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1.
Pan Afr Med J ; 33: 121, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31489099

RESUMO

Gestational trophoblastic disease (GTD) develops from abnormal cellular proliferation of trophoblasts following fertilization. It includes benign trophoblastic disease (hydatidiform moles (HM)) and the malignant trophoblastic diseases or gestational trophoblastic neoplasia (GTN). The frequency of the GTD in Tunisia is one per 918 deliveries. The aim of this study is to analyze the clinical characteristics, treatment and outcomes of GTD at Salah Azaiez Institute (ISA). Medical records of women diagnosed with GTD at ISA from January 1st, 1981 to December 31st, 2012 were retrospectively reviewed. FIGO score was determined retrospectively for patients treated before 2002. One hundred and nine patients with GTN were included. Patients presented with metastases at 43% of cases. The most common metastatic sites were lung (30%) and vagina (13%). Fifty six (56 (51%) patients had low-risk and 21 (19%) cases had high-risk, the FIGO score was not assessed in 32 cases. After a median follow-up of 46 months, 21 patients were lost to follow-up, 12 patients died, 19 progressed and 8 relapsed. At 10 years, the OS rate was 85% and the PFS rate 79%. OS was significantly influenced by the presence of metastases at presentation (M0 100 % vs. Metastatic 62 %; p < 0.0001), FIGO stage (I-II 100% VS 61% and 65% for stage III and IV; p < 0.001), FIGO score (low-risk 99 % vs. high-risk 78 %; p < 0.001). GTN is a significant source of maternal morbidity with increased risk of mortality from complications if not detected early and treated promptly.


Assuntos
Doença Trofoblástica Gestacional/epidemiologia , Mola Hidatiforme/epidemiologia , Adolescente , Adulto , Feminino , Seguimentos , Doença Trofoblástica Gestacional/patologia , Doença Trofoblástica Gestacional/terapia , Humanos , Mola Hidatiforme/patologia , Mola Hidatiforme/terapia , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/secundário , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Gravidez , Intervalo Livre de Progressão , Estudos Retrospectivos , Taxa de Sobrevida , Tunísia , Neoplasias Vaginais/epidemiologia , Neoplasias Vaginais/secundário , Adulto Jovem
2.
Anticancer Res ; 39(9): 4775-4779, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519578

RESUMO

BACKGROUND: Osteosarcoma is a recalcitrant disease treated with surgery and intensive chemotherapy as standard. The 5-year survival rate of patients with relapsed and lung metastatic osteosarcoma is as low as 20%. MATERIALS AND METHODS: A 16-year-old patient developed left distal femoral high-grade osteosarcoma and underwent cisplatinum-based neoadjuvant chemotherapy and surgery. From the resected tumor, a patient-derived orthotopic xenograft (PDOX) model was established in the femur of nude mice. PDOX models were randomized into the following groups: untreated control, or treatment with doxorubicin (3 mg/kg, i.p., weekly for 14 days), sunitinib (40 mg/kg, oral gavage, daily for 14 days), pazopanib (100 mg/kg, oral gavage, daily for 14 days), temozolomide(25 mg/kg, oral gavage, daily for 14 days), and eribulin (1.5 mg/kg, i.p., daily for 14 days). Tumor volume and body weight were monitored twice a week. RESULTS: The osteosarcoma PDOX was resistant to doxorubicin, sunitinib, and pazopanib. In contrast, eribulin and temozolomide arrested tumor growth. CONCLUSION: This study demonstrated the utility of the PDOX model in allowing effective from non-effective drugs to be distinguished in a model in which the tumor was growing on the organ corresponding to that of the patient.


