Doctors occasionally make diagnoses in strangers outside of formal medical settings by using the medical skill of visual inspection, such as noticing signs of melanoma or the symptoms of hyperthyroidism. This may cause considerable moral unease and doubts on the side of the diagnosing physician. Such encounters force physicians to consider whether or not to intervene by introducing themselves to the stranger and offering an unsolicited medical opinion despite the absence of a formal doctor-patient relationship. A small body of (...) literature has addressed the topic of the unsolicited medical opinion, often with a primary focus on practical advice. This article seeks to establish an ethical-theoretical basis for physicians' ethical obligation to offer an unsolicited medical opinion when they make a diagnosis by visual inspection in a stranger outside of the formal medical context. Using a utilitarian approach, it is argued that, if it is in the physicians' power to prevent a possible loss of well-being, without thereby sacrificing anything of equal value, physicians have an ethical obligation to intervene. (shrink)

In this article, I begin by giving a brief history of melanoma causation. I then discuss the current manner in which malignant melanoma is classified. In general, these systems of classification do not take account of the manner of tumour causation. Instead, they are based on phenomenological features of the tumour, such as size, spread, and morphology. I go on to suggest that misclassification of melanoma is a major problem in clinical practice. I therefore outline an alternative (...) means of classifying these tumours based on causal factors. By analogy with similar systems that have recently emerged for other cancers, I suggest that this causal classification is likely to be both workable and helpful, even in the absence of a full causal-mechanistic understanding of the aetiology of the tumour. (shrink)

Cancer is one of the most frequent fatal human diseases. It is a genetic disease, and molecular analysis of the genes involved revealed that they belong to several distinct classes of molecules, one of which is the receptor tyrosine kinases. Neoplastic transformation is regarded as the result of a multistep process and, in most cases, it is hard to evaluate what the initial events in tumor formation are. What makes it difficult to approach this question is the paucity of animal (...) models for tumorigenesis allowing investigation of the mechanisms leading to uncontrolled cell proliferation. Melanoma formation in Xiphophorus is one of these model systems. Here, overexpression and activation of a receptor tyrosine kinase causes neoplastic transformation of pigment cells. Xiphophorus provides all the advantages of a well‐characterised genetic system. In addition, some crucial components of the transformation pathway have been identified at the molecular level. As a vertebrate, Xiphophorus might serve as a model system to aid understanding, in more general terms, of the mechanisms of tumorigenesis in human diseases. (shrink)

Modeling metastasis in animal systems has been an important focus for developing cancer therapeutics. Xenopus laevis is a well‐established model, known for its use in identifying genetic mechanisms underlying diseases and disorders in humans. Prior literature has suggested that the drug, ivermectin, can be used in Xenopus to induce melanocytes to convert into a metastatic melanoma‐like state, and thus could be ideal for testing possible melanoma therapies in vivo. However, there are notable inconsistencies between ivermectin studies in Xenopus (...) and the application of ivermectin in mammalian systems, that are relevant to cancer and melanoma research. In this review, we examine the ivermectin‐induced phenotypes in Xenopus, and we explore the current uses of ivermectin in human research. We conclude that while ivermectin may be a useful drug for many biomedical purposes, it is not ideal to induce a metastatic melanocyte phenotype in Xenopus for testing the effects of potential melanoma therapeutics. (shrink)

The complexity of intracellular molecular pathways can be simplified by the use of Network Biology that breaks down the intricacy of biological processes into components and interactions among them. In the paper we show that any complex interactome, that is, a biological network representing protein-protein, protein-DNA and DNA-RNA interactions, can be decomposed into a conjunction of logical theorems expressed in terms of Zsyntax, a formal language which allows representing biological pathways. This result, illustrated with the case study of melanoma (...) network, opens the possibility for a computable model of the cell expressed in a logical language and shows how a formal way of intending philosophy can be useful to cope with the complexity of the biological world. (shrink)

