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

A 3-year-old male grey collie and 4-year-old female grey collie were part of a cyclic hematopoiesis study. Both dogs had experienced numerous bacterial infections, and both dogs were receiving various treatment regimens, including lithium and hematopoietic growth factors, to control the cyclic hematopoiesis. The first dog was presented in acute collapse and had a rapid clinical course. The second dog was presented with pyrexia and subsequently developed anorexia, disorientation, tremors, mild diarrhea, and bruising at venipuncture sites. Postmortem examination revealed pancreatic adenocarcinoma with metastasis in both cases. Pancreatic adenocarcinoma is a rare neoplasm in dogs. The incidence of pancreatic adenocarcinoma noted in this report is more than 150 times that previously reported in dogs. The cause of the increased incidence of pancreatic malignancy in these grey collies is unknown; possible factors include chronic inflammation or infections, chronic drug therapy, or genetic predisposition. Development of an uncommon neoplasm in two young grey collies may offer an opportunity to study the mechanisms of carcinogenesis.
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PMID:Pancreatic adenocarcinoma in two grey collie dogs with cyclic hematopoiesis. 747 71

Gastric hypomotility, loss of appetite, nausea, and vomiting frequently accompany critical infectious illness, radiation sickness, and carcinogenesis. The present studies examined the possibility that the pro-inflammatory cytokine, tumor necrosis factor-alpha (TNF-alpha), may be responsible for provoking some of these autonomic signs associated with illness. Gastric motility of urethane-anesthetized rats was prestimulated with intracisternal applications of thyrotropin-releasing hormone (TRH), a peptide known to activate parasympathetic vagal excitatory pathways to the stomach. Microinjection of TNF-alpha (as low as 0.02 fmol) directly into the dorsal vagal comples (DVC) suppressed TRH-stimulated gastric motility for prolonged periods of time. Duration of suppression ranged from 5 min to more than an hour, dependent on both the dose of TNF-alpha and accuracy of placement of the microinjection within the DVC. This suppression demonstrated a dose-dependent effect of TNF-alpha that required an intact vagal pathway. These studies indicate that TNF-alpha may represent a unique cytokine 'afferent' signal which directly regulates the excitability of vago-vagal reflex circuits resulting in altered gastric motility during disease states.
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PMID:Tumor necrosis factor-alpha in the dorsal vagal complex suppresses gastric motility. 852 Nov 42

The goal of this short review is to summarize recent data on gastrointestinal changes with aging, focusing on gastrointestinal motility disorders, and mucosal variations. First of all, this review focused on gastrointestinal motility disorders with aging, even though an increased prevalence of several gastrointestinal motor disorders (i.e., dysphagia, dyspepsia, anorexia, and constipation) occurs in older people, aging per se appears to have a minor direct effect on most gastrointestinal functions. Secondly, this review focused on histological changes with aging, i.e., regulation of gastrointestinal mucosal growth, gastrointestinal carcinogenesis, and gastric mucosal changes, especially changes in gastric acid secretion, bacterial overgrowth and its consequences on elderly patients.
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PMID:Basic mechanisms of the aging gastrointestinal tract. 1746 45

Medication for the treatment of attention-deficit hyperactivity disorder (ADHD) is in widespread use globally. There is considerable data suggesting that overall, the adverse effect burden from this use is dose dependent and is in the mild to moderate category, but few comprehensive reviews exist of the epidemiology of adverse effects alone. This review provides a general and systems-specific summary of the scientific literature regarding adverse effect data for the drugs in general use for the treatment of ADHD. Although several areas lack definitive data, current evidence suggests that, for the majority of those treated for ADHD, the medications currently available pose little in the way of risk of significant harm. Epidemiological data suggest a low incidence of serious adverse effects, whilst the less serious adverse effects, such as insomnia and anorexia, are relatively common. Also, some specific areas of study suggest lower risks of harm than previously thought, e.g. tic disorders and seizures. However, pre-existing conditions and other interindividual differences may raise the risk of harmful adverse effects, which adds emphasis to the need for careful pretreatment assessment and monitoring. Potential but unlikely long-term treatment effects need to be investigated as carefully as possible, particularly with regard to cardiac sequelae and carcinogenesis. There are both overlaps and differences between the adverse effects of stimulants and nonstimulants, such as atomoxetine. For example, the latter shares the stimulant group's potential for changing cardiovascular parameters, but may not cause insomnia.
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PMID:Adverse effects of pharmacotherapies for attention-deficit hyperactivity disorder: epidemiology, prevention and management. 1827 77

