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Prevalence, Attributes, and Risk Factors of QT-Interval-Prolonging Drugs and Potential Drug-Drug Interactions in Cancer Patients: A Prospective Study in a Tertiary Care Hospital.

Introduction Cancer chemotherapy regimens include multiple classes of adjuvant drugs as supportive therapy. Because of the concurrent intake of other drugs (like antiemetics, antidepressants, analgesics, and antimicrobials), there is a heightened risk for possible QT interval prolongation. There is a dearth of evidence in the literature regarding the usage of QT-prolonging anticancer drugs and associated risk factors that have the propensity to prolong QT interval. The purpose was to explore the extent of the use of QT-interval-prolonging drugs and potential QT-prolonging drug-drug interaction

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… Etoposide, gemcitabine, and mitoxantrone have low emetogenic capability, with emesis occurring in 10-30% of subjects. Age of less than 50 years, female gender, history of low prior chronic alcohol intake, history of motion sickness, and emesis during pregnancy are notable risk factors for CINV. …

Best of JACC: Case Reports From ACC.23.

This dedicated issue of JACC: Case Reports highlights the top ranked Complex Clinical Cases from the ACC 2023 Scientific Sessions. These cases were reviewed and selected by a committee of peers in the months leading up to the annual meeting. These reviewers were ACC members with no affiliation to the JACC: Case Reports Editorial Board. While the cases were presented at the meeting and included in the formal Abstract Book from ACC, they have not been published elsewhere. These cases illustrate how the ACC can be a place for cardiovascular professionals to come together to learn, grow, and share

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… Patient was initiated on ifosfomide and etoposide and underwent proton beam radiation. Conclusion Outcomes of patients with high-grade cardiac sarcomas are generally poor. …

Advances and Challenges in Cancer Stem Cells for Onco-Therapeutics.

Six decades have passed since the foundational recognition of the primary properties of the stem cells. Research on stem cells has since remained at the forefront of efforts to combat a spectrum of diseases, most notably cancer. Despite remarkable progress in medical science, a definitive cure for cancer has remained elusive, spurring the pursuit of diverse therapeutic strategies, among which stem cell therapy is a particularly promising avenue. Moreover, the utilization of cancer stem cells as a therapeutic source holds immense potential for addressing intractable diseases. The strategy of ta

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… 11 | Central nervous system nongerminomatous germ cell tumor|Choriocarcinoma|Embryonal carcinoma|Immature teratoma|Malignant teratoma|Mixed germ cell tumor|Pineal region germ cell tumor|Pineal region immature teratoma|Pineal region yolk sac tumor|Suprasellar germ cell tumor | Drug: carboplatin|Drug: etoposide …

Recent Progress in CDK4/6 Inhibitors and PROTACs.

Cell division in eukaryotes is a highly regulated process that is critical to the life of a cell. Dysregulated cell proliferation, often driven by anomalies in cell Cyclin-dependent kinase (CDK) activation, is a key pathological mechanism in cancer. Recently, selective CDK4/6 inhibitors have shown clinical success, particularly in treating advanced-stage estrogen receptor (ER)-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer. This review provides an in-depth analysis of the action mechanism and recent advancements in CDK4/6 inhibitors, categorizing them based

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… On 12 February 2021, trilaciclib received its first approval in the USA to decrease the incidence of chemotherapy-induced myelosuppression in adult patients when administered prior to a platinum/etoposide-containing regimen or topotecan-containing regimen for extensive-stage small cell lung cancer (ES-SCLC …

Maintenance therapy in acute myeloid leukemia: advances and controversies.

The last decade has seen steadfast progress in drug development in acute myeloid leukemia (AML) which has moved progressively towards genomic-based therapy. With these advances, outcomes in AML have improved but remains far from satisfactory. One approach towards preventing relapse in AML is to use maintenance therapy in patients, after attaining remission. Allogeneic hematopoietic stem cell transplantation (HSCT) is an effective post-remission therapy that has been proven to reduce the risk of relapse. However, in patients who are ineligible for HSCT or have a high risk of relapse, other effe

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… The Southwest Leukemia Group, in a small study, failed to show improvements in RFS and OS with 6-thioguanine, etoposide and CCNU-based maintenance. 24 The EORTC-HOVON trial showed an improvement in DFS but not OS with low-dose cytarabine maintenance compared to observation at remission after intensive …

Targeted Drug Delivery and Theranostic Strategies in Malignant Lymphomas.

