Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 23.950
Filtrar
1.
Anticancer Res ; 41(9): 4411-4416, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34475062

RESUMO

BACKGROUND/AIM: Detection of hepatocellular carcinoma using intraoperative ultrasonography (IOUS) is indispensable for successful laparoscopic hepatectomy (LH). This study was performed to evaluate patients with intraoperatively unidentified tumours undergoing LH. PATIENTS AND METHODS: Seven patients who underwent LH for hepatocellular carcinoma and whose tumours were not detected using IOUS were included in this study. Clinical features, preoperative imaging, intraoperative imaging, surgical procedures, and pathological findings were evaluated. RESULTS: Using gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging, all the tumours were enhanced in the arterial phase and rapidly washed out, becoming hypointense to the remainder of the liver. All tumours except one were <2 cm in size. Severe liver fibrosis was observed in all cases. Tumours that were invisible on preoperative ultrasonography also could not be detected using IOUS or indocyanine green fluorescence imaging. Five patients underwent hepatectomy based on anatomical landmarks and achieved curative resection, whereas curative resection failed in two patients. CONCLUSION: When tumours cannot be identified by IOUS, LH based on anatomical landmarks should be preferred. Importantly, invisible tumours on preoperative ultrasonography may not be identified intraoperatively during LH.


Assuntos
Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Cirrose Hepática/patologia , Cirrose Hepática/cirurgia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Idoso , Carcinoma Hepatocelular/diagnóstico por imagem , Feminino , Gadolínio DTPA/administração & dosagem , Hepatectomia , Humanos , Verde de Indocianina/administração & dosagem , Laparoscopia , Cirrose Hepática/diagnóstico por imagem , Neoplasias Hepáticas/diagnóstico por imagem , Imagem por Ressonância Magnética Intervencionista , Masculino , Pessoa de Meia-Idade , Carga Tumoral , Ultrassonografia de Intervenção
2.
Anticancer Res ; 41(9): 4489-4495, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34475074

RESUMO

BACKGROUND/AIM: The chemokine receptors C-X-C chemokine receptor type 4 (CXCR4) and C-C chemokine receptor type 7 (CCR7) play an important role in the invasion and metastasis of cancer. This study investigated the relationship between relative expression of CXCR4 and CCR7 mRNA, clinicopathological factors, and outcomes in patients with colorectal cancer (CRC). PATIENTS AND METHODS: We studied 202 patients who underwent surgery for CRC. The expression levels of CXCR4 and CCR7 mRNA in cancerous tissue were measured using quantitative real-time reverse-transcriptase polymerase chain reaction. RESULTS: High CCR7 mRNA expression levels in CRC tissues were positively associated with tumour size and were more frequently associated with cancer of the rectum than of the colon. Moreover, outcomes were significantly poorer in patients with high CCR7 mRNA expression than in those with low expression. On multivariate Cox regression analysis, a higher CCR7 mRNA expression level was a significant independent predictor of poorer overall survival in patients with CRC. CONCLUSION: Overexpression of CCR7 mRNA may be a useful independent prognostic factor in patients with CRC.


Assuntos
Neoplasias Colorretais/cirurgia , Perfilação da Expressão Gênica/métodos , Receptores CCR7/genética , Receptores CXCR4/genética , Regulação para Cima , Idoso , Biomarcadores Tumorais/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Análise de Sobrevida , Resultado do Tratamento , Carga Tumoral
3.
JAMA Netw Open ; 4(9): e2124483, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34495337

RESUMO

Importance: The COVID-19 pandemic has been associated with substantial reduction in screening, case identification, and hospital referrals among patients with cancer. However, no study has quantitatively examined the implications of this correlation for cancer patient management. Objective: To evaluate the association of the COVID-19 pandemic lockdown with the tumor burden of patients who were diagnosed with metastatic colorectal cancer (mCRC) before vs after lockdown. Design, Setting, and Participants: This cohort study analyzed participants in the screening procedure of the PANIRINOX (Phase II Randomized Study Comparing FOLFIRINOX + Panitumumab vs FOLFOX + Panitumumab in Metastatic Colorectal Cancer Patients Stratified by RAS Status from Circulating DNA Analysis) phase 2 randomized clinical trial. These newly diagnosed patients received care at 1 of 18 different clinical centers in France and were recruited before or after the lockdown was enacted in France in the spring of 2020. Patients underwent a blood-sampling screening procedure to identify their RAS and BRAF tumor status. Exposures: mCRC. Main Outcomes and Measures: Circulating tumor DNA (ctDNA) analysis was used to identify RAS and BRAF status. Tumor burden was evaluated by the total plasma ctDNA concentration. The median ctDNA concentration was compared in patients who underwent screening before (November 11, 2019, to March 9, 2020) vs after (May 14 to September 3, 2020) lockdown and in patients who were included from the start of the PANIRINOX study. Results: A total of 80 patients were included, of whom 40 underwent screening before and 40 others underwent screening after the first COVID-19 lockdown in France. These patients included 48 men (60.0%) and 32 women (40.0%) and had a median (range) age of 62 (37-77) years. The median ctDNA concentration was statistically higher in patients who were newly diagnosed after lockdown compared with those who were diagnosed before lockdown (119.2 ng/mL vs 17.3 ng/mL; P < .001). Patients with mCRC and high ctDNA concentration had lower median survival compared with those with lower concentration (14.7 [95% CI, 8.8-18.0] months vs 20.0 [95% CI, 14.1-32.0] months). This finding points to the potential adverse consequences of the COVID-19 pandemic and related lockdown. Conclusions and Relevance: This cohort study found that tumor burden differed between patients who received an mCRC diagnosis before vs after the first COVID-19 lockdown in France. The findings of this study suggest that CRC is a major area for intervention to minimize pandemic-associated delays in screening, diagnosis, and treatment.


