WorldWideScience

Sample records for renal cancer myeloma

  1. Occurrence of breast cancer, renal cancer and multiple myeloma in a Nagasaki atomic bomb survivor

    International Nuclear Information System (INIS)

    Yanagisawa, Tsutomu; Kubota, Kazuo; Tamura, Jun'ichi; Kurabayashi, Hitoshi; Shirakura, Takuo; Hayashida, Masayoshi; Nagayama, Tadao.

    1990-01-01

    A 60-year-old female, who was exposed to the Nagasaki atomic bomb at 18 years old, had renal cancer and subsequently was found to have multiple myeloma (IgGk). She underwent the left mastectomy for breast cancer at 43 years old but was not given chemotherapy or radiotherapy. The karyotype of bone marrow cells was 46, XX. The estimated radiation dose was under 10 rads. While the effect of such a low-dose of radiation is considered to be almost negligible, there would be a possibility that in this case the risk of carcinogenesis was enhanced as her age advanced. (author)

  2. Renal failure in patients with multiple myeloma.

    Science.gov (United States)

    Almueilo, Samir H

    2015-01-01

    Renal dysfunction is encountered in 20-25% of patients with multiple myeloma (MM) at the time of diagnosis. There is often a precipitating event. Several biochemical and clinical correlations with renal failure in MM have been reported. Renal failure in MM is associated with worse outcome of the disease. We retrospectively analyzed the medical records of 64 patients with MM admitted to our institution during the period January 1992 to December 2012. Abnormal renal function was observed in 24 (37.5%) patients and 17 (26.6%) of them had renal failure; 14 of the 17 (82.4%) of patients with renal failure had Stage III MM. Urine Bence- Jones protein was positive in ten (58.8%) patients with renal failure versus ten (21.3%) patients without renal failure (P = 0.004). Potential precipitating factors of renal failure were determined in nine patients. Renal function normalized in 11 patients with simple measures, while six patients required hemodialysis; one remained dialysis dependent till time of death. Early mortality occurred in five (29.4%) patients with renal failure as compared with two (4.3%) patients in the group without renal failure (P = 0.005). In conclusion, renal failure is associated with a higher tumor burden and Bence-Jones proteinuria in patients with MM. It is reversible in the majority of patients; however, early mortality tends to be higher in patients with persistent renal failure.

  3. Myeloma: making sense of a complex blood cancer.

    LENUS (Irish Health Repository)

    Kelly, Mary B

    2012-01-31

    Myeloma is a challenging blood cancer characterized by bone destruction, hypercalcaemia, renal insufficiency and anaemia. Although myeloma remains incurable, recent advancements in treatments have resulted in significant improvements in morbidity. The use of immunomodulatory drugs-thalidomide, lenalidomide, pomalidomide (in clinical trials)-and the proteasome inhibitor, bortezomib, in conjunction with conventional chemotherapy and supportive therapies, have resulted in a significant shift in approaches to treatment and an improvement in patients\\' quality of life. Nurses must remain up-to-date with current treatments for myeloma and their related side-effects. In addition, nurses play a key role in the coordination of a multidisciplinary approach to care for myeloma patients.

  4. Renal cancer.

    NARCIS (Netherlands)

    Corgna, E.; Betti, M.; Gatta, G.; Roila, F.; Mulder, P.H.M. de

    2007-01-01

    In Europe, renal cancer (that is neoplasia of the kidney, renal pelvis or ureter (ICD-9 189 and ICD-10 C64-C66)) ranks as the seventh most common malignancy in men amongst whom there are 29,600 new cases each year (3.5% of all cancers). Tobacco, obesity and a diet poor in vegetables are all

  5. Renal cancer

    NARCIS (Netherlands)

    Corgna, Enrichetta; Betti, Maura; Gatta, Gemma; Roila, Fausto; De Mulder, Pieter H. M.

    2007-01-01

    In Europe, renal cancer (that is neoplasia of the kidney, renal pelvis or ureter (ICD-9 189 and ICD-10 C64-C66)) ranks as the seventh most common malignancy in men amongst whom there are 29,600 new cases each year (3.5% of all cancers). Tobacco, obesity and a diet poor in vegetables are all

  6. Renal complications in multiple myeloma and related disorders: survivorship care plan of the International Myeloma Foundation Nurse Leadership Board.

    Science.gov (United States)

    Faiman, Beth M; Mangan, Patricia; Spong, Jacy; Tariman, Joseph D

    2011-08-01

    Kidney dysfunction is a common clinical feature of symptomatic multiple myeloma. Some degree of renal insufficiency or renal failure is present at diagnosis or will occur during the course of the disease and, if not reversed, will adversely affect overall survival and quality of life. Chronic insults to the kidneys from other illnesses, treatment, or multiple myeloma itself can further damage renal function and increase the risk for additional complications, such as anemia. Patients with multiple myeloma who have light chain (Bence Jones protein) proteinuria may experience renal failure or progress to end-stage renal disease (ESRD) and require dialysis because of light chain cast nephropathy. Kidney failure in patients with presumed multiple myeloma also may result from amyloidosis, light chain deposition disease, or acute tubular necrosis caused by nephrotoxic agents; therefore, identification of patients at risk for kidney damage is essential. The International Myeloma Foundation's Nurse Leadership Board has developed practice recommendations for screening renal function, identifying positive and negative contributing risk and environmental factors, selecting appropriate therapies and supportive care measures to decrease progression to ESRD, and enacting dialysis to reduce and manage renal complications in patients with multiple myeloma.

