RESUMEN
Biomechanical contributions of the ECM underpin cell growth and proliferation, differentiation, signal transduction, and other fate decisions. As such, biomaterials whose mechanics can be spatiotemporally altered - particularly in a reversible manner - are extremely valuable for studying these mechanobiological phenomena. Herein, we introduce a poly(ethylene glycol) (PEG)-based hydrogel model consisting of two interpenetrating step-growth networks that are independently formed via largely orthogonal bioorthogonal chemistries and sequentially degraded with distinct bacterial transpeptidases, affording reversibly tunable stiffness ranges that span healthy and diseased soft tissues (e.g., 500 Pa - 6 kPa) alongside terminal cell recovery for pooled and/or single-cell analysis in a near "biologically invisible" manner. Spatiotemporal control of gelation within the primary supporting network was achieved via mask-based and two-photon lithography; these stiffened patterned regions could be subsequently returned to the original soft state following sortase-based secondary network degradation. Using this approach, we investigated the effects of 4D-triggered network mechanical changes on human mesenchymal stem cell (hMSC) morphology and Hippo signaling, as well as Caco-2 colorectal cancer cell mechanomemory at the global transcriptome level via RNAseq. We expect this platform to be of broad utility for studying and directing mechanobiological phenomena, patterned cell fate, as well as disease resolution in softer matrices.
RESUMEN
INTRODUCTION: Parathyroid carcinoma is a rare diagnosis. The association of clinical and pathologic factors as well as treatment on overall survival (OS) is not well established. METHODS: A retrospective review of patients with parathyroid carcinoma was performed using the National Cancer Database for patients diagnosed from 2004 through 2017. Clinical and demographic variables were assessed. A Cox proportional hazards model was used to assess for factors associated with survival. OS rates were determined for 5 and 10 y. RESULTS: Data for 1057 patients were analyzed. The mean age at diagnosis was 57.5 y (standard deviation [SD] 14.0), and 542 (51.3%) were male. The median tumor size was 2.7 cm (interquartile range 2.0-3.7 cm). For the extent of surgery, 38 (3.6%) had no surgery, 568 (53.7%) had incomplete resection, 359 (34.0%) had complete resection, 58 (5.5%) had radical resection, and 34 (3.2%) did not have specified and were not used in the Cox proportional hazard regression model. For the cohort, 488 (46.2%) had lymph nodes resected with a mean of 5.5 (SD 6.6) removed. Of these, 32 (8.3%) had nodal metastases with one to six positive nodes. For adjuvant therapy, 159 (15.0%) had external beam radiation with a mean dose of 5463 cGy (SD 1464). Overall, 214 patients died (21.55%), and the estimated 5- and 10-y OS were 82.9% and 57.0%, respectively. In a Cox proportional hazard regression model, age at diagnosis as a continuous variable with hazard ratio (HR) 1.04, 95% confidence interval (CI) 1.01-1.06, P = 0.003, and extent of surgery as a categorical variable with no surgery as the referent group: incomplete surgery HR 0.05, 95% CI 0.01-0.19, P < 0.001; complete surgery HR 0.04, 95% CI 0.01-0.19, P < 0.001; radical surgery HR 0.10, 95% CI 0.02-0.45, P < 0.001; and tumor size as a continuous variable was not associated with OS with an HR of 1.00, 95% CI 0.99-1.00, P = 0.738. CONCLUSIONS: Patient age and extent of surgery are modestly associated with survival for parathyroid carcinoma but not patient sex, nodal metastases, or adjuvant therapy in this cohort.
