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Epigenetic and Transcriptomic Regulation Landscape in HPV+ Cancers: Biological and Clinical Implications.

Human Papillomavirus (HPV) is an oncogenic virus that causes the highest number of viral-associated cancer cases and deaths worldwide, with more than 690,000 new cases per year and 342,000 deaths only for cervical cancer (CC). Although the incidence and mortality rates for CC are declining in countries where screening and vaccination programs have been implemented, other types of cancer in which HPV is involved, such as oropharyngeal cancer, are increasing, particularly in men. Mutational and transcriptional profiles of various HPV-associated neoplasms have been described, and accumulated evid

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… Subsequent phase III clinical trials in patients with advanced CC showed a more prolonged median survival (10 months) when treated with chemotherapy + valproic acid + hydralazine than chemotherapy + placebo (6 months). … A Double-Blind, Placebo-Controlled, Randomized Phase III Trial of Chemotherapy Plus Epigenetic Therapy with Hydralazine Valproate for Advanced Cervical Cancer. Preliminary Results. Med. …

Transforming tumor microenvironments: nanotechnology and gene therapy in cellular signaling and epigenetic insight into chemo-resistance.

Chemoresistance remains the primary cause of cancer treatment failure, yet current understanding remains fragmented across isolated mechanistic studies. This review provides a unified framework linking tumor microenvironment (TME) signaling, epigenetic reprogramming, and nanotherapeutic intervention as an integrated axis driving and potentially reversing chemoresistance. We systematically examine how TME components: hypoxia (HIF-1α pathway), acidosis, cancer-associated fibroblasts (TGF-β/PDGF signaling), and immune cells (NF-κB-mediated immunosuppression) activate signaling cascades that direc

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… In fact, a pioneering phase II trial added hydralazine (a demethylating agent) and valproate (an HDAC inhibitor) to chemotherapy in patients who had been progressing on chemotherapy; the combination achieved partial responses or stable disease in 80% of these refractory patients [ 75 ], regardless of …

Brown Tumor From Secondary Hyperparathyroidism Mimicking Metastatic Renal Cell Carcinoma in a Patient With End-Stage Renal Disease.

Brown tumors (also known as osteitis fibrosa cystica) are rare complications of end-stage renal disease (ESRD) and secondary hyperparathyroidism (HPT), characterized by focal bone lesions that resemble neoplasms. They are often misdiagnosed as metastatic bone disease, especially in patients with a history of malignancy. We present a case of a 60-year-old man with a history of renal cell carcinoma (RCC), and ESRD on hemodialysis (HD), who developed diffuse bone lesions on imaging with osteolytic/osteoblastic appearance concerning metastases, but on further workup was found to have brown tumors.

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… Additionally, he was on amlodipine, carvedilol, and hydralazine for hypertension, and allopurinol for gout. On physical examination, the patient had tenderness in his left forearm over the ulnar bone. Motor and sensory function was intact, and he had palpable pulses in the left upper extremity. …

Advancing Medulloblastoma Treatment: Molecular Mechanisms, Drug Repurposing, and Precision Therapies.

Medulloblastomas are the most common malignant pediatric brain tumors, representing approximately 20% of the central nervous system cancers in children. These tumors are highly heterogeneous and classified into four molecular subgroups-WNT, SHH, Group 3, and Group 4-each with distinct genetic and epigenetic profiles that influence tumor behavior, therapeutic response, and patient outcomes. Advances in molecular diagnostics have improved the subclassification of medulloblastomas, yet treatment outcomes for high-risk subtypes, particularly Group 3, remain poor, with current modalities often asso

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… promotes radiosensitization and differentiation Improves event-free survival when combined with chemotherapy Phase II trials Metformin Targets mitochondrial complex I, induces energy stress, activates AMPK Preclinical evidence supporting use for KDM6A-linked metabolic dysregulation Preclinical studies Hydralazine … Hydralazine, an antihypertensive agent, induces DNA demethylation, reactivates PRDM6 , and reduces chemotherapy resistance in preclinical studies [ 87 ] . …

Interpreting clinical assays for histone deacetylase inhibitors.

