Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033774 (pruritus)
 14,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A significant proportion of cancer patients develop malignant wounds. Malignant wounds are generally nonhealable and are managed with palliative methods. Palliative wound care encompasses the pain and symptom management of such wounds. Sixty-seven of 472 cancer patients from a prospective sequential case series of palliative medicine consultations demonstrated malignant wounds at the time of referral and were studied to determine the most common symptoms and anatomic sites associated with malignant wounds. Data were collected from patients' own reports of up to three wound-related symptoms. Overall, 67.7% of malignant wounds were associated with at least one of the following eight symptoms: pain, mass effect, esthetic distress, exudation, odor, pruritus, bleeding, and crusting; 21.9% of wounds were associated with two or more symptoms; and 11.5% of wounds were associated with three symptoms. The symptom point prevalence was 31.3% for pain, 23.9% for mass effect, 19.4% for esthetic distress, 17.9% for exudation, 11.9% for odor, 6% for pruritus, 6% for bleeding, and 1.5% for crusting. Breast cancer patients had the highest prevalence of malignant wounds (47.1%). The anterior chest wall and breast was the site of 31.2% of wounds. The perineum and genitalia presented with the highest ratio of symptoms per wound (2.2). The results of this study reflect that malignant wounds are associated with a significant symptomatic burden, and reinforces the need for thorough clinical assessment and evaluation of symptoms. Further research is required to define the optimal methods of pain and symptom management for malignant wounds.
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PMID:Symptoms associated with malignant wounds: a prospective case series. 1861 64

In humans, as in all mammals and most chordates, three forms of superoxide dismutase (SOD) are present: SOD1 is located in the cytoplasm, SOD2 in the mitochondria, and SOD3 is extracellular. SOD is used in cosmetic products to reduce free radical damage to the skin, for example, to reduce fibrosis following radiation for breast cancer. Pruritus is one of the most common symptoms of skin diseases, but can also be a major symptom of systemic diseases (e.g., malignancy, infection or metabolic disorders). There are various antihistaminics used as antipruritogenic substances. In the genesis of pruritus there are many pruritogens involved, not only histamine and leukotrienes such as acetylcholine, cytokines, kallikreins, proteases, kinins, opioids, etc., which are described. On many occasions, we observed that topical SOD seemed to possess strong antipruritic activity, even in anti-histamine-resistant pruritus. We analyzed literature data on the effect of SOD as an anti-pruritogen on NK-1 receptors and proinflammatory cytokines, its regulatory role in calcitonin gene-related peptide production and expression, down-regulation of TNF- and numerous cytokines, and suppression of nitric oxide production.
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PMID:The basis of topical superoxide dismutase antipruritic activity. 1938 13

ErbB4, a member of the epidermal growth factor receptor family, plays a role in normal breast and breast cancer development by regulating mammary epithelial cell proliferation, survival and differentiation. In this study, we show that WWP1, a C2-WW-HECT type E3 ubiquitin ligase, binds, ubiquitinates and destructs ErbB4-CYT1, but much less efficiently for CYT2, isoforms (both JMa and JMb). The protein-protein interaction occurs primarily between the first and third WW domains of WWP1 and the second PY motif of ErbB4. Knockdown of WWP1 by two different small interfering RNAs increases the endogenous ErbB4 protein levels in both MCF7 and T47D breast cancer cell lines. In addition, overexpression of the wild type, but not the catalytic inactive WWP1, dramatically decreases the endogenous ErbB4 protein levels in MCF7. Importantly, we found that WWP1 negatively regulates the heregulin-beta1-stimulated ErbB4 activity as measured by the serum response element report assay and the BRCA1 mRNA expression. After a systematic screening of all WWP1 family members by small interfering RNA, we found that AIP4/Itch and HECW1/NEDL1 also negatively regulate the ErbB4 protein expression in T47D. Interestingly, the protein expression levels of both WWP1 and ErbB4 are higher in estrogen receptor-alpha-positive than in estrogen receptor-alpha-negative breast cancer cell lines. These data suggest that WWP1 and its family members suppress the ErbB4 expression and function in breast cancer.
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PMID:WW domain containing E3 ubiquitin protein ligase 1 targets the full-length ErbB4 for ubiquitin-mediated degradation in breast cancer. 1956 40