Multifunctional macrophage inhibitory cytokine-1, MIC-1, is a member of the transforming growth factor-beta (TGF-beta) superfamily that plays key roles in the prenatal development and regulation of the cellular responses to stress signals and inflammation and tissue repair after acute injuries in adult life. The stringent control of the MIC-1 expression, secretion, and functions involves complex regulatory mechanisms and the interplay of other growth factor signaling networks that control the cell behavior. The deregulation of MIC-1 expression and signaling pathways has been associated with diverse human diseases and cancer progression. The MIC-1 expression levels substantially increase in cancer cells, serum, and/or cerebrospinal fluid during the progression of diverse human aggressive cancers, such as intracranial brain tumors, melanoma, and lung, gastrointestinal, pancreatic, colorectal, prostate, and breast epithelial cancers. Of clinical interest, an enhanced MIC-1 expression has been positively correlated with poor prognosis and patient survival. Secreted MIC-1 cytokine, like the TGF-beta prototypic member of the superfamily, may provide pleiotropic roles in the early and late stages of carcinogenesis. In particular, MIC-1 may contribute to the proliferation, migration, invasion, metastases, and treatment resistance of cancer cells as well as tumor-induced anorexia and weight loss in the late stages of cancer. Thus, secreted MIC-1 cytokine constitutes a new potential biomarker and therapeutic target of great clinical interest for the development of novel diagnostic and prognostic methods and/or cancer treatment against numerous metastatic, recurrent, and lethal cancers.
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PMID:Divergent molecular mechanisms underlying the pleiotropic functions of macrophage inhibitory cytokine-1 in cancer. 2057 39

Cocaine- and amphetamine-regulated transcript peptide (CART) is a major anorectic agent present in the hypothalamus. We investigated the possible role of CART in mammary cancer-induced anorexia and body weight loss in rats. Mammary carcinogenesis was induced in the female Sprague-Dawley rats by intraperitoneal injection of N-methyl-N-nitrosourea (MNU). Following administration of MNU, rats progressively showed a reduction in food intake and body weight. Fourteen weeks after MNU treatment, rats were injected daily with CART or CART-antibody intracerebroventricularly for 5days, and food intake and body weight were monitored (g) before the next injection time-point. In normal rats, while a distinct anorexia and weight loss was observed following CART administration, injection of CART-antibody produced opposite effects. However, both the agents failed to produce any significant alterations in food intake and body weight of mammary tumor-bearing animals. An immunohistochemical application of antibodies against CART to the brain sections of cancerous rats showed a reduced immunoreactivity in the hypothalamic dorsomedial, ventromedial, lateral, paraventricular and arcuate nuclei. The results suggest that, cancerous condition might down-regulate the CART system in the hypothalamus. Alternatively, reduction in hypothalamic CART activity might be a counter-regulatory strategy to reverse food under-consumption or body mass erosion.
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PMID:Hypothalamic cocaine- and amphetamine-regulated transcript peptide is reduced and fails to modulate feeding behavior in rats with chemically-induced mammary carcinogenesis. 2083 97

Anorexia and muscle wasting are frequently observed in cancer patients and influence their clinical outcome. The better understanding of the mechanisms underlying behavioral changes and altered metabolism yielded to the development of specialized nutritional support, which enhances utilization of provided calories and proteins by counteracting some of the metabolic derangements occurring during tumor growth. Inflammation appears to be a key factor determining the cancer-associated biochemical abnormalities eventually leading to anorexia and cachexia. Interestingly, inflammation is also involved in carcinogenesis, cancer progression and metastasis by impairing immune surveillance, among other mechanisms. Therefore, nutritional interventions aiming at modulating inflammation to restore nutritional status may also result in improved response to pharmacological anti-cancer therapies. Recent clinical data show that supplementation with nutrients targeting inflammation and immune system increases response rate and survival in cancer patients. This suggests that nutrition therapy should be considered as an important adjuvant strategy in the multidimensional approach to cancer patients.
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PMID:Beyond anorexia -cachexia. Nutrition and modulation of cancer patients' metabolism: supplementary, complementary or alternative anti-neoplastic therapy? 2181 Apr 20

