Lysine methylation has been traditionally associated with histones and epigenetics. Recently, lysine methyltransferases and demethylases – which are involved in methylation of non‐histone substrates – have been frequently found deregulated in human tumours. In this realm, a new discovery has unveiled the methyltransferase SMYD3 as an enhancer of Ras‐driven cancer. SMYD3 is up‐regulated in different types of tumours. SMYD3‐mediated methylation of MAP3K2 increases mutant K‐Ras‐induced activation of ERK1/2. Methylation of MAP3K2 prevents it from binding to the phosphatase PP2A, thereby (...) impeding the impact of this negative regulator on Ras‐ERK1/2 signals, leading to the formation of lung and pancreatic adenocarcinomas. Furthermore, depletion of SMYD3 synergises with a MEK inhibitor, currently in clinical trials, to block Ras‐driven pancreatic neoplasia. These results underscore the importance of lysine methylation in the regulation of signalling pathways relevant for tumourigenesis and endorse the development of drugs targeting unregulated lysine methylation as therapeutic agents in the struggle against cancer. (shrink)

The gut microbiota is an important component of the human body and its immune‐modulating and metabolic activities are critical to maintain good health. Gut microbes, however, are sensitive to changes in diet, exposure to antibiotics, or infections, all of which cause transient disruptions in the microbial composition, a phenomenon known as dysbiosis. It is now recognized that microbial dysbiosis is at the root of many gastrointestinal disorders. However, the mechanisms through which bacterial dysbiosis initiates disease are not fully understood. Microbially‐derived (...) metabolites and their role in disease have also attracted significant attention. Identification of cancer‐associated bacteria and understanding the contributions of microbial metabolism in health and disease are exciting but challenging areas that will allow defining microbial biomarkers for predicting gastrointestinal disorders. Understanding the complex interactions between gut microbiota, diet, host immune system and host genetics will be critical to developing more personalized therapies and approaches to treat disease. (shrink)

Illness narratives from patients with colorectal cancer commonly record patterns of change in social relationships that follow the diagnosis and treatment of the condition. We believe that these changes are best explained as a process of facework, which reflects losses of face on the part of the patient, and which assists in the creation of new faces that convey new senses of identity. Facework is familiar in the work by E. Goffman (1955) and has been extensively reworked since his (...) time. There is considerable agreement that face is a pervasive and universal constituent of all social interaction, and that it expresses the subject's view of the way he or she would like to be considered by others in interactions. Ho's concept of multiple faces negotiated dynamically according to social context is particularly useful in understanding the purpose and techniques of facework (D. Y.-F. Ho, 1994). We propose a model of face that uses dignity as the face-expression of personal attributes and acquisitions, and honor as the face-expression of systemic capabilities and attainments. This model can be used to examine individual variations in response and adaptation to colon cancer and its treatment, and it provides a useful means of teaching health care workers about the experience of illness. (shrink)

Although hope is a pervasive concept in cancer treatment, we know little about how ambulatory patients with cancer define or experience hope. We explored hope through semistructured interviews with ten patients with advanced (some curable, some incurable) colon cancer at one Midwestern, university–based cancer center. We conducted a thematic analysis to identify key concepts related to patient perceptions of hope. Although we did ask specifically about hope, patients also often revealed their hopes in response to (...) indirect questions or by telling stories about their cancer experience. We identified four major themes related to hope: 1) hope is essential, 2) a change in perspective, 3) the content of hope, and 4) communicating about hope. The third theme, the content of hope, included three subthemes: a) the desire for normalcy, b) future plans, and c) hope for a cure. We conclude that hope is an essential concept for patients undergoing treatment for cancer as it pertains to their psychological well–being and quality of life, and hope for a cure is not and should not be the only consideration. In a clinical context, the exploration of patients’ hopes and aspirations in light of their cancer diagnosis is important because it provides a frame for understanding their goals for treatment. Exploration of the content of patients’ hope can not only help to illuminate misunderstandings but also clarify how potential treatments may or may not contribute to achieving patients’ goals. (shrink)

ContextColon cancer is the 3rd most common cancer in the world. The diagnosis leads the patient and his relatives into a process of mourning for their health and previous life. The literature highlights the impact of the disease on couples. Cancer can either alter or strengthen the relationship. The disease will directly or indirectly affect both partners. Such impact starts with the diagnosis and lasts long after treatments. No study has analyzed both emotional and sexual interactions between (...) partners throughout the illness so far.ObjectiveThis research aims to identify and describe whether congruence within couples tends to improve emotional and sexual adjustment.MethodThirteen couples took part in this research by answering a set of questionnaires investigating, in particular, dyadic coping strategies, marital and sexual satisfaction. Non-parametric analyses were performed on the quantitative data.ResultsEmotional satisfaction is good among the couples in our study. There are important similarities in partners’ emotional adjustment. Patients who are most satisfied with their couple typically have a partner who is also satisfied. This was an expected result based on the literature. Overall, sexual satisfaction is described as average, which is either related to a low frequency of sexual intercourse, or a gap between the ideal and actual frequency of intercourse. In terms of dyadic coping, similarities within couples tend to improve emotional and sexual adjustment. Couples in which communication about stress between the patient and their partner is congruent tend to report good marital satisfaction. We found the same results for delegated coping of both the patient and the partner, and for negative coping of the partner. Sexual adjustment is linked to a similar perception within the couple of a common dyadic coping.ConclusionEmotional and sexual adjustment is largely linked to the quality of the partner’s support. The congruence of couple support strategies has been identified as an important factor in emotional satisfaction. In addition, the more couples implement joint stress management, the better their sexual satisfaction. (shrink)

