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Lomitapide repurposing for treatment of malignancies: A promising direction.

The development of novel drugs from basic science to clinical practice requires several years, much effort, and cost. Drug repurposing can promote the utilization of clinical drugs in cancer therapy. Recent studies have shown the potential effects of lomitapide on treating malignancies, which is currently used for the treatment of familial hypercholesterolemia. We systematically review possible functions and mechanisms of lomitapide as an anti-tumor compound, regarding the aspects of apoptosis, autophagy, and metabolism of tumor cells, to support repurposing lomitapide for the clinical treatme

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… In addition, AMPK also increases the utilization of cellular stored lipids through activating lipases and stimulating the release of fatty acids [ 99 ]. …

Why do patients with cancer die?

Cancer is a major cause of global mortality, both in affluent countries and increasingly in developing nations. Many patients with cancer experience reduced life expectancy and have metastatic disease at the time of death. However, the more precise causes of mortality and patient deterioration before death remain poorly understood. This scarcity of information, particularly the lack of mechanistic insights, presents a challenge for the development of novel treatment strategies to improve the quality of, and potentially extend, life for patients with late-stage cancer. In addition, earlier depl

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… Lipid metabolism is impacted by TNFα reducing the expression of lipoprotein lipase and free fatty acid transporters, thereby reducing the accumulation of fat ( 133 ). TNFα can also reduce appetite through the production of corticotropin-releasing hormone [G] (CRH). …

Abstracts of the 3rd International Conference on Cancer Cachexia, September 23–25, 2016 in Washington, DC, USA

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… This study was designed to determine whether C‐26 modulates the regulation of insulin secretion and pancreatic lipase (Pnlip), factors that can modify, and are themselves affected by glucose levels. …

Obesity, inflammation, and cancer in dogs: Review and perspectives.

Obesity is the most common nutritional disease in dogs, and its prevalence has increased in recent decades. Several countries have demonstrated a prevalence of obesity in dogs similar to that observed in humans. Chronic low-grade inflammation is a prominent basis used to explain how obesity results in numerous negative health consequences. This is well known and understood, and recent studies have pointed to the association between obesity and predisposition to specific types of cancers and their complications. Such elucidations are important because, like obesity, the prevalence of cancer in

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… A study with mice with hepatocellular carcinoma was able to identify that the oncogenes Carboxyl ester lipase (Cel) gene and Harvey rat sarcoma virus oncogene 1 (Hras) had a higher frequency of mutations in obese mice when compared to lean mice ( 149 ). …

Clinical development of gene therapy: results and lessons from recent successes.

Therapeutic gene transfer holds the promise of providing lasting therapies and even cures for diseases that were previously untreatable or for which only temporary or suboptimal treatments were available. For some time, clinical gene therapy was characterized by some impressive but rare examples of successes and also several setbacks. However, effective and long-lasting treatments are now being reported from gene therapy trials at an increasing pace. Positive outcomes have been documented for a wide range of genetic diseases (including hematological, immunological, ocular, and neurodegenerativ

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… Approval of the first-gene therapy product Glybera, an AAV vector for treatment of lipoprotein lipase deficiency, by the European Medicines Agency was an important first step in gene-based drug development. 6 Recent breakthroughs in clinical gene therapy trials have now emerged in a variety of monogenic …

Curcumin as a promising therapeutic agent for diabetic neuropathy: from molecular mechanisms to functional recovery.

Diabetes mellitus is an endocrine disorder characterized by prolonged hyperglycemia. It results from either insulin deficiency (type 1 diabetes mellitus, T1DM) or insulin resistance (type 2 diabetes mellitus, T2DM). This condition has emerged as a significant health concern in recent years. Hyperglycemia induces the overproduction of reactive oxygen species (ROS), which can modulate multiple pathways, including AGEs-RAGE, PKC stimulation, NF-κB and PI3K/AKT. These pathways contribute to diabetes-related complications such as inflammation, oxidative stress, insulin resistance, and reduced gluco

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… Reduced inhibition of hormone-sensitive lipase in adipocytes leads to the continuous release of FFAs [ 71 ]. … These clinical benefits are supported by curcumin’s broader metabolic effects, including improvements in insulin resistance (HOMA-IR), serum FFAs, and lipoprotein lipase activity in patients with T2DM [ 216 ]. …

Curcumin Rewires the Tumor Metabolic Landscape: Mechanisms and Clinical Prospects.

