China
Africa
Explore chapters and articles related to this topic
Ocular Tumors
Published in Ching-Yu Cheng, Tien Yin Wong, Ophthalmic Epidemiology, 2022
Vishal Raval, Alexander Melendez, Hansell Soto, Alléxya Affonso, Rubens Belfort Neto, Arun D. Singh
Retinoblastoma is the most common intraocular tumor in children, accounting for approximately 11% of cancers occurring in the first year of life, with 95% diagnosed before 5 years of age. Retinoblastoma is a genetic disease; inactivation of both alleles of the retinoblastoma susceptibility gene (RB1) predisposes an individual to the disease.1 It is a prototype of hereditary cancers and the paradigm for the “two-hit hypothesis” proposed by Alfred Knudson in 1971.2 The RB1 gene located on the long arm of chromosome 13 (13q14) is a negative regulator element in the cell cycle process and was the first tumor suppressor gene to be identified.3 In developed countries, the goal of treatment has shifted from globe salvage to vision preservation, whereas in underdeveloped countries, which account for more than 90% of retinoblastoma children, the intraocular tumor often goes undiagnosed and presents with advanced disease threatening the globe.4,5 The key to globe salvation and vision preservation in retinoblastoma depends on early diagnosis and appropriate treatment.6 In this chapter, the incidence of retinoblastoma and various etiological factors implicated in the pathogenesis of retinoblastoma are discussed.
Oncogenesis and Metastasis
Published in Karl H. Pang, Nadir I. Osman, James W.F. Catto, Christopher R. Chapple, Basic Urological Sciences, 2021
Alfred Knudsen, 1971 – ‘Two Hit Hypothesis’Children with inherited retinoblastoma inherited one mutation, but only required an additional or ‘second hit’ before a tumour developed.Those with non-inherited tumours needed to acquire inactivation mutations or deletion of both alleles, signifying RB as a TSG.
Familial Adenomatous Polyposis
Published in Dongyou Liu, Handbook of Tumor Syndromes, 2020
Mariann Unhjem Wiik, Bente A. Talseth-Palmer
Individuals with FAP are born with a disadvantage in the form of a germline mutation. According to Knudson's two-hit hypothesis, two mutational events are crucial for cancer development [76]. People with an inherited germline mutation already have one of these two mutations at birth and cancer can develop when a second, somatic mutation occurs [76]. In sporadic cancer, both of the mutations occur somatically, which explains the difference seen in age of onset [76].
Investigational IGF1R inhibitors in early stage clinical trials for cancer therapy
Published in Expert Opinion on Investigational Drugs, 2019
Haim Werner, Rive Sarfstein, Ilan Bruchim
Further support to the notion that IGF1R is a rational target for therapeutic purposes was provided by seminal studies from the laboratory of Renato Baserga that demonstrated that fibroblasts derived from IGF1R knockout embryos (the total deficiency of IGF1R is a lethal condition), with a few exceptions, do not undergo malignant transformation when exposed to viral or cellular oncogenes [65,66]. These early studies had a huge impact in the developing field of IGFs and cancer and positioned the IGF1R as a key candidate in future targeting protocols. In this context, it is important to emphasize that IGF1R expression, by itself, is neither a genotoxic nor a transforming event [13]. In other words, activation of IGF1R by IGF1 or IGF2 does not lead to oncogenesis. However, IGF1 is a progression factor indispensable for cell survival. In the framework of the two-hit hypothesis, IGF1R activation should be regarded as a second hit (i.e. not the oncogenic, first hit). Activation of the IGF1R signaling pathway (i.e. phosphorylation of the receptor tyrosine kinase domain and downstream mediators), not the overexpression in itself, is recognized as a fundamental requirement in transformation [67]. Therefore, the relevance and implication of IGF1R expression in cancer must be evaluated in a broader context, including analyses of signaling pathways (e.g. IRS-1, ras–raf–MAPK, Akt/PKB) and physical and functional interactions with cancer genes.
Black esophagus: a case series and literature review of acute esophageal necrosis
Published in Scandinavian Journal of Gastroenterology, 2018
C. R. Lamers, W. G. N. Mares, D. J. Bac
The etiology is unclear although several theories have been proposed. An ischemic phenomenon and gastric outlet obstruction seem to be the main underlying causes. An ischemic phenomenon is most frequently referred to since there is evidence suggesting a temporary reduction in esophageal blood flow and decreased perfusion may lead to rapid development of extensive esophageal necrosis which may be reversible when flow is restored [6,7,9]. The distal third of the esophagus is more prone to ischemic injury since this part is usually less vascularized compared with other parts of the esophagus [5,7,9]. Transient or complete gastric outlet obstruction leads to an accumulation of large volumes of fluid in the stomach which increases the chance of direct injury caused by esophageal reflux and may lead to prolonged esophageal reflux. Normally esophageal mucosa resists the effects of gastric acid by an increased mucosal blood flow. In the light of the previous two associations a ‘two hit’ hypothesis is suggested. An initial event causing a hypoperfusion state predisposes the esophageal mucosa to a severe topical injury like acid reflux leading to acute esophageal necrosis [5–7]. Malnutrition is another important co-factor in the development of AEN, since it can compromise the mucosal defense system and the capacity for healing after injury [5,6]. In addition, case reports describe an association with viral infections, gastric volvulus, hypersensitivity to antibiotics, Stevens–Johnson syndrome, hyperglycemia, diabetic ketoacidosis, lactic acidosis, and trauma [4,7,9].
Combined Amelioration of Prebiotic Resveratrol and Probiotic Bifidobacteria on Obesity and Nonalcoholic Fatty Liver Disease
Published in Nutrition and Cancer, 2021
Danhong Hu, Wenjuan Yang, Peijiang Mao, Minyu Cheng
It is widely accepted that NAFLD pathogenesis is more complex than the “two-hit” hypothesis. Recent studies have provided sufficient evidence that the gut microbiota participates in NAFLD development through obesity induction, inflammatory response, gut barrier dysfunction, and so on [3, 4]. On the other hand, fecal microbiota transplantation could increase beneficial taxa (such as Bifidobacteriaceae, and Lactobacillaceae) and attenuate high-fat diet (HFD)-induced NAFLD in mice [5]. What’s more, treatment with probiotics, including Bifidobacteriaceae, and Lactobacillaceae, also inhibited the progression of NAFLD in obese animals and patients [6, 7]. Unfortunately, the effects of probiotics are sometimes ambiguous in the absence of prebiotics. One approach to enrich probiotics and enhance their beneficial effect would be supplementation with prebiotics, which have been used to manipulate microorganisms in the host to improve health outcomes. The well-known prebiotics are carbohydrates, but their effects may not always be beneficial. Inulin, pectin and fructooligosaccharides were recently demonstrated to increase the risk of liver cancer [8]. Thus, new prebiotic alternatives are needed. Polyphenols are a common group of plant based bioactive compounds and proven to stimulate the growth of beneficial bacteria [9]. Resveratrol (RSV) is a well-known polyphenol that shows excellent beneficial effect against NAFLD in various animal models [10]. Recent clinical studies, however, showed that RSV supplementation did not considerably improve liver fat content [11] nor oxidative/anti-oxidative status [12, 13], which may be caused by its poor bioavailability. Nevertheless, this property of long retention in bowel lumen enabled this polyphenol as a favorable prebiotic.