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Topic Review
Autotaxin (ATX) in Breast Cancer
       This entry deals with the role of the secreted enzyme, autotaxin (ATX), in the progression of breast cancer. ATX produces lysophosphatidate (LPA), which signals through six G-protein coupled receptors, promoting tumor growth, metastasis, immune evasion and survival from chemotherapy and radiotherapy. Many cancer cells produce ATX, but breast cancer cells express little ATX. Instead, in breast cancer, ATX is produced by tumor-associated stroma. Breast tumors are also surrounded by adipose tissue, which is a major bodily source of ATX. In mice, a high-fat human type diet increases ATX production in adipocytes. ATX production in obesity is also increased because of low-level inflammation in the expanded adipose tissue. This increased ATX secretion and consequent LPA signaling is associated with decreased adiponectin production, which results in adverse metabolic profiles and glucose homeostasis. Increased ATX production by inflamed adipose tissue could contribute to the association between obesity and breast cancer. This would result from the cross talk between breast tumors and adjacent adipose tissue. Breast tumors produce inflammatory mediators that stimulate ATX transcription in adipocytes adjacent to the tumors. This drives a feedforward inflammatory cycle since increased LPA signaling increases the production of more inflammatory cytokines/chemokines and cyclooxygenase-2 resulting in more ATX secretion. This cycle is typical of a wound healing response, which in the case of cancers become maladaptive. Thus, inhibiting ATX activity derived from adipocytes and/or tumor stromal cells has implications as an adjuvant for breast cancer treatments by attenuating the inflammatory cycle. Targeting ATX activity and LPA signaling could potentially increase the efficacy of chemotherapy and radiotherapy independently of the breast cancer type because most ATX is not derived from breast cancer cells. Blocking ATX activity and LPA signaling could also decrease morbidity from radiation-induced fibrosis.
  • 1.3K
  • 30 Oct 2020
Topic Review
The Coming of Age of Biosimilars
The first biosimilar, Sandoz’s Omnitrope  (human growth hormone), was approved in 2006 by both the FDA and EMA; it was approved by the FDA under the 505(b)(2) generic product legislation and by the EU as a biosimilar. Later, Sandoz received the first licensing of Zarzio/Zarxio (filgrastim) in 2015; this was the first biosimilar product approved under the 351(k) BLA legislation in the US. Biosimilars have come of age from 2005 to the present, with 84 approvals in the EU and 35 in the US, representing almost 90% of the world market. While the acceptance of biosimilars in the US is catching up with that in the EU, the cost benefits remain elusive due to the high development barrier and complex distribution system involved, mainly in the US. In the EU, the cost of biosimilars has already dropped 70% or more, and interchangeability is a routine in some European jurisdictions, unlike in the US, where a separate regulatory approval is required.
  • 1.3K
  • 27 Apr 2022
Topic Review
Dietary Macronutrients That Prompt MetS via Mitochondria
Metabolic syndrome (MetS) is a cluster of metabolic risk factors for diabetes, coronary heart disease, non-alcoholic fatty liver disease, and some tumors. It includes insulin resistance, visceral adiposity, hypertension, and dyslipidemia. MetS is primarily linked to lipotoxicity, with ectopic fat deposition from fat storage exhaustion, more than obesity per se. Excessive intake of long-chain saturated fatty acid and sugar closely relates to lipotoxicity and MetS through several pathways, including toll-like receptor 4 activation, peroxisome proliferator-activated receptor-gamma regulation (PPARγ), sphingolipids remodeling, and protein kinase C activation. These mechanisms prompt mitochondrial dysfunction, which plays a key role in disrupting the metabolism of fatty acids and proteins and in developing insulin resistance. 
  • 1.3K
  • 21 Mar 2023
Topic Review
Additive Manufacturing Processes
Additive manufacturing (AM, 3D printing) is used in many fields and different industries. In the medical and dental field, every patient is unique and, therefore, AM has significant potential in personalized and customized solutions. This text explores what additive manufacturing processes and materials are utilized in medical and dental applications, especially focusing on processes that are less commonly used. The processes are categorized in ISO/ASTM process classes: powder bed fusion, material extrusion, VAT photopolymerization, material jetting, binder jetting, sheet lamination and directed energy deposition combined with classification of medical applications of AM. Based on the findings, it seems that directed energy deposition is utilized rarely only in implants and sheet lamination rarely for medical models or phantoms. Powder bed fusion, material extrusion and VAT photopolymerization are utilized in all categories. Material jetting is not used for implants and biomanufacturing, and binder jetting is not utilized for tools, instruments and parts for medical devices. The most common materials are thermoplastics, photopolymers and metals such as titanium alloys. If standard terminology of AM would be followed, this would allow a more systematic review of the utilization of different AM processes.