Theodicy wrestles with suffering and pain, while seeking to understand God's engagement with these realities. Cancer raises similar questions, while focusing on specific aspects of those questions. Cancer appears to challenge many aspects of Christian doctrine, in particular issues regarding the origin of sin, Christology, and ultimately ones doctrine of God. This article explores how my own personal diagnosis of colon cancer has led to an exploration and re-evaluation of these traditional doctrines and their relevance for (...) my own faith journey. The realities of cancer, and random cell mutation as an evolutionary driver, appear to call into question traditional understandings of the origin of suffering and sin, and, I would argue, the very role of Jesus. A process theology that redefines core features of the nature of God is proposed as one way of addressing these doctrines and their impact for faith. These features will note the limited nature of God with regard to power and knowledge as well as the nature of a God who truly risks. (shrink)

Cancer and its treatment pose challenges that affect not only patients but also their significant others, including intimate partners. Accumulating evidence suggests that couples’ ability to communicate effectively plays a major role in the psychological adjustment of both individuals and the quality of their relationship. Two key conceptual models have been proposed to account for how couple communication impacts psychological and relationship adjustment: the social-cognitive processing (SCP) model and the relationship intimacy (RI) model. These models posit different mechanisms and (...) outcomes, and thus have different implications for intervention. The purpose of this project is to test and compare the utility of these models using comprehensive and methodologically rigorous methods. Aims are: (1) to examine the overall fit of the SCP and RI models in explaining patient and partner psychological and relationship adjustment as they occur on a day-to-day basis and over the course of 1 year; (2) to examine the fit of the models for different subgroups (males vs. females, and patients vs. partners); and (3) to examine the utility of various methods of assessing communication by examining the degree to which baseline indices from different measurement strategies predict self-reported adjustment at 1-year follow up. The study employs a longitudinal, multi-method approach to examining communication processes including: standard self-report questionnaires assessing process and outcome variables collected quarterly over the course of 1 year; smartphone-based ecological momentary assessments to sample participant reports in real time; and laboratory-based couple conversations from which we derive observational measures of communicative behavior and affective expression, as well as vocal indices of emotional arousal. Participants are patients with stage II-IV breast, colon, rectal, or lung cancer and their spouses/partners, recruited from two NCI-designated comprehensive cancer centers. Results will be published in scientific journals, presented at scientific conferences, and conveyed to a larger audience through infographics and social media outlets. Findings will inform theory, measurement, and the design and implementation of efficacious interventions aimed at optimizing both patient and partner well-being. (shrink)

Familial clustering of a disease is defined as the occurrence of the disease within some families in excess of what would be expected from the occurrence in the population. It has been demonstrated for several cancer types, ranging from rare cancers as the adenomatosis-coli-associated colon cancer or the Li-Fraumeni syndrome to more common cancers as breast cancer and colon cancer. Familial clustering, however, is merely an epidemiological pattern, and it does not tell whether genetic (...) or environmental causes or both in combination are responsible for the familial clustering. Familial clustering may be due to genetic predisposition to the disease, but exposure to environmental factors — shared by members of some families, but not by members of other families — may also cause familial clustering and hence mimic genetic inheritance in the study of nuclear families. Based on assumptions regarding the individual steps in the biological process starting with exposure to carcinogens and ending with death from disseminated cancer we suggest that genetic and environmental factors may both be involved in most of these steps. The present paper focuses on research methodologies necessary to discriminate between the effect of genes and family environment in the development of cancer. (shrink)

Metastatic spread of tumor cells is one of the most common causes of death in cancer patients. Therefore, elucidation of the molecular mechanisms that underlie the formation of metastatic colonies has been one of the major objectives of cancer research during the last two decades. In this review we will mainly discuss the mechanisms that cause a malignant cell to grow at a given site rather than at other possible sites, taking into account experimental and clinical evidence published (...) on the subject. As a whole this evidence tends to confirm the hypothesis that organ‐specific colonization by malignant cells often follows very specific and close interactions between the cancer cell and the target organ, either in terms of specific cellular adhesion or growth promotion. In this paper we would like to underscore the fact that cellular adhesion, either specific or unspecific, is a necessary but, by itself, insufficient condition for the development of metastases. It is the ability of the tumor cells to grow at the site where they arrested that ultimately determines whether a metastatic colony develops or fails to develop at that site. (shrink)

