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1.
Anticancer Res ; 41(5): 2473-2476, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33952473

RESUMEN

BACKGROUND/AIM: During surgery for patients with known, diffuse metastatic bone disease (MBD), lesional tissue is routinely sent for pathological evaluation. However, there are limited data to assess whether there is a role for histopathology for MBD despite time and cost of interpretation, as well as whether a positive sample changes the subsequent treatment course. PATIENTS AND METHODS: Sixty-six cases from 2017 to 2020 were reviewed retrospectively. The median age at surgery was 63.5 years (range of 23 to 84 years), and the primary tumor was most frequently breast (24.2%, n=16), renal (21.2%, n=14) or lung (15.2%, n=10). The most common location of MBD was the femur (60.6%, n=40). RESULTS: The overall yield of a positive tissue sample of MBD was 77.3% (n=51). The positive rate from sending intramedullary reamings was 65.4% (n=17 of 26). Among the 66 cases (63 patients), a change in the subsequent clinical management was recorded in 9.1% (n=6). The most common change was related to the medication regimen (n=5), with one change related to recognition of the carcinoma origin via histology, which was previously unknown. CONCLUSION: Despite the routine practice of sending tissue for histology during surgery for known and diffuse MBD, a change in the subsequent clinical management is uncommon. Prior to sending tissue, surgeons should discuss this practice with the multidisciplinary care team on a per-patient basis.


Asunto(s)
Enfermedades Óseas/cirugía , Neoplasias de la Mama/cirugía , Fémur/cirugía , Neoplasias Renales/cirugía , Neoplasias Pulmonares/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Enfermedades Óseas/diagnóstico por imagen , Enfermedades Óseas/patología , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/patología , Femenino , Fémur/diagnóstico por imagen , Fémur/patología , Humanos , Neoplasias Renales/diagnóstico por imagen , Neoplasias Renales/patología , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Resultado del Tratamiento
2.
Anticancer Res ; 41(5): 2553-2561, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33952483

RESUMEN

BACKGROUND/AIM: Regorafenib (REG) and trifluridine/tipiracil (FTD/TPI) have have been shown to improve overall survival in patients with refractory metastatic colorectal cancer. The aim of our study was to evaluate the efficacy and safety profiles of these agents administered in sequence in real world practice. PATIENTS AND METHODS: Clinical data of patients treated beyond the 2°line with REG or FTD/TPI between January 2016 and August 2020, were retrospectively collected from eight institutes in the Lazio Region. RESULTS: We included 49 patients treated with both drug sequences. A total of 28 G3/G4 toxicity events (53.8%) were recorded in the FTD/TPI-to-REG sequence vs. 24 (46.1%) in the reverse sequence. Median overall survival for the patients included in the FTP/TPI-to-REG group was 20 months (95%CI=16.7-23.3) vs. 27 months in the reverse group (95%CI=17.8-36.2). The disease control rate was 45.0% for patients treated with the REG-to-FTD/TPI sequence vs. 24.1% in those treated with the FTD/TPI-to-REG sequence (p=0.18). CONCLUSION: The sequence REG-to-FTD/TPI and vice versa can extend survival, whereas only REG-to-FTD/TPI stabilizes cancer growth.


Asunto(s)
Neoplasias Colorrectales/tratamiento farmacológico , Compuestos de Fenilurea/administración & dosificación , Piridinas/administración & dosificación , Pirrolidinas/administración & dosificación , Timina/administración & dosificación , Trifluridina/administración & dosificación , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Esquema de Medicación , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Compuestos de Fenilurea/efectos adversos , Supervivencia sin Progresión , Piridinas/efectos adversos , Pirrolidinas/efectos adversos , Timina/efectos adversos , Trifluridina/efectos adversos
3.
Anticancer Res ; 41(5): 2597-2603, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33952489

RESUMEN

BACKGROUND/AIM: Platinum-based chemotherapy with pemetrexed or paclitaxel/bevacizumab are regimens used in combination with checkpoint inhibitors in non-squamous non-small cell lung cancer (NSCLC) treatment. We conducted a real-world study to compare the outcomes of these chemotherapeutic regimens. PATIENTS AND METHODS: We investigated 1,534 patients with advanced non-squamous NSCLC treated with platin/pemetrexed (n=1212) or platin/paclitaxel/bevacizumab (n=322) in 9 cancer centres in the Czech Republic. RESULTS: The regimen containing platin/paclitaxel/bevacizumab showed significantly better overall response rate (ORR) compared to the platin/pemetrexed [40.8% vs. 32.7% (p=0.008)] in the overall population and [55.0% vs. 38.8% (p=0.002)] in the Eastern Cooperative Oncology Group performance status 0 group. There was no significant improvement in progression-free survival (PFS) and overall survival (OS) in either of these two groups of patients. CONCLUSION: In our real-world data analysis, patients treated with platin/paclitaxel/bevacizumab had better overall response rate (ORR), but not PFS or OS. Thus, both treatment regimens are similarly effective. Their selection should therefore be based on the potential side effects.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , /administración & dosificación , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bevacizumab/administración & dosificación , Bevacizumab/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Paclitaxel/administración & dosificación , Paclitaxel/efectos adversos , Pemetrexed/administración & dosificación , Pemetrexed/efectos adversos , Supervivencia sin Progresión
4.
Anticancer Res ; 41(5): 2605-2610, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33952490