Assuntos
Cisplatino/farmacologia , Doxorrubicina/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Furanos/farmacologia , Cetonas/farmacologia , Neoplasias Pulmonares/secundário , Osteossarcoma/patologia , Adolescente , Animais , Modelos Animais de Doenças , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Camundongos , Osteossarcoma/tratamento farmacológico , Carga Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
4.
Anticancer Res ; 39(8): 4065-4071, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366489

RESUMO

BACKGROUND: Surgical orthotopic implantation of human colon cancer tissue to the ceca of mice has been used to mimic behavior of cancer in human patients for the development of precision cancer medicine. However, with the current method of serosal surface implantation (SSI) of pieces of human colon cancer tissue, cancer cells are exposed to the peritoneum, which can artificially increase the rate of peritoneal carcinomatosis (PC) during the disease course. The objective of the present study was to introduce a tumor-sealing method (TSM) and compare it with SSI for the ability to produce clinically-relevant metastases without artificial PC. MATERIALS AND METHODS: HCT116 colon cancer cells transfected with green fluorescence protein (GFP) were cultured and then injected into the subcutaneous layer of athymic nude mice. Subcutaneous tumors were allowed to grow sufficiently to supply adequate tumor for orthotopic implantation. For SSI, a 1 mm3-sized tumor fragment was sutured to partially torn serosa of the cecum. For TSM, the blind end of the cecum was folded over the tumor fragment and sealed with sutures. At 20 days after implantation, all mice were opened to visualize PC by intravital fluorescence imaging. At necropsy, distant metastasis was investigated using frozen section of whole blocks of organs. RESULTS: At 20 days after implantation, PC rates in the SSI group and the TSM group were 80% (12/15) and 20% (3/15), respectively (p<0.001). The liver metastasis rate was 41.7% (5/12) in the SSI group and 50% (5/10) in the TSM group (p=0.696). The lung metastasis rate was 0% (0/12) in the SSI group and 10% (1/10) in the TSM group (p=0.201). The mean survival of mice without PC on the 20th day was significantly longer than that of mice with PC on the 20th day (69.1±14.7 vs. 44.5±12.4 days, p=0.001). CONCLUSION: These results suggest that TSM might be a more patient-like and useful method as a model of metastatic colon cancer than SSI.


Assuntos
Carcinogênese/genética , Neoplasias do Colo/patologia , Neoplasias Hepáticas/patologia , Neoplasias Pulmonares/patologia , Animais , Neoplasias do Colo/genética , Neoplasias do Colo/cirurgia , Modelos Animais de Doenças , Proteínas de Fluorescência Verde/química , Células HCT116 , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/secundário , Camundongos , Metástase Neoplásica , Transplante de Neoplasias/métodos , Imagem Óptica , Neoplasias Peritoneais/genética , Neoplasias Peritoneais/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
5.
Life Sci ; 234: 116771, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31421084

RESUMO

AIMS: We aimed to elucidate the effects and mechanisms of MAT1 in the progression of osteosarcoma, especially for its lung metastasis. MAIN METHODS: CCK-8 and flow cytometry assays were carried out to detect the proliferation and apoptosis of osteosarcoma cells. Wound healing and transwell assays were used to determine cell migration and invasion abilities. Real time quantitative PCR (RT-PCR) and western blot technologies were applied to detect the expression levels of RNA and protein, respectively. KEY FINDS: The results showed that both the mRNA and protein expression levels of MAT1 were elevated in osteosarcoma tissues with lung metastasis and metastatic lung tissues, particularly in the metastatic lung tissues, as compared to the osteosarcoma tissues without lung metastasis. High expression level of MAT1 in osteosarcoma patients showed a negative association with the overall survival. In addition, upregulation of MAT1 induced significant increases in cell growth, migration and invasion and an obvious inhibition in cell apoptosis in osteosarcoma MG63 and 143B cells, as well as elevated AKT1 expression level. Moreover, knockdown of AKT1 obviously impaired MAT1-mediated promotions in cell migration and invasion in vitro, as well as repressed tumor growth and reduced the number of metastatic lung tumors in xenografted nude mice. SIGNIFICANCE: This study reveals that high expression of MAT1 closely related to the poor prognosis and malignant clinical process of osteosarcoma patients. MAT1 serves as a promoter in the lung metastasis of osteosarcoma through increasing AKT1 expression. Our study may provide a potent therapeutic target for the lung metastasis of osteosarcoma.