Recently, we reported that melanoma risk in redheads is linked not only to pale skin, but also to the synthesis of the pigment – called pheomelanin – that gives red hair its color. We demonstrated that pheomelanin synthesis is associated with increased oxidative stress in the skin, yet we have not uncovered the chemical pathway between the molecule pheomelanin and the DNA damage that drives melanoma formation. Here, we hypothesize two possible pathways. On one hand, pheomelanin might generate (...) reactive oxygen species (ROS) that directly or indirectly cause oxidative DNA damage. On the other hand, pheomelanin synthesis might consume cellular antioxidant stores and make the cell nucleus more vulnerable to other endogenous ROS. Uncovering the mechanistic pathway between pheomelanin and oxidative DNA damage will be an important step in developing strategies to lower melanoma risk in redheads. (shrink)

Somatic mutations arising in human skin cancers are heterogeneously distributed across the genome, meaning that certain genomic regions (e.g., heterochromatin or transcription factor binding sites) have much higher mutation densities than others. Regional variations in mutation rates are typically not a consequence of selection, as the vast majority of somatic mutations in skin cancers are passenger mutations that do not promote cell growth or transformation. Instead, variations in DNA repair activity, due to chromatin organization and transcription factor binding, have been (...) proposed to be a primary driver of mutational heterogeneity in melanoma. However, as discussed in this review here, recent studies indicate that chromatin organization and transcription factor binding also significantly modulate the rate at which UV lesions form in DNA. The authors propose that local variations in lesion susceptibility may be an important driver of mutational hotspots in melanoma and other skin cancers, particularly at binding sites for ETS transcription factors. (shrink)

Machine‐learning algorithms have the potential to revolutionise diagnostic and prognostic tasks in health care, yet algorithmic performance levels can be materially worse for subgroups that have been underrepresented in algorithmic training data. Given this epistemic deficit, the inclusion of underrepresented groups in algorithmic processes can result in harm. Yet delaying the deployment of algorithmic systems until more equitable results can be achieved would avoidably and foreseeably lead to a significant number of unnecessary deaths in well‐represented populations. Faced with this dilemma (...) between equity and utility, we draw on two case studies involving breast cancer and melanoma to argue for the selective deployment of diagnostic and prognostic tools for some well‐represented groups, even if this results in the temporary exclusion of underrepresented patients from algorithmic approaches. We argue that this approach is justifiable when the inclusion of underrepresented patients would cause them to be harmed. While the context of historic injustice poses a considerable challenge for the ethical acceptability of selective algorithmic deployment strategies, we argue that, at least for the case studies addressed in this article, the issue of historic injustice is better addressed through nonalgorithmic measures, including being transparent with patients about the nature of the current epistemic deficits, providing additional services to algorithmically excluded populations, and through urgent commitments to gather additional algorithmic training data from excluded populations, paving the way for universal algorithmic deployment that is accurate for all patient groups. These commitments should be supported by regulation and, where necessary, government funding to ensure that any delays for excluded groups are kept to the minimum. We offer an ethical algorithm for algorithms—showing when to ethically delay, expedite, or selectively deploy algorithmic systems in healthcare settings. (shrink)

Long non‐coding RNAs (lncRNAs) have recently gained increasing attention because of their crucial roles in gene regulatory processes. Functional studies using mammalian skin as a model system have revealed their role in controlling normal tissue homeostasis as well as the transition to a diseased state. Here, we describe how lncRNAs regulate differentiation to preserve an undifferentiated epidermal progenitor compartment, and to maintain a functional skin permeability barrier. Furthermore, we will reflect on recent work analyzing the impact of lncRNAs on the (...) progression from normal epithelium to the development of skin disorders and cancer. (shrink)