RESUMEN

BACKGROUND/AIM: Recently, elevated levels of postoperative inflammatory markers have been reported to be associated with poorer long-term survival outcomes, regardless of the occurrence of infectious complications, in gastroenterological malignancies. The aim of this study was to evaluate the association between postoperative inflammation and shorter long-term survival after resection of colorectal liver metastases. PATIENTS AND METHODS: A total of 104 patients who underwent R0 resection for colorectal liver metastases were enrolled. The CRPmax levels were defined as the highest postoperative serum C-reactive protein levels during hospital stay. RESULTS: The high-CRPmax group had a significantly lower relapse-free survival rate than the low-CRPmax group, regardless of the occurrence of infectious complications. CONCLUSION: In colorectal liver metastasis as well as other malignancies, elevated postoperative levels of serum C-reactive protein are associated with shorter long-term survival, regardless of the occurrence of infectious complications.


Asunto(s)
Proteína C-Reactiva/metabolismo , Neoplasias Colorrectales/cirugía , Neoplasias Hepáticas/cirugía , Complicaciones Posoperatorias/sangre , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Colorrectales/sangre , Neoplasias Colorrectales/microbiología , Neoplasias Colorrectales/patología , Femenino , Humanos , Inflamación/sangre , Inflamación/microbiología , Inflamación/patología , Inflamación/cirugía , Neoplasias Hepáticas/sangre , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/secundario , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Complicaciones Posoperatorias/microbiología , Complicaciones Posoperatorias/cirugía
5.
Int J Mol Sci ; 22(5)2021 Mar 09.
Artículo en Inglés | MEDLINE | ID: mdl-33803458

RESUMEN

Tumor aggressiveness and progression is highly dependent on the process of metastasis, regulated by the coordinated interplay of genetic and epigenetic mechanisms. Metastasis involves several steps of epithelial to mesenchymal transition (EMT), anoikis resistance, intra- and extravasation, and new tissue colonization. EMT is considered as the most critical process allowing cancer cells to switch their epithelial characteristics and acquire mesenchymal properties. Emerging evidence demonstrates that epigenetics mechanisms, DNA methylation, histone modifications, and non-coding RNAs participate in the widespread changes of gene expression that characterize the metastatic phenotype. At the chromatin level, active and repressive histone post-translational modifications (PTM) in association with pleiotropic transcription factors regulate pivotal genes involved in the initiation of the EMT process as well as in intravasation and anoikis resistance, playing a central role in the progression of tumors. Herein, we discuss the main epigenetic mechanisms associated with the different steps of metastatic process, focusing in particular on the prominent role of histone modifications and the modifying enzymes that mediate transcriptional regulation of genes associated with tumor progression. We further discuss the development of novel treatment strategies targeting the reversibility of histone modifications and highlight their importance in the future of cancer therapy.


Asunto(s)
Transición Epitelial-Mesenquimal , Regulación Neoplásica de la Expresión Génica , Histonas/metabolismo , Proteínas de Neoplasias/metabolismo , Neoplasias/metabolismo , Procesamiento Proteico-Postraduccional , Animales , Humanos , Metástasis de la Neoplasia , Neoplasias/patología
6.
Int J Mol Sci ; 22(5)2021 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-33807717

RESUMEN

Genes showing higher expression in either tumor or metastatic tissues can help in better understanding tumor formation and can serve as biomarkers of progression or as potential therapy targets. Our goal was to establish an integrated database using available transcriptome-level datasets and to create a web platform which enables the mining of this database by comparing normal, tumor and metastatic data across all genes in real time. We utilized data generated by either gene arrays from the Gene Expression Omnibus of the National Center for Biotechnology Information (NCBI-GEO) or RNA-seq from The Cancer Genome Atlas (TCGA), Therapeutically Applicable Research to Generate Effective Treatments (TARGET), and The Genotype-Tissue Expression (GTEx) repositories. The altered expression within different platforms was analyzed separately. Statistical significance was computed using Mann-Whitney or Kruskal-Wallis tests. False Discovery Rate (FDR) was computed using the Benjamini-Hochberg method. The entire database contains 56,938 samples, including 33,520 samples from 3180 gene chip-based studies (453 metastatic, 29,376 tumorous and 3691 normal samples), 11,010 samples from TCGA (394 metastatic, 9886 tumorous and 730 normal), 1193 samples from TARGET (1 metastatic, 1180 tumorous and 12 normal) and 11,215 normal samples from GTEx. The most consistently upregulated genes across multiple tumor types were TOP2A (FC = 7.8), SPP1 (FC = 7.0) and CENPA (FC = 6.03), and the most consistently downregulated gene was ADH1B (FC = 0.15). Validation of differential expression using equally sized training and test sets confirmed the reliability of the database in breast, colon, and lung cancer at an FDR below 10%. The online analysis platform enables unrestricted mining of the database and is accessible at TNMplot.com.


