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Journal of Pharmaceutical Analysis Jun 2017In this study, the molecular interactions between valrubicin, an anticancer drug, and fish sperm DNA have been studied in phosphate buffer solution (pH 7.4) using UV-Vis...
In this study, the molecular interactions between valrubicin, an anticancer drug, and fish sperm DNA have been studied in phosphate buffer solution (pH 7.4) using UV-Vis spectrophotometry and cyclic voltammetry techniques. Valrubicin intercalated into double stranded DNA under a weak displacement reaction with methylene blue (MB) molecule in a competitive reaction. The binding constant () of valrubicin-DNA was determined as 1.75×10 L/mol by spectrophotometric titration. The value of non-electrostatic binding constant ([Formula: see text]) was almost constant at different ionic strengths while the ratio of [Formula: see text]/ increased from 4.51% to 23.77%. These results indicate that valrubicin binds to ds-DNA via electrostatic and intercalation modes. Thermodynamic parameters including ΔH, ΔS and ΔG for valrubicin-DNA interaction were determined as -25.21×10 kJ/mol, 1.55×10 kJ/mol K and -22.03 kJ/mol, respectively. Cyclic voltammetry study shows a pair of redox peaks for valrubicin at 0.45 V and 0.36 V (vs. Ag/AgCl). The peak currents decreased and peak positions shifted to positive direction in the presence of DNA, showing intercalation mechanism due to the variation in formal potential.
PubMed: 29404035
DOI: 10.1016/j.jpha.2017.01.003 -
Oncology (Williston Park, N.Y.) May 2000Approximately 54,400 new cases of transitional cell carcinoma of the bladder were reported in the United States in 1999, with an estimated 12,500 deaths attributable to... (Review)
Review
Approximately 54,400 new cases of transitional cell carcinoma of the bladder were reported in the United States in 1999, with an estimated 12,500 deaths attributable to this cancer. Close to 75% of all bladder tumors are confined to the urothelium (stage Ta, or carcinoma in situ), and nearly 30% of papillary tumors invade the lamina propria (stage T1). The majority of superficial tumors are low grade with low rates of progression. Transurethral resection is the standard initial treatment for transitional cell carcinoma. Intravesical therapy is an important adjunct to transurethral resection in patients with superficial bladder cancer, many of whom are at risk for disease recurrence and progression. Cytotoxic and immunomodulating agents and, more recently, photosensitizers have demonstrated utility against superficial transitional cell carcinoma. Many studies have assessed and continue to examine the efficacy of various agents at different doses and in different combinations and schedules. Recently, valrubicin (Valstar) won Food and Drug Administration (FDA) approval only for the treatment of refractory carcinoma in situ. However, bacillus Calmette-Guérin (BCG) and mitomycin (Mutamycin) remain the most commonly used, most effective agents available for prophylaxis against recurrence and subsequent progression of superficial bladder cancer. This article reviews traditional and alternative intravesical agents useful in the therapy and prophylaxis of superficial transitional cell carcinoma of the bladder.
Topics: Adjuvants, Immunologic; Administration, Intravesical; Antibiotics, Antineoplastic; Anticarcinogenic Agents; Antineoplastic Agents; Carcinoma, Transitional Cell; Doxorubicin; Epirubicin; Humans; Interferons; Mitomycin; Mycobacterium bovis; Neoplasm, Residual; Photochemotherapy; Photosensitizing Agents; Thiotepa; Urinary Bladder Neoplasms
PubMed: 10853462
DOI: No ID Found -
Biosensors Oct 2023A novel electrochemical DNA sensor was developed for the detection of the anthracycline drug, valrubicin, on the base of poly(Azure C) electropolymerized from the deep...
