Interferons (IFNs) are a diverse group of cytokines whose potent antitumor effects have piqued the interest of scientists for decades. Some of the most sustained clinical accomplishments have been in the field of myeloproliferative neoplasms (MPNs). Here, we discuss how both historical and novel breakthroughs in our understanding of IFN function may lead to more effective therapies for MPNs. The particular relevance and importance of modulating the novel IFN‐regulated ULK1 pathway to optimize IFN responses is highlighted.

Due to advances in medicine, a malignant neoplasm is a chronic disease that can be treated for a lot of patients for many years. It may lead to profound changes in everyday life and may induce fear of life. The ability to adjust to a new situation may depend on temperamental traits and stress coping strategies. The research presented in this paper explores the relationships between quality of life, PTSD symptoms, temperamental traits, and stress coping in a sample of patients (...) diagnosed with cancer. One hundred and twenty nine participants aged 24–81 years, 69 females diagnosed with breast cancer and 60 males diagnosed with lung cancer completed Formal Characteristics of Behavior – Temperament Inventory, Coping Inventory for Stressful Situations, PTSD Inventory, and Quality of life SF-36 questionnaire. Higher level of emotional reactivity and higher level of perseveration was associated with lower emotional quality of life. Higher level of emotion oriented-coping and higher level of avoidant-distracted coping was associated with higher level of PTSD symptoms. Emotion-oriented coping and avoidant-distracted coping are ineffective in dealing with stress in the case of patients diagnosed with cancer, because they are associated with a higher level of PTSD symptoms. The significance of temperamental traits for quality of life in the situation of the patients is marginal. Control of specific factors concerned with current health and treatment status is needed the future research. (shrink)

Human neoplasms develop following the progressive accumulation of genetic and epigenetic alterations to oncogenes and tumor suppressor genes. These alterations confer a growth advantage to the cancer cell, leading to its clonal proliferation, invasion into surrounding tissues, and spread to distant organs. Genes that are altered in neoplasia affect three major biologic pathways that normally regulate cell growth and tissue homeostasis: the cell cycle, apoptosis, and differentiation. While each of these pathways can be defined by a unique set of (...) molecular events, they are not biologically separate. Rather, they function more as an integrated molecular network, and perturbations in one pathway can have profound consequences on another. Insights into what distinguishes the regulation of growth and differentiation in a normal cell versus a cancer cell have led to the development of novel anticancer therapies. BioEssays 24:83–90, 2002. © 2002 John Wiley & Sons, Inc. (shrink)

The somatic mutation theory (SMT) of cancer has been and remains the prevalent theory attempting to explain how neoplasms arise and progress. This theory proposes that cancer is a clonal, cell‐based disease, and implicitly assumes that quiescence is the default state of cells in multicellular organisms. The SMT has not been rigorously tested, and several lines of evidence raise questions that are not addressed by this theory. Herein, we propose experimental strategies that may validate the SMT. We also call (...) attention to an alternative theory of carcinogenesis, the tissue organization field theory (TOFT), which posits that cancer is a tissue‐based disease and that proliferation is the default state of all cells. Based on epistemological and experimental evidence, we argue that the TOFT compellingly explains carcinogenesis, while placing it within an evolutionarily relevant context.magnified imagemagnified imageAna Soto and Carlos Sonnenschein are at Tufts University School of Medicine, Boston, MA, USA. (shrink)

Many philosophers and medical scientists assume thatdisease categories or entities used to classify concrete cases ofdisease, are often defined by disease mechanisms or causalprocesses. Others suggest that diseases should always be definedin this manner. This paper discusses these standpoints criticallyand concludes that they are untenable, not only when `diseasemechanism' refers to an objective mechanism, but also when`mechanism' refers to a pragmatically demarcated part of thetotal ``objective'' causal structure of diseases. As an alternativeto principles that use the concept of disease mechanism (...) oranalogous concepts, a pragmatic approach is suggested anddescribed. This approach has been suggested before, but inproblematic or inadequate versions. This paper proposes a versioncompiled of two ``pragmatic principles'' and shows that they aremuch more adequate than the principle of disease mechanism. Withreference to a case study of a still ongoing internationaldiscussion of various candidates for a classification system formalignant lymphomas, including REAL (Revised European–AmericanClassification of Lymphoid Neoplasms) in which the concept ofdisease mechanism or analogous concepts plays a very small part,it is shown just how pivotal these two pragmatic principles canbe in actual discussions of definitions of diseases. Finally, itis pointed out that with regard to modern philosophy of languageit may, at least in some cases, be problematic to distinguishbetween the two pragmatic principles as they stand. (shrink)

