In this paper an Artificial Neural Network (ANN) model, for predicting the category of a tumor was developed and tested. Taking patients’ tests, a number of information gained that influence the classification of the tumor. Such information as age, sex, histologic-type, degree-of-diffe, status of bone, bone-marrow, lung, pleura, peritoneum, liver, brain, skin, neck, supraclavicular, axillar, mediastinum, and abdominal. They were used as input variables for the ANN model. A model based on the Multilayer Perceptron Topology was established and trained using (...) data set which its title is “primary tumor” and was obtained from the University Medical Centre, Institute of Oncology, Ljubljana, Yugoslavia Test data evaluation shows that the ANN model is able to correctly predict the tumor category with 76.67 % accuracy. (shrink)

I argue that ductal carcinoma in situ (DCIS), the tumor most commonly diagnosed by breast mammography, cannot be confidently classified as cancer, that is, as pathological. This is because there may not be dysfunction present in DCIS—as I argue based on its high prevalence and the small amount of risk it conveys—and thus DCIS may not count as a disease by dysfunction-requiring approaches, such as Boorse’s biostatistical theory and Wakefield’s harmful dysfunction account. Patients should decide about treatment for DCIS based (...) on the risks it poses and the risks and benefits of treatment, not on its disease status. (shrink)

The practice and development of modern medicine requires large amounts of data, particularly in the domain of cancer. The future of personalized medicine lies neither with “genomic medicine” nor with “precision medicine”, but with “data medicine”. The establishment of this DM has required far-reaching changes, to establish four essential elements connecting patients and doctors: biobanks, databases, bioinformatic platforms and genomic platforms. The “transformation” of scientific research areas, such as genetics, bioinformatics and biostatistics, into clinical specialties has generated a new vision (...) of care. Molecular tumor boards are one response to these changes and are now providing better access to next-generation sequencing and new cancer treatments to patients with inoperable or metastatic cancers, and those for whom the usual treatment has failed. However, MTB face a crucial ethical challenge: maintaining and improving the trust of patients, clinicians, researchers and industry in academic medical centers supported by private or public funding rather than providing genetic data directly to private companies. We believe that, in this era of DM, appropriate modern digital communication networks will be required to maintain this trust and to improve the organization and effectiveness of the system. There is, therefore, a need to reconsider the form and content of informed consent documents at all academic medical centers and to introduce dynamic and electronic informed consent. (shrink)

The practice and development of modern medicine requires large amounts of data, particularly in the domain of cancer. The future of personalized medicine lies neither with “genomic medicine” nor with “precision medicine”, but with “data medicine”. The establishment of this DM has required far-reaching changes, to establish four essential elements connecting patients and doctors: biobanks, databases, bioinformatic platforms and genomic platforms. The “transformation” of scientific research areas, such as genetics, bioinformatics and biostatistics, into clinical specialties has generated a new vision (...) of care. Molecular tumor boards are one response to these changes and are now providing better access to next-generation sequencing and new cancer treatments to patients with inoperable or metastatic cancers, and those for whom the usual treatment has failed. However, MTB face a crucial ethical challenge: maintaining and improving the trust of patients, clinicians, researchers and industry in academic medical centers supported by private or public funding rather than providing genetic data directly to private companies. We believe that, in this era of DM, appropriate modern digital communication networks will be required to maintain this trust and to improve the organization and effectiveness of the system. There is, therefore, a need to reconsider the form and content of informed consent documents at all academic medical centers and to introduce dynamic and electronic informed consent. (shrink)

Tumor necrosis is a common histological feature and poor prognostic predictor in various cancers. Despite its significant clinical implications, the mechanism underlying tumor necrosis remains largely unclear due to lack of appropriate pre‐clinical modeling. We propose that tumor necrosis is a synergistic consequence of metabolic stress and inflammation, which lead to oxidative stress‐induced cell death, such as ferroptosis. As a natural consequence of tumor expansion, tumor cells are inevitably stripped of vascular supply, resulting in deprivation of oxygen and nutrients. The (...) resulting metabolic stress has commonly been considered the cause of tumor necrosis. Recent studies found that immune cells, such as neutrophils, when recruited to tumors, can directly trigger ferroptosis in tumor cells, suggesting that immune cells can be involved in amplifying tumor necrosis. This article will discuss potential mechanisms underlying tumor necrosis development and its impact on tumor progression as well as the immune response to tumors. (shrink)