Malignant lymphomas represent the most common type of hematologic malignancies. The first clinically approved TDD modalities in lymphoma patients were anti-CD20 radioimmunoconjugates (RIT) 131I-tositumomab and 90Y-ibritumomab-tiuxetan. The later clinical success of the first approved antibody-drug conjugate (ADC) for the treatment of lymphomas, anti-CD30 brentuximab vedotin, paved the path for the preclinical development and clinical testing of several other ADCs, including polatuzumab vedotin and loncastuximab tesirine. Other modalities of TDD are based on new formulations of "old" cytostatic

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… therapy of malignant lymphomas is still based on chemotherapy, i.e., on standard genotoxic cytostatic drugs, e.g., alkylating agents (cyclophosphamide, cisplatin), anthracyclines (doxorubicin), nucleoside analogues (cytarabine, fludarabine), vinca alkaloids (vincristine), topoisomerase inhibitors (etoposide …

Muscle wasting in cancer: opportunities and challenges for exercise in clinical cancer trials.

BACKGROUND: Low muscle in cancer is associated with an increase in treatment-related toxicities and is a predictor of cancer-related and all-cause mortality. The mechanisms of cancer-related muscle loss are multifactorial, including anorexia, hypogonadism, anaemia, inflammation, malnutrition, and aberrations in skeletal muscle protein turnover and metabolism. METHODS: In this narrative review, we summarise relevant literature to (i) review the factors influencing skeletal muscle mass regulation, (ii) provide an overview of how cancer/treatments negatively impact these, (iii) review factors be

Delivery of Drugs into Cancer Cells Using Antibody-Drug Conjugates Based on Receptor-Mediated Endocytosis and the Enhanced Permeability and Retention Effect.

Innumerable people worldwide die of cancer every year, although pharmaceutical therapy has actualized many benefits in human health. For background, anti-cancer drug development is difficult due to the multifactorial pathogenesis and complicated pathology of cancers. Cancer cells excrete hydrophobic low-molecular anti-cancer drugs by overexpressed efflux transporters such as multiple drug resistance 1 (MDR1) at the apical membrane. Mutation-driven drug resistance is also developed in cancer. Moreover, the poor distribution of drug to cancer cells is a serious problem, because patients suffer f

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… MDR1 inhibition increases sensitivity to doxorubicin and etoposide in adrenocortical cancer. Endocr. Relat. Cancer. 2019;26:367–378. doi: 10.1530/ERC-18-0500. 83. Jobin M.-L., Alves I.D. …

Cancer-Associated Thrombosis: A New Light on an Old Story.

Cancer-associated thrombosis (CAT) is a rising and significant phenomenon, becoming the second leading cause of death in cancer patients. Pathophysiology of CAT differs from thrombosis in the non-cancer population. There are additional risk factors for thrombosis specific to cancer including cancer type, histology, and treatment, such as chemotherapy. Recently developed scoring systems use these risk factors to stratify the degree of risk and encourage thromboprophylaxis in intermediate- to high-risk patients. Anticoagulation is safely used for prophylaxis and treatment of CAT. Both of these h

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… Recurrent Peripheral Arterial Thrombosis Induced by Cisplatin and Etoposide. Pharmacotherapy. 2002;22:1200–1204. doi: 10.1592/phco.22.13.1200.33524. 59. Cunningham D., Starling N., Rao S., Iveson T., Nicolson M., Coxon F., Middleton G., Daniel F., Oates J., Norman A.R., et al. …

Pulmonary Hypertension in an Oncologic Intensive Care Unit

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… embolism but prominent enlarged main pulmonary artery with mosaic attenuation (yellow arrows, decreased lung perfusion; red arrow, increased lung perfusion) within lung parenchyma. ( c ) Ovarian cancer (status post five cycles of vinblastine, cisplatin, cyclophosphamide, bleomycin, doxorubicin, and etoposide …

Natural Killer Cells: Angels and Devils for Immunotherapy.

In recent years, the relevance of the immune system to fight cancer has led to the development of immunotherapy, including the adoptive cell transfer of immune cells, such as natural killer (NK) cells and chimeric antigen receptors (CAR)-modified T cells. The discovery of donor NK cells' anti-tumor activity in acute myeloid leukemia patients receiving allogeneic stem cell transplantation (allo-SCT) was the trigger to conduct many clinical trials infusing NK cells. Surprisingly, many of these studies did not obtain optimal results, suggesting that many different NK cell parameters combined with

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… ; Allo: allogeneic; Allo-SCT: allogeneic stem cell transplantation; Flu: Fludarabine; Bu: Busulfan, ATG: Anti-Thymocyte Globulin; Ta: Tacrolimus, Mx: Methotrexate; Cy: Cyclophosphamide; Cs: Cyclosporine; Len: Lenalidomide; Bort: Bortezomib; Dex: Dexamethasone; Mel: Melphalan; Clo: Clofarabine, Eto: Etoposide …

Targeting signaling pathways in lymphoma: From molecular mechanisms to clinical breakthroughs.

