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Topic Review
Microbeam Radiotherapy
Melanoma is the deadliest type of skin cancer, due to its invasiveness and limited treatment efficacy. The main therapy for primary melanoma and solitary organ metastases is wide excision. Adjuvant therapy, such as chemotherapy and targeted therapies are mainly used for disseminated disease. Radiotherapy (RT) is a powerful treatment option used in more than 50% of cancer patients, however, conventional RT alone is unable to eradicate melanoma. Its general radioresistance is attributed to overexpression of repair genes in combination with cascades of biochemical repair mechanisms. A novel sophisticated technique based on synchrotron-generated, spatially fractionated RT, called Microbeam Radiation Therapy (MRT), has been shown to overcome these treatment limitations by allowing increased dose delivery. With MRT, a collimator subdivides the homogeneous radiation field into an array of co-planar, high-dose microbeams that are tens of micrometres wide and spaced a few hundred micrometres apart. Different preclinical models demonstrated that MRT has the potential to completely ablate tumours, or significantly improve tumour control while dramatically reducing normal tissue toxicity.
  • 417
  • 09 Aug 2021
Topic Review
Enzymatic Metabolism of Flavonoids
Gastrointestinal (GI) cancer is a prevalent global health disease with a massive burden on health care providers. Internal and external factors such as obesity, smoking, diet (red meat), low socioeconomic status and infection with Helicobacter pylori are the critical risk factors of GI cancers. Flavonoids are natural phenolic compounds found abundantly in fruits and vegetables. Upon ingestion, 90% of flavonoids consumed require further enzymatic metabolism by the gut microbiome to enhance their bioavailability and absorption. Several epidemiological studies reported that consumption of flavonoids and their enzymatic conversion by gut microbes is strongly associated with the reduced risk of GI cancer development. This review summarizes the current knowledge on the enzymatic conversion of flavonoids by the human gut microbiome. It also addresses the underlying anti-GI cancer effects on metabolic pathways such as apoptosis and cellular proliferation. Overall, metabolites produced from flavonoid’s enzymatic conversion illustrate anti-GI cancer effects, but the mechanisms of action need further clarification.
  • 554
  • 09 Aug 2021
Topic Review
PIPAC
Theoretical considerations as well as comprehensive preclinical and clinical data suggest that optimizing physical parameters of intraperitoneal drug delivery might help to circumvent initial or acquired resistance of peritoneal metastasis (PM) to chemotherapy. Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) is a novel minimally invasive drug delivery system systematically addressing the current limitations of intraperitoneal chemotherapy. The rationale behind PIPAC is: (1) optimizing homogeneity of drug distribution by applying an aerosol rather than a liquid solution; (2) applying increased intraperitoneal hydrostatic pressure to counteract elevated intratumoral interstitial fluid pressure; (3) limiting blood outflow during drug application; (4) steering environmental parameters (temperature, pH, electrostatic charge etc.) in the peritoneal cavity for best tissue target effect. In addition, PIPAC allows repeated application and objective assessment of tumor response by comparing biopsies between chemotherapy cycles. 
  • 620
  • 09 Aug 2021
Topic Review
Non-Coding RNAs in Tamoxifen Resistance
Despite the clinical efficacy of Tam, intrinsic or acquired resistance is an important obstacle limiting the success of ER + breast cancer patient treatment. It is a challenge that needs to be overcome to improve the prognosis of these patients. The main mechanisms of resistance to tamoxifen can be divided according to different causes: mechanisms that involve genetic mutations and lead to loss or gain of function of the receptor and mechanisms that modulate other protumorigenic pathways, including other receptors involved in estrogen’s pathway of action.
  • 410
  • 09 Aug 2021
Topic Review
Subclinical Hypothyroidism and Incident Hypertension
Subclinical hypothyroidism (SCH) represents an early form of thyroid dysfunction and is biochemically defined as an elevated TSH (thyroid-stimulating hormone or thyrotropin) level with a normal level of free thyroxine (FT4) within the reference range. SCH can affect about 1–11% of adults depending on the cohort studied, and such wide variability in its incidence can be attributed to the environmental and ethnic differences as well as the different TSH reference ranges used in each country.
  • 564
  • 06 Aug 2021
Topic Review
Premature Aging in CKD
The characteristics of CKD (chronic kidney disease) are similar to those of the aging process; therefore, it has been hypothesized that CKD promotes premature aging associated with related diseases. Furthermore, chronic diseases usually observed in aging, such as CVD, inflammation, vascular calcification, mineral, and bone disorders, and chronodisruption (chronic alteration of circadian rhythms), are markedly frequent in patients with CKD.
  • 502
  • 04 Aug 2021
Topic Review
Antidiabetic Potential of Medicinal Plants
Diabetes mellitus is one of the major health problems in the world, the incidence and associated mortality are increasing. Inadequate regulation of the blood sugar imposes serious consequences for health. Conventional antidiabetic drugs are effective, however, also with unavoidable side effects. On the other hand, medicinal plants may act as an alternative source of antidiabetic agents. 
  • 645
  • 04 Aug 2021
Topic Review
Nrf2 and NF-κB for Cancer
Nrf2 (nuclear factor erythroid 2-related factor 2) and NF-κB (nuclear factor–kappa B) signaling pathways play a central role in suppressing or inducing inflammation and angiogenesis processes. Therefore, they are involved in many steps of carcinogenesis through cooperation with multiple signaling molecules and pathways. Targeting both transcription factors simultaneously may be considered an equally important strategy for cancer chemoprevention and therapy.
  • 543
  • 04 Aug 2021
Topic Review
ADAM 17 and Epithelial-to-Mesenchymal Transition
For decades, metalloproteinase 17 (ADAM17) has been the goal of wide investigation. Since its discovery as the tumour necrosis factor-α convertase, it has been studied as the main drug target, especially in the context of inflammatory conditions and tumour. In fact, evidence is mounting to support a key role of ADAM17 in the induction of the proliferation, migration and progression of tumour cells and the trigger of the pro-fibrotic process during chronic inflammatory conditions; this occurs, probably, through the activation of epithelial-to-mesenchymal transition (EMT). EMT is a central morphologic conversion that occurs in adults during wound healing, tumour progression and organ fibrosis. EMT is characterised by the disassembly of cell–cell contacts, remodelling of the actin cytoskeleton and separation of cells, and generates fibroblast-like cells that express mesenchymal markers and have migratory properties. This transition is characterised by loss of epithelial proteins such as E-cadherin and the acquisition of new mesenchymal markers, including vimentin and a-smooth muscle actin.
  • 824
  • 03 Aug 2021
Topic Review
Stem Cell-Derived Organoids in Disease
Organoids represent one of the most important advancements in the field of stem cells during the past decade. The earliest usage of the term goes back to 1946 when Smith and Cochrane described a cystic teratoma case by referring to it as “cystic organoid teratoma”. Organoids, or as the term literally signifies “resembling an organ”, are three-dimensional (3D) in vitro culturing systems that originate from self-organizing stem cells, capable of mimicking the in vivo structural and functional specificities of an organ.
  • 598
  • 28 Jul 2021
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