Targeting of c-MET and AXL by cabozantinib is a potential therapeutic strategy for patients with head and neck cell carcinoma.

Local or metastatic relapse following surgery, radiotherapy, and cisplatin is the leading cause of death in patients with head and neck squamous cell carcinoma (HNSCC). Our study shows overexpression of c-MET and AXL in HNSCC cells and patients resistant to radiotherapy and cisplatin. We demonstrate that cabozantinib, an inhibitor of vascular endothelial growth factor receptor (VEGFR), c-MET, and AXL, decreases migration, invasion, and proliferation and induces mitotic catastrophe and apoptotic cell death of naive and radiotherapy- and cisplatin-resistant HNSCC cells.

The Polo-like kinase 1 inhibitor onvansertib represents a relevant treatment for head and neck squamous cell carcinoma resistant to cisplatin and radiotherapy.

Head and neck squamous cell carcinoma (HNSCC) represent the 4 most aggressive cancer. 50% of patients relapse to the current treatments combining surgery, radiotherapy and cisplatin and die two years after the diagnosis. Elevated expression of the polo-like kinase 1 (Plk1) correlated to a poor prognosis in epidermoid carcinomas.

Plk1, upregulated by HIF-2, mediates metastasis and drug resistance of clear cell renal cell carcinoma.

Polo-like kinase 1 (Plk1) expression is inversely correlated with survival advantages in many cancers. However, molecular mechanisms that underlie Plk1 expression are poorly understood. Here, we uncover a hypoxia-regulated mechanism of Plk1-mediated cancer metastasis and drug resistance.

Identification of a new aggressive axis driven by ciliogenesis and absence of VDAC1-ΔC in clear cell Renal Cell Carcinoma patients.

: Renal cell carcinoma (RCC) accounts for about 2% of all adult cancers, and clear cell RCC (ccRCC) is the most common RCC histologic subtype. A hallmark of ccRCC is the loss of the primary cilium, a cellular antenna that senses a wide variety of signals. Loss of this key organelle in ccRCC is associated with the loss of the von Hippel-Lindau protein (VHL).

Co-culture of human fibroblasts, smooth muscle and endothelial cells promotes osteopontin induction in hypoxia.

Arteriovenous fistulas (AVFs) are the preferred vascular access for haemodialysis of patients suffering from end-stage renal disease, a worldwide public health problem. However, they are prone to a high rate of failure due to neointimal hyperplasia and stenosis. This study aimed to determine if osteopontin (OPN) was induced in hypoxia and if OPN could be responsible for driving AVF failure.

New CXCR1/CXCR2 inhibitors represent an effective treatment for kidney or head and neck cancers sensitive or refractory to reference treatments.

Clear cell Renal Cell (RCC) and Head and Neck Squamous Cell Carcinomas (HNSCC) are characterized by a pro-angiogenic/pro-inflammatory context. Despite conventional or targeted therapies, metastatic RCC and HNSCC remain incurable. Alternative treatments to reference therapies (sunitinib, a multi tyrosine kinase inhibitor for RCC or cisplatin for HNSCC) are urgently needed on relapse.

Resistance to lysosomotropic drugs used to treat kidney and breast cancers involves autophagy and inflammation and converges in inducing CXCL5.

Lysosomotropic agents such as sunitinib, lapatinib, and chloroquine belong to a drug family that is being used more frequently to treat advanced cancers. Sunitinib is standard care for metastatic renal cell carcinomas (mRCC) and lapatinib is used for trastuzumab/pertuzumab-refractory cancers. However, patients ineluctably relapse with a delay varying from a few months to a few years.

Soluble CD146 is a predictive marker of pejorative evolution and of sunitinib efficacy in clear cell renal cell carcinoma.

The objective of the study was to use CD146 mRNA to predict the evolution of patients with non-metastatic clear cell renal cell carcinoma (M0 ccRCC) towards metastatic disease, and to use soluble CD146 (sCD146) to anticipate relapses on reference treatments by sunitinib or bevacizumab in patients with metastatic ccRCC (M1). : A retrospective cohort of M0 patients was used to determine the prognostic role of intra-tumor CD146 mRNA. Prospective multi-center trials were used to define plasmatic sCD146 as a predictive marker of sunitinib or bevacizumab efficacy for M1 patients.

ATP-competitive Plk1 inhibitors induce caspase 3-mediated Plk1 cleavage and activation in hematopoietic cell lines.

Polo-like kinases (Plks) define a highly conserved family of Ser/Thr kinases with crucial roles in the regulation of cell division. Here we show that Plk1 is cleaved by caspase 3, but not by other caspases in different hematopoietic cell lines treated with competitive inhibitors of the ATP-binding pocket of Plk1. Intriguingly, Plk1 was not cleaved in cells treated with Rigosertib, a non-competitive inhibitor of Plk1, suggesting that binding of the inhibitor to the ATP binding pocket of Plk1 triggers a conformational change and unmasks a cryptic caspase 3 cleavage site on the protein.

CXCL7 is a predictive marker of sunitinib efficacy in clear cell renal cell carcinomas.

Background: Sunitinib is one of the first-line standard treatments for metastatic clear cell renal cell carcinoma (ccRCC) with a median time to progression shorter than 1 year. The objective is to discover predictive markers of response to adapt the treatment at diagnosis.

