Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Zoledronic acid is a potent bisphosphonate licensed for the treatment of myeloma and bone metastases from solid tumors. Renal deterioration is the most significant toxicity associated with zoledronic acid. We attempted to define the incidence and clinical significance of renal deterioration in patients receiving zoledronic acid and to develop a risk-factor profile for this treatment sequela. This study is a retrospective analysis of all patients who received zoledronic acid at Fox Chase Cancer Center, Philadelphia, Pa, between 1/10/02 and 1/30/04. Data recorded included patient demographics, tumor characteristics, comorbid illnesses, concomitant medications, cancer therapy, number of zoledronic acid doses administered, and serial creatinine measurements. In total, 3,115 evaluable doses of zoledronic acid were administered to 446 patients (median, 4 doses; mean, 6.98 doses; range, 1-28 doses) at a dose of 4 mg over 15 minutes every 3-4 weeks. Of these 446 patients, 42 experienced renal deterioration (median rise in creatinine level, 1.0 mg/dL; range, 0.5-4.4 mg/dL), requiring discontinuation of zoledronic acid therapy in 8 cases. No patient required dialysis and no patient died as a result of zoledronic acid-induced renal dysfunction. On multivariable analysis, predictive factors for the development of renal deterioration were patient age, a diagnosis of myeloma or renal cell cancer, cumulative number of doses, concomitant therapy with a nonsteroidal anti-inflammatory drug, and current or prior therapy with cisplatin. Using these factors, we constructed a predictive model with an area under the receiver operating characteristic curve of 0.75. The incidence of clinically significant renal deterioration in patients treated with zoledronic acid is low.We present a predictive model for decision support when estimating this risk.
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PMID:Impact of zoledronic acid on renal function in patients with cancer: Clinical significance and development of a predictive model. 1713 70

The therapeutic opportunities for an improved management of malignant bone disease are currently extensively studied. The conventional management of symptomatic bone lesions in patients with advanced cancer involves various combinations of local and systemic standard anticancer therapies and the symptomatic treatment of skeletal complications. In recent years, bisphosphonates have demonstrated high efficacy to avoid skeletal complications from metastatic bone lesions and to prevent cancer treatment-induced bone loss. Especially in the treatment of patients with bone metastases, secondary to breast cancer, a widespread use of bisphosphonates has been established. With the development of highly potent new-generation bisphosphonates, such as zoledronate, the therapeutic opportunities for bisphosphonates are going to expand. Several current studies have investigated the benefit of zoledronate therapy for bone metastases from a variety of tumor types, including prostate cancer, lung and renal cell cancer and multiple myeloma. Furthermore, bisphosphonates have been shown to significantly reduce antineoplastic therapy-induced bone loss. According to recently published data, it is suggested that bisphosphonates not only play a role in the inhibition of osteoclast-mediated bone resorption, but also have antitumor effects inhibiting tumor cell proliferation, adhesion and invasion, as well as angiogenesis and induction of apoptosis. Further preclinical and clinical investigations are necessary to elucidate the role of bisphosphonates, and large randomized clinical trials should be conducted to confirm the clinical value of bisphosphonates for the prevention of relapse, as well as for the maintainance of net bone density, e.g. during aromatase inhibitor therapy.
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PMID:Clinical value of bisphosphonates in cancer therapy. 1764 70

The purpose of this study is to assess the impact on clinical decision making of chest computed tomography (CT) in immunocompetent emergency department (ED) patients with chest radiographic (CXR) findings of pneumonia. We retrospectively identified 1,373 patients from our ED who underwent chest CT between 7/05 and 6/06. Report of CXR within 24 h before CT were reviewed to identify patients with findings of pneumonia. The following were the exclusion criteria: recommendation of CT on CXR report and immunocompromised status on chart review. Fifty-one patients met the inclusion criteria: 26 women and 25 men, with a mean age of 60 (range 29-103) years. Age- and sex-matched controls from the ED with CXR findings of pneumonia who did not undergo CT were identified. Charts were reviewed for clinical presentation, management, and follow-up. Patient and control groups were compared using Fisher exact and paired Student's t tests. The patients were sicker than the controls with more signs and symptoms including auscultation abnormalities, 64 (33 of 51) vs 47% (24 of 51), abnormal sputum 32 (16 of 51) vs 0%, hypoxemia 22 (11 of 51) vs 2% (1 of 51), weight loss, 20 (10 of 51) vs 4% (2 of 51), and night sweats, 16 (8 of 51) vs 2% (1 of 51; p < 0.05 each). Clinical management, (based on CT findings in 31% [16 of 51]), was more extensive for patients than controls: antibiotics initiated 82 (41 of 51) vs 47% (24 of 51), antibiotics changed 29 (15 of 31) vs 0%, procedures performed 24 (12 of 51) vs 0%, and mean length of stay was 8 days vs less than 1 (p < 0.05, each). Sixteen percent (8 of 51) of the patients had alternative/additional diagnosis based on CT: pulmonary embolism, lung cancer, hypersensitivity pneumonitis, multiple myeloma, renal cell carcinoma, small bowel obstruction, lung nodule, and endobronchial mass (n = 1, each). Eight percent (4 of 51) of the patients and no controls were diagnosed with tuberculosis (p = 0.06). Immunocompetent ED patients with CXR findings of pneumonia who underwent chest CT were sicker than those who were not imaged with CT. Chest CT was often useful in guiding therapy or providing an alternative diagnosis.
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PMID:Impact of chest CT on the clinical management of immunocompetent emergency department patients with chest radiographic findings of pneumonia. 1770 Dec 35

