Bevacizumab Treatment for Low-Grade Serous Ovarian Cancer: A Systematic Review.

Serous epithelial ovarian cancer, classified as either high-grade (90%) or low-grade (10%), varies in molecular, histological, and clinicopathological presentation. Low-grade serous ovarian cancer (LGSOC) is a rare histologic subtype that lacks disease-specific evidence-based treatment regimens. However, LGSOC is relatively chemo-resistant and has a poor response to traditional treatments. Alternative treatments, including biologic therapies such as bevacizumab, have shown some activity in LGSOC. Thus, the objective of this systematic review is to determine the effect and safety of bevacizumab in the treatment of LGSOC. Following PRISMA guidelines, Medline ALL, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Embase all from the OvidSP platform, ClinicalTrials.gov, International Clinical Trials Registry Platform, International Standard Randomised Controlled Trial Number Registry were searched from inception to February 2022. Articles describing bevacizumab use in patients with LGSOC were included. Article screening, data extraction, and critical appraisal of included studies were completed by two independent reviewers. The effect of bevacizumab on the overall response rate, progression-free survival, overall survival, and adverse effects were summarized. The literature search identified 3064 articles, 6 of which were included in this study. A total of 153 patients were analyzed; the majority had stage IIIC cancer (56.2%). The overall median response rate reported in the studies was 47.5%. Overall, bevacizumab is a promising treatment for LGSOC, with response rates higher than traditional treatment modalities such as conventional chemotherapy, and is often overlooked as a treatment tool. A prospective clinical trial evaluating the use of bevacizumab in LGSOC is necessary to provide greater evidence and support these findings.

Identifying Borderline Ovarian Tumor Recurrence Using Routine Ultrasound Follow-Up.

Borderline ovarian tumors (BOTs) are non-invasive tumors frequently diagnosed in young patients. Surgical removal of the uterus, fallopian tubes, ovaries, and omentum is considered definitive management, however fertility-sparing approach is a recognized option. Surveillance is important due to known recurrence, but there is controversy over the effectiveness of follow-up modalities. The objective is to determine the efficacy of ultrasound screening in identifying tumor recurrence. This retrospective chart review evaluated all patients consulted and/or treated surgically at our institution from January 2015 to June 2020 diagnosed with BOT. Patients were excluded if concurrently diagnosed with another gynecologic malignancy, did not have yearly ultrasound follow-up, or were lost to follow-up. This study included 56 patients, 17 of whom underwent fertility preserving surgery. The overall rate of recurrence was 10.7%; with recurrence rates of 23.5% for the fertility preserving surgery population and 5.1% for the definitive surgery population. Ultrasound first identified 5 of the 6 (83.3%) recurrences. Overall time to recurrence was 51.5 months. In conclusion, recurrences were identified on routine ultrasound screening prior to symptom onset or detection via physical exam in 83.3% of cases. While the best modality of follow-up remains controversial, this review provides evidence supporting the use of routine ultrasound follow-up for early detection of BOT recurrence.

Hormone maintenance therapy for women with low-grade serous ovarian cancer in the front-line setting: A systematic review.

OBJECTIVE: Low-grade serous ovarian cancer (LGSOC) is a rare form of ovarian cancer that accounts for 5-10% of epithelial ovarian cancers. LGSOCs are difficult to treat as they respond poorly to traditional chemotherapy treatments. This systematic review aims to appraise the literature describing the efficacy of hormone maintenance therapy (HMT) in patients with LGSOC given after cytoreductive surgery. METHODS: Medline, EMBASE, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews were searched from inception to November 2020. No language restrictions were applied. Publications describing HMT in the primary setting following cytoreductive surgery with or without chemotherapy in women with LGSOC were included. Publications describing HMT in recurrence, non-LGSOC carcinomas, and in-vitro or animal studies were excluded along with case reports, case series, and conference proceedings. We summarized oncologic outcomes, HMT used, and hormone receptor status where reported. Studies were assessed for risk of bias and quality of evidence. RESULTS: The literature search identified 14,799 records. Four cohort studies met eligibility criteria. A total of 558 patients were included, of which 127 were treated with HMT. There was significant heterogeneity between studies demonstrated by differences in HMT regimens used, dosing, and study population, leading to various outcomes following treatment with HMT. CONCLUSIONS: Treatment of LGSOC remains a challenge. One retrospective study demonstrated improved progression-free survival following HMT for LGSOC, while two others failed to show significant improvements. However, there is limited data available in the literature which restricts the generalizability of these results. Therefore, well-designed, prospective, and randomized trials are needed to confirm the benefit of HMT in patients with this rare subgroup of ovarian cancer.

