Assessment of thyme honey oral gel for the prevention of adriamycin and cyclophosphamide chemotherapy-induced oral mucositis in patients with breast cancer.

PURPOSE: Oral mucositis (OM) is a common complication of cancer treatment that has an impact on a patient's quality of life and the outcome of cancer therapy. This trial evaluated the effect of thyme honey oral gel for the prevention of chemotherapy-induced OM. METHODS: One hundred ten breast cancer patients who received their first cycle of chemotherapy with adriamycin (60 mg/m2) and cyclophosphamide (600 mg/m2) were randomly recruited into two groups: group A were patients who followed general oral hygiene recommendations and rinsing saline 3 times a day, and group B were patients with similar protocol but supplied with our formulated oral gel to be applied 2 to 4 times a day. Patients were assessed by the World Health Organization (WHO) oral mucositis grading scales and self-assessment daily questionnaire. RESULTS: The use of thyme honey was associated with diminishing incidence of OM grade ≥ 2 (95% CI, 0.12 to 0.90; P = 0.030), duration of OM (- 3.36 days; 95% CI, - 5.50 to - 1.22; P = 0.037) and delayed occurrence of OM grade ≥ 2 (95% CI, 0.10 to 0.80; P = 0.017). CONCLUSION: Thyme honey can be considered as a prophylactic agent for OM and decrease the severity of its symptoms. TRIAL REGISTRATIONS: This protocol was registered at the Iranian Registry of Clinical Trials: registration number IRCT201506063106N25, on June 12, 2015; approved by the institutional review board at the Deputy of Research, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran; and approved by the Ethics Committee of Medical Researches of Pharmaceutical Sciences Branch of Islamic Azad University, Tehran, Iran-reference number 5936, on August 17, 2014.

Evaluation of Adherence to Antiemetic Treatment Guidelines in Patients With Chemotherapy-Induced Nausea and Vomiting in Teaching Hospitals in Tehran.

The present study evaluated adherence to antiemetic guidelines for prevention and treatment of chemotherapy-induced nausea and vomiting (CINV) in four tertiary university teaching hospitals in Tehran. This prospective observational study enrolled 382 adult patients on chemotherapy at oncology centers affiliated to medical universities located in Tehran. Patients were followed up during their chemotherapy cycles. Risk factors related to CINV were evaluated, and information on antiemetic prescribing patterns was gathered using direct interview and patient medical records. Guideline adherence was found to be low; however, 81.3% of the patients experienced chemotherapy without CINV. Low frequency of adherence to the guidelines in prescription patterns does not mean that prescription patterns were very different. Indeed, some drugs were added to base guideline recommendation regiments, since in high and moderate emetogenic chemotherapy categories, some novel antiemetics recommended by international guidelines are not yet included in Iranian pharmacopeia. It was shown that two drug classes were added as a common practice, namely, H1/H2 antagonists and dopamine receptor antagonist (metoclopramide). Statistically significant differences were found between antiemetic prescribing patterns of physicians and chemotherapy regimen category (aspect of emetogenic potential) (p < 0.001). The most commonly prescribed regimen in the minimal-emetic-risk category and the low-emetic-risk category was reported to be the combination of corticosteroids, 5HT3, and H1/H2 antagonists, 33% and 66.1% respectively. Moreover, corticosteroids +5HT3 and H1/H2 antagonists + NK1 antagonist were found to be the most frequently prescribed regimen in the moderate-emetic-risk category (39.7%) and high-emetic-risk category (41.8%). Antiemetic prescribing patterns were not completely compatible with the guidelines in moderate and high emetogenic chemotherapy categories. Differences were detected in two states of over- and undertreatment. The present study confirmed low level of adherence of antiemetic prescribing patterns with international guidelines. However, it could not be proved that high levels of adherence with the guidelines result in reduction of CINV incidence. Complete success in CINV control cannot be achieved only by adherence to the established guidelines as novel antiemetics recommended by the guidelines have not been included in the Iranian pharmacopeia as yet. The authors do recommend implementation of strategies for increasing guideline-compliant prescriptions with the aim of improving patients' outcomes. We also suggest that policymakers in healthcare system point more critically to overprescribing as an issue of concern.

A New Eucalyptol-Rich Lavender (Lavandula stoechas L.) Essential Oil: Emerging Potential for Therapy against Inflammation and Cancer.

