Heating cancer stem cells to reduce tumor relapse

Tumour relapse is believed to be caused by rare cancer-cells with stem-cell properties (cancer stem cells) that are intrinsically resistant to available treatments. The identification of novel strategies to increase their sensitivity has major clinical implications. Latest clinical trials have shown a positive antitumoral effect of hyperthermia in combination with chemotherapy or radiotherapy. In a recent paper, the combination of increased temperature at the tumour site, generated by laser treatment of intravenously-injected gold nanoshells, and ionizing radiations enhances radiosensitivity of cancer stem cells and tumor response. At the root of the success of hyperthermia in enhancing radio-sensitization of cancer stem cells is the inhibition of their capacity to repair DNA damage, affecting the survival rate of these cells

Hallmarks of cancer-the new testament.

Diagnosis and treatment of disease demand a sound understanding of the underlying mechanisms, determining any Achilles' heel that can be targeted in effective therapies. Throughout history, this endeavour to decipher the origin and mechanism of transformation of a normal cell into cancer has led to various theories-from cancer as a curse to an understanding at the level of single-cell heterogeneity, meaning even among a single sub-type of cancer there are myriad molecular challenges to overcome. With increasing insight into cancer genetics and biology, the disease has become ever more complex to understand. The complexity of cancer as a disease was distilled into key traits by Hanahan and Weinberg in their seminal 'Hallmarks of Cancer' reviews. This lucid conceptualization of complex cancer biology is widely accepted and has helped advance cancer therapeutics by targeting the various hallmarks but, with the advancement in technologies, there is greater granularity in how we view cancer as a disease, and the additional understanding over the past decade requires us to revisit the hallmarks of cancer. Based on extensive study of the cancer research literature, we propose four novel hallmarks of cancer, namely, the ability of cells to regress from a specific specialized functional state, epigenetic changes that can affect gene expression, the role of microorganisms and neuronal signalling, to be included in the hallmark conceptualization along with evidence of various means to exploit them therapeutically

Neurology Case Reporting: a call for all

From antiquity to present day, the act of recording and publishing our observations with patients remains essential to the art of medicine and the care of patients. Neurology is rich with case reports over the centuries. They contribute to our understanding and knowledge of disease entities, and are a cornerstone of our professional development as physicians and the care of our patients. This editorial seeks to enthuse and invigorate house staff and practicing physicians everywhere to continue the long and time-honored tradition of neurology case reporting

Male breast cancer

Male breast cancer (MBC) is a rare disease representing less than 1% of all breast cancers (BC) and less than 1% of cancers in men. Age at presentation is mostly in the late 60s. MBC is recognized as an estrogen-driven disease, specifically related to hyperestrogenism. About 20% of MBC patients have family history for BC. Mutations in BRCA1 and, predominantly, BRCA2, account for approximately 10% of MBC cases. Because of its rarity, MBC is often compared with female BC (FBC). Based on age-frequency distribution, age-specific incidence rate patterns and prognostic factors profiles, MBC is considered similar to late-onset, postmenopausal estrogen/progesterone receptor positive (ER+/PR+) FBC. However, clinical and pathological characteristics of MBC do not exactly overlap FBC. Compared with FBC, MBC has been reported to occur later in life, present at a higher stage, and display lower histologic grade, with a higher proportion of ER+ and PR+ tumors. Although rare, MBC remains a substantial cause for morbidity and mortality in men, probably because of its occurrence in advanced age and delayed diagnosis. Diagnosis and treatment of MBC generally is similar to that of FBC. Men tend to be treated with mastectomy rather than breast-conserving surgery. The backbone of adjuvant therapy or palliative treatment for advanced disease is endocrine, mostly tamoxifen. Use of FBC-based therapy led to the observation that treatment outcomes for MBC are worse and that survival rates for MBC do not improve like FBC. These different outcomes may suggest a non-appropriate utilization of treatments and that different underlying pathogenetic mechanisms may exist between male and female BC

Water and power: Reintegrating the state into the study of Egyptian irrigation

The study of irrigation in ancient Egypt has swung between two poles. Early environmental‐determinist scholarship stressed the imperative of state control while the most recent work denies the state any significant role and instead emphasizes the agency of local communities. This article briefly explores the historiography of Egyptian irrigation, critiquing both its colonialist roots and the extreme reaction against colonialist preconceptions that marks current scholarship. A case study of Roman state coordination is then presented as an argument for reintegrating the state into the history of Egyptian water management.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138919/1/hic312394.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138919/2/hic312394_am.pd

The Historical, Jurisprudential, and Empirical Wisdom of Parental Responsibility Laws

The parent-child relationship is woven deep within historical and contemporary culture, but strong retributive ideals have led to blaming parents because of their presumed vicarious role in juvenile crime. The current article will discuss the history, forms, legal challenges, and empirical research related to parental involvement laws in the United States. The parent-child relationship provides the historical framework behind the separate juvenile justice parens patriae system; however, with the juvenile justice system not as successful as originally imagined, blame has shifted to the parents. We examine the potential constitutional implications of enacting and enforcing parental involvement statutes and ordinances and also the potential efficacy of parental involvement laws in reducing juvenile delinquency. In addition, we propose empirical research to test the underlying assumptions about blame made by parental involvement laws

Barbarians at the British Museum: Anglo-Saxon Art, Race and Religion

A critical historiographical overview of art historical approaches to early medieval material culture, with a focus on the British Museum collections and their connections to religion