MNK1 and MNK2 enforce expression of E2F1, FOXM1, and WEE1 to drive soft tissue sarcoma

Soft tissue sarcoma (STS) is a heterogeneous disease that arises from connective tissues. Clinical outcome of patients with advanced tumors especially de-differentiated liposarcoma and uterine leiomyosarcoma remains unsatisfactory, despite intensive treatment regimens including maximal surgical resection, radiation, and chemotherapy. MAP kinase-interacting serine/threonine-protein kinase 1 and 2 (MNK1/2) have been shown to contribute to oncogenic translation via phosphorylation of eukaryotic translation initiation factor 4E (eIF4E). However, little is known about the role of MNK1/2 and their downstream targets in STS. In this study, we show that depletion of either MNK1 or MNK2 suppresses cell viability, anchorage-independent growth, and tumorigenicity of STS cells. We also identify a compelling antiproliferative efficacy of a novel, selective MNK inhibitor ETC-168. Cellular responsiveness of STS cells to ETC-168 correlates positively with that of phosphorylated ribosomal protein S6 (RPS6). Mirroring MNK1/2 silencing, ETC-168 treatment strongly blocks eIF4E phosphorylation and represses expression of sarcoma-driving onco-proteins including E2F1, FOXM1, and WEE1. Moreover, combination of ETC-168 and MCL1 inhibitor S63845 exerts a synergistic antiproliferative activity against STS cells. In summary, our study reveals crucial roles of MNK1/2 and their downstream targets in STS tumorigenesis. Our data encourage further clinical translation of MNK inhibitors for STS treatment

Single Ray Amputation for Tumors of the Hand

Single ray amputation after hand trauma or infection can result in good aesthetic and functional outcomes. The role of this procedure in the management of aggressive benign or malignant hand tumors has been described only in case reports and small case series. We retrospectively reviewed the records of all 25 patients who underwent single ray amputations at our center during a 10-year period; there were seven index, five middle, six ring, and seven small ray amputations performed. The minimum followup was 2 months (mean, 36 months; range, 2–120 months), with four patients having a followup of 1 year or less. No patients had local recurrences, although two patients had positive resection margins. One underwent repeat resection followed by radiotherapy. The other was treated with radiotherapy alone, as local tumor control would have required a hand amputation. Functional assessment based on the Musculoskeletal Tumor Society staging system showed an average of 27.5 (range, 21–30). Patients who underwent perioperative radiotherapy experienced a decrease in functional ability. Grip strength was an average of 66% (range, 38%–100%) of the contralateral side. Our study suggests single ray amputation for hand tumors has a low local recurrence rate and high functional scores. However, function can be compromised by radiotherapy and a decrease in grip strength by a mean of 34% is to be expected

Functional Restoration Following Resection of Malignant Peripheral Nerve Sheath Tumour of the Median Nerve: A Case Report

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Sustaining a national surgical training programme during the COVID-19 pandemic.

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