Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Colorectal cancer is one of the leading causes of death from malignant diseases in the Western world. Worldwide, approximately 50% of patients who present with colorectal cancer will develop metastatic disease and eventually die from this malignancy. Recently, significant advances have been made in the medical treatment of advanced colorectal cancer with the introduction of novel cytotoxic drugs, such as irinotecan and oxaliplatin. Based on the results of recent Phase III trials, combination regimens of infusional 5-fluorouracil/leucovorin and oxaliplatin (FOLFOX) have emerged as a new standard of care in the palliative and adjuvant treatment of colorectal cancer. The addition of biological agents targeting angiogenesis or oncogenes such as epidermal growth factor receptor (EGFR) to FOLFOX will conceivably further enhance the activity of treatment regimens. Making use of all available active therapeutic options in the course of disease has significantly improved median overall survival of metastatic colorectal cancer into a chronic disease, with implications for treatment strategies and pharmacoeconomic considerations.
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PMID:A review of oxaliplatin and its clinical use in colorectal cancer. 1546 51

Diabetes mellitus (DM) is a chronic disease that is characterized by deteriorating glycemic control. The disease is known to be caused by imbalance between reactive oxygen species (ROS) and antioxidant defense systems. Hyperglycemia is commonly observed in a wide variety of diseases, including cancer. Although, therapy against glycemic control, is used in all these diseases, the diabetic cancer patients are on additional therapy with anticancer drugs. The objective of present study was to study if Glucophage (metformin), a very popular antidiabetic agent can avert the mutagenicity and lipid peroxidation caused by adriamycin (ADR), which is a commonly used cytotoxic drug. The experimental protocol included oral treatment of mice with different doses (62.5, 125 and 250 mg/kg day) of metformin for 7 days. Some mice in each group were injected i.p. with ADR (15 mg/kg). In each case animals were killed, 30 or 24, 48 and 72 h after the last treatment and femurs were excised for cytological studies by micronucleus test. Additional experiments on estimation of glutathione (GSH) and malondialdehyde (MDA) were undertaken in blood and serum, respectively. Twenty-four hour after the treatment, blood from each mouse was collected from heart and preserved for analysis. The results obtained revealed that pretreatment with metformin: (i) reduced the ADR-induced frequency of micronuclei without any alteration in its cytotoxicity and (ii) protected against the ADR-induced increase and decrease of MDA and GSH, respectively. The exact mechanism of action is not known, however, the inhibition of ADR-induced clastogenicity and lipid peroxidation by metformin may be attributed to the antioxidant action of the latter. Our results demonstrate that metformin might be useful to avert secondary tumor risk by decreasing the accumulation of free radicals and inhibition of mutagenicity.
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PMID:Effect of metformin on clastogenic and biochemical changes induced by adriamycin in Swiss albino mice. 1769 28

Proteolytic remodeling of the extracellular matrix is an important component of disease progression in many chronic disease states and is the initiating event in the formation of the tumor microenvironment in cancer. It is the balance of extracellular matrix degrading enzymes, the matrix metalloproteinases (MMPs) and their endogenous inhibitors that determine the extent of tissue remodeling. Unchecked MMP activity can result in significant tissue damage, facilitate disease progression and is associated with host responses to pathologic injury such as angiogenesis and inflammation. The tissue inhibitors of metalloproteinases (TIMPs) have been shown to regulate MMP activity. However, recent findings demonstrate that the tissue inhibitor of metalloproteinases-2 (TIMP-2) inhibits the mitogenic response of human microvascular endothelial cells to growth factors, such as VEGF-A and FGF-2 in vitro and angiogenesis in vivo. The mechanism of this effect is independent of metalloproteinase inhibition. Our lab is the first to demonstrate a cell-surface signaling receptor for a member of the TIMP family and suggest that TIMP-2 functions to regulate cellular responses to growth factors. These new findings are discussed in terms of a model of TIMP-2 regulation of cellular functions in the tumor microenvironment.
Cancer Metastasis Rev 2008 Mar
PMID:The tumor microenvironment: regulation by MMP-independent effects of tissue inhibitor of metalloproteinases-2. 1805 95

