Ultrasound targeted microbubble destruction using docetaxel and Rose Bengal loaded Microbubbles for targeted Chemo-Sonodynamic therapy treatment of prostate cancer.

Docetaxel (DTX) chemotherapy is commonly used in the treatment of patients with advanced prostate cancer demonstrating modest improvements in survival. As these patients are often elderly and the chemotherapy treatment is not targeted, it is often poorly tolerated. More targeted approaches that increase therapeutic efficacy yet reduce the amount of toxic chemotherapy administered are needed.

Non-Invasive, Targeted Nanoparticle-Mediated Drug Delivery across a Novel Human BBB Model.

The blood-brain barrier (BBB) is a highly sophisticated system with the ability to regulate compounds transporting through the barrier and reaching the central nervous system (CNS). The BBB protects the CNS from toxins and pathogens but can cause major issues when developing novel therapeutics to treat neurological disorders. PLGA nanoparticles have been developed to successfully encapsulate large hydrophilic compounds for drug delivery.

Exploring sex as a moderator of other prognostic variables in whiplash associated disorder: An observational study.

Background: Prognostic variables for assessing people with whiplash associated disorder (WAD) following a motor vehicle collision (MVC) have been evaluated in numerous studies. However, there is minimal evidence assessing how these variables may differ between males and females.

Question/purpose: 1) To assess if the sex of a person interacts with known prognostic variables within the development of chronic WAD.

A single microbubble formulation carrying 5-fluorouridine, Irinotecan and oxaliplatin to enable FOLFIRINOX treatment of pancreatic and colon cancer using ultrasound targeted microbubble destruction.

FOLFIRINOX and FOLFOXIRI are combination chemotherapy treatments that incorporate the same drug cocktail (folinic acid, 5-fluorouracil, oxaliplatin and irinotecan) but exploit an altered dosing regimen when used in the management of pancreatic and colorectal cancer, respectively. Both have proven effective in extending life when used to treat patients with metastatic disease but are accompanied by significant adverse effects. To facilitate improved tumour-targeting of this drug combination, an ultrasound responsive microbubble formulation loaded with 5-fluorouridine, irinotecan and oxaliplatin (FIRINOX MB) was developed and its efficacy tested, together with the non-toxic folinic acid, in preclinical murine models of pancreatic and colorectal cancer.

Sonodynamic therapy complements PD-L1 immune checkpoint inhibition in a murine model of pancreatic cancer.

The emergence of immune checkpoint inhibitors (ICI's) in the past decade has proven transformative in the area of immuno-oncology. The PD-1/PD-L1 axis has been particularly well studied and monoclonal antibodies developed to block either the receptor (anti PD-1) or its associated ligand (anti PD-L1) can generate potent anti-tumour immunity in certain tumour models. However, many "immune cold" tumours remain unresponsive to ICI's and strategies to stimulate the adaptive immune system and make these tumours more susceptible to ICI treatment are currently under investigation.

Synthesis of a gemcitabine-modified phospholipid and its subsequent incorporation into a single microbubble formulation loaded with paclitaxel for the treatment of pancreatic cancer using ultrasound-targeted microbubble destruction.

Gemcitabine and nab-paclitaxel (Abraxane®) is a standard of care chemotherapy combination used in the treatment of patients with advanced pancreatic cancer. While the combination has shown a survival benefit when compared to gemcitabine monotherapy, it is associated with significant off-target toxicity. Ultrasound targeted microbubble destruction (UTMD) has emerged as an effective strategy for the site-specific deposition of drug-payloads.

Exploiting a Rose Bengal-bearing, oxygen-producing nanoparticle for SDT and associated immune-mediated therapeutic effects in the treatment of pancreatic cancer.

Sonodynamic therapy (SDT) is an emerging stimulus-responsive approach for the targeted treatment of solid tumours. However, its ability to generate stimulus-responsive cytotoxic reactive oxygen species (ROS), is compromised by tumour hypoxia. Here we describe a robust means of preparing a pH-sensitive polymethacrylate-coated CaO nanoparticle that is capable of transiently alleviating tumour hypoxia.

An ultrasound responsive microbubble-liposome conjugate for targeted irinotecan-oxaliplatin treatment of pancreatic cancer.