Asunto(s)
Bases de Datos de Ácidos Nucleicos , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Internet , Neoplasias , Programas Informáticos , Humanos , Metástasis de la Neoplasia , Neoplasias/genética , Neoplasias/metabolismo
7.
Int J Mol Sci ; 22(6)2021 Mar 16.
Artículo en Inglés | MEDLINE | ID: mdl-33809749

RESUMEN

Metastatic castration-resistant prostate cancer (mCRPC) represents a condition of progressive disease in spite of androgen deprivation therapy (ADT), with a broad spectrum of manifestations ranging from no symptoms to severe debilitation due to bone or visceral metastatization. The management of mCRPC has been profoundly modified by introducing novel therapeutic tools such as antiandrogen drugs (i.e., abiraterone acetate and enzalutamide), immunotherapy through sipuleucel-T, and targeted alpha therapy (TAT). This variety of approaches calls for unmet need of biomarkers suitable for patients' pre-treatment selection and prognostic stratification. In this scenario, imaging with positron emission computed tomography (PET/CT) presents great and still unexplored potential to detect specific molecular and metabolic signatures, some of whom, such as the prostate specific membrane antigen (PSMA), can also be exploited as therapeutic targets, thus combining diagnosis and therapy in the so-called "theranostic" approach. In this review, we performed a web-based and desktop literature research to investigate the prognostic and theranostic potential of several PET imaging probes, such as 18F-FDG, 18F-choline and 68Ga-PSMA-11, also covering the emerging tracers still in a pre-clinical phase (e.g., PARP-inhibitors' analogs and the radioligands binding to gastrin releasing peptide receptors/GRPR), highlighting their potential for defining personalized care pathways in mCRPC.


Asunto(s)
Tomografía de Emisión de Positrones , Medicina de Precisión , Neoplasias de la Próstata Resistentes a la Castración/diagnóstico , Neoplasias de la Próstata Resistentes a la Castración/terapia , Biomarcadores de Tumor/metabolismo , Humanos , Masculino , Metástasis de la Neoplasia , Pronóstico , Neoplasias de la Próstata Resistentes a la Castración/diagnóstico por imagen , Neoplasias de la Próstata Resistentes a la Castración/patología
8.
Pan Afr Med J ; 38: 50, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33854679

RESUMEN

Introduction: breast cancer is the commonest malignant disease in Ghanaian women and accounts for 17% of cancer-related deaths in the country. It has been classified into molecular subtypes depending on the presence or absence of hormone receptors and the human epidermal growth factor receptor 2. Computed tomography is often the preferred modality for monitoring metastatic disease due to its ability to determine the extent of local and metastatic disease. Methods: this was a retrospective study conducted at Sweden Ghana Medical Centre (SGMC). Hospital records and chest and abdominal computed tomography (CT) scan images of breast cancer patients who had been managed at SGMC between June 2016 and August 2019 were used to document age, gender, histological group, type of surgical intervention done, molecular subtypes of the disease and imaging findings. Microsoft Excel 2016 and SPSS version 20.0 were used to summarise the data obtained into tables, charts and to test for significant associations. Results: the most common site of breast cancer metastasis was lymph nodes. The three commonest sites of distant metastases were the lung seen in 44 patients (55.3%), bone in 37 patients (44.6%) and liver in 33 patients (39.8%). Chi square test for association between the molecular subtypes of the breast cancer and proportion of patients that showed a particular type of metastases revealed that, the differences noted for lung, pleural and cardiac metastases were statistically significant, that for bone and liver were not. Conclusion: breast cancer commonly metastasised to lymph nodes, lung, bone, liver, pleura and heart in descending order. The commonest CT patterns for metastases were multiple nodules for lung, effusion for pleura and heart and osteolytic lesions for bone.


Asunto(s)
Neoplasias de la Mama Masculina/diagnóstico por imagen , Neoplasias de la Mama/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/patología , Neoplasias de la Mama Masculina/patología , Femenino , Ghana , Humanos , Metástasis Linfática/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia/diagnóstico por imagen , Estudios Retrospectivos
9.
World J Surg Oncol ; 19(1): 126, 2021 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-33866970

RESUMEN

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with poor prognosis. Radical surgery is the best option for cure and, nowadays, it is performed by many surgeons also in cases of vascular infiltration. Whether this aggressive approach to a locally advanced PDAC produces a survival benefit is under debate. Most data in the literature come from retrospective comparative studies; therefore, it is still unclear if such an extensive surgery for an advanced cancer is justified. METHODS: A retrospective review of patients with PDAC treated at our institution over a 12-year period was performed. Data concerning patients' characteristics, operative details, postoperative course, and long-term survival were retrieved from prospective databases and analysed. Factors associated with poor survival were assessed via Cox regression analysis. RESULTS: A total of 173 patients with PDAC were included in the analysis, 41 subjects underwent pancreatectomy with vascular resection for locally advanced disease, and in 132 patients, only a pancreatic resection was undertaken. Demographics, major comorbidities, and tumour characteristics were similar between the two groups. Length of surgery (P=0.0006), intraoperative blood transfusions (P<0.0001), and overall complications (P<0.0001) were significantly higher in the vascular resection group. Length of hospital stay (P=0.684) and 90-day mortality (P=0.575) were comparable between groups. Overall median survival (P= 0.717) and survival rates at 1, 3, and 5 years (P=0.964, P=0.500, and P=0.445, respectively) did not differ significantly between groups. Age ≥70 years and postoperative complications were independent predictors of lower survival. CONCLUSIONS: Our study confirms that pancreatectomy with vascular resection for a locally advanced PDAC is a complex operation associated with a significant longer operating time that may increase morbidity; however, in selected patients, R0 margins can be obtained with an acceptable long-term survival rate. Older patients are less likely to benefit from surgery.