Tumor‐infiltrating lymphocyte (TIL) therapy is a promising approach for treating refractory or advanced solid cancers by using autologous TILs harvested from cancer tissues. Despite the heterogeneity of cancer, TIL therapy can potentially produce a positive therapeutic response, including complete remission.After decades of research on lymphocyte functions, culture/expansion methods, therapeutic protocols, and multiple clinical trials, TIL therapy has finally reached a stage where it can be formally approved for clinical use.TIL therapy is expected to hold a unique position among anti‐cancer therapeutic (...) options as a standard intervention. To successfully introduce TIL therapy into clinical settings, there is a need to expand therapeutic indications and set up the best protocols for cancer tissue sampling and manufacturing, and related clinical trials. Moreover, studies on next‐generation TIL therapy have already begun, and post‐approval real‐world data will promote and support further research. (shrink)

Information transmission from tumor cells to non‐tumor cells in the surrounding microenvironment via microvesicles is a more recently studied form of intercellular signaling that can have a marked impact on the tumor microenvironment. Tumor‐derived microvesicles (TMVs) are packed with information including signaling proteins and nucleic acids, and can be taken up by target cells, enabling paracrine signaling. While previous research has focused on how vesicles released from pathologic cells differ from normal cells, the heterogeneity that exists within the TMV population (...) itself is not fully characterized, and only beginning to be appreciated. In this review, we summarize current understanding of the biogenesis and roles of shed TMVs in the tumor microenvironment, and speculate on the consequences for tumor cell signaling in light of the hypothesis that there exists variance within the TMV population. The analysis of differential signaling upon cell‐TMV interactions provides insights into potential mechanisms of intercellular communication. (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)

Cancer drugs are broadly classified into two categories: cytotoxic chemotherapies and targeted therapies that specifically modulate the activity of one or more proteins involved in cancer. Major advances have been achieved in targeted cancer therapies in the past few decades, which is ascribed to the increasing understanding of molecular mechanisms for cancer initiation and progression. Consequently, monoclonal antibodies and small molecules have been developed to interfere with a specific molecular oncogenic target. Targeting gain‐of‐function mutations, in general, has been productive. However, (...) it has been a major challenge to use standard pharmacologic approaches to target loss‐of‐function mutations of tumor suppressor genes. Novel approaches, including synthetic lethality and collateral vulnerability screens, are now being developed to target gene defects in p53, PTEN, and BRCA1/2. Here, we review and summarize the recent findings in cancer genomics, drug development, and molecular cancer biology, which show promise in targeting tumor suppressors in cancer therapeutics. (shrink)

Tumor progression involves the transition from normal to malignant cells, through a series of cumulative alterations. During this process, invasive and migratory properties are acquired, enabling cells to metastasize (reach and grow in tissues far from their origin). Numerous cellular changes take place during epithelial malignancy, and disruption of E‐cadherin based cell‐cell adhesion is a major event. The small Rho GTPases (Rho, Rac and Cdc42) have been implicated in multiple steps during cellular transformation, including alterations on the adhesion status of (...) the tumor cells. This review focuses on recent in vivo evidence that implicates RhoGTPases in epithelial tumor progression. In addition, we discuss different hypotheses to explain disruption of cadherin‐mediated cell–cell adhesion, directly or indirectly, through activation of Rho GTPases. Understanding the molecular mechanism of how cadherin adhesion and RhoGTPases interplay in normal cells and how this balance is altered during cellular transformation will provide clues as to how to interfere with tumor progression. © 2003 Wiley Periodicals, Inc. BioEssays 25:452–463, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

The present paper deals with a free boundary problem modeling the growth process of necrotic multi-layer tumors. We prove the existence of flat stationary solutions and determine the linearization of our model at such an equilibrium. Finally, we compute the solutions of the stationary linearized problem and comment on bifurcation.