A novel electrochemical DNA sensor was developed for the detection of the anthracycline drug, valrubicin, on the base of poly(Azure C) electropolymerized from the deep eutectic solvent reline and covered with adsorbed DNA from calf thymus. Biosensor assembling was performed by multiple scanning of the potential in one drop (100 µL) of the dye dissolved in reline and placed on the surface of a screen-printed carbon electrode. Stabilization of the coating was achieved by its polarization in the phosphate buffer. The electrochemical characteristics of the electron transfer were determined and compared with a similar coating obtained from phosphate buffer. The use of deep eutectic solvent made it possible to increase the monomer concentration and avoid using organic solvents on the stage of electrode modification. After the contact of the DNA sensor with valrubicin, two signals related to the intrinsic redox activity of the coating and the drug redox conversion were found on voltammogram. Their synchronous changes with the analyte concentration increased the reliability of the detection. In the square-wave mode, the DNA sensor made it possible to determine from 3 µM to 1 mM (limit of detection, 1 µM) in optimal conditions. The DNA sensor was successfully tested in the voltammetric determination of valrubicin in spiked artificial urine, Ringer-Locke solution mimicking plasma electrolytes and biological samples (urine and saliva) with a recovery of 90-110%. After further testing on clinical samples, it can find application in the pharmacokinetics studies and screening of new drugs' interaction with DNA.
Topics: Deep Eutectic Solvents; Solvents; Reproducibility of Results; Electrodes; DNA; Phosphates; Electrochemical Techniques
PubMed: 37887124
DOI: 10.3390/bios13100931 -
Open Access Journal of Urology May 2010Transitional cell carcinoma (TCC) is the second most common urologic malignancy, and 70% of patients present with superficial or nonmuscle invasive bladder cancer... (Review)
Review
Transitional cell carcinoma (TCC) is the second most common urologic malignancy, and 70% of patients present with superficial or nonmuscle invasive bladder cancer (NMIBC). Intravesical bacillus Calmette-Guerin (BCG) is the most effective agent for preventing disease recurrence, and the only therapy able to inhibit disease progression. However, recurrence rates as high as 30% and significant local and systemic toxicity have led to increased interest in alternative intravesical therapies. In patients refractory or intolerant to BCG, BCG-interferon α2b, gemcitabine, and anthracyclines (doxorubicin, epirubicin, valrubicin) have demonstrated durable clinical responses. Phase I trials investigating alternative cytotoxic agents, such as apaziquone, taxanes (docetaxel, paclitaxel), and suramin are reporting promising data. Novel immunomodulating agents have demonstrated promise as efficacious alternatives in patients refractory to BCG. Optimization of existing chemotherapeutic regimens using hyperthermia, photodynamic therapy, magnetically-targeted carriers, and liposomes remains an area of active investigation. Despite enthusiasm for new intravesical agents, radical cystectomy remains the treatment of choice for patients with NMIBC who have failed intravesical therapy and selected patients with naïve T1 tumors and aggressive features. This report provides a comprehensive review of contemporary intravesical therapy for NMIBC and refractory NMIBC, with an emphasis on emerging agents and novel treatment modalities.
PubMed: 24198616
DOI: No ID Found -
International Journal of Nanomedicine 2012Among numerous drug-delivery approaches, reconstituted high-density lipoprotein (rHDL) nanocarriers have proven particularly applicable for delivering highly hydrophobic...