AbstractThe treatment paradigm for lymphoma, a highly heterogeneous group of hematologic malignancies, has been revolutionized by the development of therapies targeting oncogenic signaling pathways. This shift from conventional chemotherapy to precision medicine is driven by a deep molecular understanding of the pathways that govern lymphoma cell survival and proliferation. This review comprehensively surveys the landscape of these targeted therapies, from fundamental molecular mechanisms to clinical breakthroughs. We first dissect the molecular architecture of key oncogenic drivers, covering

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… CD79B mutation subtype; Mut: Mutation; N1: NOTCH1 mutation subtype; NGS: Next-generation sequencing; NOS: Not otherwise specified; ORR: Overall response rate; PFS: Progression-free survival; PTCL: Peripheral T-cell lymphoma; R-CHOP: Rituximab plus CHOP; R-ICE: Rituximab, ifosfamide, carboplatin, and etoposide … The GUIDANCE-06 trial evaluated a genetic subtype-guided approach for R/R DLBCL, adding targeted agents to the R-ICE regimen (rituximab, ifosfamide, carboplatin, and etoposide) salvage chemotherapy backbone (R-ICE-X) [Figure 2 C]. [ 233 ] This strategy yielded impressive outcomes, with a 2-year PFS of …

PPAR-γ in Melanoma and Immune Cells: Insights into Disease Pathogenesis and Therapeutic Implications.

Changes in skin pigmentation, like hyperpigmentation or moles, can affect appearance and social life. Unlike locally containable moles, malignant melanomas are aggressive and can spread rapidly, disproportionately affecting younger individuals with a high potential for metastasis. Research has shown that the peroxisome proliferator-activated receptor gamma (PPAR-γ) and its ligands exhibit protective effects against melanoma. As a transcription factor, PPAR-γ is crucial in functions like fatty acid storage and glucose metabolism. Activation of PPAR-γ promotes lipid uptake and enhances sensitivi

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… The previous studies have shown that cancer cells exposed to DNA-damaging agents such as carboplatin, etoposide, and doxorubicin exhibit a higher level of phosphorylated Ser273. … This mechanism effectively shields melanoma cells from various chemotherapeutic agents, including DNA intercalating agents and topoisomerase inhibitors (e.g., cisplatin, etoposide, daunorubicin, and doxorubicin), as well as cytoskeleton-disrupting toxins, like vinblastine, irrespective of their mode …

The Cancer Antioxidant Regulation System in Therapeutic Resistance.

Antioxidants play a pivotal role in neutralizing reactive oxygen species (ROS), which are known to induce oxidative stress. In the context of cancer development, cancer cells adeptly maintain elevated levels of both ROS and antioxidants through a process termed "redox reprogramming". This balance optimizes the proliferative influence of ROS while simultaneously reducing the potential for ROS to cause damage to the cell. In some cases, the adapted antioxidant machinery can hamper the efficacy of treatments for neoplastic diseases, representing a significant facet of the resistance mechanisms ob

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… radiotherapy)/high-grade glioma (combination with radiotherapy and temozolomide)/advanced cancers | Phase I/II, completed | NCT01359982 [ 278 ] NCT02518958 [ 279 ] NCT02215512 [ 280 ] NCT02871843 [ 281 ] Metastatic CRC (combination with irinotecan)/platinum-resistant SCLC (combination with platinum and etoposide …

Cytokine release syndrome in solid tumours: mechanism-based therapeutic strategies for prevention and management.

Cytokine release syndrome (CRS) represents a spectrum of immune hyperactivation initiated by rapid T-cell engagement and amplified through innate immune cells, particularly monocytes and macrophages, with downstream cytokine cascades driving endothelial dysfunction, capillary leak and organ impairment. CRS is a frequent, class-associated toxicity of T-cell-engaging immunotherapies and is being observed with increasing regularity as T-cell-redirecting therapies progress through clinical development in solid tumours. Although CRS is typically less severe in patients with solid tumours relative t

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… Efficacy of carboplatin–etoposide rechallenge after first-line chemo-immunotherapy in ES-SCLC: an international multicentric analysis . Ther Adv Med Oncol 2024 ; 16 : 17588359241272957. 10.1177/17588359241272957 PMC11443580 39355343 9 Labrijn AF Janmaat ML Reichert JM , et al . …

Терапия сотовой связи для руматоидного артрита.

