A special issue on DNA damage responses and genome maintenance

There is nothing more fundamental than the genome for the existence and maintenance of all living beings. The importance of the genome is increasingly appreciated as recent discoveries have revealed that changes in the human genome, regardless of being inherited or induced, can result in diseases that either significantly shorten lives （as seen in cancer） or dramatically affect the quality of lives （often seen in neurodegenerative diseases）. Therefore, maintaining genome integrity is critical for not only the continuation of a species in evolution （although mutations may be occasionally beneficial during evolution） but also for longevity and general health.     

Urimem,a membrane that can store urinary proteins simply and economically,makes the large-scale storage of clinical samples possible

By nature,biomarker is the measurable change associated with a physiological or pathophysiological process.Unlike blood which has mechanisms to minimize changes and to keep the internal environment homeostatic,urine is more likely to reflect changes of the body and is a better biomarker source.Because of its potential in biomarker discovery,urinary proteins should be preserved comprehensively as the duration of the patients’corresponding medical records.Here,we propose a method to adsorb urinary proteins onto a membrane we named Urimem.This simple and inexpensive method requires minimal sample handling,uses no organic solvents,and is environmentally friendly.Urine samples were filtered through the membrane,and urinary proteins were adsorbed onto the membrane.The proteins on the membrane were dried and stored in a vacuum bag,which keeps the protein pattern faithfully preserved.The membrane may even permit storage at room temperature for weeks.Using this simple and inexpensive method,it is possible to begin preserving urine samples from all consenting people.Thus,medical research especially biomarker research can be conducted more economically.Even more objective large-scale prospective studies will be possible.This method has the potential to change the landscape of medical research and medical practice.     

Frequent Mutation of rs13281615 and Its Association with PVT1 Expression and Cell Proliferation in Breast Cancer

The q24 band of chromosome 8 （8q24） is frequently amplified in human cancers including breast cancer, and several SNPs （single nucleotide polymorphisms） at 8q24, including rs13281615, have been identified for their association with cancer risks. These SNPs are in a ＂gene desert＂ region, and their functions in cancer development remain to be illustrated, although several of the SNPs appear to influence the genes in the ＂desert＂ in a long-range manner, including the v-myc avian myelocytomatosis viral oncogene homolog （MYC） and the non- protein coding plasmacytoma variant translocation 1 （PVT1）, both of which have been implicated in human cancers. In the current study, we examined rs13281615 for its potential role in breast cancer using normal and cancer tissues from 121 Chinese women with breast cancer. In addition to confirming the association of the GG genotype of rs 13281615 with breast cancer risk, we found that germline GG genotype was significantly associated with estrogen receptor （ER） positivity, higher tumor grade and higher proliferation index. We also found frequent somatic mutations （22/121 or 18.2%） of this SNP in breast cancer. Interestingly, the majority of the mutations （17/22 or 77%） involved a G→ A change, resulting in a decrease in the number of cancers with the GG risk genotype and subsequent loss of GG association with higher tumor grade and proliferation index in cancers. Furthermore, PVT1 expression was increased in cancers, and the increase was associated with the GG genotype of rs13281615. These results suggest that the GG genotype of SNP rs13281615 plays a role in breast cancer likely by influencing PVT1 expression, and that during oncogenesis, ＂protective＂ mutations could occur.     

New insights into pancreatic cancer stem cells

Pancreatic cancer(PC) has been one of the deadliest of all cancers, with almost uniform lethality despite aggressive treatment. Recently, there have been important advances in the molecular, pathological and biological understandingof pancreatic cancer. Even after the emergence of recent new targeted agents and the use of multiple therapeutic combinations, no treatment option is viable in patients with advanced cancer. Developing novel strategies to target progression of PC is of intense interest. A small population of pancreatic cancer stem cells(CSCs) has been found to be resistant to chemotherapy and radiation therapy. CSCs are believed to be responsible for tumor initiation, progression and metastasis. The CSC research has recently achieved much progress in a variety of solid tumors, including pancreatic cancer to some extent. This leads to focus on understanding the role of pancreatic CSCs. The focus on CSCs may offer new targets for prevention and treatment of this deadly cancer. We review the most salient developments in important areas of pancreatic CSCs. Here, we provide a review of current updates and new insights on the role of CSCs in pancreatic tumor progression with special emphasis on Dcl K1 and Lgr5, signaling pathways altered by CSCs, and the role of CSCs in prevention and treatment of PC.     

Advances in cellular technology in the hematology field: What have we learned so far?

Despite the advances in the hematology field, blood transfusion-related iatrogenesis is still a major issue to be considered during such procedures due to blood antigenic incompatibility. This places pluripotent stem cells as a possible ally in the production of more suitable blood products. The present review article aims to provide a comprehensive summary of the state-of-theart concerning the differentiation of both embryonic stem cells and induced pluripotent stem cells to hematopoietic cell lines. Here, we review the most recently published protocols to achieve the production of blood cells for future application in hemotherapy, cancer therapy and basic research.     