Narrative analysis is well established as a means of examining the subjective experience of those who suffer chronic illness and cancer. In a study of perceptions of the outcomes of treatment of cancer of the colon, we have been struck by the consistency with which patients record three particular observations of their subjective experience: the immediate impact of the cancer diagnosis and a persisting identification as a cancer patient, regardless of the time since treatment and (...) of the presence or absence of persistent or recurrent disease; a state of variable alienation from social familiars, expressed as an inability to communicate the nature of the experience of the illness, its diagnosis and treatment; and a persistent sense of boundedness, an awareness of limits to space, empowerment and available time. These subjectivities were experienced in varying degree by all patients in our study. Individual responses to these experiences were complex and variable. The experiences are best understood under the rubric of a category we call “liminality”. We believe that all cancer patients enter and experience liminality as a process which begins with the first manifestations of their malignancy. An initial acute phase of liminality is marked by disorientation, a sense of loss and of loss of control, and a sense of uncertainty. An adaptive, enduring phase of suspended liminality supervenes, in which each patient constructs and reconstructs meaning for their experience by means of narrative. This phase persists, probably for the rest of the cancer patient’s life. The experience of liminality is firmly grounded in the changing and experiencing body that houses both the disease and the self. Insights into the nature of the experience can be gained from the Existentialist philosophers and from the history of attitudes to death. Understanding liminality helps us to understand what it is that patients with cancer seek from the system to which they turn for help. Its explication should therefore be important for those who provide health care, those who educate health care workers and those concerned to study and use outcomes as administrative and policy making instruments. (shrink)

Recently, Quyn et al. demonstrated that cells within the stem cell zone of human and mouse intestinal crypts tend to align their mitotic spindles perpendicular to the basal membrane of the crypt. This is associated with asymmetric division, whereby particular proteins and individual chromatids are preferentially segregated to one daughter cell. In colonic mucosa containing a heterozygous adenomatous polyposis coli gene (APC) mutation the asymmetry is lost. Here, we discuss asymmetric stem cell division as an anti‐tumourigenic mechanism. We describe how (...) hierarchical tissue structures suppress somatic evolution, and discuss the relative merits of template strand retention to limit the accumulation of DNA replication errors. We suggest experiments to determine whether somatic mutations resulting in loss of spindle alignment confer an advantage within the stem cell niche. Finally, we discuss whether lack of spindle alignment constitutes an oncogenic event per se, with particular reference to studies in model organisms, and the timing of chromosomal instability in human cancers. (shrink)

Recent work by Fernández‐Sánchez and coworkers examining the impact of applied pressure on the malignant phenotype of murine colon tissue in vivo revealed that mechanical perturbations can drive malignant behavior in genetically normal cells. Their findings build upon an existing understanding of how the mechanical cues experienced by cells within a tissue become progressively modified as the tissue transforms. Using magnetically stimulated ultra‐magnetic liposomes to mimic tumor growth ‐induced solid stress, Fernández‐Sánchez and coworkers were able to stimulate β‐catenin to (...) promote the cancerous behavior of both a normal and genetically modified colon epithelium. In this perspective, we discuss their findings in the context of what is currently known regarding the role of the mechanical landscape in cancer progression and β‐catenin as a mechanotransducer. We review data that suggest that mechanically regulated activation of β‐catenin fosters development of a malignant phenotype in tissue and predict that mechanical cues may contribute to tumor heterogeneity. (shrink)

Most people know precious little about the risks and benefits of participating in a clinical trial--a medical research study involving some innovative treatment for a medical problem. Yet millions of people each year participate anyway. Patients at Risk explains the reality: that our current system intentionally hides much of the information people need to make the right choice about whether to participate. Witness the following scenarios: -Hundreds of patients with colon cancer undergo a new form of keyhole surgery (...) at leading cancer centersnever -Tens of thousands of women at high risk of developing breast cancer are asked to participate in a major research study. They are told about the option of having both breasts surgically removed but not told about the option of taking a standard osteoporosis pill that might cut the risk of getting breast cancer by one-half or more. Patients at Risk written by two nationally prominent experts, is the first book to reveal the secrets that many in the research establishment have fought long and hard to keep from patients. It shows why options not commonly knownincluding getting a new treatment outside of a research studycan often be the best choice. It explains how patients can make good decisions even if there is only limited information about a treatments effect. And it does this through the eye-opening stories of what is happening daily to thousands of people. Day after day, we are learning how little we know about what really works. Headlines regularly announce that a previously unquestioned treatmenthormone replacement therapy, drugs such as Vioxx or Celebrexmay now be much riskier than we thought. The latest book in a surge of recent books criticizing the medical establishment (but the first to look at clinical trials specifically), Patients at Risk helps to empower patients to survive in a world of medical uncertainty, and makes positive recommendations for systemic reform. (shrink)

ABSTRACT The part played by time in ethics is often taken for granted, yet time is essential to moral decision making. This paper looks at time in ethical decisions about having a genetic test. We use a patient‐centred approach, combining empirical research methods with normative ethical analysis to investigate the patients' experience of time in (i) prenatal testing of a foetus for a genetic condition, (ii) predictive or diagnostic testing for breast and colon cancer, or (iii) testing for (...) Huntington's disease (HD). We found that participants often manipulated their experience of time, either using a stepwise process of microdecisions to extend it or, under the time pressure of pregnancy, changing their temporal ‘depth of field’. We discuss the implications of these strategies for normative concepts of moral agency, and for clinical ethics. (shrink)

