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International Journal of Molecular... Feb 2024The use of vitamin C (VC) in high doses demonstrates a potent tumor suppressive effect by mediating a glucose-dependent oxidative stress in Kirsten rat sarcoma (KRAS)...
The use of vitamin C (VC) in high doses demonstrates a potent tumor suppressive effect by mediating a glucose-dependent oxidative stress in Kirsten rat sarcoma (KRAS) mutant cancer cells. VC with arsenic trioxide (ATO) is a promising drug combination that might lead to the development of effective cancer therapeutics. Considering that a tumor suppressive effect of VC requires its high-dose administration, it is of interest to examine the toxicity of two enantiomers of VC (enantiomer d-optical isomer D-VC and natural l-optical isomer L-VC) in vitro and in vivo. We show that the combinations of L-VC with ATO and D-VC with ATO induced a similar cytotoxic oxidative stress in Kras-expressing mutant cancer cells as indicated by a substantial increase in reactive oxidative species (ROS) production and depolarization of mitochondria. To examine the L-VC and D-VC toxicity effects, we administered high doses of D-VC and L-VC to CD1 mice and carried out an evaluation of their toxic effects. The daily injections of L-VC at a dose of 9.2 g/kg for 18 days were lethal to mice, while 80% of mice remained alive following the similar high-dose administration of D-VC. Following the drug injection courses and histopathological studies, we determined that a natural form of VC (L-VC) is more harmful and toxic to mice when compared to the effects caused by the similar doses of D-VC. Thus, our study indicates that the two enantiomers of VC have a similar potency in the induction of oxidative stress in cancer cells, but D-VC has a distinctive lower toxicity in mice compared to L-VC. While the mechanism of a distinctive toxicity between D-VC and L-VC is yet to be defined, our finding marks D-VC as a more preferable option compared to its natural enantiomer L-VC in clinical settings.
Topics: Animals; Mice; Ascorbic Acid; Proto-Oncogene Proteins p21(ras); Oxidative Stress; Vitamins; Arsenic Trioxide; Neoplasms
PubMed: 38473779
DOI: 10.3390/ijms25052531 -
Medical Science Monitor : International... Jan 2024This publication has been retracted by the Editor due to the identification of non-original figure images and manuscript content that raise concerns regarding the...
This publication has been retracted by the Editor due to the identification of non-original figure images and manuscript content that raise concerns regarding the credibility and originality of the study. Reference: Jin-Cheng Zheng, Ke-Jie Chang, Yu-Xiang Jin, Xue-Wei Zhao, Bing Li, Meng-Hang Yang. Arsenic Trioxide Inhibits the Metastasis of Small Cell Lung Cancer by Blocking Calcineurin-Nuclear Factor of Activated T Cells (NFAT) Signaling. Med Sci Monit 2019; 25:2228-2237. DOI: 10.12659/MSM.913091.
PubMed: 38288559
DOI: 10.12659/MSM.943940 -
Reumatismo Dec 2023Granulomatosis with polyangiitis (GPA) is a rare autoimmune disease that affects multiple organs and causes inflammation, necrosis, and vasculitis in small blood...
Granulomatosis with polyangiitis (GPA) is a rare autoimmune disease that affects multiple organs and causes inflammation, necrosis, and vasculitis in small blood vessels. Treatment for GPA involves achieving and maintaining remission. In recent studies, cyclophosphamide-based regimens have been linked to comorbidity hazards, including an increased risk of malignancies, especially hematological ones. Acute myeloid leukemia is the main hematologic malignancy that can complicate GPA. In this context, we report the case of a middle-aged woman with GPA who developed acute promyelocytic leukemia (APL) during maintenance with cyclophosphamide. She was treated with all-trans retinoic acid at 50 mg/day and arsenic trioxide at 10 mg/day, along with steroids. This case highlights the unique emergence of APL in a GPA patient during cyclophosphamide therapy. A single case has previously been reported on the development of APL in a patient with GPA while using azathioprine monotherapy for 2 years.
Topics: Middle Aged; Female; Humans; Leukemia, Promyelocytic, Acute; Granulomatosis with Polyangiitis; Cyclophosphamide; Arsenic Trioxide; Azathioprine
PubMed: 38115775
DOI: 10.4081/reumatismo.2023.1593 -
Acta Medica Indonesiana Jan 2024Incidents of leukemia in pregnancy are infrequent with only one case found from 75,000 to 100,000 pregnancies. The pathophysiological mechanism of leukemia during...