Assuntos
Sistemas de Transporte de Aminoácidos Neutros/genética , Neoplasias Ósseas/patologia , Proteínas de Transporte/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/secundário , Osteossarcoma/patologia , Proteínas Proto-Oncogênicas c-akt/genética , Adulto , Animais , Neoplasias Ósseas/genética , Linhagem Celular Tumoral , Feminino , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Osteossarcoma/genética , Regulação para Cima , Adulto Jovem
6.
Int J Nanomedicine ; 14: 5109-5123, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31371950

RESUMO

Background: Renal cell carcinoma (RCC) is notorious for its resistance towards chemotherapy and radiation therapy in general. Combination therapy is often helpful in alleviating the resistance mechanisms by targeting multiple signaling pathways but is usually more toxic than monotherapy. Co-encapsulation of multiple therapeutic agents in a tumor-targeted drug delivery platform is a promising strategy to mitigate these limitations. Methods: A tumor-targeted liposomal formulation was prepared using phospholipids, cholesterol, DSPE-(PEG)2000-OMe and a proprietary tumor-targeting-peptide (TTP)-conjugated lipopeptide. An efficient method was optimized to encapsulate everolimus and vinorelbine in this liposomal formulation. Single drug-loaded liposomes were also prepared for comparison. Finally, the drug-loaded liposomes were tested in vitro and in vivo in two different RCC cell lines. Results: The tumor-targeted liposomal formulation demonstrated excellent tumor-specific uptake. The dual drug-loaded liposomes exhibited significantly higher growth inhibition in vitro compared to the single drug-loaded liposomes in two different RCC cell lines. Similarly, the dual drug-loaded liposomes demonstrated significantly higher suppression of tumor growth compared to the single drug-loaded liposomes in two different subcutaneous RCC xenografts. In addition, the dual drug-loaded liposomes instigated significant reduction in lung metastasis in those experiments. Conclusion: Taken together, this study demonstrates that co-delivery of everolimus and vinorelbine with a tumor-targeted liposomal formulation is an effective approach to achieve improved therapeutic outcome in RCC.


Assuntos
Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/patologia , Composição de Medicamentos , Sistemas de Liberação de Medicamentos/métodos , Everolimo/administração & dosagem , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia , Vinorelbina/administração & dosagem , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Antígeno Ki-67/metabolismo , Lipossomos , Neoplasias Pulmonares/secundário , Camundongos SCID , Fosfatidiletanolaminas/química , Polietilenoglicóis/química , Distribuição Tecidual , Ensaios Antitumorais Modelo de Xenoenxerto
7.
Kyobu Geka ; 72(4): 321-323, 2019 Apr.
Artigo em Japonês | MEDLINE | ID: mdl-31266919

RESUMO

Pulmonary epithelioid hemangioendthelioma(PEH) is rare malignant disease known to originate from hemangioendthelial cells. We report a case of PEH that is difficult to differential diagnosis on image. A 55-year-old woman was diagnosed with malignant lymphoma 15 years ago and had been followed-up. She referred to our hospital due to abnormal shadow on chest X-ray. Multiple nodules of 0.2~1.0 cm in size with clear but irregular margin were found in bilateral lungs on chest computed tomography(CT) scan. Nodules were found to be increased both in size and in number compared to those of 10 years ago. Pulmonary metastases of lymphoma, lung cancer or granulomatous disease were suspected and a thoracoscopic lung biopsy was performed, which led to a diagnosis of PEH pathologically.


Assuntos
Hemangioendotelioma Epitelioide , Hemangioendotelioma , Neoplasias Pulmonares , Feminino , Humanos , Pulmão , Neoplasias Pulmonares/secundário , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X
8.
J Cancer Res Clin Oncol ; 145(8): 2061-2069, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31309301