The twenty‐six‐year‐old patient requested a prophylactic bilateral mastectomy with reconstruction because of an extensive family history of cancer. She reported that she had developed melanoma at twenty‐five; that her mother, sister, aunts, and a cousin all had breast cancer; that a cousin had ovarian cancer at nineteen; and that a brother was treated for esophageal cancer at fifteen. The treating team was skeptical about this history, and they could find no documentation of the patient's reported melanoma. The surgeon (...) wrote the patient's primary care physician, explaining that he had seen the patient and planned to proceed with the bilateral mastectomy and reconstruction. The primary care physician responded that he was unable to substantiate several of the patient's claims; some of his colleagues believed the family history to be fabricated. Trying to make sense of the discrepancies, the genetic counselor called a counselor colleague who had met with this patient. The colleague suggested that the in‐house genetic counselor “google” the patient. The search revealed two Facebook pages linked to the patient. In one, apparently a personal profile, the patient stated that in addition to battling stage four melanoma, she had recently been diagnosed with breast cancer. She provided a link to a site where she solicited donations to attend a summit for young cancer patients. The other Facebook page featured numerous pictures of her with a bald head, as though she has been through chemotherapy. The genetic counselor showed the Facebook pages to the surgeon, who then decided not to operate. Should health care professionals “google” their patients? (shrink)

The use of tanning beds has been identified as being among the most significant causes of melanoma and non-melanoma skin cancer. Accordingly, the activity is properly seen as one that involves profound harm to self. The article examines paternalistic reasons for restricting sunbed usage. We argue that both so-called soft and hard paternalistic arguments support prohibiting the use of sunbeds. We make the following three arguments: an argument from oppressive patterns of socialization suggesting that the autonomous nature of (...) the conduct in question is questionable; an argument from so-called evaluative delusions in which individuals attach incorrect weights to some of their values; a strictly hard paternalistic argument appealing to the harm in itself pertaining to the use of sunbeds. (shrink)

At the Liverpool Ocular Oncology Centre (LOOC), patients with an eye tumour are offered rapid treatment. Procedures such as enucleation (surgical removal of the eye) are usually performed within 24 hours of initial assessment. Such expedited treatment can be challenged on the basis that it is incompatible with valid consent. We present the results of a questionnaire audit exploring the views of patients on how long they waited to undergo invasive procedures for intraocular melanoma. The findings inform a discussion (...) of three plausible reasons for doubting the validity of consent to rapid intervention: the distress of diagnosis may temporarily undermine patients' capacity to choose; the decision may be too complex to make quickly; and rapid availability of treatment may be unduly influential, undermining the voluntariness of the decision. Using the example of enucleation, we argue that, with adequate safeguards, rapid intervention does not undermine the validity of patients' consent. (shrink)

The nm23 gene, a putative metastasis suppressor gene, was originally identified by its reduced expression in highly metastatic K‐1735 murine melanoma cell lines, as compared to related, low metastatic melanoma cell lines. Transfection of nm23 cDNA has been reported to suppress malignant progression in Drosophila and mammalian cells. Highly conserved homologues of nm23 have been found in organisms ranging from the prokaryote Myxococcus xanthus to Drosophila, where the gene is involved in normal development and differentiation. The product of (...) the nm23 gene exhibits a nucleoside diphosphate kinase activity, yet the nucleoside diphosphate kinase activity of Nm23 does not correlate with its apparent biological functions. We review recent cellular, genetic, biochemical and X‐ray crystallographic data to formulate and evaluate hypotheses concerning the molecular mechanism of nm23 action. (shrink)

The use of human tissue for scientific research is a highly sensitive issue. A lack of confidence in patient recruitment is one reason for the failure of many studies to be funded and it is important therefore that recruitment procedures are as effective and sympathetic as possible. The authors recruited patients with uveal melanoma into a postmortem study investigating tumour latency in this cancer. Two approaches were used—firstly a direct approach when patients attended clinic and secondly an initial approach (...) by mail followed by telephone contact. In the first year of study the authors had a take up rate of 88.5%, significantly higher than the average rate of 40% quoted by the National Institute for Clinical Excellence . Key features are a sympathetic personal approach by experienced oncology nurses, the provision of clear information, and the inclusion of the next of kin in the recruitment procedure. (shrink)