Asunto(s)
Carcinoma Ductal Pancreático/cirugía , Pancreatectomía/métodos , Neoplasias Pancreáticas/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Ductal Pancreático/mortalidad , Carcinoma Ductal Pancreático/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Pancreatectomía/mortalidad , Neoplasias Pancreáticas/mortalidad , Neoplasias Pancreáticas/patología , Complicaciones Posoperatorias , Pronóstico , Estudios Retrospectivos , Análisis de Supervivencia , Tasa de Supervivencia , Sobrevivientes
10.
Anticancer Res ; 41(4): 1793-1802, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33813384

RESUMEN

BACKGROUND/AIM: Human epidermal growth factor receptor 2 (HER2) P95-isoform could be involved in trastuzumab resistance in HER2 metastatic breast cancer. MATERIALS AND METHODS: A total of 114 metastatic breast cancer patients treated with trastuzumab were evaluated retrospectively. HER2 was centrally reviewed. P95 was evaluated along with other markers possibly affecting trastuzumab efficacy in regards to progression-free survival and overall survival. RESULTS: HER2 was centrally negative in 54 cases. P95 expression was significantly higher in HER2-positive tumors. High p95 was associated with gain of HER2 copy number variations (CNVs), high pHER2Tyr877, Ki67 and HER2 mRNA. P95 as a continuous variable was positively correlated with mRNA expression of HER2 and negatively correlated with HER4 and IGF1. HER2-negative p95-high patients had a marginally higher risk for death (HR=2.15, p=0.055). CONCLUSION: p95 was associated with higher HER2 CNVs and mRNA expression, pHER2Tyr877 expression and high Ki67, indicating a more aggressive phenotype.


Asunto(s)
Antineoplásicos Inmunológicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Receptor ErbB-2/antagonistas & inhibidores , Trastuzumab/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/enzimología , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Resistencia a Antineoplásicos , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Isoenzimas , Antígeno Ki-67/metabolismo , Persona de Mediana Edad , Metástasis de la Neoplasia , Supervivencia sin Progresión , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Estudios Retrospectivos
11.
Int J Mol Sci ; 22(6)2021 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-33809315

RESUMEN

Patients with advanced breast cancer are at high risk of developing bone metastasis. Despite treatment advances for primary breast cancer, metastatic bone disease remains incurable with a low relative survival. Hence, new therapeutic approaches are required to improve survival and treatment outcome for these patients. Bone is among the most frequent sites of metastasis in breast cancer. Once in the bone, disseminated tumor cells can acquire a dormant state and remain quiescent until they resume growth, resulting in overt metastasis. At this stage the disease is characterized by excessive, osteoclast-mediated osteolysis. Cells of the bone microenvironment including osteoclasts, osteoblasts and endothelial cells contribute to the initiation and progression of breast cancer bone metastasis. Direct cell-to-cell contact as well as soluble factors regulate the crosstalk between disseminated breast cancer cells and bone cells. In this complex signaling network interleukins (ILs) have been identified as key regulators since both, cancer cells and bone cells secrete ILs and express corresponding receptors. ILs regulate differentiation and function of bone cells, with several ILs being reported to act pro-osteoclastogenic. Consistently, the expression level of ILs (e.g., in serum) has been associated with poor prognosis in breast cancer. In this review we discuss the role of the most extensively investigated ILs during the establishment of breast cancer bone metastasis and highlight their potential as therapeutic targets in preventing metastatic outgrowth in bone.


Asunto(s)
Neoplasias Óseas/genética , Neoplasias de la Mama/genética , Comunicación Celular/genética , Interleucinas/genética , Neoplasias Óseas/patología , Neoplasias Óseas/secundario , Huesos/metabolismo , Huesos/patología , Neoplasias de la Mama/patología , Linaje de la Célula/genética , Femenino , Humanos , Metástasis de la Neoplasia
12.
Int J Mol Sci ; 22(6)2021 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-33801148

RESUMEN

Chemotherapeutics are the mainstay treatment for metastatic breast cancers. However, the chemotherapeutic failure caused by multidrug resistance (MDR) remains a pivotal obstacle to effective chemotherapies of breast cancer. Although in vitro evidence suggests that the overexpression of ATP-Binding Cassette (ABC) transporters confers resistance to cytotoxic and molecularly targeted chemotherapies by reducing the intracellular accumulation of active moieties, the clinical trials that target ABCB1 to reverse drug resistance have been disappointing. Nevertheless, studies indicate that ABC transporters may contribute to breast cancer development and metastasis independent of their efflux function. A broader and more clarified understanding of the functions and roles of ABC transporters in breast cancer biology will potentially contribute to stratifying patients for precision regimens and promote the development of novel therapies. Herein, we summarise the current knowledge relating to the mechanisms, functions and regulations of ABC transporters, with a focus on the roles of ABC transporters in breast cancer chemoresistance, progression and metastasis.