Increasing emphasis on patient self-management, including having patients advocate for their needs and priorities, is generally a good thing, but it is not always wanted or attainable by patients. The aim of this critical ethical review is to deepen the current discourse in patient self-advocacy by exposing various situations in which patients struggle to self-advocate. Using examples from oncology patient populations, we disambiguate different notions of self-advocacy and then present limits to the more demanding varieties (i.e., health-related, trust-based, and psychological); (...) we argue that these limits create ethical dilemmas with respect to whether it is always desirable to encourage patients to self-advocate. We conclude that self-advocacy can be both under and overrated with respect to how much it benefits the patient with cancer, with many instances being indeterminate. Ultimately, providers must understand the patient's perspective relative to the challenges they are experiencing and work with them to meet their needs. (shrink)

In this work, the evolution of demographic and health patterns in a Basque rural population from Spain is analysed, as they relate to progress in demographic and epidemiological transition. For this purpose, parochial record data on 13,298 births and 9215 deaths, registered during the 19th and 20th centuries (180090) resulting from cardiovascular diseases and malignant neoplasms (post-transition causes). This last point is in contrast with observations from the first four decades of the 20th century, when infectious diseases and respiratory (...) ailments were determining factors in mortality among this population. The data provided by the study of the variation over time in demographic and health patterns indicate that reducing the risk of mortality is one of the most important preconditions for fertility decline. (shrink)

Thousands of candidate cancer biomarkers have been proposed, but so far, few are used in cancer screening. Failure to implement these biomarkers is attributed to technical and design flaws in the discovery and validation phases, but a major obstacle stems from cancer biology itself. Oncogenomics has revealed broad genetic heterogeneity among tumors of the same histology and same tissue (or organ) from different patients, while tumors of different tissue origins also share common genetic mutations. Moreover, there is wide intratumor genetic (...) heterogeneity among cells within any single neoplasm. These findings seriously limit the prospects of finding a single biomarker with high specificity for early cancer detection. Current research focuses on developing biomarker panels, with data assessment by machine‐learning algorithms. Whether such approaches will overcome the inherent limitations posed by tumor biology and lead to tests with true clinical value remains to be seen. (shrink)

Background: Despite a gradual shift in the focus of medical care among terminally ill patients to a palliative model, studies suggest that many children with life-limiting chronic illnesses continue to die in hospital after prolonged periods of inpatient admission and mechanical ventilation.Objectives: To examine the characteristics and location of death among hospitalised children, investigate yearwise trends in these characteristics and test the hypothesis that professional ethical guidance from the UK Royal College of Paediatrics and Child Health would lead to significant (...) changes in the characteristics of death among hospitalised children.Methods: Routine administrative data from one large tertiary-level UK children’s hospital was examined over a 7-year period for children aged 0–18 years. Demographic details, location of deaths, source of admission , length of stay and final diagnoses were studied. Statistical significance was tested by the Kruskal–Wallis analysis of ranks and median test , χ2 test and Cochran–Armitage test .Results: Of the 1127 deaths occurring in hospital over the 7-year period, the majority were among infants. The main diagnoses at death included congenital malformations , perinatal diseases , cardiovascular disorders and neoplasms . Most deaths occurred in an intensive care unit environment , with a significant increase over the years . There was a clear increase in the proportion of admissions from in-hospital among the ICU cohort . Infants with congenital malformations and perinatal conditions were more likely to die in an ICU , and older children with malignancy outside the ICU . Children stayed for a median of 13 days on a hospital ward before being admitted to an ICU where they died.Conclusions: A greater proportion of hospitalised children are dying in an ICU environment. Our experience indicates that professional ethical guidance by itself may be inadequate in reversing the trends observed in this study. (shrink)

BackgroundTo limit selective and incomplete publication of the results of clinical trials, registries including ClinicalTrials.gov were introduced. The ClinicalTrials.gov registry added a results database in 2008 to enable researchers to post the results of their trials as stipulated by the Food and Drug Administration Amendment Act of 2007. This study aimed to determine the direction and magnitude of any change in publication proportions of registered breast cancer trials that occurred since the inception of the ClinicalTrials.gov results database.MethodsA cross-sectional study design (...) was employed using ClinicalTrials.gov, a publicly available registry/results database as the primary data source. Registry contents under the subcategories ‘Breast Neoplasms’ and ‘Breast Neoplasms, Male’ were downloaded on 1 August 2015. A literature search for included trials was afterwards conducted using MEDLINE and DISCOVER databases to determine publication status of the registered breast cancer trials.ResultsNearly half (168/340) of the listed trials had been published, with a median time to publication of 24 months (Q1 = 14 months, Q3 = 42 months). Only 86 trials were published within 24 months of completion. There was no significant increase in publication proportions of trials that were completed before the introduction of the results database compared to those completed after (OR = 1.00, 95 % CI =.61 to 1.63; adjusted OR = 0.84, 95 % CI =.51 to 1.39). Characteristics associated with publication included trial type (observational versus interventional adjusted OR =.28, 95 % CI =.10 to.74) and completion/termination status (terminated versus completed adjusted OR =.22, 95 % CI =.09 to.51).ConclusionsLess than a half of breast cancer trials registered in ClinicalTrials.gov are published in peer-reviewed journals. (shrink)