RESUMO

PURPOSE: Cervical cancer metastases to the ovary may occur with advanced tumor stage, deep cervical stromal involvement and corpus involvement. Endocervical adenocarcinoma in situ (AIS) with ovarian involvement is exceptionally rare with about twelve reported cases. METHODS: Here we present a case of endocervical AIS with ovarian and pulmonary involvement 39 months after the initial diagnosis. The characteristics of that case were compared and summarized with the eleven previously published cases. RESULTS: The patients' age ranged between 30 and 40 years (median 37.4 years). The time interval between the diagnosis of AIS and ovarian involvement was 26.7 months (range 2-84 months). Majority of the patients are alive without evidence of disease after a median time of 63.4 months (range 9-156 months). All reported cases were positive for high-risk HPV which was associated with strong p16 expression on immunohistochemistry. CONCLUSIONS: The ovarian involvement by endocervical AIS suggests the concept of a transtubal spread of the neoplastic cervical cells with or without previous colonization within the endometrium without evidence of invasive growth, suggesting a seed and soil spread of the disease. In cases with ovarian involvement by the AIS and without additional extragenital spread, the prognosis may be favorable.


Assuntos
Adenocarcinoma in Situ/patologia , Suscetibilidade a Doenças , Neoplasias Pulmonares/secundário , Neoplasias Ovarianas/secundário , Neoplasias do Colo do Útero/patologia , Adenocarcinoma in Situ/virologia , Adulto , Suscetibilidade a Doenças/etiologia , Suscetibilidade a Doenças/patologia , Suscetibilidade a Doenças/virologia , Feminino , Humanos , Neoplasias Pulmonares/virologia , Pessoa de Meia-Idade , Neoplasias Ovarianas/virologia , Papillomaviridae/fisiologia , Infecções por Papillomavirus/complicações , Neoplasias do Colo do Útero/virologia
9.
J Surg Oncol ; 120(4): 729-735, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31290159

RESUMO

BACKGROUND AND OBJECTIVES: While knowledge has grown extensively regarding the impact of mutations on colorectal cancer prognosis, their role in outcomes after pulmonary metastasectomy (PM) remains minimally understood. We sought to determine the prognostic role of mutant disease on survival and recurrence after metastasectomy. METHODS: Patients with available tumor sequencing profiles who underwent PM for colorectal cancer at a single institution from 2011 to 2017 were reviewed. Various demographic and clinicopathologic factors, as well as mutational status, were tested in the Cox regression analyses to identify predictors of survival and disease-free survival (DFS). RESULTS: A total of 130 patients met inclusion criteria, among whom 78 (60%) were male and the mean age was 57 years. The median survival time and 5-year survival rate were 58.2 months and 47%, respectively. A single pulmonary nodule was present in 54%. Disease recurrence occurred for 87 (67%) patients, including 75 (58%) who had at least one lung recurrence after metastasectomy at a median time to recurrence of 19.4 months. Upon multivariable analysis, RAS and TP53 mutations were associated with shorter survival DFS, while APC is associated with prolonged survival. CONCLUSIONS: After metastasectomy for colorectal cancer, mutations in RAS, TP53, and APC play an important role in survival and recurrence.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias Colorretais/mortalidade , Neoplasias Pulmonares/mortalidade , Metastasectomia/mortalidade , Mutação , Recidiva Local de Neoplasia/mortalidade , Pneumonectomia/mortalidade , Adulto , Idoso , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/secundário , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
10.
Nat Commun ; 10(1): 2510, 2019 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-31175290

RESUMO

Metastasis-associated recurrence is the major cause of poor prognosis in hepatocellular carcinoma (HCC), however, the underlying mechanisms remain largely elusive. In this study, we report that expression of choroideremia-like (CHML) is increased in HCC, associated with poor survival, early recurrence and more satellite nodules in HCC patients. CHML promotes migration, invasion and metastasis of HCC cells, in a Rab14-dependent manner. Mechanism study reveals that CHML facilitates constant recycling of Rab14 by escorting Rab14 to the membrane. Furthermore, we identify several metastasis regulators as cargoes carried by Rab14-positive vesicles, including Mucin13 and CD44, which may contribute to metastasis-promoting effects of CHML. Altogether, our data establish CHML as a potential promoter of HCC metastasis, and the CHML-Rab14 axis may be a promising therapeutic target for HCC.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Neoplasias Primárias Múltiplas/metabolismo , Proteínas rab de Ligação ao GTP/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/secundário , Células HEK293 , Humanos , Receptores de Hialuronatos/metabolismo , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/secundário , Camundongos , Camundongos Nus , Mucinas/metabolismo , Invasividade Neoplásica , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/metabolismo , Transplante de Neoplasias , Neoplasias Primárias Múltiplas/patologia , RNA Mensageiro/metabolismo , Carga Tumoral
11.
Rev Med Suisse ; 15(655): 1221-1225, 2019 Jun 12.
Artigo em Francês | MEDLINE | ID: mdl-31194297

