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How to Use a Prioritised Approach for Treating Hematological Disorders During the COVID-19 Pandemic in India?

The current pandemic coronavirus, SARS-CoV-2, is known to cause severe infection (COVID-19) in patients with comorbidities, particularly cancer or an immunosuppressed state. Most healthcare systems in the country are likely to be overwhelmed soon if the pandemic moves to a stage of community transmission. Currently, limited evidence is available for managing patients with hematological disorders during the COVID-19 pandemic. The current review summarises the possible challenges clinicians are likely to face, key considerations to guide decision making, and possible solutions to the anticipated

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… In patients with acute promyelocytic leukemia we recommend using arsenic trioxide and all trans retinoic acid (ATO/ATRA) combination even in high risk patients considering our institutional experience of high long term term remission rates with this regimen [ 36 ].Table 4 summaries our recommendations …

Potential Therapeutic Targets of Resveratrol, a Plant Polyphenol, and Its Role in the Therapy of Various Types of Cancer.

Cancer is among the most prominent causes of mortality worldwide. Different cancer therapy modes employed, including chemotherapy and radiotherapy, have been reported to be significant in cancer management, but the side effects associated with these treatment strategies are still a health problem. Therefore, alternative anticancer drugs based on medicinal plants or their active compounds have been generating attention because of their less serious side effects. Medicinal plants are an excellent source of phytochemicals that have been recognized to have health-prompting effects through modulati

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… Furthermore, an isobolographic study revealed a synergistic effect between arsenic trioxide and resveratrol. In the combined therapy group, there was more apoptosis and ROS production and identical synergistic effects were found in mice in vivo [ 198 ]. …

At-Home Care Program for Acute Myeloid Leukemia Induction Phase in Patients Treated with Venetoclax-Based Low-Intensity Regimens.

Background: Even though venetoclax in combination with azacitidine (VenAza) is considered a low-intensity regimen, its patients present a high incidence of cytopenia and infections during the first courses, making the initial management a challenging phase. Methods: This difficulty in our center led to the establishment of an At-Home (AH) program for ramp-up and follow-up patients during the VenAza combination induction phase focused on therapy administration, patient and caregiver education, and management of adverse events (AEs). A total of 70 patients with newly diagnosed acute myeloid leuk

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… At-home management has subsequently been extended to other procedures such as the aplastic phase after consolidation therapy in AML, consolidation therapy with arsenic trioxide (ATO) for acute promyelocytic leukemia, a pilot program in selected patients for allogeneic hematopoietic stem cell transplant …

Pricing and Reimbursement Pathways of New Orphan Drugs in South Korea: A Longitudinal Comparison.

This study aimed to analyze four current pathways affecting the listing and post-listing prices of new orphan drugs (ODs) in South Korea. These mechanisms were: (1) essential OD, (2) pharmacoeconomic evaluation (PE) waiver OD, (3) weighted average price OD, and (4) PE OD. We analyzed the ratio of the listing price of 48 new ODs to the average adjusted price (AAP) of seven advanced countries and examined the change in the post-listing price. Descriptive statistics were used to analyze the listing and post-listing price changes. The mean and median ratios of the listing price of total new OD to

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… AAP Ratio (%) (Generic Name) | List Price (USD) 1 | Torisel | Renal cell carcinoma | 01/06/2011 | NA | 793,000 | 30 mg | 60.9 (temsirolimus) | 720.9 2 | Trisenox | Acute promyelocytic leukemia | 01/06/2011 | NA | 373,000 | 10 mg/mL | 64.3 (arsenic trioxide) | 339.1 3 | Xtandi | Castration-resistant prostate …

Isotype-specific inhibition of the phosphatidylinositol-3-kinase pathway in hematologic malignancies.

In the last decade, the advent of biological targeted therapies has revolutionized the management of several types of cancer, especially in the realm of hematologic malignancies. One of these pathways, and the center of this review, is the phosphatidylinositol-3-kinase (PI3K) pathway. The PI3K pathway seems to play an important role in the pathogenesis and survival advantage in hematologic malignancies, such as leukemia, lymphoma, and myeloma. The objectives of the present review, hence, are to describe the current knowledge on the PI3K pathway and its isoforms, and to summarize preclinical an

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… IC87114 has also been shown to reverse acute promyelocytic leukemia cells protective mechanisms against doxorubicin or arsenic trioxide, which correlates with downregulation of MCL-1. …

Bone targeted nano-drug and nano-delivery.

