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2.
Medicine (Baltimore) ; 98(38): e17033, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31567939

RESUMO

RATIONALE: Compared with most malignant tumors, papillary thyroid carcinoma (PTC) is usually associated with favorable survival and low recurrence rate. The prognostic factors of PTC include age, sex, tumor size, enlarged lymph nodes, and extrathyroidal extension. Among the extrathyroidal extension, upper aerodigestive tract (ADT) invasion by PTC is a marker of more aggressive tumor behavior, defining a subpopulation of patients at a greater risk of recurrence and death. PATIENT CONCERNS: A 61-year-old woman had a cervical mass that was slowly growing for three years. Additionally, she had haemoptysis of 1-year duration. During the month prior to her visit, she had difficulty breathing. DIAGNOSIS: Neck ultrasonography (US) and thyroid computed tomography (CT) images both showed a well-defined calcified mass on the left lobe of the thyroid gland. Additionally, the thyroid CT revealed that part of the mass protruded into the lumen which resulted in the thickening on the left side of the trachea. Accordingly, her diagnoses were as follows: firstly, a solid mass on the left lobe of the thyroid gland with tracheal compression; and finally, the space-occupying airway lesion. INTERVENTIONS: She underwent a bronchoscopic examination, which revealed a mass blocking most of the upper endoluminal trachea. Thus, the mass was resected at the upper tracheal segment, followed by electrotome and argon plasma coagulation treatment. She was then transferred to the Thyroid Surgery Department. Thyroid surgeons took the surgical type of bilateral subtotal thyroidectomy + exploration of bilateral recurrent laryngeal nerve + dissection of the lymph node in neck central area + circumferential sleeve resection + end-to-end anastomosis + tracheotomy in the patient. OUTCOMES: After surgery, she recovered well without any local recurrence or distant metastasis. LESSONS: When patients with PTC have haemoptysis, hoarseness, dyspnea, or any other symptoms, and the imaging examinations reveal a space-occupying lesion in the thyroid and airway, clinicians should focus on PTC with tracheal invasion, a bronchoscopic examination must be immediately performed because the subsequent surgical management depends on the degree of tracheal invasion.


Assuntos
Câncer Papilífero da Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Traqueia/diagnóstico por imagem , Diagnóstico Diferencial , Feminino , Hemoptise/etiologia , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Câncer Papilífero da Tireoide/complicações , Câncer Papilífero da Tireoide/secundário , Câncer Papilífero da Tireoide/cirurgia , Neoplasias da Glândula Tireoide/complicações , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/cirurgia , Tomografia Computadorizada por Raios X , Neoplasias da Traqueia/complicações , Neoplasias da Traqueia/secundário , Neoplasias da Traqueia/cirurgia , Ultrassonografia
3.
Medicine (Baltimore) ; 98(39): e17384, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31574891