Methods: Prospective phase 2 multi-centre trials were conducted in ccRCC patients initiating sunitinib (54 patients) or bevacizumab (45 patients) in the first-line metastatic setting (SUVEGIL and TORAVA trials).

Sunitinib Stimulates Expression of VEGFC by Tumor Cells and Promotes Lymphangiogenesis in Clear Cell Renal Cell Carcinomas.

Sunitinib is an antiangiogenic therapy given as a first-line treatment for renal cell carcinoma (RCC). While treatment improves progression-free survival, most patients relapse. We hypothesized that patient relapse can stem from the development of a lymphatic network driven by the production of the main growth factor for lymphatic endothelial cells, VEGFC.

Resistance to sunitinib in renal clear cell carcinoma results from sequestration in lysosomes and inhibition of the autophagic flux.

Metastatic renal cell carcinomas (mRCC) are highly vascularized tumors that are a paradigm for the treatment with antiangiogenesis drugs targeting the vascular endothelial growth factor (VEGF) pathway. The available drugs increase the time to progression but are not curative and the patients eventually relapse. In this study we have focused our attention on the molecular mechanisms leading to resistance to sunitinib, the first line treatment of mRCC.

Nutritional status and blood pressure assessment in vulnerable children from two schools in Cutral Co and Plaza Huincul: a quantitative and qualitative study.

Introduction: Knowing the nutritional status of children is critical to plan primary health care interventions in the setting of the present obesity epidemic and the great increase in the prevalence of childhood metabolic syndrome. For this reason, nutritional status and blood pressure were assessed among children from two schools of high social vulnerability, results were qualitatively analyzed, and community members feedback was obtained in order to be fully aware of the situation and accordingly plan local health interventions.

Population And Methods: Cross-sectional study conducted at purposively selected schools, with results analyzed using focus groups.

Ion jelly: a tailor-made conducting material for smart electrochemical devices.

We present a new concept for the design of a polymeric conducting material that combines the chemical versatility of an organic salt (ionic liquid) with the morphological versatility of a biopolymer (gelatin); the resulting 'ion jelly' can be applied in electrochemical devices, such as batteries, fuel cells, electrochromic windows or photovoltaic cells.

[Extraction of intravascular foreign bodies].

Objective: Loss or displacement of foreign material within the cardiovascular system is not an uncommon event. Foreign bodies include fragments of diagnosis equipment, ruptured catheters or malpositioned or displaced intravascular prostheses. The incidence has increased with the development of endovascular catheterism and raises the problem of extraction.

[Indirect approach of stenosis of transplanted kidneys by Doppler echography].

Pulsed Doppler ultrasound for the detection of rejection and renal artery stenoses involving transplanted kidneys was evaluated. Using mean velocity curves, the time interval between the ECG R wave and the onset of peak velocity was measured successively on the renal and ipsilateral iliac arteries and divided by the R-R interval. In 27 patients, a Doppler index defined as the ratio of the standardized renal artery and iliac artery time intervals, was determined and compared to angiographic data.

[Role of computerized pulmonary angiography by peripheral venous approach in the study of deep venous thromboses of the legs].

A pulmonary angiography through peripheral venous approach was systematically performed in 40 consecutive patients presenting a recent deep venous thrombosis. None of these patients had been sent for a suspected pulmonary embolus. The analysis of the images that were obtained, enabled to confirm the diagnosis of pulmonary migration in 9 of these patients (22.

[Comparative study of the carrying out of iliac angioplasty with digital and conventional angiography. Impact on real (consumable) costs].

Differences in time and cost were evaluated between the performance of iliac angioplasty with conventional (AC) and digital subtraction (AN) angiography, after a total of 27 angioplasties (13 with AC and 14 with AN). Excluding amortization of material and personnel costs, findings confirmed a certain number of advantages for AN: gain in time of about 34%, decrease of about 14% in charges, and notably of 83% in expenditure on films and 50% on contrast media.

Acute peripheral arterial and graft occlusion: treatment with selective infusion of urokinase and lysyl plasminogen.

Thirty-five patients hospitalized for recent angiographically documented arterial occlusion in the legs (27 femoropopliteal arteries and eight grafts) benefited from local fibrinolytic therapy delivered at the site of the occlusion with a 4- or 5-F catheter. This therapy combined a continuous urokinase (UK) infusion of 1,000 U/kg/hour and a lysyl plasminogen (LYS-PLG) infusion of 15 microkatals every 30 minutes. Angiographically confirmed lysis was obtained in 85% of the cases.

[Posttraumatic occlusion of the 2 vertebral arteries].

Initial radioclinical examination of a 24 year old patient following a road accident showed a hemomediastinum on computed tomography imaging. Digital subtraction angiography by the arterial route demonstrated integrity of abdominal aorta and occlusion of both vertebral arteries soon after their origin. This bilateral occlusion had failed to provoke any neurologic sign imputable to the vascular lesion.

[Determination of the ejection fraction of the left ventricle by videodensitometric analysis of digital angiography. Preliminary results].

Digitalisation enables angiocardiography to be performed by a peripheral intravenous injection. Computer-assisted analysis of the date widens the possibilities of quantification. The authors have developed a videodensitometric method of studying the left ventricular ejection fraction.