Asunto(s)
Transportadoras de Casetes de Unión a ATP/genética , Transportadoras de Casetes de Unión a ATP/metabolismo , Neoplasias de la Mama/etiología , Neoplasias de la Mama/metabolismo , Transportadoras de Casetes de Unión a ATP/química , Transportadoras de Casetes de Unión a ATP/clasificación , Animales , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Transformación Celular Neoplásica/genética , Transformación Celular Neoplásica/metabolismo , Progresión de la Enfermedad , Susceptibilidad a Enfermedades , Resistencia a Antineoplásicos/efectos de los fármacos , Resistencia a Antineoplásicos/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Familia de Multigenes , Metástasis de la Neoplasia , Estadificación de Neoplasias , Relación Estructura-Actividad
13.
Int J Mol Sci ; 22(7)2021 Mar 31.
Artículo en Inglés | MEDLINE | ID: mdl-33807419

RESUMEN

Osteosarcoma (OSA) represents the most common bone tumor in dogs. The malignancy is highly aggressive, and most of the dogs die due to metastasis, especially to the lungs. The metastatic process is complex and consists of several main steps. Assessment of the molecular mechanisms of metastasis requires in vitro and especially in vivo studies for a full evaluation of the process. The molecular and biological resemblance of canine OSA to its human counterpart enables the utilization of dogs as a spontaneous model of this disease in humans. The aim of the present review article is to summarize the knowledge of genes and proteins, including p63, signal transducer and activator of transcription 3 (STAT3), Snail2, ezrin, phosphorylated ezrin-radixin-moesin (p-ERM), hepatocyte growth factor-scatter factor (HGF-SF), epidermal growth factor receptor (EGFR), miR-9, and miR-34a, that are proven, by in vitro and/or in vivo studies, to be potentially involved in the metastatic cascade of canine OSA. The determination of molecular targets of metastatic disease may enhance the development of new therapeutic strategies.


Asunto(s)
Metástasis de la Neoplasia/fisiopatología , Osteosarcoma/metabolismo , Animales , Neoplasias Óseas/genética , Neoplasias Óseas/metabolismo , Neoplasias Óseas/fisiopatología , Línea Celular Tumoral , Proteínas del Citoesqueleto/metabolismo , Modelos Animales de Enfermedad , Perros , Receptores ErbB/metabolismo , Regulación Neoplásica de la Expresión Génica/genética , Factor de Crecimiento de Hepatocito/metabolismo , MicroARNs , Metástasis de la Neoplasia/genética , Osteosarcoma/veterinaria , Fosforilación , Factor de Transcripción STAT3/metabolismo , Factores de Transcripción de la Familia Snail/metabolismo , Proteínas Supresoras de Tumor/metabolismo
14.
Medicine (Baltimore) ; 100(14): e25369, 2021 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-33832120

RESUMEN

ABSTRACT: Colon cancer patients suffer from high incidence and mortality rates worldwide. More novel molecular biomarkers should be used for the diagnosis and treatment of colon cancer. Long noncoding RNAs (lncRNAs) are found to be involved in colon cancer tumorigenesis and metastasis. This study aimed to identify novel lncRNAs in colon cancer.Two independent datasets (GSE70880 and GSE110715) were downloaded from the Gene Expression Omnibus database and merged with the sva package. R software was used to distinguish differentially expressed lncRNAs and mRNAs in the merged dataset. The competing endogenous RNA (ceRNA) network was constructed using differentially expressed lncRNAs and mRNAs with Cytoscape. Differentially expressed RNAs in the ceRNA network were further verified using the Cancer Genome Atlas database. Gene oncology analysis, Kyoto Encyclopedia of Genes and Genomes pathway enrichment and survival analysis were also performed to identify hub genes.A total of 99 differentially expressed lncRNAs and 95 differentially expressed mRNAs were identified in the merged database. Ten lncRNAs, 8 miRNAs, and 6 mRNAs were involved in the ceRNA network, in which LINC00114 and UCA1 were highly expressed in colon cancer. They were both associated with early tumor stages and might be used for the early diagnosis of colon cancer. High expression of LINC00114 can lead to poor overall survival of colon cancer patients. Furthermore, new pathways such as LINC00114/miR-107/PCKS5, UCA1/miR-107/PCKS5, and UCA1/miR-129-5p/SEMA6A were identified.Two novel lncRNAs (LINC00114 and UCA1) in colon cancer were identified by bioinformatics analysis. They might contribute to the occurrence and development of colon cancer. In addition, LINC00114 may be involved in the overall survival of colon cancer patients.