RESUMO

BACKGROUND: Irinotecan (IRI)-based and oxaliplatin (OXA)-based regimens are available for the treatment of metastatic colorectal cancer (mCRC). Several studies have published inconsistent results in their comparisons of the efficacy and toxicity of IRI ±â€Šbevacizumab and OXA ±â€Šbevacizumab. This meta-analysis was performed to evaluate the efficacy and safety of these 2 regimens in patients with mCRC. METHODS: We searched several databases to identify relevant studies, including PubMed, EMBASE, and the Cochrane Controlled Trials Register. The primary endpoints were overall survival (OS) and time to progression (TTP). The secondary comparisons were overall response rate (ORR) and toxicity. In addition, the hazard ratio (HR) or risk ratio (RR) values with their corresponding 95% confidence intervals (CIs) were extracted from these studies. RESULTS: Pooled data of 13 studies demonstrated no significant differences in OS (HR = 0.96, 95% CI: 0.86-1.08, P = .53) and TTP (HR = 0.88, 95% CI: 0.72-1.08, P = .24) between the 2 groups. However, the ORR (RR = 0.87, 95% CI: 0.78-0.97, P = .02) was clearly improved in the OXA ±â€Šbevacizumab arm. Higher incidences of grade 3/4 nausea (RR = 1.63, 95% CI: 1.28-2.07, P < .001), vomiting (RR = 1.40, 95% CI: 1.09-1.81, P = .01), diarrhea (RR = 1.44, 95% CI: 1.23-1.70, P < .001), and anemia (RR = 4.13, 95% CI: 2.75-6.22, P < .001) were observed in the IRI group. However, the incidences of grade 3/4 neutropenia (RR = 0.75, 95% CI: 0.68-0.83, P < .001), thrombocytopenia (RR = 0.43, 95% CI: 0.26-0.73, P = .002), and paresthesia/neurological disturbances (RR = 0.04, 95% CI: 0.02-0.07, P < .001) were higher in the OXA group. CONCLUSION: This meta-analysis confirmed that the OXA ±â€Šbevacizumab regimen as a maintenance therapy significantly improved the ORR in patients with mCRC. Exhibiting strong efficacy and safety, the OXA and OXA plus bevacizumab regimens are preferred as first-line treatments for mCRC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Bevacizumab/administração & dosagem , Neoplasias Colorretais/tratamento farmacológico , Irinotecano/administração & dosagem , Oxaliplatina/administração & dosagem , Adulto , Idoso , Neoplasias Colorretais/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Resultado do Tratamento
4.
Anticancer Res ; 39(10): 5339-5344, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570427

RESUMO

BACKGROUND/AIM: Gemcitabine is standard first-line treatment for patients with advanced pancreatic cancer, however the efficacy is limited. Although acquired drug resistance and side-effects are known to limit efficacy, opposite effects of a drug, which enhance the malignancy of treated cancer, have been observed but are not well understood. The aim of the present study was to determine whether gemcitabine has such opposite effects on the BxPC-3 human pancreatic cancer cell line expressing green fluorescent protein (BxPC-3-GFP) in an orthotopic mouse model. MATERIALS AND METHODS: BxPC-3-GFP tumors grown subcutaneously in nude mice were harvested. Tumor fragments were orthotopically implanted in the tail of the pancreas of nude mice using the technique of surgical orthotopic implantation. The BxPC-3-GFP orthotopic models were divided randomly into three groups: Group 1: untreated control; Group 2: low-dose gemcitabine (weekly intraperitoneal injection at 25 mg/kg for 6 weeks); Group 3: high-dose gemcitabine (weekly intraperitoneal injection at 125 mg/kg for 6 weeks). Each group comprised eight mice. Tumor size, fluorescent area of metastases, and body weight were measured. RESULTS: Low- and high-dose gemcitabine inhibited primary tumor growth in a dose-dependent manner, and to the greatest extent by high-dose gemcitabine compared to the untreated control (p=0.0134). In contrast, the extent of metastasis on the peritoneum was significantly increased by low-dose gemcitabine compared to the untreated control (p=0.0112). The extent of metastasis showed no significant difference between the untreated control and mice treated with high-dose gemcitabine. Body weight of the treated mice was not significantly different from that of the untreated mice. CONCLUSION: The use of very bright GFP expressing of BxPC-3 cells and the orthotopic model demonstrated an unexpected increase in metastasis by low-dose gemcitabine. Future experiments will investigate the mechanism of this phenomenon.


Assuntos
Antimetabólitos Antineoplásicos/administração & dosagem , Desoxicitidina/análogos & derivados , Metástase Neoplásica/tratamento farmacológico , Neoplasias Pancreáticas/tratamento farmacológico , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Desoxicitidina/administração & dosagem , Modelos Animais de Doenças , Proteínas de Fluorescência Verde/metabolismo , Humanos , Camundongos , Camundongos Nus , Pâncreas/efeitos dos fármacos , Pâncreas/metabolismo , Neoplasias Pancreáticas/metabolismo
5.
Anticancer Res ; 39(10): 5653-5662, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570463