Metabolic reprogramming is a fundamental hallmark and a key driver of malignant tumors. By reshaping glucose, lipid, and amino acid metabolism, as well as mitochondrial function, it sustains the abnormal proliferation and survival of tumor cells, making it a crucial target for anti-tumor therapy. Curcumin, a natural multi-target compound, exhibits unique advantages in intervening in tumor metabolic reprogramming due to its low toxicity and broad-spectrum regulatory properties. In various tumor models, it can directly modulate the activity of key glycolytic enzymes, such as hexokinase 2, lactat

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… It also downregulates the expression of key lipolysis proteins, including hormone-sensitive lipase (HSL), adipose triglyceride lipase (ATGL), and uncoupling protein 1 (UCP1), while reversing the cachexia-induced downregulation of FASN. …

Antibody-Drug Conjugates: Pharmacotherapeutic Properties and Future Perspectives.

Background: The clinical landscape for antibody-drug conjugates (ADCs) is currently experiencing an unprecedented expansion, with more than 20 agents approved to date and hundreds presently under clinical evaluation, underscoring their growing impact in precision oncology. By combining the cytotoxic potency of chemotherapy with the selectivity of monoclonal antibodies, ADCs have redefined targeted cancer therapy. Nevertheless, challenges related to toxicity, resistance, and suboptimal drug delivery continue to limit their full clinical potential. Objectives: This review provides a comprehensiv

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… reproductive toxicity | Due to elevated risk of infections and hemorrhagic reactions, patients should undergo complete blood count prior to each administration | [ 64 , 65 ] Inotuzumab ozogamicin | Hepatotoxicity (especially, VOD/SOS), myelosuppression, QT interval prolongation, TLS and increased amylase and lipase …

Recent Progress of CircRNAs in Hematological Malignancies.

Circular RNAs (circRNAs) are now recognized as key regulators in the epigenetic control of genetic expression, being involved in a wide range of cellular activities such as proliferation, differentiation, and apoptosis. Their unique closed-loop structure endows them with stability and resistance to exonuclease degradation, making them not only key regulatory molecules within the cell but also promising biomarkers for disease diagnosis and prognosis, particularly in hematological malignancies. This review comprehensively explores the role of circRNAs in the pathogenesis, progression, and therap

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… CircRIC8B acted as a sponge for miR-199b-5p, preventing it from reducing lipoprotein lipase (LPL) mRNA levels. Furthermore, ezetimibe inhibited the development of CLL cells and reduced LPL mRNA expression 93 . …

Cancer Cell Metabolism in Hypoxia: Role of HIF-1 as Key Regulator and Therapeutic Target.

In order to meet the high energy demand, a metabolic reprogramming occurs in cancer cells. Its role is crucial in promoting tumor survival. Among the substrates in demand, oxygen is fundamental for bioenergetics. Nevertheless, tumor microenvironment is frequently characterized by low-oxygen conditions. Hypoxia-inducible factor 1 (HIF-1) is a pivotal modulator of the metabolic reprogramming which takes place in hypoxic cancer cells. In the hub of cellular bioenergetics, mitochondria are key players in regulating cellular energy. Therefore, a close crosstalk between mitochondria and HIF-1 underl

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… As a consequence of HIG2 upregulation, the adipose triglyceride lipase (ATGL) is inhibited, resulting in impairment of intracellular lipolysis in various cancer cells [ 80 ]. Another aspect of lipid metabolism concerns the lipid droplets’ composition. …

Can Hemp Help? Low-THC Cannabis and Non-THC Cannabinoids for the Treatment of Cancer.

