- Combination Chemotherapy of Multidrug-resistant Early-stage Colon Cancer: Determining Optimal Dose Schedules by High-performance Computer Simulation. [Journal Article]
- The goal of this project was to utilize mechanistic simulation to demonstrate a methodology that could determine drug combination dose schedules and dose intensities that would be most effective in eliminating multidrug resistant cancer cells in early-stage colon cancer. An agent-based model of cell dynamics in human colon crypts was calibrated using measurements of human biopsy specimens. Mutant…
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- Indene-Derived Hydrazides Targeting Acetylcholinesterase Enzyme in Alzheimer's: Design, Synthesis, and Biological Evaluation. [Journal Article]
- As acetylcholinesterase (AChE) plays a crucial role in advancing Alzheimer's disease (AD), its inhibition is a promising approach for treating AD. Sulindac is an NSAID of the aryl alkanoic acid class, consisting of a indene moiety, which showed neuroprotective behavior in recent studies. In this study, newer Indene analogs were synthesized and evaluated for their in vitro AChE inhibition. Additio…
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- Molecular dynamics simulation and docking analysis of NF-κB protein binding with sulindac acid. [Journal Article]
- It is of interest to document the Molecular Dynamics Simulation and docking analysis of NF-κB target with sulindac sodium in combating COVID-19 for further consideration. Sulindac is a nonsteroidal anti-inflammatory drug (NSAID) of the arylalkanoic acid class that is marketed by Merck under the brand name Clinoril. We show the binding features of sulindac sodium with NF-κB that can be useful in d…
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- Influence of chitosan and chitosan oligosaccharide on dual antibiotic-loaded bone cement: In vitro evaluations. [Journal Article]
- The purpose of this study was to investigate the effect of incorporating chitosan (Ch) and chitosan oligosaccharides (ChO) into the commercially premixed antibiotic-loaded bone cement (ALBC). We compare antibiotic release profiles, antibacterial activity, and mechanical properties among different ALBC formulations. The hypothesis was that increasing the amount of Ch and ChO in the cement mixture …
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- Inflammation as a chemoprevention target in asbestos-induced malignant mesothelioma. [Journal Article]
- Malignant mesothelioma (MM) is an incurable cancer of the serosal lining that is often caused by exposure to asbestos. Therefore, novel agents for the prevention and treatment of this disease are urgently needed. Asbestos induces the release of pro-inflammatory cytokines such as IL-1β and IL-6, which play a role in MM development. IL-6 is a component of the JAK-STAT3 pathway that contributes to i…
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- StatPearls: Sulindac [BOOK]StatPearls. StatPearls Publishing: Treasure Island (FL)BOOK
- Sulindac is a medication used in a host of conditions. This activity reviews the indications, contraindications, activity, adverse events, and other key elements of therapy in the clinical setting related to the essential points needed by members of an interprofessional team.
- Phosphodiesterase 10A (PDE10A) as a novel target to suppress β-catenin and RAS signaling in epithelial ovarian cancer. [Journal Article]
- A leading theory for ovarian carcinogenesis proposes that inflammation associated with incessant ovulation is a driver of oncogenesis. Consistent with this theory, nonsteroidal anti-inflammatory drugs (NSAIDs) exert promising chemopreventive activity for ovarian cancer. Unfortunately, toxicity is associated with long-term use of NSAIDs due to their cyclooxygenase (COX) inhibitory activity. Previo…
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- Mechanical strength of antibiotic-loaded PMMA spacers in two-stage revision surgery. [Journal Article]
- CONCLUSIONS: This study suggests that mechanical strength of antibiotic-loaded PMMA bone cement critically decreases even over the short time period of six weeks, which is the recommended interim period in the setting of two-stage revision. This potentially results in an increased risk for PMMA spacer fracture at the end of the interim period and especially in patients with prolonged interim periods. Finally, we conclude that intraoperative addition of 4 g of vancomycin powder per 40 g of gentamicin-premixed Palacos R + G (Group D) is mechanically the preparation of choice if a dual antibiotic-loaded bone cement spacer with high antibiotic concentrations and good stability is warranted. In any case the written and signed informed consent including the off-label use of custom-made antibiotic-loaded PMMA bone cement spacers must be obtained before surgery.
