Multi-Modality Therapeutics with Potent Anti-Tumor Effects: Photochemical Internalization Enhances Delivery of the Fusion Toxin scFvMEL/rGel

BACKGROUND: There is a need for drug delivery systems (DDS) that can enhance cytosolic delivery of anti-cancer drugs trapped in the endo-lysosomal compartments. Exposure of cells to specific photosensitizers followed by light exposure (photochemical internalization, PCI) results in transfer of agents from the endocytic compartment into the cytosol. METHODOLOGY AND PRINCIPAL FINDINGS: The recombinant single-chain fusion construct scFvMEL/rGel is composed of an antibody targeting the progenitor marker HMW-MAA/NG2/MGP/gp240 and the highly effective toxin gelonin (rGel). Here we demonstrate enhanced tumor cell selectivity, cytosolic delivery and anti-tumor activity by applying PCI of scFvMEL/rGel. PCI performed by light activation of cells co-incubated with scFvMEL/rGel and the endo-lysosomal targeting photosensitizers AlPcS(2a) or TPPS(2a) resulted in enhanced cytotoxic effects against antigen-positive cell lines, while no differences in cytotoxicity between the scFvMEL/rGel and rGel were observed in antigen-negative cells. Mice bearing well-developed melanoma (A-375) xenografts (50-100 mm(3)) were treated with PCI of scFvMEL/rGel. By 30 days after injection, approximately 100% of mice in the control groups had tumors>800 mm(3). In contrast, by day 40, 50% of mice in the PCI of scFvMEL/rGel combination group had tumors<800 mm(3) with no increase in tumor size up to 110 days. PCI of scFvMEL/rGel resulted in a synergistic effect (p<0.05) and complete regression (CR) in 33% of tumor-bearing mice (n = 12). CONCLUSIONS/SIGNIFICANCE: This is a unique demonstration that a non-invasive multi-modality approach combining a recombinant, targeted therapeutic such as scFvMEL/rGel and PCI act in concert to provide potent in vivo efficacy without sacrificing selectivity or enhancing toxicity. The present DDS warrants further evaluation of its clinical potential

Biological control of the millet head miner Heliocheilus albipunctella in the Sahelian region by augmentative releases of the parasitoid wasp Habrobracon hebetor: effectiveness and farmers’ perceptions

On-farm augmentative releases of the parasitoid Habrobracon hebetor (Say) for controlling the millet head miner (MHM) Heliocheilus albipunctella (de Joannis) were tested in Burkina Faso, Mali and Niger from 2007 to 2009. In addition, a survey of farmers’ perceptions of insect pests, with particular focus on MHM, and the biological control program (BCP) was carried out. There was a significant increase of MHM parasitization rate after the releases, with up to 97% mortality. The survey on farmers’ perceptions revealed a fair knowledge of the MHM and the ability of farmers to describe the pest and the damage it caused. Farmers claimed that the biocontrol agent H. hebetor is effective and perceived a significant gain in grain yield due to this control strategy. Implications of these findings for a large extension of the MHM biocontrol program are discussed

Travel burden and clinical presentation of retinoblastoma: analysis of 1024 patients from 43 African countries and 518 patients from 40 European countries

BACKGROUND: The travel distance from home to a treatment centre, which may impact the stage at diagnosis, has not been investigated for retinoblastoma, the most common childhood eye cancer. We aimed to investigate the travel burden and its impact on clinical presentation in a large sample of patients with retinoblastoma from Africa and Europe. METHODS: A cross-sectional analysis including 518 treatment-naïve patients with retinoblastoma residing in 40 European countries and 1024 treatment-naïve patients with retinoblastoma residing in 43 African countries. RESULTS: Capture rate was 42.2% of expected patients from Africa and 108.8% from Europe. African patients were older (95% CI -12.4 to -5.4, p<0.001), had fewer cases of familial retinoblastoma (95% CI 2.0 to 5.3, p<0.001) and presented with more advanced disease (95% CI 6.0 to 9.8, p<0.001); 43.4% and 15.4% of Africans had extraocular retinoblastoma and distant metastasis at the time of diagnosis, respectively, compared to 2.9% and 1.0% of the Europeans. To reach a retinoblastoma centre, European patients travelled 421.8 km compared to Africans who travelled 185.7 km (p<0.001). On regression analysis, lower-national income level, African residence and older age (p<0.001), but not travel distance (p=0.19), were risk factors for advanced disease. CONCLUSIONS: Fewer than half the expected number of patients with retinoblastoma presented to African referral centres in 2017, suggesting poor awareness or other barriers to access. Despite the relatively shorter distance travelled by African patients, they presented with later-stage disease. Health education about retinoblastoma is needed for carers and health workers in Africa in order to increase capture rate and promote early referral