Assuntos
Neoplasias Colorretais/patologia , Controle de Doenças Transmissíveis/organização & administração , Aceitação pelo Paciente de Cuidados de Saúde , Carga Tumoral , Adulto , Idoso , Biomarcadores Tumorais/genética , COVID-19/epidemiologia , DNA Tumoral Circulante/sangue , Ensaios Clínicos Fase II como Assunto , Estudos de Coortes , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/terapia , Estudos Controlados Antes e Depois , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Ensaios Clínicos Controlados Aleatórios como Assunto , SARS-CoV-2
4.
Zhonghua Zhong Liu Za Zhi ; 43(9): 939-943, 2021 Sep 23.
Artigo em Chinês | MEDLINE | ID: mdl-34530576

RESUMO

Objective: Establishment of a new model of human primary colon cancer transplantation tumor in normal immune mice and to provide a reliable experimental animal model for studying the pathogenesis of colon cancer under normal immunity. Methods: Human colon cancer cells come from colon cancer patients who underwent surgery in the Affiliated Hospital of Jining Medical College in 2017. The mice in the cell control group were inoculated with phosphate buffered solution (PBS) containing colon cancer cells, the microcarrier control group was inoculated with PBS containing microcarrier 6, and the cell-microcarrier complex group was inoculated with the PBS containing colon cancer cell-microcarrier complex. The cells of each group were inoculated under the skin of the right axilla of mice by subcutaneous injection, and the time, size, tumor formation rate and pathological changes under microscope were recorded. The transplanted tumor tissue was immunohistochemically stained with the EnVisiion two-step method, and the tumor formation rate of the transplanted tumor was judged according to the proportion of positive cells in the visual field. The polymerase chain reaction (PCR) method was used to detect the expression of human-specific Alu sequence in mice tumor tissue. Results: After inoculation with tumor cells, the mice in the cell control group and the microcarrier control group did not die and did not form tumors; the mice in the cell-microcarrier complex group had palpable subcutaneous tumors in the right axillary subcutaneously on the 5th to 7th days after inoculation, and tumor formation rate is 67% (10/15), and the tumor volume can reach about 500 mm(3) 2 to 3 weeks after vaccination. The immunohistochemistry results showed that CK20, CDX-2 and carcinoembryonic antigen were all positively expressed. The PCR results showed that the expression of human-specific Alu sequence can be detected in the transplanted tumor tissue of tumor-bearing mice. Conclusion: Human primary colon cancer cells used microcarrier 6 as a carrier to form tumors in normal immunized mice, and successfully established a new model of human colon cancer transplantation tumor in normal immune mice.


Assuntos
Neoplasias do Colo , Animais , Linhagem Celular Tumoral , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Transplante de Neoplasias , Carga Tumoral
5.
Hinyokika Kiyo ; 67(7): 339-342, 2021 Jul.
Artigo em Japonês | MEDLINE | ID: mdl-34353017

RESUMO

A 34-year-old woman underwent total hysterectomy for management of uterine leiomyoma. At the same time, a paraurethral tumor (2 cm in size) was diagnosed based on magnetic resonance imaging (MRI). However, the patient was not treated for the tumor considering its small size. Eight years later, the patient was referred to our institution with a chief complaint of urethral bleeding. Computed tomography revealed a paraurethral mass at the same location, which was 13 cm in size. A percutaneous needle biopsy was performed and the tumor was diagnosed as leiomyoma. Tumor extirpation was performed and immunohistochemical analysis of the specimen demonstrated positive estrogen and progesterone receptors. Recurrence was not observed on MRI taken 6 months after the surgery. Paraurethral leiomyoma is rare, but relatively common in young women.