Der Artikel untersucht einen Fall, in dem jemand von einem Mediziner die Offenlegung der Resultate eines Gentests seines verstorbenen Vaters verlangt. Die vorläufigen Ergebnisse der Studie des Mediziners lassen auf ein um 10% erhöhtes Risiko für Darmkrebs in Verbindung mit der Beschaffenheit eines der Gene des Vaters schließen. Dieser Fall wirft Fragen im Hinblick auf zumindest drei unterschiedliche Aspekte auf: die Offenlegung von Informationen mit geringem Aussagewert; die Offenlegung von Untersuchungsergebnissen gegenüber unmittelbaren Abkömmlingen der Testperson; und die Offenlegung von Untersuchungsergebnissen (...) nach dem Tod der Testperson.Der vorliegende Artikel kommt zu folgenden Ergebnissen: Testresultate mit geringem Aussagewert sollten den Testpersonen auf Anforderung zugänglich gemacht werden; unter bestimmten Umständen sollten genetische Informationen Familienmitgliedern gegenüber offengelegt werden, auch ohne die Zustimmung der Testperson; obwohl die Rechte und Verantwortlichkeiten im Zusammenhang mit der Verpflichtung, das Vertrauensverhältnis gegenüber dem Patienten zu bewahren, normalerweise mit dem Tod des Patienten nicht verringert oder gar aufgehoben werden, könnten im vorliegenden Fall doch bestimmte Faktoren zu einer Verschiebung der Balance hin zu einer Offenlegung der Information führen; und gibt es zu diesem Fall eine Reihe von Varianten, in denen der Mediziner wegen eines Zusammenspiels zwischen den genannten Faktoren berechtigterweise die Testresultate des Vaters dem Sohn gegenüber offenlegen kann. This article explores a case in which a son asks researchers to disclose his deceased father's genetic test results. The preliminary results of the researchers' study suggest a 10% increase in risk of colon cancer associated with the presence of gene. The case raises issues related to at least three distinct policy areas: the disclosure of/ow-value information, the disclosure of research results to immediate biological relatives of research subjects, and the disclosure of research results after the death of a research subject. The article concludes the following: low-value test results should be made available upon request to research subjects, in some circumstances genetic information may be revealed to family members without the subjects' consent, while the rights and responsibilities associated with the obligation to maintain subjects' confidentiality may not generally diminish or end upon their death, certain factors in this case may shift that balance in favor of disclosure, and in this case, because of the interplay between the factors, there are a number of scenarios in which the researchers could justifiably disclose the father's test results to the son. (shrink)

Modern medicine emphasizes treatment of the sick. It is often said that the widespread genetic testing soon to follow the completion of the Human Genome Project will usher in a new era of preventive medicine. Such changes require new ways of thinking, however. For example, there may be nothing clinically wrong with a healthy patient who requests genetic testing, even if the tests reveal disease genes. Since all individuals have genetic skeletons in their closets, it is important to be careful (...) not to confuse having disease genes with having the diseases that they cause. Unfortunately, many in the public have adopted a kind of genetic determinism that sees genes as destiny: for example, having the gene associated with colon cancer means they will develop colon cancer. Physicians tend to be more careful, yet even they are not immune to subtle versions of genetic determinism. One example of this is the uncritical categorization of certain diseases as “genetic”. In fact, an adequate concept of genetic disease is extremely difficult to come by. The simplest notion would require a 1:1 correspondence between a disease and its genes, but this is the exception rather than the rule. For example, cystic fibrosis (CF) is often put forward as a good example of a genetic disease, since it seems to result from mutations in a single gene, CFTR. Even in this case, however, the exact relationship between CFTR mutations and disease is not clear, as virtually every possible combination of sweat chloride test results, genetic test results, and symptoms has been observed.[1] If a patient presents with the classic symptoms of CF and is found to have a mutation in the CFTR gene, the physician might understandably infer that the mutation caused the disease. But if an asymptomatic patient is tested and it is discovered that he or she has a CFTR mutation, it is unclear what this means. The doctor might tell the patient the gene is abnormal and that he or she is likely to develop pulmonary problems, etc., but it’s not really known whether even this qualified prognosis is true.. (shrink)

Researchers summoned a Baltimore County woman to an office at the Johns Hopkins School of Public Health last spring to tell her the bad news. They had found a genetic threat lurking in her 7-year-old son's DNA—a mutant gene that almost always triggers a rare form of colon cancer. It was the same illness that led surgeons to remove her colon in 1979. While the boy, Michael, now 8, is still perfectly healthy, without surgery he is almost (...) certain to develop cancer by age 40.This genetic fortune-telling was no parlor trick. It was the product of astonishing advances in recent decades in understanding how genes build and regulate our bodies. And as scientists pinpoint new genes and learn to forecast the onset of more inherited disorders, millions of people are likely to demand their medical prognosis. (shrink)

Background: Discussing treatment risks has become increasingly important in medical communication. Still, despite regulations, physicians must decide how much and what kind of information to present. Objective: To investigate patients’ preference for information about a small risk of a complication of colonoscopy, and whether medical and personal factors contribute to such preference. To propose a disclosure policy related to our results. Design: Vignettes study. Setting: Department of Gastroenterology, Academic Medical Centre, the Netherlands. Patients: 810 consecutive colonoscopy patients. Intervention: A home-sent (...) questionnaire containing three vignettes. Vignettes varied in the indication for colonoscopy, complication severity and level of risk. Patients were invited to indicate their wish to be informed and the importance of such information. In addition, sociodemograhic, illness-related and psychological characteristics were assessed. Main outcome measurements: Wish to be informed and importance of information. Results: Of 810 questionnaires, 68% were returned. Patients generally wished to be informed about low-risk complications, regardless of the indication for colonoscopy or the severity of the complication. The level of risk did matter, though (OR = 2.48, SE = 0.28, p = 0.001). The information was considered less important if done for population screening purposes or diagnosis of colon cancer, if the complication was less severe (bleeding) and if the risk was smaller (0.01% and 0.1%). Patients’ information preference was also related to age, mood and coping style. Limitations: Difficulty of vignettes. Conclusions: Patients generally wish to be informed about all possible risks. However, this might become uninformative. A stepwise approach is suggested. (shrink)