Asunto(s)
Neoplasias del Colon/genética , Biología Computacional/métodos , ARN Largo no Codificante/genética , ARN Mensajero/genética , Anciano , Biomarcadores de Tumor/genética , Carcinogénesis/genética , Carcinogénesis/patología , Neoplasias del Colon/epidemiología , Neoplasias del Colon/mortalidad , Bases de Datos Genéticas/estadística & datos numéricos , Femenino , Regulación Neoplásica de la Expresión Génica/genética , Humanos , Incidencia , Masculino , MicroARNs/genética , Persona de Mediana Edad , Metástasis de la Neoplasia/genética , Metástasis de la Neoplasia/patología , Estadificación de Neoplasias/métodos , Análisis de Supervivencia
15.
Medicine (Baltimore) ; 100(14): e25415, 2021 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-33832139

RESUMEN

BACKGROUND: Circular RNAs (circRNAs) regulate multiple pathways during lung cancer pathogenesis. Apart from functional significance, many circRNAs have been shown to be associated with clinicopathological characteristics and predict lung cancer prognosis. Our aim is to summarize the expanding knowledge of clinical roles of circRNAs in lung cancer. METHODS: A thorough search of literature was conducted to identify articles about the correlation between circRNA expression and its prognostic and clinicopathological values. Biological mechanisms were summarized. RESULTS: This study included 35 original articles and 32 circRNAs with prognostic roles for lung cancer. Increased expression of 25 circRNAs and decreased expression of 7 circRNAs predicted poor prognosis. For non-small cell lung cancer, changes of circRNAs were correlated with tumor size, lymph node metastasis, distant metastasis, tumor node metastasis (TNM) stage, and differentiation, indicating the major function of circRNAs is to promote lung cancer invasion and migration. Particularly, meta-analysis of ciRS-7, hsa_circ_0020123, hsa_circ_0067934 showed increase of the 3 circRNAs was associated with positive lymph node metastasis. Increase of ciRS-7 and hsa_circ_0067934 was also related with advanced TNM stage. The biological effects depend on the general function of circRNA as microRNA sponge. CONCLUSIONS: CircRNAs have the potential to function as prognostic markers and are associated with lung cancer progression and metastasis.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Neoplasias Pulmonares/diagnóstico , ARN Circular/metabolismo , Progresión de la Enfermedad , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Invasividad Neoplásica , Metástasis de la Neoplasia , Estadificación de Neoplasias , Pronóstico
16.
BMC Cancer ; 21(1): 385, 2021 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-33836674

RESUMEN

BACKGROUND: Herein, we investigate the relationship between pancreatic stem cell markers (PCSC markers), CD44, and epithelial-specific antigen (ESA), tumor stroma, and the impact on recurrence outcomes in pancreatic ductal adenocarcinoma (PDAC) patients. METHODS: PDAC patients who underwent surgical resection between 01/2012-06/2014 were identified. CD44 and ESA expression was assessed by immunohistochemistry. Stroma was classified as loose, moderate, and dense based on fibroblast content. Overall survival (OS) and relapse-free survival (RFS) were estimated using the Kaplan-Meier method and compared between subgroups by log-rank test. The association between PCSC markers and stroma type was assessed by Fisher's exact test. RESULTS: N = 93 PDAC patients were identified. The number of PDAC patients with dense, moderate density, and loose stroma was 11 (12%), 51 (54%), and 31 (33%) respectively. PDAC with CD44+/ESA- had highest rate of loose stroma (63%) followed by PDAC CD44+/ESA+ (50%), PDAC CD44-/ESA+ (35%), CD44-/ESA- (9%) (p = 0.0033). Conversely, lack of CD44 and ESA expression was associated with the highest rate of moderate and dense stroma (91% p = 0.0033). No local recurrence was observed in patients with dense stroma and 9 had distant recurrence. The highest rate of cumulative local recurrence was observed in patients with loose stroma. No statistically significant difference in RFS and OS was observed among subgroups (P = 0.089). CONCLUSIONS: These data indicate PCSCs may have an important role in stroma differentiation in PDAC. Our results further suggest that tumor stroma may influence the recurrence pattern in PDAC patients.


Asunto(s)
Fibroblastos Asociados al Cáncer/metabolismo , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/patología , Células Madre Neoplásicas/metabolismo , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patología , Células del Estroma/metabolismo , Biomarcadores , Fibroblastos Asociados al Cáncer/patología , Carcinoma Ductal Pancreático/mortalidad , Carcinoma Ductal Pancreático/terapia , Terapia Combinada , Femenino , Humanos , Inmunohistoquímica , Masculino , Clasificación del Tumor , Metástasis de la Neoplasia , Estadificación de Neoplasias , Células Madre Neoplásicas/patología , Neoplasias Pancreáticas/mortalidad , Neoplasias Pancreáticas/terapia , Pronóstico , Recurrencia , Células del Estroma/patología , Resultado del Tratamiento , Microambiente Tumoral
17.
BMC Cancer ; 21(1): 383, 2021 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-33836675

