Transforming growth factor-β (TGF-β) regulates cell growth and differentiation, apoptosis, cell motility, extracellular matrix production, angiogenesis, and cellular immunity. It has a paradoxical role in cancer. In the early stages it inhibits cellular transformation and prevents cancer progression. In later stages TGF-β plays a key role in promoting tumor progression through mainly 3 mechanisms: facilitating epithelial to mesenchymal transition, stimulating angiogenesis and inducing immunosuppression. As a result of its opposing tumor promoting and tumor suppressive abilities, TGF-β and its pathway has represented potential opportunities for drug development and several therapies targeting the TGF-β pathway have been identified. This review focuses on identifying the mechanisms through which TGF-β is involved in tumorigenesis and current therapeutics that are under development.

We identified and validated differential expression of 5 lncRNA in HPV-negative HNSCC. Low MEG3 expression was associated with favorable 3-year RFS, although the significance of this finding remains unclear.

Objectives: Salvage surgical resection is the preferred treatment for head and neck squamous cell carcinoma (HNSCC) patients who develop locally recurrent disease after failing primary therapy. However, salvage surgical resection is not always feasible, and survival outcomes for those that do undergo salvage remain poor. It is well known that patients with adverse pathological features (extracapsular extension (ECE) of lymph nodes (LN), positive margins, peri-neural spread (PNI), lymphovascular invasion (LVI), and multiple LN metastases) at the time of primary surgical resection are likely to have relatively poor outcomes. However, the impact of adverse pathological features on outcomes in the salvage setting remains controversial. Materials and Methods: We retrospectively analyzed 73 patients at a single institution from 2008–2017 who developed recurrence and subsequently underwent salvage surgery (SS) after definitive curative-intent therapy including radiation. Demographic and disease control outcomes were reviewed. Kaplan-Meier curves were used to estimate relapse free survival (RFS) and overall survival (OS). Results: Median age at diagnosis was 61 years (range 40–86), 49/73 (67%) were male, and 55/73 (75%) had smoked. Patients with any adverse pathological features at SS had worse RFS (HR 3.15 p=0.0008) and worse OS (3.97 p=0.0008). Patients who relapsed <6 months after initial therapy had worse OS (HR 2.96 p=0.004). Conclusions: Patients with adverse pathological features at time of salvage surgery as well as those who have an early recurrence after definitive treatment and salvage surgery have worse outcomes. Prospective studies are necessary to clarify which patients should receive more intense treatment at salvage.

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Background: There is little research that examines the impact of frailty on stroke outcomes. The objective of our study was to develop a frailty index (FI) and analyze its relationship to stroke outcomes in a nationally representative population-based study of ischemic stroke. Methods: Within a population of 1.3 million, all ischemic strokes among Greater Cincinnati/Northern Kentucky residents in 2005 were ascertained from local hospitals and clinics using ICD-9 discharge codes 430-436 (n=2226). Using previously validated methodology, a FI was created based on 35 age-related deficits including co-morbidities (e.g. prior stroke, dementia), pre-stroke functional status (e.g. as measured by the modified Rankin Scale [mRS], use of walking aids) and admission lab values (e.g. abnormal creatinine, hemoglobin). The FI for each subject (expressed as a %) was calculated as the number of deficits divided by the maximum number (n=35). Multiple logistic regression models were used to examine the association between the FI and in-hospital mortality, poor functional outcome (discharge mRS≥3), and discharge to home, with adjustment for age, sex, race, and NIH Stroke Scale score. Odds ratios were specified for a 3% increase in the FI (which is approximately equivalent to a 1 deficit increase in the FI i.e. 1/35) Results: The median age of the study sample was 73 years and the median FI was 17% (IQR 11%-26%). The in-hospital mortality was 10%. Amongst survivors, 53% were discharged with an mRS≥3 and 68% were discharged home. Logistic regression models demonstrated that after adjustment, for every 3% increase in the FI, the odds of dying in hospital increased by 16% (p<0.01), the odds of being discharged with an mRS≥ 3 increased by 8% (p<0.01) and the odds of being discharged home was decreased by 7% (p<0.01). ( Table ) Conclusions: Frailty was associated with increased in-hospital mortality, poorer outcome at discharge (mRS≥3) and decreased likelihood of being discharged home. Importantly frailty’s effects on stroke outcomes were shown to be independent of age, which suggest that frailty may represent a biological rather than chronological measure of aging. Further work needs to be done to examine the relationship between frailty, its sub-components and stroke outcomes. Frailty indices may represent an important new contribution to prognostic models of stroke.