RESUMO

The lung is the second site of metastasis after the liver, affecting 30 to 40 % of all patients with a malignant tumor. Chemotherapy seems to be ineffective for some types of tumor. Although there are no prospective randomized studies that confirm the benefit of surgical pulmonary metastasectomy, many studies have shown the existence of a group of patients with pulmonary metastases who benefit from a complete resection for curative purposes in case of complete resection of lung metastases. Different approaches are known to achieve a complete resection with maximum lung parenchyma sparing. Minimal invasive approaches appear to offer a better quality of life and have equivalent oncologic outcomes compared to the open approach.


Assuntos
Neoplasias Pulmonares , Metastasectomia , Pneumonectomia , Humanos , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/cirurgia , Complicações Pós-Operatórias , Estudos Prospectivos , Qualidade de Vida , Estudos Retrospectivos
13.
Medicine (Baltimore) ; 98(23): e15853, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31169689

RESUMO

INTRODUCTION: Meningioma is mostly a benign tumor, but sometimes it is malignant, and there have been reports of distant metastases. PATIENT CONCERNS: The patient, a woman in her 40s, was under follow-up after resection of an ectopic malignant meningioma originating in the left axilla. She was referred to our department because of a nodule shadow in the right lung on chest computed tomography (CT) 3 years and 5 months postoperatively. DIAGNOSIS: Chest CT showed a 1.0 cm nodule shadow in the right S4, which was positive on positron emission tomography-CT; no abnormality was found in any other organ. Therefore, it was considered to be a metastatic lung tumor. INTERVENTIONS: Right middle lobe partial resection was performed using thoracoscopic surgery, and a diagnosis of pulmonary metastasis of ectopic malignant meningioma was made by histopathology and immunohistochemistry. OUTCOMES: In this case, complete resection was possible. CONCLUSION: Meningioma occurs mainly in the cranium, and occurrence in the soft tissue of the extremities is extremely rare. To our knowledge, ours is the first report of a histologically malignant ectopic meningioma with metastasis to the thoracic cavity.


Assuntos
Neoplasias Pulmonares/secundário , Neoplasias Meníngeas/patologia , Meningioma/patologia , Adulto , Feminino , Humanos , Neoplasias Pulmonares/cirurgia , Neoplasias Meníngeas/cirurgia , Meningioma/cirurgia
14.
Gene ; 710: 258-264, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31176731

RESUMO

OBJECTIVE: Increasing evidence indicated that cancer-secreted exosomes played an important role in tumor metastasis. However, the function of exosomes in breast cancer pulmonary metastasis remains unknown. The aim of the study was to investigate the role of exosome-derived from breast cancer-secreted long non-coding RNAs (LncRNAs) on pre-metastatic niche formation in pulmonary metastasis. METHODS: Exosomes-derived from breast cancer were separated by ultracentrifugation. The high-throughput sequencing, Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were used to detect and evaluate the differential expression of LncRNAs in lung fibroblasts with exosomes treated. And quantitative real-time polymerase chain reaction (qRT-PCR) was performed to verify candidate LncRNAs expression. RESULTS: We found that exosomes-derived from breast cancer induced lung fibroblasts proliferation and migration. In addition, a large number of LncRNAs expression abnormalities were involved in the breast cancer lung metastasis microenvironment. CONCLUSION: Our findings suggested that exosomal LncRNAs facilitated tumor pre-metastatic niche formation and represented a novel mechanistic insight into the molecular mechanism of cancer metastasis microenvironment.