Deoxynivalenol (DON [vomitoxin]), one of trichothecene mycotoxins produced by the fungus Fusarium, is commonly detected in cereal foods across the world. DON induces diverse toxic effects in humans and animals, including emesis and diarrhea, anorexia, and immunotoxicity, and impaired maternal reproduction and fetal development. Recently, the teratogenic potential of DON has been shown and has received much attention. DON can cause various skeletal deformities in fetuses, but the underlying mechanisms have not yet been fully examined. In this study, fetal skeletal malformations in DON-treated maternal mice were thoroughly investigated using microarray assay. The results showed that DON administration caused various skeletal defects in fetuses, including misaligned or fused sternebrae and vertebrae, divided or fused ribs and polydactyly, hemivertebrae, short toes, and tail anomalies. Microarray analysis showed that 282 genes, including 148 downregulated and 134 upregulated genes, were abnormally expressed in fetal vertebral bones after maternal DON exposure. These identified genes can be classified into several categories: skeletal development, carcinogenesis, nervous disorders, sperm development and embryogenesis, and inflammation. Of these, 6 genes, mostly related to bone development, were intentionally selected for further validation using real-time reverse transcription-Polymerase Chain Reaction (RT-PCR). It was confirmed that the mRNA expression of 4 genes, i.e., fibrillin-1, Col9A2, 3'-phosphoadenosine 5'-phosphosulfate synthase 2, and Pax1, was upregulated significantly by DON administration, whereas that of 2 other genes, Runx2 and parathyroid hormone-like hormone, was downregulated significantly. Taken together, the results of our study suggest that altered expression of these 6 genes plays a critical role in fetal skeletal deformities induced by DON and thus they are worthy of further investigation.
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PMID:Evaluation of fetal skeletal malformations in deoxynivalenol-treated mice using microarray analysis. 2287 31

Gastrointestinal stromal tumors (GIST) are rare mesenchymal smooth muscle sarcomas that can arise anywhere within the gastrointestinal tract. Sporadic mutations within the tyrosine kinase receptors of the interstitial cells of Cajal have been identified as the key molecular step in GIST carcinogenesis. Although many patients are asymptomatic, the most common associated symptoms include: abdominal pain, dyspepsia, gastric outlet obstruction, and anorexia. Rarely, GIST can perforate causing life-threatening hemoperitoneum. Most are ultimately diagnosed on cross-sectional imaging studies (i.e., computed tomography and/or magnetic resonance imaging in combination with upper endoscopy. Endoscopic ultrasonographic localization of these tumors within the smooth muscle layer and acquisition of neoplastic spindle cells harboring mutations in the c-KIT gene is pathognomonic. Curative treatment requires a complete gross resection of the tumor. Both open and minimally invasive operations have been shown to reduce recurrence rates and improve long-term survival. While there is considerable debate over whether GIST can be benign neoplasms, we believe that all GIST have malignant potential, but vary in their propensity to recur after resection and metastasize to distant organ sites. Prognostic factors include location, size (i.e., > 5 cm), grade (> 5-10 mitoses per 50 high power fields and specific mutational events that are still being defined. Adjuvant therapy with tyrosine kinase inhibitors, such as imatinib mesylate, has been shown to reduce the risk of recurrence after one year of therapy. Treatment of locally-advanced or borderline resectable gastric GIST with neoadjuvant imatinib has been shown to induce regression in a minority of patients and stabilization in the majority of cases. This treatment strategy potentially reduces the need for more extensive surgical resections and increases the number of patients eligible for curative therapy. The modern surgical treatment of gastric GIST combines the novel use of targeted therapy and aggressive minimally invasive surgical procedures to provide effective treatment for this lethal, but rare gastrointestinal malignancy.
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PMID:Modern treatment of gastric gastrointestinal stromal tumors. 2323 9

Oxytocin (OXT) is a hypothalamic neuropeptide composed of nine amino acids. The functions of OXT cover a variety of social and nonsocial activity/behaviors. Therapeutic effects of OXT on aberrant social behaviors are attracting more attention, such as social memory, attachment, sexual behavior, maternal behavior, aggression, pair bonding, and trust. The nonsocial behaviors/functions of brain OXT have also received renewed attention, which covers brain development, reproduction, sex, endocrine, immune regulation, learning and memory, pain perception, energy balance, and almost all the functions of peripheral organ systems. Coordinating with brain OXT, locally produced OXT also involves the central and peripheral actions of OXT. Disorders in OXT secretion and functions can cause a series of aberrant social behaviors, such as depression, autism, and schizophrenia as well as disturbance of nonsocial behaviors/functions, such as anorexia, obesity, lactation failure, osteoporosis, diabetes, and carcinogenesis. As more and more OXT functions are identified, it is essential to provide a general view of OXT functions in order to explore the therapeutic potentials of OXT. In this review, we will focus on roles of hypothalamic OXT on central and peripheral nonsocial functions.
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PMID:Nonsocial functions of hypothalamic oxytocin. 2496 4


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