  • 1.3K
  • 09 Apr 2021
Topic Review
Italian Experts’ Statements on Paracetamol/Ibuprofen in Children Fever/Pain
Fever and pain are challenging symptoms in children and adolescents and are common reasons for consultations in primary care and hospital. Paracetamol and ibuprofen are currently the only recommended drugs for treating fever in Italy, but the therapeutic approaches are discrepant in the different settings.
  • 1.3K
  • 08 Nov 2021
Topic Review
Music and Obsessive-Compulsive Disorder
Obsessive-compulsive disorder (OCD) is a severe psychiatric disorder, which can be associated with music-related symptoms. Music may also be used as an adjunct treatment for OCD. Patients with OCD might benefit from music therapy, which includes listening to music.
  • 1.3K
  • 22 Nov 2021
Topic Review
Protein-Energy Wasting: Acute Kidney Injury
Acute kidney injury is a heterogeneous group of conditions characterised by a sudden decrease in glomerular filtration rate, manifested by an increase in serum creatinine concentration or oliguria. Protein energy wasting is a state of decreased body stores of protein and energy fuels.
  • 1.3K
  • 27 Oct 2020
Topic Review
Poliomyelitis
Poliomyelitis, often called polio or infantile paralysis, is an infectious disease caused by the poliovirus. In about 0.5 percent of cases there is muscle weakness resulting in an inability to move. This can occur over a few hours to a few days. The weakness most often involves the legs but may less commonly involve the muscles of the head, neck and diaphragm. Many people fully recover. In those with muscle weakness about 2 to 5 percent of children and 15 to 30 percent of adults die. Another 25 percent of people have minor symptoms such as fever and a sore throat and up to 5 percent have headache, neck stiffness and pains in the arms and legs. These people are usually back to normal within one or two weeks. In up to 70 percent of infections there are no symptoms. Years after recovery post-polio syndrome may occur, with a slow development of muscle weakness similar to that which the person had during the initial infection. Poliovirus is usually spread from person to person through infected fecal matter entering the mouth. It may also be spread by food or water containing human feces and less commonly from infected saliva. Those who are infected may spread the disease for up to six weeks even if no symptoms are present. The disease may be diagnosed by finding the virus in the feces or detecting antibodies against it in the blood. The disease only occurs naturally in humans. The disease is preventable with the polio vaccine; however, multiple doses are required for it to be effective. The US Centers for Disease Control and Prevention recommends polio vaccination boosters for travelers and those who live in countries where the disease is occurring. Once infected there is no specific treatment. In 2016, there were 37 cases of wild polio and 5 cases of vaccine-derived polio. This is down from 350,000 wild cases in 1988. In 2014 the disease was only spreading between people in Afghanistan, Nigeria, and Pakistan . In 2015 Nigeria had stopped the spread of wild poliovirus but it reoccurred in 2016. Poliomyelitis has existed for thousands of years, with depictions of the disease in ancient art. The disease was first recognized as a distinct condition by the English physician Michael Underwood in 1789 and the virus that causes it was first identified in 1908 by the Austrian immunologist Karl Landsteiner. Major outbreaks started to occur in the late 19th century in Europe and the United States. In the 20th century it became one of the most worrying childhood diseases in these areas. The first polio vaccine was developed in the 1950s by Jonas Salk. It was hoped that vaccination efforts and early detection of cases would result in global eradication of the disease by 2018.
  • 1.3K
  • 10 Nov 2022
Topic Review
CBL Mutations
CBL mutations are progressively being described as involved in different clinical manifestations. Somatic CBL mutations can be found in different type of cancer. The clinical spectrum of germline mutations configures the so-called CBL syndrome, a cancer-predisposing condition that includes multisystemic involvement characterized by variable phenotypic expression and expressivity.
  • 1.3K
  • 24 Feb 2022
Topic Review
Cardiac IKs (KCNQ1/KCNE1) Channels
The cardiac IKs (KCNQ1/KCNE1) channel is one of the main contributors to the repolarizing currents that regulate the ventricular action potential duration (APD) and thus the QT interval in the electrocardiogram. Mutations in cardiac KCNQ1/KCNE1 channels are the most common cause of congenital defects that cause long QT syndrome (LQTS).
  • 1.3K
  • 08 Jan 2021
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