Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The terms 'biocompatibility', 'blood compatibility', and 'thrombogenicity' are often used interchangeably which leads to confusion in the scientific and medical literatures. No single test can reliably predict the 'blood compatibility' of materials, and tests for thrombogenicity are not necessarily indicators of blood compatibility. Although the toxicological screening of biomaterials is important, the absence of adverse effects does not assure biocompatibility. Acute toxicological screenings should be carried in the biological evaluation phases of biomaterials but the results should be interpreted with caution because polymers degrade in the physiological environment by time-dependent mechanisms leading to the formation of potentially toxic products, including carcinogens. Increased efforts are needed to screen potential biomaterials for carcinogenesis and mutagenesis. Biological tests should be conducted with animals whose haematological profile closely resembles that of humans rather than rely on results obtained wity species such as dogs and calves. Accelerated fatigue testing of elastomers must be conducted under condition that closely approximate the properties of the biological environment to avoid catastrophic failures.
 ...
PMID:Problems and artefacts in the evaluation of polymeric materials for medical uses. 747 May 55

Periprosthetic osteolysis caused by wear debris released from the bearing surface of polyethylene components is the major problem in contemporary hip arthroplasty. Several types of metal on metal prostheses were developed in the 1960s, but by the mid 1970s they were completely displaced by polyethylene bearings. There have been several generations of all metal components with significant variation in design, tolerances, and bearing surface quality. A number of these hips have survived for more than 25 years because of low wear rates and minimal osteolysis. Identification of the characteristics that contributed to long term function is important. The historical development and clinical results of metal on metal hip arthroplasties are presented. Factors that led to the abandonment of the metal on metal bearings are related to: (1) the early success of the Charnley prosthesis; (2) the frictional torque issue; (3) carcinogenesis concerns; (4) metal sensitivity concerns; (5) high infection rates; and (6) increased strain rates in periprosthetic bone and fatigue fractures of the acetabular floor. The accumulated experience to date enables one to evaluate all the factors with a different perspective and makes the use of newer metal on metal bearings a viable option in younger patients.
 ...
PMID:Metal on metal bearings in hip arthroplasty. 922 68

Increasing dietary fat content increases mammary gland tumorigenesis in laboratory rodents. The effect can be attributed only in part to increasing energy intake, which itself increases tumorigenesis. Restriction of dietary or energy intake, sufficient to reduce body weight, reduces mammary gland tumorigenesis. Consideration of these effects has led to discussion of the possible need for changes in the feeding of laboratory rodents in carcinogenesis bioassays and other chronic studies. Studies of endocrine or other growth factors for the mammary gland have not identified specific effects of dietary fat or energy. In addition, tumorigenesis in other organs responds similarly to increased fat or decreased energy intake, indicating that the mechanisms are not, or not entirely, specific for the mammary gland. Extrapolations of results between species must always be made with caution, but the marked effects of dietary fat and energy in rodent tumorigenesis models must be considered in designing diet advice for humans.
 ...
PMID:Diet and breast cancer: studies in laboratory animals. 916 67

Retinoids have been shown to be potent inhibitors of epithelial carcinogenesis. Recent evidence has demonstrated that retinoid actions are mediated through nuclear receptors, which are proteins encoded by the retinoic acid receptor and retinoid X receptor gene families. These receptors are activated by binding to specific retinoids; of the known naturally occurring retinoids, 9-cis retinoic acid is unique in its ability to bind to both receptor families. Because of its unique receptor-binding characteristics, 9-cis retinoic acid may have biological activity not possible with other retinoids. For this reason, we conducted a Phase I trial of 9-cis retinoic acid in adult patients with solid tumors. Twenty-two patients were treated twice daily with p.o. 9-cis retinoic acid at doses ranging from 20 mg/m2/day to 150 mg/m2/day. The patients had non-small cell lung cancer (n = 8), breast cancer (n = 5), colorectal cancer (n = 3), head and neck cancer (n = 2), nonmelanoma skin cancer (n = 2), or ovarian cancer (n = 2). The dose-limiting (WHO grade III) toxic effects, which occurred at the 150-mg/m2/day dose level, were headaches and diarrhea. Less severe (grades I and II) toxic effects included cheilitis, dry skin, conjunctivitis, fatigue, hypertriglyceridemia, alkaline phosphatase elevation, myalgia/arthralgia, and hypercalcemia. Of the 15 patients evaluable for tumor response, no objective responses were observed. Pharmacokinetic analysis revealed a reduction in peak 9-cis retinoic acid plasma levels with chronic administration. Based on this study, the recommended Phase II dose of 9-cis retinoic acid in adult patients with solid tumors is 100 mg/m2/day administered in a divided dose twice daily.
 ...
PMID:Phase I trial of 9-cis retinoic acid in adults with solid tumors. 981 71