In both academic literature and the media, financial conflicts of interest in human subjects research have come center-stage. The cover of a recent edition of Time magazine features a research subject in a cage with the caption human guinea pigs, signifying perhaps that human research subjects are no more protected from research abuses than are laboratory animals. That magazine issue highlights three well-publicized cases of human subjects research violations that occurred at the University of Oklahoma, the University of Pennsylvania, and (...) Johns Hopkins University.At St. John Medical Center in Tulsa, Oklahoma, a study that was co-sponsored by the University of Oklahoma Health Sciences Center investigated an experimental vaccine for malignant melanoma. In that case, the chair of the university's institutional review board — the committee within each medical institution charged with ethics review of human research projects undertaken at that institution — and the dean of the University's College of Medicine allegedly concealed from both the IRB and the United States Food and Drug Administration a report by an outside consulting firm that had found severe deficiencies with the melanoma vaccine study being conducted at the medical center. (shrink)

In both academic literature and the media, financial conflicts of interest in human subjects research have come center-stage. The cover of a recent edition of Time magazine features a research subject in a cage with the caption human guinea pigs, signifying perhaps that human research subjects are no more protected from research abuses than are laboratory animals. That magazine issue highlights three well-publicized cases of human subjects research violations that occurred at the University of Oklahoma, the University of Pennsylvania, and (...) Johns Hopkins University.At St. John Medical Center in Tulsa, Oklahoma, a study that was co-sponsored by the University of Oklahoma Health Sciences Center investigated an experimental vaccine for malignant melanoma. In that case, the chair of the university's institutional review board — the committee within each medical institution charged with ethics review of human research projects undertaken at that institution — and the dean of the University's College of Medicine allegedly concealed from both the IRB and the United States Food and Drug Administration a report by an outside consulting firm that had found severe deficiencies with the melanoma vaccine study being conducted at the medical center. (shrink)

The twenty‐six‐year‐old patient requested a prophylactic bilateral mastectomy with reconstruction because of an extensive family history of cancer. She reported that she had developed melanoma at twenty‐five; that her mother, sister, aunts, and a cousin all had breast cancer; that a cousin had ovarian cancer at nineteen; and that a brother was treated for esophageal cancer at fifteen. The treating team was skeptical about this history, and they could find no documentation of the patient's reported melanoma. The surgeon (...) wrote the patient's primary care physician, explaining that he had seen the patient and planned to proceed with the bilateral mastectomy and reconstruction. The primary care physician responded that he was unable to substantiate several of the patient's claims; some of his colleagues believed the family history to be fabricated. Trying to make sense of the discrepancies, the genetic counselor called a counselor colleague who had met with this patient. The colleague suggested that the in‐house genetic counselor “google” the patient. The search revealed two Facebook pages linked to the patient. In one, apparently a personal profile, the patient stated that in addition to battling stage four melanoma, she had recently been diagnosed with breast cancer. She provided a link to a site where she solicited donations to attend a summit for young cancer patients. The other Facebook page featured numerous pictures of her with a bald head, as though she has been through chemotherapy. The genetic counselor showed the Facebook pages to the surgeon, who then decided not to operate. Should health care professionals “google” their patients? (shrink)

Over the last few years, oncolytic virus therapy has been recognised as a promising approach in cancer treatment, due to the potential of these viruses to induce systemic anti-tumour immunity and selectively killing tumour cells. However, the effectiveness of these viruses depends significantly on their interactions with the host immune responses, both innate and adaptive. In this article, we consider a mathematical approach to investigate the possible outcomes of the complex interactions between two extreme types of macrophages, effector $$\hbox {CD8}^{+}$$ (...) T cells and an oncolytic Vesicular Stomatitis Virus, on the growth/elimination of B16F10 melanoma. We discuss, in terms of VSV, $$\hbox {CD8}^{+}$$ and macrophages levels, two different types of immune responses which could ensure tumour control and eventual elimination. We show that both innate and adaptive anti-tumour immune responses, as well as the oncolytic virus, could be very important in delaying tumour relapse and eventually eliminating the tumour. Overall this study supports the use mathematical modelling to increase our understanding of the complex immune interaction following oncolytic virotherapies. However, the complexity of the model combined with a lack of sufficient data for model parametrisation has an impact on the possibility of making quantitative predictions. (shrink)