As opposed to genetics, dealing with gene expressions by direct DNA sequence modifications, the term epigenetics applies to all the external influences that target the chromatin structure of cells with impact on gene expression unrelated to the sequence coding of DNA itself. In normal cells, epigenetics modulates gene expression through all development steps. When "imprinted" early by the environment, epigenetic changes influence the organism at an early stage and can be transmitted to the progeny. Together with DNA sequence alterations, DNA aberrant cytosine methylation and microRNA deregulat

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… Candelaria M Gallardo-Rincon D Arce C A Phase II study of epigenetic therapy with hydralazine and magnesium valproate to overcome chemotherapy resistance in refractory solid tumors Ann Oncol 2007 18 9 1529 1538 17761710 10.1093/annonc/mdm204 113. … Segura-Pacheco B Perez-Cardenas E Taja-Chayeb L Global DNA hypermethylation-associated cancer chemotherapy resistance and its reversion with the demethylating agent hydralazine J Transl Med 2006 4 32 16893460 10.1186/1479-5876-4-32 PMC1563479 116. …

Medicine manipulation: An alternative to mitigate therapeutic gaps in the Brazilian Unified Health System?

Despite the various initiatives carried out in Brazil and in the world, the challenge of offering essential medicines in adequate presentations remains, especially to the public affected by diseases considered neglected and the pediatric population, for whom the therapeutic options remain limited. The main objective of this study was to evaluate the production of manipulated medicines as a strategy to mitigate therapeutic and access gaps to essential medicines within the Brazilian public health system, called the Unified Health System (SUS). The evaluation, carried out between 2020 and 2021, i

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… . | Infantile Hydralazine | 5 mg/mL Oral solution | Severe and refractory systemic arterial hypertension; Hypertensive emergency. | Infantile Hydrochlorothiazide | 5 mg/mL Oral solution | Systemic arterial hypertension; Edema of different causes. | Infantile Hydrocortisone | 5 mg/mL Oral solution | Congenital …

Epigenetic and Genetic Keys to Fight HPV-Related Cancers.

Cervical cancer ranks as the fourth most prevalent cancer among women globally, with approximately 600,000 new cases being diagnosed each year. The principal driver of cervical cancer is the human papillomavirus (HPV), where viral oncoproteins E6 and E7 undertake the role of driving its carcinogenic potential. Despite extensive investigative efforts, numerous facets concerning HPV infection, replication, and pathogenesis remain shrouded in uncertainty. The virus operates through a variety of epigenetic mechanisms, and the epigenetic signature of HPV-related tumors is a major bottleneck in our

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… Subsequent phase III clinical trials involving patients with advanced cervical cancer revealed that those treated with the combination of chemotherapy, valproic acid, and hydralazine, experienced a longer median survival period (10 months) than those who received chemotherapy with placebo (6 months) …

Drug Repurposing for Cancer Treatment: A Comprehensive Review.

Cancer ranks among the primary contributors to global mortality. In 2022, the global incidence of new cancer cases reached about 20 million, while the number of cancer-related fatalities reached 9.7 million. In Saudi Arabia, there were 13,399 deaths caused by cancer and 28,113 newly diagnosed cases of cancer. Drug repurposing is a drug discovery strategy that has gained special attention and implementation to enhance the process of drug development due to its time- and money-saving effect. It involves repositioning existing medications to new clinical applications. Cancer treatment is a therap

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… Hydralazine induces demethylation in prostate cancer cells, re-expressing suppressed genes [ 97 , 98 ]. A Phase II trial is currently underway to evaluate minoxidil, a direct vasodilator antihypertensive medication, as a single treatment for ovarian cancer. … pathway and ROS. | Beta receptors | Phase I trials ( NCT03633747 ) Phase II trials ( NCT02596867 ) | [ 81 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 95 , 96 ] Direct Vasodilator | Minoxidil | | Ovarian cancer | Caspase-3 | ATP-sensitive potassium channels | Phase II trials ( NCT05272462 ) | [ 99 , 100 , 101 ] Hydralazine …

Rhabdomyolysis secondary to COVID-19 infection and vaccination: a review of literature.