Significant progress in the molecular investigation of endogenous bioelectric signals during pattern formation in growing tissues has been enabled by recently developed techniques. Ion flows and voltage gradients produced by ion channels and pumps are key regulators of cell proliferation, migration, and differentiation. Now, instructive roles for bioelectrical gradients in embryogenesis, regeneration, and neoplasm are being revealed through the use of fluorescent voltage reporters and functional experiments using well‐characterized channel mutants. Transmembrane voltage gradients (Vmem) determine anatomical polarity and function as (...) master regulators during appendage regeneration and embryonic left‐right patterning. A state‐of‐the‐art recent study reveals that they can also serve as prepatterns for gene expression domains during craniofacial patterning. Continued development of novel tools and better ways to think about physical controls of cell‐cell interactions will lead to mastery of the morphogenetic information stored in physiological networks. This will enable fundamental advances in basic understanding of growth and form, as well as transformative biomedical applications in regenerative medicine. (shrink)

While primary malignant brain tumors account for only two percent of all adult cancers, these neoplasms cause a disproportionate amount of cancer-related disabilities and death. The five-year survival rates for brain tumors are the third lowest among all types of cancer. Malignant gliomas comprise the most common types of primary central nervous system tumors and have a combined incidence of five to eight cases per 100,000 people. The median survival rate of conservatively treated patients with malignant gliomas is 14 (...) weeks; with surgical resection alone, 20 weeks; with surgery and radiation, 36 weeks; and with the addition of newer biochemotherapies such as temozolomide and bevacizumab, upward of 14-18 months.The profound cost of caring for terminally ill patients with primary malignant brain tumors raises ethical considerations for the American public; the stewardship of health care dollars for the population at large maintains a juxtaposed tension against a dynamic, necessary balance of hope, care, rehabilitation and research efforts for affected patients and their advocates. (shrink)

The set of symbols of success is a set of cultural determinants of activity and their functioning is connected with the fundamental functions of culture as a system of historically developing supra-biological programs of life. The relevance of considering the symbolization of success in modern cinema is due to several factors. First, according to the majority of art historians and film theorists, cinema remains the leading, most widespread form of art throughout the 20th and 21st centuries. If we understand art (...) as a figurative comprehension of reality, its process and result, which is expressed in works, then the symbolization of success in cinema can be considered one of the most common practices for representing the determinants of activity through a figurative comprehension of reality. An analysis of this process in modern cinematography reveals the mechanisms of functioning of one of the elements of the totality of joint life programs as a segment of modern culture, limited by the boundaries of film communication. Secondly, the development of cinematography largely determines the fundamental changes in the culture of the 20th century. and there is no reason to believe that its influence is diminishing in recent times. Consequently, modern cinema remains one of the most important areas of cultural life, the study of which allows expanding scientific understanding of the patterns of changes taking place in culture. Thirdly, the development of information and communication technologies at the end of the 20th century. led to the fact that the value complexes of traditional cultures of different peoples of the world and expansive global neoplasms of a supranational nature (mass, elite, corporate, fandom, etc.) are simultaneously transmitted into the space of personal culture. Cinema in the new conditions only strengthened its position as the leading relay of value complexes. The special socio-forming qualities of cinema were noted both by its pioneers (L. Delluk, A. Dovzhenko, Ch. Chaplin, S. Eisenstein, etc.), scientists (B. Balash, V. A. Gottwald, E. M. Samuylenko, etc.) , and the ideologists of cultural revolutions at the beginning of the 20th century. G. Turner, in particular, drew attention to the fact that “to achieve control over the everyday representation of the world for a nation means to acquire strong power over the representation of individuals about themselves and about each other”, referring to the threat to the integrity and coherence of an individual’s understanding of the world under the pressure of foreign cultural domination over film communication. In this regard, the search for ways to relevantly measure the trends in the development of modern culture by marking in cinema the cultural determinants of activity, which are the symbols of success, seems to be an urgent theoretical and scientific-practical task, the solution of which expands the predictive potential of culture and its projective possibilities. (shrink)