The retinoblastoma sensitivity protein (Rb) and the p53 gene product both appear to function as negative regulators of cell division or abnormal cellular growth in some differentiated cell types. Several types of cancers have been shown to be derived from cells that have extensively mutated both alleles of one or both of these genes, resulting in a loss‐of‐function mutation. In the case of the p53 gene, this mutational process appears to occur in two steps, with the first mutation at the (...) p53 locus resulting in a trans‐dominant phenotype. The mutant p53 gene product enters into an oligomeric protein complex with the wild‐type p53 protein derived from the other normal allele and such a complex is inactive or less efficient in its negative regulation of growth control. This intermediate stage of carcinogenesis selects for the proliferation of cells with one mutant allele, enhancing the probability of obtaining a cancer cell with both alleles damaged.The DNA tumor viruses have evolved mechanisms to interact with the Rb and p53 negative regulators of cellular growth in order to enhance their own replication in growing cells. SV40 and adenovirus type 5 produce viral encoded proteins that also form oligomeric protein complexes with p53 and Rb, presumably inactivating their functions. These viral proteins are also the oncogene products of these viruses. Thus, the mechanisms by which cancer may arise in a host, via mutations or virus infections, have fundamental common pathways effecting the same cellular genes and gene products; Rb and p53. (shrink)

Over the past thirty years, the doctrine of informed consent has become a focal point in discussions of medical ethics. The literature of informed consent explores the evolution of the principle of autonomy, purportedly emerging from the mists of 19th Century medical practice, and finding its earliest articulation in legal cases where wronged citizens asserted their rights against medical authority. A commonplace, if not obligatory, feature of that literature is a reference to the case of Mary Schloendorff and the opinion (...) written by Judge Benjamin Cardozo by which the case is remembered. Commentators today applaud the prescience of Cardozo for an early articulation of what eventually would become bioethical orthodoxy concerning informed consent and its place as a bulwark of patient autonomy. They inevitably quote Cardozo's famous statement, “Every human being of adult years and sound mind has a right to determine what shall be done with his own body.”. (shrink)

Over the past thirty years, the doctrine of informed consent has become a focal point in discussions of medical ethics. The literature of informed consent explores the evolution of the principle of autonomy, purportedly emerging from the mists of 19th Century medical practice, and finding its earliest articulation in legal cases where wronged citizens asserted their rights against medical authority. A commonplace, if not obligatory, feature of that literature is a reference to the case of Mary Schloendorff and the opinion (...) written by Judge Benjamin Cardozo by which the case is remembered. Commentators today applaud the prescience of Cardozo for an early articulation of what eventually would become bioethical orthodoxy concerning informed consent and its place as a bulwark of patient autonomy. They inevitably quote Cardozo's famous statement, “Every human being of adult years and sound mind has a right to determine what shall be done with his own body.”. (shrink)

When talking about decisionmaking for children with a life-threatening condition, the death of children with brain tumors deserves special attention. The last days of the lives of these children can be particularly harsh for bystanders, and raise questions about the suffering of these children themselves. In the Netherlands, these children are part of the group for whom a wide range of end-of-life decisions are discussed, and questions raised. What does the end-of-life for these children look like, and what motivates (...) physicians and parents to make decisions that may affect the life and death of these children? This article highlights the story of the parents of the sisters Roos and Noor. When both their daughters were diagnosed with a hereditary brain tumor, they had to make similar decisions twice. Their story sheds light on the suffering of children in the terminal phase, and how this suffering may motivate parents and physicians to make decisions that influence the end of life of these children’s lives.We argue that complete knowledge about suffering in the terminal phase of children with brain tumors is impossible. However, by collecting experiences like those of Roos and Noor, we can move toward an experienced-based understanding and better guide parents and physicians through these hardest of decisions. (shrink)