Nanoengineering the surface of corneal implants: towards functional anti-microbial and biofilm materials.

We report the development and use of a light-mediated in situ grafting technology for the surface modification of biosynthetic corneal implants with peptide-capped nanoparticles (15-65 nm). The resulting materials have antimicrobial properties in bacterial suspension and also reduced the extent of biofilm formation. Our in situ grafting technology offers a rapid route for the introduction of antimicrobial properties to premoulded corneal implants, and potentially other soft implant targets.

Multifunctional Nano and Collagen-Based Therapeutic Materials for Skin Repair.

A novel strategy is needed for treating nonhealing wounds, which is able to simultaneously eradicate pathogenic bacteria and promote tissue regeneration. This would improve patient outcome and reduce the number of lower limb amputations. In this work, we present a multifunctional therapeutic approach able to control bacterial infections, provide a protective barrier to a full-thickness wound, and improve wound healing in a clinically relevant animal model. Our approach uses a nanoengineered antimicrobial nanoparticle for creating a sprayable layer onto the wound bed that prevents bacterial proliferation and also eradicates preformed biofilms. As a protective barrier for the wound, we developed a thermoresponsive collagen-based matrix that has prohealing properties and is able to fill wounds independent of their geometries. Our results indicate that using a combination of the matrix with full-thickness microscopic skin tissue columns synergistically contributed to faster and superior skin regeneration in a nonhealing wound model in diabetic mice.

Light-Activated Peptide-Based Materials for Sutureless Wound Closure.

Using chemically modified extracellular matrix proteins, such as collagen, in combination with light for tissue bonding reduces inflammation and minimizes scarring. However, full length animal or recombinant human collagen proteins are difficult to isolate/produce. Thus, short biomimetic collagen peptides with properties equivalent to collagen at both structural and functional levels may be ideal building blocks for the development of remotely triggered adhesives and fillers. In this work, the conjugation of self-assembling collagen-like peptides to acrylate functionalized polyethylene glycol units yielded adhesive filler materials activated by visible light through the incorporation of a photosensitizer. When tested in a murine skin wound model, the photoactivated adhesives showed reduced scar formation and promoted epithelial regeneration.

Peptide-Based Functional Biomaterials for Soft-Tissue Repair.

Synthetically derived peptide-based biomaterials are in many instances capable of mimicking the structure and function of their full-length endogenous counterparts. Combine this with the fact that short mimetic peptides are easier to produce when compared to full length proteins, show enhanced processability and ease of modification, and have the ability to be prepared under well-defined and controlled conditions; it becomes obvious why there has been a recent push to develop regenerative biomaterials from these molecules. There is increasing evidence that the incorporation of peptides within regenerative scaffolds can result in the generation of structural recognition motifs that can enhance cell attachment or induce cell signaling pathways, improving cell infiltration or promote a variety of other modulatory biochemical responses. By highlighting the current approaches in the design and application of short mimetic peptides, we hope to demonstrate their potential in soft-tissue healing while at the same time drawing attention to the advances made to date and the problems which need to be overcome to advance these materials to the clinic for applications in heart, skin, and cornea repair.

Nanoparticle Concentration vs Surface Area in the Interaction of Thiol-Containing Molecules: Toward a Rational Nanoarchitectural Design of Hybrid Materials.

The effect of accounting for the total surface in the association of thiol-containing molecules to nanosilver was assessed using isothermal titration calorimetry, along with a new open access algorithm that calculates the total surface area for samples of different polydispersity. Further, we used advanced molecular dynamic calculations to explore the underlying mechanisms for the interaction of the studied molecules in the presence of a nanosilver surface in the form of flat surfaces or as three-dimensional pseudospherical nanostructures. Our data indicate that not only is the total surface area available for binding but also the supramolecular arrangements of the molecules in the near proximity of the nanosilver surface strongly affects the affinity of thiol-containing molecules to nanosilver surfaces.