Last month, a fifty-eight-year old man developed bleeding into his cheek and oozing from sites where previously he had had blood samples drawn. This bleeding was caused by disseminated intravascular coagulation, a complication of colon cancer that had spread to his liver and lungs. This complication occurred even though he was on chemotherapy for the cancer. In the hospital, he received transfusions and was administered medicine to stop the bleeding. However, his condition did not improve. He developed (...) more bruises. When he tried to go to the bathroom without assistance, he fell, struck his head, requiring stitches, and developed a black, swollen eye. The patient, a successful businessman, had already overcome another type of cancer—lymphoma—through chemotherapy, twenty-five years ago. In a few days, this dynamic individual who expected to start experimental chemotherapy now saw his quality of life deteriorate steadily.We talked about more chemotherapy, about hospice, and about withholding attempts at resuscitation if his heart should stop. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Dying is DifficultClarice DouilleHayden had been a constant in my life since I was eight, as our families were close. He was a single dad who loved to talk and always had a smile on his face. He was obsessed with anything related to his kids and attended every school activity or sporting event.In 2015, Hayden was diagnosed with stage III colon cancer. He was adamant that (...) he didn't want to share any information about his condition with his kids, waiting several months until the eve of his first surgery before breaking the news to them. Hayden made the operation seem trivial and underplayed the severity of the chemotherapy treatments that would follow. Despite whatever he was feeling, he seemed committed to maintaining his happy demeanor, which was probably an effort to convince himself and others to feel better about the situation.Hayden survived his first operation and rounds of chemotherapy. And, over the next several years, he chose to undergo a regimen of additional aggressive treatments, submitting to surgery after surgery, as well as several more rounds of chemotherapy, followed by radiation treatments. I was already working as a home care aide, and because of the close relationship between our families, Hayden asked me to help as his caregiver, including running errands and babysitting for his younger kids. Hayden made it clear that he wanted his kids to remain ignorant of the progression of his condition so that they wouldn't worry and become anxious. It seemed he was motivated by his desire to preserve his young kids' happiness and innocence. In hindsight, I think this prevented his kids from being able to fully savor moments with their dad or prepare for the possibility of his death. I also think Hayden was trying to shelter himself from his own fear of mortality. And it was this fear that made Hayden a "difficult patient."Hayden suffered both physically and mentally, not only from his disease and treatment but also from his fear of mortality. I noticed how he tried to hide his suffering by shutting himself in his bedroom and making excuses when he wasn't eating. He often forgot to take his medications; he refused to use pill boxes and objected to reminders from others. The consequences often meant additional hospitalizations. I wish more palliative options had been introduced to him earlier in his disease course. I believe a palliative care team would have encouraged Hayden to think about and discuss death, helped him change his outlook for treatment and living with cancer, and most importantly, enabled him to better enjoy the remainder of his life with his kids.Nevertheless, I understood why Hayden was worried about his kids, and I could see how his recent personal experiences since his initial diagnosis might have contributed to his choice for the most aggressive treatments: his sister and both his parents had died, leaving no other relatives to care for his kids. He wanted to be there for his kids, yet the side effects of treatment made him so sick that he couldn't leave his bed. He couldn't even do the very activities that made him want to live.Hayden was an extremely social person, but when he found out his cancer was terminal, he [End Page E6] isolated himself from his loved ones for nearly six weeks. Even though I was likely the only person he was communicating with, as the person who helped him and his family, I often didn't see him for weeks at a time. He would text me requests, leave money on the front table, and ask me to drop off the items I purchased and then leave. Hayden's kids continued their daily routines, despite comments from them about his absence.In early August 2020, Hayden was admitted to the hospital. His doctor called the kids at home and told them that their dad would immediately be enrolled in hospice care. They were, as one might expect, shocked at this news. They knew their dad was sick and had been dealing with his cancer for years. But Hayden's health deteriorated slowly, and the kids hadn't known... (shrink)

Surgical resection of a primary tumour is often not sufficient to cure a patient. Even when no residual cancer can be detected at time of surgery, metastases may appear in the following years, which indicates that the primary tumour had apparently spread before surgery. Following surgery, systemic chemotherapy may be used to eradicate micro‐metastatic disease. Here we present two unconventional strategies that implement new insights into tumour biology and tumour immunology in the treatment of patients with cancer. Both (...) experimental strategies use the individual characteristics of the patient's primary tumour to optimise the control of life‐threatening micro‐metastases. We aim to modulate the patient's adaptive immune system, targeting it towards the patient's own tumour cells to eradicate residual disease following local treatment. In one approach, this is done by autologous tumour cell vaccinations as adjuvant treatment for colon cancer patients and, in a second approach, by giving chemo‐imunotherapy before local treatment to women with locally advanced breast cancer. BioEssays 25:79–86, 2003. © 2002 Wiley Periodicals, Inc. (shrink)