Assuntos
Leiomioma , Neoplasias Uretrais , Neoplasias Uterinas , Adulto , Feminino , Humanos , Leiomioma/diagnóstico por imagem , Leiomioma/cirurgia , Imageamento por Ressonância Magnética , Recidiva Local de Neoplasia , Carga Tumoral , Neoplasias Uretrais/diagnóstico por imagem , Neoplasias Uretrais/cirurgia
6.
Nat Commun ; 12(1): 5056, 2021 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-34417458

RESUMO

Melanoma cells rely on developmental programs during tumor initiation and progression. Here we show that the embryonic stem cell (ESC) factor Sall4 is re-expressed in the Tyr::NrasQ61K; Cdkn2a-/- melanoma model and that its expression is necessary for primary melanoma formation. Surprisingly, while Sall4 loss prevents tumor formation, it promotes micrometastases to distant organs in this melanoma-prone mouse model. Transcriptional profiling and in vitro assays using human melanoma cells demonstrate that SALL4 loss induces a phenotype switch and the acquisition of an invasive phenotype. We show that SALL4 negatively regulates invasiveness through interaction with the histone deacetylase (HDAC) 2 and direct co-binding to a set of invasiveness genes. Consequently, SALL4 knock down, as well as HDAC inhibition, promote the expression of an invasive signature, while inhibition of histone acetylation partially reverts the invasiveness program induced by SALL4 loss. Thus, SALL4 appears to regulate phenotype switching in melanoma through an HDAC2-mediated mechanism.


Assuntos
Epigênese Genética , Melanoma/genética , Melanoma/patologia , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Fator de Células-Tronco/metabolismo , Fatores de Transcrição/metabolismo , Acetilação , Animais , Sequência de Bases , Carcinogênese/genética , Carcinogênese/patologia , Adesão Celular/genética , Linhagem Celular Tumoral , Linhagem da Célula , Proliferação de Células , Proteínas de Ligação a DNA/metabolismo , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Histona Desacetilase 2/metabolismo , Histonas/metabolismo , Humanos , Melanócitos/metabolismo , Melanócitos/patologia , Camundongos Nus , Camundongos Transgênicos , Invasividade Neoplásica , Micrometástase de Neoplasia , Ligação Proteica , Carga Tumoral
7.
J Pak Med Assoc ; 71(7): 1907-1908, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34410274

RESUMO

"Superscan" features have been described in 18F FDG PET-CT (F18 fluorodeoxyglucose Positron Emission Tomography­Computed Tomography) scan; characterized by significantly increased uptake in one or more organ systems resulting in absent or decreased uptake in the organs which normally show physiological uptake. The importance of the awareness has evolved over the years in order to avoid false interpretation of scan findings as well as in determination of a high tumour burden. We present images of three patients who underwent 18F FDG PET-CT scan showing findings consistent with FDG PET-CT superscan.


Assuntos
Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Humanos , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Tomografia Computadorizada por Raios X , Carga Tumoral
8.
Acta Derm Venereol ; 101(8): adv00525, 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34396424

RESUMO

The aim of this study was to compare tumour burden in patients who underwent surgery for melanoma and cutaneous squamous cell carcinoma during nationwide lockdown in Spain due to COVID-19 (for the period 14 March to 13 June 2020) and during the same dates in 2019 before the COVID-19 pandemic. In addition, associations between median tumour burden (Breslow thickness for melanoma and maximum clinical diameter for cutaneous squamous cell carcinoma) and demographic, clinical, and medical factors were analysed, building a multivariate linear regression model. During the 3 months of lockdown, there was a significant decrease in skin tumours operated on (41% decrease for melanoma (n = 352 vs n = 207) and 44% decrease for cutaneous squamous cell carcinoma (n = 770 vs n = 429)) compared with the previous year. The proportion of large skin tumours operated on increased. Fear of SARS-CoV-2 infection, with respect to family member/close contact, and detection of the lesion by the patient or doctor, were related to thicker melanomas; and fear of being diagnosed with cancer, and detection of the lesion by the patient or relatives, were related to larger size cutaneous squamous cell carcinoma. In conclusion, lockdown due to COVID-19 has resulted in a reduction in treatment of skin cancer.


Assuntos
COVID-19 , Carcinoma de Células Escamosas , Melanoma , Neoplasias Cutâneas , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/cirurgia , Controle de Doenças Transmissíveis , Humanos , Melanoma/epidemiologia , Melanoma/cirurgia , Pandemias , SARS-CoV-2 , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/cirurgia , Carga Tumoral
9.
Eur J Endocrinol ; 185(4): 587-595, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34374649

RESUMO

Objective: Transsphenoidal surgery (TSS) is mainly indicated in prolactinomas when dopamine agonist treatment fails. However, there is no established early predictor of cabergoline (CBG) response. The present study was aimed to identify predictors of CBG resistance in order to select patients who may benefit from early TSS. Design: Retrospective longitudinal study. Methods: We reviewed the medical record of patients diagnosed with prolactinoma after 2010. Inclusion criteria: macroprolactinomas under CBG treatment with serial prolactin levels and MRI before treatment and 3 and 12 months afterwards. The main outcome was tumour size shrinkage ≥ 50% (using the two largest diameters in sagittal view) after 12 months of CBG (TS_50). The capacity of the most important clinical and biochemical variables in predicting the main outcome was examined. Results: A total of 185 prolactinomas where included: 124 (67.0%) were microadenomas and 61 (33.0%) were macroadenomas of which 27 patients meet de inclusion criteria; median age (42.5 years; (IQR: 28.0)). The median follow-up was (67.5 months; (IQR: 30.2)). Ten patients (37.0%) underwent surgery after more than 1 year of CBG. The volume reduction at the first MRI (3-4 months) was the unique valuable predictor: (OR: 1.16 (95% CI: 1.02-1.32)) of TS_50. A tumour volume shrinkage of ≥ 30% in the first 3-4 months of CBG therapy predicts TS_50 with an AUC (0.95 (CI: 0.76-0.99)). Conclusion: Tumour shrinkage in the first 3-4 months after starting treatment with CBG is a good tool for predicting the long-term response and can help clinicians to take more appropriated and personalized decisions.


