Control over imidazoquinoline immune stimulation by pH-degradable poly(norbornene) nanogels

The reactivation of the innate immune system by toll-like receptor (TLR) agonists holds promise for anticancer immunotherapy. Severe side effects caused by unspecific and systemic activation of the immune system upon intravenous injection prevent the use of small-molecule TLR agonists for such purposes. However, a covalent attachment of small-molecule imidazoquinoline (IMDQ) TLR7/8 agonists to pH-degradable polymeric nanogels could be shown to drastically reduce the systemic inflammation but retain the activity to tumoral tissues and their draining lymph nodes. Here, we introduce the synthesis of poly(norbornene)-based, acid-degradable nanogels for the covalent ligation of IMDQs. While the intact nanogels trigger sufficient TLR7/8 receptor stimulation, their degraded version of soluble, IMDQ-conjugated poly(norbornene) chains hardly activates TLR7/8. This renders their clinical safety profile, as degradation products are obtained, which would not only circumvent nanoparticle accumulation in the body but also provide nonactive, polymer-bound IMDQ species. Their immunologically silent behavior guarantees both spatial and temporal control over immune activity and, thus, holds promise for improved clinical applications

The relationship between vascularity, p53 gene mutations and distant metastatic disease in epithelial ovarian carcinoma

Mutations of the p53 tumor suppressor gene are associated with large differences (>7 vessels/HPF) in Microvessel density (MVD) counts between primary and metastatic tumor sites in patients with epithelial ovarian cancer. These data are consistent with models demonstrating p53 mutation functions directly to influence angiogenesis. This information supports continued therapy and research involving angiogenesis inhibitors in patients with ovarian cancer, especially in the setting of increased differences in MVD between primary and metastatic sites

The effect of weight-based chemotherapy dosing in a cohort of gynecologic oncology patients

The American Society of Clinical Oncology recommends that full weight-based doses of chemotherapy be used to treat obese patients with cancer. However, many oncologists limit the dose of chemotherapy based on ideal body weight or a maximum body surface area (BSA) of m2. The objective of our study is to determine how weight-based chemotherapy dosing affects toxicity, treatment delays, and laboratory values in a cohort of obese gynecologic cancer patients at our institution. We hypothesize that full weight-based dosing in obese patients does not increase adverse chemotherapy outcomes

Lymphoid Enhancing Factor 1 (Lef-1) overexpression in epithelial ovarian, fallopian tube and peritoneal cancer and associations with clinical factors

Lef-1 mRNA levels were statistically elevated in cases of ovarian, fallopian tube or peritoneal cancer when compared to non-cancerous controls. Among cancer cases, levels of Lef-1 were statistically different between stage and histology. Lef-1 overexpression may be predictive of poor overall survival. These findings suggest that Lef-1 overexpression may contribute to ovarian, fallopian tube and peritoneal carcinogenesis, and that further investigation is warranted

Zmiz1 is overexpressed in epithelial ovarian cancer and associated with p53 gene mutations

Zmiz1 staining is elevated in patients with epithelial ovarian cancer. Tumors that are Zmiz1 positive are associated with mutations of the p53 gene. Zmiz1 overexpression may be associated with decreased survival in patients with epithelial ovarian cancer. Additional studies are needed to more clearly determine the role of Zmiz1 in patients with epithelial ovarian cancer

Zmiz1 is overexpressed in epithelial ovarian cancer and associated with p53 gene mutations

Zmiz1 staining is elevated in patients with epithelial ovarian cancer. Tumors that are Zmiz1 positive are associated with mutations of the p53 gene. Zmiz1 overexpression may be associated with decreased survival in patients with epithelial ovarian cancer. Additional studies are needed to more clearly determine the role of Zmiz1 in patients with epithelial ovarian cancer

Myositis ossificans : another condition with USP6 rearrangement, providing evidence of a relationship with nodular fasciitis and aneurysmal bone cyst

Myositis ossificans is defined as a self-limiting pseudotumor composed of reactive hypercellular fibrous tissue and bone. USP6 rearrangements have been identified as a consistent genetic driving event in aneurysmal bone cyst and nodular fasciitis. It is therefore an integral part of the diagnostic workup when dealing with (myo)fibroblastic lesions of soft tissue and bone. Two cases of myositis ossificans with USP6 rearrangement were published so far. We determine herein the incidence of USP6 rearrangement in myositis ossificans using USP6 fluorescence in situ hybridization analysis (FISH). Of the 11 cases included, seven patients were female and four were male. Age ranged from 6 to 56 years (mean 27 years). Lesions were located in the thigh (n = 5), knee (n = 1), lower leg (n = 1), lower arm (n = 1), perineum (n = 1), gluteal (n = 1) and thoracic wall (n = 1). All assessable cases except one (8/9) showed rearrangement of USP6 providing evidence that myositis ossificans is genetically related to nodular fasciitis and aneurysmal bone cyst

Efficacy and safety of bevacizumab in recurrent sex cord-stromal ovarian tumors: Results of a phase 2 trial of the Gynecologic Oncology Group: Bevacizumab for Stromal Ovarian Tumors

The Gynecologic Oncology Group conducted this phase II trial to estimate the anti-tumor activity of bevacizumab and to determine the nature and degree of toxicity in patients with recurrent sex cord-stromal tumors of the ovary

A future agenda for research on climate change and human mobility

In the past 15 years, research activities focusing on the interlinkages between climate change and human mobility have intensified. At the same time, an increasing number of actors and processes have sought to address human mobility in the context of climate change from a policy perspective. Hitherto, research has been limited in terms of geographical preferences as well as conceptual and methodological focus areas. This paper argues that to address the evolving policy space, future research on climate change in the context of human mobility needs to become more differentiated, integrated and generalized. This includes concerted efforts to better integrate researchers from the global South, improved cross‐linkages between different datasets, approaches and disciplines, more longitudinal and comparative studies and development of innovative qualitative and quantitative methods

A future agenda for research on climate change and human mobility

In the past 15 years, research activities focusing on the interlinkages between climate change and human mobility have intensified. At the same time, an increasing number of actors and processes have sought to address human mobility in the context of climate change from a policy perspective. Hitherto, research has been limited in terms of geographical preferences as well as conceptual and methodological focus areas. This paper argues that to address the evolving policy space, future research on climate change in the context of human mobility needs to become more differentiated, integrated and generalized. This includes concerted efforts to better integrate researchers from the global South, improved cross-linkages between different datasets, approaches and disciplines, more longitudinal and comparative studies and development of innovative qualitative and quantitative methods.</p