In order to investigate patients’ experience of healthcare, repeated assessments of patient-reported outcomes are increasingly performed in observational studies and clinical trials. Changes in PRO can however be difficult to interpret in longitudinal settings as patients’ perception of the concept being measured may change over time, leading to response shift and possibly to erroneous interpretation of the observed changes in PRO. Several statistical methods for response shift analysis have been proposed, but they usually assume that response shift occurs in the (...) same way in all individuals within the sample regardless of their characteristics. Many studies aim at comparing the longitudinal change of PRO into two groups of patients. The group variable could have an effect on PRO change but also on response shift effect and the perception of the questionnaire at baseline. In this paper, we propose to enhance the ROSALI algorithm based on Rasch Measurement Theory for the analysis of longitudinal PRO data to simultaneously investigate the effects of group on item functioning at the first measurement occasion, on response shift and on changes in PRO over time. ROSALI is subsequently applied to a longitudinal dataset on change in emotional functioning in patients with breast cancer or melanoma during the year following diagnosis. The use of ROSALI provides new insights in the analysis of longitudinal PRO data. (shrink)

The successful delivery of patient-centered care hinges on clinical affiliation for patients' personal needs and experiences. Narrative competence is a mode of thinking and set of actions that widens the clinical gaze beyond logico-scientific cognition. In this article, we investigate a tool that enables clinicians to rehearse their skills in narrative competence. We apply the narrative competence framework developed by the founding practitioners of narrative medicine to personal accounts of illness and patienthood published on the Internet. We describe our use (...) of the five-point framework in the close reading of 214 accounts by people with the life-threatening skin cancer melanoma. (shrink)

The unprecedented development of medical informatics is constantly transforming the concept of expertise in medical sciences in a way that has far-reaching consequences for both the theory of knowledge and the philosophy of informatics. Deep medicine is based on the assumption that medical diagnosis should take into account the wide array of possible health factors involved in the diagnostic process, such as not only genome analysis alone, but also the metabolome (analysis of all body metabolites important for e.g. drug-drug interactions), (...) microbiome (i.e. analysis of all bodily microorganisms interacting with host cells) or exposome (analysis of all environmental factors triggering potentially harmful cell mutations, such as UV radiation, heavy metals, various carcinogens, etc.). Deep data analysis is of tantamount importance for personalized diagnosis but, at the same time, hardly achievable by a regular human being. However, adequately designed artificial intelligence (e.g. a deep neural network) can undeniably be of great help for finding correlations between symptoms and underlying diseases. Nowadays AI applies to nearly every aspect of medicine, starting from the data analysis of scientific literature, through the diagnostic process, to the act of communication between physicians and their patients. Medical image processing algorithms greatly enhance the chances of successful recognition of melanoma or intestinal polyps. Communication tools designed for physicians use techniques known from social media to provide users with an opportunity to consult the case with colleagues from the same discipline. Natural language processing tools significantly improve doctor-patient communication by the automation of note-taking. Is this enough to support the claim that the non-epistemic competences in medicine are becoming more and more important? Can we attribute expertise only to a person? How is medical informatics changing the way most people usually understand human-computer interactions? (shrink)

Publics are key stakeholders in population genomic screening and their perspectives on ethical considerations are relevant to programme design and policy making. Using semi-structured interviews, we explored social views and attitudes towards possible future provision of personalised genomic risk information to populations to inform prevention and/or early detection of relevant conditions. Participants were members of the public who had received information on their personal genomic risk of melanoma as part of a research project. The focus of the analysis presented (...) here is participants’ views regarding ethical considerations relevant to population genomic screening more generally. Data were analysed thematically and four key themes related to ethical considerations were identified: personal responsibility for health: ‘forewarned is forearmed’; perceptions of, and responses to, genetic fatalism; implications for parenting and reproduction; divided views on choosing to receive genomic risk information. Ethical considerations underlying these themes include the valorisation of information and choice, paternalism, non-directiveness and increasing responsibilisation of individuals in health and healthcare. These findings arguably indicate a thin public conceptualisation of population genomic testing, which draws heavily on how these themes tend to be described in existing social discourses. Findings suggest that further public engagement is required to increase complexity of debate, to consider the appropriate place of individual and social interests in population genomic testing. Further discernment of relevant ethical approaches, drawing on ethical frameworks from both public health and clinical settings, will also assist in determining the appropriate implementation of population genomic screening for complex conditions. (shrink)