RESUMEN

BACKGROUND: Malignant struma ovarii (MSO) is a unique type of ovarian malignancy that data on the survival outcome is limited and management strategy remains controversial due to its extreme rarity. METHODS: To investigate the clinical characteristics and treatment options in patients with MSO confined to the ovary, while also evaluating the recurrent-free survival (RFS) and overall survival (OS) rate in this population, a retrospective study was conducted. One hundred twenty-five cases of MSO confined to the ovary were enrolled and their clinical characteristics, treatment strategies, and results of follow-up were analyzed. OS and RFS were assessed by Kaplan-Meier analyses and Cox regression models. RESULTS: The most common pathological subtype in this cohort was papillary carcinoma (44.8%). Other reported subtypes, in order of prevalence, were follicular variant of papillary carcinoma, follicular carcinoma, and mixed follicular-papillary carcinoma. Surgical treatment options varied in this cohort that 8.0% of the patients received ovarian cystectomy, 33.6% underwent unilateral salpingo-oophorectomy (USO), 5.6% received bilateral salpingo-oophorectomy (BSO), 21.6% received total abdominal hysterectomy with BSO (TAH/BSO), and 17.6% were treated with debulking surgery; 20.0% of them received radioiodine therapy (RAI). Twenty-seven patients experienced recurrence with a median RFS of 14.0 years (95% confidence interval [CI], 9.5-18.5). The 5-year and 10-year recurrent rate were 27.1, 35.2%, respectively. Eight patients died during follow-up, with five attributed to MSO; the 5-year, 10-year, and 20-year OS rate was 95.3, 88.7 and 88.7%, respectively. However, the univariate and multivariate Cox regression showed no potential risk factor for RFS and OS. CONCLUSION: Patients with MSO confined to the ovary had an excellent survival outcome, despite varied treatment strategies, and the recurrent rate was relatively high. We recommend USO as the preferred surgical option in this population since more aggressive surgery does not improve outcomes and the benefits of RAI are uncertain.


Asunto(s)
Neoplasias Ováricas/diagnóstico , Neoplasias Ováricas/mortalidad , Estruma Ovárico/diagnóstico , Estruma Ovárico/mortalidad , Adulto , Anciano , Biopsia , Toma de Decisiones Clínicas , Terapia Combinada , Manejo de la Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Persona de Mediana Edad , Clasificación del Tumor , Metástasis de la Neoplasia , Estadificación de Neoplasias , Neoplasias Ováricas/terapia , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Estruma Ovárico/terapia , Resultado del Tratamiento
18.
BMC Cancer ; 21(1): 379, 2021 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-33836680

RESUMEN

BACKGROUND: Immunotherapy is a vital component in cancer treatment. However, due to the complex genetic bases of cancer, a clear prediction index for efficacy has not been established. Tumor mutation burden (TMB) is one of the essential factors that affect immunotherapeutic efficacies, but it has not been determined whether the mutation is associated with the survival of Skin Cutaneous Melanoma (SKCM) patients. This study aimed at evaluating the correlation between TMB and immune infiltration. METHODS: Somatic mutation profiles (n = 467), transcriptome data (n = 471), and their clinical information (n = 447) of all SKCM samples were downloaded from The Cancer Genome Atlas (TCGA) database. For each sample, TMB was calculated as the number of variants per megabase. Based on K-M survival analysis, they were allocated into the high-TMB and low-TMB groups (the optimal cutoff was determined by the 'surv_cutpoint' algorithm of survival R package). Then, Gene ontology (GO) and Gene Set Enrichment Analyses (GSEA) were performed, with immune-associated biological pathways found to be significantly enriched in the low-TMB group. Therefore, immune genes that were differentially expressed between the two groups were evaluated in Cox regression to determine their prognostic values, and a four-gene TMB immune prognostic model (TMB-IP) was constructed. RESULTS: Elevated TMB levels were associated with better survival outcomes in SKCM patients. Based on the cutoff value in OS analysis, they were divided into high-TMB and low-TMB groups. GSEA revealed that the low-TMB group was associated with immunity while intersection analysis revealed that there were 38 differentially expressed immune-related genes between the two groups. Four TMB-associated immune genes were used to construct a TMB-IP model. The AUC of the ROC curve of this model reached a maximum of 0.75 (95%CI, 0.66-0.85) for OS outcomes. Validation in each clinical subgroup confirmed the efficacy of the model to distinguish between high and low TMB-IP score patients. CONCLUSIONS: In SKCM patients, low TMB was associated with worse survival outcomes and enriched immune-associated pathways. The four TMB-associated immune genes model can effectively distinguish between high and low-risk patients.


Asunto(s)
Biomarcadores de Tumor , Regulación Neoplásica de la Expresión Génica , Melanoma/inmunología , Mutación , Anciano , Algoritmos , Bases de Datos Genéticas , Susceptibilidad a Enfermedades , Femenino , Humanos , Estimación de Kaplan-Meier , Linfocitos Infiltrantes de Tumor/inmunología , Linfocitos Infiltrantes de Tumor/metabolismo , Linfocitos Infiltrantes de Tumor/patología , Masculino , Melanoma/genética , Melanoma/mortalidad , Melanoma/patología , Persona de Mediana Edad , Clasificación del Tumor , Metástasis de la Neoplasia , Estadificación de Neoplasias , Pronóstico , Microambiente Tumoral
19.
BMC Cancer ; 21(1): 395, 2021 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-33845800

