I onizing radiation is used to treat a variety of primary tumors, as well as to palliate metastatic disease. Dermatologists are no strangers to this modality of therapy and, since the discovery of x-rays by Roentgen in 1895, have incorporated radiation into their practice to treat malignant skin tumors, as well as benign skin diseases such as acne, eczema, and cutaneous fungal infections. In the past 30 years, other therapeutic modalities have largely supplanted radiation in the treatment of these benign disorders. Dermatologists today are more commonly called on to treat the cutaneous repercussions of radiation therapy (RT), which are a function of technique, target, total dose, volume, as well as individual variations. RT, either as monotherapy or in combination with other treatment modalities, is a powerful tool in tumor control, limited primarily by injury adjacent to normal tissue. Radiation-induced skin changes were recognized soon after the discovery of x-rays and were scientifically reported as early as 1902. Even when the skin is not the primary target, it may be injured as an ‘‘innocent bystander’’ and develop profound alterations on functional, gross, and molecular levels. This is not only true after therapeutic radiation, but also after interventional procedures. Serious radiationinduced skin injuries have been reported after unexpectedly high doses of kilovoltage irradiation exposure during fluoroscopic imaging, including cardiac catheterization. Increasingly sophisticated therapeutic regimens and modern equipment have improved the delivery and ameliorated, but not

https://www.jaad.org/article/S0190-9622(05)02707-6/pdf

Radiation dermatitis: Clinical presentation, pathophysiology, and treatment 2006

Between 100,000 and 170,000 patients with cancer develop central nervous system (CNS) metastases each year in the U.S., of which approximately 20% carry a primary diagnosis of breast cancer. As a consequence of improvements in systemic therapy, which have allowed patients to live longer with advanced cancer, CNS metastases are emerging as an important sanctuary site, and the incidence may be increasing in patients with particular tumor subtypes. Unless there are improvements in the treatment of CNS disease, a growing proportion of patients may be at risk of experiencing both morbidity and mortality as a result of uncontrolled CNS progression, often at a time when their extra-CNS disease is apparently under control. This article reviews changes in the epidemiology and natural history of women with brain metastases from HER2-positive breast cancer over the last decade and presents the therapeutic challenges and opportunities that have arisen in this setting. First, the apparent increase in CNS disease among women with HER2-positive breast cancer, relative to historical controls, is discussed, followed by consideration of potential causes of this observation. Next, the implications of CNS disease, in terms of prognosis and the potential development of preventive strategies are considered. Finally, new developments in systemic approaches to the treatment of CNS disease, including cytotoxic chemotherapy and targeted therapy, are explored.

https://clincancerres.aacrjournals.org/content/clincanres/13/6/1648.full.pdf

Brain Metastases: The HER2 Paradigm

The red swamp crayfish, Procambarus clarkii, native to northeastern Mexico and southcentral USA, is today the dominant macroinvertebrate in several European countries. While the first introduction of this species into Spain is well-documented, little is known about its pathways of invasion and the reason for its rapid spread in several European countries. Study of the biology of the species has revealed a number of properties that makes this crayfish a successful invader. Procambarus clarkii exhibits properties characteristic of an r-selected species, including early maturity at small body size, rapid growth rates, large numbers of offspring at a given parental size, and relatively short life spans. It is also plastic in its life cycle, able to disperse widely in the habitat and to tolerate environmental extremes. It displays generalist and opportunistic feeding habits, consuming macrophytes and preying on amphibians. Procambarus clarkii can also replace indigenous crayfish by a combination of mechanisms,...

/pdf/crayfish-invading-europe-the-case-study-of-procambarus-1usm484kdn.pdf

Crayfish invading Europe: the case study of Procambarus clarkii

BACKGROUND Cancer patients receive numerous medications, including antineoplastic agents, drugs for supportive care, and medications for comorbid illnesses. Therefore, they are at risk for drug interactions and duplicate prescribing. METHODS A questionnaire eliciting information on demographics and medications taken in the previous 4 weeks was given to adult outpatients receiving systemic anticancer therapy for solid tumors. The Drug Interaction Facts software, version 4.0, was used to identify potential drug interactions and to classify them by level of severity (major, moderate, or minor) and the strength of scientific evidence for them (using categories [1-5] of decreasing certainty). Summary statistics and logistic regression were used to analyze the data. All statistical tests were two-sided. RESULTS The survey was completed by 405 patients. We observed 276 potential drug interactions, and at least one potential interaction was identified in 109 patients (27%; 95% confidence interval [CI] = 23% to 31%). Of the potential interactions, 25 (9%) were classified as major and 211 (77%) as moderate. Nearly half (49%) of potential interactions were supported by level 1 or 2 scientific evidence. Most potential drug interactions (87%) involved non-anticancer agents such as warfarin, antihypertensive drugs, corticosteroids, and anticonvulsants, but some (n = 36, 13%) involved antineoplastic agents. In multivariable analysis, increased risk of receiving drug combinations in which there were potential drug interactions was associated with receipt of increasing numbers of drugs (odds ratio [OR] = 1.4 per additional drug, 95% CI = 1.26 to 1.58, P<.001 from the Wald chi-square test), type of medication (drugs to treat comorbid conditions versus supportive care medications only; OR = 8.6, 95% CI = 2.9 to 25, P<.001), and the presence of brain tumors. Thirty-two (8%) patients were exposed to duplicate medications, most often corticosteroids, proton pump inhibitors, or benzodiazepines. CONCLUSION Potential drug interactions were common among cancer patients and most often involved medications to treat comorbid conditions. Duplicate medications were infrequent.

