RESUMO
Despite recent advances in cancer therapeutics, pancreatic ductal adenocarcinoma (PDAC) remains a lethal disease with a 5-year overall survival of only 10%. Since either at or within a few months of diagnosis, most patients with PDAC will present with metastatic disease, a more individualized approach to select patients who may benefit from more aggressive therapy has been suggested. Although studies have reported improved survival in PDAC and isolated pulmonary metastasis (ISP) compared to extrapulmonary metastases, such findings remain controversial. Furthermore, the added benefit of pulmonary metastasectomy and other lung-directed therapies remains unclear. In this review, we discuss the metastatic pattern of PDAC, evaluate the available evidence in the literature for improved survival in PDAC and ISP, evaluate the evidence for the added benefit of pulmonary metastasectomy and other lung-directed therapies, identify prognostic factors for survival, discuss the biological basis for the reported improved survival and identify areas for further research.
Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pulmonares , Neoplasias Pancreáticas , Humanos , Estudos Retrospectivos , Neoplasias Pancreáticas/patologia , Carcinoma Ductal Pancreático/patologia , Prognóstico , Neoplasias PancreáticasRESUMO
Aquaporins (AQPs) are small (~30 kDa monomers) integral membrane water transport proteins that allow water to flow through cell membranes in reaction to osmotic gradients in cells. In mammals, the family of AQPs has thirteen (AQP0-12) unique members that mediate critical biological functions. Since AQPs can impact cell proliferation, migration and angiogenesis, their role in various human cancers is well established. Recently, AQPs have been explored as potential diagnostic and therapeutic targets in gastrointestinal (GI) cancers. GI cancers encompass multiple sites including the colon, esophagus, stomach and pancreas. Research in the last three decades has revealed biological aspects and signaling pathways critical for the development of GI cancers. Since the majority of these cancers are very aggressive and rapidly metastasizes, identifying effective targets is crucial for treatment. Preclinical studies have utilized inhibitors of specific AQPs and knock down of AQP expression using siRNA. Although several studies have explored the role of AQPs in colorectal, esophageal, gastric, hepatocellular and pancreatic cancers, there is no comprehensive review compiling the available information on GI cancers as has been published for other malignancies such as ovarian cancer. Due to the similarities and association of various sites of GI cancers, it is helpful to consider these results collectively in order to better understand the role of specific AQPs in critical GI cancers. This review summarizes the current knowledge of the role of AQPs in GI malignancies with particular focus on diagnosis and therapeutic applications.
Assuntos
Aquaporinas/metabolismo , Biomarcadores Tumorais/metabolismo , Neoplasias Gastrointestinais/metabolismo , Animais , Antineoplásicos/uso terapêutico , Aquaporinas/antagonistas & inibidores , Aquaporinas/química , Aquaporinas/genética , Biomarcadores Tumorais/genética , Desenho de Fármacos , Neoplasias Gastrointestinais/tratamento farmacológico , Neoplasias Gastrointestinais/genética , Neoplasias Gastrointestinais/patologia , Regulação Neoplásica da Expressão Gênica , Humanos , Terapia de Alvo Molecular , Valor Preditivo dos Testes , Conformação Proteica , Transdução de Sinais , Relação Estrutura-AtividadeRESUMO
Colon and pancreatic cancers have high mortality rates due to early metastasis prior to the onset of symptoms. Screening tests for colorectal cancer are invasive and expensive. No effective screening is available for pancreatic cancer. Identification of biomarkers for early detection in both of these cancers is being extensively researched. MicroRNAs (miRNA) are small non-coding molecule biomarkers that regulate cancers. Measurement of miRNAs in pancreatic fluid or blood could be a preferred non-invasive screening method. The regulation of colon and pancreatic cancers by miRNA is complex. miRNA play a central role in inflammation, invasiveness, and tumor progression in these two cancers, as well as regulation of the NF-κB pathway. miRNA's evolving role in screening is also reviewed.
Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias do Colo/metabolismo , Regulação Neoplásica da Expressão Gênica , MicroRNAs/metabolismo , NF-kappa B/metabolismo , Neoplasias Pancreáticas/metabolismo , Neoplasias do Colo/genética , Neoplasias do Colo/terapia , Progressão da Doença , Perfilação da Expressão Gênica , Humanos , Inflamação , Invasividade Neoplásica , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/terapia , Resultado do TratamentoRESUMO
Adiponectin is produced in the white adipose tissue and is known to have anti-metabolic and anti-inflammatory properties. Serum/plasma adiponectin levels depend on diet, physical activity, and inheritance. Epidemiologic observations suggest a potential link between obesity and gastrointestinal malignancies. Low levels of adiponectin, which are known to occur in obesity, may contribute to the high incidence of cancer in this population. This review discusses the biochemical and molecular evidence regarding the relationship between adiponectin and gastrointestinal carcinogenesis and provides several future perspectives on the role of adiponectin as a target for prevention and therapy.