Hormone receptor-positive breast cancer is increasingly considered a chronic disease, as there remains an ongoing risk of local and distant relapse for years after diagnosis. While early recurrence risk peaks 2-3 years post diagnosis, the majority of breast cancer recurrences and deaths occur following 5 years of adjuvant tamoxifen. Aromatase inhibitors have achieved greater relative reductions in recurrence risk than tamoxifen alone and are now widely recommended as adjuvant therapy for postmenopausal women with hormone-sensitive breast cancer. Although both anastrozole and letrozole have demonstrated superior disease-free survival compared with tamoxifen, letrozole to date offers the greatest significant reduction in the risk of distant metastases in patients with hormone-sensitive breast cancer. Anastrozole and exemestane also reduce local and distant recurrence risk in the "switch setting" following 2-3 years of tamoxifen. Extended adjuvant letrozole, given after 5 years of tamoxifen, significantly reduces local and distant recurrence as well as mortality in patients with node-positive disease. Specialist nurses and nurse practitioners facilitate informed choice for breast cancer patients through explaining treatment options and side effects; they thus need an understanding of which treatment strategies reduce recurrence risk, especially the risk of distant metastases.
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PMID:The role of endocrine therapies in reducing risk of recurrence in postmenopausal women with hormone receptor-positive breast cancer. 1837 13

Thyroid hormones (TH) are essential for an adequate growth and development of the kidney. Conversely, the kidney is not only an organ for metabolism and elimination of TH, but also a target organ of some of the iodothyronines' actions. Thyroid dysfunction causes remarkable changes in glomerular and tubular functions and electrolyte and water homeostasis. Hypothyroidism is accompanied by a decrease in glomerular filtration, hyponatremia, and an alteration of the ability for water excretion. Excessive levels of TH generate an increase in glomerular filtration rate and renal plasma flow. Renal disease, in turn, leads to significant changes in thyroid function. The association of different types of glomerulopathies with both hyper- and hypofunction of the thyroid has been reported. Less frequently, tubulointerstitial disease has been associated with functional thyroid disorders. Nephrotic syndrome is accompanied by changes in the concentrations of TH due primarily to loss of protein in the urine. Acute kidney injury and chronic kidney disease are accompanied by notable effects on the hypothalamus-pituitary-thyroid axis. The secretion of pituitary thyrotropin (TSH) is impaired in uremia. Contrary to other non-thyroidal chronic disease, in uraemic patients it is not unusual to observe the sick euthyroid syndrome with low serum triodothyronine (T(3)) without elevation of reverse T(3) (rT(3)). Some authors have reported associations between thyroid cancer and kidney tumors and each of these organs can develop metastases into the other. Finally, data from recent research suggest that TH, especially T(3), can be considered as a marker for survival in patients with kidney disease.
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PMID:Thyroid dysfunction and kidney disease. 1909 79

In many chronic disease processes subjects are at risk of two or more types of events. We describe a bivariate mixed Poisson model in which a copula function is used to model the association between two gamma distributed random effects. The resulting model is a bivariate negative binomial process in which each type of event arises from a negative binomial process. Methods for parameter estimation are described for parametric and semiparametric models based on an EM algorithm. We also consider the issue of event-dependent censoring based on one type of event, which arises when one event is sufficiently serious that its occurence may influence the decision of whether to withdraw a patient from a study. The asymptotic biases of estimators of rate and mean functions from naive marginal analyses are discussed, as well as associated treatment effects. Because the joint model is fit based on a likelihood, consistent estimates are obtained. Simulation studies are carried out to evaluate the empirical performance of the proposed estimators with independent and event-dependent censoring and applications to a trial of breast cancer patients with skeletal metastases and a study of patients with chronic obstructive pulmonary disease illustrate the approach.
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PMID:A copula-based mixed Poisson model for bivariate recurrent events under event-dependent censoring. 2014 40

Addressing the sexual sequelae of chronic disease and its treatment is now accepted as a fundamental part of healthcare. Most of the sexual effects of chronic disease are negative, and ongoing illness continues to modulate a woman's sexual self-image, energy and interest in sexual activity, as well as her ability to respond to sexual stimuli with pleasurable sensations, excitement, orgasm and freedom from pain with genital stimulation or intercourse. Nevertheless, for many women with chronic illness, sexuality remains extremely important despite the commonly associated fatigue and acquired sexual dysfunctions; sexual resilience can be substantial. Following recovery from cancer surgery, chemotherapy and radiation, prognosis can be excellent and a return to full health can often be expected, and yet, there may have been devastating changes to sexual function owing to the cancer treatment. Women with metastatic disease may still treasure sexual intimacy. Assessment and management of sexual dysfunction is therefore necessary in all women with chronic illness or past or present cancer.
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PMID:Sexual function of women with chronic illness and cancer. 2042 7