BackgroundSarcomas are a diverse group of neoplasms that vary greatly in clinical presentation and responsiveness to treatment. Given the differences in the sites of involvement, rarity, and treatment modality, a multidisciplinary approach is required. Previous literature suggests patients with sarcoma suffer from poorer quality of life especially physical and functional wellbeing. Adolescent and young adult patients are an underrepresented population in cancer research and have differing factors influencing QoL.MethodsRetrospective analysis of Young Adult patients enrolled in the Sarcoma Tissue Repository (...) at University of Iowa. QoL was assessed using the self-report FACT-G questionnaire at enrollment and 12 months post-diagnosis; overall scores and the 4 wellbeing subscales were calculated. Linear mixed effects models were used to measure the association between the rate of change in FACT-G subscale scores and baseline clinical, comorbidity, and treatment characteristics.Results49 patients were identified. 57.1% of patients had a malignancy involving an extremity. Mean FACT-G scores of overall wellbeing improved from baseline to 12 months. Social and emotional wellbeing did not differ significantly between baseline and 12 months. Physical wellbeing and functional wellbeing scores improved from baseline to 12 months. No difference was seen for FACT-G overall scores for age, sex, laterality, marital status, performance status, having children, clinical stage, limb surgery, chemotherapy, or tumor size. A difference was demonstrated in physical wellbeing scores for patients with baseline limitation compared to those with no baseline limitation. A difference was demonstrated in social wellbeing based on anatomical site.ConclusionYoung adults with sarcoma treated at a tertiary center had improvements in overall reported QoL at 12 months from diagnosis. Overall baseline QoL scores on FACT-G were lower than the general adult population for YA patients with sarcoma but at 12 months became in line with general population norms. The improvements seen merit further investigation to evaluate how these change over the continuum of care. Quality of life changes may be useful outcomes of interest in sarcoma trials. (shrink)

This paper examines mortality by cause of death in a rural area of Machakos district in Kenya. The cause-of-death data collected between 1975 and 1978 were likely to be of fairly good quality. The number of deaths was higher among infants and children. Infectious diseases and diseases of the respiratory system were the leading causes of death among children below 5 years of age. Next in prominence were the causes ascribed to congenital anomalies and perinatal conditions.Among adolescents and young adults, (...) injury and poisoning, together with tuberculosis and other infectious and parasitic diseases, were the leading causes of death. Degenerative diseases, especially diseases of the circulatory system and neoplasms and respiratory illness, were responsible for the majority of deaths among the older population. (shrink)

Variation or rearrangement of regulatory genes is responsible for cellular malignant change. These types of chromosomal variations also produce heterochrony or paedomorphic evolution at the organismal level. Analogously, neoplasia represents a cellular macroevolutionary event, and a tumour can be said to be an evolved population of cells. To understand this cellular evolution to malignancy, it may be necessary to go beyond a clonal selection (adaptationist) explanation of neoplastic alteration. In the pericellular environment natural selection consists of the organizational restraints of (...) surrounding cells as well as the host's immunological surveillance and non-specific monocyte-macrophage systems. Indirect evidence suggests that success for the neoplasm depends not upon clonal selection, but solely upon a genetic methodology—the function of which is to elude selection.The author has coined the term cellular heterochrony to illustrate analogic similarities in the molecular modes of speciation between anaplastic cancer cells and the heterochronic evolution of organisms. By reverting to a juvenile (embryonic) repertoire of cellular behaviour a tumour secures its own tenure or niche by usurping the host's armamentarium of selection forces, employing many of the same or similar methods by which implanting and invading tissues of the mammalian embryo forestall maternal detection and rejection. A number of ways by which the tumour blocks, subverts or evades selection are discussed. (shrink)

Biomedical science has been remarkably successful in explaining illness by categorizing diseases and then by identifying localizable lesions such as a virus and neoplasm in the body that cause those diseases. Not surprisingly, researchers have aspired to apply this powerful paradigm to addiction. So, for example, in a review of the neuroscience of addiction literature, Hyman and Malenka (2001, p. 695) acknowledge a general consensus among addiction researchers that “[a]ddiction can appropriately be considered as a chronic medical illness.” Like other (...) diseases, “Once addiction has taken hold, it tends to follow a chronic course.” (Koob and La Moal 2006, p. ?). Working from this perspective, much effort has gone into characterizing the symptomology of addiction and the brain changes that underlie them. Evidence for involvement of dopamine transmission changes in the ventral tegmental area (VTA) and nucleus accumbens (NAc) have received the greatest attention. Kauer and Malenka (2007, p. 844) put it well: “drugs of abuse can co-opt synaptic plasticity mechanisms in brain circuits involved in reinforcement and reward processing”. Our goal in this chapter to provide an explicit description of the assumptions of medical models, the different forms they may take, and the challenges they face in providing explanations with solid evidence of addiction. <br>. (shrink)

