Senescent stroma induces nuclear deformations in cancer cells via the inhibition of RhoA/ROCK/myosin II-based cytoskeletal tension

The presence of senescent cells within tissues has been functionally linked to malignant transformations. Here, using tension-gauge tethers technology, particle-tracking microrheology, and quantitative microscopy, we demonstrate that senescent associated secretory phenotype (SASP) derived from senescent fibroblasts impose nuclear lobulations and volume shrinkage on malignant cells, which stems from the loss of RhoA/ROCK/myosin II-based cortical tension. This loss in cytoskeletal tension induces decreased cellular contractility, adhesion, and increased mechanical compliance. These SASP-induced morphological changes are in part mediated by lamin A/C. These findings suggest that SASP induces a defective outside-in mechanotransduction, from actomyosin fibers in the cytoplasm to the nuclear lamina, thereby triggering a cascade of biophysical and biomolecular changes in cells that associate with malignant transformations.

Aetiology and Pathogenesis of Cutaneous Melanoma: Current Concepts and Advances

Melanoma develops from malignant transformations of the pigment-producing melanocytes. If located in the basal layer of the skin epidermis, melanoma is referred to as cutaneous, which is more frequent. However, as melanocytes are be found in the eyes, ears, gastrointestinal tract, genitalia, urinary system, and meninges, cases of mucosal melanoma or other types (e.g., ocular) may occur. The incidence and morbidity of cutaneous melanoma (cM) are constantly increasing worldwide. Australia and New Zealand are world leaders in this regard with a morbidity rate of 54/100,000 and a mortality rate of 5.6/100,000 for 2015. The aim of this review is to consolidate and present the data related to the aetiology and pathogenesis of cutaneous melanoma, thus rendering them easier to understand. In this article we will discuss these problems and the possible impacts on treatment for this disease.

318 Management of Incidental Pancreatic Cysts –Are We Adhering to Guidelines?

Background The majority of pancreatic cysts (PC) are incidentally diagnosed. Most NHS Trusts do not have pathways to manage them. We reviewed the management of incidental PC and adherence to guidelines. Method Data was collected across three hospitals in our Trust between January 2018-January 2019 when there were no guidelines. Reaudit was performed between July 2019-February 2020 following the introduction of trust guidelines that recommend all PC be discussed in MDT meetings. Results The first audit identified 79 patients and 28 in the second. 53% (42) and 64% (18) patients were referred to HPB/GI MDT during the two periods. There was an 11% increase in MDT referrals, however, 35.71% of patients were still not referred. During the initial audit, 62 % (23/37) of patients in the Non-MDT group had no surveillance scans, potentially missing high-risk patients and 38% of patients (14/37) still underwent surveillance scans from non-GI specialists which could be unnecessary. 44% of patients underwent surveillance following MDT in the second period as compared to 83% prior to guidelines (p = 0.002). Conclusions Robust guidelines for incidental PC identify high risk cysts that warrant future surveillance/treatment and avoid unnecessary scans releasing radiology capacity.MDT referral ensures malignant transformations are identified early and reduce morbidity and mortality.