Cannabis has been used to relieve the symptoms of disease for thousands of years. However, social and political biases have limited effective interrogation of the potential benefits of cannabis and polarised public opinion. Further, the medicinal and clinical utility of cannabis is limited by the psychotropic side effects of ∆9-tetrahydrocannabinol (∆9-THC). Evidence is emerging for the therapeutic benefits of cannabis in the treatment of neurological and neurodegenerative diseases, with potential efficacy as an analgesic and antiemetic for the management of cancer-related pain and treatment-r

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… Both AEA and 2-AG are derived from the non-oxidative metabolism of membrane phospholipids [ 42 ], with AEA degraded by the fatty acid amide hydrolase (FAAH) [ 40 ], whereas the monoacylglycerol lipase (MAGL) enzyme is primarily responsible for terminal 2-AG degradation [ 43 ]. pCBs (or simply cannabinoids …

Biomarkers in the diagnosis of lysosomal storage disorders: proteins, lipids, and inhibodies.

A biomarker is an analyte indicating the presence of a biological process linked to the clinical manifestations and outcome of a particular disease. In the case of lysosomal storage disorders (LSDs), primary and secondary accumulating metabolites or proteins specifically secreted by storage cells are good candidates for biomarkers. Clinical applications of biomarkers are found in improved diagnosis, monitoring disease progression, and assessing therapeutic correction. These are illustrated by reviewing the discovery and use of biomarkers for Gaucher disease and Fabry disease. In addition, rece

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… Adult cholesteryl ester storage disease (CESD) with anemia, mesenteric lipodystrophy, increased plasma chitotriosidase activity and a homozygous lysosomal acid lipase -1 exon 8 splice junction mutation J Hepatol 1999 31 741 746 10551400 10.1016/s0168-8278(99)80356-0 Wennekes T van den Berg RJ Boot RG …

Mechanisms of spinal glial activation in chemotherapy-induced peripheral neuropathy: Focus on microglia and astrocytes.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common complication in patients with malignant tumors during chemotherapy. The pathological mechanisms of CIPN remain unclear, and effective preventive and therapeutic strategies are still lacking, posing a major challenge in clinical practice. Aberrant activation of spinal glial cells, particularly microglia and astrocytes, is a key pathological hallmark of CIPN. Evidence from multiple animal models supports a causal link between glial activation and CIPN, suggesting that glial cells may serve as potential therapeutic targets. However, ow

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… Microglia | Syringaresinol | [ 79 ] | Bortezomib | Astrocyte | Thalidomide and IL‐1ra | [ 80 ] Endocannabinoid system | Paclitaxel | Microglia | Cannabidiol | [ 81 ] | | Both | Hyperbaric oxygen | [ 82 ] | Cisplatin | Both | JZL195 (a dual inhibitor of fatty acid amide hydrolase and monoacylglycerol lipase …

The Role of Progranulin (PGRN) in the Pathogenesis of Glioblastoma Multiforme.

Glioblastoma multiforme (GBM) represents the most common and aggressive malignant form of brain tumour in adults and is characterized by an extremely poor prognosis with dismal survival rates. Currently, expanding concepts concerning the pathophysiology of GBM are inextricably linked with neuroinflammatory phenomena. On account of this fact, the identification of novel pathomechanisms targeting neuroinflammation seems to be crucial in terms of yielding successful individual therapeutic strategies. In recent years, the pleiotropic growth factor progranulin (PGRN) has attracted significant atten

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… Sortilin/Neurotensin Receptor-3 Binds and Mediates Degradation of Lipoprotein Lipase. J. Biol. Chem. 1999;274:8832–8836. doi: 10.1074/jbc.274.13.8832. 51. Tang W., Lu Y., Tian Q.-Y., Zhang Y., Guo F.-J., Liu G.-Y., Syed N.M., Lai Y., Lin E.A., Kong L., et al. …

Obesity and Cancer: A Current Overview of Epidemiology, Pathogenesis, Outcomes, and Management.

BackgroundObesity or excess body fat is a major global health challenge that has not only been associated with diabetes mellitus and cardiovascular disease but is also a major risk factor for the development of and mortality related to a subgroup of cancer. This review focuses on epidemiology, the relationship between obesity and the risk associated with the development and recurrence of cancer and the management of obesity.MethodsA literature search using PubMed and Google Scholar was performed and the keywords 'obesity' and cancer' were used. The search was limited to research papers publish

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… antagonist/dopamine and noradrenaline reuptake inhibitor causing appetite suppression | 32 mg/360 mg oral twice daily | dose dependent 1.3% to 6.1% | headaches, hypertension, sleep disorders, nausea, constipation, vomiting, diarrhea, palpitation, dizziness, tremor, and others Orlistat | Pancreatic lipase …

Acute Generalized Exanthematous Pustulosis: Clinical Features, Differential Diagnosis, and Management.