BACKGROUND/AIM: natural products are a potential source for drug discovery and development of cancer chemoprevention. Considering that drugs currently available for the treatment of inflammatory and cancer conditions show undesirable side effects, this research was designed to evaluate, for the first time, the in vitro anticancer activity of Algerian Lavandula stoechas essential oil (LSEO) against different cancer cell lines, as well as its in vitro and in vivo topical and acute anti-inflammatory properties. MATERIALS AND METHODS: the LSEO was extracted by steam distillation, and chemical composition analysis was performed using gas chromatography. The main compounds identified in LSEO were oxygenated monoterpenes, such as 1,8-Cineole (61.36%). LSEO exhibited a potent anti-inflammatory activity using the xylene-induced mouse ear edema model. RESULTS: LSEO (200 and 20 mg/kg) was able to significantly reduce (p < 0.05) the carrageenan-induced paw edema with a similar effect to that observed for the positive control. Topical application of LSEO at doses of 82 and 410 mg/kg significantly reduced acute ear edema in 51.4% and 80.1% of the mice, respectively. Histological analysis confirmed that LSEO inhibited the skin inflammatory response. Moreover, LSEO was tested for its antitumor activity against different cancer cell lines. LSEO was found to be significantly active against human gastric adenocarcinoma (AGS), Melanoma MV3, and breast carcinoma MDA-MB-231 cells, with median inhibitory concentration (IC50) values of 0.035 ± 0.018, 0.06 ± 0.022 and 0.259 ± 0.089 µL/mL, respectively. Altogether, these results open a new field of investigation into the characterization of the molecules involved in anti-proliferative processes. CONCLUSION: We suggest that LSEO, with 1,8-Cineole as the major active component, is a promising candidate for use in skin care products with anti-inflammatory and anticancer properties. The results of this study may provide an experimental basis for further systematic research, rational development, and clinical utilization of lavender resources.

An Observational Study of QTc Prolongation in Critically Ill Patients: Identification of Incidence and Predictors.

AIMS: Despite the importance of abnormal QTc interval values in intensive care unit (ICU) patients, there is a paucity of information on this topic. The current study was designed to identify the incidence and predictors of QTc prolongation in medical (M), surgical (S), and emergency (E) ICUs. MATERIALS AND METHODS: A prospective observational study was conducted for 6 months. Patients more than 18 years old who admitted to MICU, SICU, and EICU were included in the study. Electrocardiogram (ECG) was taken on day 1, 3, and 5 of ICU admission. The QTc intervals >460 ms in male and >470 ms in female and increased >60 ms above baseline were considered QTc prolongation. Comparative analysis was done between two groups of patients (normal vs prolonged QTc). Logistic regression models were carried out to determine the predictors of QTc prolongation. RESULTS: Incidence of QTc prolongation was 6.5, 9.8, and 15.7% on day 1, 3, and 5 of ICU admission, respectively. On day 1, the history of alcohol addiction and the reason of ICU admission were associated with a prolonged QTc. A significant association was demonstrated between administration of azithromycin and QTc prolongation on day 3. High serum creatinine and hospitalization in EICU were predictors of QTc prolongation on day 5 of ICU admission. CONCLUSION: The QTc prolongation is relatively common among patients admitted to ICUs and its incidence increases with increasing length of hospital stay. Predictors of QTc prolongation may be affected by the duration of ICU admission. Physicians should consider these predictors particularly before prescribing QTc-prolonging drugs. HOW TO CITE THIS ARTICLE: Farzanegan B, Hosseinpoor Z, Baniasadi S, Seyyedi SR, Rajabi M. An Observational Study of QTc Prolongation in Critically Ill Patients: Identification of Incidence and Predictors. Indian J Crit Care Med 2020;24(4):270-275.

Triazole Modified Tetraiodothyroacetic Acid Conjugated to Polyethylene Glycol: High Affinity Thyrointegrin αvß3 Antagonist with Potent Anticancer Activities in Glioblastoma Multiforme.