In researching the biomedically-engineered drug Neulasta (filgrastim), a breast cancer patient becomes aware of the extent to which knowledge about the development and marketing of drugs influences her decisions with regard to treatment. Time spent on understanding the commercial interests of insurers and pharmaceutical companies initially thwarts but ultimately aids the healing process. This first-person narrative calls for physicians to recognize that the alignment of commercial interests transgresses the patient’s humanity.

Tumor‐cell diversification mechanisms insure that malignant neoplasms contain diversified tumor‐cell subpopulations. Because of the instability of tumor cell phenotypes, some malignant cells will evolve with the most favorable properties for their progression to highly metastatic cells. The rates of cellular phenotypic diversification vary greatly among different tumors, and they are probably modulated, in part, by genetic and chromosome defects and by epigenetic events that may vary widely depending upon the nature of the tumor cells and their microenvironments. As tumor (...) diversification and selection proceed, the most malignant cell subpopulations may eventually become dominant and gradually lose their microenvironmental responsiveness. Tumor‐cell diversification mechanisms may be similar or identical to normal, developmentally regulated diversification mechanisms that are used during embryonic cell diversification and differentiation. (shrink)

My office is in a medical building in suburban Washington, D.C. —in Bethesda, named for the Biblical healing pool. All of the offices of my building are occupied by medical specialists, representing the most sophisticated training in the application of the scientific method. Downstairs and of service to all of us is a pharmacy, looking for all the world like a research laboratory with its gleaming surface, meticulous cleanliness, micro-balances, records, reference books, and cash register. It is neatly stocked with (...) modern, physiologically-defined preparations of active, predictable drugs. Among the enzymes, hormones, antibiotics, and chemo therapeutics for neoplasm, are a few newly hatched, unfledged remedies, but most are dependable and thoroughly assayed. The intently busy, white-coated, unsentimental pharmacists serve a hard-headed group of practitioners and a neighborhood of upper-class, well-educated patients. It is disconcerting, then, to see the undersurface of this sophistication, the irrational shadows beneath the science. On the front counter of the pharmacy are displayed attractive colored advertisements and pleasantly seductive inducements to self-improvement through diet cults and foods, tranquilizers, energizers, protein supplements, happiness promisers, preparations to enhance sexuality, vitamins artfully combined, and many packeted stuffs of no rational or pretended use whatsoever. “Why,” I ask the gimlet-eyed pharmacist, “do you have this large display of ‘Il Wah Genuine Chinese Ginseng, the Miraculous Herb of Life’? Doesn't it violate your university training? Your integrity as a modernist?” “Oh,” says he, “ginseng makes you feel better! You have more energy. You can do more! Lots of athletes use it, and people who work too hard and feel exhausted. It's only $3.45 a package. The prescriptions you give me once in a while yield no profit, but I sell a lot of ginseng. I use it myself!” Bemused, I walk back to my office, wondering about the easy abandonment of rationality, and pull down a box of medicinals collected the year before at an open-air pharmacy in the riverside markets of Brazil. The box gives forth deliciously rich forest smells. The packets within contain barks, roots, seeds, all of purported medical value. Other packets have amulets, charms, and protectives. The colorful labels on some of the patent medicines invoke ancient saints and healers, and promise happiness, health, prosperity and power. The essential rationale for their use in indigenous medicine was illusive to me despite many conversations with indigenous healers, and many times I have gone through the hundreds of items trying to find the key to what Brazilian and North American people fundamentally want from a pharmacy. In both cultures, where does magic stop and science begin? Do shops in both countries vend talismans in the search for the enhanced life, and fetishes against death? How much of all drug use is ritual and inchoate expectation? How can we reduce the mystification and incrementally increase the rationality of our pharmacopeia? (shrink)

It has been unclear why certain defined DNA regions are consistently sites of chromosomal translocations. Some of these are simply sequences of recognition by endogenous recombination enzymes, but most are not. Recent progress indicates that some of the most common fragile sites in human neoplasm assume non‐B DNA structures, namely deviations from the Watson–Crick helix. Because of the single strandedness within these non‐B structures, they are vulnerable to structure‐specific nucleases. Here we summarize these findings and integrate them with other recent (...) data for non‐B structures at sites of consistent constitutional chromosomal translocations. BioEssays 28: 480–494, 2006. © 2006 Wiley Periodicals, Inc. (shrink)