CD200 was recently described as a new prognosis factor in multiple myeloma and acute myeloid leukemia. CD200 is a membrane glycoprotein that imparts an immunoregulatory signal through CD200R, leading to the suppression of T-cell-mediated immune responses. We investigated the expression of CD200 in cancer using publicly available gene expression data. CD200 gene expression in normal or malignant human tissues or cell lines was obtained from the Oncomine Cancer Microarray database, Amazonia database and the ITTACA database. We found significant overexpression of CD200 in renal carcinoma, head and neck carcinoma, testicular cancer, malignant mesothelioma, colon carcinoma, MGUS/smoldering myeloma, and in chronic lymphocytic leukemia compared to their normal cells or their tissue counterparts. Moreover, we show that CD200 expression is associated with tumor progression in various cancers. Taken together, these data suggest that CD200 is a potential therapeutic target and prognostic factor for a large array of malignancies.
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PMID:CD200: a putative therapeutic target in cancer. 1806 Aug 62

A 52-year-old patient presented himself with weight loss and night sweats. Laboratory analyses revealed a high sedimentation rate, elevated immunoglobulines and anaemia with sludge phenomenon. Differential diagnoses included Multiple Myeloma and Lymphoma. Having a risk constellation for HIV infection and just having recovered from oral thrush also made this diagnosis possible. Urinary analysis and chest x-ray were normal; however, CT-scan detected renal cell cancer with pulmonary metastases. Renal cell cancer is heterogeneous in presentation, symptoms are unspecific, therefore they are often discovered late when they have already metastasized. Paraneoplastic syndromes, e.g. hypercalcaemia or hypertension are not infrequent in renal cell cancer.
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PMID:[Weight loss and night sweats with unexpected tumor localization]. 1807 82

An 80-year-old man was admitted because of appetite loss, mild proteinuria, and leg edema. A computed tomography examination revealed a tumor in his left kidney, and a left nephrectomy was performed. The tumor was histologically diagnosed as a clear cell type renal cell carcinoma, and hematoxylin eosin staining of the non-tumor region of the resected kidney showed an almost normal morphology. Three months later, he was readmitted because of the development of nephrotic syndrome with a urinary protein excretion of 4.2 g/day, a serum total protein concentration of 5.0 g/dL, a serum albumin concentration of 2.4 g/dL, a serum total cholesterol concentration of 214 mg/dL, and generalized edema. A full examination revealed no evidence of metastasis or recurrence of the renal cell carcinoma or any other malignant tumor. Congo red staining and immunohistochemical staining were performed using the non-tumor region of his resected kidney, and the presence of amyloid deposits in the microvascular walls and glomeruli that did not disappear when treated with potassium permanganate was disclosed. In this manner, the patient was diagnosed as having AL-type primary amyloidosis. Bence-Jones proteinuria and gastric amyloidosis were also observed, but a bone marrow examination showed no signs of multiple myeloma. Previous studies have reported an association between renal cell carcinoma and renal amyloidosis, mainly AA-type secondary amyloidosis. To our knowledge, only two cases of renal cell carcinoma associated with primary amyloidosis have been previously reported. Therefore, the present patient not only represents a rare case of renal cell carcinoma associated with primary amyloidosis, but also reminds us that careful histological examination of the non-tumor region of the resected kidney is needed to evaluate the proteinuria associated with renal cell carcinoma, particularly in elderly patients.
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PMID:[Case of nephrotic syndrome due to AL-type primary amyloidosis associated with renal cell carcinoma]. 1818 30