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- Development of Genomic Resources in Mexican Bursera (Section: Bullockia: Burseraceae): Genome Assembly, Annotation, and Marker Discovery for Three Copal Species. [Journal Article]
- Bursera comprises ~100 tropical shrub and tree species, with the center of the species diversification in Mexico. The genomic resources developed for the genus are scarce, and this has limited the study of the gene flow, local adaptation, and hybridization dynamics. In this study, based on ~155 million Illumina paired-end reads per species, we performed a de novo genome assembly and annotation of…
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- Colorectal Carcinoma, Cyclooxygenases, and COX Inhibitors. [Review]
- Colorectal carcinoma (CRC) is the most common of gastrointestinal cancers, the majority presenting with sporadic occurrence compared to the less frequently inherited syndromes. The increasing incidence, decreasing gender and age disparities, and the prevalent risk factors are concerning. The malignancy arising from benign precursor polyps transforms slowly over time. The adenoma variant polyps re…
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- Lifespan benefits for the combination of rapamycin plus acarbose and for captopril in genetically heterogeneous mice. [Journal Article]
- Mice bred in 2017 and entered into the C2017 cohort were tested for possible lifespan benefits of (R/S)-1,3-butanediol (BD), captopril (Capt), leucine (Leu), the Nrf2-activating botanical mixture PB125, sulindac, syringaresinol, or the combination of rapamycin and acarbose started at 9 or 16 months of age (RaAc9, RaAc16). In male mice, the combination of Rapa and Aca started at 9 months and led t…
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- In-line sample concentration in capillary electrophoresis by cyclodextrin to admicelle microextraction. [Journal Article]
- Cyclodextrins (CDs) as a pseudophase in pseudophase-to-pseudophase microextraction (P2ME) in capillary zone electrophoresis (CZE) are proposed. In this P2ME mode called CD to admicelle ME, a long plug of dilute analyte solution prepared in cetyltrimethylammonium bromide (CTAB) at the critical micellar concentration was injected into the capillary. This formed CTAB admicelles at the interface betw…
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- Pseudophase-to-solvent microextraction for in-line sample concentration of anionic analytes in capillary zone electrophoresis. [Journal Article]J Chromatogr A. 2022 Aug 30; 1679:463383.JC
- We present pseudophase-to-solvent microextraction (PSME) as a simple pressure-driven in-line sample concentration technique in capillary zone electrophoresis (CZE) for small organic anions. The developed technique is like solid-phase extraction; however, the chromatographic phase is a pseudophase, i.e., in-situ cetyltrimethylammonium bromide (CTAB) interfacial micelles. A large volume of sample (…
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- The efficacy of chemopreventive agents on the incidence of colorectal adenomas: A systematic review and network meta-analysis. [Review]Prev Med. 2022 09; 162:107169.PM
- Colorectal cancer (CRC) is the fourth most common cancer and third leading cause of cancer-related death worldwide. Use of chemopreventive agents (CPAs) to reduce the incidence of precursor colorectal adenomas could lower the future burden of CRC. Many classes of potential CPAs have been investigated. To identify the most effective CPAs, we conducted a systematic review and a network meta-analysi…
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- Sulindac acetohydrazide derivative attenuates against cisplatin induced organ damage by modulation of antioxidant and inflammatory signaling pathways. [Journal Article]