Rhabdomyolysis (RML), characterized by the breakdown of skeletal muscle fibers and the release of muscle contents into the bloodstream, has emerged as a notable complication associated with Coronavirus disease 2019 (COVID-19) infection and vaccination. Studies have reported an increased incidence of RML in individuals with severe COVID-19 infection. However, the exact mechanisms remain unclear and are believed to involve the host's immune response to the virus. Furthermore, RML has been documented as a rare adverse event following COVID-19 vaccination, particularly with mRNA vaccines. Proposed

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… The patient was on Hydralazine 50 (BID), Furosemide 40 (QD), and Rosuvastatin 5 (QD) with positive past myotoxic DH. Lab results showed a peak CK of 1,083,744, AST/ALT of 3995/751, and creatinine of 7.6 with positive blood test in U/A. … He expired. | ( 100 ) Singh et al. (2020) | A 43-year-old male with end-stage renal disease, on Hydralazine, presented with fever, myalgia, cough, and dyspnea. His CK was 9,793, AST/ALT of 142/43, LDH of 478 and creatinine was 20. …

Skin manifestations associated with systemic diseases - Part I.

The skin demonstrates what is happening in the body in many diseases, as it reflects some internal processes on the surface. In this sense, skin as an organ, goes beyond its protective and barrier functions, as it provides clues for the identification of some systemic diseases. The dermatologist then raises diagnostic hypotheses for conditions related to all systems and refers them to the appropriate specialty. With easy access to examination by trained eyes and biopsies, the skin can present specific or non specific alterations on histopathology. In the first case this combination establishes

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… Medications (resolution with drug withdrawal) anti-TNFa, levamisole, propylthiouracil, hydralazine, rituximab, montelukast, statins. 39 Neoplasms Paraneoplastic syndromes (lymphoproliferative and myeloproliferative diseases) Others Dermatomyositis Systemic sclerosis Inflammatory bowel diseases COVID … Medications (resolution with drug withdrawal) | anti-TNFa, levamisole, propylthiouracil, hydralazine, rituximab, montelukast, statins. 39 Neoplasms | Paraneoplastic syndromes (lymphoproliferative and myeloproliferative diseases) Others | Dermatomyositis Systemic sclerosis Inflammatory bowel diseases …

Alcohol Consumption and Autoimmune Diseases.

Alcohol is the second-most misused substance after tobacco. It has been identified as a causal factor in more than 200 diseases and 5.3% of all deaths and is associated with significant behavioral, social, and economic difficulties. As alcohol consumption may modulate the immune system's regulatory mechanisms to avoid attacking the body's tissues, it has been proven to play a dichotomic role in autoimmune diseases (ADs) based on the quantity of consumption. In this review, we report updated evidence on the role of alcohol in ADs, with a focus on alcohol addiction and the human biological immun

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… Genetic susceptibility (HLA-DR2, HLA-DR3, PTPN22, STAT4, IRF5), environmental triggers (ultraviolet light, Epstein–Barr virus, estrogen, procainamide, hydralazine), and immune dysregulation are at the base of its pathophysiology [ 174 , 175 ]. …

Autoimmune Disease Risk With GLP-1RA, DPP-4i, and SGLT2i Treatment in Patients With Diabetes.

OBJECTIVE: Dipeptidyl peptidase-4 inhibitors (DPP-4i), glucagon-like peptide-1 receptor agonists (GLP-1RA), and sodium-glucose cotransporter-2 inhibitors (SGLT2i) are widely used for type 2 diabetes, yet their comparative immunologic safety is uncertain. To address this gap, we evaluated autoimmune disease incidence among patients treated with these agents. METHODS: We conducted emulated target trials using electronic health record data from 152 health care organizations in the TriNetX network (2016-2023). Adults with type 2 diabetes initiating DPP-4i, GLP-1RA, or SGLT2i monotherapy and no pr

