Multimodal sexual signals are not precise indicators of fertility in female Kinda baboons.

Female fertility signals are found across taxa, and the precision of such signals may be influenced by the relative strength of different sexual selection mechanisms. Among primates, more precise signals may be found in species with stronger direct male-male competition and indirect female mate choice, and less precise signals in species with stronger indirect male-male competition (e.g.

COLUMBUS-AD: phase III study of adjuvant encorafenib + binimetinib in resected stage IIB/IIC BRAF V600-mutated melanoma.

Stage IIB/IIC melanoma has a high risk of recurrence after surgical resection. While, for decades, surgery was the only option for high-risk stage II disease in most countries, adjuvant therapies now exist. Anti-programmed cell death protein 1 (PD-1) antibodies significantly improve recurrence-free survival versus placebo in patients with fully resected stage IIB/IIC melanoma.

Tumor Microenvironment Modifications Induced by Afatinib in Squamous Cell Carcinoma of the Head and Neck: A Window-of-Opportunity Study (EORTC-90111-24111).

Purpose: The EORTC-90111-24111 phase II window study evaluated afatinib versus no preoperative treatment in patients with primary squamous cell carcinoma of the head and neck (HNSCC). We investigated afatinib-induced tumor and microenvironment modifications by comparing pre- and posttreatment tumor biopsies.

Patients And Methods: Thirty treatment-naïve patients with primary HNSCC were randomized.

Unconfined Compression Experimental Protocol for Cartilage Explants and Hydrogel Constructs: From Sample Preparation to Mechanical Characterization.

Mechanical characterization of articular cartilage and cell-seeded hydrogel constructs is a challenging task due to the complex biphasic behavior of these materials. Here we describe a step-by-step unconfined compression testing protocol for inverse mechanical characterization of these materials from sample preparation to parameter identification. Examples from our ongoing experiments on alginate hydrogel constructs and preserved and damaged cartilage explants obtained from human hip samples are presented.

Organ Preservation and Late Functional Outcome in Oropharyngeal Carcinoma: Rationale of EORTC 1420, the "Best of" Trial.

Dysphagia represents one of the most serious adverse events after curative-intent treatments with a tremendous impact on quality of life in patients with head and neck cancers. Novel surgical and radiation therapy techniques have been developed to better preserve swallowing function, while not negatively influencing local control and/or overall survival. This review focuses on the current literature of swallowing outcomes after curative treatment strategies.

Distribution and bioaccumulation of POPs and mercury in the Ga-Selati River (South Africa) and the rivers Gudbrandsdalslågen and Rena (Norway).

Biomagnification of Hg and persistent organic pollutants (POPs: polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs), polybrominated diphenyl ethers (PBDEs)) in aquatic food chains can lead to high pollutant concentrations in top predators, including humans. Despite this threat to human health, research concerning bioaccumulation is still underrepresented in the southern hemisphere and in (sub)arctic and (sub)tropical areas, emphasizing the need for research in these locations. In this study, samples of water, sediment and aquatic biota were analyzed to determine concentrations of POPs and total mercury (THg) in the Ga-Selati river (South Africa) and two rivers Rena and Gudbrandsdalslågen in Norway.

Personalized biomarker-based treatment strategy for patients with squamous cell carcinoma of the head and neck: EORTC position and approach.

The molecular landscape of squamous cell carcinoma of the head and the neck (SCCHN) has been characterized and actionable or targetable genomic alterations have been identified. However, targeted therapies have very limited activity in unselected SCCHN, and the current treatment strategy is still based on tumor location and disease stage and not on tumor biology. Trying to select upfront the patients who will benefit from a specific treatment might be a way to improve patients' outcome.

Pharmacologically directed strategies in academic anticancer drug discovery based on the European NCI compounds initiative.

Background: The European NCI compounds programme, a joint initiative of the EORTC Research Branch, Cancer Research Campaign and the US National Cancer Institute, was initiated in 1993. The objective was to help the NCI in reducing the backlog of in vivo testing of potential anticancer compounds, synthesised in Europe that emerged from the NCI in vitro 60-cell screen.

Methods: Over a period of more than twenty years the EORTC-Cancer Research Campaign panel reviewed ∼2000 compounds of which 95 were selected for further evaluation.

Morphological and physiological differences in the upper trapezius muscle in patients with work-related trapezius myalgia compared to healthy controls: A systematic review.

Background: Trapezius myalgia is a common musculoskeletal complaint, characterized by pain, stiffness and tightness of the upper trapezius muscle. It is often work-related and caused by prolonged static and repetitive work tasks. It is hypothesized that this leads to various morphological and physiological alterations in muscle tissue but the pathophysiology is poorly understood.