- This study aimed to explore the mechanisms of action of a sulindac acetohydrazide derivative, N'-(4-dimethylaminobenzylidene)-2-1-(4-(methylsulfinyl) benzylidene)-5-fluoro-2-methyl-1H-inden-3-yl) acetohydrazide, against anticancer drug cisplatin induced organ damage. Using a rodent model, various markers of organ function and signaling pathways were examined and validated by molecular docking stu…
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- Chemo-photodynamic Activity of Silicon Phthalocyanines Bearing Cyclooxygenase Inhibitors on Colorectal Cancer Cell Lines. [Journal Article]ACS Appl Bio Mater. 2022 08 15; 5(8):3936-3950.AA
- Colorectal cancer ranks as the third most lethal cancer worldwide, resulting in over 1 million cases and 900 000 deaths per year. According to population-based studies, administration of long-term non-steroidal anti-inflammatory drugs (NSAIDs) was proven to reduce the risk of a subject developing colorectal cancer. In the present study, the anti-cancer activity of two different NSAIDs, sulindac- …
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- Usefulness of Optimized Human Fecal Material in Simulating the Bacterial Degradation of Sulindac and Sulfinpyrazone in the Lower Intestine. [Journal Article]Mol Pharm. 2022 07 04; 19(7):2542-2548.MP
- The first aim of this study was to evaluate the usefulness of optimized human fecal material in simulating sulforeductase activity in the lower intestine by assessing bacterial degradation of sulindac and sulfinpyrazone, two sulforeductase substrates. The second aim was to evaluate the usefulness of drug degradation half-life generated in simulated colonic bacteria (SCoB) in informing PBPK models…
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- A novel sulindac derivative protects against oxidative damage by a cyclooxygenase-independent mechanism. [Journal Article]
- Oxidative damage is believed to play a major role in the etiology of many age-related diseases and the normal aging process. We previously reported that sulindac, a cyclooxygenase (COX) inhibitor and FDA approved anti-inflammatory drug, has chemoprotective activity in cells and intact organs by initiating a pharmacological preconditioning response, similar to ischemic preconditioning (IPC). The m…
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- Weight Loss and/or Sulindac Mitigate Obesity-associated Transcriptome, Microbiome, and Protumor Effects in a Murine Model of Colon Cancer. [Journal Article]
- Obesity is associated with an increased risk of colon cancer. Our current study examines whether weight loss and/or treatment with the NSAID sulindac suppresses the protumor effects of obesity in a mouse model of colon cancer. Azoxymethane-treated male FVB/N mice were fed a low-fat diet (LFD) or high-fat diet (HFD) for 15 weeks, then HFD mice were randomized to remain on HFD (obese) or switch to …
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- Phase II trial of weekly erlotinib dosing to reduce duodenal polyp burden associated with familial adenomatous polyposis. [Clinical Trial, Phase II]
- CONCLUSIONS: In this single-arm, multi-centre trial of participants with FAP, erlotinib one time per week resulted in markedly lower duodenal polyp burden, and modestly reduced lower GI polyp burden, after 6 months of intervention. While AEs were still reported by nearly three-quarters of all participants, these events were generally lower grade and well-tolerated. These findings support further investigation of erlotinib as an effective, acceptable cancer preventive agent for FAP-associated GI polyposis.