On the basis of the evidence that tumor development is suppressed by the embryonic microenvironment, some experiments using the factors taken from Zebrafish embryo at precise stages of cell differentiation were made. These experiments demonstrated a significant growth inhibition on different tumor cell lines in vitro. The observed mechanism of tumor growth inhibition is connected with the key-role cell cycle regulation molecules, such as p53 and pRb, which are modified by transcriptional or post-translational processes. Research on apoptosis and differentiation revealed (...) that treatment with these factors induces caspase-3 with a p73 apoptotic-dependent pathway activation and a concurrent significant normalization of e-cadherin and beta-catenin ratio. Other experiments found a synergistic effect on the colon cancer proliferation curve after the concurrent treatment with these factors and 5-fluorouracil. Finally, a product prepared for human therapy demonstrated 19.8% regression and 16% stable disease in an... (shrink)

Health and disease are core concepts in health care and have attracted substantial interest and controversy. In recent and interesting contributions to the debate it has been argued that the challenges with the concept of disease can be resolved by a prototype concept of disease. As a robin is a more prototypical of a bird than a penguin, some diseases are more prototypical than others. If disease is a prototype concept, it would change nosology, but also health care and the (...) study of health and disease. However, the statement that “disease is a prototype concept” forms an empirically testable hypothesis. Therefore, this study aims to test the hypothesis that health professionals have a prototype concept of disease. Two hundred twenty-three health care professionals in Norway were invited to participate in a survey where they were asked to rank a wide range of diseases according to how typical they considered them to be as diseases. Results were analysed with descriptive statistics. The response rate was 90%. Lung cancer, leukemia, colon cancer, myocardial infarction, and AIDS are the diseases ranged to be most typical, while homosexuality, pregnancy, drapetomania, dissidence, and nostalgia are considered to be the least typical diseases. The results also show that the answers to how typical various diseases are vary greatly, even amongst a relatively homogenous group of health professionals. This study falsifies the hypothesis that disease is a prototype concept for health professionals. This has implications for the debate on core concepts for health care. If health professionals do not have a prototype concept of disease, it is unlikely that there is a prototype concept of disease in general. Consequently, nosologies should not be based on prototypes. (shrink)

The National Cancer Institute’s Thesaurus (NCIT) has been created with the goal of providing a controlled vocabulary which can be used by specialists in the various sub-domains of oncology. It is intended to be used for purposes of annotation in ways designed to ensure the integration of data and information deriving from these various sub-domains, and thus to support more powerful cross-domain inferences. In order to evaluate its suitability for this purpose, we examined the NCIT’s treatment of the kinds (...) of entities which are fundamental to an ontology of colon carcinoma. We here describe the problems we uncovered concerning classification, synonymy, relations and definitions, and we draw conclusions for the work needed to establish the NCIT as a reference ontology for the cancer domain in the future. (shrink)

In vitro fertilization using donated oocytes has proven to be an effective treatment option for many prospective parents struggling with infertility, and the usage of donated oocytes in assisted reproduction has increased markedly since the technique was first successfully used in 1984. Data published by the Centers for Disease Control and Prevention on the use of assisted reproductive technologies in the United States indicate that approximately 12% of all ART cycles in the country now use donated oocytes. The increased use (...) of oocyte donation in the United States has prompted discussion regarding risks associated with the process and how best to ensure the safety of oocyte donors.Physical risks associated with oocyte donation include bleeding, infection, ovarian hyperstimulation syndrome and a potential, although unconfirmed, increased risk of developing various forms of cancer, such as uterine, colon, breast, ovarian, and endometrial cancers. (shrink)

DNA mismatch repair is an important pathway of mutation avoidance. It also contributes to the cytotoxic effects of some kinds of DNA damage, and cells defective in mismatch repair are resistant, or tolerant, to the presence of some normally cytotoxic base analogues in their DNA. The absence of a particular mismatch binding function from some mammalian cells confers resistance to the base analogues O6‐methylguanine and 6‐thioguanine in DNA. Cells also acquire a spontaneous mutator phenotype as a consequence of this defect. (...) Impaired mismatch binding can cause an instability in DNA microsatellite regions that comprise repeated dinucleotides. Microsatellite DNA instability is common in familial and sporadic colon carcinomas as well as in a number of other tumours. Several independent lines of investigation have identified defects in mismatch repair proteins that are causally related to these cancers. (shrink)

General knowledge of the role of vitamin D3 in human physiology has been shaped by its discovery as a preventive agent of nutritional rickets, a defect in bone development due to inadequate uptake of dietary calcium. Studies on the function of the hormonal form of vitamin D3, 1α,25‐dihydroxyvitamin D3, have been greatly accelerated by the molecular cloning and structural analysis of the vitamin D3 receptor, which is a ligand‐activated regulator of gene transcription. Molecular genetic techniques including genomics have helped reveal (...) that 1α,25‐dihydroxyvitamin D3 can control more than calcium homeostasis. It has widespread effects on cellular differentiation and proliferation, and can modulate immune responsiveness, and central nervous system function. Moreover, accumulating epidemiological and molecular evidence suggests that 1α,25‐dihydroxyvitamin D3 acts as a chemopreventive agent against several malignancies including cancers of the prostate and colon. Here, we survey the most‐recent findings and discuss their implications for the potential therapeutic uses of vitamin D analogues. BioEssays 26:21–28, 2004. © 2003 Wiley Periodicals, Inc. (shrink)