Survival rates in pancreatic cancer have remained largely unchanged over the past four decades with less than 5% of patients surviving five years following initial diagnosis. FOLFIRINOX chemotherapy, a combination of folinic acid, 5-fluoruracil, irinotecan and oxaliplatin, has shown the greatest survival benefit for patients with advanced disease but is only indicated for those with good physical performance status due to its extreme off-target toxicity. Ultrasound targeted microbubble destruction (UTMD) has emerged as an effective strategy for the targeted delivery of drug payloads to solid tumours and involves using low intensity ultrasound to disrupt (burst) MBs in the tumour vasculature, releasing encapsulated or attached drugs in a targeted manner.

Liposome mimicking polymersomes; A comparative study of the merits of polymersomes in terms of formulation and stability.

The past few decades have seen a significant rise in research into alternative polymer based nanosized unilamellar drug delivery systems, termed polymersomes. The reported benefits of polymersomes over the more traditional liposomes include increased stability, higher encapsulation efficacies, better adaptability and reduced water permeation due to an increased bilayer thickness. Together, these advantages render them suitable for a plethora of therapies.

Rose Bengal-Amphiphilic Peptide Conjugate for Enhanced Photodynamic Therapy of Malignant Melanoma.

Malignant melanoma is an aggressive skin cancer with poor survival outcomes for patients diagnosed at an advanced stage. While targeted serine/threonine-protein kinase B-Raf (BRAF) and immune checkpoint inhibitors have improved survival outcomes for a proportion of these patients, response rates remain variable. There is a need, therefore, for more effective treatments to bolster the options available for melanoma patients.

Targeted chemo-sonodynamic therapy treatment of breast tumours using ultrasound responsive microbubbles loaded with paclitaxel, doxorubicin and Rose Bengal.

Mastectomy is a common surgical treatment used in the management of breast cancer but has associated physical and psychological consequences for the patient. Breast conservation surgery (BCS) is an alternative to mastectomy but is only possible when the tumour is of an appropriate size. Neo-adjuvant chemotherapy has been successfully used to downstage tumours and increase the number of patients eligible for BCS.

An Overview of Canadian Research Activities on Diseases Caused by Phytophthora ramorum: Results, Progress, and Challenges.

International trade and travel are the driving forces behind the spread of invasive plant pathogens around the world, and human-mediated movement of plants and plant products is now generally accepted as the primary mode of their introduction, resulting in huge disturbance to ecosystems and severe socio-economic impact. These problems are exacerbated under the present conditions of rapid climatic change. We report an overview of the Canadian research activities on Phytophthora ramorum.

Electroneutral polymersomes for combined cancer chemotherapy.

Combination cancer chemotherapy provides an important treatment tool, both as an adjuvant and neoadjuvant treatment, this shift in focus from mono to combination therapies has led to increased interest in drug delivery systems (DDS). DDSs, such as polymersomes, are capable of encapsulating large amounts of multiple drugs with both hydrophilic and hydrophobic properties simultaneously, as well as offering a mechanism to combat multi drug resistant cancers and poor patient tolerance of the cytotoxic compounds utilised. In this article, we report the formulation and evaluation of a novel electroneutral polymersome capable of high encapsulation efficacies for multiple drugs (Doxorubicin, 5-Fluorouracil and leucovorin).

The cup fungus Pestalopezia brunneopruinosa is Pestalotiopsis gibbosa and belongs to Sordariomycetes.

Pestalopezia brunneopruinosa, the type species of Pestalopezia in Leotiomycetes, produces typical cup-shaped ascomata. Because its asexual morph has conidia comprised of five cells including apical and basal appendages and three pigmented median cells, it was first described as Pestalotia gibbosa, which belongs to Sordariomycetes. This contradiction has not been resolved due to the difficulty in isolating this fungus in culture.

Rapid paper based colorimetric detection of glucose using a hollow microneedle device.

The monitoring of blood glucose is a key aspect of diabetes care in limiting the negative effects of hyperglycaemia to both the microvasculature and macrovasculature. Self-monitoring of blood glucose (SMBG) gives an indication of blood glucose at a specific point in time and is recommended to be carried out four times daily. However, due to the inconvenience and associated pain of blood withdrawal, SMBG is often carried out less frequently than recommended or not at all.