/pdf/potential-drug-interactions-and-duplicate-prescriptions-1x4r9zrkqw.pdf

Potential Drug Interactions and Duplicate Prescriptions Among Cancer Patients

Drawing on a disparate set of naturalcultural phenomena from regenerative biology, quantum field theory, and queer and trans theories that include lightning, primordial ooze, frogs, bioelectricity, monstrosity, trans rage, virtual particles, and errant pathways, this article is about the materiality of political imageries and the possibilities for making queer alliance with nature’s nonessentialist nature. In particular, it makes an argument for the radically deconstructive, queer, and trans nature of nature, including nature’s own engagement with materialist practices of imagining.

TransMaterialities Trans*/Matter/Realities and Queer Political Imaginings

Characterizing the phenomenon of radiation recall dermatitis.

Try to put all images of crackling Van de Graaff generators and lumbering, moaning, bolt necked monsters from your mind. Nearly 200 years of oversimplification and spoofs have completely overshadowed the original version of this tale, first published in 1818. So let's set the record straight. While still a student of natural philosophy Victor Frankenstein had an epiphany—although its precise nature is never revealed. Through studying death and decay he discovers “the cause of generation and life,” becoming himself “capable of bestowing animation on lifeless matter.” Although now this would probably first be demonstrated on nematodes, then drosophila, Frankenstein goes straight for the big one: creating …

https://www.bmj.com/content/bmj/335/7620/617.2.full.pdf

Frankenstein: or, The Modern Prometheus

The discovery in 1988 of endothelin-1 (ET-1) by Yanagisawa and colleagues in Japan represented a landmark in the field of cardiovascular research.1 A combination of molecular and pharmacological approaches revealed ET-1 as the most powerful vasoconstrictor yet identified in biological systems. Since its discovery, a great deal of effort has been made towards gaining a better understanding of the key roles—developmental, physiological, and pathological—played by this peptide, particularly with regard to the cardiovascular system. In this review, we will describe current knowledge on the endothelin system and focus on the cardiovascular effects of ET-1 and its antagonism. We will review the evidence for the two therapeutic areas mainly investigated, pulmonary arterial hypertension and heart failure, as well as outline its important role in hypertension, renal dysfunction, and atherosclerosis.

### Endothelin synthesis and clearance

The endothelin family consists of three closely related peptides, ET-1, ET-2, and ET-3, each 21 amino acids in length and derived from separate genes. ET-1[1–21] is the main isoform produced in the cardiovascular system and about which most is known; ET-2 is mainly produced within the kidney and intestine, whereas ET-3 is predominantly found within the central nervous system (tables 1 and 2). However, the roles of ET-2 and ET-3, except in embryonic development, remain unclear.

View this table:

 Table 1 
 Sites of production of ET-1, ET-2, and ET-3



View this table:

 Table 2 
 Classification of endothelin receptors



ET-1 is not stored and released but instead generated in response to a range of stimuli, which vary between different tissues (fig 1).2 It is generated mainly in endothelial cells of blood vessels and requires several processing steps before the mature peptide is formed (fig 1). The final step in the ET-1 pathway involves cleavage of the 38 amino acid “big ET-1” by the highly selective membrane bound metalloproteinase, endothelin converting enzyme (ECE-1). ECE independent pathways of ET-1 formation have also …

https://heart.bmj.com/content/heartjnl/91/6/825.full.pdf

Endothelin antagonism in pulmonary hypertension, heart failure, and beyond

Purpose Clinical cases of capecitabine and other fluorouracil-based chemotherapies potentiating the effects of coumarin derivatives have been reported. This study assessed the influence of capecitabine on the pharmacokinetics (PK) and pharmacodynamics (PD) of warfarin. Patients and Methods Four patients with advanced/metastatic cancer completed the study, receiving a single oral dose of 20 mg warfarin before the start of standard capecitabine treatment (day 1), and again during the third cycle of capecitabine (day 61). PK parameters of warfarin and capecitabine and PD parameters of warfarin were assessed on days 1 and 61. Results During capecitabine treatment, the area under the plasma concentration time curve from 0 to infinity (AUC0-∞) of S-warfarin increased by 57% (90% CI, 32% to 88%) with a 51% prolongation of the elimination half-life (t1/2; 90% CI, 32% to 74%). Exposure to R-warfarin was not significantly affected. Plasma concentrations of capecitabine and its metabolites were not influenced by war...

https://ascopubs.org/doi/pdf/10.1200/JCO.2005.09.129

Ross Camidge

Papers

Characterizing the phenomenon of radiation recall dermatitis.

Frankenstein: or, The Modern Prometheus

Endothelin antagonism in pulmonary hypertension, heart failure, and beyond

Significant Effect of Capecitabine on the Pharmacokinetics and Pharmacodynamics of Warfarin in Patients With Cancer

Radiation recall dermatitis may represent the Koebner phenomenon.