Urogenital disorders associated with oestrogen deficiency affect many women throughout menopausal transition. Symptoms such as vaginal dryness, burning, pruritus, dyspareunia, urinary tract urgency/frequency and incontinence have a significant impact on the individual's quality of life. For younger and healthy menopausal women, systemic oestrogen replacement may improve both vasomotor and urogenital symptoms and will be the treatment of choice. However, a proportion of women on systemic therapy still experience symptoms associated with urogenital atrophy, and patients with oestrogen-dependent cancers may be at risk from systemic oestrogen replacement. For women with mainly urogenital symptoms, local oestrogen is a logical choice and it is often more effective than systemic hormone replacement therapy. Generally speaking, there are no contraindications to local therapy. In terms of which topical preparation to use, a wide range of products are available. Promestriene is an analogue of oestradiol which is minimally absorbed and it has been shown to be effective in reversing atrophic changes caused by oestrogen deficiency in women undergoing natural or surgically induced menopause. Given the absence of systemic activity, promestriene may be a good choice in women requiring purely locally oestrogen, and those who have survived, or who are at risk of breast cancer and who have severe vulvo-vaginal symptoms.
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PMID:Urogenital disorders associated with oestrogen deficiency: the role of promestriene as topical oestrogen therapy. 2037 67

Unlike hot flushes and night sweats which resolve spontaneously in time, atrophic symptoms affecting the vagina and lower urinary tract are often progressive and frequently require treatment. The prevalence of vaginal dryness increases as a woman advances through the postmenopausal years, causing itching, burning and dyspareunia, and sexual activity is often compromised. But, despite the various safe and effective options, only a minority (about 25% in the Western world and probably considerably less in other areas) will seek medical help. Some of this reluctance is due to the adverse publicity for hormone replacement therapy (HRT) over recent years that has suggested an increased risk of breast cancer, heart disease and stroke. But, regardless of whether these scares are justified, local treatment of vaginal atrophy is not associated with these possible risks of systemic HRT. Other reasons for the continued suffering in silence may be cultural and an understandable reluctance to discuss such matters, particularly with a male doctor, but the medical profession must also take much of the blame for failing to enquire of all postmenopausal women about the possibility of vaginal atrophic symptoms. Vaginal dryness can be helped by simple lubricants but the best and most logical treatment for urogenital atrophy is to use local estrogen. This is safe, effective and with few contraindications. It is hoped that these guidelines and recommendations, produced to coincide with World Menopause Day 2010, will help to highlight this major cause of distress and reduced quality of life and will encourage women and their medical advisers all over the world to seek and provide help.
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PMID:Recommendations for the management of postmenopausal vaginal atrophy. 2156 97

The histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA, vorinostat) is undergoing clinical trials as an antitumor drug and has received regulatory approval for cancer treatment. Here, we show that pre-treatment of human breast cancer cells with SAHA makes them susceptible to apoptosis induced by TRAIL (tumour necrosis factor-related apoptosis-inducing ligand). The apoptosis of breast tumour cells induced by TRAIL is blocked at the level of apical activation of caspase-8 and SAHA enhances the TRAIL-induced processing of procaspase-8. Consequently, a TRAIL associated pathway of apoptosis operated via mitochondria is activated in cells treated with SAHA. Interestingly, degradation of cellular FLICE-inhibitory proteins (cFLIP(L) and cFLIP(S)) by an ubiquitin/proteasome-dependent Itch/AIP4-independent mechanism is observed upon exposure to SAHA. Targeting cFLIP(L) directly with siRNA oligonucleotides also sensitizes human breast tumour cells to TRAIL-induced apoptosis. Furthermore, cFLIP(L) over-expression significantly inhibits the apoptosis elicited through the combined effects of SAHA and TRAIL. Together, these results indicate that SAHA sensitizes breast cancer cells to TRAIL-induced apoptosis by facilitating the activation of early events in the apoptotic TRAIL pathway. Therefore, the combination of TRAIL and SAHA may represent a therapeutic tool to combat breast tumours.
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PMID:Itch/AIP4-independent proteasomal degradation of cFLIP induced by the histone deacetylase inhibitor SAHA sensitizes breast tumour cells to TRAIL. 2110 85

