Matrix metalloproteinase-11 (MMP11) is an enzyme with proteolytic activity against matrix and nonmatrix proteins. Although most MMPs are secreted as inactive proenzymes and are later activated extracellularly, MMP11 is activated intracellularly by furin within the constitutive secretory pathway. It is a key factor in physiological tissue remodeling and its alteration may play an important role in the progression of epithelial malignancies and other diseases. TCGA colon and colorectal adenocarcinoma data showed that upregulation of MMP11 expression correlates with tumorigenesis and malignancy. Here, we provide evidence that a germline variant in the MMP11 gene (NM_005940: c.232C>T; p.(Pro78Ser)), identified by whole exome sequencing, can increase the tumorigenic properties of colorectal cancer (CRC) cells. P78S is located in the prodomain region, which is responsible for blocking MMP11's protease activity. This variant was detected in the proband and all the cancer-affected family members analyzed, while it was not detected in healthy relatives. In silico analyses predict that P78S could have an impact on the activation of the enzyme. Furthermore, our in vitro analyses show that the expression of P78S in HCT116 cells increases tumor cell invasion and proliferation. In summary, our results show that this variant could modify the structure of the MMP11 prodomain, producing a premature or uncontrolled activation of the enzyme that may contribute to an early CRC onset in these patients. The study of this gene in other CRC cases will provide further information about its role in CRC development, which might improve patient treatment in the future. 相似文献
BackgroundInvestigation of lymph node micrometastasis (mN) of gastric cancer has been focused on either T1 disease or T1-4N0 disease. Yet, it is unclear whether standard management algorithm toward poorly differentiated gastric cancer (PDGC) is more vulnerable to existence of mN, given its inherently biological aggressiveness, as compared with other histological types.Patients and methodsA surgical series (n = 3456) of gastric cancer categorized by histological differentiation was enrolled to analyze survival stratification. Of them, a cohort of T1-T4 N0 PDGC (n = 100) were subjected to cytokeratin immunohistochemistry, a surrogate of mN.ResultsCancer-specific survival by AJCC8 staging system could be nicely differentiated in both well-/moderately differentiated and signet ring cell types, while those between stage IA versus IB (p = 0.105), and stage IB versus IIA (p = 0.141) in PDGC could not. Thirteen (13%) out of 100 node-negative PDGC cases exhibited mN, with 5, 2, 5 and 1 cases occurring in T1, T2, T3, and T4 stage, respectively, without identifiable contributing factors. Prognostic performance of AJCC8 working upon PDGC became more discriminative by incorporating mN, as hazard ratio of stage IIIC referenced to stage IA increased from 43 to 78.ConclusionDefective discriminative survival of PDGC by standard staging algorithm prompted us to survey mN occurring in T1-T4N0 PDGC. The prognostic performance of AJCC8 working upon PDGC was enhanced by incorporating mN. As so, we recommend documentation of mN exclusively on node-negative PDGC that helps unveil stage migration phenomenon and switch to appropriate adjuvant therapy in need. 相似文献
Introduction: Ocular dysfunctions and toxicities induced by antiepileptic drugs (AEDs) are rarely reviewed and not frequently received attention by treating physicians compared to other adverse effects (e.g. endocrinologic, cognitive and metabolic). However, some are frequent and progressive even in therapeutic concentrations or result in permanent blindness. Although some adverse effects are non-specific, others are related to the specific pharmacodynamics of the drug.
Areas covered: This review was written after detailed search in PubMed, EMBASE, ISI web, SciELO, Scopus, and Cochrane Central Register databases (from 1970 to 2019). It summarized the reported ophthalmologic adverse effects of the currently available AEDs; their risks and possible pathogenic mechanisms. They include ocular motility dysfunctions, retinopathy, maculopathy, glaucoma, myopia, optic neuropathy, and impaired retinal vascular autoregulation. In general, ophthalmo-neuro- or retino-toxic adverse effects of AEDs are classified as type A (dose-dependent), type B (host-dependent or idiosyncratic) or type C which is due to the cumulative effect from long-term use.
Expert opinion: Ocular adverse effects of AEDs are rarely reviewed although some are frequent or may result in permanent blindness. Increasing knowledge of their incidence and improving understanding of their risks and pathogenic mechanisms are crucial for monitoring, prevention, and management of patients’ at risk. 相似文献
The rise in popularity of hyaluronic acid (HA) dermal filler injection has caused an exceptional increase in the number of cases of reported irreversible blindness. Here, we reported a case of ischemic optic neuropathy and ophthalmoplegia following subcutaneous HA filler injection with complete visual recovery. A 31-year-old Chinese woman presented with sudden onset of right monocular visual impairment associated with diplopia. Patient had received a hyaluronic acid-containing ?ller injection for nasal dorsum augmentation twelve hours prior to presentation. Visual acuity of the right eye was counting finger. A right relative afferent pupillary defect was demonstrated with ophthalmoplegia. Humphrey visual field test disclosed a right inferior altitudinal field defect with impairment of colour vision. Computed tomography of the orbit revealed mild enlargement of the right medial and inferior recti muscles. Our patient showed a tremendous improvement of vision after a subcutaneous hyaluronidase injection with complete visual recovery within 2 weeks. 相似文献
BackgroundSingle-anastomosis duodeno-ileal bypass (SADI) and the one-anastomosis gastric bypass (OAGB) are 2 revisional procedures to address the problem of weight recidivism after laparoscopic sleeve gastrectomy (LSG).ObjectivesTo evaluate the efficacy and safety of SADI and OAGB as revisional bariatric surgery (RBS) in initially super-obese patients (body mass index [BMI] >50 kg/m2).SettingAcademic hospital, bariatric center of excellence, Germany.MethodsObservational study of outcomes in 84 initially super-obese patients who had undergone RBS after LSG (SADI n = 42, OAGB n = 42) between July 2013 and April 2018. Follow-up examinations were performed at 1, 6, 12, 24, and 36 months after RBS. The variables analyzed included time between LSG and RBS, BMI, excess weight loss, total weight loss, operation time, and complications.ResultsThe time interval between LSG and RBS was 45.5 ± 22.8 and 43.5 ± 24.2 months for SADI and OAGB, respectively. At the time of RBS, the mean BMI was 42.8 ± 7.9 kg/m2 for SADI and 43.4 ± 9.2 kg/m2 for OAGB. The follow-up examinations rates (%) after SADI were 97.6, 92.8, 90.5, 78.6, 57.1, and 100, 97.6, 95.2, 85.7, and 59.5 after OAGB. The BMI at the follow-up examinations were 39.1 ± 7.2, 34.2 ± 6.9, 31.2 ± 5.8, 30.2 ± 5.3, 29.3 ± 5.1 for SADI, and 39.5 ± 8.1, 36.6 ± 7.4, 34.7 ± 7.9, 32.9 ± 6.3, and 31.6 ± 5.9 for OAGB. The mean operating times for SADI and OAGB were 138 ± 40 and 123 ± 39 minutes, respectively. Three patients in the SADI group and 1 patient in the OAGB group developed a major complication within the first 30 postoperative days.ConclusionSADI and OAGB were effective second-step procedures for further weight reduction after LSG in initially super-obese patients after short to medium follow-up. There was a trend toward higher weight loss for SADI though this did not reach statistical significance. Substantial differences concerning surgery time and complications between the 2 procedures were not observed. 相似文献