Synergistic Effects of Temozolomide and Doxorubicin in the Treatment of Glioblastoma Multiforme: Enhancing Efficacy through Combination Therapy.

Glioblastoma multiforme (GBM), a grade IV (WHO classification) malignant brain tumor, poses significant challenges in treatment. The current standard treatment involves surgical tumor removal followed by radiation and chemotherapeutic interventions. However, despite these efforts, the median survival for GBM patients remains low.

Targeted c-Myc Inhibition and Systemic Temozolomide Therapy Extend Survival in Glioblastoma Xenografts.

Glioblastoma is a highly aggressive disease with poor patient outcomes despite current treatment options, which consist of surgery, radiation, and chemotherapy. However, these strategies present challenges such as resistance development, damage to healthy tissue, and complications due to the blood-brain barrier. There is therefore a critical need for new treatment modalities that can selectively target tumor cells, minimize resistance development, and improve patient survival.

Analysing Monday discharges to identify lost opportunities for weekend discharge.

Lower rates of hospital discharge occur on weekends compared with weekdays. The authors performed a retrospective chart review of Monday discharges from the Hospital Medicine service at an academic hospital over a 3-month period to identify reasons for delayed discharge despite medical stability. Of 202 eligible patients, 81 (40%) had documentation indicating stability for earlier discharge.

In Vitro Comparison Between Ovine and Human Recombinant Hyaluronidase on Hyaluronic Acid Fillers.

Injectable hyaluronic acid (HA) fillers are commonly used to provide tissue augmentation and combat the effects of facial aging. Ovine and human recombinant formulations of the enzyme hyaluronidase (HAse) are used interchangeably; however, it is unknown if there exists a difference in their ability to degrade HA. To compare rates at which ovine and human recombinant forms of HAse degrade various HA fillers in vitro.

Elastin-like Polypeptide Hydrogels for Tunable, Sustained Local Chemotherapy in Malignant Glioma.

Glioblastoma (GBM) is a primary brain tumor that carries a dismal prognosis, which is primarily attributed to tumor recurrence after surgery and resistance to chemotherapy. Since the tumor recurrence appears near the site of surgical resection, a concept of immediate and local application of chemotherapeutic after initial tumor removal could lead to improved treatment outcome. With the ultimate goal of developing a locally-applied, injectable drug delivery vehicle for GBM treatment, we created elastin-like polypeptide (ELP) hydrogels.

Targeted Drug Delivery Biopolymers Effectively Inhibit Breast Tumor Growth and Prevent Doxorubicin-Induced Cardiotoxicity.

The anticancer agent doxorubicin(dox) has been widely used in the treatment of a variety of hematological malignancies and solid tumors. Despite doxorubicin's efficiency in killing tumor cells, severe damage to healthy tissues, along with cardiotoxicity, limits its clinical use. To overcome these adverse side effects, improve patient safety, and enhance therapeutic efficacy, we have designed a thermally responsive biopolymer doxorubicin carrier that can be specifically targeted to tumor tissue by locally applying mild hyperthermia (41 °C).

Circumventing Doxorubicin Resistance Using Elastin-like Polypeptide Biopolymer-Mediated Drug Delivery.

Although doxorubicin (dox), an anthracycline antibiotic, is widely used and effective in treating cancer, its treatment efficiency is limited by low blood plasma solubility, poor pharmacokinetics, and adverse side effects, including irreversible cardiotoxicity. Moreover, cancer cells often develop drug resistance over time, which decreases the efficacy of anti-cancer drugs, including dox. In this study, we examine a macromolecular drug delivery system for its ability to specifically deliver doxorubicin to cancer cells with and without drug resistance.

Prenatal diagnosis of major aortopulmonary collateral arteries (MAPCA) in fetuses with pulmonary atresia with ventricular septal defect and agenesis of ductus arteriosus.

Objective: The aim of this study was to describe the prenatal diagnosis of Major Aortopulmonary Collateral Arteries (MAPCAs), and to present a systematic ultrasound method for evaluating lung vascularity in fetuses with pulmonary atresia with ventricular septal defect (PAVSD) and agenesis of ductus arteriosus (DA).

Method: This retrospective study evaluated fetuses diagnosed with PAVSD with agenesis of DA, for the presence of the MAPCAs anomaly. Fetal pulmonary vasculature was investigated by 2D and 4D Spatio Temporal Image Correlation (STIC) technology using High Definition Color Doppler.