Assuntos
Neoplasias da Mama/genética , Exossomos/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Neoplasias Pulmonares/secundário , RNA Longo não Codificante/genética , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica , Ontologia Genética , Redes Reguladoras de Genes , Humanos , Neoplasias Pulmonares/genética , Análise de Sequência de RNA/métodos , Microambiente Tumoral
15.
Int J Nanomedicine ; 14: 3311-3330, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31190795

RESUMO

Background: Oral route of administration is preferred for treating breast cancer, especially when continued disease management with good tolerability is required; however, orally administered chemotherapeutics combined with near-infrared (NIR) dyes are hindered by the low bioavailability, insufficient for the desired therapeutic efficacy. In this study, we developed a hybrid self-microemulsifying drug delivery system for co-loading curcumin-phospholipid complex and NIR dye IR780 (CUR/IR780@SMEDDS), to achieve combined phototherapeutic and chemotherapeutic effects against lung metastasis of breast cancer. Methods: CUR/IR780@SMEDDS were characterized. The efficacy against breast cancer metastasis was evaluated by photothermal and photodynamic assessment, cytotoxicity, invasion, and migration in metastatic 4T1 breast cancer cells in vitro, and in vivo oral bioavailability study in rats and pharmacodynamics studies in tumor-bearing nude mice. Results: CUR/IR780@SMEDDS improved oral bioavailability of curcumin and IR780 in rats compared with curcumin and IR780 suspensions. CUR/IR780@SMEDDS exhibited remarkable photothermal and photodynamic effects in vitro. In metastatic 4T1 breast cancer cells, CUR/IR780@SMEDDS combined with localized NIR laser irradiation induced significant cytotoxicity and inhibited invasion and migration of 4T1 cells, an outcome attributable to cumulative effects of IR780-induced hyperthermia and pharmacological effects of curcumin. In orthotopic 4T1 tumor-bearing nude mice, combination of oral administration of CUR/IR780@SMEDDS with local NIR laser irradiation inhibited tumor progression and suppressed lung metastasis.


Assuntos
Neoplasias da Mama/patologia , Corantes/administração & dosagem , Curcumina/administração & dosagem , Curcumina/uso terapêutico , Sistemas de Liberação de Medicamentos , Indóis/administração & dosagem , Neoplasias Pulmonares/secundário , Fosfolipídeos/química , Administração Oral , Animais , Linhagem Celular Tumoral , Curcumina/farmacologia , Feminino , Humanos , Hipertermia Induzida , Camundongos Nus , Ratos Sprague-Dawley
16.
J Surg Oncol ; 120(3): 438-445, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31168858

RESUMO

BACKGROUND: Synchronous metastases are considered a negative prognostic factor in patients with metastatic colorectal cancer (CRC). We investigated the outcomes of stage IV CRC patients undergoing complete gross resection (R0/1) of both the primary tumor and the metastases under the guidance of a multidisciplinary team (MDT). METHODS: All CRC patients with synchronous metastases were retrieved from a prospective database. Patients treated from 2006 to 2017 who underwent complete resection were analyzed. Various factors, including multiple metastatic sites and complex procedures, were investigated. Univariate and multivariate overall survival (OS) calculations were performed. RESULTS: Of 330 consecutive patients with synchronous metastases, 101 (30.6%) achieved an R0/1 status including 12 (11.9%) patients with multiple metastatic sites. Complex procedures were necessary in 45 (44.6%) patients. Five-year OS was 53.0% for the R0/1 patient group. Multivariate analysis could not detect factors associated with prognosis. CONCLUSIONS: With modern treatment, the prognosis of patients with synchronous CRC metastases can be improved. Decisions made by a MDT offered one-third of patients a potentially curative approach to their stage IV disease. Despite the treatment of a high rate of patients with complex metastases necessitating complex procedures, we achieved a favorable 5-year OS rate.