Among numerous drug-delivery approaches, reconstituted high-density lipoprotein (rHDL) nanocarriers have proven particularly applicable for delivering highly hydrophobic drugs. In this study, we have investigated the enhancement of the therapeutic impact of valrubicin (AD-32), an antineoplastic agent that has been limited to intravesicular application against bladder cancer, despite the encouraging original preclinical data. Earlier studies validated the superior therapeutic efficacy of AD-32 over doxorubicin. In the present study, rHDL/AD-32 nanoparticles were formulated and characterized with regard to encapsulation efficiency, physicochemical properties, selective toxicity, and receptor-mediated uptake. The half maximal inhibitory concentration values (IC(50)) for rHDL/AD-32 nanoparticles were 1.8 and 2.6 times lower than the free AD-32 for prostate (PC-3) and ovarian (SKOV-3) cancer cell lines, respectively, whereas nonmalignant cell lines demonstrated 5 and 1.48 times higher IC(50) doses with rHDL/AD-32 formulations. The data obtained demonstrated effective receptor- mediated uptake of AD-32 from the rHDL nanocarriers by PC-3 and SKOV-3 cancer cells via a targeted drug-delivery process. The rHDL/AD-32 formulation was stable for 6 months when stored at 4°C or at -20°C, as 92% of the AD-32 was retained in the nanoparticles. The findings from this study show that the rHDL/AD-32 formulation can overcome the solubility barriers of AD-32 and thus serve as an effective systemically administered chemotherapeutic agent.
Topics: Cell Line; Cell Line, Tumor; Cell Survival; Doxorubicin; Drug Stability; Humans; Inhibitory Concentration 50; Lipoproteins, HDL; Nanocapsules; Nanoparticles; Particle Size; Solubility; Temperature
PubMed: 22393294
DOI: 10.2147/IJN.S28029 -
Archivos Espanoles de Urologia Sep 2021Most patients at first diagnosis of bladder cancer (BC) present with non muscle invasive disease (NMIBC). BCG intravesical therapy after transurethral resection of the... (Review)
Review
Most patients at first diagnosis of bladder cancer (BC) present with non muscle invasive disease (NMIBC). BCG intravesical therapy after transurethral resection of the bladder tumor is the gold standard in intermediate and high risk NMIBC patients. However, it is estimated that approximately 50% of these patients will present with BCG failure which increases their risk for progression to muscle invasive disease. Currently, the best option for these patients is radical cystectomy. Thus, it is of great interest to pursue new, therapeutic options for BCG failure patients to avoid the necessity of radical cystectomy. We hereby review novel treatment modalities for BCG failure patients. METHODS: This is a narrative review. Keywords for the search were BCG failure, BCG unresponsive, BCG refractory, BCG relapsing and BCG intolerance. Evidence was identified through a search for publications with a ''BCG unresponsive'' tag through 2020. Studies were selected if they contained clinical data on BCG unresponsive therapeutics with near-term availability. Clinical trial landscape evaluation for emerging therapies was performed by searching ClinicalTrials.gov for recruiting/ open interventional trials in 2020. RESULTS: Novel treatment modalities for BCG failure include intravesical chemotherapy, BCG re-challenge or combination of BCG with IFN-α2β, valrubicin, radiotherapy, electromotive drug administration, vicinium, chemohyperthermia, photodynamic therapy, gene therapy, vaccine therapy and immunotherapy. For patients in whom BCG has once failed a repeat course of BCG or BCG plus interferon appears to be a reasonable practice. Likewise, single agent gemcitabine may be considered a treatment modality. However, after 2 or more BCG failures, especially in patients with earlier relapses or cancer persistence, single agent intravesical chemotherapy with valrubicin, gemcitabine or docetaxel appears to be less active than doublet/triplet intravesical chemotherapy or mitomycin chemothermotherapy. Gene therapy or conjugated antibodies may play a role upon further relapse. Single agent pembrolizumab is unlikely to be used as first line, but may be useful, along with multiple new immunotherapeutics, as part of a multimodal approach towards BCG unresponsive disease. CONCLUSIONS: Results from ongoing trials will provide us useful information about many of the existing regimens and probably new drugs will soon be available for this group of patients.
Topics: Adjuvants, Immunologic; Administration, Intravesical; BCG Vaccine; Cystectomy; Humans; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Urinary Bladder Neoplasms
PubMed: 34472437
DOI: No ID Found -
Cell Death & Disease May 2024We created valrubicin-loaded immunoliposomes (Val-ILs) using the antitumor prodrug valrubicin, a hydrophobic analog of daunorubicin. Being lipophilic, valrubicin readily...
