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The Wnt/ß-catenin pathway is an important, dysregulated pathway in several tumor types, including pancreatic ductal adenocarcinoma. Although the activation of this pathway is an important component of normal development, its aberrant activation resulting from activating or inactivating mutations in the CTNNB1 gene locus, or in the negative regulators AXIN and APC involving stabilization of ß-catenin, and activation of target genes leads to a more aggressive phenotype, suggesting its potential value as a therapeutic target in the treatment of pancreatic ductal adenocarcinoma. A number of small molecule and biologic agents have now been developed for targeting this pathway. This review summarizes the current knowledge about the therapeutic potential of targeting the Wnt pathway with particular emphasis on preclinical/clinical studies in the treatment of pancreatic ductal adenocarcinoma.
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Tumor necrosis factor a (TNFa) is an inflammatory cytokine that plays a crucial role in the immune response and the progression of cervical lesions. There is a growing body of data evaluating the value of a genetic variant in the TNFa gene with the risk of developing cervical cancer. The aim of this study was to explore the association of a variant, TNF-308 G>A, residing in the TNFa gene with cervical cancer. A total of 91 women with cervical cancer and 161 women as the control group were recruited. DNA was extracted, and Taqman®-probes-based assay was used for genotyping. Our results showed that the minor allele frequency was 0.3 in total population, and the frequency of minor allele A was more in the case group compared with the control. The regression models in different genetic models also revealed that the allele A is a potential risk factor for the development of cervical cancer. In particular, in the dominant model, patients with AG and AA genotypes had a higher risk of developing cervical cancer with odds ratio (OR) of 2.75 (95% confidence interval [CI]: 1.57-4.83, <0.001) and OR of 7.27 (95%CI: 2.5-20.8, <0.001), compared with the GG genotype. Moreover, a similar outcome was obtained for smear test results. Our study demonstrated that TNF-308 G>A located on TNF-a was associated with the risk of cervical cancer, supporting further studies in a larger population and multicenter setting to show the value of emerging markers as risk stratification biomarkers in cervical cancer.
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Teste de Papanicolaou , Polimorfismo de Nucleotídeo Único , Fator de Necrose Tumoral alfa/genética , Neoplasias do Colo do Útero/genética , Esfregaço Vaginal , Alelos , Biomarcadores Tumorais , Feminino , Frequência do Gene , Genótipo , Humanos , Modelos Logísticos , Razão de Chances , Fatores de RiscoRESUMO
The transforming growth factor-ß (TGF-ß) signaling pathway is one of the important pathways involved in the cancer cell proliferation, invasion, migration, angiogenesis, apoptosis, as well as in metastasis by agitation or invasion of metastasis-related factors, including matrix metalloproteinase (MMP), epithelial-to-mesenchymal transition (EMT), tumor microenvironment (TME), cancer stem cells (CSCs), and cell adhesion molecules (CAMs). These data suggest its potential value as a therapeutic object in the treatment of malignancies including breast cancer. Several pharmacological approaches have been established to suppress TGF-ß pathway; such as vaccines, small molecular inhibitors, antisense oligonucleotides, and monoclonal antibodies. Some of these are now approved by the US Food and Drug Administration for targeting the TGF-ß signaling pathway. This study attempts to summarize the current data about the functions of TGF-ß in cancer cells, and their probable application in the cancer therapy with a specific emphasis on recent preclinical and clinical research in the treatment of breast cancer and its prognostic value.
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Toll-like receptors (TLRs) play an important role in the innate and adaptive immune system. They are expressed in various regions of the female reproductive tract, and their regulation may be involved in the pathogenesis of gynecological lesions. There is growing evidence that ligands for several TLRs are potentially anticancer agents, some of which have already been approved by the FDA, and these compounds are now undergoing clinical evaluation. There is a rationale for using these ligands as adjuvants in the treatment or prevention of gynecological cancer. Some TLR agonists that are of potential interest in the treatment of gynecological lesions include imiquimod, motolimod, cervarix, and CpG-oligodeoxynucleotides (ODNs). In this review, we outline the different functions of TLRs in gynecological cancer with particular emphasis on the value of TLR agonists as a potential therapeutic target in the treatment of gynecological cancer. © 2019 IUBMB Life, 71(5):549-564, 2019.