Assuntos
Cabergolina/uso terapêutico , Neoplasias Hipofisárias/tratamento farmacológico , Prolactinoma/tratamento farmacológico , Carga Tumoral/efeitos dos fármacos , Adolescente , Adulto , Idoso , Cabergolina/farmacologia , Criança , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neoplasias Hipofisárias/diagnóstico , Neoplasias Hipofisárias/patologia , Prognóstico , Prolactinoma/diagnóstico , Prolactinoma/patologia , Indução de Remissão , Estudos Retrospectivos , Espanha , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
10.
Medicine (Baltimore) ; 100(31): e26189, 2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34397790

RESUMO

BACKGROUND AND OBJECTIVES: Postoperative major complications after esophageal cancer resection vary and may significantly impact long-term outcomes. This study aimed to build an individualized nomogram to predict post-esophagectomy major morbidity. METHODS: This retrospective study included 599 consecutive patients treated at a single center between January 2017 and April 2019. Of them, 420 and 179 were assigned to the model development and validation cohorts, respectively. Major morbidity predictors were identified using multiple logistic regression. Model discrimination and calibration were evaluated by validation. Regarding clinical usefulness, we examined the net benefit using decision curve analysis. RESULTS: The mean age was 64 years; 79% of the patients were male. The most common comorbidities were hypertension, diabetes mellitus, and stroke history. The 30-day postoperative major morbidity rate was 24%. Multivariate logistic regression analysis showed that age, smoking history, coronary heart disease, dysphagia, body mass index, operation time, and tumor size were independent risk factors for surgery-associated major morbidity. Areas under the receiver-operating characteristic curves of the development and validation groups were 0.775 (95% confidence interval, 0.721-0.829) and 0.792 (95% confidence interval, 0.709-0.874), respectively. In the validation cohort, the nomogram showed good calibration. Decision curve analysis demonstrated that the prediction nomogram was clinically useful. CONCLUSION: Morbidity models and nomograms incorporating clinical and surgical data can be used to predict operative risk for esophagectomy and provide appropriate resources for the postoperative management of high-risk patients.


Assuntos
Neoplasias Esofágicas/cirurgia , Carcinoma de Células Escamosas do Esôfago/cirurgia , Esofagectomia/efeitos adversos , Nomogramas , Complicações Pós-Operatórias/etiologia , Fatores Etários , Idoso , Área Sob a Curva , Índice de Massa Corporal , Comorbidade , Doença das Coronárias/epidemiologia , Transtornos de Deglutição/etiologia , Neoplasias Esofágicas/complicações , Neoplasias Esofágicas/epidemiologia , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/complicações , Carcinoma de Células Escamosas do Esôfago/epidemiologia , Carcinoma de Células Escamosas do Esôfago/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Curva ROC , Estudos Retrospectivos , Fatores de Risco , Fumar/epidemiologia , Carga Tumoral
11.
Medicine (Baltimore) ; 100(31): e26801, 2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34397833

RESUMO

RATIONALE: At present, the prognosis of patients with giant lung squamous cell carcinoma (LSCC) is poor, and there is no safe and effective treatment for elderly patients with large LSCC. PATIENT CONCERNS: Here, we reported a 77-year-old man admitted to the hospital with cough for 3 months and significant chest pain. Computed tomography (CT) imaging showed a large mass in the left lung with pleural effusion. DIAGNOSES: Chest CT scan revealed a 12.5 cm × 7.3 cm mass in the left upper lobe adjacent to the pulmonary vein, with left pleural effusion. Pulmonary tumor markers were significantly elevated, and CT-guided percutaneous lung mass biopsy specimens showed LSCC. INTERVENTIONS: After diagnosis, the patient was treated with sintilimab combined with endostar and nab-paclitaxel. After 2 cycles of treatment, the lung mass in the patient shrank rapidly and the clinical symptoms were relieved. OUTCOMES: The patient's tumor dramatically shrank, and the pleural effusion was decreased after 4 cycles of treatment without any adverse effects. Meanwhile, the high-level tumor marker resumed normal. LESSONS: Sintilimab combined with endostar and nab-paclitaxel may be a good treatment option for lung squamous cell cancer, especially for that in elderly patients.