Acute radiation skin reactions (ARSR) are a major problem in curative radiotherapy (RT). A number of studies have failed to show a positive effect of different skin care products to reduce or prevent ARSR. The aims for this study were to describe frequency and severity of ARSR in patients with breast cancer undergoing adjuvant RT and to test the suitability in clinical use of two assessment instruments. A majority (93%) of the 93 patients with breast cancer included in this study developed ARSR, most of them mild reactions. Low scores for pain and itching (VAS) were reported. ARSR were assessed using the modified version of RTOG/EORTC acute radiation morbidity scoring criteria and the World Health Organisation (WHO) grading system for acute and subacute toxicity by two independent observers after the completion of RT. The percentages of discordant assessment between the two observers were 21% for the WHO scale and 32% for the RTOG/EORTC. Severe ARSR, classified as grades 2-4 on both instruments resulted in good agreement between the two instruments. However, the assessments using RTOG/EORTC resulted in an almost 10% higher proportion of severe ARSR. Comparisons of health related quality of life and sleep revealed no statistically significant differences between patients with mild or severe ARSR assessed by the RTOG/EORTC scale with the exception of cognitive functioning. The use of assessment instruments to describe treatment-related symptoms is complicated and clinical experience is not always enough. More research is needed to validate these instruments to guarantee sound and precise assessments.
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PMID:Frequency and severity of skin reactions in patients with breast cancer undergoing adjuvant radiotherapy, the usefulness of two assessment instruments - a pilot study. 2177 30

Advanced breast cancers preferentially metastasize to bone where cells in the bone microenvironment produce factors that enhance breast cancer cell homing and growth. Expression of the ubiquitin E3 ligase WWP1 is increased in some breast cancers, but its role in bone metastasis has not been investigated. Here, we studied the effects of WWP1 and itch, its closest family member, on breast cancer bone metastasis. First, we immunostained a multi-tumor tissue microarray and a breast cancer tissue microarray and demonstrated that WWP1 and ITCH are expressed in some of breast cancer cases. We then knocked down WWP1 or itch in MDA-MB-231 breast cancer cells using shRNA and inoculated these cells and control cells into the left ventricle of athymic nude mice. Radiographs showed that mice given shWWP1 cells had more osteolytic lesions than mice given control MDA-MB-231 cells. Histologic analysis confirmed osteolysis and showed significantly increased tumor area in bone marrow of the mice. WWP1 knockdown did not affect cell growth, survival or osteoclastogenic potential, but markedly increased cell migration toward a CXCL12 gradient in vitro. Furthermore, WWP1 knockdown significantly reduced CXCL12-induced CXCR4 lysosomal trafficking and degradation. In contrast, itch knockdown had no effect on MDA-MB-231 cell bone metastasis. Taken together, these findings demonstrate that WWP1 negatively regulates cell migration to CXCL12 by limiting CXCR4 degradation to promote breast cancer metastasis to bone and highlight the potential utility of WWP1 as a prognostic indicator for breast cancer bone metastasis.
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PMID:The ubiquitin E3 ligase WWP1 decreases CXCL12-mediated MDA231 breast cancer cell migration and bone metastasis. 2226 93

Malignant lymphomas represent about 9% of cardiac neoplasms. Despite its life-threatening nature, the cardiac manifestations are often subclinical. In about 20% of deaths from lymphoma, cardiac involvement is found only in autopsy. The authors present the case of a 77-year-old female admitted due to intense back pain, vomiting, generalised pruritus, fatigue and weight loss. She had a personal history of hypertension and breast cancer was noted 10 years before admission. The thoracoabdominopelvic CT showed a mass in the left atrium with extension to the right atrium and inferior vena cava, and a paravertebral mass at D10-D11 with invasion of the spinal canal and hepatic hilum. The transthoracic paravertebral mass biopsy was compatible with a diffuse large B cell lymphoma. The patient developed a complete atrioventricular block, with haemodynamic instability, requiring urgent chemoreduction of the paracardiac mass and implantation of an epicardial pacemaker.
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PMID:Complete heart block as a complicating feature of a mediastinal lymphoma. 2260 4

A healthy 27-year-old woman presented to an outside institution with unilateral nipple pruritus and a slight brown discolouration. When her symptoms failed to respond to topical therapy, nipple biopsy revealed Paget's disease of the nipple. The patient sought further evaluation and care at our institution. Further investigation revealed multifocal breast cancer and the patient underwent bilateral mastectomies with sentinel lymph node biopsy followed by adjuvant systemic therapy. She is currently more than 4 years out from surgery and chemotherapy and has had no evidence of breast cancer recurrence.
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PMID:An unusual presentation of breast cancer in a very young woman. 2269 8


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