Assuntos
Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Neoplasias Primárias Múltiplas/secundário , Neoplasias Primárias Múltiplas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/cirurgia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Peritoneais/secundário , Neoplasias Peritoneais/cirurgia , Estudos Retrospectivos
17.
Medicine (Baltimore) ; 98(24): e15888, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31192921

RESUMO

RATIONALE: Suppression and of cancer metastasis is one of the most important issues in cancer care. Considering the typical clinical course of metastases, cancer cells might prefer certain environments or conditions. However, favorable environments for cancer metastasis have not been clearly identified. We had previously described a case of dual, yet separate, pancreatic and colon cancer, in which the metastatic pancreatic cancer was localized at the invasive portion of the colon cancer. We hypothesized that metastatic pancreatic cancer took over the colon cancer microenvironment. PATIENT CONCERNS: We experienced an another case of double cancer in a 65-year-old man who had lung squamous cell carcinoma and an independent pancreatic adenocarcinoma that metastasized to the liver as well as to the lung cancer lesion and pulmonary fibrotic regions associated with pneumothorax and bronchiolization. INTERVENTIONS: The pneumothorax could not be controlled by conservative treatment. Thus, an emergency surgery with partial resection of the lower lobe of right lung was performed. DIAGNOSES: We found multiple pancreatic cancer metastases in the lung cancer and fibrotic lesions in the surgical specimen. However, we detected no metastasis in normal lung tissues except inside small arteries, although the lung cancer and fibrotic tissue areas were smaller than the normal lung tissue areas in the surgical specimen. OUTCOMES: The patient died 50 days after the surgery. LESSONS: This case may thus provide evidence to strengthen our hypothesis that pancreatic cancer prefers to metastasize to other independent cancer lesions, overtaking the cancer microenvironment constructed by other independent cancers. The lung cancer microenvironment, rich in myofibroblasts and/or cancer-associated fibroblasts, might be suitable for pancreatic carcinoma metastasis. In addition, we propose the hypothesis that compared with normal tissues, noncancerous fibrotic lesions are preferable destinations for cancer metastasis. Furthermore, metastasis of pancreatic carcinoma to lung cancer and fibrotic tissues might be more common, although such cases have not been previously reported.


Assuntos
Carcinoma de Células Escamosas/cirurgia , Neoplasias Pulmonares/cirurgia , Segunda Neoplasia Primária/cirurgia , Neoplasias Pancreáticas/cirurgia , Pneumotórax/cirurgia , Idoso , Carcinoma de Células Escamosas/diagnóstico , Evolução Fatal , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/secundário , Masculino , Segunda Neoplasia Primária/diagnóstico , Neoplasias Pancreáticas/diagnóstico , Pneumotórax/diagnóstico , Pneumotórax/etiologia , Fibrose Pulmonar/diagnóstico , Fibrose Pulmonar/cirurgia , Microambiente Tumoral
18.
Medicine (Baltimore) ; 98(25): e15873, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31232921

RESUMO

RATIONALE: Ameloblastoma is generally characterized as a benign tumor originating in odontogenic epithelium. However, few cases of metastatic malignant ameloblastoma have also been reported. Due to the low incidence of malignant ameloblastoma, there is no established treatment regimen. To explore effective treatment for malignant ameloblastoma, we reported this case study. PATIENTS CONCERNS: This report described a case of a 28-year-old malignant ameloblastoma female patient with multiple metastasis (brain and lung). DIAGNOSES: The patient presented ameloblastoma of the left mandible in 2012. Three years later, local recurrence and brain metastasis was observed during a follow-up examination. Five years later, malignant ameloblastoma was detected by imaging and immunohistochemistry in the bilateral multiple pulmonary nodules and mediastinal lymph nodes. INTERVENTIONS: The patient was initially treated with tumor resection. Three years later after local recurrence and brain metastasis, she was accepted the extensive mandibulectomy supplemented with brain stereotactic body radiotherapy (SBRT). When diagnosed with pulmonary metastasis, the patient received combined chemotherapy regimen of MAID (mesna, adriamycin, ifosfamide and dacarbazine) for 6 cycles. OUTCOMES: The efficacy evaluation was partial remission (PR) after the 6 cycles of MAID. The last patient follow-up was July 24th 2018, and no evidence of progression was observed. The progression-free survival (PFS) of the patient was more than 9 months. LESSONS: Surgical resection is the optimal treatment for locally recurrent ameloblastoma. SBRT may be an effective treatment for unresectable oligometastasis of malignant ameloblastoma. Finally, combined chemotherapy of MAID showed encouraging effects in the management of metastatic malignant ameloblastoma.