We created valrubicin-loaded immunoliposomes (Val-ILs) using the antitumor prodrug valrubicin, a hydrophobic analog of daunorubicin. Being lipophilic, valrubicin readily incorporated Val-lLs that were loaded with specific antibodies. Val-ILs injected intravenously rapidly reached the bone marrow and spleen, indicating their potential to effectively target cancer cells in these areas. Following the transplantation of human pediatric B-cell acute lymphoblastic leukemia (B-ALL), T-cell acute lymphoblastic leukemia (T-ALL), or acute myeloid leukemia (AML) in immunodeficient NSG mice, we generated patient-derived xenograft (PDX) models, which were treated with Val-ILs loaded with antibodies to target CD19, CD7 or CD33. Only a small amount of valrubicin incorporated into Val-ILs was needed to induce leukemia cell death in vivo, suggesting that this approach could be used to efficiently treat acute leukemia cells. We also demonstrated that Val-ILs could reduce the risk of contamination of CD34 hematopoietic stem cells by acute leukemia cells during autologous peripheral blood stem cell transplantation, which is a significant advantage for clinical applications. Using EL4 lymphoma cells on immunocompetent C57BL/6 mice, we also highlighted the potential of Val-ILs to target immunosuppressive cell populations in the spleen, which could be valuable in impairing cancer cell expansion, particularly in lymphoma cases. The most efficient Val-ILs were found to be those loaded with CD11b or CD223 antibodies, which, respectively, target the myeloid-derived suppressor cells (MDSC) or the lymphocyte-activation gene 3 (LAG-3 or CD223) on T4 lymphocytes. This study provides a promising preclinical demonstration of the effectiveness and ease of preparation of Val-ILs as a novel nanoparticle technology. In the context of hematological cancers, Val-ILs have the potential to be used as a precise and effective therapy based on targeted vesicle-mediated cell death.
Topics: Animals; Humans; Liposomes; Mice; Xenograft Model Antitumor Assays; Cell Death; Hematologic Neoplasms; Leukemia, Myeloid, Acute; Cell Line, Tumor; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 38734740
DOI: 10.1038/s41419-024-06715-5 -
Cureus Apr 2023A 75-year-old male was diagnosed with carcinoma in-situ of the bladder. He failed standard therapy and was started on pembrolizumab to prevent the need for cystectomy....
A 75-year-old male was diagnosed with carcinoma in-situ of the bladder. He failed standard therapy and was started on pembrolizumab to prevent the need for cystectomy. His malignancy recurred, and he was treated with intravesical valrubicin and gemcitabine/docetaxel. Three years after starting pembrolizumab, he developed severe neutropenia and thrombocytopenia. He was treated for suspected auto-immune cytopenias but was later found to have acute promyelocytic leukemia on peripheral blood smear and cytometry. He was hospitalized, treated with all-trans retinoic acid and arsenic trioxide, and is currently in molecular remission. This case describes therapy-related acute promyelocytic leukemia (t-APL) diagnosed while on pembrolizumab. Pembrolizumab is an immune checkpoint inhibitor that exhibits anti-tumor effects. Development of hematologic malignancies after immune checkpoint inhibitor therapy is rare. The definitive etiology of our patient's t-APL is uncertain; however, it is more likely that he developed de novo acute promyelocytic leukemia (APL), which was suppressed by pembrolizumab and later revealed when pembrolizumab was discontinued.