Химерическая антигенная рецепторная (CAR) клеточная терапия Т произвела революцию в лечении лейкемии, лимфомы и множественных миеломы, реанимировав на поверхности этих клеток антигены CD19 и BCMA. В последнее время появляется все больше свидетельств того, что эти клеточные методы лечения могут также быть направлены против аутоиммунных заболеваний, включая системный волчаньий эритематос, системный склероз, расстройство спектрального спектра нейромиелита, миастения гравис, идиопатический воспалительный миосит, множественный склероз и ревматоидный артрит. На сегодняшний день ten Пациенты с ревмат

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… Cyclosporin, LEF Leflunomide, IFN β - 1a Interferon β−1a, Fingo Fingolimod, Alemtuz Alemtuzumab, PLQ Plaquenil, SLZ Sulfasalazine, Igur Iguratimod, EC Eculizumab, Thy thymectomy, Dex Dexamethasone, FK506 Tacrolimus, R-CNOP rituximab, cyclophosphamide, mitoxantrone, vincristine and prednisolone, EPOCH-R etoposide …

Pharmacogenomics and Big Data in medical oncology: developments and challenges.

Medical oncology, through conventional chemotherapy as well as targeted drugs, remains an important component of cancer patient management, particularly for systemic disease. Despite advances in all areas of medical oncology, certain challenges persist in the form of drug resistance and severe normal tissue toxicity. These unwanted effects can be counteracted through a patient-tailored treatment approach, which in chemotherapy is translated as pharmacogenomics. This research field investigates the way genetic makeup influences a patient's response to various drugs with the aim to minimize tria

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… Wide-ranging cancers | 8 , 9 Nitrosoureas (similar to alkylating agents) | Carmustine, Lomustine Semustin, Streptozocin | Inhibit DNA repair; they can cross the blood–brain barrier thus are useful for brain tumours | Brain | 10 , 11 Topoisomerase inhibitors (plant alkaloids) | Irinotecan, Topotecan Etoposide …

Disparity in survival benefits of pembrolizumab between Asian and non-Asian patients with advanced cancers: A systematic review and meta-regression analysis.

BackgroundImmune checkpoint inhibitors have revolutionized the treatment of malignancies. However, disproportionate enrollment among races and ethnicities places the generalizability of global trial results in doubt.MethodsIn this systematic review, phase 3 randomized controlled trials investigating pembrolizumab in advanced cancers and providing subgroup analyses of Asian and non-Asian participants were included. The primary and secondary effect measures were the mean differences (MDs) in the natural logarithms of the hazard ratios (HRs) for overall survival (OS) and progression-free survival

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… Pembrolizumab or placebo plus etoposide and platinum as first‐line therapy for extensive‐stage small‐cell lung cancer: randomized, double‐blind, phase III KEYNOTE‐604 study . …

Therapeutic Potential of Cannabinoids on Tumor Microenvironment: A Molecular Switch in Neoplasia Transformation.

The efficacy of chemotherapy depends on the tumor microenvironment. This microenvironment consists of a complex cellular network that can exert both stimulatory and inhibitory effects on tumor genesis. Given the increasing interest in the effectiveness of cannabis, cannabinoids have gained much attention as a potential chemotherapy drug. Cannabinoids are a group of marker compounds found in Cannabis sativa L., more commonly known as marijuana, a psychoactive drug used since ancient times for pain management. Although the anticancer potential of C. sativa, has been recognized previously, increa

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… Serine palmitoyltransferase regulates de novo ceramide generation during etoposide-induced apoptosis. J Biol Chem. 2000;275:9078-9084. 57. Salazar M, Carracedo A, Salanueva IJ, et al. Cannabinoid action induces autophagy-mediated cell death through stimulation of ER stress in human glioma cells. …

Safety, tolerability, and pharmacokinetics/pharmacodynamics of JMT103 in patients with bone metastases from solid tumors.

Bone metastases are common complications of solid tumors. The outcome is poor despite major progress in cancer therapies. We describe a multicenter, open-label, phase 1, dose escalation and expansion trial of JMT103, a novel fully humanized receptor activator of nuclear factor kappa-B ligand (RANKL)-targeting monoclonal antibody, in adults with bone metastases from solid tumors. The study assessed the safety, tolerability, and pharmacokinetics/pharmacodynamics of JMT103. Patients received JMT103 at doses of 0.5, 1.0, 2.0, and 3.0 mg/kg every 4 weeks for 3 cycles. Among 59 patients enrolled, 20

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… Lenvatinib with etoposide plus ifosfamide in patients with refractory or relapsed osteosarcoma (Itcc-050): A multicentre, open-label, multicohort, phase 1/2 study . …