Assuntos
Ameloblastoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Maxilomandibulares/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Adulto , Ameloblastoma/diagnóstico por imagem , Ameloblastoma/secundário , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/secundário , Dacarbazina/administração & dosagem , Dacarbazina/uso terapêutico , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Doxorrubicina/uso terapêutico , Feminino , Humanos , Ifosfamida/administração & dosagem , Ifosfamida/uso terapêutico , Neoplasias Maxilomandibulares/diagnóstico por imagem , Neoplasias Maxilomandibulares/patologia , Neoplasias Pulmonares/secundário , Mesna/administração & dosagem , Mesna/uso terapêutico , Metástase Neoplásica , Resultado do Tratamento
19.
Nat Commun ; 10(1): 2698, 2019 06 20.
Artigo em Inglês | MEDLINE | ID: mdl-31221959

RESUMO

The different stages of the metastatic cascade present distinct metabolic challenges to tumour cells and an altered tumour metabolism associated with successful metastatic colonisation provides a therapeutic vulnerability in disseminated disease. We identify the aldo-keto reductase AKR1B10 as a metastasis enhancer that has little impact on primary tumour growth or dissemination but promotes effective tumour growth in secondary sites and, in human disease, is associated with an increased risk of distant metastatic relapse. AKR1B10High tumour cells have reduced glycolytic capacity and dependency on glucose as fuel source but increased utilisation of fatty acid oxidation. Conversely, in both 3D tumour spheroid assays and in vivo metastasis assays, inhibition of fatty acid oxidation blocks AKR1B10High-enhanced metastatic colonisation with no impact on AKR1B10Low cells. Finally, mechanistic analysis supports a model in which AKR1B10 serves to limit the toxic side effects of oxidative stress thereby sustaining fatty acid oxidation in metabolically challenging metastatic environments.


Assuntos
Aldeído Redutase/metabolismo , Neoplasias da Mama/patologia , Neoplasias Pulmonares/patologia , Recidiva Local de Neoplasia/patologia , Animais , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Ácidos Graxos/metabolismo , Feminino , Glicólise , Células HEK293 , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/secundário , Camundongos , Recidiva Local de Neoplasia/metabolismo , Oxirredução , Estresse Oxidativo , Esferoides Celulares , Ensaios Antitumorais Modelo de Xenoenxerto
20.
Medicine (Baltimore) ; 98(20): e15755, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31096541

RESUMO

RATIONALE: Hepatocellular carcinoma (HCC), one of the most common cancers worldwide, is an aggressive tumor with very poor prognosis. Regorafenib was the first agent to show a survival benefit over placebo in patients who showed progression while being treated with sorafenib, but it remains an unsatisfactory agent owing to its serious side effects. Therefore, more efficient and milder therapies are needed. PATIENT CONCERNS: Herein, we report a patient with advanced HCC with many lung metastases who showed progression during sorafenib treatment. DIAGNOSES: HCC with lung metastases (stage IVB). INTERVENTIONS: SHR-1210 alone was used as second-line treatment. OUTCOMES: Although the lung metastases did not decrease 3 months after the treatment, they decreased significantly at 6 months after the treatment and partially disappeared. The tumor response indicated partial response. Furthermore, all of the lung metastases continued to decrease at about 17 months after treatment. The alpha-fetoprotein levels showed a similar trend. After a follow up of 19 months, the patient remains in good health. LESSONS: SHR-1210 alone as a second-line treatment for a patient with HCC showed excellent antitumor effects. We think that SHR-1210 may exert its antitumor effects through a late-onset model, which persist for a long time. The side effects were mild and well tolerated.


Assuntos
Antineoplásicos Imunológicos/administração & dosagem , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Antineoplásicos Imunológicos/farmacologia , Carcinoma Hepatocelular/metabolismo , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/secundário , Masculino , Pessoa de Meia-Idade , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Sorafenibe , Resultado do Tratamento , alfa-Fetoproteínas/metabolismo
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