PubMed: 37220434
DOI: 10.7759/cureus.37919 -
Biochemical Pharmacology Jan 2021The outbreak of a novel coronavirus (SARS-CoV-2) has caused a major public health concern across the globe. SARS-CoV-2 is the seventh coronavirus that is known to cause... (Review)
Review
The outbreak of a novel coronavirus (SARS-CoV-2) has caused a major public health concern across the globe. SARS-CoV-2 is the seventh coronavirus that is known to cause human disease. As of September 2020, SARS-CoV-2 has been reported in 213 countries and more than 31 million cases have been confirmed, with an estimated mortality rate of ∼3%. Unfortunately, a drug or vaccine is yet to be discovered to treat COVID-19. Thus, repurposing of existing cancer drugs will be a novel approach in treating COVID-19 patients. These drugs target viral replication cycle, viral entry and translocation to the nucleus. Some can enhance innate antiviral immune response as well. Hence this review focuses on comprehensive list of 22 drugs that work against COVID-19 infection. These drugs include fingolimod, colchicine, N4-hydroxycytidine, remdesivir, methylprednisone, oseltamivir, icatibant, perphanizine, viracept, emetine, homoharringtonine, aloxistatin, ribavirin, valrubicin, famotidine, almitrine, amprenavir, hesperidin, biorobin, cromolyn sodium, and antibodies- tocilzumab and sarilumab. Also, we provide a list of 31 drugs that are predicted to function against SARS-CoV-2 infection. In summary, we provide succinct overview of various therapeutic modalities. Among these 53 drugs, based on various clinical trials and literature, remdesivir, nelfinavir, methylpredinosolone, colchicine, famotidine and emetine may be used for COVID-19. SIGNIFICANCE: It is of utmost important priority to develop novel therapies for COVID-19. Since the effect of SARS-CoV-2 is so severe, slowing the spread of diseases will help the health care system, especially the number of visits to Intensive Care Unit (ICU) of any country. Several clinical trials are in works around the globe. Moreover, NCI developed a recent and robust response to COVID-19 pandemic. One of the NCI's goals is to screen cancer related drugs for identification of new therapies for COVID-19. https://www.cancer.gov/news-events/cancer-currents-blog/2020/covid-19-cancer-nci-response?cid=eb_govdel.
Topics: Adenosine Monophosphate; Alanine; Anti-Inflammatory Agents; Antioxidants; Antiviral Agents; Drug Repositioning; Humans; SARS-CoV-2; Treatment Outcome; Virus Internalization; COVID-19 Drug Treatment
PubMed: 33191206
DOI: 10.1016/j.bcp.2020.114296 -
Antioxidants (Basel, Switzerland) Jun 2021More than a year ago, the first case of infection by a new coronavirus was identified, which subsequently produced a pandemic causing human deaths throughout the world....
More than a year ago, the first case of infection by a new coronavirus was identified, which subsequently produced a pandemic causing human deaths throughout the world. Much research has been published on this virus, and discoveries indicate that oxidative stress contributes to the possibility of getting sick from the new SARS-CoV-2. It follows that free radical scavengers may be useful for the treatment of coronavirus 19 disease (COVID-19). This report investigates the antioxidant properties of nine antivirals, two anticancer molecules, one antibiotic, one antioxidant found in orange juice (Hesperidin), one anthelmintic and one antiparasitic (Ivermectin). A molecule that is apt for scavenging free radicals can be either an electron donor or electron acceptor. The results I present here show Valrubicin as the best electron acceptor (an anticancer drug with three F atoms in its structure) and elbasvir as the best electron donor (antiviral for chronic hepatitis C). Most antiviral drugs are good electron donors, meaning that they are molecules capable of reduzing other molecules. Ivermectin and Molnupiravir are two powerful COVID-19 drugs that are not good electron acceptors, and the fact that they are not as effective oxidants as other molecules may be an advantage. Electron acceptor molecules oxidize other molecules and affect the conditions necessary for viral infection, such as the replication and spread of the virus, but they may also oxidize molecules that are essential for life. This means that the used to defend us from COVID-19 may also harm us. This study posits the idea that oxide reduction balance may help explain the toxicity or efficacy of these drugs. These results represent a further advance on the road towards understanding the action mechanisms of drugs used as possible treatments for COVID-19. Looking ahead, clinical studies are needed to define the importance of antioxidants in treating COVID-19.
PubMed: 34207391
DOI: 10.3390/antiox10060979