Search Results (5)

The development of effective cancer vaccines remains a significant challenge due to immune tolerance and limited clinical benefits. Oncolytic herpes simplex virus type 1 (oHSV-1) has shown promise as a cancer therapy, but efficacy is often limited in advanced cancers. In this study, we constructed and characterized a novel oHSV-1 virus (VG22401) expressing the human epidermal growth factor receptor 2 (HER2), a transmembrane glycoprotein overexpressed in many carcinomas. VG22401 exhibited efficient replication and HER2 payload expression in both human and mouse colorectal cancer cells. Mice immunized with VG22401 showed significant binding of serum anti-HER2 antibodies to HER2-expressing tumor cells, inducing antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). Furthermore, mice primed with VG22401 and intratumorally boosted with the same virus showed enhanced antitumor efficacy in a bilateral syngeneic HER2(+) tumor model, compared to HER2-null backbone virus. This effect was accompanied by the induction of anti-HER2 T cell responses. Our findings suggest that peripheral priming with HER2-expressing oHSV-1 followed by an intratumoral boost with the same virus can significantly enhance antitumor immunity and efficacy, presenting a promising strategy for cancer immunotherapy. Full article

Oncolytic viruses (OVs) can specifically replicate in the host and cause cancer cell lysis while inducing an antitumor immune response. The aim of this study is to investigate the impact of either pre-existing immunity against herpes simplex virus type-1 (HSV-1) or multicycle treatment with OVs on anticancer efficacy of VG161, an HSV-1 OV in phase 2 clinical trial. VG161 efficacy was tested in CT26 mouse models by comparing the efficacy and immune response in naïve mice or in mice that were immunized with VG161. Moreover, VG161 efficacy in HLA-matched CD34+ humanized intrahepatic cholangiocarcinoma (ICC) patient-derived xenograft (PDX) models was also tested in multicycle treatment and was compared to standard chemotherapy for this type of cancer (gemcitabine). The HSV-1-immunized mice significantly inhibited tumor growth in VG161-treated mice compared to control naïve treated mice. RNA expression profiling and ELISPOT analyses indicated changes in the tumor’s immune profile in the immunized and treated group compared to naïve and treated mice, as well as enhanced T cell function depicted by higher numbers of tumor specific lymphocytes, which was enhanced by immunization. In the ICC PDX model, repeated treatment of VG161 with 2 or 3 cycles seemed to increase the anticancer efficacy of VG161. In conclusion, the anticancer efficacy of VG161 can be enhanced by pre-immunization with HSV-1 and multicycle administration when the virus is given intratumorally, indicating that pre-existing antiviral immunity might enhance OV-induced antitumor immunity. Our results suggest potential clinical benefits of HSV-1-based OV therapy in HSV-1-seropositive patients and multicycle administration of VG161 for long-term maintenance treatment. Full article

Background: Epilepsy surgery failure is not uncommon, with several explanations having been proposed. In this series, we detail cases of epilepsy surgery failure subsequently attributed to insular involvement. Methods: We retrospectively identified patients investigated at the epilepsy monitoring units of two Canadian tertiary care centers (2004–2020). Included patients were adults who had undergone epilepsy surgeries with recurrence of seizures post-operatively and who were subsequently determined to have an insular epileptogenic focus. Clinical, electrophysiological, neuroimaging, and surgical data were synthesized. Results: We present 14 patients who demonstrated insular epileptic activity post-surgery-failure as detected by intracranial EEG, MEG, or seizure improvement after insular resection. Seven patients had manifestations evoking possible insular involvement prior to their first surgery. Most patients (8/14) had initial surgeries targeting the temporal lobe. Seizure recurrence ranged from the immediate post-operative period to one year. The main modality used to determine insular involvement was MEG (8/14). Nine patients underwent re-operations that included insular resection; seven achieved a favorable post-operative outcome (Engel I or II). Conclusions: Our series suggests that lowering the threshold for suspecting insular epilepsy may be necessary to improve epilepsy surgery outcomes. Detecting insular epilepsy post-surgery-failure may allow for re-operations which may lead to good outcomes. Full article

Object detection is one of the vital and challenging tasks of computer vision. It supports a wide range of applications in real life, such as surveillance, shipping, and medical diagnostics. Object detection techniques aim to detect objects of certain target classes in a given image and assign each object to a corresponding class label. These techniques proceed differently in network architecture, training strategy and optimization function. In this paper, we focus on animal species detection as an initial step to mitigate the negative impacts of wildlife–human and wildlife–vehicle encounters in remote wilderness regions and on highways. Our goal is to provide a summary of object detection techniques based on R-CNN models, and to enhance the performance of detecting animal species in accuracy and speed, by using four different R-CNN models and a deformable convolutional neural network. Each model is applied on three wildlife datasets, results are compared and analyzed by using four evaluation metrics. Based on the evaluation, an animal species detection system is proposed. Full article

TiO₂-based photocatalysis under visible light is an attractive way to abate air pollutants. Moreover, developing photocatalytic materials on a large-scale requires safe and low-cost precursors. Both high-performance TiO₂ nanopowders and visible-light active noble metals do not match these requirements. Here, we report the design of novel Mn-decorated micrometric TiO₂ particles. Pigmentary TiO₂ replaced unsafe nano-TiO₂ and firmly supported MnO_x particles. Mn replaced noble metals such as Au or Ag, opening the way for the development of lower cost catalysts. Varying Mn loading or pH during the impregnation affected the final activity, thus giving important information to optimize the synthesis. Photocatalytic activity screening occurred on the gas-phase degradation of ethanol as a reference molecule, both under ultraviolet (UV) (6 h) and Light Emitting Diode (LED) (24 h) irradiation. Mn-doped TiO₂ reached a maximum ethanol degradation of 35% under visible light after 24 h for the sample containing 20% of Mn. Also, we found that an acidic pH increased both ethanol degradation and mineralization to CO₂, while an alkaline pH drastically slowed down the reaction. A strict correlation between photocatalytic results and physico-chemical characterizations of the synthesized powders were drawn. Full article