Discovery of bioactive molecules that target integrins has implicated their role in tumor angiogenesis, tumor growth, metastasis, and other pathological angiogenesis processes. Integrins are members of a family of cell surface receptors that play a critical role in the angiogenesis process. Tetraiodothyroacetic acid (tetrac), a deaminated derivative of l-thyroxine (T4), is a "thyrointegrin" antagonist that blocks the actions of l-triiodothyronine (T3) and T4 with an interaction site that is located at or near the RGD recognition site identified on integrin αvß3's binding pocket (thyrointegrin αvß3 receptors). We have enhanced the biological activity of a tetrac-based inhibitor via significantly improving its αvß3 receptor binding affinity by introducing a triazole ring on the outer ring of tetrac and covalently conjugating to polymer to increase the product's hydrophilicity via PEGylation. The product, P-bi-TAT, was restricted from nuclear translocation and demonstrated high blood brain barrier permeability and retention in contrast to the non-PEG conjugated derivative. Results of biological activity indicated that this macromolecule new chemical entity P-bi-TAT has greater than 400-fold potent integrin αvß3 affinity versus the parent compound tetrac and has potent anticancer/anti-angiogenesis efficacy against glioblastoma multiforme (GBM). P-bi-TAT administered subcutaneously once daily for 21 days at 1-10 mg/kg mouse body weight resulted in a dose-dependent suppression of GBM tumor growth and viability as monitored with IVIS imaging (P < 0.001). GBM tumors had >95% volume loss and maximal loss of GBM cell viability during the 21 days ON-treatment experiment as well as in the 21 days ON followed by 21 days OFF-treatment experiment (P < 0.001). In conclusion, P-bi-TAT is a promising lead clinical candidate effective in the treatment of human GBM.

Synthesis of new analogs of tetraiodothyroacetic acid (tetrac) as novel angiogenesis inhibitors for treatment of cancer.

In the angiogenesis process, integrins, which are members of a family of cell surface transmembrane receptors, play a critical role particularly in blood vessel formation and the local release of vascular growth factors. Thyroid hormones such as l-thyroxine (T4) and 3,5,3'-triiodo-l-thyronine (T3) promote angiogenesis and tumor cell proliferation via integrin αvß3 receptor. At or near an arginine-glycine-aspartate (RGD) recognition site on the binding pocket of integrin αvß3, tetraiodothyroacetic acid (tetrac, a deaminated derivative of T4) is a thyrointegrin receptor antagonist and blocks the actions of T3 and T4 as well as different growth factors-mediated angiogenesis. In this study, we synthesized novel tetrac analogs by modifying the phenolic moiety of tetrac and tested them for their anti-angiogenesis activity using a Matrigel plug model for angiogenesis in mice. Pharmacological activity results showed that tetrac can accommodate numerous modifications and maintain its anti-angiogenesis activity.

Synthesis of MR-49, a deiodinated analog of tetraiodothyroacetic acid (tetrac), as a novel pro-angiogenesis modulator.

The tyrosine-based hormones 3,3',5-triiodo-l-thyronine (l-T3) and l-thyroxine (l-T4) that are produced by the thyroid gland control metabolic functions. Iodothyronine deiodinase enzymes convert l-T4 to l-T3, the form of thyroid hormone critical to genomic actions within cells and regulation of metabolism, and to reverse-l-T3, a hormone isoform that is largely inactive. We used tertiary amines in a study of deiodination based on derivatives of tetraiodothyroacetic acid (tetrac)-a naturally occurring derivative of l-T4-to mimic the action of the iodothyronine deiodinases and deiodination of the outer ring iodines. Deiodinated tetrac, MR-49, was found to be pro-angiogenic, with this activity exceeding that of l-T3 and l-T4 in a hemoglobin Matrigel® plug assay of angiogenesis. Tetrac is anti-angiogenic via several nongenomic pathways, and the present studies of MR-49 reveal the critical contribution of outer ring iodines to the angiogenic properties of thyroid hormone analogues, which may have utility as pro-angiogenic pharmaceuticals.

RETRACTED: Godugu et al. Anti-Cancer Activities of Thyrointegrin αvß3 Antagonist Mono- and Bis-Triazole Tetraiodothyroacetic Acid Conjugated via Polyethylene Glycols in Glioblastoma. Cancers 2021, 13, 2780.

The journal retracts the article, "Anti-Cancer Activities of Thyrointegrin αvß3 Antagonist Mono- and Bis-Triazole Tetraiodothyroacetic Acid Conjugated via Polyethylene Glycols in Glioblastoma" [...].

Comparison of Perioperative Pregabalin and Duloxetine for Pain Management After Total Knee Arthroplasty: A Double-Blind Clinical Trial.