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… 4,517 (3.8) 0.003 Methimazole 643 (0.4) 993 (0.4) 0.005 444 (0.4) 438 (0.4) 0.001 Propylthiouracil 86 (0.0) 58 (0.0) 0.013 25 (0.0) 33 (0.0) 0.004 Sulfonamides 31,991 (17.8) 41,997 (16.5) 0.034 20,102 (17.0) 19,847 (16.8) 0.006 Spironolactone 7,522 (4.2) 14,349 (5.7) 0.068 5,330 (4.5) 5,275 (4.5) 0.002 Hydralazine …

Intestinal/Multivisceral Transplantation

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… ciprofloxacin, clindamycin, dapsone, fluconazole, ganciclovir, gentamicin, imipenem, linezolid, macrolides, metronidazole, penicillins, rifampicin, trimethoprim–sulfamethoxazole, valganciclovir, vancomycin Anticonvulsants Phenytoin, valproic acid Cardiovascular drugs and diuretics Acetazolamide, coumarins, hydralazine … ciprofloxacin, clindamycin, dapsone, fluconazole, ganciclovir, gentamicin, imipenem, linezolid, macrolides, metronidazole, penicillins, rifampicin, trimethoprim–sulfamethoxazole, valganciclovir, vancomycin Anticonvulsants | Phenytoin, valproic acid Cardiovascular drugs and diuretics | Acetazolamide, coumarins, hydralazine …

Randomized phase II study of valproic acid in combination with bevacizumab and oxaliplatin/fluoropyrimidine regimens in patients with RAS-mutated metastatic colorectal cancer: the REVOLUTION study protocol.

BackgroundDespite effective treatments, metastatic colorectal cancer (mCRC) prognosis is still poor, mostly in RAS-mutated tumors, thus suggesting the need for novel combinatorial therapies. Epigenetic alterations play an important role in initiation and progression of cancers, including CRC. Histone-deacetylase inhibitors (HDACi) have shown activity in combination with chemotherapy in the treatment of solid tumors. Owing to its HDACi activity and its safe use for epileptic disorders, valproic acid (VPA) is a good candidate for anticancer therapy that we have largely explored preclinically tra

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… inhibit deacetylase activity in solid tumors has been demonstrated in monotherapy at oral doses between 20 and 60 mg/kg. 15 VPA oral doses of 30 mg/kg daily induced HDAC inhibition in the peripheral blood of patients in a neoadjuvant epigenetic therapy study in combination with the demethylating agent hydralazine …

Novel therapeutic agents in clinical trials: emerging approaches in cancer therapy.

Novel therapeutic agents in clinical trials offer a paradigm shift in the approach to battling this prevalent and destructive disease, and the area of cancer therapy is on the precipice of a trans formative revolution. Despite the importance of tried-and-true cancer treatments like surgery, radiation, and chemotherapy, the disease continues to evolve and adapt, making new, more potent methods necessary. The field of cancer therapy is currently witnessing the emergence of a wide range of innovative approaches. Immunotherapy, including checkpoint inhibitors, CAR-T cell treatment, and cancer vacc

Resveratrol and Cardiovascular Diseases.

The increased incidence of cardiovascular diseases (CVDs) has stimulated research for substances that could improve cardiovascular health. Among them, resveratrol (RES), a polyphenolic compound notably present in grapes and red wine, has been involved in the "French paradox". RES is known for its antioxidant and anti-inflammatory properties and for its ability to upregulate endothelial NO synthase (eNOS). RES was able to scavenge (•)OH/O₂(•-) and peroxyl radicals, which can limit the lipid peroxidation processes. Moreover, in bovine aortic endothelial cells (BAEC) under glucose-induced oxidati

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… In a recent study [ 51 ], RES alone has been shown to be ineffective at reducing blood pressure in 28 weeks old spontaneously hypertensive rats, but a combination of RES with hydralazine (a blood pressure lowering agent) was more effective than hydralazine alone in improving CV parameters. …

Pamidronate-induced irreversible symptomatic hypocalcemia in a dog with hypercalcemia after glucocorticoid withdrawal: a case report.