Assuntos
Albuminas/administração & dosagem , Anticorpos Monoclonais Humanizados/administração & dosagem , Carcinoma de Células Escamosas , Endostatinas/administração & dosagem , Neoplasias Pulmonares , Paclitaxel/administração & dosagem , Derrame Pleural , Proteínas Recombinantes/administração & dosagem , Idoso , Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Biópsia/métodos , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/fisiopatologia , Humanos , Pulmão/diagnóstico por imagem , Pulmão/patologia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/fisiopatologia , Masculino , Estadiamento de Neoplasias , Derrame Pleural/diagnóstico por imagem , Derrame Pleural/etiologia , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento , Carga Tumoral
12.
Medicine (Baltimore) ; 100(34): e27070, 2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34449503

RESUMO

ABSTRACT: The objective of the current study is to analyze the clinical and demographic characteristics of patients with bone metastasis of small cell lung cancer (SCLC) and explore their survival predictors.We retrospectively extracted patients with bone metastasis of SCLC from the Surveillance, Epidemiology, and End Results database. We applied Cox regression analyses to identify independent survival predictor of overall survival (OS) and cancer-specific survival (CSS). Only significant predictors from univariable analysis were included for multivariable Cox analysis. Kaplan-Meier method was used to evaluate survival differences between groups by the log-rank test.A total of 5120 patients with bone metastasis of SCLC were identified and included for survival analysis. The 1-year OS and CSS rates of bone metastasis of SCLC were 19.8% and 21.4%, respectively. On multivariable analysis, gender, age, radiotherapy, chemotherapy, liver metastasis, brain metastasis, insurance status, and marital status independently predicted OS and CSS. There was no significant difference of OS and CSS in terms of race and tumor size.Independent predictors of survival were identified among patients with bone metastasis of SCLC, which could be valuable to clinicians in treatment decision. Patients with bone metastasis of SCLC may benefit from radiotherapy and chemotherapy.


Assuntos
Neoplasias Ósseas/secundário , Carcinoma de Pequenas Células do Pulmão/mortalidade , Carcinoma de Pequenas Células do Pulmão/patologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/secundário , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Programa de SEER , Fatores Sexuais , Carcinoma de Pequenas Células do Pulmão/terapia , Fatores Socioeconômicos , Análise de Sobrevida , Carga Tumoral
13.
Nutrients ; 13(7)2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-34371939

RESUMO

A high-fat diet (HFD) and obesity are risk factors for many diseases including breast cancer. This is particularly important with close to 40% of the current adult population being overweight or obese. Previous studies have implicated that Mediterranean diets (MDs) partially protect against breast cancer. However, to date, the links between diet and breast cancer progression are not well defined. Therefore, to begin to define and assess this, we used an isocaloric control diet (CD) and two HFDs enriched with either olive oil (OOBD, high in oleate, and unsaturated fatty acid in MDs) or a milk fat-based diet (MFBD, high in palmitate and myristate, saturated fatty acids in Western diets) in a mammary polyomavirus middle T antigen mouse model (MMTV-PyMT) of breast cancer. Our data demonstrate that neither MFBD or OOBD altered the growth of primary tumors in the MMTV-PyMT mice. The examination of lung metastases revealed that OOBD mice exhibited fewer surface nodules and smaller metastases when compared to MFBD and CD mice. These data suggest that different fatty acids found in different sources of HFDs may alter breast cancer metastasis.


Assuntos
Neoplasias da Mama/patologia , Dieta Hiperlipídica/efeitos adversos , Gorduras na Dieta/toxicidade , Ácidos Graxos/toxicidade , Neoplasias Pulmonares/secundário , Leite/toxicidade , Ração Animal , Animais , Antígenos Transformantes de Poliomavirus , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Feminino , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Vírus do Tumor Mamário do Camundongo/genética , Azeite de Oliva/toxicidade , Medição de Risco , Fatores de Risco , Carga Tumoral , Fator de Necrose Tumoral alfa/metabolismo
14.
Nat Commun ; 12(1): 4840, 2021 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-34376661

RESUMO

Gastric cancer (GC) is commonly treated by chemotherapy using 5-fluorouracil (5-FU) derivatives and platinum combination, but predictive biomarker remains lacking. We develop patient-derived xenografts (PDXs) from 31 GC patients and treat with a combination of 5-FU and oxaliplatin, to determine biomarkers associated with responsiveness. When the PDXs are defined as either responders or non-responders according to tumor volume change after treatment, the responsiveness of PDXs is significantly consistent with the respective clinical outcomes of the patients. An integrative genomic and transcriptomic analysis of PDXs reveals that pathways associated with cell-to-cell and cell-to-extracellular matrix interactions enriched among the non-responders in both cancer cells and the tumor microenvironment (TME). We develop a 30-gene prediction model to determine the responsiveness to 5-FU and oxaliplatin-based chemotherapy and confirm the significant poor survival outcomes among cases classified as non-responder-like in three independent GC cohorts. Our study may inform clinical decision-making when designing treatment strategies.


Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/genética , Neoplasias Gástricas/tratamento farmacológico , Ensaios Antitumorais Modelo de Xenoenxerto/métodos , Adenocarcinoma/genética , Animais , Feminino , Fluoruracila/administração & dosagem , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Camundongos Endogâmicos NOD , Camundongos Knockout , Camundongos SCID , Oxaliplatina/administração & dosagem , Neoplasias Gástricas/genética , Análise de Sobrevida , Carga Tumoral/efeitos dos fármacos , Carga Tumoral/genética
15.
Cancer Sci ; 112(9): 3585-3597, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34252986

RESUMO

Diffuse large B cell lymphoma (DLBCL) heterogeneity promotes recurrence and anti-CD20-based therapeutic resistance. Previous studies have shown that downregulation of MS4A1/CD20 expression after chemoimmunotherapy with rituximab leads to rituximab resistance. However, the mechanisms of CD20 loss remain unknown. We identified that pyruvate dehydrogenase kinase 4 (PDK4) is markedly elevated in DLBCL cells derived from both patients and cell lines with R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) resistance. We found that overexpression of PDK4 in DLBCL cells resulted in cell proliferation and resistance to rituximab in vitro and in vivo. Furthermore, loss of PDK4 expression or treatment with the PDK4 inhibitor dichloroacetate was able to significantly increase rituximab-induced cell apoptosis in DLBCL cells. Further studies suggested PDK4 mediates a metabolic shift, in that the main energy source was changed from oxidative phosphorylation to glycolysis, and the metabolic changes could play an important role in rituximab resistance. Importantly, by knocking down or overexpressing PDK4 in DLBCL cells, we showed that PDK4 has a negative regulation effect on MS4A1/CD20 expression. Collectively, this is the first study showing that targeting PDK4 has the potential to overcome rituximab resistance in DLBCL.


Assuntos
Antígenos CD20/metabolismo , Antineoplásicos Imunológicos/administração & dosagem , Reprogramação Celular/genética , Resistencia a Medicamentos Antineoplásicos/genética , Glicoproteínas/metabolismo , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/metabolismo , Piruvato Desidrogenase Quinase de Transferência de Acetil/metabolismo , Rituximab/administração & dosagem , Transdução de Sinais/genética , Adolescente , Adulto , Idoso , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Feminino , Humanos , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/patologia , Masculino , Camundongos , Pessoa de Meia-Idade , Piruvato Desidrogenase Quinase de Transferência de Acetil/genética , Transfecção , Resultado do Tratamento , Carga Tumoral/efeitos dos fármacos , Carga Tumoral/genética , Ensaios Antitumorais Modelo de Xenoenxerto , Adulto Jovem
16.
Am J Clin Oncol ; 44(9): 482-486, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34269693

RESUMO

PURPOSE: Neoadjuvant chemoradiation followed by surgery is the current standard of care in the treatment of locally advanced rectal cancer. Those who achieved pathologic complete response, following this standard of care, complete pathologic response (pCR) had better outcome. Until now there are no reliable clinical parameters to predict this response. The purpose of the study was to evaluate whether tumor volume may serve as a predictive factor in patients treated with neoadjuvant chemoradiotherapy. MATERIALS AND METHODS: Between September 2015 and September 2019, patients diagnosed with stage IIA to IIIC rectal adenocarcinoma, who were treated with neoadjuvant chemoradiation, were enrolled to this study. All patients underwent rectal ultrasound, pelvic magnetic resonance imaging, fluorodeoxyglucose-positron emission tomography-computed tomography and the diagnosis was confirmed by pathology report. Radiation therapy was consisted of 50 Gy delivered to the tumor site, 2 Gy a day, 5 times a week and to the pelvic lymph nodes for a total of 45 Gy in 1.8 Gy a day, 5 times a week. The gross tumor volume (GTV) was contoured by radiation oncology expert, reviewed by radiology and nuclear medicine expert and approved by radiation therapy tumor board. Chemotherapy was consisted of either capecitabine 875 mg/m2 twice a day or continuous. IV infusion of 5 fluorouracil 375 mg/m2 for 4 consecutive days in a 3 weeks apart. Operation, either low anterior or abdominoperineal resection was carried out 6 to 8 weeks following completion of treatment. Patients were assigned to either complete pathologic response (pCR) or non-pCR groups. GTV, among other clinical and treatment parameters, were evaluated for prediction of pCR. Statistical methods included independent t test, logistic regression, area under the curve-receiver operating characteristic, Bayesian independent statistics and multilayer perceptron model. RESULTS: One hundred ninety-three patients were enrolled to this study, 6 were excluded due to metastatic disease detected at the time of operation. Seventy had stage II and 117 had stage III. Forty-four of 187 (23.5%) patients achieved pCR and 143 patients had either partial or no response/progressive disease. Among the 44 pCR group, 21 had stage II and 23 had stage III disease. Treatment interruption, defined as either a delay of up to 1 week in radiation, and a dose reduction to 75%, was occurred in 42 patients. Sex, ethnicity, distance from anal verge to tumor, height, weight, age, delivered radiation dose, radiotherapy techniques, clinical T and N stage and GTV were evaluated for prediction of pCR. GTV at the volume of <39.5 cm3 was the only significant predictive factor to detect pCR by logistic regression model (P<0.01) and by Bayesian independent test (P=0.026). Area under the receiver operating characteristic curve of GTV <39.5 cm3 showed area under the curve of 0.715 (P=0.009) for stage II and area under the curve of 0.62 (P>0.05) for stage III. CONCLUSION: GTV may serve as a predictive factor for achieving pCR in locally advanced rectal cancer after neoadjuvant chemoradiotherapy.