RESUMO

BACKGROUND/AIM: Factors influencing fulvestrant efficacy may be useful in selecting the optimal treatment regimen for postmenopausal Japanese women with metastatic/recurrent HR-positive, HER2-negative breast cancer. PATIENTS AND METHODS: We retrospectively evaluated progression-free and overall survival (PFS and OS) in 100 fulvestrant-treated patients according to metastatic site. RESULTS: Median PFS was significantly better in patients with non-visceral (bone and regional metastases; 22.8 months) vs. visceral metastasis (lung, liver, and other organs; 8.2 months; p=0.024), although median OS did not differ (p=0.922). Median PFS in patients with lung metastasis (20.8 months) and non-visceral metastasis (22.8 months) were comparable; patients with liver metastasis (6.1 months) and other organ metastases (3.7 months) had worse prognoses. CONCLUSION: Patients with non-visceral metastases had a better prognosis than those with visceral metastases. Fulvestrant induced a longer PFS in patients with non-visceral metastasis, and also in those with lung metastasis without liver or other organ involvement.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Fulvestranto/uso terapêutico , Metástase Neoplásica/prevenção & controle , Recidiva Local de Neoplasia/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica/genética , Metástase Neoplásica/patologia , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Prognóstico , Intervalo Livre de Progressão , Receptor ErbB-2/genética , Receptores de Superfície Celular/genética , Estudos Retrospectivos
6.
Medicine (Baltimore) ; 98(36): e16658, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31490360

RESUMO

RATIONALE: Pelvic tumor had great impact on patients' quality of life. After tumor resection, how to accurately fill bone defect remained challenging for orthopedic surgeons. Due to lack of individual design, high incidence of prosthetic mismatching, and loosening were reported in pelvic reconstruction surgery with conventional modular prostheses. Nowadays, with rapid development of three-dimensional (3D) print technology, pelvic prostheses could be designed according to patients' own anatomy. The objective of this study was to describe the application of 3D printed customized hemi-pelvic prosthesis for patients with pelvic tumor. PATIENT CONCERNS: A 62-year-old female had developed severe right joint pain without obvious inducement from 5 months before she sought medical advice. Pain, swelling, and limited range of motion of right joint were founded during physical examination. DIAGNOSIS: The patients were diagnosed as "right acetabulum metastatic carcinoma" INTERVENTION:: 3D printed titanium alloy hemi-pelvic prosthesis was designed according the morphology of unaffected side hemi-pelvis and subsequently implanted in surgery to reconstruct the pelvis. 3D printed osteotomy guide and pelvic model were also manufactured and applied to improve accuracy of osteotomy and reduce operation time. X-Ray of pelvis, Harris score, musculoskeletal tumor society score (MSTS) and The MOS item short from health survey (SF-36) were recorded during the period of preoperation, 1, 3, 6, 12 months follow-up after operation. OUTCOMES: 3D printed hemi-pelvic prosthesis matched precisely with pelvis and implanted successfully. There was no sign of prosthetic loosening within 12 months' follow-up. No sign of peri-prosthetic infection from laboratory examination. Harris score, MSTS, and SF-36 were gradually increasing during follow-up period. LESSONS: Satisfactory effect of pelvic reconstruction could be achieved by 3D printed hemi-pelvic prostheses. It also provided a promising way to the treatment of pelvic tumor in similar cases.


Assuntos
Neoplasias Pélvicas/cirurgia , Impressão Tridimensional , Desenho de Prótese/métodos , Procedimentos Cirúrgicos Reconstrutivos/métodos , Feminino , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Neoplasias Pélvicas/patologia , Implantação de Prótese
7.
Medicine (Baltimore) ; 98(36): e16705, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31490362