The study of the history of ideas is usually devoted to big problems and to concluded debates. We have attempted to analyze a current theory whose fate and explanatory power is still not determined. The term microparadigm is used to define a currently and widely accepted theory limited in time and in the field of application, compared to the greater problems usually investigated by historians of science. Among the characteristics defining a microparadigm we found: 1) the status of an accepted (...) theory with creative scientific power; 2) the presence of anomalies and unproven inferences; 3) a limited field of application; 4) the peculiarity of interaction with non-scientific ideas. In this context, we discuss the rise of the current microparadigm concerning the pathogenesis and biology of lymphoid neoplasms. We show that the current view of the neoplastic lymphoid cells as populations frozen at a particular differentiative stage has been creative for the last 10 years, thus allowing the generation of a large body of data that would not have been collected within the previous view of the leukemic cell as completely “anarchic”. This paradigm, although containing some anomalies, has survived the impact of molecular biology in hematology and is still creative. We think that microparadigms are widely distributed in everyday science and that an analysis of them is as useful for active scientist as is the study of macroparadigms, which by themselves cannot be representative of everyday science. Finally, the study of microparadigms while they are still operative can be useful to evidence the weakness of the theory and to suggest where new data should be sought. (shrink)

The complexity of biobank research raises concerns about individuals’ understanding of the information conveyed in the consent process for such research.. We report the results of a qualitative, cognitive interview study with an ethnically, linguistically, and educationally diverse sample of 43 respondents to assess the clarity and utility of a multimedia tool developed for a biobank. Using weighted randomization, respondents were assigned to either view the multimedia tool or read a written consent document . The study illustrates the utility of (...) cognitive interviews for gaining insights from prospective research participants about the clarity of informed consent tools. Findings suggest that a multimedia tool is useful for communicating key messages but should be combined with a written consent document and personal interaction with the study staff. We recommend that the potential value of multimedia tools should be more rigorously tested in a randomized controlled trial. (shrink)

The experience of losing a child to cancer represents an emotional burden for the parents with extreme individual, family and social effects that do not end with death. This integrative review is intended to identify key aspects in the experience of losing a child to cancer. The results show a pattern surrounding six moments in the mourning process These can serve as elements of intervention to accompany parents as they try to cope. It is concluded this pattern is an important (...) phenomenon for the development of palliative care at the end of life and afterwards. (shrink)

The major cause of death from cancer is the relentless growth of metastases that are resistant to conventional therapy. The pathogenesis of a metastasis is complex and requires that tumor cells complete a sequence of potentially lethal interactions with various host factors. The finding in 1973 that metastasis is selective process and the finding in 1977 that malignant neoplasms are heterogeneous and contain few preexisting metastatic subpopulations have added a new dimension to our understanding of cancer and its spread. (...) This understanding is now contributing to the design of better therapies against disseminated metastasis. (shrink)