Assuntos
Adenocarcinoma/patologia , Adenocarcinoma/terapia , Neoplasias Retais/patologia , Neoplasias Retais/terapia , Carga Tumoral , Adenocarcinoma/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Capecitabina/administração & dosagem , Capecitabina/uso terapêutico , Quimiorradioterapia , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/uso terapêutico , Humanos , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Dosagem Radioterapêutica , Neoplasias Retais/diagnóstico por imagem , Estudos Retrospectivos , Resultado do Tratamento
17.
Int J Nanomedicine ; 16: 4661-4674, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34262274

RESUMO

Purpose: Gold nanoparticles (AuNPs) are widely studied as radiosensitizers, but their radiosensitization in carbon ion radiotherapy is unsatisfactory. There is a lack of in vivo data on the radiosensitization of AuNPs under carbon ion irradiation. This study focused on the radiosensitization effect of AuNPs in the mouse melanoma cell line B16-F10 in vitro and in vivo. Materials and Methods: 11-mercaptoundecanoic acid (11-MUA)-coated gold (Au) nanoparticles (mAuNPs) formulations were prepared and characterized. To verify the radiosensitization effect of mAuNPs, hydroxyl radicals were generated in aqueous solution, and the detection of intracellular reactive oxygen species (ROS) and clone survival were carried out in vitro. The tumor growth rate (TGR) and survival of mice were analyzed to verify the radiosensitization effect of mAuNPs in vivo. The apoptosis of tumor cells was detected, and the expression of key proteins in the apoptosis pathway was verified by immunohistochemistry. Results: The intracellular ROS level in B16-F10 cells was enhanced by mAuNPs under carbon ion irradiation. The sensitization rate of mAuNPs was 1.22 with a 10% cell survival rate. Compared with irradiation alone, the inhibitory effect of mAuNPs combined with carbon ion irradiation on tumor growth was 1.94-fold higher, the survival time of mice was prolonged by 1.75-fold, and the number of apoptotic cells was increased by 1.43-fold. The ratio of key proteins Bax and Bcl2 in the apoptosis pathway was up-regulated, and the expression of caspase-3, a key executor of the apoptosis pathway, was up-regulated. Conclusion: In in vivo and in vitro experiments, mAuNPs showed radiosensitivity to carbon ion irradiation. The sensitization effect of mAuNPs on mice tumor may be achieved by activating the mitochondrial apoptosis pathway and increasing tumor tissue apoptosis. To our best knowledge, the present study is the first in vivo evidence for radiosensitization of mAuNPs in tumor-bearing mice exposed to carbon ion irradiation.


Assuntos
Ácidos Graxos/química , Ouro/química , Radioterapia com Íons Pesados , Nanopartículas Metálicas/química , Compostos de Sulfidrila/química , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Células Clonais , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Melanoma Experimental/patologia , Melanoma Experimental/radioterapia , Nanopartículas Metálicas/ultraestrutura , Camundongos Endogâmicos C57BL , Espécies Reativas de Oxigênio/metabolismo , Análise de Sobrevida , Resultado do Tratamento , Carga Tumoral
18.
Zhonghua Zhong Liu Za Zhi ; 43(7): 795-800, 2021 Jul 23.
Artigo em Chinês | MEDLINE | ID: mdl-34289575

RESUMO

Objective: To investigate the value of (18)F-fluorodeoxy glucose ((18)F-FDG) positron emission tomography/computed tomography (PET-CT) in predicting the epidermal growth factor receptor (EGFR) mutations in patients with lung squamous cell carcinoma. Methods: We retrospectively analyzed the clinical data and (18)F-FDG PET-CT imaging data of 206 patients with lung squamous cell carcinoma confirmed by pathology and underwent EGFR mutation test in the First Affiliated Hospital of Nanjing Medical University from June 2013 to October 2018. Receiver operating characteristic (ROC) curve analysis was performed to quantify the predictive value of maximum standard uptake value (SUV(max)), metabolic tumor volume (MTV), total lesion glycolysis (TLG). The Chi-squared test was used to assess the difference in PET parameters. A multivariate Logistic regression analysis was performed to yield the parameters with statistic difference. Results: All of 206 patients with lung squamous cell carcinoma showed a high (18)F-FDG uptake. The median of SUV(max), MTV and TLG were 19.14, 37.69 cm(3) and 291.73, respectively. Among the 206 patients, EGFR mutations were identified in 14 cases, including 7 with exon 21 (L858R) mutation, 6 with exon 19 mutation and 1 with exon 20 mutation. ROC curve showed that the AUC of SUV(max), MTV and TLG were 0.624 (95% CI=0.454-0.794, P=0.122), 0.892 (95% CI=0.811-0.973, P<0.001) and 0.860 (95% CI=0.768-0.952, P<0.001), respectively. The median SUV(max) (19.14) was used as the cutoff points due to the small value of AUC. The cutoff point of MTV was 20.09 cm(3), the cutoff point of TLG was 211.07. Univariate analysis showed that the sex, smoking history, M stage, MTV and TLG were associated with EGFR mutations (all P<0.05). Logistic multivariate analysis showed that the sex, smoking history and TLG were the independent predictors of EGFR mutation (all P<0.05). Conclusion: TLG detected by (18)F-FDG PET/CT is an independent factor for predicting EGFR mutation in patients with lung squamous cell carcinoma, and has certain reference value for predicting EGFR mutation.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Pulmonares , Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/genética , Receptores ErbB/genética , Fluordesoxiglucose F18 , Humanos , Pulmão , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/genética , Mutação , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Prognóstico , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Carga Tumoral
19.
Nat Commun ; 12(1): 4626, 2021 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-34330913