Reactions to oral contraceptive therapy tend to be maximal during the first few months of use. They include nausea or epigastric discomfort, malaise, dizziness, nervousness, fatigue, weakness, leg cramps, headache, and depression. The estrogenic component is thought to be the cause. There may also be a psychogenic basis reflecting apprehension. Breast tenderness is an occasional complaint and intermenstrual spotting or breakthrough bleeding is often reported. Increasing dosage has reduced this symptom. Dysmenorrhea prior to treatment may be improved but occasionally it is aggravated. Drug-induced amenorrhea presents a double problem in that failure to resume medication 7 days after completion of a cycle results in a risk of conception. Episodes of severe uterine bleeding in patients discontinuing use after several months or years have been reported. Other side effects include a skin reaction resembling acne, pruritus, hirsutism, thinning of scalp hair, increased skin pigmentation, and weight gain or loss. Serious vascular complications and hepatic dysfunction have been shown and deviation of thyroid function may be shown by increase of serum protein-bound iodine (PBI). Clinical signs of hyperthyroidism have not been described. Oral contraception is associated with elevated plasma cortisol (hydrocortisone) levels and decreased urinary levels of 17-hydroxycorticosteroids (17-OCHS). Suppression of ovarian activity by oral contraceptives is rapidly reversible. Fear of carcinogenesis has caused much alarm but no proof as of the present time. Safety of long term use will require additional years of experience.
 ...
PMID:Side-effects and possible complications of oral contraceptive drugs. 1225 41

Toxigenic mold activities produce metabolites that are either broad-spectrum antibiotics or mycotoxins that are cytotoxic. Indoor environmental exposure to these toxigenic molds leads to adverse health conditions with the main outcome measure of frequent neuroimmunologic and behavioral consequences. One of the immune system disorders found in patients presenting with toxigenic mold exposure is an abnormal natural killer cell activity. This paper presents an overview of the neurological significance of abnormal natural killer cell (NKC) activity in chronic toxigenic mold exposure. A comprehensive review of the literature was carried out to evaluate and assess the conditions under which the immune system could be dysfunctionally interfered with leading to abnormal NKC activity and the involvement of mycotoxins in these processes. The functions, mechanism, the factors that influence NKC activities, and the roles of mycotoxins in NKCs were cited wherever necessary. The major presentations are headache, general debilitating pains, nose bleeding, fevers with body temperatures up to 40 degrees C (104 degrees F), cough, memory loss, depression, mood swings, sleep disturbances, anxiety, chronic fatigue, vertigo/dizziness, and in some cases, seizures. Although sleep is commonly considered a restorative process that is important for the proper functioning of the immune system, it could be disturbed by mycotoxins. Most likely, mycotoxins exert some rigorous effects on the circadian rhythmic processes resulting in sleep deprivation to which an acute and transient increase in NKC activity is observed. Depression, psychological stress, tissue injuries, malignancies, carcinogenesis, chronic fatigue syndrome, and experimental allergic encephalomyelitis could be induced at very low physiological concentrations by mycotoxin-induced NKC activity. In the light of this review, it is concluded that chronic exposures to toxigenic mold could lead to abnormal NKC activity with a wide range of neurological consequences, some of which were headache, general debilitating pains, fever, cough, memory loss, depression, mood swings, sleep disturbances, anxiety, chronic fatigue, and seizures.
 ...
PMID:The neurological significance of abnormal natural killer cell activity in chronic toxigenic mold exposures. 1462 99

A 62-year-old patient with low grade fever, fatigue, arthralgia and newly discovered mitral regurgitation was diagnosed with subacute endocarditis. Streptococcus bovis grew from all six blood culture bottles. Streptococcus bovis is known to be associated with gastrointestinal neoplasias. Therefore a colonoscopy was performed and two polyps were removed. Histological analysis revealed a tubulovillous adenoma and a serrated adenoma. Colonoscopy is mandatory for all patients with Streptococcus bovis endocarditis even without any symptoms for colorectal neoplasia. The significance of Streptococcus bovis for the carcinogenesis of colorectal neoplasias and the possible alternative pathway for colorectal carcinomas through serrated adenomas will be discussed.
 ...
PMID:[Fever, malaise and new onset mitral valve insufficiency. Subacute Streptococcus bovis mitral valve endocarditis ]. 1518 88