BACKGROUND: Pamidronate is used for the treatment of hypercalcemia. However, a rare but potential adverse event of pamidronate treatment is hypocalcemia. This report describes an unusual case of severe, irreversible hypocalcemia after a single injection of pamidronate for the treatment of hypercalcemia due to glucocorticoid withdrawal in a dog. CASE PRESENTATION: An 11-year-old castrated male Maltese dog presented with anorexia, vomiting, and diarrhea (day 0). The patient had calcinosis cutis throughout the body, calcification of intraabdominal organs, mild azotemia, and severe hypercalcemia.

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… Five hours later, systemic hypertension occurred (systemic blood pressure > 200 mmHg), and monitoring was continued using the Doppler method after administering hydralazine 0.5 mg/kg IV (Samjin Pharmaceutical, Seoul, Republic of Korea) and nitroprusside 0.5 µg/kg/min CRI (Nitropress, Pfizer, USA). …

SARC018_SPORE02: Phase II Study of Mocetinostat Administered with Gemcitabine for Patients with Metastatic Leiomyosarcoma with Progression or Relapse following Prior Treatment with Gemcitabine-Containing Therapy.

Histone deacetylase inhibitors (HDACi) can reverse chemoresistance, enhance chemotherapy-induced cytotoxicity, and reduce sarcoma proliferation in cell lines and animal models. We sought to determine the safety and toxicity of mocetinostat and its ability to reverse chemoresistance when administered with gemcitabine in patients with metastatic leiomyosarcoma resistant to prior gemcitabine-containing therapy. Participants with metastatic leiomyosarcoma received mocetinostat orally, 70 mg per day, three days per week, increasing to 90 mg after three weeks if well tolerated. Gemcitabine was admin

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… DNA methylation-independent reversion of gemcitabine resistance by hydralazine in cervical cancer cells PLoS One 2012 7 3 e29181 10.1371/journal.pone.0029181 2-s2.0-84858044285 PMC3299634 22427797 49 Donadelli M. Costanzo C. Beghelli S. …

Drugs and Epigenetic Molecular Functions. A Pharmacological Data Scientometric Analysis.

Interactions of drugs with the classical epigenetic mechanism of DNA methylation or histone modification are increasingly being elucidated mechanistically and used to develop novel classes of epigenetic therapeutics. A data science approach is used to synthesize current knowledge on the pharmacological implications of epigenetic regulation of gene expression. Computer-aided knowledge discovery for epigenetic implications of current approved or investigational drugs was performed by querying information from multiple publicly available gold-standard sources to (i) identify enzymes involved in c

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… | Major depression | [ 65 ] Fluoxetine | Serotonin reuptake pump of neuronal membranes | Induction of methyl-CpG-binding proteins | | [ 66 , 67 ] Gemcitabine | DNA repair machinery | Inhibition of DNA repair process and the associated demethylation process à DNA hypermethylation | Cancer | [ 68 ] Hydralazine … Hydralazine tar-get: From blood vessels to the epigenome. J. Transl. Med. 2006;4:10. doi: 10.1186/1479-5876-4-10. 70. Singh N., Duenas-Gonzalez A., Lyko F., Medina-Franco J.L. Molecular modeling and molecular dynamics studies of hy-dralazine with human DNA methyltransferase 1. …

Revitalizing Cancer Treatment: Exploring the Role of Drug Repurposing.

Cancer persists as a global challenge necessitating continual innovation in treatment strategies. Despite significant advancements in comprehending the disease, cancer remains a leading cause of mortality worldwide, exerting substantial economic burdens on healthcare systems and societies. The emergence of drug resistance further complicates therapeutic efficacy, underscoring the urgent need for alternative approaches. Drug repurposing, characterized by the utilization of existing drugs for novel clinical applications, emerges as a promising avenue for addressing these challenges. Repurposed d

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… Synergistic combination of doxorubicin with hydralazine, and disulfiram against MCF-7 breast cancer cell line. PLoS ONE. 2023;18:e0291981. doi: 10.1371/journal.pone.0291981. 33. Makena M.R., Ranjan A., Thirumala V., Reddy A.P. …