There are currently no targeted delivery systems to satisfactorily treat bone-related disorders. Many clinical drugs consisting of small organic molecules have a short circulation half-life and do not effectively reach the diseased tissue site. This coupled with repeatedly high dose usage that leads to severe side effects. With the advance in nanotechnology, drugs contained within a nano-delivery device or drugs aggregated into nanoparticles (nano-drugs) have shown promises in targeted drug delivery. The ability to design nanoparticles to target bone has attracted many researchers to develop n

Essential Medicinal Chemistry of Essential Medicines.

Since 1977, the World Health Organization publishes a list of essential medicines, i.e., those that satisfy the priority health care needs of the population and are selected with regard to disease prevalence and public health relevance, evidence of clinical efficacy, and safety, as well as comparative costs and cost-effectiveness. The Essential Medicines List (EML) is an invaluable tool for all countries to select those medicines that have an excellent risk/benefit ratio and that are reputed to be of pivotal importance to health. In the present perspective, we describe the chemical composition

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… Table 1 Inorganic EMs inorganic active principle | WHO EML section/s arsenic trioxide | cytotoxic medicines cisplatin calcium salts | vitamins and minerals iodine sodium fluoride ferrous salt | antianemia medicines lithium carbonate | medicines used in bipolar disorders nitrous oxide | general anesthetics …

Immunotherapy in Acute Myeloid Leukemia: A Literature Review of Emerging Strategies.

In the last twenty years, we have witnessed a paradigm shift in the treatment and prognosis of acute myeloid leukemia (AML), thanks to the introduction of new efficient drugs or approaches to refine old therapies, such as Gemtuzumab Ozogamicin, CPX 3-5-1, hypomethylating agents, and Venetoclax, the optimization of conditioning regimens in allogeneic hematopoietic stem cell transplantation and the improvement of supportive care. However, the long-term survival of non-M3 and non-core binding factor-AML is still dismal. For this reason, the expectations for the recently developed immunotherapies,

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… For instance, the most illustrative case is the drug-free combination of all-trans retinoic acid/arsenic trioxide for acute promyelocytic leukemia (APL), capable of curing the disease in the vast majority of patients [ 3 , 4 ]. … Retinoic acid and arsenic trioxide for acute promyelocytic leukemia N. Engl. J. Med. 2013 369 111 121 10.1056/NEJMoa1300874 23841729 4. Guarnera L. Ottone T. Fabiani E. Divona M. Savi A. Travaglini S. Falconi G. Panetta P. Rapanotti M.C. Voso M.T. …

Application of cell-derived exosomes in the hematological malignancies therapy.

Exosomes are small membrane vesicles of endocytic origin that are produced by both tumor and normal cells and can be found in physiological fluids like plasma and cell culture supernatants. They include cytokines, growth factors, proteins, lipids, RNAs, and metabolites and are important intercellular communication controllers in several disorders. According to a vast amount of research, exosomes could support or inhibit tumor start and diffusion in a variety of solid and hematological malignancies by paracrine signaling. Exosomes are crucial therapeutic agents for a variety of illnesses, such

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… Hematological malignancies | Exosomes | Cancer cell line or target | Finding | References Acute myeloid leukemia (AML) | hMS-bone marrow (BM)Arsenic trioxide and derived exosomes | NB4 cell line | more significant amounts of apoptosis markers | Abbaszade Dibavar et al. (2018) BM-MSC-exo treatment | NB4 … The effect of simultaneous administration of arsenic trioxide and microvesicles derived from human bone marrow mesenchymal stem cells on cell proliferation and apoptosis of acute myeloid leukemia cell line. Artif. …

Targeting the two-pore channel 2 in cancer progression and metastasis.

The importance of Ca2+ signaling, and particularly Ca2+ channels, in key events of cancer cell function such as proliferation, metastasis, autophagy and angiogenesis, has recently begun to be appreciated. Of particular note are two-pore channels (TPCs), a group of recently identified Ca2+-channels, located within the endolysosomal system. TPC2 has recently emerged as an intracellular ion channel of significant pathophysiological relevance, specifically in cancer, and interest in its role as an anti-cancer drug target has begun to be explored. Herein, an overview of the cancer-related functions

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… Further, tetrandrine can also synergistically enhance the effects of numerous chemotherapeutics, including 5-flourouracil, imatinib, paclitaxel, vincristine, daunorubicin, cisplatin, sorafenib, arsenic trioxide, chloroquine, and the protein kinase inhibitor H89 both in vitro and in vivo [ 169 , 175 , … Tetrandrine enhances the anticancer effects of arsenic trioxide in vitro . Int J Clin Pharmacol Ther. 2014 ; 52 : 416 – 24 . 10.5414/CP201939 24548979 197. …