RESUMO

Deregulation of miR-153 has recently been observed in several common human cancer, while miR-153 serves an oncogene or tumor suppressive role in different cancer types. Previously, miR-153 has been identified to be overexpressed in prostate cancer. miR-153 played an important role in promoting proliferation of human prostate cancer cells and presented a novel mechanism of microRNA-mediated direct suppression of phosphatase and tensin homolog (PTEN) expression in prostate cancer cells. Until now, little is known about the clinical significance of miR-153 expression in prostate cancer.The miR-153 expression in 143 pairs of prostate cancer and adjacent non-cancerous prostate tissues was measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis. Student t test was conducted for intergroup comparison. Pearson correlation test was used for correlation analysis. Survival curves were carried out by the Kaplan-Meier method and evaluated using the log-rank test. Multivariable Cox proportional hazard risk regression model was performed to screen the independent factor affected the prognosis of prostate cancer patients.qRT-PCR analysis showed that the expression of miR-153 was significantly increased in the prostate cancer tissues in comparison with the adjacent noncancerous prostate tissues (P < .001). The high expression of miR-153 in prostate cancer tissues is closely correlated with aggressive clinical pathological parameters such as lymph node metastasis (P = .001); bone metastasis (P < .001); Gleason score (P < .001); and tumor-node-metastasis (TNM) stage (P < .001). Prostate cancer patients with a high expression of miR-153 had an evidently lower 5-year overall survival as compared with those with a low expression of miR-153 (P = .019). Notably, the multivariate Cox regression analysis indicated that miR-153 expression was an independent factor for predicting the 5-year overall survival of prostate cancer patients (hazard ratio [HR] = 2.481, 95% confidence interval [CI]: 1.582-10.727; P = .018).Our study demonstrated that high miR-153 expression was significantly associated with a poor overall survival independently of other factors in prostate cancer. Therefore, miR-153 may be an available biomarker for prostate cancer prognosis.


Assuntos
MicroRNAs/biossíntese , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Idoso , Biomarcadores Tumorais , Intervalo Livre de Doença , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Metástase Neoplásica , Prognóstico , Reação em Cadeia da Polimerase Via Transcriptase Reversa
8.
Medicine (Baltimore) ; 98(36): e16797, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31490366

RESUMO

Malignant triton tumor (MTT) is an extraordinarily uncommon and aggressive tumor which have poor prognosis. Malignant peripheral nerve sheath tumors with additional rhabdomyoblasts are found in MTT histologically. The prognosis of patients is poor. The goal of our study is to describe the largest number of cases characteristic and outcome, to our knowledge, such a presentation was not described in the English-language literature until now.From 1999 to 2014, 10 patients (5 women and 5 men) with a malignant triton tumor were treated at our institution. All these cases were followed-up and patient charts were analyzed for outcome.In our study, 3 cases of the Malignant triton tumors originate in the head, 2 cases in the joints, 2 cases in the retroperitoneum, 2 cases in the soft tissues of the thoracic wall, and 1 case in the prostate. Neoplasm associated with pain was the main manifestation. Patients have a poor prognosis. Completely surgical excision of the tumor is the only treatment. Additional radiation or chemotherapy show little effect.Malignant triton tumor is a rare sarcoma. The high probability of developing local recurrence and distant metastases could account for its poor prognosis.


Assuntos
Neoplasias da Bainha Neural/patologia , Neurilemoma/patologia , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Neoplasias da Bainha Neural/terapia , Neurilemoma/terapia , Prognóstico
9.
Medicine (Baltimore) ; 98(36): e17028, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31490389

RESUMO

Vasculogenic mimicry (VM) involves a tubular structure with a basement membrane that is similar to and communicates with vessels but functions independent of blood vessels to nourish tumor cells, promote tumor progression, invasion, and metastasis, with reduced 5-year survival rates. Tumor cell proliferation, invasion, and metastasis are promoted by the epithelial-mesenchymal transition (EMT). Paired-related homeobox 1 (PRRX1), a newly discovered EMT inducer, has been shown to correlate with metastasis and prognosis in diverse cancer types. Cancerous inhibitor of protein phosphatase 2A (CIP2A) was initially recognized as an oncoprotein. In this study, we aimed to investigate the expression and clinical significance of the EMT markers PRRX1, CIP2A and VM in clear cell renal cell carcinoma (CCRCC) and their respective associations with clinicopathological parameters and survival.Expression of PRRX1, CIP2A and VM in whole CCRCC tissues from 110 patients was analyzed by immunohistochemical and histochemical staining. Fisher's exact test or the chi square test was used to assess associations with positive or negative staining of these markers and clinicopathological characteristics.Positive expression of CIP2A and VM presence was significantly higher and that of PRRX1 was significantly lower in CCRCC tissues than in corresponding normal tissues. Furthermore, positive expression of CIP2A and VM was significantly associated with tumor grade, size, lymph node metastasis (LNM) stage, and tumor node metastasis (TNM) stage and inversely associated with overall survival time (OST). Moreover, levels of PRRX1 were negatively associated with tumor grade, size, LNM stage, and TNM stage. The PRRX1 subgroup had a significantly longer OST time than did the PRRX1 subgroup. In multivariate analysis, high VM and CIP2A, tumor grade, LNM stage, TNM stage, and low PRRX1 levels were identified as potential independent prognostic factors for OST in CCRCC patients.VM and expression of CIP2A and PRRX1 represent promising biomarkers for metastasis and prognosis and potential therapeutic targets in CCRCC.