Deep learning techniques, which use a massive technology known as convolutional neural networks, have shown excellent results in a variety of areas, including image processing and interpretation. However, as the depth of these networks grows, so does the demand for a large amount of labeled data required to train these networks. In particular, the medical field suffers from a lack of images because the procedure for obtaining labeled medical images in the healthcare field is difficult, expensive, and requires specialized expertise (...) to add labels to images. Moreover, the process may be prone to errors and time-consuming. Current research has revealed transfer learning as a viable solution to this problem. Transfer learning allows us to transfer knowledge gained from a previous process to improve and tackle a new problem. This study aims to conduct a comprehensive survey of recent studies that dealt with solving this problem and the most important metrics used to evaluate these methods. In addition, this study identifies problems in transfer learning techniques and highlights the problems of the medical dataset and potential problems that can be addressed in future research. According to our review, many researchers use pre-trained models on the Imagenet dataset in many applications such as skin cancer, breast cancer, and diabetic retinopathy classification tasks. These techniques require further investigation of these models, due to training them on natural, non-medical images. In addition, many researchers use data augmentation techniques to expand their dataset and avoid overfitting. However, not enough studies have shown the effect of performance with or without data augmentation. Accuracy, recall, precision, F1 score, receiver operator characteristic curve, and area under the curve were the most widely used measures in these studies. Furthermore, we identified problems in the datasets for melanoma and breast cancer and suggested corresponding solutions. (shrink)

At the age of sixty, Cory Taylor was dying of melanoma-related brain cancer. With her illness no longer treatable, she began at the start of 2016 to write about her experiences and, in an extraordinary creative surge, wrote what would become Dying: A Memoir. This is a brief and clear-eyed account of what dying taught Cory: amid the tangle of her feelings, she reflects on the patterns of her life, and remembers the lives and deaths of her parents. She (...) tells us why she would like to be able to choose the circumstances of her own death.Dying is about the vulnerability and strength, courage and humility, anger and acceptance that it takes to live a good life and say goodbye to it in peace. (shrink)

The transcriptional co‐activators YAP (or YAP1) and TAZ (or WWTR1) are frequently activated during the growth and progression of many solid tumors, including lung, colorectal, breast, pancreatic, and liver carcinomas as well as melanoma and glioma. YAP/TAZ bind to TEAD‐family co‐activators to drive cancer cell survival, proliferation, invasive migration, and metastasis. YAP/TAZ activation may also confer resistance to chemotherapy, radiotherapy, or immunotherapy. YAP‐TEAD cooperates with the RAS‐induced AP‐1 (FOS/JUN) transcription factor to drive tumor growth and cooperates with MRTF‐SRF to (...) promote activation of cancer‐associated fibroblasts, matrix stiffening, and metastasis. The key upstream repressor of YAP/TAZ activation is the Hippo (MST1/2‐LATS1/2) pathway and the key upstream activators are mechanically induced Integrin‐SRC and E‐cadherin‐AJUBA/TRIP6/LIMD1, growth factor induced PI3K‐AKT, and inflammation‐induced G‐protein coupled receptor (GPCR) signals, all of which antagonize the Hippo pathway. In this review, strategies to target YAP/TAZ activity in cancer are discussed along with the prospects for synergy with established pillars of cancer therapy. (shrink)