Gemcitabine loaded microbubbles for targeted chemo-sonodynamic therapy of pancreatic cancer.

Pancreatic cancer remains one of the most lethal forms of cancer with a 10-year survival of <1%. With little improvement in survival rates observed in the past 40 years, there is a significant need for new treatments or more effective strategies to deliver existing treatments. The antimetabolite gemcitabine (Gem) is the most widely used form of chemotherapy for pancreatic cancer treatment, but is known to produce significant side effects when administered systemically.

A descriptive systematic review of salivary therapeutic drug monitoring in neonates and infants.

Aims: Saliva, as a matrix, offers many benefits over blood in therapeutic drug monitoring (TDM), in particular for infantile TDM. However, the accuracy of salivary TDM in infants remains an area of debate. This review explored the accuracy, applicability and advantages of using saliva TDM in infants and neonates.

Oxygen generating nanoparticles for improved photodynamic therapy of hypoxic tumours.

Photodynamic therapy (PDT) is a clinically approved anti-cancer treatment that involves the activation of an otherwise inactive sensitiser drug with light, which in the presence of molecular oxygen, generates cytotoxic reactive oxygen species (ROS). As oxygen is a key requirement for the generation of ROS in PDT and given the fact that hypoxia is a characteristic of most solid cancerous tumours, treating hypoxic tumours using PDT can be a challenge. In this manuscript, we have prepared a CaO nanoparticle (NP) formulation coated with a pH-sensitive polymer to enable the controlled generation of molecular oxygen as a function of pH.

The integration of triggered drug delivery with real time quantification using FRET; creating a super 'smart' drug delivery system.

The ability to control drug release at a specific physiological target enables the possibility of an enhanced therapeutic effect with reduced off-target toxic side effects. The discipline of controlled drug release has grown to include most areas of medicine with examples in the literature of targeted drug delivery to the majority of organs within the human body. In addition, a variety of external stimuli used to meditate the drug release process have also been investigated.

Magnetically responsive microbubbles as delivery vehicles for targeted sonodynamic and antimetabolite therapy of pancreatic cancer.

Magnetically responsive microbubbles (MagMBs), consisting of an oxygen gas core and a phospholipid coating functionalised with Rose Bengal (RB) and/or 5-fluorouracil (5-FU), were assessed as a delivery vehicle for the targeted treatment of pancreatic cancer using combined antimetabolite and sonodynamic therapy (SDT). MagMBs delivering the combined 5-FU/SDT treatment produced a reduction in cell viability of over 50% when tested against a panel of four pancreatic cancer cell lines in vitro. Intravenous administration of the MagMBs to mice bearing orthotopic human xenograft BxPC-3 tumours yielded a 48.

Iodinated cyanine dyes: a new class of sensitisers for use in NIR activated photodynamic therapy (PDT).

A new class of iodinated cyanine dyes have been prepared for use in NIR excited photodynamic therapy (PDT) and demonstrated improved efficacy in two pancreatic cell lines as well as excellent tumour control in a murine model of the disease.

A versatile, stimulus-responsive nanoparticle-based platform for use in both sonodynamic and photodynamic cancer therapy.

Unlabelled: A PLGA-based multifunctional biodegradable nanoparticle platform co-harboring hematoporphyrin and indocyanine green has been developed. In vitro studies demonstrate ultrasound and light stimulated generation of cytotoxic reactive oxygen species. In vivo studies show that the ICG component facilitates nIR fluorescence imaging that demonstrates accumulation of IV- administered nanoparticles in tumours.

Cholesteryl to improve the cellular uptake of polymersomes within HeLa cells.

The need to develop a greater understanding of drug delivery systems has arisen through the development of alternative biological based therapeutics. Drug delivery systems need to adapt and respond to this increasing demand for cellular transportation of highly charged species. Polymersomal drug delivery systems have displayed great potential and versatility for such a task.

Metastatic Hip Tumor in a Middle-Aged Woman.

A 44-year-old woman was referred to physical therapy by a podiatrist for "iliotibial band syndrome." No imaging had been done, and she denied all constitutional symptoms, but reported having breast cancer 5 years earlier. Following an increase in pain, radiographs and magnetic resonance imaging were performed, and biopsy confirmed a metastatic breast cancer tumor.