New Therapeutic Strategies for Adult Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) is a genetically heterogeneous hematological malignancy. Chromosomal and genetic analyses are important for the diagnosis and prognosis of AML. Some patients experience relapse or have refractory disease, despite conventional cytotoxic chemotherapies and allogeneic transplantation, and a variety of new agents and treatment strategies have emerged. After over 20 years during which no new drugs became available for the treatment of AML, the CD33-targeting antibody-drug conjugate gemtuzumab ozogamicin was developed. This is currently used in combination with standard

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… After stratification, the results were incorporated into clinical trials, including all-trans retinoic acid (ATRA) plus arsenic trioxide for acute promyelocytic leukemia (APL0406, [ 13 ]), and FLT3 -ITD-positive AML treated with midostaurin plus chemotherapy and allogeneic transplantation (AMLSG16-10 … Improved Outcomes With Retinoic Acid and Arsenic Trioxide Compared With Retinoic Acid and Chemotherapy in Non-High-Risk Acute Promyelocytic Leukemia: Final Results of the Randomized Italian-German APL0406 Trial J. Clin. Oncol. 2017 35 605 612 10.1200/JCO.2016.67.1982 27400939 14. Schlenk R.F. …

High-Dose Intravenous Vitamin C Combined with Docetaxel in Men with Metastatic Castration-Resistant Prostate Cancer: A Randomized Placebo-Controlled Phase II Trial.

UNLABELLED: High-dose intravenous vitamin C (HDIVC) administered to produce pharmacologic concentrations shows promise in preclinical models and small clinical trials, but larger prospective randomized trials are lacking. We evaluated the clinical benefit of combining HDIVC with docetaxel in patients with progressive metastatic castration-resistant prostate cancer (mCRPC). In this double-blind, placebo-controlled phase II trial, 47 patients were randomized 2:1 to receive docetaxel (75 mg/m2 i.v.) with either HDIVC (1 g/kg) or placebo. Coprimary endpoints were PSA50 response and adverse event r

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… A phase I/II study of arsenic trioxide/bortezomib/ascorbic acid combination therapy for the treatment of relapsed or refractory multiple myeloma. Clin Cancer Res 2007;13:1762–8. 13. Schoenfeld JD, Alexander MS, Waldron TJ, Sibenaller ZA, Spitz DR, Buettner GR, et al. …

Metabolic Rewiring in Radiation Oncology Toward Improving the Therapeutic Ratio.

To meet the anabolic demands of the proliferative potential of tumor cells, malignant cells tend to rewire their metabolic pathways. Although different types of malignant cells share this phenomenon, there is a large intracellular variability how these metabolic patterns are altered. Fortunately, differences in metabolic patterns between normal tissue and malignant cells can be exploited to increase the therapeutic ratio. Modulation of cellular metabolism to improve treatment outcome is an emerging field proposing a variety of promising strategies in primary tumor and metastatic lesion treatme

Ascorbic Acid in Colon Cancer: From the Basic to the Clinical Applications.

Given the safety and potential benefits of intravenous ascorbic acid (AA) administration in cancer patients, there is merit in further exploring this therapeutic concept. In this review, we discuss the potential benefits of intravenous AA administration on colorectal cancer and we specifically focus on its effect on glycolysis in mutant and wild type RAS. We perform a PubMed and Ovid MEDLINE search using ascorbic acid, intravenous vitamin C, KRAS mutation, BRAF mutation and colorectal cancer (CRC) as keywords. At the cellular level, colorectal cancer cells undergo a metabolic shift called the

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… Efficacy and safety results with the combination therapy of arsenic trioxide, dexamethasone, and ascorbic acid in multiple myeloma patients Med. Oncol. 2006 23 263 272 10.1385/MO:23:2:263 16720927 51. Vollbracht C. Schneider B. Leendert V. Weiss G. Auerbach L. Beuth J. …

The Dual Role of Autophagy in Crizotinib-Treated ALK+ ALCL: From the Lymphoma Cells Drug Resistance to Their Demise.

Autophagy has been described as harboring a dual role in cancer development and therapy. Depending on the context, it can exert either pro-survival or pro-death functions. Here, we review what is known about autophagy in crizotinib-treated ALK+ ALCL. We first present our main findings on the role and regulation of autophagy in these cells. Then, we provide literature-driven hypotheses that could explain mechanistically the pro-survival properties of autophagy in crizotinib-treated bulk and stem-like ALK+ ALCL cells. Finally, we discuss how the potentiation of autophagy, which occurs with combi

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… Autophagic degradation of the BCR-ABL oncoprotein and generation of antileukemic responses by arsenic trioxide. Blood. 2012;120:3555–3562. doi: 10.1182/blood-2012-01-402578. 76. …

Molecularly targeted therapy and immunotherapy in leukemias.