This paper is about the ontology of a cancer diagnosis at high-end hospitals in Colombia. Drawing on a seventeen-month ethnographic fieldwork study in this country, it pays attention to how dermatologists, pathologists, and oncologists looked at my partner’s skin during a routine medical checkup and enacted two seemingly contradictory diagnoses: a lethal melanoma and a benign dysplastic nevus—commonly known as mole. Because their differences under the microscope or through dermatology goggles may be subtle, physicians often disagree on what they (...) see. When medical services are not unrelated to the economic possibilities of patients to pay for them, what emerges through a microscope might be different. With neoliberal medical reforms in Colombia as background, this paper focuses on the ontological indeterminacy of cancer and its relationship to high-end hospitals and a patient who could, albeit not without effort, pay for the treatment. Thus, I argue that how physicians saw was not unrelated to what they saw and therefore to their practices of medicine in neoliberal Colombia. How do medical practices and ways of seeing in Colombia enter into composition with the bodies they study? Could the same skin tissue simultaneously be cancerous and noncancerous? (shrink)

Genes that exert their function when they are introduced into a foreign genetic background pose many questions to our current understanding of the forces and mechanisms that promote either the maintenance or divergence of gene functions over evolutionary time. The melanoma inducing Xmrk oncogene of the Southern platyfish (Xiphophorus maculatus) is a stable constituent of the genome of this species. It displays its tumorigenic function, however, almost exclusively only after inter‐populational or, even more severely, interspecific hybridization events. The Xiphophorus (...) hybrid melanoma system has gained attention in biomedical research as a genetic model for studying tumor formation. From an evolutionary perspective, a prominent question is: how could this gene persist over millions of years? An attractive hypothesis is that Xmrk, acting as a detrimental gene in a hybrid genome, could be a speciation gene that shields the gene pool of its species from mixing with other closely related sympatric species. In this article, I briefly review our current knowledge of the molecular genetics and biochemical functions of the Xmrk gene and discuss aspects of its evolutionary history and presence with respect to this idea. While Xmrk as a potentially injurious oncogene has clearly survived for millions of years, its role as a speciation gene has to be questioned. BioEssays 30:822–832, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

Surgeons are in a unique position, serving as gatekeepers to the operating room. They determine if operations are possible, are indicated, and have a reasonable risk–to–benefit profile. When an operation is indicated and the patient is amenable to it, the conversation between surgeon and patient is usually straightforward. On the other hand, when a patient’s co–morbidities substantially increase the risk of operative intervention, surgeons often question the utility of offering their services. These situations become immensely more difficult when patients have (...) the expectation of being offered surgical treatment. This case describes the clinical encounter between an endocrine surgeon and an 83–year–old woman who has been incidentally found to have adrenal metastasis from melanoma. The patient wants an operation that the surgeon is reluctant to offer because of her frailty and high operative risk. The case focuses on the ethical dilemma that arises when a patient wants an operation that a surgeon does not want to perform. I was the resident in the endocrine surgery clinic the day that Ms. M came in. Given my background in bioethics, the attending physician told me about the patient’s history beforehand and asked for advice on how to approach the clinical encounter. I then accompanied him into her room to talk with her and her husband. (shrink)

Cancer stem cells (CSC) represent malignant cell subsets in hierarchically organized tumors, which are selectively capable of tumor initiation and self‐renewal and give rise to bulk populations of non‐tumorigenic cancer cell progeny through differentiation. Robust evidence for the existence of prospectively identifiable CSC among cancer bulk populations has been generated using marker‐specific genetic lineage tracking of molecularly defined cancer subpopulations in competitive tumor development models. Moreover, novel mechanisms and relationships have been discovered that link CSC to cancer therapeutic resistance and (...) clinical tumor progression. Importantly, proof‐of‐principle for the potential therapeutic utility of the CSC concept has recently been provided by demonstrating that selective killing of CSC through a prospective molecular marker can inhibit tumor growth. Herein, we review these novel and translationally relevant research developments and discuss potential strategies for CSC‐targeted therapy in the context of resistance mechanisms and molecular pathways preferentially operative in CSC. (shrink)