Incidents of leukemia in pregnancy are infrequent with only one case found from 75,000 to 100,000 pregnancies. The pathophysiological mechanism of leukemia during pregnancy is still unclear. Leukemia which occurs in pregnancy is usually acute and predominantly the myeloid type.A 35-year-old woman in her fourth pregnancy with a gestational age of 38-39 weeks, came to the emergency department (ED) with complaints of contractions since 4.5 hours before admission. The contraction was not accompanied by discharge, mucus, or blood, and fetal movements was still active. She denied complaints of fever, nausea, vomiting, dizziness, shortness of breath, weakness, fatigue, lethargy, and bleeding. Physical examination results, both palpebral conjunctiva were pale. Laboratory examination results of a complete blood count, white blood cell count were 2,930/uL, hemoglobin 8.3 g/dL, Hct 24.10%, erythrocytes 2.78x106/µL, platelets 62,000/µL. Bone Marrow Aspiration (BMA) revealed Acute Promyelocytic Leukemia (APL).APL is a subtype of Acute Myelogenous Leukemia (AML). Persistent fatigue, recurrent infections, and bleeding are common manifestations of APL. The diagnosis of APL is made by bone marrow aspiration examination, and it is safe for pregnancy. APL therapy in pregnancy uses All-Trans Retinoic Acid (ATRA) and Arsenic Trioxide (ATO). ATRA and ATO are highly teratogenic, but recent studies have reported no fetal abnormalities.Accuracy and speed in diagnosing and initiating APL therapy in pregnancy are essential in preventing serious complications.
Topics: Adult; Female; Humans; Pregnancy; Antineoplastic Combined Chemotherapy Protocols; Arsenic Trioxide; Leukemia, Promyelocytic, Acute; Tretinoin
PubMed: 38561886
DOI: No ID Found -
Cell Death & Disease Jun 2024The cavity-creating p53 cancer mutation Y220C is an ideal paradigm for developing small-molecule drugs based on protein stabilization. Here, we have systematically...
The cavity-creating p53 cancer mutation Y220C is an ideal paradigm for developing small-molecule drugs based on protein stabilization. Here, we have systematically analyzed the structural and stability effects of all oncogenic Tyr-to-Cys mutations (Y126C, Y163C, Y205C, Y220C, Y234C, and Y236C) in the p53 DNA-binding domain (DBD). They were all highly destabilizing, drastically lowering the melting temperature of the protein by 8-17 °C. In contrast, two non-cancerous mutations, Y103C and Y107C, had only a moderate effect on protein stability. Differential stabilization of the mutants upon treatment with the anticancer agent arsenic trioxide and stibogluconate revealed an interesting proximity effect. Crystallographic studies complemented by MD simulations showed that two of the mutations, Y234C and Y236C, create internal cavities of different size and shape, whereas the others induce unique surface lesions. The mutation-induced pockets in the Y126C and Y205C mutant were, however, relatively small compared with that of the already druggable Y220C mutant. Intriguingly, our structural studies suggest a pronounced plasticity of the mutation-induced pocket in the frequently occurring Y163C mutant, which may be exploited for the development of small-molecule stabilizers. We point out general principles for reactivating thermolabile cancer mutants and highlight special cases where mutant-specific drugs are needed for the pharmacological rescue of p53 function in tumors.
Topics: Tumor Suppressor Protein p53; Humans; Mutation; Neoplasms; Arsenic Trioxide; Molecular Dynamics Simulation; Protein Stability; Antineoplastic Agents
PubMed: 38862470
DOI: 10.1038/s41419-024-06739-x -
Journal of Hepatocellular Carcinoma 2024In recent years, there have been limited reports on the efficacy of later-line anti-programmed cell death -1 (PD-1) therapy in achieving prolonged and complete remission...