Acute generalized exanthematous pustulosis (AGEP) is a rare, acute, severe cutaneous adverse reaction mainly attributed to drugs, although other triggers, including infections, vaccinations, ingestion of various substances, and spider bites, have also been described. AGEP is characterized by the development of edema and erythema followed by the eruption of multiple punctate, non-follicular, sterile pustules and subsequent desquamation. AGEP typically has a rapid onset and prompt resolution within a few weeks. The differential diagnoses for AGEP are broad and include infectious, inflammatory, a

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… .) | CBC with diff and direct smear (atypical lymphocytes, eosinophilia), ESR, CRP, CMP (LFTs, creatinine), lipase, amylase, CK, troponin, urinary protein and cells, PCR for HHV6, HHV7, CMV, EBV | Patients with genetic predisposition and possible concurrent viral disease | Many cases, for example AGEP …

Adding recombinant AAVs to the cancer therapeutics mix.

Gene therapy is a powerful biological tool that is reshaping therapeutic landscapes for several diseases. Researchers are using both non-viral and viral-based gene therapy methods with success in the lab and the clinic. In the cancer biology field, gene therapies are expanding treatment options and the possibility of favorable outcomes for patients. While cellular immunotherapies and oncolytic virotherapies have paved the way in cancer treatments based on genetic engineering, recombinant adeno-associated virus (rAAV), a viral-based module, is also emerging as a potential cancer therapeutic thr

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… | patient CD34 + cells transduced with corrected ADA sequence then infused back into patient 76 Abecma | CAR-T Cells | relapsed/refractory multiple myeloma | CAR-T cells recognize MM via BCMA targeting, leads to CAR-T activation, then targeted destruction of MM 49 Glybera (EU) | rAAV1 | lipoprotein lipase …

Р

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… pancreatin [ pan′kre- -tin ] a substance from the pancreas of the pig or ox containing digestive enzymes, principally amylase, protease, and lipase; used in the treatment of pancreatic exocrine insufficiency. … pancrelipase [ pan″kre-li′pās ] a preparation of pig pancreas containing enzymes, principally lipase with amylase and protease, having the same digestive actions as pancreatic juice; used in the treatment of exocrine pancreatic insufficiency. …

BCL-2 and BCL-xL in Cancer: Regulation, Function, and Therapeutic Targeting.

The BCL-2 family of proteins plays a central role in the regulation of apoptosis, with BCL-2 and BCL-xL representing two of its most prominent antiapoptotic members. This review explores the molecular regulation of BCL-2 and BCL-xL genes, emphasizing the structural domains that define the functions of the broader BCL-2 family. Beyond their canonical roles in preventing mitochondrial outer membrane permeabilization, both proteins contribute significantly to cancer development. Their overexpression enhances invasiveness and tumor progression, supports angiogenesis, and critically modulates cellu

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… In SCLC and other solid tumors, Navitoclax induced partial responses or stable disease in a minority of patients, though severe adverse events (AEs) such as fatal respiratory failure, left ventricular systolic dysfunction, and asymptomatic lipase elevation were occasionally reported [ 308 ]. … Serious AEs were reported in 3 patients (fatal respiratory failure, left ventricular systolic dysfunction and asymptomatic lipase elevation). | [ 324 ] Relapsed or refractory CLL | Navitoclax | Phase I | Among 29 patients, 7 achieved stable disease and 9 had a partial response. …

A comprehensive review on pain: Model, target, therapy, and prospect (Review).

Pain serves as both a protective physiological response essential for species survival and a global health issue affecting human well‑being and societal development. The present review systematically summarized and analyzed the research progresses on pain through a multidimensional analytical framework encompassing animal models, molecular targets, therapeutic approaches and future prospects. In animal modeling, neuropathic pain paradigms have evolved from traditional mechanical compression to composite models that combine dynamic displacement and chemical stimulation. Cancer‑induced pain mode