The complex process of cell immortalization and transformation is likely to involve the inactivation of growth regulatory genes. Mutations (deletions, missense mutations) in the p53 gene are the most frequently observed genetic alteration in human tumors, making p53 a candidate for a cellular protein involved in the control of cell growth. Two recent studies have examined the role of p53 in immortalization and tumorigenesis(27,28). In the first study(27), p53 expression was examined in both mortal and immortal chick embryo fibroblasts. All (...) mortal clones expressed p53 but the loss of wild‐type p53 expression was observed in every immortal cell line examined. In the second study(28), a line of mice carrying two null p53 alleles has been created and characterized. Although these mice develop normally, they show a predisposition to develop a variety of neoplasms at an early age (< 6 months). Although it is unclear whether p53 regulates the same, different, or overlapping pathways in the two experimental systems, these data demonstrate that p53 function is critical for the maintenance of normal growth control and support the current classification of p53 as a growth suppressive or tumor suppressor gene. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:An Encounter with the Art and Science of MedicineAnonymous Five“Let Nothing Upset YouLet Nothing Frighten YouEverything is ChangingOnly God is Changeless”—St. Theresa of AvilaSt. Teresa’s prayer is on the front cover of each of four binders dedicated to storing insurance authorizations, studies, references, and reports about our daughter’s brain tumor treatment. They represent our experience, what we learned, the information we were given, and the information we sought out. (...) I kept them in case our daughter ever wanted to understand how my husband and I arrived at a decision for her treatment that was in direct opposition to the strong recommendation of her primary treatment team of physicians.On December 10, 2003, I received an urgent call from our daughter’s neurologist requesting that we meet with the doctor late that afternoon. For six months prior to that appointment, our daughter had been telling us about odd sensations with breathing, nausea, and balance. Sometimes she would seem extremely distressed for a short period of time or report that her friends told her about doing or saying things that didn’t make sense and that she didn’t remember. We consulted a series of physicians as her symptoms became steadily more intense and more prevalent. Our family practice physician referred us to an allergy specialist and a pulmonologist. There were a number of tests for allergies and lung problems. As the tests and treatments did not help, our daughter became increasingly unwilling to go to doctor’s appointments. My husband and I were confused and deeply concerned about the lack of progress. The next series of referrals included a gastroenterologist and a neurologist. The gastroenterologist suggested our daughter had partial–complex epilepsy, concurred with our plan to see a neurologist, and mentioned she should have an MRI.I remember the neurologist putting the MRI scans up, pointing to the large dark spot which he called a “large mass” (5 cm), that could be either a cluster of blood vessels or a neoplasm. He said his office had arranged for us to meet a neurosurgeon the following day. We all remember the same thing about that visit—the image of the large dark mass on the scan—and the neurologists flat, brisk tone. We met with the neuro-surgeon the next day. Her team was kind and sympathetic—she was positive, up beat and direct. She did not think this mass was blood vessels. She thought it was a large tumor that needed to be removed right away. Our daughters surgery was scheduled for the following Friday—December 19, 2003. She had turned 15 on November 5.Four and a half hours after our daughter was wheeled into the operating room, her surgeon told us they had removed 98% of the tumor. She said there was no cure, but there was a good prognosis based on the surgical outcome. Several days later, she called us and said she had more data, and it looked like the resection was closer to 90%. The first pathology report, a “first impression” directly after surgery, described our daughter’s tumor as an astrocytoma, probably high grade. Three weeks after surgery, we met with a panel of doctors—two oncologists and radiologist—who explained that based on the final pathology report, our daughter’s tumor was classified as an ependymoma, grade 2. We were dismayed. First, there had been the change in the estimated success of the resection and now a complete shift in both grade and tumor type.The team recommended radiation to follow her surgery, which they said was standard treatment. We began to try to inform ourselves about her tumor. Her father, an agronomist, did an extensive search in PubMed to evaluate and sort through the literature on low–grade gliomas and radiation. What he could find was inconclusive and grim. Most reports in the literature suggested at best delayed mortality at five years after radiation. [End Page E7] Meanwhile, our daughter went through a spinal MRI and the preparatory “fitting” of the mask to immobilize her head during radiation.E7I consulted with a friend who had worked as an EKG tech. She urged... (shrink)

Background: Patients in different countries have different attitudes toward self‐determination and medical information. Little is known how much respect Japanese patients feel should be given for their wishes about medical care and for medical information, and what choices they would make in the face of disagreement. Methods: Ambulatory patients in six clinics of internal medicine at a university hospital were surveyed using a self‐administered questionnaire. Results: A total of 307 patients participated in our survey. Of the respondents, 47% would accept (...) recommendations made by physicians, even if such recommendations were against their wishes; 25% would try to persuade their physician to change their recommendations; and 14% would leave their physician to find a new one. Seventy‐six percent of the respondents thought that physicians should routinely ask patients if they would want to know about a diagnosis of cancer, while 5% disagreed; 59% responded that physicians should inform them of the actual diagnosis, even against the request of their family not to do so, while 24% would want their physician to abide by their family's request and 14% could not decide. One‐third of the respondents who initially said they would want to know the truth would yield to the desires of the family in a case of disagreement. Interpretations: In the face of disagreement regarding medical care and disclosure, Japanese patients tend to respond in a diverse and unpredictable manner. Medical professionals should thus be prudent and ask their patients explicitly what they want regarding medical care and information. (shrink)

Transmissible cancers are elusive and understudied parasitic life forms caused by malignant clonal cells (nine lineages are known so far). They emerge by completing sequential steps that include breaking cell cooperation, evade anti‐cancer defences and shedding cells to infect new hosts. Transmissible cancers impair host fitness, and their importance as selective force is likely largely underestimated. It is, therefore, crucial to determine how common they might be in the wild. Here, we draw a parallel between the steps required for a (...) transmissible cancer to emerge and the steps required for an intelligent civilisation to emerge in the Milky Way using a modified Drake equation. Using numerical analyses, we estimate the potential number of extant marine and bivalve species in which transmissible cancers might exist. Our results suggest that transmissible cancers are more common than expected, and that new lineages can be found by screening a large number of species. (shrink)