There are a number of existing classifications and staging schemes for carcinomas, one of the most frequently used being the TNM classification. Such classifications represent classes of entities which exist at various anatomical levels of granularity. We argue that in order to apply such representations to the Electronic Health Records one needs sound ontologies which take into consideration the diversity of the domains which are involved in clinical bioinformatics. Here we outline a formal theory for addressing these issues in a (...) way that the ontologies can be used to support inferences relating to entities which exist at different anatomical levels of granularity. Our case study is the colon carcinoma, one of the most common carcinomas prevalent within the European population. (shrink)

As we have discussed elsewhere, Franz Boas and John Dewey were intellectual and political allies at Columbia University for over thirty years.1 Dewey advocated for an increased role of anthropology for philosophical insight, and he often used anthropological knowledge as a starting point for his ethics and politics, including such knowledge as learned from Boas. We hold that Boas and Dewey shared a common core understanding of human global and evolutionary diversity, and that this shared understanding itself forms a core (...) component of their progressive projects.However, with regard to the problem of racism in the United States, Boas and Dewey had different engagements. Boas made the questioning... (shrink)

Rousseau has always had an uncertain relationship with the theory of constituent power. On the one hand, his distrust of political representation and support for popular sovereignty seem consistent with the idea of the people as a legally unlimited constitution-maker. On the other hand, if, from those views about representation and sovereignty, it follows that Rousseau is a proponent of direct democracy, then there seems to be no place in his thought for a theory that presupposes, above all, a separation (...) between those who exercise a delegated authority and those who possess an original constitution-making power. In a legal order in which all laws must be directly made by the people, such a separation is absent: the constituent and the legislative body are one and the same. It is therefore not surprising that Rousseau’s name is largely absent from contemporary literature on constituent power. In this article, however, I will show that once Rousseau’s particular conception of law, as well as his distinction between sovereignty and government, are properly understood, one finds in his work not only the first major formulation of the theory of constituent power, but also a careful exploration of its implications for actual constitutional practice. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:The Problem with BreathÉglantine Colon (bio)On day 1, when my comrades and I talked about it, we couldn't quite figure out how it happened. It just seemed as though we had suddenly been incited not to communicate or enact our love for each other. This time, no policy had been formulated, no law had been issued. It was harder than usual to locate where, to which parts of (...) the apparatus, we should direct our attention.On day 2, we were at a loss. We had gotten so good at reading the apparatus. We had developed wonderfully efficient techniques of resistance. Each and every one of us had become most brilliant at crafting discrete gestures of love. On day 3 onwards, we were misfiring on a regular basis, falling in and out of love with the same wrong comrades, over and over again, and always out of sync. The loving gestures we composed were barely legible and when we would intuitively find a genre in which to communicate our love, something would inevitably break down. Voices, generally. Sometimes the entire figurative system. Bodies, always. We would lose sleep and appetite over love and get useless for weeks.And then, the problem with love became a problem with breath. On day 6, the air got hot and busy with ashes and all sunsets turned red. At every breath, for all we knew, we could be inhaling particles of carbonized pine sap, debris of melted trailer parts, or burnt baby birds in bits. I quit smoking. I bought boxes of white masks at the construction store. The dominant smell during these days was a cagey mix of ghost paint, polymer fibers, and dry chemistry.On day 17, the air got cold and saturated with drops of viral poison. The city shut down. An incredibly sad number of lungs, too. The perspective to live in pods and die alone, disconnected from each other's breath, hyper-connected to life-support machines, plunged many of us, myself included, into brand new strands of historical despair. For those of us whose lungs had been weakened by bad inner-city fumes, evil chemicals, or entire centuries of racialized exposure to horrendous air quality, the problem with breath became plain lethal.Our neighborhoods were saturated with wildfire smoke and unnecessary death. Elsewhere, the streets were not empty. And when I say not empty, I mean they were just not. Or not yet. Usual metallic densities on the bridge. Geometrical glows of digital light in the underground. [End Page 237]Abnormally, no bodies of any ancestries were being captured, or hanged, or tortured, or kneeled upon. Nothing tangible, nothing blatantly repressive this time. No gas, no gag, no name, no whip, no rope. No strangulating remnant of sovereignty within no softness of biopower. A racist and classist brand of distributive pneumocracy is what it was, or at least this is how it initially appeared.On day 25, "Critical Pandemic Studies" became a thing, and "Pod Theory" a subgenre in post-social anthropology. Denounced as a "white fantasy of networked individualism," (in one of its purest forms) as "domestic fascism dressed as elective affinity," the pod appeared to us, from the get-go, as a thoroughly ratchet social formation. On day 29, the "podtag" emerged as a timely intervention in existing forms of street art. Equational in its form, efficient in its power of evocation, and satirical in its poetic economy, the podtag proliferated on the privatized walls of neighborhoods where the biggest challenges presented to breathing were unreasonably difficult Pilates classes on Zoom. Click for larger view View full resolutionOn day 35, the air got complex and full of knots, so striated that we could no longer count on our capacity to share the same air. A meal was being cooked, an instrument was being played, a child was given birth to, and suddenly the rhythm of all breaths would break. Sometimes a pair of lungs would refuse, stubbornly, to take in any oxygen until someone else's pair of lungs had released its own dose of carbon dioxide. At other times, the quantity of air available to each one of us would decrease with... (shrink)