In recent years, there have been limited reports on the efficacy of later-line anti-programmed cell death -1 (PD-1) therapy in achieving prolonged and complete remission in patients with hepatocellular carcinoma (HCC). Tislelizumab, a humanized anti-PD-1 monoclonal IgG4 antibody, has shown promising results in the treatment of HCC. This report highlights the case of a patient with HCC who experienced the development of lung metastatic lesions following HCC resection and chemotherapy, but achieved a prolonged complete response (CR) after receiving tislelizumab treatment. In April 2017, a 56-year-old male diagnosed with primary HCC underwent hepatectomy and hepatic arterial infusion pump placement. Following the surgery, the patient received adjuvant hepatic arterial infusion chemotherapy (HAIC) with 4 cycles of cisplatin+5-fluorouracil (PF) regimen starting in June 2017. In May 2018, lung metastatic lesions were detected, and the patient underwent 4 cycles of oxaliplatin+leucovorin+5-fluorouracil (FOLFOX) chemotherapy. However, the disease progressed in August 2018, leading to the administration of arsenic trioxide treatment. Despite this, further progression was observed in October 2018, prompting the patient's enrollment in a clinical trial for tislelizumab therapy. Initially, the patient achieved a partial response (PR) to tislelizumab, which was followed by a CR that lasted for almost 4 years. Unfortunately, tislelizumab treatment had to be discontinued due to immune-related adverse events (AE). Subsequently, the patient received lenvatinib and maintained a CR until July 2023. Tislelizumab monotherapy, when used as a third-line treatment, has demonstrated remarkable efficacy in facilitating patients with advanced HCC to attain a durable CR.
PubMed: 38854817
DOI: 10.2147/JHC.S464519 -
Research Square Feb 2024The authors have requested that this preprint be removed from Research Square.
The authors have requested that this preprint be removed from Research Square.
PubMed: 38464079
DOI: 10.21203/rs.3.rs-3951960/v1 -
Cureus May 2024The introduction of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) has transformed the outcome of acute promyelocytic leukemia (APL) from a uniformly fatal...
Acute Promyelocytic Leukemia With Long and Short Isoforms of PML::RARA Fusion Transcripts Complicated by Abdominal Distension and Acute Edematous Pancreatitis During Induction Treatment: A Case Report.
The introduction of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) has transformed the outcome of acute promyelocytic leukemia (APL) from a uniformly fatal disease to one of the most curable human malignancies in recent decades. However, early mortality caused by coagulopathy, infection, multi-organ failure, and differentiation syndrome (DS) during disease onset and induction treatment remains a major issue in APL, especially in elderly patients who may suffer from higher treatment-related mortality due to a higher vulnerability to treatment toxicities. Herein, we present a case of an elderly patient with APL with rare mixed long (L-) and short (S-) isoforms of PML::RARA fusion transcripts who had multiple complications at disease onset. In addition, the initiation of treatment with ATRA in combination with ATO led to the rapid onset of severe DS. In particular, this patient experienced a rare clinical feature of DS, acute edematous pancreatitis (AEP). Furthermore, due to the patient's refractory abdominal distension related to the dose of ATRA, ATO, and Realgar-Indigo Naturalis Formula (RIF), we have to repeatedly adjust the doses of these drugs that the patient can maximally tolerate. Nevertheless, the patient achieved complete remission (CR) even after receiving a substandard dose of these drugs. However, the patient relapsed, acquired the FLT3-ITD mutation nine months later, and experienced abdominal distension again while receiving the standard doses of ATRA and RIF. Therefore, these drugs were adjusted to the maximum tolerated dose based on the experience with the initial induction treatment, and the patient achieved CR after four weeks of reinduction treatment. We report that this case may provide some clinical information for the diagnosis and treatment of similar patients with APL.
PubMed: 38883104
DOI: 10.7759/cureus.60321 -
Oncology Letters Jun 2024Acute promyelocytic leukemia (APL), especially cases of high-risk with complex chromosomes (CK), is rare in individuals infected with human immunodeficiency virus (HIV),...
Acute promyelocytic leukemia (APL), especially cases of high-risk with complex chromosomes (CK), is rare in individuals infected with human immunodeficiency virus (HIV), making the establishment of therapeutic approaches challenging; often the treatment is individualized. This report describes a 49-year-old female patient with HIV who was diagnosed with high-risk APL with a new CK translocation and presents a literature review. At diagnosis, the patient presented with typical t(15;17)(q24;q21) with additional abnormalities, including add(5)(q15), add(5)(q31), add(7)(q11.2) and add(12) (p13). The results of acute myeloid leukemia mutation analysis suggested positivity for calreticulin and lysine methyltransferase 2C genes. The patient received all-trans retinoic acid combined with arsenic trioxide and chemotherapy, with morphologically complete remission after the first cycle of chemotherapy. The present report provided preliminary data for future clinical research.
PubMed: 38694571
DOI: 10.3892/ol.2024.14407