Cancer treatment and research最新文献

Histone proteins in eukaryotic cells are subjected to a wide variety of post-translational modifications, which are known to play an important role in the partitioning of the genome into distinctive compartments and domains. One of the major functions of histone modifications is to recruit reader proteins, which recognize the epigenetic marks and transduce the molecular signals in chromatin to downstream effects. Histone readers are defined protein domains with well-organized three-dimensional structures. In this Chapter, we will outline major histone readers, delineate their biochemical and structural features in histone recognition, and describe how dysregulation of histone readout leads to human cancer.

When a decision-maker has the option of diagnostic testing, they face a typical dilemma: (1) do not administer treatment and do not test, (2) test and decide to administer treatment based on the test result, and (3) administer treatment without testing. In this chapter, we will discuss the theory behind threshold modeling when diagnostic testing is available; we will illustrate the approach by presenting a case vignette.

Today, every country struggles to provide adequate health care to its citizens. Globally, an average of $8.3 trillion or 10% of gross domestic product (GDP) is annually spent on health services. In 2019, the USA spent nearly 18% ($3.2 trillion) of its GDP on health care, projected to reach $6.2 trillion by 2028.

There are approximately 300 million members of the Greek Orthodox Church worldwide. It is the second-largest Christian church. Followers of this religion believe in eternal life. Thus, the church strongly emphasizes a positive outcome in death- "the deceased is alive with God." God is believed to be the healer of our souls and bodies, which is facilitated through prayer and participation in the life of the Church. Traditional medical interventions are generally accepted. Artificial life support is justifiable only when it offers a hope for meaningful recovery. Just as death should not be hastened, the natural dying process should not be prolonged. Timely advance care planning and early treatment goals discussions to help understand how the patient would define quality of life is paramount to setting limitations on what could be considered as nonbeneficial care. The medical team should not assume that all patients of the Greek Orthodox faith will feel the same around end-of-life beliefs and practices. This chapter aims to identify common themes and the historical contextual framework that may influence the way in which medical decision making is made by those who specifically subscribe to the Greek Orthodox faith.

The weight of grief is heavy on both patients with terminal illness, and their loved ones. We are now aware that grief is not limited to the time of death-grief reactions begin to occur at the time of diagnosis of terminal illness and evolve over time, impacting the patient and family unit in a variety of ways. Loss of what life "could have been" with better health, decline in physical functioning due to illness, and loss of identity and role within the family or community all play a part in the grieving process.

Judaism offers a rich body of traditional beliefs and practices surrounding end-of-life, death, mourning, and the afterlife. A more detailed understanding of these topics might prove helpful to clinicians seeking guidance for how best to care for Jewish patients, to anyone supporting dying individuals, or to anyone interested in learning more about the subject. The objectives of this chapter are to examine Jewish approaches to key bioethical issues surrounding palliative care, to analyze meaning-making rituals following a loss, at a funeral, and throughout mourning, and to explore Jewish beliefs in an afterlife. Research was collected from sacred texts, legal codes, modern rabbinic responsa literature, and secondary sources. Core, guiding principles include human beings' creation "in the image of God," an obligation to save life, an obligation to mitigate pain, a prohibition against self-harm and hastening death, respect for the dead, and ritualized mourning periods ("shiva," "shloshim," and "shanah"), which feature special liturgy ("kaddish") and practices. Judaism is a religion that values thorough questioning, debate, and argumentation. It also encompasses diverse cultural and ethnic backgrounds, and various denominations. Many Jews are also unaffiliated with a movement or rarely engage with traditional law altogether. For all of these reasons, no summary can comprehensively encapsulate the wide range of opinions that exist around any given topic. That said, what follows is a detailed overview of traditional Jewish approaches to artificial nutrition/hydration, extubation, dialysis, euthanasia and more. It also outlines rituals surrounding and following death. Finally, views and beliefs of the afterlife are presented, as they often serve to imbue meaning and comfort in times of grief, uncertainty, and transition.

The human desire to explore our world has led to dramatic shifts in science, technology, and culture. As our knowledge expands so too has our ability to more definitively reach places once thought inhospitable or beyond our grasp. In the early ages of human history, the oceans represented a vast unknown, full of rage and danger suggesting the domain of a tempestuous god or gods. As sailing and navigation developed our eyes turned to the stars and heavens as the new, final frontier. The emptiness beyond Earth's atmosphere has only recently become a destination to sate our natural curiosity and, at present, life in outer space remains a dream of science fiction or the lucky few who participate in the scientific study of our universe. For those who feel cheated in being born too late to explore Earth, but also born too early to explore the cosmos, there is a burgeoning space memorials industry that may give some consolation.

The qualitative experience of sickness and death matters. Modern medicine has made important strides in addressing physical-and to some extent psychological-suffering at the end of life, but biomedical models are not properly equipped to respond to spiritual distress. Medical professionals and spiritual care professionals have an obligation, grounded in the bioethical principle of beneficence, to address all forms of suffering and to advocate for better dying. At the same time, they must approach care from a patient-centered standpoint that avoids spiritual or medical paternalism. The bond that clinicians and patients form through discussing and addressing spiritual distress allows patients to develop a clearer perspective of how their values can be best honored by the medical care team. Ultimately, modern individuals, caught between the dizzying array of possible life choices and the inevitability of mortality, experience immense spiritual need. The drive to care for these needs among dying individuals is a worthwhile pursuit, and traditional ideas of spirituality must expand to meet the needs of the modern individual.

Prostate cancer is a genetically heterogenous disease and a subset of prostate tumors harbor alterations in DNA damage and repair (DDR) genes. Prostate tumor DDR gene alterations can arise via germline or somatic events and are enriched in high-grade and advanced disease. Alterations in genes in the homologous recombination (HR) repair pathway are associated with sensitivity to PARP inhibition in breast and ovarian cancer, and data from recently completed randomized trials also demonstrate benefit of PARP inhibitor therapy in patients with advanced metastatic castration-resistant prostate cancer (mCRPC) and tumor HR gene alterations. PARP inhibitors have been investigated in first-line mCRPC in biomarker-selected and unselected populations, and are currently under study in earlier disease states in patients with DDR gene alterations. This chapter focuses on the current state of PARP inhibitor development in prostate cancer with particular emphasis on biomarkers and combination therapy approaches.

Chemical modifications on macromolecules such as DNA, RNA and proteins play important roles in almost all biological processes. The revival of RNA modification research began with the discovery of RNA modification machineries, and with the development of better techniques for characterizing and profiling these modifications at the transcriptome-wide level. Hematopoietic system is maintained by hematopoietic stem cells that possess efficient self-renewal capacity and the potential of differentiation into all lineages of blood cells, and the imbalance of this homeostasis frequently causes hematologic malignancies such as leukemia. Recent studies reveal that dysregulated RNA modifications play essential roles in hematologic malignancies. Herein, we summarize recent advances in some major RNA modifications, the detection methods, roles and mechanisms of these RNA modifications in hematologic malignancies.