Suzan Colon, yoga teacher and former senior editor at O, The Oprah Magazine, digs deep into the spiritual philosophy behind yoga and distills thirty essential components to enrich your practice and revolutionize your life from the inside out. We live in an increasingly stressful world, and we know about the hazardous effects stress can have on our health. But meditating and mindfulness can sometimes seem elusive, unattainable, and impossible to fit into our busy days. Even the word “yoga” usually (...) makes many people think of complicated, twisty poses—but that’s not everything. In its complete sense, yoga is a collection of life lessons for wellness and well-being and a spiritual technology from ancient times that is now more relevant, and necessary, than ever. In Yoga Mind, Suzan Colon shares thirty essential components to increase self- awareness and inner balance to use throughout your day—in traffic, on the train, at your job, and home. She outlines how we can use yoga to cultivate resilience in challenging times, reduce stress, and enrich our relationships with family, work, and ourselves. This guide contains a 30-day program designed to create subtle yet powerful shifts in awareness and attitude that lead to real, lasting change. Whether you’re a hardcore yogi or a beginner to the practice, Yoga Mind can help you unite your body, mind, and heart to become your best self and cultivate lasting happiness in your life. (shrink)

El conjunto de ensayos que el lector tiene entre sus manos expresa un cuerpo sistemático de ideas provocadoras sobre la tensión entre el constitucionalismo y la democracia. Su autor, el profesor Joel Colón-Ríos, boricua, formado en las dos facultades de derecho canadienses de mayor renombre, e investigador de una de las mejores universidades de Oceanía, las ha fraguado a lo largo de más de un lustro y debatido con gran éxito ante la elite intelectual de Norteamérica. La propuesta central del (...) libro es una original reivindicación de la democracia frente al constitucionalismo. Su institucionalización consiste en un constitucionalismo débil. La piedra angular de este modelo es una constitución inacabada, permanentemente abierta al cambio, que permite y promueve la participación y la deliberación popular continua, en particular, mediante el potencial ejercicio del poder constituyente en cualquier momento. De esta manera, el pueblo tiene la posibilidad de hablar por sí mismo cuando lo juzgue pertinente. Puede cuestionar y reformular los principios básicos de la organización social. No está supeditado a las decisiones adoptadas por los ancestros que expidieron la Constitución, ni por sus representantes que, en el Congreso, ostentan el poder de reformarla. Precio: 49.000 pesos. (shrink)

Nearly twenty years after SubStance devoted a special issue to the contemporary French writer we know as Antoine Volodine, we are thoroughly pleased to be publishing in this issue the opening of Dondog, a novel that Ben Streeter has translated with inspired exactitude and brilliant tonal precision. In English or in French, entering Dondog is not unlike entering any other "post-exotic" text. One has to learn how to orient oneself to the ruination of Modernity, within the dysfunctional memories of post-traumatic (...) subjects, between dark humor and luminous despair, in the liminal space between life and death, between humanity and animality, and, in the odd beauty... (shrink)

Salomón de la Selva (1893-1959) was a Nicaraguan writer/activist who authored many books of verse in Spanish, but only one in English: TropicalTown, And Other Poems (1918). Published in New York by John Lane–and regarded by Silvio Sirias as the first book of English verse published in the U.S.by a Latin American–Tropical Town exhibits a curious dynamic of avantgarde impulse: radically subversive in invoking counter-politics resisting U.S. colonial transnationalism, yet tending toward inherited, traditional aesthetic forms of poetry meant to legitimize (...) Selva’s Latin American identity with an impression of authority that contiguous Modernist experimental poetries could not. Through its sympathy for the U.S. immigrant’s nostalgia for homeland, coupled with express disapproval of U.S. international affairs, Tropical Town leaves a poetic record that challenges presuppositions about the integral relationships between ethos, aesthetics, and consciousness vis-à-vis assumed understandings of what constitutes radical poetry in the Modernist moment. (shrink)

In 1903, W. E. B. Du Bois addressed the question "How does it feel to be a social problem?". In 2008, Moustafa Bayoumi answered the same question for Muslims in the United States. Both Du Bois and Bayoumi provide powerful critiques against any notion that racialized minorities are inherently problematic. Both men generally argue that one cannot blame racialized minorities for the ill treatment they endure under systematic oppression. Du Bois and Bayoumi are two of many voices fighting against the (...) popular stigmatization of racialized peoples that include public intellectuals, civil rights activists, politicians, community leaders, educators, and many others. One of the things that all these voices have in common... (shrink)

El estudio de la conciencia es de considerable relevancia en la filosofía de la mente contemporánea. Sin embargo, el enfoque “cientificista” imperante en esta disciplina, aunque de indiscutible utilidad, ha contribuido al rechazo de perspectivas cuyo valor explicativo resulta revelador en la investigación sobre la mente, la consciencia y el cuerpo. Una de estas perspectivas la podemos encontrar en la obra filosófica de Friedrich Nietzsche. El determinismo causal de la relación mente-cuerpo que propuso el filósofo alemán ha sido defendido por (...) medio de propuestas similares de neurocientíficos y filósofos de probada pericia. No obstante, la relevancia de la aportación nietzscheana no ha sido reconocida en su importancia histórica y teórica. El propósito de este artículo es señalar las particularidades sobre la determinación causal de la relación mente/cuerpo y sus implicaciones en los debates actuales sobre la naturaleza de la consciencia. (shrink)