Telomeres are the repeat DNA sequences at the end of chromosomes necessary for successful DNA replication and chromosomal integrity. Telomeres shorten at cell division at a rate determined by oxidative DNA damage, and cells are triggered into replicative senescence once telomeres shorten to a critical length. Telomere-related chromosomal maintenance also has a role in carcinogenesis. Type 2 diabetes is characterised by increased oxidative stress, increased oxidative DNA damage, senescent retinal and renal phenotypes, and an increased risk of epithelial malignancy. We suggest that increased oxidative DNA damage and telomere attrition in type 2 diabetes leads to: (1) carcinogenic telomere-dependent chromosomal non-reciprocal translocations, genomic instability, and the development of epithelial cancers; (2) senescent retinal and renal phenotypes (expressed as diabetic retinopathy and nephropathy); and (3) senescent vascular endothelial, monocyte-macrophage and vascular smooth muscle cells (expressed as endothelial dysfunction and accelerated atherogenesis). An adverse intrauterine environment leads to increased feto-placental oxidative stress and feto-placental oxidative DNA damage. We also suggest that intrauterine oxidative DNA damage and telomere shortening is another point at which increased oxidative stress could contribute to a pre-programmed increased risk of senescent phenotypes in adult offspring, characterised by type 2 diabetes and epithelial malignancy. These suggestions can be used to understand early glucose intolerance in the young children of type 1 diabetes pregnancies, poor cancer outcomes in type 2 diabetes, beta cell fatigue in type 2 diabetes and the absence of increased epithelial cancer risk in type 1 diabetes.
 ...
PMID:Chromosomal telomere attrition as a mechanism for the increased risk of epithelial cancers and senescent phenotypes in type 2 diabetes. 1679 17

Chemical defensive system consisting of bio-sensoring, transmitting, and responsive elements has been evolved to protect multi-cellular organisms against environmental chemical insults (xenobiotics) and to maintain homeostasis of endogenous low molecular weight metabolites (endobiotics). Both genetic and epigenetic defects of the system in association with carcinogenesis and individual sensitivity to anti-tumor therapies have been intensely studied. Recently, several non-tumor human pathologies with evident environmental components such as rather rare functional syndromes (multiple chemical sensitivity, chronic fatigue, Persian Gulf, and fibromyalgia now collectively labeled as idiopathic environmental intolerances) and common diseases (vitiligo and systemic lupus erythematosus) have become subjects of the research on the impaired metabolism and detoxification of xenobiotics and endogenous toxins. Here, we collected and critically reviewed epidemiological, genetic, and biochemical data on the involvement and possible role of cytochrome P450 super family enzymes, glutathione-S-transferase isozymes, catechol-O-methyl-transferase, UDP-glucuronosyl transferases, and proteins detoxifying inorganic and organic peroxides (catalase, glutathione peroxidase, and peroxiredoxin) in the above pathologies. Genetic predisposition assessed mainly by single nucleotide polymorphism and gene expression analyses revealed correlations between defects in genes encoding xenobiotic-metabolizing and/or detoxifying enzymes and risk/severity of these syndromes/diseases. Proteome analysis identified abnormal expression of the enzymes. Their functions were affected epigenetically leading to metabolic impairment and, as a consequence, to the negative health outcomes shared by some of these pathologies. Data obtained so far suggest that distinct components of the chemical defensive system could be suitable molecular targets for future pathogenic therapies.
 ...
PMID:The chemical defensive system in the pathobiology of idiopathic environment-associated diseases. 2020 26

Personality refers to an individual's enduring and pervasive personal motivation, emotion, interpersonal style, attitudes and behavior that are stable over a long time after young adulthood. In relation to the cancer trajectory, three basic and one other personality traits have been studied with some frequency, namely neuroticism, extraversion, conscientiousness and optimism. The considerable stability of personality over time makes it a potential long-acting etiological factor for the development of cancer. However, the studies performed so far do not give much support to personality as a causative factor for cancer. Some studies of cancer survival have found significant associations between lower optimism and higher neuroticism with shorter survival. More mental distress and fatigue and poorer quality of life is significantly associated with higher neuroticism and lower optimism at cancer screening, diagnosis and primary treatment, short- and long-term follow-up and towards the end of life. Neuroticism is a strong predictor of post-traumatic stress disorder triggered by cancer as a life-threatening experience eventually leading to negative personality changes. To what extent cancer leads to positive personality changes (post-traumatic growth) is currently unsettled. Basic personality traits are strongly associated with lifestyle, which is considered an important etiological factor for the development of cancer. The methodological problems in the study of personality and cancer are considerable, and many research designs used so far may have been too simplistic. Studies of potential biomarkers for personality traits combined with inflammation markers of cellular carcinogenesis in longitudinal designs could be promising for the future. High neuroticism is important for the clinical management of cancer patients and should gain more attention from oncologists in the future.
 ...
PMID:Link between personality and cancer. 2046 85


1 2 Next >>