The advent of next-generation high-throughput sequencing and precision medicine has allowed the identification of recurrent genetic events of vital interest for leukemic cells and for the management of patients with leukemia, since it has a direct impact on prognosis and therapeutic stratification. The precise cytogenetic characterization of these diseases has rapidly enabled the development of innovative therapeutic strategies to improve outcomes and limit toxicities. New targeted therapies, including small molecule inhibitors, monoclonal antibodies, bispecific T cell engagers, antibody-drug

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… N-methyltransferase 2A, ND: newly diagnosed, NPM1: nucleophosmin 1, RR: relapsed/refractory Generic name of the drug | FDA approved date | Indication All trans-retinoic acid (ATRA) | 1995 | Treatment of adults and pediatric patients 1 year of age and older with APL characterized by presence of t(15;17) Arsenic … trioxide (ATO) | 2000 | Treatment of adults and pediatric patients 1 year of age and older with RR APL characterized by presence of t(15;17) Arsenic trioxide (ATO) | 2018 | Treatment of adults with ND low risk APL characterized by presence of t(15;17) Midostaurin | 2017 | Treatment of adult patients …

Targeting the p53 signaling pathway in cancers: Molecular mechanisms and clinical studies.

Tumor suppressor p53 can transcriptionally activate downstream genes in response to stress, and then regulate the cell cycle, DNA repair, metabolism, angiogenesis, apoptosis, and other biological responses. p53 has seven functional domains and 12 splice isoforms, and different domains and subtypes play different roles. The activation and inactivation of p53 are finely regulated and are associated with phosphorylation/acetylation modification and ubiquitination modification, respectively. Abnormal activation of p53 is closely related to the occurrence and development of cancer. While targeted t

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… These include arsenic trioxide (ATO) and COTI‐2 targeting R175H; APR‐246 and APR‐548 targeting R273H; atorvastatin targeting R280K; phenethyl isothiocyanate (PEITC) targeting both R273H and R280K; and PC14586 targeting Y220C. … ATO, arsenic trioxide; AML, acute myeloid leukemia; BrC, breast cancer; CMML, chronic myelomonocytic leukemia; CRC, colorectal cancer; EC, endometrial cancer; ESCA, esophageal carcinoma; GBM, glioblastoma; MDS, myelodysplastic syndromes; MPN, myeloproliferative neoplasm; OC, ovarian cancer; PEITC, phenethyl …

Acute and Chronic Cardiovascular Adverse Events in Patients with Acute Myeloid Leukemia: A Systematic Review.

Background/Objectives: Patients with acute myeloid leukemia (AML) have a higher propensity for adverse cardiovascular outcomes, primarily due to the toxic effects of chemotherapeutic agents. The purpose of this systematic review is to explore the association of acute myeloid leukemia treatment with adverse cardiovascular events. Methods: We systematically screened the literature for studies providing comparative data on cardiovascular toxicities in patients treated for acute myeloid leukemia. After the initial search, 3649 papers were screened and a final total number of 46 were included for t

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… All-trans retinoic acid (ATRA), a vitamin A derivative, in combination with arsenic trioxide is an effective treatment for this condition [ 24 ]. …

Current Data and Future Perspectives on Patients with Atrial Fibrillation and Cancer

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… Arsenic trioxide, which is used to treat promyelocytic leukemia, may also cause QTc interval prolongation. Some anti-emetic drugs, such as ondansetron, which is commonly used in cancer patients to prevent and treat nausea, may also contribute to QTc prolongation [ 29 ]. …

From HDAC to Voltage-Gated Ion Channels: What's Next? The Long Road of Antiepileptic Drugs Repositioning in Cancer.

Cancer is a major health burden worldwide. Although the plethora of molecular targets identified in the last decades and the deriving developed treatments, which significantly improved patients' outcome, the occurrence of resistance to therapies remains the major cause of relapse and mortality. Thus, efforts in identifying new markers to be exploited as molecular targets in cancer therapy are needed. This review will first give a glance on the diagnostic and therapeutic significance of histone deacetylase (HDAC) and voltage gated ion channels (VGICs) in cancer. Nevertheless, HDAC and VGICs hav

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… Another interesting combination has been recently described for VPA and Arsenic Trioxide (ATO; As2O3), another anti-cancer agent for various solid tumors and hematological malignancy, which has been reported to efficiently inhibit the growth of lung cancer cells both in vitro and in vivo. …