RESUMO
Procalcitonin (PCT) is widely used to diagnose a bacterial infection. An increased serum PCT can also be observed in tumors. We presented an unusual case of a metastatic PNET producing and secreting PCT. Immunohistochemistry was used to demonstrate that PCT can be secreted by PanNET.
RESUMO
Inactivating mutations in the liver kinase B1 (LKB1) tumor suppressor gene underlie Peutz-Jeghers syndrome (PJS) and occur frequently in various human cancers. We previously showed that LKB1 regulates centrosome duplication via PLK1. Here, we report that LKB1 further helps to maintain genomic stability through negative regulation of survivin, a member of the chromosomal passenger complex (CPC) that mediates CPC targeting to the centromere. We found that loss of LKB1 led to accumulation of misaligned and lagging chromosomes at metaphase and anaphase and increased the appearance of multi- and micro-nucleated cells. Ectopic LKB1 expression reduced these features and improved mitotic fidelity in LKB1-deficient cells. Through pharmacological and genetic manipulations, we showed that LKB1-mediated repression of survivin is independent of AMPK, but requires p53. Consistent with the key influence of LKB1 on survivin expression, immunohistochemical analysis indicated that survivin is highly expressed in intestinal polyps from a PJS patient. Lastly, we reaffirm a potential therapeutic avenue to treat LKB1-mutated tumors by demonstrating the increased sensitivity to survivin inhibitors of LKB1-deficient cells.
Assuntos
Centrômero/efeitos dos fármacos , Genes p53/efeitos dos fármacos , Genoma/efeitos dos fármacos , Síndrome de Peutz-Jeghers/genética , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Survivina/biossíntese , Survivina/genética , Quinases Proteína-Quinases Ativadas por AMP , Linhagem Celular Tumoral , Aberrações Cromossômicas , Humanos , Pólipos Intestinais/genética , Mitose/efeitos dos fármacos , Proteínas Serina-Treonina Quinases/genética , RNA Interferente Pequeno/biossíntese , RNA Interferente Pequeno/genética , Ensaio Tumoral de Célula-Tronco , Regulação para Cima/genéticaRESUMO
Exosomes are key mediators of intercellular communication and play a role in the pathogenesis and progression of cancer. Exosomes in circulating body fluids serve as molecular markers for cancer diagnosis. This study aimed to investigate the role of exosomal microRNA (miR)-1910-3p in breast cancer and determine its clinical diagnostic value. MiR-1910-3p promoted proliferation and migration of breast cancer cells in vitro and in vivo. In vitro, exosomes enriched in miR-1910-3p transferred miR-1910-3p to mammary epithelial cells and breast cancer cells, promoting proliferation and migration, inhibiting apoptosis, and inducing autophagy. In vivo, exosomes enriched in miR-1910-3p promoted the proliferation and migration of breast cancer cells. MiR-1910-3p downregulated myotubularin-related protein 3, activated the NF-κB and wnt/ß-catenin signaling pathway, and promoted breast cancer progression. Serum miR-1910-3p in exosomes was an effective diagnostic marker that improved the sensitivity of breast cancer diagnosis when used in combination with the traditional tumor marker CA153. In conclusion, breast cancer cell-derived exosomes promoted the growth, metastasis, and autophagy of breast cancer cells by transferring miR-1910-3p. MiR-1910-3p in serum exosomes may serve as a novel molecular marker for breast cancer diagnosis.
Assuntos
Neoplasias da Mama/patologia , Exossomos/metabolismo , Regulação Neoplásica da Expressão Gênica/fisiologia , MicroRNAs/metabolismo , NF-kappa B/metabolismo , Proteínas Tirosina Fosfatases não Receptoras/metabolismo , Animais , Autofagia/fisiologia , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Proliferação de Células/genética , Exossomos/genética , Feminino , Xenoenxertos , Humanos , Camundongos , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Transdução de Sinais/fisiologiaRESUMO
OBJECTIVE: To investigate the efficiency of perforator pedicled propeller flaps for soft tissue coverage of lower leg and foot defects. METHODS: Twenty patients (12 male, 8 females; mean age 28 years, range, 5-75) with soft tissue defects of the lower leg and foot were retrospectively reviewed. Their defects had been repaired with perforator pedicled propeller flaps from September 2011 to October 2013 and included five cases of injuries caused by spokes, four of infection with postoperative skin necrosis, two of dorsal skin defects caused by heavy objects and nine caused by car accidents. The areas of soft tissue defect were from 2 cm × 8 cm to 10 cm × 20 cm. Fifteen cases had terminal branch of the peroneal artery perforator flaps and five posterior tibia artery perforator flaps, flap size ranging from 5 cm × 11 cm to 12 cm × 28 cm. Color Doppler ultrasound was used to locate all perforator vessels, the calibers of which ranged from 0.8 mm to 1.0 mm. RESULTS: The intraoperative coincidence rate of the color Doppler ultrasound was 96.7%. The donor sites were sutured directly in 12 cases and skin grafted in 8. One case had a venous crisis within 24 h that was treated by removal some sutures and drainage. All cases were followed up for 1-18 months; all flaps survived well and pedicles had a satisfactory appearance. The patients were extremely satisfied with the results for repair. CONCLUSION: Perforator pedicled propeller flaps have the advantages over other pedicle flap of being simple, safe, and effective and not involving vascular anastomosis.