Assuntos
Autoantígenos/metabolismo , Carcinoma de Células Renais/metabolismo , Proteínas de Homeodomínio/metabolismo , Neoplasias Renais/metabolismo , Proteínas de Membrana/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/patologia , Feminino , Humanos , Rim/patologia , Neoplasias Renais/diagnóstico , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Prognóstico
10.
Stud Health Technol Inform ; 267: 181-186, 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31483271

RESUMO

Gene expression data is commonly available in cancer research and provides a snapshot of the molecular status of a specific tumor tissue. This high-dimensional data can be analyzed for diagnoses, prognoses, and to suggest treatment options. Machine learning based methods are widely used for such analysis. Recently, a set of deep learning techniques was successfully applied in different domains including bioinformatics. One of these prominent techniques are convolutional neural networks (CNN). Currently, CNNs are extending to non-Euclidean domains like graphs. Molecular networks are commonly represented as graphs detailing interactions between molecules. Gene expression data can be assigned to the vertices of these graphs, and the edges can depict interactions, regulations and signal flow. In other words, gene expression data can be structured by utilizing molecular network information as prior knowledge. Here, we applied graph CNN to gene expression data of breast cancer patients to predict the occurrence of metastatic events. To structure the data we utilized a protein-protein interaction network. We show that the graph CNN exploiting the prior knowledge is able to provide classification improvements for the prediction of metastatic events compared to existing methods.


Assuntos
Neoplasias da Mama , Aprendizado Profundo , Humanos , Aprendizado de Máquina , Metástase Neoplásica , Redes Neurais (Computação)
11.
Cancer Radiother ; 23(6-7): 496-499, 2019 Oct.
Artigo em Francês | MEDLINE | ID: mdl-31471251

RESUMO

Stereotactic radiotherapy of oligometastases, mono- or hypofractionated, represents a fundamental change in the practice of the specialty as it was developed for a century. Despite the great heterogeneity of sites, techniques, and doses, most studies found a high local control rate, around 70 to 90% at 2 years, and reduced toxicity, around 5% of grade 3 at 2 years. Four main phase II and III trials are underway in France. Future research concerns the association of stereotactic radiotherapy with immunotherapy or different conventional chemotherapy protocols, the identification of the best clinical presentations, and optimization of fractionation and biological dose for poor prognosis localizations.


Assuntos
Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Neoplasias/radioterapia , Radiocirurgia/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Anticorpos Monoclonais/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/radioterapia , Neoplasias Ósseas/secundário , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/radioterapia , Terapia Combinada/métodos , Previsões , França , Humanos , Imunoterapia , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/radioterapia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/radioterapia , Masculino , Metástase Neoplásica , Neoplasias/patologia , Neoplasias/terapia , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/radioterapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia
13.
Cancer Radiother ; 23(6-7): 486-495, 2019 Oct.
Artigo em Francês | MEDLINE | ID: mdl-31501025

RESUMO

The basis of treatment of primary disease in case of metastatic cancer at diagnosis is based on the knowledge of the natural history of the disease, the biology of the primary tumour and its metastases, advances in modern radiotherapy techniques (modulated intensity, stereotactic radiotherapy) in order to improve the survival of patients with advanced disease. The clinical concept of oligometastatic disease at diagnosis has repositioned the interest of local treatment for primitive disease because these patients have a slower evolutionary profile than metastatic disease extended from the outset. This article reviews the indication of radiotherapy as a local treatment for primary cancer in a de novo metastatic diagnosed disease in the case of breast cancer, non-small cell lung cancer and prostate cancer.