Fingerprinting Biogenic Aldehydes through Pattern Recognition Analyses of Excitation-Emission Matrices.

Biogenic carbonyls, especially aldehydes, have previously demonstrated their potential to serve as early diagnostic biomarkers for disease and injury that have not been fully realized owing, in part, to the lack of a rapid and simple point-of-care method for aldehyde identification. The ability to determine which carbonyl compound is elevated and not just the total aldehydic load may provide more disease- or injury-specific diagnostic information. Toward this end, a novel fluorophore is presented that is able to form a complex with biogenic carbonyls under catalyst-free conditions so as to give a fluorescent fingerprint of the resulting hydrazone. The successful identification of bound carbonyls was accomplished with a newly described algorithm that applied principal curvature analysis of excitation-emission matrices to reduce surface features to ellipse representations, followed by a pattern-matching routine. With this algorithm, carbonyls were identified over a range of concentrations, and mixture components were successfully parsed. Overall, the results presented lay the groundwork for novel implementations of chemometrics to low-cost, rapid, and simple-to-implement point-of-care diagnostics.

Methyl 5-MeO-N-aminoanthranilate, a minimalist fluorogenic probe for sensing cellular aldehydic load.

Methyl 5-MeO-N-aminoanthranilate, a fluorogenic probe comprising a single substituted benzene ring has been applied towards the fluorescence detection of endogenous carbonyls through rapid, catalyst-free complexation of these bio-derived markers of cell stress under physiological conditions. The products formed during the reaction between the probe and aldehydic products of lipid peroxidation, including malondialdehyde and long-chain aliphatic aldehydes relevant to the oxidative decomposition of cell membranes, have been evaluated. Live cell imaging of diethyl maleate-induced oxidative stress with or without pretreatment with α-tocopherol was carried out, with the result suggesting that the presented molecule might serve as a minimalist molecular probe capable of cellular "Aldehydic Load" detection by fluorescence microscopy. This work also outlines functional constraints of the fluorogenic probe (i.e. intramolecular cyclization), providing a realistic evaluation of methyl 5-MeO-N-aminoanthranilate for fluorescence-based aldehyde detection.

Hydrazo-CEST: Hydrazone-Dependent Chemical Exchange Saturation Transfer Magnetic Resonance Imaging Contrast Agents.

The rapid formation of hydrazones under physiological conditions was exploited for the detection of aldehydes through chemical exchange saturation transfer magnetic resonance imaging (CEST-MRI). A metal-free, diamagnetic contrast agent derived from N-amino anthranilic acid was introduced, which selectively "turned-on" upon hydrazone formation through an effect termed Hydrazo-CEST. While the hydrazine form of the probe produced no CEST-MRI signal enhancement, the formation of the aryl hydrazone resulted in >20 % intensity decrease in the bulk water signal through the CEST effect, as measured by 300 MHz 1 H NMR, 3 T and 7 T MRI. Both the electronic contributions of the N-amino anthranilate and the aldehyde binding partner were shown to directly impact the exchange rate of the proton on the ring-proximal nitrogen, and thus the imaging signal. Additionally, the presence of the carboxylic acid moiety ortho to the hydrazine was necessary not only for contrast production, but also for rapid hydrazone formation and prolonged hydrazone product stability under physiological conditions. This work provided the first example of an MRI-based contrast agent capable of a "turn on" response upon reaction with bioactive aldehydes, and outlined both the structural and electronic requirements to expand on Hydrazo-CEST, a novel, hydrazone-dependent subtype of diamagnetic CEST-MRI.

NANoPoLC algorithm for correcting nanoparticle concentration by sample polydispersity.

Variability in the polydispersity of colloidal nanoparticles results in significant differences in the total number of nanoparticles available for the determination of their concentration, which ultimately affects their bioavailability and biodistribution. In the current work, we developed a novel algorithm, named Nanoparticle Polydispersity Corrector (NANoPoLC), which was shown to render a more realistic calculation of the actual nanoparticle concentration in solution.