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Antineoplásicos/uso terapêutico , Neoplasias dos Genitais Femininos/tratamento farmacológico , Receptores Toll-Like/agonistas , Adjuvantes Imunológicos , Animais , Feminino , Neoplasias dos Genitais Femininos/metabolismo , HumanosAssuntos
Linfonodos , Metástase Linfática , Biópsia de Linfonodo Sentinela , Ultrassonografia , Axila , Neoplasias da Mama/patologia , Pesquisa Comparativa da Efetividade , Feminino , Humanos , Excisão de Linfonodo/métodos , Excisão de Linfonodo/estatística & dados numéricos , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Metástase Linfática/diagnóstico por imagem , Metástase Linfática/patologia , Estadiamento de Neoplasias , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Biópsia de Linfonodo Sentinela/métodos , Biópsia de Linfonodo Sentinela/normas , Ultrassonografia/métodos , Ultrassonografia/normasRESUMO
OBJECTIVES: COVID-19 infection demonstrates characteristic findings in chest CT. The optimal timing of repeated CT scans still needs to be clarified, and the optimal time to assess imaging clearance in COVID-19 is still unknown. It is crucial to have a roadmap of the imaging course of COVID-19 pneumonia to develop guidelines for prompt diagnosis of pulmonary complications, especially fibrosis, at the earliest stage. PURPOSE: To assess the temporal changes of chest CT findings in patients with COVID-19 pneumonia and evaluate the rate of a complete resolution and determine the patients are at excessive risk for residual parenchymal abnormalities. MATERIALS AND METHODS: This retrospective observational study included 48 patients with real-time polymerase chain reaction-confirmed COVID-19 who were admitted to three academic hospitals. These patients underwent at least one initial chest CT before or after admission and at least one follow-up CT scan four weeks or more after the onset of the symptoms. All chest CTs were categorized according to time of performance into four groups, including the first week, second week, third-fourth week, and more than 28 days. Lung involvement was categorized as predominantly alveolar (ground-glass opacity and consolidation), organizing pneumonia, and reticular patterns. The severity of involvement was also evaluated by the reader. RESULTS: Forty-eight patients and a total of 130 chest CT scans were evaluated. The alveolar pattern showed a gradual decrease in frequency from 91% in the first week to 9% after the fourth week of the disease but the organizing pneumonia pattern gradually increased with disease progression and the frequency of reticular pattern increased significantly after third week. Complete resolution of CT findings was seen in 17 patients (13.1%) and was significantly more prevalent in patients of younger age (p value<0.001) and with lower initial CT severity scores (p value=0.048). CT severity scores in the second week were significantly higher in ICU admitted patients (p value=0.003). CONCLUSION: There are temporal patterns of lung abnormalities in patients with COVID-19 pneumonia. The predominant CT pattern was alveolar infiltrate in the first and second weeks of the disease, replaced with an organizing pneumonia pattern in the third and fourth weeks. Progression of lung involvement was correlated with ICU admission due to the highest CT severity score in the second and third weeks of presentation but not in the first week in patients who were admitted at ICU. Complete CT resolution was significantly more common in patients of younger age and lower initial CT severity scores.
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COVID-19 , Pneumonia , Humanos , COVID-19/diagnóstico por imagem , SARS-CoV-2 , Tomografia Computadorizada por Raios X/métodos , Pulmão/diagnóstico por imagemRESUMO
Sacrococcygeal chordoma is a rare malignant bone tumor. Although there are tough membranes such as the periosteum and presacral fascia (which resist transgression by the tumors), chordoma usually invades the rectal wall. The serious problem with these tumors is the late diagnosis and its high likelihood to become enlarged. The main treatment options for this tumor is surgical resection, radiotherapy, and chemotherapy. Due to the tumor vicinity to important organs such as bladder and its neurovascular structures, it makes surgical excision extremely challenging. The aim of this study is to describe a 50-year-old man with a giant sacrococcygeal mass. The novelty of this case report is the huge and unique size of the tumor which has not reported previously as well the special surgical approaches performed to remove the tumor.
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Teratomas are benign germ cell tumors that usually found out of their anatomical origin. Teratomas usually are found in sacrococcygeal area, gonads, mediastinum, cervicofacial region and intracranial fossa. Spinal teratomas are rare. In this study we describe a case of conus medullaris teratoma which was diagnosed based on imaging studies. The patient underwent surgery. We did bilateral laminectomy. The mass lesion had an obvious and rigid attachment to the conus medullaris. The wall of the lesion was resected as much as possible, but total resection of the lesion's wall could not be done due to changes in neural monitoring. Previous related studies are reviewed.
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Angiogenesis refers to the formation of recent blood vessels, which is one of the characteristics of cancer progression and it has been deliberated as a putative target to the treatment of many kinds of cancers. The VEGF signaling substrate is very important for angiogenesis and is commonly high-regulated in tumors. As a result, this molecule has attracted the attention of most of the researchers to develop antiangiogenic therapies. We have presented that VEGF blockage in neoadjuvant setting via bevacizumab, aflibercept and sunitinib not only has revealed some promising benefits but also has shown a large negative outcome in the adjuvant trials. However, at an advanced stage of tumors, suppression of VEGF alone is inadequate to stop advancement, encouraging drug resistance, and probably enhancing metastasis and invasion in the tumor microenvironment, thereby suggesting the therapeutic potential of targeting angiogenic pathways in gastrointestinal cancers.
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Inibidores da Angiogênese/farmacologia , Neoplasias Colorretais/tratamento farmacológico , MicroRNAs/antagonistas & inibidores , Neovascularização Patológica/tratamento farmacológico , Neoplasias Colorretais/metabolismo , Humanos , MicroRNAs/metabolismo , Neovascularização Patológica/metabolismo , Microambiente Tumoral/efeitos dos fármacosRESUMO
Hematological parameters have emerged as independent determinants of high serum concentrations of uric acid (UA) and predictive factors in the evaluation of the total cardiovascular risk in patients with essential hypertensive. Here, we have investigated the possible relationships between hematological factors and serum uric acid levels in hypertensive patients recruited as part of Mashhad Stroke and Heart Atherosclerotic Disorders cohort study. Two-thousand three-hundred and thirty-four hypertensive individuals were recruited from this cohort and these were divided into two groups; those with either high or low serum UA concentrations. Demographic, biochemical, and hematological characteristics of population were evaluated in all the subjects. Logistic-regression analysis was performed to determine the association of hematological parameters with hypertension (HTN). Of the 2334 hypertensive subjects, 290 cases had low UA, and 2044 had high serum UA concentrations. Compared with the low UA group, the patients with high serum UA, had higher values for several hematological parameters, whilst platelet counts (PLT) were lower. Multiple linear regression analysis showed that PLT and serum high sensitivity-c reactive protein (hs-CRP) were correlated with serum UA level. Stepwise multiple logistic regression model confirmed that platelet distribution width (PDW) and gender were independent determinant of a high serum UA. PDW and PLT appear to be independently associated with serum UA level in patients with HTN. © 2018 BioFactors, 44(6):532-538, 2018.