Assuntos
Neoplasias da Mama/radioterapia , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias Pulmonares/radioterapia , Neoplasias da Próstata/radioterapia , Neoplasias da Mama/patologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Metástase Neoplásica , Estudos Prospectivos , Neoplasias da Próstata/patologia , Estudos Retrospectivos
14.
Cancer Treat Rev ; 79: 101893, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31499407

RESUMO

BACKGROUND: The management of locally advanced rectal cancer (RC) is an evolving clinical field where the multidisciplinary approach can reach its best, and liquid biopsy for obtaining tumor-derived component such as circulating tumor DNA (ctDNA) might provide complementary informations. METHODS: A systematic review of studies available in literature of liquid biopsy in non-metastatic RC has been performed according to PRISMA criteria to assess the role of ctDNA as a diagnostic, predictive and prognostic biomarker in this setting. RESULTS: Twenty-five publications have been retrieved, of which 8 full-text articles, 7 abstracts and 10 clinical trials. Results have been categorized into three groups: diagnostic, predictive and prognostic. Few but promising data are available about the use of liquid biopsy for early diagnosis of RC, with the main limitation of sensitivity due to low concentrations of ctDNA in this setting. In terms of prediction of response to chemoradiation, still inconclusive data are available about the utility of a pre-treatment liquid biopsy, whereas some studies report a positive correlation with a dynamic (pre/post-treatment) monitoring. The presence of minimal residual disease by ctDNA was consistently associated with worse prognosis across studies. CONCLUSIONS: The use of liquid biopsy for monitoring response to chemoradiation and assess the risk of disease recurrence are the most advanced potential applications for liquid biopsy in RC, with implications also in the context of non-operative management strategies.


Assuntos
Biomarcadores Tumorais , Biópsia Líquida , Neoplasias Retais/diagnóstico , DNA Tumoral Circulante , DNA de Neoplasias , Humanos , Biópsia Líquida/métodos , Metástase Neoplásica , Estadiamento de Neoplasias , Células Neoplásicas Circulantes , Prognóstico , Neoplasias Retais/etiologia , Neoplasias Retais/mortalidade , Neoplasias Retais/terapia , Recidiva , Resultado do Tratamento
15.
Medicine (Baltimore) ; 98(37): e17178, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31517873

RESUMO

The role of palliative primary tumor resection (PPTR) in improving survival in patients with synchronous unresectable metastatic colorectal cancer (mCRC) is controversial. In this study, we aimed to evaluate whether our novel scoring system could predict survival benefits of PPTR in mCRC patients.In this retrospective cohort study consecutive patients with synchronous mCRC and unresectable metastases admitted to Sir Run Run Shaw Hospital between January 2005 and December 2013 were identified. A scoring system was established by the serum levels of carcinoembryonic antigen (CEA), cancer antigen 19-9 (CA19-9), neutrophil/lymphocyte ratio (NLR), and lactate dehydrogenase (LDH). Patients with scores of 0, 1-2, or 3-4 were considered as being in the low, intermediate, and high score group, respectively. Primary outcome was overall survival (OS).A total of 138 eligible patients were included in the analysis, of whom 103 patients had undergone PPTR and 35 had not. The median OS of the PPTR group was better than that of the Non-PPTR group, with 26.2 and 18.9 months, respectively (P < .01). However, the subgroup of PPTR with a high score (3-4) showed no OS benefit (13.3 months) compared with that of the Non-PPTR group (18.9 months, P = .11). The subgroup of PPTR with a low score (52.1 months) or intermediate score (26.2 months) had better OS than that of the Non-PPTR group (P < .001, P = .017, respectively).A novel scoring system composed of CEA, CA19-9, NLR, and LDH values is a feasible method to evaluate whether mCRC patients would benefit from PPTR. It might guide clinical decision making in selecting patients with unresectable mCRC for primary tumor resection.