Haematopoietic stem cell transplantation is a treatment modality that saves the health and lives of a growing number of patients around the world. In the majority of cases, the procedure is conducted to treat haematologic neoplasms, although it can also be used as a therapy for some non-haematooncological diseases. The progress that has been taking place in the field of haematopoietic stem cell transplantation involves the need for recruiting more and more potential unrelated bone marrow donors for allotransplantation. In (...) Poland, the number of people registering as potential bone marrow donors has been continuously growing and in order to maintain this trend, it is necessary, above all, to consistently spread the noble idea of bone marrow donation and to raise Poles’ awareness and knowledge about haematopoietic stem cell transplantation. Unfortunately, the situation caused by the severe acute respiratory syndrome coronavirus 2 pandemic limited the opportunities to act in public space and, as a consequence, it has become more difficult to achieve the objectives associated with recruiting new potential donors. The article provides a presentation of ethical and practical aspects associated with bone marrow donations as well as an overview of the legal situation concerning bone marrow donating and transplantation in Poland. The purpose of the paper is to also present some of the changes in transplantation procedures that have emerged as a consequence of the current epidemiological situation. The authors would like to emphasize the importance and the rightfulness of taking action that enables further development of transplantology. (shrink)

In the nearly 40 years since implementation of federal regulations governing the protection of human participants in research, the number of clinical studies has grown exponentially. These studies have become more complex, with multisite trials now common, and there is increasing use of archived biospecimens and related data, including genomics data. In addition, growing emphasis on targeted cancer therapies requires greater collaboration and sharing of research data to ensure that rare patient subsets are adequately represented. Electronic records enable more extensive (...) data collection and mining, but also raise concerns about the potential for inappropriate or unauthorized use of data, bringing patient protections into a new landscape. There are also long-standing concerns about the processes and forms used to obtain informed consent from patients participating in clinical studies. These changes and challenges raise new ethical and practical questions for the oversight of clinical studies, and for protecting patients and their health information in an efficient manner that does not compromise the progress of biomedical research. Contemporary Issues for Protecting Patients in Cancer Research is the summary of a workshop convened by the National Cancer Policy Forum of the Institute of Medicine in February 2014 to explore contemporary issues in human subjects protections as they pertain to cancer research, with the goal of identifying potential relevant policy actions. Clinical researchers, government officials, members of Institutional Review Boards, and patient advocates met to discuss clinical cancer research and oversight. This report examines current regulatory provisions that may not adequately protect patients or may be hindering research, and discusses potential strategies and actions to address those challenges. (shrink)

With the aging of the general population and the ability of intensivists to support patients using ventilator support, tracheostomy has become a vital tool in the medical management of critically ill patients. While much of the medical literature on tracheostomy has focused on the optimal timing of and indications for performing this procedure, little is written on the ethical tensions that can revolve around decisions by patients, surrogates, and physicians on its use. This article will elucidate the ethical dilemmas that (...) can arise surrounding the use of tracheostomy in critically ill patients and how ethics consultants and committees can approach these cases to allow resolution. (shrink)

Men, culture and hegemonic masculinity: understanding the experience of prostate cancer Following a diagnosis of, and treatment for prostate cancer, there is an expectation that men will cope with, adjust to and accept the psychosocial impact on their lives and relationships. Yet, there is a limited qualitative world literature investigating the psychosocial experience of prostate cancer, and almost no literature exploring how masculinity mediates in such an experience. This paper will suggest that the experience of prostate cancer, the process by (...) which it is investigated, and the way in which it is understood has been shaped by an essentialist interpretation of gender, exemplified by hegemonic masculinity as the archetypal mechanism of male adaptation. In response to this static and limiting view of masculinity, this paper will offer a reframe of hegemonic masculinity. This reframe, being more aligned with common experience, will portray masculinity as a dynamic and contextual construct, better understood as one of a number of cultural reference points around which each man organises and adopts behaviour. It will be suggested that the extant literature, in being organised around hegemonic masculinity, obfuscates the experience of prostate cancer and acts to render covert any collateral masculinities, public or private, that may also be operating. (shrink)

It is well established that chronic infections can lead to cancer. Almost unknown is that, in contrast, acute brief viral and bacterial infections may have beneficial effects in cases of established neoplastic disease, while exposure to pathogenic products by infection, vaccination, and inhalation can cause prophylactic effects. In the following I will align evidence from case studies of spontaneous regression and from epidemiological studies with recent immunology to conclude that pathogenic substances belonging to the group of “pathogen‐associated molecular patterns” can (...) trigger the innate immune system to establish anti‐neoplastic immune responses. A better understanding of the protective role of the innate immune system might leverage considerable prophylactic potential. (shrink)