While uncommon, isolated avulsion fractures of the lesser trochanter occur in children and adolescents prior to the fusion of this apophysis as a result of athletic activities. In the elderly, isolated fractures of the lesser trochanter are rare but can occur as a result of trauma. They have been identified in patients with primary or secondary bone malignancies, which were previously considered pathognomonic for metastatic disease. In the absence of trauma, weakening of the bone due to systemic disorders such as osteoporosis or osteomalacia chronica renal failure may also be responsible. Diagnosis may be difficult with physical examination and radiographs alone. This case report details this rare fracture in 2 patients suffering from debilitating chronic disease. Patient 1 was a 30-year-old woman with an 18-year history of type 1 diabetes mellitus, a 6-year history of end-stage renal disease, hypertension, hypothyroidism, peripheral vascular disease, and a 3-year history of systemic lupus erythematosus with antiphospholipid syndrome treated with warfarin. Patient 2 was a 66-year-old woman with a history of type 2 diabetes mellitus, peripheral neuropathy, obesity, chronic obstructive pulmonary disease, gout, hypertension, and chronic neck and low back pain. Both were assessed with magnetic resonance imaging following physical examination, which revealed atraumatic avulsion of the distal iliopsoas tendon from the lesser trochanter. Following retraction of the iliopsoas tendon, the patients were treated with conservative therapy and anti-inflammatory medication. These 2 cases broaden the range of patients for whom spontaneous avulsion of the distal iliopsoas tendon should be considered in the differential diagnosis.
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PMID:Atraumatic avulsion of the distal iliopsoas tendon: an unusual cause of hip pain. 2070

In the last years, incurable oncologic diseases have become increasingly viewed as chronic disease processes. In order to evaluate the treatment course of a chronic disease and to demonstrate whether the concept of a palliative oncologic situation as a chronic disease can be translated into practice, it is essential to give an overview of the entire course of the disease (i.e. from the first diagnosis of recurrence/metastases to death). There are only few reports regarding this approach in the international literature. We present Swiss long-term data (1990-2007) for breast and ovarian cancer and demonstrate drawbacks and opportunities of an exact retrospective data collection and analysis. When an incurable disease which requires periodic therapy cycles to control progressive course and symptoms is increasingly treated with a strategy that permits stabilization and uses regimens that have limited cumulative toxicity with particular consideration of quality of life, then the requirements of a chronic disease management have been fulfilled.
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PMID:[The concept of chronic disease in the palliative treatment of oncologic patients: current Swiss data and insights in the context of breast and ovarian cancer]. 2108 94

Paget disease of the bone is a chronic disease characterized by accelerated bone turnover with abnormal repair leading to expansion, pain and deformities. The disease is common in the West, but little if any information is available on its existence in the Arab world, including Saudi Arabia. We present four cases of Saudi patients with Paget disease with variable presentations. The first case, a 63-year-old woman with a history of papillary thyroid cancer, presented with bone, shoulder and chest wall pain and foci of uptake in the ribs and skull that were thought to be metastases, indicating the possibility of diagnostic difficulty in a patient with history of malignancy. Bone biopsy confirmed the diagnosis of Paget disease. The second case was a 47-year-old asymptomatic woman with an elevated alkaline phosphatase of 427 U/L, a common presentation but at an unusual age. Plain x-rays and bone scan confirmed the diagnosis. The third case was a 43-year-old man who presented with hearing impairment and right knee osteoarthritis, unusual presentations at a young age leading to a delay in diagnosis. The fourth case was a 45-year-old man who presented with sacroiliac pain and normal biochemical values, including a normal alkaline phosphatase. Bone biopsy unexpectedly revealed features of Paget disease, which evolved over time into a classical form. A common feature in all except the first case was the relatively young age. Paget disease does exist in Saudi Arabia, and it should be considered in the differential diagnosis of similar cases.
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PMID:Paget disease of the bone: does it exist in Saudi Arabia? 2124 39


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