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer that has remained clinically challenging to manage. Here we employ an RNAi-based in vivo functional genomics platform to determine epigenetic vulnerabilities across a panel of patient-derived PDAC models. Through this, we identify protein arginine methyltransferase 1 (PRMT1) as a critical dependency required for PDAC maintenance. Genetic and pharmacological studies validate the role of PRMT1 in maintaining PDAC growth. Mechanistically, using proteomic and transcriptomic analyses, we demonstrate that global inhibition of asymmetric arginine methylation impairs RNA metabolism, which includes RNA splicing, alternative polyadenylation, and transcription termination. This triggers a robust downregulation of multiple pathways involved in the DNA damage response, thereby promoting genomic instability and inhibiting tumor growth. Taken together, our data support PRMT1 as a compelling target in PDAC and informs a mechanism-based translational strategy for future therapeutic development.Statement of significancePDAC is a highly lethal cancer with limited therapeutic options. This study identified and characterized PRMT1-dependent regulation of RNA metabolism and coordination of key cellular processes required for PDAC tumor growth, defining a mechanism-based translational hypothesis for PRMT1 inhibitors.


Assuntos
Carcinoma Ductal Pancreático/genética , Dano ao DNA , Neoplasias Pancreáticas/genética , Proteína-Arginina N-Metiltransferases/genética , RNA/genética , Proteínas Repressoras/genética , Animais , Biocatálise/efeitos dos fármacos , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/prevenção & controle , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Inibidores Enzimáticos/farmacologia , Feminino , Humanos , Camundongos Endogâmicos NOD , Camundongos Knockout , Camundongos SCID , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/prevenção & controle , Proteína-Arginina N-Metiltransferases/metabolismo , RNA/metabolismo , Interferência de RNA , Proteínas Repressoras/metabolismo , Carga Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto/métodos
20.
Cell Death Dis ; 12(7): 689, 2021 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-34244473

RESUMO

Renal cell carcinoma is the second malignant tumors in the urinary system with high mortality and morbidity. Increasing evidence suggests that long non-coding RNAs (lncRNAs) play critical roles in tumor development and progression. In the current study, based on the publicly available data obtained from GEO and TCGA database, we identified five prognosis-related lncRNAs with the ability to predict the prognosis of patients with renal cell carcinoma. Among them, the uncharacterized and upregulated lncRNA RCAT1 (renal cancer-associated transcript 1) was identified as the key lncRNA. Our data further revealed that the expression of lncRNA RCAT1 was significantly upregulated in renal cell carcinoma tissues and cells. Gain-of-function and loss-of-function studies showed that lncRNA RCAT1 promoted cell proliferation, migration, and invasion in vitro and in vivo. Furthermore, we verified that lncRNA RCAT1 could abundantly sponge miR-214-5p, which served as a tumor suppressor in renal cell carcinoma. Significantly, miR-214-5p overexpression could attenuate the promotion of cell proliferation and metastasis induced by lncRNA RCAT1. Moreover, we found that E2F2 was a direct target of miR-214-5p, and lncRNA RCAT1 could protect E2F2 from miR-214-5p-mediated degradation. Taken together, our findings suggested that lncRNA RCAT1 could enhance the malignant phenotype of renal cell carcinoma cells by modulating miR-214-5p/E2F2 axis, and lncRNA RCAT1 might be a novel prognostic biomarker and a potential therapeutic target for renal cell carcinoma.


Assuntos
Carcinoma de Células Renais/metabolismo , Movimento Celular , Fator de Transcrição E2F2/metabolismo , Neoplasias Renais/metabolismo , Neoplasias Pulmonares/metabolismo , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , Animais , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/secundário , Linhagem Celular Tumoral , Proliferação de Células , Progressão da Doença , Fator de Transcrição E2F2/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Renais/genética , Neoplasias Renais/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/secundário , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/genética , Invasividade Neoplásica , RNA Longo não Codificante/genética , Transdução de Sinais , Carga Tumoral
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...