Assuntos
Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/cirurgia , Metástase Neoplásica/terapia , Cuidados Paliativos , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Projetos de Pesquisa , Estudos Retrospectivos , Adulto Jovem
16.
Anticancer Res ; 39(9): 4699-4709, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519569

RESUMO

BACKGROUND/AIM: Metformin, a drug for type 2 diabetes, also exerts anticancer effects. This study addressed the immunological effects of metformin on peritoneal dissemination. MATERIALS AND METHODS: We developed a mouse model of peritoneal dissemination via intraperitoneal injection of RLmale1, an X-ray-induced leukemia cell line, into BALB/c mice. Cell-surface markers, cytokine production, and myeloid-derived suppressor cells (MDSCs) were examined in cells from spleen and peritoneal lavage fluid. RESULTS: Metformin-treated mice exhibited suppressed intraperitoneal tumor growth and extended survival, and these effects were lost in mice with severe combined immunodeficiency. MDSCs induction was inhibited in metformin-treated mice. Although MDSC mobilization into the peritoneal cavity was correlated with suppression of interferon-γ production by tumor-infiltrating lymphocytes, the T-helper 1 ability of these lymphocytes was preserved in metformin-treated mice. CONCLUSION: Our findings demonstrate the action of metformin on both intraperitoneal tumors and immune-suppressive cells and might contribute to the development of immunotherapy against peritoneal dissemination.


Assuntos
Imunomodulação/efeitos dos fármacos , Metformina/farmacologia , Neoplasias Peritoneais/imunologia , Neoplasias Peritoneais/patologia , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/imunologia , Animais , Biomarcadores , Linhagem Celular Tumoral , Modelos Animais de Doenças , Humanos , Imunofenotipagem , Masculino , Camundongos , Células Supressoras Mieloides/efeitos dos fármacos , Células Supressoras Mieloides/imunologia , Células Supressoras Mieloides/metabolismo , Metástase Neoplásica , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/mortalidade , Modelos de Riscos Proporcionais , Ensaios Antitumorais Modelo de Xenoenxerto
17.
Anticancer Res ; 39(9): 4729-4736, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519572

RESUMO

BACKGROUND/AIM: Amphiregulin (AREG) and epiregulin (EREG) mRNA expression levels are predictors of response to anti-EGFR antibody therapy. Left-sided colon cancer is more sensitive to anti-EGFR antibodies than right-sided, although the mechanism is unclear. The aim of this study was to determine the relationship between AREG, EREG mRNA expression levels and tumor location as well as the efficacy of anti-EGFR antibody agents. MATERIALS AND METHODS: Real-time PCR was used to assess AREG and EREG mRNA expression in metastatic colorectal cancer (CRC) samples from 153 patients. RESULTS: Among KRASwt samples, high AREG expression (AREGHigh) was significantly more common in left-sided tumors than in right-sided. Among patients who received anti-EGFR antibody, response rates were significantly higher in AREGHigh than in AREGLow In the left-sided tumor group, overall survival was significantly longer in patients with high EREG levels than with low levels, whereas the right-sided tumor group showed no survival difference between them. CONCLUSION: AREG and EREG mRNA expression levels in left-sided CRC were higher than in right-sided tumors. This may help explain why left-sided CRC is more responsive to anti-EGFR antibodies.


Assuntos
Anfirregulina/genética , Neoplasias Colorretais/genética , Epirregulina/genética , Regulação Neoplásica da Expressão Gênica , RNA Mensageiro/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Imunológicos/farmacologia , Linhagem Celular Tumoral , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Especificidade de Órgãos/genética , Prognóstico , Proteínas Proto-Oncogênicas p21(ras)/genética
18.
Anticancer Res ; 39(9): 4917-4924, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519596

