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Small leucine-rich proteoglycans (SLRPs) are major regulators of extracellular matrix assembly and cell signaling. Lumican, a member of the SLRPs family, and its derived peptides were shown to possess antitumor activity by interacting directly with the catalytic domain of MMP-14 leading to the inhibition of its activity. The aim of the present report was to characterize by in silico three-dimensional (3D) modeling the structure and the dynamics of four SLRPs including their core protein and their specific polysaccharide chains to assess their capacity to bind to MMP-14 and to regulate its activity. Molecular docking experiments were performed to identify the specific amino acids of MMP-14 interacting with each of the four SLRPs. The inhibition of each SLRP (100 nM) on MMP-14 activity was measured and the constants of inhibition ( Ki) were evaluated. The impact of the number of glycan chains, structures, and dynamics of lumican on the interaction with MMP-14 was assessed by molecular dynamics simulations. Molecular docking analysis showed that all SLRPs bind to MMP-14 through their concave face, but in different regions of the catalytic domain of MMP-14. Each SLRPs inhibited significantly the MMP-14 activity. Finally, molecular dynamics showed the role of glycan chains in interaction with MMP-14 and shielding effect of SLRPs. Altogether, the results demonstrated that each SLRP exhibited inhibition of MMP-14 activity. However, the differential targeting of MMP-14 by the SLRPs was shown to be related not only to the core protein conformation but also to the glycan chain structures and dynamics.

Purpose Patient autonomy is a key concept in medical ethics, which consists of recognizing each person as a free individual capable of judging and determining for himself or herself. The objectives of this study were to describe digestive cancer patients’ desire for autonomy in therapeutic decision-making and to identify variables associated with these preferences. Methods An observational prospective study in a French university cancer center has been conducted. Patients completed two questionnaires to qualify and quantify their desire for autonomy in therapeutic decision-making: the Control Preference Scale (CPS) and the Autonomy Preference Index (API), which is composed of the Decision Making (DM) score and the Information Seeking (IS) score. Associations between these scores and socio-demographic data, disease-related data, coping strategies (Brief-COPE), physical (QLQ-C30) and psychological (HADS) quality of life were tested. Results One-hundred fifteen patients returned the questionnaires. The majority of patients reported a passive (49.1%) or a collaborative (43.0%) CPS status. The mean DM score was 51.5. Variables associated with decision-making preferences were occupational status and time since diagnosis. Conclusion The identification of variables associated with patients' preferences for autonomy and participation in decision-making can help make clinicians aware of patients' needs and wishes. However, it can only be determined by interviewing the patient individually.

Purpose The aim of this study was to explore the beliefs, perceptions and representations of patients in order to identify the determinants of oral anticancer drugs adherence and to take action in current practice to improve patient support in digestive oncology. Methods We constructed a semi-directed interview guide which aimed to explore the patient’s relationship with medication, their health history, their experiences at the time of the announcement of treatment, their confidence, their fears, their motivations to adhere to their treatment and the constraints linked to their treatment. The data were analysed and discussed using a thematic approach. Results Seventeen patients agreed to participate in the study. The median age was 60 years. Ten patients had colorectal cancer, 3 patients had hepatocellular carcinoma, 3 patients had gastrointestinal stromal tumour and 1 patient had neuroendocrine pancreatic tumour. We identified five categories of factors influencing adherence: demographic and socioeconomic, disease-related, treatment-related, care system-related, and patient representation and pathways’ factors. A majority of patients emphasised the importance of family support in the adherence process and the convenience of per os treatment compared to other intravenous treatments. However, several negative determinants emerged such as the toxicity of the treatment, fears of forgetting to take the medication, difficulties with the galenic formulation and negative beliefs of the family. Conclusion This study demonstrates the need to address the different dimensions of the patient in order to understand his or her behaviour with regard to adherence and to identify the levers for improvement.

Purpose This study aims to explore the experience of caregivers of patients with digestive cancer and to compare the perspectives of patients and caregivers. Methods This was a mixed-methods study on caregiver-patient dyads. Semi-structured interviews with caregivers and their patients were conducted to explore each perspective. Two questionnaires were distributed to caregivers, the Caregiver Reaction Assessment (CRA) and the Supportive Care Needs Survey for Partners and Caregivers (SCNS-PC). Results Thirty-two caregivers completed the questionnaires. The CRA showed great self-esteem (3.8 +/- 0.7) and the burden on schedule (3.3 +/- 1). The SCNS-PC showed a need for healthcare service and information (2.0 +/- 0.8). Ten dyads participated in semi-structured interviews. Three themes emerged from caregiver’s interviews: the illness is an upheaval; the feeling of loneliness and helplessness and its consequences; a natural role with positive outcomes. Four themes emerged from the patient's side: the caregiver naturally takes on this role and gets closer; the caregiver is the patient's anchor; the disruption of the caregiver's life; anxiety, guilt, and the desire to protect the caregiver. Comparison of the data identifies many similarities between patients and caregivers, as well as discrepancies with the main theme being their relationship. Conclusion This demonstrates the importance of caring for caregivers and considering them in the context of their relationship with the patient to better understand their experience.