Approaches to induce tumor differentiation often result in manageable and therapy‐naïve cellular states in cancer cells. This transformation is achieved by activating pathways that drive tumor cells away from plasticity, a state that commonly correlates with enhanced aggression, metastasis and resistance to therapy. Here, we discuss signaling pathways, epigenetics and non‐coding RNAs as three main regulatory levels with the potential to drive tumor differentiation and hence as potential targets in differentiation therapy approaches. The success of an effective therapeutic regimen in (...) one cancer, however, does not necessarily sustain across cancer types; a phenomenon largely resulting from heterogeneity in the genetic and physiological landscapes of tumor types necessitating an approach designed for each cancer's unique genetic and phenotypic build‐up. (shrink)

This narrative symposium brings to light the extreme difficulties faced by parents of children diagnosed with brain tumors. NIB editorial staff and narrative symposium editors, Gigi McMillan and Christy A. Rentmeester, developed a call for stories that was distributed on several list serves and posted on Narrative Inquiry in Bioethics’ website. The call asks parents to share their personal experience of diagnosis, treatment, long–term effects of treatment, social issues and the doctor–patient–parent dynamic that develops during this process. Thirteen stories (...) are found in the print version of the journal and an additional six supplemental stories are published online only through Project MUSE. One change readers may notice is that the story authors are not listed in alphabetical order. The symposium editors had a vision for this issue that included leading readers through the timeline of this topic: diagnosis–treatment–acute recovery–recurrence–treatment (again)– acute recovery (again)– long-term quality of life– (possibly) end of life. Stories are arranged to help lead the reader through this timeline. Gigi McMillan is a patient and research subject advocate, co-founder of We Can, Pediatric Brain Tumor Network, as well as, the mother of a child who suffered from a pediatric brain tumor. She also authored the introduction for this symposium. Christy Rentmeester is an Associate Professor of Health Policy and Ethics in the Creighton University School of Medicine. She served as a commentator for this issue. Other commentators for this issue are Michael Barraza, a clinical psychologist and board member of We Can, Pediatric Brain Tumor Network ; Lisa Stern, a pediatrician who has diagnosed six children with brain tumors in her 20 years of practice; and Katie Rose, a pediatric brain tumor patient who shares her special insights about this world. (shrink)

The tumor microenvironment (TME) plays a pivotal role in the behavior and development of solid tumors as well as shaping the immune response against them. As the tumor cells proliferate, the space they occupy and their physical interactions with the surrounding tissue increases. The growing tumor tissue becomes a complex dynamic structure, containing connective tissue, vascular structures, and extracellular matrix (ECM) that facilitates stimulation, oxygenation, and nutrition, necessary for its fast growth. Mechanical cues such as stiffness, solid stress, interstitial (...) fluid pressure (IFP), matrix density, and microarchitecture influence cellular functions and ultimately tumor progression and metastasis. In this fight, our body is equipped with T cells as its spearhead against tumors. However, the altered biochemical and mechanical environment of the tumor niche affects T cell efficacy and leads to their exhaustion. Understanding the mechanobiological properties of the TME and their effects on T cells is key for developing novel adoptive tumor immunotherapies. (shrink)

High-resolution neuroimaging modalities are used often in studies involving healthy volunteers. Subsequently, a significant increase in the incidental discovery of asymptomatic intracranial abnormalities raised the important ethical issues of when follow-up and treatment may be necessary. We examined the literature to establish a practical set of criteria for approaching incidental findings. Our objective is to develop an algorithm for when follow-up may be important and to provide recommendations that would increase the likelihood of follow-up. A systematic literature search was performed (...) using the PubMed and MEDLINE databases to identify articles describing brain tumors and intracranial aneurysms. The treatment algorithm we present suggests that incidental intracranial masses suspicious for glioma should be biopsied or resected, while other masses are to be followed with serial imaging based on the expected growth pattern. Lack of follow-up can result in adverse outcomes that can be mitigated by using technology to facilitate communication and improve follow-up care. The importance of training physicians to be good communicators is also stressed. New technology including automated telephone systems, texting and email will improve access to patients and hopefully encourage compliance and follow-up. (shrink)

