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

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

A teacher's manual accompanying the Breasted-Huth ancient history maps /

Includes bibliographies and index.Mode of access: Internet

The Origin of Technical Drawing in the Narmer Palette

Over 5000 years ago, together with the proto-hieroglyphics that helped to understand the events recorded in bas-relief, there also appeared, as we will demonstrate, a technical “description” of the plan for a fortified city wall that, though schematic, provided sufficient elements to perform a mathematical calculation of form and structure. Properly illuminated and enlarged, the image, according to the manner and technology used, allows for measurement, justifying the representative and configurative choices of the methodologically deduced three-dimensional model. Comparison with the remnants of structures of the same age and the geographic location of the relic supports and confirms such decision