Purpose In France, 40,000 Port-a-Cath (PAC) are inserted each year. These medical devices are prone to complications during their insertion or use. The education of patients wearing these devices could be a lever to reduce the risk of complications. The objective of this work was to develop, in a multi-professional and consensual manner, a unique and specific skills reference framework for patients with PAC and to propose it as a reference tool for health professionals. Methods A multidisciplinary working group was set up to draw up this reference framework of skills. The first stage of the work consisted of a reflection leading to an exhaustive list of competencies necessary for the patient. These skills were then classified according to three different fields of knowledge (theoretical, know-how and attitudes). Finally, the working group identified priority competencies and established a grid that can be used to evaluate the level of acquisition of these competencies. Results Fifteen competencies were identified: five relating to theoretical knowledge, six relating to know-how and four relating to attitudes. These competencies were broken down into sub-competences. Seven competencies or sub-competencies were selected to constitute the list of priority competencies. Discussion This competency framework provides a reference framework for the education of patients with PAC and will help to harmonise practices within the different teams that care for patients with PAC.

Objectives Numerous adverse drug events (ADEs) are not identified by doctors in medical emergencies, and they are a barrier to optimal treatment of patients. Identification of the factors that influence awareness of ADEs by doctors could allow events that compromise patient safety to be avoided. The aims of this study were to quantify the recognition of ADEs by emergency room (ER) doctors and to identify the factors associated with the lack of identification of drug-related risks. Methods This study was carried out at the ER of a French teaching hospital between January 1, 2014, and the December 31, 2017. A previously used form was administered to the patients being treated in the ER, and it was completed using medical files to identify ADEs. The ADEs were then validated by a doctor and a senior pharmacist. Results Of the 1870 included patients, 279 (14.9%) exhibited an ADE. Of these 279 ADEs, 201 (72%) had been identified by the doctor. The probability of an ADE being identified was higher when the drug was directly linked with the main ailment of the patient (odds ratio, 1.72; 95% confidence interval, 1.01-2.97). Adverse drug events were identified less well when their severity was limited (spontaneous regression without treatment) (odds ratio, 0.5; 95% confidence interval, 0.27-0.93). Conclusions This study showed that ADEs are identified less well when their severity is limited, as well as when the ADE is not directly linked with the main ailment of the patient.

Simple Summary Lumican, a small leucine-rich proteoglycan (SLRP), maintains extracellular matrix (ECM) integrity while inhibiting melanoma primary tumor development, as well as metastatic spread. The aim of this study was to analyze the effect of lumican on tumor growth of murine ovarian carcinoma. C57BL/6 wild type mice (n = 12) and lumican-deficient mice (n = 10) were subcutaneously injected with murine ovarian epithelial carcinoma ID8 cells, and sacrificed after 18 days. Label-free infrared spectral imaging (IRSI) generated high contrast IR images allowing identification of different ECM regions of the skin and the ovarian tumor. IRSI showed a good correlation with collagen distribution as well as organization, as analyzed using second harmonic generation imaging within the tumor area. The results demonstrated that lumican inhibited the growth of ovarian cancer mainly by altering collagen fibrilogenesis. Abstract Ovarian cancer remains one of the most fatal cancers due to a lack of robust screening methods of detection at early stages. Extracellular matrix (ECM) mediates interactions between cancer cells and their microenvironment via specific molecules. Lumican, a small leucine-rich proteoglycan (SLRP), maintains ECM integrity and inhibits both melanoma primary tumor development, as well as metastatic spread. The aim of this study was to analyze the effect of lumican on tumor growth of murine ovarian epithelial cancer. C57BL/6 wild type mice (n = 12) and lumican-deficient mice (n = 10) were subcutaneously injected with murine ovarian epithelial carcinoma ID8 cells, and then sacrificed after 18 days. Analysis of tumor volumes demonstrated an inhibitory effect of endogenous lumican on ovarian tumor growth. The ovarian primary tumors were subjected to histological and immunohistochemical staining using anti-lumican, anti-αv integrin, anti-CD31 and anti-cyclin D1 antibodies, and then further examined by label-free infrared spectral imaging (IRSI), second harmonic generation (SHG) and Picrosirius red staining. The IR tissue images allowed for the identification of different ECM tissue regions of the skin and the ovarian tumor. Moreover, IRSI showed a good correlation with αv integrin immunostaining and collagen organization within the tumor. Our results demonstrate that lumican inhibits ovarian cancer growth mainly by altering collagen fibrilogenesis.

Ovarian cancer remains one of the most fatal cancers due to a lack of robust screening methods of detection at early stages. Extracellular matrix (ECM) mediates interactions between cancer cells and their microenvironment via specific molecules. Lumican, a small leucine-rich proteoglycan (SLRP), maintains ECM integrity and inhibits both melanoma primary tumor development, as well as metastatic spread. The aim of this study was to analyze the effect of lumican on tumor growth of murine ovarian epithelial cancer. C57BL/6 wild type mice (n = 12) and lumican-deficient mice (n = 10) were subcutaneously injected with murine ovarian epithelial carcinoma ID8 cells, and then sacrificed after 18 days. Analysis of tumor volumes demonstrated an inhibitory effect of endogenous lumican on ovarian tumor growth. The ovarian primary tumors were subjected to histological and immunohistochemical staining using anti-lumican, anti-αv integrin, anti-CD31 and anti-cyclin D1 antibodies, and then further examined by label-free infrared spectral imaging (IRSI), second harmonic generation (SHG) and Picrosirius red staining. The IR tissue images allowed for the identification of different ECM tissue regions of the skin and the ovarian tumor. Moreover, IRSI showed a good correlation with αv integrin immunostaining and collagen organization within the tumor. Our results demonstrate that lumican inhibits ovarian cancer growth mainly by altering collagen fibrilogenesis.