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Successful delivery of drugs and nanomedicine to tumors requires a functional vascular network, extravasation across the capillary wall, penetration through the extracellular matrix, and cellular uptake. Nanomedicine has many merits, but penetration deep into the tumor interstitium remains a challenge. Failure of cancer treatment can be caused by insufficient delivery of the therapeutic agents. After intravenous administration, nanomedicines are often found in off-target organs and in the tumor extracellular matrix close to the capillary wall. With circulating microbubbles, ultrasound exposure focused toward the tumor shows great promise in improving the delivery of therapeutic agents. In this review, we address the impact of focused ultrasound and microbubbles to overcome barriers for drug delivery such as perfusion, extravasation, and transport through the extracellular matrix. Furthermore, we discuss the induction of an immune response with ultrasound and delivery of immunotherapeutics. The review discusses mainly preclinical results and ends with a summary of ongoing clinical trials.Biomarkers are assayed to assess biological and pathological status. Recent advances in high-throughput proteomic technology provide opportunities for developing next generation biomarkers for clinical practice aided by artificial intelligence (AI) based techniques. We summarize the advances and limitations of cancer biomarkers based on genomic and transcriptomic analysis, as well as classical antibody-based methodologies. selleckchem Then we review recent progresses in mass spectrometry (MS)-based proteomics in terms of sample preparation, peptide fractionation by liquid chromatography (LC) and mass spectrometric data acquisition. We highlight applications of AI techniques in high-throughput clinical studies as compared with clinical decisions based on singular features. This review sets out our approach for discovering clinical biomarkers in studies using proteomic big data technology conjoined with computational and statistical methods.The emergence of SARS-CoV-2, and the ensuing global pandemic, has resulted in an unprecedented response to identify therapies that can limit uncontrolled inflammation observed in patients with moderate to severe COVID-19. The immune pathology behind COVID-19 is complex and involves the activation and interaction of multiple systems including, but not limited to, complement, inflammasomes, endothelial as well as innate and adaptive immune cells to bring about a convoluted profile of inflammation, coagulation and tissue damage. To date, therapeutic approaches have focussed on inhibition of coagulation, untargeted immune suppression and/or cytokine-directed blocking agents. Regardless of recently achieved improvements in individual patient outcomes and survival rates, improved and focussed approaches targeting individual systems involved is needed to further improve prognosis and wellbeing. This review summarizes the current understanding of molecular and cellular systems involved in the pathophysiology of COVID-19, and their contribution to pathogen clearance and damage to then discuss possible therapeutic options involving immunomodulatory drug delivery systems as well as summarising the complex interplay between them.Complex and miniaturized oral drug delivery systems are being developed rapidly for targeted, controlled drug release and improved bioavailability. Standard analytical techniques are widely used to characterize i) drug carrier and active pharmaceutical ingredients before loading into a delivery device (to ensure the solid form), and ii) the entire drug delivery system during the development process. However, in light of the complexity and the size of some of these systems, standard techniques as well as novel sensing technologies and experimental platforms need to be used in tandem. These technologies and platforms are discussed in this review, with a special focus on passive delivery systems in size range from a few 100 µm to a few mm. Challenges associated with characterizing these systems and evaluating their effect on oral drug delivery in the preclinical phase are also discussed.Infections related to antibiotic resistant bacteria are accelerating on a global scale, and hence to encounter this problem in case of urinary tract infections; bacteriophages were isolated for biocontrol of multi-drug resistant (MDR) uropathogenic Escherichia coli (UPECs) isolates. Four lytic phages were purified, characterized, and evaluated for their effectiveness in the form of cocktail and in synergy with antibiotics. Morphological features and other life cycle specifications of phages revealed that two phages Escherichia phage FS11 and Escherichia phage FS17 belonged to Myoviridae and the other two phages Escherichia phage PS8 and Escherichia phage PS6 belonged to Siphoviridae family of order Caudovirales. One step growth curve analysis demonstrated that phage FS11 and phage FS17 had latent time of 24 min and 26 min, and a burst size of ~121 and 98 phage particles/ cell respectively; while for phage PS8 and phage PS6, the latent time was 42 min and 35 min, and the burst size was 87 and 78 particles/ cell, respectively; depicting the lytic nature of phages. The use of all four phages together in the form of a cocktail resulted into a considerable enhancement in the lytic ability; the phage cocktail lysed 86.7% of the clinical isolates, compared to lysis in the range of 50%-66% by individual phages. Studies on in vitro evaluation of phage-antibiotic combinations revealed synergism between antibiotics and the phage cocktail (phage PS6 and phage FS17), wherein the phage cocktail was observed to efficiently inhibit the strains in the presence of sub-lethal doses of antibiotics. The study thus concludes that the use of multiple phages and phage-antibiotic combinations could prove beneficial in the era of rapidly increasing drug-resistant strains.

Locally recurrent rectal cancer (LRRC) is associated with considerable morbidity, poor quality of life and an overall survival of 9months. The non-operative treatment of LRRC is an understudied area, there is no consensus on management in this setting. We aim to perform a retrospective, multicentre analysis of patients treated with SABR reirradiation.

All patients were identified who received SABR re-irradiation for LRRC, at 3 UK centres, between August 2015 and September 2020. Eligible patients had pelvic recurrence and were either not suitable/opted not for surgery, or margin positive after exenturative surgery. Patients were treated with 30Gy in 5 fractions and followed up with clinical review and CT scan at 3, 6, 12, 18 and 24months.

69 patients with 81 lesions were identified and median follow up was 28months. Median progression free survival (PFS) and overall survival (OS) were 12.1months (10.4, 17.7) and 38.7months (28.9,-) respectively. 2-year OS was 0.77 (0.66, 0.89). 58.3% of deaths were as a result of consequences of local relapse.