Journal of Experimental Pathology

Fluoropyrimidines compose the backbone of regimens to treat many common solid tumors, including gastrointestinal (GI), breast and head/neck. As we continue to use these agents routinely, recognition of rare but real toxicities, such as cardiotoxicity, has also improved. The treatment options for patients who have encountered fluoropyrimidine-induced cardiotoxicity are limited as many anti-angiogenic drugs also pose a cardiac risk.

Worldwide, obesity is a public health concern and a metabolic ailment characterized by excessive adipose tissue accumulation resulting from an imbalance of energy expenditure and energy intake [1]. This disorder is a known risk factor for cardiovascular disease, type 2 diabetes mellitus, dyslipidemia, hypertension, and metabolic

Fluoropyrimidines have been extensively used for almost 6 decades to treat a variety of solid cancers, especially colon, gastric, anal, rectal, head & neck and breast. However, 31–34% of patients encountered grade 3–4 adverse events (AEs) with 0.5% mortality oftennecessitating dose reduction or discontinuation. A significant proportion of these AEs are likely to be the result of inter-individual genetic variation, in particularly such as dihydropyrimidine dehydrogenase (DPYD). DPYD gene encodes DPD, the rate-limiting enzyme responsible for catabolism of 5-FU and is responsible for >85% of 5-FU elimination.

Lower extremity fractures in individuals with a spinal cord injury (SCI) cause significant morbidity [1] and contribute to excess mortality [2]. Early identification of persons at highest risk for fracture is possible using bone mineral density (BMD) testing by dual-energy X-ray absorptiometry (DXA) imaging

Advances in oncology such as better access to health care system, earlier cancer diagnosis and new chemotherapies have led to longer survival of oncologic patients over the last decades. However, this population is vulnerable to cardiovascular drug-related adverse events like cardiomyopathy, which leads to heart failure and impairs survival and quality of life.

Immune checkpoint inhibitor (ICI)-associated cardiotoxicity is a rare immune-related adverse event with high mortality. In recent years, more and more reports were reported. It is urgent to improve understanding and management. Cardiac toxicity often occurs in the early stage after ICI treatment, and its clinical manifestations are diverse and nonspecific, and its pathogenesis is still unclear. Among them, the incidence of immune myocarditis is more than 1%, which can be manifested as fulminant, acute or chronic.

Recently we published the article ‘Accumulation of protoporphyrin IX in medulloblastoma cell lines and sensitivity to subsequent photodynamic treatment’. In this commentary, we review protoporphyrin IX accumulation after application of 5-aminolaevulinic acid and the resulting sensitivity of medulloblastoma cells to photodynamic therapy. We compare the results to glioblastoma cells, including glioblastoma stem-like cells, and address the contribution of the transporter adenosine triphosphate binding cassette subfamily G member 2 (ABCG2) as well as the enzyme ferrochelatase to the process.

In the peripheral nervous system (PNS), Schwann cells (SCs) are responsible for myelin production, which contributes to axonal protection and allows for efficient action potential transmission. Unfortunately, acquired and hereditary demyelinating diseases of the PNS are numerous and affect an increasing number of people.

Head and neck squamous cell carcinomas (HNSCCs) are a group of aggressive and genetically complex cancers, derived from the mucosal epithelium in the oral cavity, pharynx, and larynx. Radiotherapy, often combined with chemotherapy remains the mainstay treatment options for patients.

The western diet and overuse of anti-inflammatory medication have caused a great deal of stress on the liver. Obesity and the associated inflammatory state in insulin-responsive tissues result in the release of pro-inflammatory cytokine that activates the stress-responsive MAPKs, p38 MAPK, and JNK. These MAPKs have figured prominently as critical effectors in physiological and pathophysiological hepatic inflammation.

Inhalational anaesthetics have been used for induction and maintenance of general anaesthesia for more than 150 years. In human medicine desflurane, sevoflurane, and isoflurane are commonly used.

Sepsis is highly prevalent, and is one of the main causes of mortality among hospitalized patients. Ethanol consumption in large quantities compromises the normal functioning of the body, leading to dysfunction of multiple different organ systems. The association between sepsis and ethanol is not fully understood, but it is well accepted that ethanol

Cardiotoxicity is a well-known side-effect for the patients who are treated with different classes of anticancer drugs. In order to prevent potential drug-induced adverse effects, it is crucial to develop predictable human-based models and assays for drug screening. To that end, human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are becoming promising and important for disease modeling and drug-induced toxicity screening.

The Germ Theory of Disease was solidified in the 19^th century by Louise Pasteur and Robert Koch. They systematically visualized, isolated, and quantified microscopic pathogens as causative agents of diseases and epidemics. Viruses are submicroscopic; therefore, they were discovered later as pathogens by indirect methods.

Until recently, oral glucocorticoid (GC) therapies were the mainstay of treatment for uncontrolled inflammatory disease across many body systems. The last 30 years, however, have witnessed a transformation in the management of many diseases due to the development of targeted biological agents leading to a reduction, albeit not a removal, of the dependence on oral GCs.

Neuroblastoma is derived from the developing sympathetic nervous system and is the most common extracranial solid tumor of childhood.

Tenofovir disoproxil fumarate (TDF) is one of the main antiretroviral drugs of people living with human immunodeficiency virus (PLWHIV). Despite its efficacy and tolerability, there is conflicting evidence regarding TDF-associated nephrotoxicity, which is proposed to cause injury by accumulation of tenofovir (TFV) within proximal tubular cells leading to mitochondrial injury and tissue hypoxia. 

A role for oxidative stress in the etiology of myriad neuropathologies is well accepted. However, the specific effects of oxidative DNA damage in the onset or promotion of neuronal dysfunction have been less studied. In our recent publication by Behrouzi et al. (Oxidative DNA Damage and Cisplatin Neurotoxicity Is Exacerbated by Inhibition of OGG1 Glycosylase Activity and APE1 Endonuclease Activity in Sensory Neurons), inhibition of enzymes that play a role in repairing oxidative DNA damage exacerbated neurotoxic effects of the chemotherapeutic agent, cisplatin. 

Stroke is the second largest cause of death worldwide, with a world annual mortality incidence of about 5.5 million people, and it is also the leading cause of disability worldwide with 50% of survivors being chronically disabled.

Twenty-five percent of small molecules in drug development for CNS indications fail in clinical trials due to complications with neurotoxicity. Unfortunately, this is not discovered earlier. Indeed, it is very infrequent that a drug is flagged for neurotoxic side effects in early drug discovery (1). The consequences are two-fold: 1) loss of time and money in bringing new drugs to market and, 2) the unwitting exposure of patents in clinical trials to the neurotoxic side effects of what otherwise could be a drug candidate that is effectively treating the problem.