Background: Chronic residual pain after total knee arthroplasty (TKA) is one of the challenges of postoperative pain management. Duloxetine, by controlling neuropathic pain, and pregabalin, by affecting nociceptors, can effectively manage postoperative pain. Objectives: This study aimed to compare the effect of perioperative oral duloxetine and pregabalin in pain management after knee arthroplasty. Methods: In this clinical trial, 60 patients scheduled for TKA under spinal anesthesia were randomly assigned to one of three groups A (pregabalin 75 mg), B (duloxetine 30 mg), and C (placebo). Drugs were administered 90 minutes before, 12, and 24 hours after surgery. The visual analog scale (VAS) score for pain, the first analgesic request time, postoperative analgesic consumption (i.v. paracetamol), and WOMAC score six months after surgery were recorded. Results: The VAS score and analgesic consumption 48 hours after TKA in groups A and B significantly decreased compared to the placebo (P < 0.05). The first analgesic request time was longer in groups A and B than in group C (P < 0.05). While the differences were statistically significant, they are most likely not clinically significant. The WOMAC score before and six months after arthroplasty did not differ between the groups (P > 0.05). Conclusions: Perioperative oral pregabalin and duloxetine similarly reduce pain and the need for analgesic consumption within 48 hours after TKA but do not affect knee mobility status.

Correction: Godugu et al. Anti-Cancer Activities of Thyrointegrin αvß3 Antagonist Mono- and Bis-Triazole Tetraiodothyroacetic Acid Conjugated via Polyethylene Glycols in Glioblastoma. Cancers 2021, 13, 2780.

In the original publication [...].

Therapeutic effects of turmeric topical cream in vitiligo: A randomized, double-blind, placebo-controlled pilot study.

BACKGROUND: Vitiligo is an autoimmune and acquired disease characterized by the destruction of epidermal melanocytes leading to depigmentation of the skin. Although vitiligo is a common disease, there is not a definite cure and conventional therapies can lead to serious adverse effects. Turmeric has been widely studied for its anti-inflammatory, antioxidant, and anti-cell proliferation, while it is a cost-benefit and available treatment for a variety of diseases. AIMS: The aim of this study was to evaluate the efficacy of topical turmeric cream on vitiligo's lesion appearance including size and repigmentation. PATIENTS/METHODS: Following the screening, 30 patients were enrolled according to inclusion criteria. The patients received training to apply turmeric and placebo cream at the specified side of their body twice a day for 4 months. Patients were evaluated at the baseline and at monthly intervals to access possible side effects. Lesion size, vitiligo area scoring index (VASI), vitiligo noticeability scale (VNS), and physician global assessment (PGA) were evaluated at the baseline and after four months to compare the changes induced by turmeric and placebo cream. RESULTS: Twenty-four patients completed the trial. Applying turmeric cream reduced the size of lesions and improved lesion's appearance significantly compared to the placebo group (p < 0.001), and also, patient's satisfaction score was higher following applying turmeric cream compared to placebo (p < 0.05). CONCLUSIONS: Turmeric cream can be used as an alternative remedy or adjuvant therapy in mild to moderate vitiligo lesions and in those who cannot tolerate the adverse effects of conventional therapies.

Impact of rapid correction of vitamin D deficiency in asthmatic patients.

BACKGROUND: Asthma is one of the most common chronic diseases, which is a growing public health concern worldwide. In recent years, there has been an increasing number of interests in the relationship between vitamin D level and asthma control. Hence, the objective of this study was to assess the effect of high doses of vitamin D3 injection on asthmatic patient's respiratory condition and quality of life. METHODS: This was a single arm, before and after interventional study involving 18 patients with moderate to severe asthma. Spirometry test, St George's respiratory questionnaire (SGRQ) and serum vitamin D assay were performed. Subjects with 25-hydroxyvitamin D3 (25-(OH) D3) < 20 ng/ml were deemed deficient (n = 18) and received 2 intramuscular injections of vitamin D3 300,000 IU at monthly intervals consecutively. RESULTS: The mean changes of forced expiratory volume in the first second (FEV1) were significantly different in subjects who received vitamin D3 injections (p = 0.008). Also, the mean changes in FEV1/forced vital capacity ratio (FEV1/FVC) were significant (p < 0.001) as well as maximum expiratory flow between 25% and 75% of FVC (MEF25-75) (p = 0.001). Interestingly, improvement in clinical parameters of SGRQ was also observed with significant differences in total score (p = 0.001). Naturally, serum vitamin D levels were increased in our patients following the injections (p < 0.001). CONCLUSIONS: Our findings suggest that screening for serum 25-(OH) D3 deficiency is important in asthmatic patients and correction of this deficiency with high doses of vitamin D3 injection may lead to improvement in pulmonary function, symptoms and quality of life (QOL).

