precise mechanisms exploration showed that lnc-LALC could recruit DNA methyltransferases (DNMTs) to the LZTS1 promoter by combining with Enhancer of zeste homolog 2(EZH2) and then altered the expression of LZTS1 via DNMTs-mediated DNA methylation. Collectively, our data demonstrated the important role of Lnc-LALC/ LZTS1 axis in CRLM development.


Assuntos
Adenocarcinoma/genética , Neoplasias Colorretais/genética , Metilação de DNA , Proteínas de Ligação a DNA/genética , Regulação Neoplásica da Expressão Gênica , Inativação Gênica , Neoplasias Hepáticas/genética , Regiões Promotoras Genéticas , RNA Longo não Codificante/genética , Proteínas Supressoras de Tumor/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/secundário , Idoso , Animais , Células CACO-2 , Movimento Celular , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , DNA (Citosina-5-)-Metiltransferases/genética , DNA (Citosina-5-)-Metiltransferases/metabolismo , Proteínas de Ligação a DNA/metabolismo , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Transição Epitelial-Mesenquimal , Feminino , Células HCT116 , Células HT29 , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/secundário , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Invasividade Neoplásica , RNA Longo não Codificante/metabolismo , Proteínas Supressoras de Tumor/metabolismo
19.
Theranostics ; 11(7): 3376-3391, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33537093

RESUMO

Background: Colorectal cancer (CRC) and the associated metastatic lesions are reported to be hypoxic. Hypoxia is a common feature in the tumor microenvironment and a potent stimulant of CRC. We have identified a regulatory role of Nur77 on Akt activation to enhance ß-catenin signaling essential for CRC progression under hypoxic conditions. Methods: The functional role of Nur77 in hypoxia-induced EMT was examined by scattering assays to monitor the morphologies of CRC cell lines under 1% O2. Sphere formation assays were performed to investigate whether Nur77 induced cancer stem cell-like properties in hypoxic CRC cells. The expression of various epithelial-to-mesenchymal transition (EMT) and stemness markers was analyzed by qPCR and Western blotting. Finally, Nur77 function and signaling in vivo was ascertained in subcutaneous tumor xenograft or liver metastasis model in nude mice using CRC cells stably transfected with appropriate constructs. Results: Herein, we show, for the first time, that Nur77 is a novel regulator of microRNA biogenesis that may underlie its significant tumor-promoting activities in CRC cells under hypoxia. Mechanistically, Nur77 interacted with the tumor suppressor protein p63, leading to the inhibition of p63-dependent transcription of Dicer, an important miRNA processor and subsequent decrease in the biogenesis of let-7i-5p which targeted the 3'UTR of p110α mRNA and regulated its stability. Knockdown of Nur77 or overexpression of let-7i-5p inhibited the tumor metastasis in vivo. Conclusion: Our data uncovered a novel mechanistic link connecting Nur77, Akt, and invasive properties of CRC in the hypoxic microenvironment.


Assuntos
Adenocarcinoma/genética , Classe I de Fosfatidilinositol 3-Quinases/genética , Neoplasias Colorretais/genética , RNA Helicases DEAD-box/genética , Hipóxia/genética , Neoplasias Hepáticas/genética , MicroRNAs/genética , Membro 1 do Grupo A da Subfamília 4 de Receptores Nucleares/genética , Proteínas Proto-Oncogênicas c-akt/genética , Ribonuclease III/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/mortalidade , Adenocarcinoma/secundário , Animais , Carcinogênese/genética , Carcinogênese/metabolismo , Carcinogênese/patologia , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Classe I de Fosfatidilinositol 3-Quinases/metabolismo , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , RNA Helicases DEAD-box/metabolismo , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Hipóxia/metabolismo , Hipóxia/mortalidade , Hipóxia/patologia , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/secundário , Camundongos , Camundongos Nus , MicroRNAs/metabolismo , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Membro 1 do Grupo A da Subfamília 4 de Receptores Nucleares/antagonistas & inibidores , Membro 1 do Grupo A da Subfamília 4 de Receptores Nucleares/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ribonuclease III/metabolismo , Transdução de Sinais , Análise de Sobrevida , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Carga Tumoral , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
20.
Aging (Albany NY) ; 13(4): 5892-5905, 2021 02 11.
Artigo em Inglês | MEDLINE | ID: mdl-33591945

RESUMO

Colorectal cancer (CRC) is one of the most common human malignant tumors in recent years. Although multiple approaches have been developed for the diagnosis and therapy of CRC, the overall survival rates of patients with metastatic and recurrent CRC remain poor. In the present study, we used the high-throughput microarray technology to screen circular RNAs (circRNAs) as a potential fingerprint for CRC. We mainly aimed to screen potential biomarkers for liver metastasis by performing risk score analysis. We detected the upregulated expression of circ_0115744 in patients with CRC with liver metastasis (CRLM). Further investigation using a validation set indicated that circ_0115744 might be considered as a fingerprint for CRLM. Functionally, the overexpression of circ_0115744 significantly promoted the invasion of CRC cell lines, while decreased expression of circ_0115744 suppressed cell invasion in vitro. Mechanistic analysis showed that circ_0115744 acted as a competing endogenous RNA of miR-144 to diminish the repressive effect of miR-144 on its target EZH2. In conclusion, we found that increased expression of circ_0115744 could differentiate CRLM from CRC and that the newly identified circ_0115744/miR-144/EZH2 axis was involved in the progression of CRC, which might be used as a potential diagnostic and therapeutic target for patients with CRC.


Assuntos
Adenocarcinoma/metabolismo , Neoplasias Colorretais/metabolismo , Neoplasias Hepáticas/metabolismo , MicroRNAs/metabolismo , RNA Circular/metabolismo , Adenocarcinoma/secundário , Biomarcadores Tumorais/metabolismo , Estudos de Casos e Controles , Neoplasias Colorretais/patologia , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Feminino , Humanos , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica
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