Convergence of normal stem cell and cancer stem cell developmental stage: Implication for differential therapies

Increased evidence shows that normal stem cells may contribute to cancer development and progression by acting as cancer-initiating cells through their interactions with abnormal environmental elements.We postulate that normal stem cells and cancer stem cells (CSC) possess similar mechanisms of self-renewal and differentiation.CSC can be the key to the elaboration of anti-cancer-based therapy.In this article,we focus on a controversial new theme relating to CSC.Tumorigenesis may have a critical stage characterized as a "therapeutic window",which can be identified by asso-ciation of molecular,biochemical and biological events.Identifying such a stage can allow the production of more effective therapies (e.g.manipulated stem cells) to treat several cancers.More importantly,confirming the existence of a similar therapeutic window during the conversion of normal stem cells to malignant CSC may lead to targeted therapy specifically against CSC.This conversion information may be derived from investigating the biological behaviour of both normal stem cells and cancerous stem cells.Currently,there is little knowledge about the cellular and molecular mechanisms that govern the initiation and maintenance of CSC.Studies on co-evolution and interdependence of cancer with normal tissues may lead to a useful treatment paradigm of cancer.The crosstalk between normal stem cells and cancer formation may converge developmental stages of different types of stem cells (e.g.normal stem cells,CSC and embryonic stem cells).The differential studies of the convergence may result in novel therapies for treating cancers.     

Pluripotency of Induced Pluripotent Stem Cells

Induced pluripotent stem （iPS） cells can be generated by forced expression of four pluripotency factors in somatic cells. This has received much attention in recent years since it may offer us a promising donor cell source for cell transplantation therapy. There has been great progress in iPS cell research in the past few years. However, several issues need to be further addressed in the near future before the clinical application of iPS cells, like the immunogenieity of iPS cells, the variability of differentiation potential and most importantly tumor formation of the iPS derivative cells. Here, we review recent progress in research into the pluripotency of iPS cells.     

Motivated research

While Europe is locked in the debate about basic versus applied research, Louis Pasteur solved the problem more than 100 years ago. Antoine Danchin comments on Pasteur''s notion of ‘motivated research'' and how it leads both to new discoveries and to new applications.Three years ago, a senior politician attended his country''s Annual Congress for the Advancement of Science to give the introductory lecture. He asked the attending scientists to make science and research more attractive to young students and the general public, and asked his countrymen to support scientists to address the urgent challenges of global climate change, energy needs and dwindling water resources. It was neither a European nor a US politician, but the Indian Prime Minister Manmohan Singh who made this speech about the relationship between research and its practical applications. This is such an important topic that one might think it deserves appropriate attention in Europe, yet we fail to address it properly. Instead, we just discuss how science should serve society or contribute to the ‘knowledge-based economy'', or how ‘basic'' or ‘fundamental'' research is opposed to ‘applied'' or ‘industrial'' research and how funding for ‘big science'' comes at the expense of ‘little academic'' research.This dichotomy between the research to generate knowledge and the application of that knowledge to benefit humankind seems to be a recent development. In fact, more than 100 years ago Louis Pasteur avoided this debate altogether: one of his major, yet forgotten, contributions to science was the insight that research and its applications are not opposed, but orthogonal to each other (Stokes, 1997). If Niels Bohr ‘invented'' basic academic research—which was nevertheless the basis for many technological inventions and industrial applications—Pasteur developed what we might call ‘motivated'' research.How is research motivated and by what? By definition, scientists are citizens and members of the general public and, like the public, they are motivated by two forces: on the one hand, in Rudyard Kipling''s words, “man''s insatiable curiosity”; on the other hand, a desire for maintaining and improving their well-being. These are not contradictory to one another; curiosity nourishes dreams of a brighter future and leads to discoveries that contribute to well-being.Pasteur understood that it is essential to take account of society''s demands and desires; that science must be motivated by what people want. Still, there are severe misgivings about the nature of research. These stem from the mistaken but popular assumption that the scientists'' main task is to find solutions to current problems or to fulfil our desires. Problems and desires, however, are not enough, because finding solutions also requires creativity and discovery, which, by their very nature, are unpredictable. Often we do not even know what we need or desire and it is only through curiosity and more knowledge that we find new ways to improve our well-being. Motivation by itself is, therefore, not enough to lead to discovery. Motivation simply helps us choose between many different goals and an infinite number of paths to gain novel knowledge. Subsequently, each path, once chosen, must be explored using the scientific method, which is the only way to new discoveries.Motivation helps us to ask relevant questions. For example, why do wine and beer go sour without any apparent reason? Pasteur set out to design experiments that showed that fermentation is caused by microorganisms. A few years later, silkworms were suddenly dying of a terrible disease in the silk factories of southern France. The French government called on Pasteur for help, who eventually found that a parasite had infected silkworm eggs and proposed solutions to eradicate the disease. The original question therefore led to germ theory and bacteriology, helped to develop solutions to infectious diseases, and eventually created the whole field of microbiology.Motivation leads to conceptual and experimental research, which generates discoveries and new technologies. Discoveries, in turn, are the basic resource for the creation of general knowledge and the development of new products, services and other goods that fulfil public demands and generate jobs. The study of the ‘diseases'' of beer and wine also led to the development of fermentation processes that are still in use today. The same motivation that drove Pasteur in the nineteenth century now enables us to tackle current problems, such as pollution, by studying microbial communities that make compost or thrive in garbage dumps. Motivated research therefore reconciles our curiosity with the creation of knowledge and enables us to address pressing needs for humanity.Because it is strongly inspired by—even rooted in—society''s demands and desires, motivated research also raises accompanying ethical, legal, social and safety issues that should be compelling for all research. As mentioned above, scientists are members of the public who share the same concerns and demands as their fellow citizens and therefore participate with a general, public intelligence that, too often, is absent from academic research. This absence of ‘common sense'' or societal expectations generates the misunderstandings concerning research in biology and the development of biotechnology. These misconceptions—whether about the purported risks of genetically modified organisms or the exaggerated expectations for cancer therapies—can create real suffering in society and inefficient allocation of limited resources. It is therefore advisable for researchers to listen more to the public at large in order to find the motivation for their work.