Amyloidosis is a systemic disorder characterized by the extracellular tissue deposition of insoluble, toxic aggregates in bundles of beta-sheet fibrillar proteins. These deposits are typically identified on the bases of their apple-green birrefringence under a polarized light microscope after staining with Congo red, and by the presence of rigid, nonbranching fibrils 8 to 10 nm in diameter on electron microscopy. The type of amyloid fibril unit can be further defined by immunohistology or by immunoelectron microscopy. It has been described at least 25 different human protein precursors of amyloid fibrils, which will describe its corresponding amyloid disease. The most common types of amyloidosis are AL (primary) and AA (secondary) types; the former, is the most frequent and is due to deposition of proteins derived from immunoglobulin light chain fragments, occurring alone or in association with multiple myeloma. The later (AA), is caused by deposition of fibrils composed of fragments of the acute phase reactant serum amyloid A (SAA) and complicates chronic diseases with ongoing or recurring inflammation, namely; rheumatoid arthritis (RA), juvenile chronic polyarthritis, ankylosing spondylitis, familial periodic fever syndromes (Familial Mediterranean Fever), chronic infections and furthermore, some neoplasms (mainly renal cell carcinoma and Hodgkin's disease). Despite its less frequent association, some benign neoplasms can subsequently complicate to AA amyloidosis, therefore, an early diagnose and successful treatment may lead indeed, to regression of the amyloid disease. Herein, we present two cases of AA amyloidosis, both of them caused by 2 different benign neoplasms: 1. A 34 year-old woman, after chronic oral contraceptive use, developed an hepatic adenoma (fig. 1) which finally lead to AA amyloidosis with primary kidney presentation (pure nephrotic syndrome) (table 1). Post-surgical complications yield to acute renal failure from which unfortunately could not be recovered. After being on hemodialysis therapy during 10 months she received a first renal allograft without any complication. 2. A 20 year old woman, was diagnosed of AA amyloidosis after a renal biopsy (fig. 2) because of nephrotic syndrome (table 1). Further investigation lead to the finding of a hialyne-vascular type Castleman's disease located in the retroperitoneum (fig. 2). Despite surgical resection and medical treatment (colchicine) she developed progressive renal failure requiring initialization of hemodialysis therapy. After 6 years being on hemodialysis, she received a first renal allograft which is currently functioning after one year of follow- up. Although other chronic inflammatory diseases complicate more frequently to AA amyloidosis, benign tumors have to be taken into account as a potential ethiological cause for secondary amyloidosis.
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PMID:[Systemic AA amyloidosis induced by benign neoplasms]. 1833 38

Multiple malignancies in the same patient are unusual. This is particularly true for patients with hematologic malignancies who have a concomitant solid tumor. We report the unexpectedly higher frequency of renal cell carcinoma (RCC) associated with plasma cell dyscrasias. We report 6 cases of RCC in our institutional database of 600 patients with plasma cell dyscrasias over the past 10 years. We discuss the possible mechanisms that predisposed these patients to a secondary malignancy.
Clin Lymphoma Myeloma 2008 Jun
PMID:Association between renal cell carcinoma and plasma cell dyscrasias: a case series of six patients. 1865 Jan 85

This note mechanistically accounts for recent unexplained findings that all-trans retinoic acid (ATRA, also termed tretinoin) exerts an anti-viral effect against hepatitis C virus (HCV) in chronically infected patients, in whom ATRA also showed synergy with interferon-alpha. How HCV replication was suppressed was unclear. Both effects of ATRA can be accounted for by ATRA's upregulation of RIG protein, an 18 kDa product of retinoic induced gene-1. Increased RIG then couples ATRA to increased Type 1 interferons' production. Details of this mechanism predict that ATRA will similarly augment interferon-a activity in treating chronic myelogenous leukemia, melanoma, myeloma and renal cell carcinoma and that the addition of ribavirin and/or bexarotene will each incrementally enhance interferon-a responses in these cancers.
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PMID:Potential for all-trans retinoic acid (tretinoin) to enhance interferon-alpha treatment response in chronic myelogenous leukemia, melanoma, myeloma and renal cell carcinoma. 1876 14

A murine (mAHM) and a humanized (AHM) monoclonal antibody against CD317 (also called tetherin, BST2, or HM1.24 antigen), expressed preferentially in neoplastic B cells such as multiple myeloma, exhibited antitumor effects as a result of antibody-dependent cellular cytotoxicity (ADCC). The putative interferon (IFN) response elements IRF-1/2 and ISGF3 are present in the promoter of the CD317 gene, and IFN has been used for the treatment of not only myeloproliferative diseases but also solid tumors such as renal cell carcinoma (RCC) and melanoma. Therefore, we examined the effects of IFN on the expression of CD317 and on the antitumor activity of AHM and mAHM in RCC and melanoma. Flow cytometry and in vitro ADCC assays with human or mouse effector cells demonstrated that IFN-alpha markedly increased the amount of cell surface CD317 and augmented the ADCC activity of mAHM and AHM in RCC cells and to a lesser extent in melanoma cells. Administration of IFN-alpha to mice bearing RCC xenografts also increased the expression of CD317 in tumor cells. When coadministered with IFN-alpha, mAHM exhibited more profound antitumor activity in both IFN-alpha-sensitive and -insensitive RCC xenograft models. Thus, AHM in combination with IFN-alpha may be an effective therapy for the treatment of RCC.
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PMID:Interferon-alpha enhances CD317 expression and the antitumor activity of anti-CD317 monoclonal antibody in renal cell carcinoma xenograft models. 1903 71


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