RESUMEN

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide, associated with a high rate of morbidity and mortality. However, the target genes of miR-221-3p and the underlying mechanism involved in HNSCC are still not clear. Therefore, in the current study, we studied the role of miR-221-3p in the HNSCC. METHODS: Tissues collected from 48 control and 21 HNSCC patients were processed to check the differential expression of miR-221-3p by RT-qPCR. Overexpression of microRNA-221-3p (miR-221-3p) is significantly correlated to the onset and progression of HNSCC. We also conducted the meta-analysis of the cancer literature from the cancer genome atlas (TCGA) and the Gene Expression Omnibus (GEO) database to estimate the expression of miR-221-3p in HNSCC. The miR-221-3p target genes in the HNSCC were predicted with the miRWalk and TCGA databases, and functionally annotated via the Gene Ontology. Finally, Spearman's analysis was used to determine the role of the related target genes in important pathways involved in the development of HNSCC. RESULTS: We observed a significantly higher expression of miR-221-3p in HNSCC compared to the normal with a summary receiver operating characteristic (sROC) of 0.86(95% Cl: 0.83,0.89). The KEGG and GO comprehensive analysis predicted that miR-221-3p might be involved in the development of HNSCC through the following metabolic pathways, viz. Drug metabolism - cytochrome P450 UGT1A7 and MAOB may be important genes for the role of miR-221-3p. CONCLUSION: Based on bioinformatics analysis, our results indicate that miR-221-3p may be used as a non-invasive and hypersensitive biomarker in the diagnosis. Thus, it can be concluded that miR-221-3p may be an extremely important gene locus involved in the process of the deterioration and eventual tumorigenesis of HNSCC. Hopefully, additional work will validate its usefulness as a target for future clinical research.


Asunto(s)
Biología Computacional , Regulación Neoplásica de la Expresión Génica , MicroARNs/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Adulto , Anciano , Biomarcadores de Tumor , Biología Computacional/métodos , Femenino , Perfilación de la Expresión Génica , Ontología de Genes , Redes Reguladoras de Genes , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Estadificación de Neoplasias , Pronóstico , Interferencia de ARN , Curva ROC , Reacción en Cadena en Tiempo Real de la Polimerasa , Transducción de Señal , Carcinoma de Células Escamosas de Cabeza y Cuello/diagnóstico , Carcinoma de Células Escamosas de Cabeza y Cuello/metabolismo
20.
BMC Cancer ; 21(1): 401, 2021 Apr 13.
Artículo en Inglés | MEDLINE | ID: mdl-33849479

RESUMEN

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors of the digestive system and has high morbidity and mortality rates. It is essential to search new biomarkers to improve the accuracy of early HCC diagnosis. Therefore, we evaluated the diagnostic value of prothrombin induced by vitamin K deficiency or antagonist- II (PIVKA-II) as a potential biomarker that complements α-fetoprotein (AFP) in HCC by detecting the serum PIVKA-II levels. METHODS: Serum PIVKA-II levels were compared in 168 HCC patients, 150 benign liver disease patients and 153 healthy controls to investigate the PIVKA-II potential to be a HCC biomarker. Receiver operating characteristic curve (ROC) analysis was used to evaluate the value of PIVKA-II in the diagnosis of HCC and its complementary role of AFP. The correlation between serum PIVKA-II levels and clinicopathological characteristics was analyzed to study the value of PIVKA-II in assessing HCC progression and prognosis. Finally, the ability of PIVKA-II in assessing the surgical treatment effects of HCC was studied by comparing the pre- and post-operative serum PIVKA-II levels in 89 HCC patients. RESULTS: Serum PIVKA-II levels in HCC patients were significantly higher than that in patients with benign liver disease and healthy controls. The PIVKA-II performance in the diagnosing HCC as an individual biomarker was remarkable. The combined detection of PIVKA-II and AFP improved the diagnostic efficiency of HCC. PIVKA-II retained significant diagnosis capabilities for AFP-negative HCC patients. Significant correlations were found between PIVKA-II expression levels and some clinicopathological characteristics, including tumor size, tumor stage, tumor metastasis, differentiation degree and complications. PIVKA-II expression obviously decreased after surgical resection. CONCLUSIONS: PIVKA-II is a promising serum biomarker for the HCC diagnosis that can be used as a supplement for AFP. The combined diagnosis of the two markers greatly improved the diagnostic efficiency of HCC. The PIVKA-II levels in HCC patients were widely associated with clinicopathological characteristics representing tumor cell dissemination and/or poor prognosis. PIVKA-II can be used to evaluate the curative effects of HCC resection.


Asunto(s)
Biomarcadores de Tumor , Biomarcadores/sangre , Carcinoma Hepatocelular/sangre , Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/sangre , Neoplasias Hepáticas/diagnóstico , Precursores de Proteínas/sangre , alfa-Fetoproteínas , Carcinoma Hepatocelular/terapia , Manejo de la Enfermedad , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Biopsia Líquida , Neoplasias Hepáticas/terapia , Masculino , Metástasis de la Neoplasia , Estadificación de Neoplasias , Pronóstico , Protrombina , Curva ROC , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Resultado del Tratamiento
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