Cell-Penetrating Doxorubicin Released from Elastin-Like Polypeptide Kills Doxorubicin-Resistant Cancer Cells in In Vitro Study.

Elastin-like polypeptides (ELPs) undergo a characteristic phase transition in response to ambient temperature. Therefore, it has been be used as a thermosensitive vector for the delivery of chemotherapy agents since it can be used to target hyperthermic tumors. This novel strategy introduces unprecedented options for treating cancer with fewer concerns about side effects.

Thermally Targeted p50 Peptide Inhibits Proliferation and Induces Apoptosis of Breast Cancer Cell Lines.

The application of rationally designed therapeutic peptides (TP) may improve outcomes in cancer treatment. These peptides hold the potential to directly target proliferative pathways and stimulate cell arrest or death pathways. Elastin-like polypeptide (ELP) is an elastin derived biopolymer that undergoes a thermally mediated phase transition.

Severity of illness and the weekend mortality effect: a retrospective cohort study.

Background: Weekend admission to the hospital has been found to be associated with higher in-hospital mortality rates, but the cause for this phenomenon remains controversial. US based studies have been limited in their characterization of the weekend patient population, making it difficult to draw conclusions about the implications of this effect.

Methods: A retrospective cohort study, examining de-identified, patient level data from 2015 to 2017 at US academic medical centers submitting data to the Vizient database, comparing demographic and clinical risk profiles, as well as mortality, cost and length of stay, between weekend and weekday patient populations.

Evaluation of Elastin-Like Polypeptides for Tumor Targeted Delivery of Doxorubicin to Glioblastoma.

To increase treatment efficiency for glioblastoma, we have developed a system to selectively deliver chemotherapeutic doxorubicin (Dox) to Glioblastoma (GBM) tumors. This carrier is based on elastin-like polypeptide (ELP), which is soluble at physiological temperatures but undergoes a phase transition and accumulates at tumor sites with externally applied, mild (40-41 °C) hyperthermia. The CPP-ELP-Dox conjugate consists of a cell penetrating peptide (CPP), which facilitates transcytosis through the blood brain barrier and cell entry, and a 6-maleimidocaproyl hydrazone derivative of doxorubicin at the C-terminus of ELP.

Design, Synthesis, and Preliminary Studies of Spiro-isoxazoline-peroxides against Human Cytomegalovirus and Glioblastoma ∥.

The association between glioblastoma (GBM) and human cytomegalovirus (HCMV) infection has been the intensely debated topic over the decades for developing new therapeutic options. In this regard, the peroxides from natural and synthetic sources served as potential antiviral and anticancer agents in the past. Herein, a concise and efficient strategy has been demonstrated to access a novel class of peroxides containing a spiro-isoxazoline to primarily investigate the biological activities.

Comparative evaluation of risk management frameworks for U.S. source waters.

The U.S. Safe Drinking Water Act required states to develop source water assessment programs identifying existing and potential contamination sources; however, comprehensive risk prioritization and management approaches for surface water supplies have seen limited application.

Adherence to fluid resuscitation guidelines and outcomes in patients with septic shock: Reassessing the "one-size-fits-all" approach.

Objective: The Surviving Sepsis Campaign and Centers for Medicare and Medicaid Services (CMS) Severe Sepsis and Septic Shock Management Bundle (SEP-1) recommend rapid crystalloid infusion (≥30 mL/kg) for patients with sepsis-induced hypoperfusion or septic shock. We aimed to assess compliance with this recommendation, factors associated with non-compliance, and how compliance relates to mortality.

Design: Retrospective, observational study.

Tumor targeting peptides: novel therapeutic strategies in glioblastoma.

Peptides are a promising new therapeutic approach for glioblastoma with potential for more effective targeting and fewer devastating side effects compared to conventional cancer therapies. With the specificity to target receptors which are uniquely or overexpressed on cancer cells as well as accurately targeting dysregulated signaling pathways, peptides demonstrate a high potential for the treatment of even the most aggressive cancers. By binding to these targets, peptides can be used to deliver drugs, serve as antagonists to various ligands, or, given some inherent anticancer activity, provide additional treatment options alone or in combination therapy.

Elastin-Like Polypeptide Delivers a Notch Inhibitory Peptide to Inhibit Tumor Growth in Combination with Paclitaxel.