New challenge of developing combined radio-drug therapy.

Combined modality treatment can be used to improve control of the local disease at the expense of increased toxicity. Several randomized trials have demonstrated that this combined modality therapy is better than radiotherapy alone or chemotherapy alone in the treatment of locally advanced diseases. Several new targets as well as potential new radio-sensitizers have been identified.

Phase I study of lonafarnib (SCH66336) in combination with trastuzumab plus paclitaxel in Her2/neu overexpressing breast cancer: EORTC study 16023.

Purpose: This phase I study was performed to determine the maximum tolerated dose (MTD), dose-limiting toxicities (DLT), safety profile, recommended dose for phase II studies, the pharmacokinetics, and antitumor activity of the combination of lonafarnib (farnesyl transferase inhibitor), trastuzumab, and paclitaxel in Her2-positive advanced breast cancer.

Methods: Twenty-three patients with Her2-overexpressing breast cancer received in the first cycle paclitaxel and trastuzumab and from cycle 2 onwards lonafarnib which was added to the combination. Dose-limiting toxicity (DLT) was determined during the second cycle.

Phase I clinical and magnetic resonance imaging study of the vascular agent NGR-hTNF in patients with advanced cancers (European Organization for Research and Treatment of Cancer Study 16041).

Purpose: This phase I trial investigating the vascular targeting agent NGR-hTNF aimed to determine the (a) dose-limiting toxicities, (b) maximum tolerated dose (MTD), (c) pharmacokinetics and pharmacodynamics, (d) vascular response by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), and (e) preliminary clinical activity in solid tumors.

Experimental Design: NGR-hTNF was administered once every 3 weeks by a 20- to 60-minute i.v.

An EORTC phase I study of Bortezomib in combination with oxaliplatin, leucovorin and 5-fluorouracil in patients with advanced colorectal cancer.

The combination of oxaliplatin, leucovorin and 5-fluorouracil (FOLFOX-4) is still a reference regimen in advanced colorectal cancer; however, the addition of new biologic compounds represents a significant way forward. Bortezomib is an inhibitor of proteasome, a multicatalytic enzyme complex that degrades several intracellular proteins. In this study, escalating doses of Bortezomib were administered along with the standard FOLFOX-4 doses, in order to evaluate the dose-limiting toxicity (DLT), toxicity profile and activity of the combination.

A phase I and pharmacokinetic study of OSI-7904L, a liposomal thymidylate synthase inhibitor in combination with oxaliplatin in patients with advanced colorectal cancer.

Purpose: OSI-7904L is a liposomal formulation of a potent thymidylate synthase (TS) inhibitor. This phase I study evaluated the safety, tolerability and pharmacokinetics (PK) of OSI-7904L administered in combination with oxaliplatin every 21 days in patients with advanced colorectal carcinoma.

Method: A 3+3 study design was utilized at predefined dose levels.

Retroviral-mediated transfer of genes encoding interleukin-2 and interleukin-12 into fibroblasts increases host antitumor responsiveness.

The transfer of genes encoding cytokines into tumor cells has emerged as a new strategy to increase in vivo host reactivity to a variety of tumors. Because gene transfer into tumor cells cannot be easily applied in the clinical setting, we have developed an experimental model of gene transfer into fibroblasts and examined the capacity of these engineered cells to elicit an antitumor immune response. Interleukin-12 (IL-12) is a heterodimeric cytokine with pleiotropic activities presenting strong antitumor and antimetastatic effects in murine models.

Retrovirus-mediated gene transfer of the human multidrug resistance-associated protein into hematopoietic cells protects mice from chemotherapy-induced leukopenia.

Utilization of chemotherapy for the treatment of tumors is mainly limited by its hematological toxicity. Because of the low-level expression of drug resistance genes, transduction of hematopoietic progenitors with multidrug resistance 1 (MDR1) or multidrug resistance-associated protein (MRP) genes should provide protection from chemotherapeutic agent toxicity. Successful transfer of drug resistance genes into hematopoietic cells may allow the administration of higher doses of chemotherapy and, thus, increase regression of chemosensitive tumors.

[Integration of carcinogenic viruses in the genome of in-vitro cultured human fibroblasts].

Avian sarcoma viruses are known for inducing no transformation of human diploid fibroblasts. Nevertheless, we show that the Rous sarcoma virus can infect and transform some human fibroblastic cell lines, replicate and express viral proteins, integrate into the host genome and prevent expression of MHC class I antigens on cell membranes. Cell transformation happens together with important and significant abnormalities of the cell karyotype and proviral integration is most often close to the c-src oncogene on chromosomes 1 and 20.