Cure du reflux gastro-oesophagien de l’adulte par voie laparoscopique: résultats d’une série de 30 cas

The fundoplication conventionally given in open surgery in the surgical treatment of gastroesophageal reflux disease (GERD) are reproducible with laparoscopic way. The aim of this study was to evaluate our results of surgical treatment of GERD refractory to medical treatment performed laparoscopically. Between 2005 and 2008, 30 patients underwent fundoplication in this way. The diagnosis of GERD was suspected clinically and confirmed in spite of lack of esophageal manometry and pH-metry by the barium esophagogram and endoscopy. Three fundoplication techniques were used in the series: Nissen-Rossetti, Toupet and Nissen. The postoperative course was uneventful with a carrying on of oral feeding on postoperative day 3, an average hospital stay of five days and low transient dysphagia. Laparoscopic fundoplication is currently the consensual surgical treatment of GERD. The debate on the type of fundoplication is not closed but the introduction of laparoscopy in our practice has improved the acceptability of surgery especially in younger patients in good health frequent relapses

Le carcinome épidermoïde de l\'urètre masculin

No Abstract. African Journal of Urology Vol. 11(3) 2005: 230-23

Chirurgie Des Méningiomes Intracrâniens Dans Une Unité Neurochirurgicale De Dakar

Objectifs Rapporter notre expérience sur la chirurgie des méningiomes intracrâniens à Dakar . Méthode Les auteurs rapportent une série rétrospective de 24 patients porteurs de méningiomes intracrâniens opérés dans une unité neurochirurgicale différente de notre institution mère à Dakar . Le recrutement s'est fait de Janvier 2001 à Juillet 2004. L'évaluation diagnostique a reposé essentiellement sur la tomodensitométrie cérébrale et l'anatomo-pathologie. Résultats Il s'agissait de 17 femmes et de 7 hommes. L'âge de nos patients variaient entre 21 et 77 ans avec un pic de fréquence à 55 ans . Le syndrome d'hypertension intracrânienne et la comitialité ont été les circonstances diagnostiques les plus fréquentes avec un taux de 37%. La tomodensitométrie cérébrale a permis d'évoquer un diagnostic présomptif de nature. Concernant la topographie, les méningiomes de la convexité ont été observés dans 50% des cas suivis par les méningiomes de la base (20%). L'évaluation de la qualité de l'exérèse chirurgicale selon le grading de Simpson a retrouvé 20% de grade I et 64% de grade II. L'insuffisance du plateau technique et le manque de compétences en neuroanesthesie rendent compte de la mortalité post-opératoire de 12%. Conclusion Ce travail nous permet de proposer une stratégie d'amélioration de la pratique neurochirurgicale tumorale en Afrique subsaharienne. Objective To report our experience of intracranial meningiomas surgery in Dakar. Method We analysed a population of 24 patients who underwent operation in a Neurosurgical unit different from our mother Institution. Brain CT scan has been done for every patient and histopathological confirmation has been reached for all patients. Results Regarding sex, we have 17 females for 7 males. The patient age was between 21 and 77 years old with a mean of 55.Intracranial hypertension and seizures were the main symptoms encountered with 37% for each. Our diagnostic evaluation is based on CT scan which showed 50% of convexity meningiomas and 20% basal one .By using Simpson grading to assess the quality of surgical resection ,we found 64% of grade II and only 20% of grade I.A 12% of postoperative death rate is related on the substandard medical set and the lack of neuroanesthesists. Conclusion We outlined a program to improve the neurosurgery practice in Sub-Saharan countries. Keywords: Afrique, méningiomes intracrâniens, neurochirurgie, Sénégal, tumeurs, Africa, intracranial tumors, meningioma, neurosurgery, SenegalAfrican Journal of Neurological Sciences Vol. 24 (1) 2005: pp. 45-55