Solvent-free microwave extraction: an eco-friendly and rapid process for green isolation of essential oil from lemongrass.

The extraction of lemongrass essential oil (LGEO) using large quantities of solvents makes this extraction a hazardous and environmentally unfriendly procedure. Our aim was to find a suitable method for the improvement of its extraction and its quality. Solvent-Free Microwave Extraction (SFME) is a combination of dry distillation and microwave heating. SFME of LGEO was compared with conventional extraction hydrodistillation (HD). SFME is quicker than conventional HD. An extraction time of 15 min with SFME provided a yield of 0.6% comparable with that obtained after 120 min using HD. The composition of these oils revealed that the main components obtained with HD and SFME were both geranial (59.93% vs 44.59%, respectively). The quality of lemongrass is determined by its citral content, and a higher amount of citral was present in SFME oil (74%) in comparison with HD oil (60%). SFME is a green and a promising technology for the extraction of essential oils.

Current Strategies in Pain Regimens for Robotic Urologic Surgery: A Comprehensive Review.

Context: Robotic surgery is becoming the most common approach in minimally invasive urologic procedures. Robotic surgery offers less pain to patients because of smaller keyhole incisions and less tissue retraction and stretching of fascia and muscular fibers. Tailored pain regimens have also evolved and allowed patients to feel minimal to no discomfort after robotic urologic surgery, allowing in parallel better surgical outcomes. This study aims to analyze the most current pain regimens in robotic urologic surgery and to evaluate the most current pain protocols and corresponding outcomes. Evidence Acquisition: A literature review was performed of published manuscripts utilizing Pubmed and Google Scholar on pain protocols for patients undergoing robotic urologic surgery. Results: Multimodal analgesia is gaining ground in robotic urologic surgery. Regional analgesia includes four major modalities: Neuroaxial analgesia, intercostal blocks, tranvsersus abdominis plane blocks, and paravertebral blocks. Each approach has a different injection site, region of analgesia coverage, and duration of coverage depending upon local anesthesia and/or adjuvant utilized with advantages and disadvantages that make each modality unique and efficacious. Conclusions: Robotic urologic surgery has offered the advantage of smaller incisions, faster recovery, less postoperative opioid consumption, and better surgical outcomes. Neuraxial, intercostal, transversus abdominis plane, and quadratus lumborum blocks are the best and most adopted approaches which offer optimal outcomes to patients.

Effects of Anticancer Agent P-bi-TAT on Gene Expression Link the Integrin Thyroid Hormone Receptor to Expression of Stemness and Energy Metabolism Genes in Cancer Cells.

Chemically modified forms of tetraiodothyroacetic acid (tetrac), an L-thyroxine derivative, have been shown to exert their anticancer activity at plasma membrane integrin αvß3 of tumor cells. Via a specific hormone receptor on the integrin, tetrac-based therapeutic agents modulate expression of genes relevant to cancer cell proliferation, survival and energy metabolism. P-bi-TAT, a novel bivalent tetrac-containing synthetic compound has anticancer activity in vitro and in vivo against glioblastoma multiforme (GBM) and other types of human cancers. In the current study, microarray analysis was carried out on a primary culture of human GBM cells exposed to P-bi-TAT (10-6 tetrac equivalent) for 24 h. P-bi-TAT significantly affected expression of a large panel of genes implicated in cancer cell stemness, growth, survival and angiogenesis. Recent interest elsewhere in ATP synthase as a target in GBM cells caused us to focus attention on expression of genes involved in energy metabolism. Significantly downregulated transcripts included multiple energy-metabolism-related genes: electron transport chain genes ATP5A1 (ATP synthase 1), ATP51, ATP5G2, COX6B1 (cytochrome c oxidase subunit 6B1), NDUFA8 (NADH dehydrogenase (ubiquinone) FA8), NDUFV2I and other NDUF genes. The NDUF and ATP genes are also relevant to control of oxidative phosphorylation and transcription. Qualitatively similar actions of P-bi-TAT on expression of subsets of energy-metabolism-linked genes were also detected in established human GBM and pancreatic cancer cell lines. In conclusion, acting at αvß3 integrin, P-bi-TAT caused downregulation in human cancer cells of expression of a large number of genes involved in electron transport and oxidative phosphorylation. These observations suggest that cell surface thyroid hormone receptors on αvß3 regulate expression of genes relevant to tumor cell stemness and energy metabolism.