Two experiments tested the hypothesis that neurological abnormalities decrease punishment by decreasing perceptions of free will. Experiment 1 found that a brain tumor decreased punishment for criminal behavior by decreasing perceptions of the afflicted criminal’s free will. This effect was stronger for liberal and non-religious participants than for conservative and religious participants. Experiment 2 replicated Experiment 1 and additionally found that a brain tumor decreased perceptions of the afflicted criminal’s conscious decisions and true self, thereby decreasing perceptions of his free (...) will, thereby decreasing his punishment. Collectively, these results suggest that neurological abnormalities decrease punishment by decreasing perceptions of free will, especially among liberals and non-religious people. These results also suggest that neurological abnormalities decrease perceptions of free will – and ultimately decrease punishment – by decreasing perceptions of conscious decisions and the true self. (shrink)

In Patricia Churchland's 2006 essay on free will, she cites the case of a middle-aged man who, without any prior history of misbehavior, suddenly became obsessed with child pornography and started to molest his 8-year-old stepdaughter. He was subsequently discovered to have a brain tumor affecting the frontal lobes, and when it is successfully treated his aberrant behavior stopped.Thomas Szasz is famous for his denunciation of the concept of mental illness, and his critique is partly responsible for instigating an enduring (...) philosophical discourse about the nature of mental disorder. Szasz's key insight was the recognition that we find it important to distinguish between situations that are characterized by... (shrink)

Considerable progress has been made toward understanding the involvement of recoverin in a cancer-associated retinopathy (CAR) that results in blindness. We describe the expression of recoverin in tumors of individuals afflicted with CAR, characterize the immunological response towards recoverin in these patients, and demonstrate how the disease can be induced in rodents using recoverin as an immunogen.

Cancer is a complex disease, necessitating research on many different levels; at the subcellular level to identify genes, proteins and signaling pathways associated with the disease; at the cellular level to identify, for example, cell-cell adhesion and communication mechanisms; at the tissue level to investigate disruption of homeostasis and interaction with the tissue of origin or settlement of metastasis; and finally at the systems level to explore its global impact, e.g. through the mechanism of cachexia. Mathematical models have been proposed (...) to identify key mechanisms that underlie dynamics and events at every scale of interest, and increasing effort is now being paid to multi-scale models that bridge the different scales. With more biological data becoming available and with increased interdisciplinary efforts, theoretical models are rendering suitable tools to predict the origin and course of the disease. The ultimate aims of cancer models, however, are to enlighten our concept of the carcinogenesis process and to assist in the designing of treatment protocols that can reduce mortality and improve patient quality of life. Conventional treatment of cancer is surgery combined with radiotherapy or chemotherapy for localized tumors or systemic treatment of advanced cancers, respectively. Although radiation is widely used as treatment, most scheduling is based on empirical knowledge and less on the predictions of sophisticated growth dynamical models of treatment response. Part of the failure to translate modeling research to the clinic may stem from language barriers, exacerbated by often esoteric model renderings with inaccessible parameterization. Here we discuss some ideas for combining tractable dynamical tumor growth models with radiation response models using biologically accessible parameters to provide a more intuitive and exploitable framework for understanding the complexity of radiotherapy treatment and failure. (shrink)

Brain tumor classification plays a niche role in medical prognosis and effective treatment process. We have proposed a combined feature and image-based classifier for brain tumor image classification in this study. Carious deep neural network and deep convolutional neural networks -based architectures are proposed for image classification, namely, actual image feature-based classifier, segmented image feature-based classifier, actual and segmented image feature-based classifier, actual image-based classifier, segmented image-based classifier, actual and segmented image-based classifier, and finally, CFIC. The Kaggle Brain Tumor Detection (...) 2020 dataset has been used to train and test the proposed classifiers. Among the various classifiers proposed, the CFIC performs better than all other proposed methods. The proposed CFIC method gives significantly better results in terms of sensitivity, specificity, and accuracy with 98.86, 97.14, and 98.97%, respectively, compared with the existing classification methods. (shrink)

Tumor suppressor genes represent a broad class of genes that normally function in the negative regulation of cell proliferation. Loss‐of‐function mutations in these genes lead to unrestrained cell proliferation and tumor formation. A fundamental understanding of how tumor suppressor genes regulate cell proliferation and differentiation should reveal important aspects of signalling pathways and cell cycle control. A recent report describing the Drosophila tumor suppressor gene warts has implications in the study of the human myotonic dystrophy gene(1). These genes encode members (...) of a cyclic AMP‐dependent protein kinase subfamily that includes other plant and animal orthologues. (shrink)