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- Cyclic Metronomic Chemotherapy for Pediatric Tumors: Six Case Reports and a Review of the Literature. [Review]
- We report a retrospective case series of six Hispanic children with tumors treated with metronomic chemotherapy. The six cases comprised one rhabdoid tumor of the kidney, one ependymoma, two medulloblastomas, one neuroblastoma, and a type II neurocytoma of the spine. Treatment included oral cyclophosphamide daily for 21 days alternating with oral etoposide daily for 21 days in a backbone of daily…
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- ¡Pásale!: Gaining Entrance to Conduct Research and Practice With Recent Hispanic Immigrants: Lessons Learned From the COPAL Study. [Journal Article]
- Given the rapidly changing political rhetoric and policies concerning immigration, and the likely impact of this rhetoric on immigrants' adjustment, it is essential to understand the experiences of recently arrived immigrant individuals and families. This article describes methods to recruit and retain recently arrived Hispanic families in longitudinal research and clinical practice. Barriers to …
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- An Evolving Role of Aqueous Piperazine to Improve the Solubility of Non-Steroidal Anti-Inflammatory Drugs. [Journal Article]J Pharm Sci. 2022 10; 111(10):2839-2847.JP
- Piperazine (PIP) is a pharmaceutically acceptable molecule and a good co-conformer in crystallographic engineering. Most of the non-steroidal anti-inflammatory drugs (NSAIDs) have poor aqueous solubility, which hinders their clinical application. The reports show that the solubility of many insoluble drugs can be significantly improved through salt formation with the PIP. In this work, we obtaine…
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- Long-term chemoprevention in patients with adenomatous polyposis coli: an observational study. [Journal Article]
- Prospective short-term studies on effectiveness of non-steroidal anti-inflammatory drugs (NSAIDs) point towards a decrease in the number and size of polyps. Effectiveness and safety in the prevention of progression in familial polyposis with NSAIDs in long-term use, which is the prerequisite for therapeutic evaluation in prospective studies, is unknown. The total absolute observation period of 54…
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- Spontaneous Regression of Metachronous Intra-Abdominal Desmoid Tumor in a Patient with Familial Adenomatous Polyposis. [Case Reports]
- Desmoid tumors are clonal fibroblastic neoplasms that arise in soft tissues. Patients with familial adenomatous polyposis (FAP) can develop intra-abdominal desmoid tumors. However, metachronous appearance of intra-abdominal desmoid tumor is rare, and its clinical course is not well known. Here, we report a case of spontaneous regression of metachronous intra-abdominal desmoid tumor in a 36-year-o…
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- Methionine Sulfoxide Reductase A in Human and Mouse Tissues is Responsible for Sulindac Activation, Making a Larger Contribution than the Gut Microbiota. [Journal Article]Drug Metab Dispos. 2021 05; 50(5):725-733.DM
- Sulindac is a nonsteroidal anti-inflammatory prodrug that is converted to its pharmacologically active metabolite, sulindac sulfide, via a reduction reaction. It is widely accepted that the gut microbiota is responsible for sulindac activation; however, sulindac-induced gastrointestinal injury, which is caused by irritation of the gastrointestinal tract by its active metabolite, is uncommon. Ther…
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- Photoisomerization of Sulindac and Ozagrel Hydrochloride by Vitamin B2 Catalyst Under Visible Light Irradiation. [Journal Article]Pharm Res. 2022 Mar; 39(3):577-586.PR
- CONCLUSIONS: The catalytic activity of vitamin B2 or FAD was demonstrated in the photoisomerization reaction of sulindac and ozagrel hydrochloride. Considering that the rate of photoisomerization in D2O is very slow, the possibility of the occurrence of photoisomerization during clinical use is low. However, this study suggests that the interfusion of vitamin B2 or FAD under excessive light exposure should be avoided as a caution during intravenous administration of sulindac or ozagrel hydrochloride.
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- Sulindac Improves Stiffness and Quality of Life in Women Taking Aromatase Inhibitors for Breast Cancer. [Journal Article]
- CONCLUSIONS: Sulindac may relieve MSS in AI patients, especially physical function and stiffness. Randomized controlled trials should further evaluate NSAIDs on AI-MSS and AI adherence.
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- Kolaviron protects rats from cognitive decline induced by Lipopolysaccharide in Wistar rat. [Journal Article]Niger J Physiol Sci. 2021 Jun 30; 36(1):67-76.NJ
- Kolaviron is a mixture of bi-flavonoids from seed Garcinia kola seed, and has been previously shown to exhibit Nrf2 antioxidant-mediated inhibition of neuroinflammation in LPS-activated BV2 microglia. In this study, we investigated neuroprotective effects of kolaviron in LPS-induced memory impairment in rats. Wistar rats (225-250) g was used for this study. Memory impairment was induced with the …
- Assessment of NSAIDs as potential inhibitors of the fatty acid amide hydrolase I (FAAH-1) using three different primary fatty acid amide substrates in vitro. [Journal Article]
- CONCLUSIONS: Our data therefore suggest potential for study of these compounds as combined FAAH-1-COX inhibitors.
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