New synthesis of 6[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid and evaluation of the influence of adamantyl group on the DNA binding of a naphthoic retinoid.

6[3-(1-Adamantyl)-4-methoxyphenyl]-2-naphthoic acid (Adapalene®), a synthetic aromatic retinoid specific for RARß and RARγ receptors, has been prepared utilizing a Pd/C-mediated Suzuki coupling between 6-bromo-2-naphthoic acid and 4-methoxyphenyl boronic acid, followed by introduction of an adamantyl group in the position 3 of the formed 6-(4-methoxyphenyl)-2-naphthoic acid. The interaction of 6-(4-methoxyphenyl)-2-naphthoic acid/ethyl ester and the 3-adamantyl analogs with DNA was studied in aqueous solution at physiological conditions by UV-vis spectroscopy. The calculated binding constants K(ligand-DNA) ranged between 1.1×10(4) M(-1) and 1.1×10(5) M(-1), the higher values corresponding to those of the adamantylated compounds. Molecular modeling studies have emphasized that the intercalative binding of adapalene and its derivatives to DNA is mainly stabilized by hydrophobic interactions related to the presence of the adamantyl group.

A mild and efficient method for the synthesis of a new class of furo[3,2-c]chromenes in aqueous media.

An efficient synthesis of 2-hydroxy-3-[2-oxo-2-phenylethylidene]-2-phenyl-2, 3-dihydro-4 H-furo[3, 2-c]chromene-4(2H)-one is described. This involves the reaction between dibenzoylacetylene and 4-hydroxycoumarine in the presence of NaH (10 mol %) in nearly quantitative yield. Treatment of this heterocyclic system with trimethyl chlorosilane in CHCl(3) leads quantitatively to 4-oxo-3-[2-oxo-2-phenylethylidene]-2-phenyl-3H, 4H-furo[3,2-c]chromene-1-ium chloride. Direct addition of nucleophiles, such as alcohols, amines or trialkyl phosphites to this salt in water as the solvent produces functionalized 2-phenyl-4H-furo[3,2-c] chromen derivatives in excellent yields.

Anti-Cancer Activities of Thyrointegrin αvß3 Antagonist Mono- and Bis-Triazole Tetraiodothyroacetic Acid Conjugated via Polyethylene Glycols in Glioblastoma.

Integrin αvß3 receptors are overexpressed in different tumors and their associated neovascularization and hence, represent a potential cancer target. We previously synthesized a high affinity thyrointegrin αvß3, P4000-bi-TAT (tetrac derivative), with potent anticancer properties. However, the long polydisperse PEG conjugate showed large scaleup and analytical/bioanalytical issues. Hence, in the present study, we synthesized a mono versus bi-triazole tetrac with discrete monodisperse PEG, which provided improvement in scaleup and bioanalysis. In the present study, we compared binding affinity and anticancer activates with a smaller PEG size (P1600-bi-TAT, Compound 2) and the removal of one TAT molecule (P1600-m-TAT, Compound 3) versus P4000-bi-TAT, Compound 1. The results of the selectivity and affinity of TATs showed greater affinity to integrin αvß3. The xenograft weights and tumor cell viabilities were decreased by >90% at all doses compared to the control (ON Treatment, *** p < 0.001) in cells treated with Compounds 1, 2, and 3 in U87-Luc-treated mice. The in vivo luminescent signals of U87-luc cells reflect the proliferation and distribution of tumor cells in the animals and the maximum intensity corresponding to the maximum tumor cells that the animals could tolerate. We found that the three thyrointegrin αvß3 antagonists exhibited optimal therapeutic efficacy against U87 or primary glioblastoma cells. Biological studies showed that decreasing the PEG linker size (1600 vs. 4000) or having mono-TAT or bi-TAT had no significant impact on their αvß3 binding affinity, anti-angiogenesis, or overall anti-cancer efficacy.