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

Cancers have a formidable capacity to develop resistance to a large and diverse array of chemical, biologic, and physical anti‐neoplastic agents. This can be largely traced to the instability of the tumor cell genome, and the resultant ability of tumor cell populations to generate phenotypic variants rapidly. It is therefore argued that anti‐cancer strategies should be directed at eliminating those genetically stable normal diploid cells that are required for the progressive growth of tumors. Micro‐vascular endothelial cells comprising the tumor (...) vasculature represent such a normal cell target. Moreover, specificity for tumor associated vasculature by anti‐cancer agents may be achieved by virtue of the fact that many of the endothelial cells that comprise these blood vessels are in an immature, cycling, and ‘activated’ state, in contrast to the endothelial cells associated with normal tissue and organ blood vessels. (shrink)

Cell–extracellular matrix interactions are important in the process of tumor cell invasion and metastasis. In particular, the interactions of tumor cells with basement membranes of tissue epithelial, as well as vascular endothelial, cells are likely to represent key steps in the metastatic process. The interactions between cells and the connective tissue matrix are mediated by a large family of cell surface receptors, the integrins, which represent multiple receptors the integrins, which represent multiple receptors for extracellular matrix and basement membrane components. (...) Here, I review recent progress in elucidating the roles of integrins in tumor cell invasion. Altered expression of this large family of receptors on invasive tumor cells, as compared with non‐invasive cells, may represent a fundamental step in the progressive expression of the invasive phenotype. (shrink)

The role of the microenvironment in cancer development is being increasingly appreciated. This paper will review data that highlight an emerging distinction between two different entities: the microenvironment that altered/preneoplastic/neoplastic cells find in the tissue where they reside, and the peculiar microenvironment inside the focal lesion (tumor) that these cells contribute to create. While alteration in the tissue environment can contribute to the selective clonal expansion of altered cells to form focal proliferative lesions, the atypical, non‐integrated growth pattern that defines (...) such focal lesions leads to the appearance of what is correctly referred to as the tumor microenvironment. The latter represents a new and unique biological milieu, characterized by hypoxia, acidosis and other biochemical and metabolic alterations, including genetic instability, that can set the stage for tumor progression to occur. Thus, the two microenvironments act in sequence and play complementary roles in the development of overt neoplasia. This distinction has important implications for the understanding of disease pathogenesis and for the management of preneoplastic/neoplastic lesions at various stages of cancer development. BioEssays 29:738–744, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

Ribosome biogenesis includes the making and processing of ribosomal RNAs, the biosynthesis of ribosomal proteins from their mRNAs in the cytosol and their transport to the nucleolus to assemble pre‐ribosomal particles. Several stresses including cellular senescence reduce nucleolar rRNA synthesis and maturation increasing the availability of ribosome‐free ribosomal proteins. Several ribosomal proteins can activate the p53 tumor suppressor pathway but cells without p53 can still arrest their proliferation in response to an imbalance between ribosomal proteins and mature rRNA production. Recent (...) results on senescence‐associated ribogenesis defects (SARD) show that the ribosomal protein S14 (RPS14 or uS11) can act as a CDK4/6 inhibitor linking ribosome biogenesis defects to the main engine of cell cycle progression. This work offers new insights into the regulation of the cell cycle and suggests novel avenues to design anticancer drugs. (shrink)

Much of the recent work on oncogenes has been interpreted as signifying that the cancerous phenotype is caused by the direct expression of ‘dominantly‐acting’ oncogenes. On the other hand, numerous somatic cell hybridization experiments suggest that there are potent tumour‐suppressor genes in the genome. The conflict between the observations and the possible nature of the relationships between oncogenes and tumour‐suppressor are discussed.