RESUMO

BACKGROUND/AIM: Recent data highlighted that location of metastatic colorectal cancer (mCRC) may have a prognostic impact and also a predictive value of the outcomes of first-line therapy. MATERIALS AND METHODS: The records of mCRC patients who underwent first-line therapy from 2011 to April 2018 at our Institute were retrospectively reviewed. Progression-free survival (PFS), overall survival (OS) and objective response rate (ORR) according to the primary tumor location were investigated. RESULTS: Overall, 130 patients were eligible. Two-year OS was 82.9% in left-sided colon cancers (LCC) and 67.5% in right-sided (RCC) (p=0.32). One-year mPFS was statistically longer in LCC (46.8% vs. 24.2%, p=0.0005). mPFS was longer in LCC treated with anti-VEGF vs. anti-EGFR (p=0.06). ORR was 51.1% in LCC, 25% in RCC (p=0.008). Overall, 11 complete responses all in LCC were observed (p=0.03). CONCLUSION: Tumor location has a prognostic impact and might influence the outcomes of mCRC patients.


Assuntos
Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/terapia , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento
19.
Anticancer Res ; 39(9): 4957-4963, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519601

RESUMO

BACKGROUND/AIM: Adjuvant radiotherapy (RT) damages multiple layers of skin, muscle, blood vessels and blood cells that are included within the RT area. Indirect, bystander systemic effects could also develop in cells not directly hit by radiation. MATERIALS AND METHODS: Ninety-three female patients recovering from breast cancer surgery and 82 female healthy blood donors were analyzed. For identification of systemic adaptive and innate immune response, rapid and low-cost blood-based biomarkers were assayed. RESULTS: Post-operated breast cancer patients had a decreased number of circulating adaptive immune response cells but increased number of circulating immunosuppressive myeloid subpopulations. RT decreased the number of T-cells and platelets without influencing the number of immunosuppressive myeloid subpopulations. Alterations in the number and phenotypes of T-cell subpopulations were associated with SNPs. CONCLUSION: The combination of RT and immunotherapy might provide optimal treatment for cancer patients.


Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/imunologia , Imunidade Celular/genética , Imunidade Celular/efeitos da radiação , Contagem de Leucócitos , Fenótipo , Polimorfismo de Nucleotídeo Único , Imunidade Adaptativa , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Neoplasias da Mama/patologia , Neoplasias da Mama/radioterapia , Estudos de Casos e Controles , Feminino , Humanos , Imunidade Inata , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Radioterapia Adjuvante , Linfócitos T/imunologia , Linfócitos T/metabolismo
20.
Anticancer Res ; 39(9): 4995-5001, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519606

RESUMO

BACKGROUND/AIM: Adoptive transfer of tumor-infiltrating lymphocytes (TILs) combined with non-myeloablative chemotherapy (NMA) has been shown to prolong survival in patients with metastatic disease. MATERIALS AND METHODS: Tissue harvesting was performed form a variety of sites. TILs were isolated, expanded and infused with bolus high-dose IL-2. RESULTS: Between 2008 and 2018, 242 lesions were resected for TILs harvesting from a range of sites form 196 patients without mortality and with minimal morbidity. Of those harvested, 75 were unable to complete therapy because of clinical deterioration during the wait period. Of 121 evaluable treated patients, there was no effect of metastatic site biopsied on the mean fold TIL expansion. Those receiving prior ipilimumab had a higher TIL fold expansion but a lower TIL fold expansion than those exposed to anti-PD1 therapy. CONCLUSION: Harvesting may be safely performed with successful TIL expansion from most sites. Prior check point inhibitory immunotherapy may potentially influence TIL fold expansion.


Assuntos
Imunoterapia Adotiva , Linfócitos do Interstício Tumoral/imunologia , Melanoma/imunologia , Melanoma/terapia , Adolescente , Adulto , Idoso , Antineoplásicos Imunológicos/farmacologia , Antineoplásicos Imunológicos/uso terapêutico , Biomarcadores Tumorais , Feminino , Humanos , Imunoterapia Adotiva/métodos , Linfócitos do Interstício Tumoral/metabolismo , Linfócitos do Interstício Tumoral/patologia , Masculino , Melanoma/metabolismo , Melanoma/patologia , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Adulto Jovem
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