This research describes a thermally responsive elastin-like polypeptide (ELP) for the delivery of dnMAML peptides that inhibit the Notch pathway. Exploiting passive targeting and a thermally active tumor-targeting technique available through the use of ELP, the dnMAML peptide was efficiently delivered to tumor tissue. Furthermore, this ELP-dnMAML was modified with the addition of a cell penetrating peptide (SynB1) for improved infiltration of ELP-dnMAML into the tumor cells.

Macromolecular Drug Carriers for Targeted Glioblastoma Therapy: Preclinical Studies, Challenges, and Future Perspectives.

Glioblastoma, the most common, aggressive brain tumor, ranks among the least curable cancers-owing to its strong tendency for intracranial dissemination, high proliferation potential, and inherent tumor resistance to radiation and chemotherapy. Current glioblastoma treatment strategies are further hampered by a critical challenge: adverse, non-specific treatment effects in normal tissue combined with the inability of drugs to penetrate the blood brain barrier and reach the tumor microenvironment. Thus, the creation of effective therapies for glioblastoma requires development of targeted drug-delivery systems that increase accumulation of the drug in the tumor tissue while minimizing systemic toxicity in healthy tissues.

Effects of cell penetrating Notch inhibitory peptide conjugated to elastin-like polypeptide on glioblastoma cells.

Notch pathway was found to be activated in most glioblastomas (GBMs), underlining the importance of Notch in formation and recurrence of GBM. In this study, a Notch inhibitory peptide, dominant negative MAML (dnMAML), was conjugated to elastin-like polypeptide (ELP) for tumor targeted delivery. ELP is a thermally responsive polypeptide that can be actively and passively targeted to the tumor site by localized application of hyperthermia.

Polymer-Based Prodrugs: Improving Tumor Targeting and the Solubility of Small Molecule Drugs in Cancer Therapy.

The majority of anticancer drugs have poor aqueous solubility, produce adverse effects in healthy tissue, and thus impose major limitations on both clinical efficacy and therapeutic safety of cancer chemotherapy. To help circumvent problems associated with solubility, most cancer drugs are now formulated with co-solubilizers. However, these agents often also introduce severe side effects, thereby restricting effective treatment and patient quality of life.

Cell-penetrating peptides: strategies for anticancer treatment.

Cell-penetrating peptides (CPP) provide an efficient strategy for the intracellular delivery of bioactive molecules in various biomedical applications. This review focuses on recent advances in the use of CPPs to deliver anticancer therapeutics and imaging reagents to cancer cells, along with CPP contributions to novel tumor-targeting techniques. CPPs are now used extensively to deliver a variety of therapeutics, despite lacking cell specificity and having a short duration of action.

Synthesis and Investigation of Novel Spiro-isoxazolines as Anti-Cancer Agents.

A series of structurally diverse 4-bromo spiro-isoxazolines possessing a variety of aromatic and aliphatic substituents at the 3 position, were synthesized through a 1,3-dipolar cycloaddition followed by intramolecular cyclization of a pendant hydroxyl or carboxylic acid group. The biochemical antiproliferative activity was evaluated by using two breast cancer cell lines (MCF-7 and MDA-MB-231) and two prostate cancer cell lines (PC-3 and DU-145) using the MTT viability assay, and the IC values were obtained. Spiro-isoxazoline derivatives bearing a -chloro or an -dichloro aromatic substituent at the 3-position of the isoxazoline showed considerable antitumor activities in all four cell lines with IC value ranging from 43μM to 56μM.

Elastin-like polypeptide for improved drug delivery for anticancer therapy: preclinical studies and future applications.

Introduction: Despite their poor specificity, small molecule drugs are considered more powerful and effective than other current chemotherapies. A promising method for targeting these anticancer drugs to tumors, elastin-like polypeptides (ELP), has recently emerged. When an anticancer drug that has been conjugated to an ELP is administered, and focal hyperthermia applied, the thermoresponsive properties and enhanced permeability and retention effects of the ELP facilitate drug aggregation within tumor tissues.

Fusion of cell-penetrating peptides to thermally responsive biopolymer improves tumor accumulation of p21 peptide in a mouse model of pancreatic cancer.

Current therapies for the treatment of pancreatic cancer are limited. The limitations of this type of treatment are abundant. The majority of chemotherapeutic agents used in clinics are highly toxic to both tumor cells and normal tissues due to the lack of specificity.