Precautions for breast cancer-related lymphoedema: risk from air travel, ipsilateral arm blood pressure measurements, skin puncture, extreme temperatures, and cellulitis.

Precautionary recommendations conveyed to survivors of cancer by health-care practitioners to reduce the risk of breast cancer-related lymphoedema are indispensable aspects of clinical care, yet remain unsubstantiated by high-level scientific evidence. By reviewing the literature, we identified 31 original research articles that examined whether lifestyle-associated risk factors (air travel, ipsilateral arm blood pressure measurements, skin puncture, extreme temperatures, and skin infections-eg, cellulitis) increase the risk of breast cancer-related lymphoedema. Among the few studies that lend support to precautionary guidelines, most provide low-level (levels 3-5) or inconclusive evidence of an association between lymphoedema and these risk factors, and only four level 2 studies show a significant association. Skin infections and previous infection or inflammation on the ipsilateral arm were among the most clearly defined and well established risk factors for lymphoedema. The paucity of high-level evidence and the conflicting nature of the existing literature make it difficult to establish definitive predictive factors for breast cancer-related lymphoedema, which could be a considerable source of patient distress and anxiety. Along with further research into these risk factors, continued discussion regarding modification of the guidelines and adoption of a risk-adjusted approach is needed.

A comprehensive review of bioimpedance spectroscopy as a diagnostic tool for the detection and measurement of breast cancer-related lymphedema.

As treatment for breast cancer improves and the threat of life-long chronic lymphedema becomes more prevalent, the need for effective screening tools emerges as crucial. This review was conducted using literature beginning in 1992 to analyze primary research testing the accuracy of bioimpedance spectroscopy as a diagnostic and early detection tool for breast cancer-related lymphedema. We concluded bioimpedance is an accurate diagnostic tool for pre-existent lymphedema, however, it has not been validated for early detection. J. Surg. Oncol. 2016;114:537-542. © 2016 Wiley Periodicals, Inc.

Origin, activation and heterogeneity of fibroblasts associated with pancreas and breast cancers.

Pancreas and breast cancers both contain abundant stromal components within the tumor tissues. A prominent cell type within the stroma is cancer-associated fibroblasts (CAFs). CAFs play critical and complex roles establishing the tumor microenvironment to either promote or prevent tumor progression. Recently, complex genetic models and single cell-based techniques have provided emerging insights on the precise functions and cellular heterogeneity of CAFs. The transformation of normal fibroblasts into CAFs is a key event during tumor initiation and progression. Such coordination between tumor cells and fibroblasts plays an important role in cancer development. Reprograming fibroblasts is currently being explored for therapeutic benefits. In this review, we will discuss recent literature shedding light on the tissues of origin, activation mechanisms, and heterogeneity of CAFs comparing pancreas and breast cancers.

PTEN in cancer associated fibroblasts.

Decades of research have concluded that disruptions to Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) have profound effects on cancer progression. However, as our understanding of the tumor stroma has evolved, we can appreciate that disruptions to tumor suppressors such as PTEN should not be studied solely in an epithelial context. Inactivation of PTEN in the stroma is associated with worse outcomes in human cancers, therefore, it is important to understand activities regulated downstream of PTEN in stromal compartments. Studies reviewed herein provide evidence for important mechanistic targets downstream of PTEN signaling in cancer-associated fibroblasts (CAFs), a major component of the tumor stroma. We also discuss the potential clinical implications for these findings.

Noncanonical activation of GLI signaling in SOX2+ cells drives medulloblastoma relapse.

SRY (sex determining region Y)-box 2 (SOX2)-labeled cells play key roles in chemoresistance and tumor relapse; thus, it is critical to elucidate the mechanisms propagating them. Single-cell transcriptomic analyses of the most common malignant pediatric brain tumor, medulloblastoma (MB), revealed the existence of astrocytic Sox2+ cells expressing sonic hedgehog (SHH) signaling biomarkers. Treatment with vismodegib, an SHH inhibitor that acts on Smoothened (Smo), led to increases in astrocyte-like Sox2+ cells. Using SOX2-enriched MB cultures, we observed that SOX2+ cells required SHH signaling to propagate, and unlike in the proliferative tumor bulk, the SHH pathway was activated in these cells downstream of Smo in an MYC-dependent manner. Functionally different GLI inhibitors depleted vismodegib-resistant SOX2+ cells from MB tissues, reduced their ability to further engraft in vivo, and increased symptom-free survival. Our results emphasize the promise of therapies targeting GLI to deplete SOX2+ cells and provide stable tumor remission.