Proteolytic cleavage of extracellular matrix (ECM) is a critical regulator of many physiological and pathological events. It affects fundamental processes such as cell growth, differentiation, apoptosis and migration. Most proteases are produced as inactive proenzymes that undergo proteolytic cleavage for activation. Proteolytic activity is additionally modified by endogenous inhibitors. Mechanisms that localize and concentrate protease activity in the pericellular microenvironment of cells are prerequisites for processes like angiogenesis, bone development, inflammation and tumor cell invasion. Methods that enable real‐time, high‐resolution imaging (...) and precise quantification of local proteolytic activity in vitro and in vivo remain major challenges. These methods will play an important role in the understanding of basic principles e.g. in cancer cell invasion, the identification of new therapeutical targets and hence drug design. This review highlights mechanisms and functions of local proteolytic activity with special emphasis on tumor cell invasion and metastasis, and focuses on techniques for the investigation of this process. BioEssays 27:1181–1191, 2005. © 2005 Wiley Periodicals, Inc. (shrink)

Preoperative diagnosis of gastric cancer and primary gastric lymphoma is challenging and has important clinical significance. Inspired by the inductive reasoning learning of the human brain, transfer learning can improve diagnosis performance of target task by utilizing the knowledge learned from the other domains (source domain). However, most studies focus on single-source transfer learning and may lead to model performance degradation when a large domain shift exists between the single-source domain and target domain. By simulating the multi-modal information learning and (...) transfer mechanism of human brain, this study designed a multisource transfer learning feature extraction and classification framework, which can enhance the prediction performance of the target model by using multisource medical data (domain). First, this manuscript designs a feature extraction network that takes the maximum mean difference based on the Wasserstein distance as an adaptive measure of probability distribution and extracts the domain-specific invariant representations between source and target domain data. Then, aiming at the random generation of parameters bringing uncertainties to prediction accuracy and generalization ability of extreme learning machine network, the 1-norm regularization is used to implement sparse constraints of the output weight matrix and improve the robustness of the model. Finally, some experiments are carried out on the data of two medical centers. The experimental results show that the area under curves (AUCs) of the method are 0.958 and 0.929 in the two validation cohorts, respectively. The method in this manuscript can provide doctors with a better diagnostic reference, which has certain practical significance. (shrink)

Diffuse‐type gastric carcinomas show diminished cell‐cell adhesion. A recent paper(1) reports that 50% of these carcinomas contain mutations in the E‐cadherin gene, resulting in the destruction of the calcium‐binding sites of E‐cadherin, and providing strong in vivo evidence that alterations in E‐cadherin play a major role in the development of this particular type of cancer and the short survival of the patients.

Context can determine whether a given gene acts as an oncogene or a tumor suppressor. Deubiquitinating enzymes (DUBs) regulate the stability of many components of the pathways dictating cell fate so it would be expected that alterations in the levels or activity of these enzymes may have oncogenic or tumor suppressive consequences. In the current review we survey publications reporting that genes encoding DUBs are oncogenes or tumor suppressors. For many DUBs both claims have been made. For such “double agents,” (...) the effects of gain or loss of function will depend on the overall status of a complex of molecular signaling networks subject to extensive crosstalk. As the TGF‐β paradox makes clear context is critical in cell fate decisions, and the disconnect between experimental findings and patient survival outcomes can in part be attributed to disparities between culture conditions and the microenvironment in vivo. Convincing claims for oncogene or tumor suppressor roles require the documentation of gene alterations in patient samples; survival curves are alone inadequate. (shrink)

Researchers have documented negative physical and emotional consequences for both family caregivers of persons with cancer as well as caregivers of persons with a neurologic disorder. However, there is a unique subset of caregivers who must provide care for someone who may suffer from both a short, terminal trajectory of disease, as well as neurological and neuropsychiatric sequelae — the caregiver of a person with a primary malignant brain tumor. The purpose of this article was to describe a conceptual framework (...) for providing care for a person with a primary malignant brain tumor. The demands of this particular care situation are described, as well as potential resources available to the caregiver to meet those demands. Finally, the stress response that results from the balance between care demands and caregiver resources is illustrated. Development of a conceptual framework for this caregiving population is the first step in assisting nurses to identify factors that place caregivers of persons with a primary malignant brain tumor at risk for negative consequences, and to design interventions to improve caregiver health. (shrink)