  7. Fatal case of Herbaspirillum seropedicae bacteremia secondary to pneumonia in an end-stage renal disease patient with multiple myeloma.

    Science.gov (United States)

    Suwantarat, Nuntra; Adams, La'Tonzia L; Romagnoli, Mark; Carroll, Karen C

    2015-08-01

    Herbaspirillum spp. are rare causes of human infections associated primarily with bacteremia in cancer patients. We report the first fatal case of bacteremia secondary to pneumonia caused by Herbaspirillum seropedicae in a 65-year-old man with end-stage renal disease and multiple myeloma. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Long-term survival of patients with multiple myeloma and acute renal failure at presentation.

    Science.gov (United States)

    Lazarus, H M; Adelstein, D J; Herzig, R H; Smith, M C

    1983-03-01

    Eight patients presented with simultaneous multiple myeloma and acute renal failure requiring hemodialysis. Patients had no known pre-existing renal disease nor exposure to nephrotoxic agents or x-ray contrast dye. Renal failure was attributed to light chain nephropathy in all cases. In 4 of these patients the diagnosis of myeloma was initially unsuspected. Renal biopsies in 3 of these patients, and post-mortem material in a fourth revealed the changes of "myeloma kidney." No patient regained renal function and all required chronic hemodialysis. Among these eight patients, three survived for periods greater than 21 months.

  9. Population pharmacokinetics of pomalidomide in patients with relapsed or refractory multiple myeloma with various degrees of impaired renal function

    Directory of Open Access Journals (Sweden)

    Li Y

    2017-11-01

    Full Text Available Yan Li,1 Xiaomin Wang,2 Edward O’Mara,1 Meletios A Dimopoulos,3 Pieter Sonneveld,4 Katja C Weisel,5 Jeffrey Matous,6 David S Siegel,7 Jatin J Shah,8 Elisabeth Kueenburg,9 Lars Sternas,9 Chloe Cavanaugh,9 Mohamed Zaki,9 Maria Palmisano,1 Simon Zhou1 1Translational Development and Clinical Pharmacology, Celgene Corporation, Summit, NJ, USA; 2Non-Clinical Development and Drug Metabolism and Pharmacokinetics, Celgene Corporation, Summit, NJ, USA; 3Department of Clinical Therapeutics, National and Kapodistrian University of Athens, Athens, Greece; 4Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands; 5Department of Hematology, University Hospital Tübingen, Tübingen, Germany; 6Department of Hematology/Oncology, Colorado Blood Cancer Institute, Denver, CO, USA; 7Myeloma Division, John Theurer Cancer Center, Hackensack University Medical Center, Hackensack, NJ, USA; 8Department of Lymphoma/Myeloma, Division of Cancer Medicine, MD Anderson Cancer Center, Houston, TX, USA; 9Global Clinical R&D, Celgene Corporation, Summit, NJ, USA Abstract: Pomalidomide is an immunomodulatory drug for treatment of relapsed or refractory multiple myeloma (rrMM in patients who often have comorbid renal conditions. To assess the impact of renal impairment on pomalidomide exposure, a population pharmacokinetics (PPK model of pomalidomide in rrMM patients with various degrees of impaired renal function was developed. Intensive and sparse pomalidomide concentration data collected from two clinical studies in rrMM patients with normal renal function, moderately impaired renal function, severely impaired renal function not requiring dialysis, and with severely impaired renal function requiring dialysis were pooled over the dose range of 2 to 4 mg, to assess specifically the influence of the impaired renal function as a categorical variable and a continuous variable on pomalidomide clearance and plasma exposure. In addition, pomalidomide

  10. Targeted Therapies for Myeloma and Metastatic Bone Cancers

    Science.gov (United States)

    2010-09-01

    Cancer J Clin 2003; 53:5. Kasugai S, Fujisawa R, Waki Y, Miyamoto K, Ohya K 2000 Selective drug delivery system to bone: small peptide (Asp)6...page. Bone targeted nanoparticles , bone cancer myeloma, mice studies, PLGA , Biodegradable materials. Targeted Therapies for Myeloma and Metastatic Bone...present results from this program at talk at the Particles 2006 –Medical/Biochemical Diagnostic , Pharmaceutical, and Drug Delivery . 3

  11. Stages of Renal Cell Cancer

    Science.gov (United States)

    ... Tumors Treatment Genetics of Kidney Cancer Research Renal Cell Cancer Treatment (PDQ®)–Patient Version General Information About Renal Cell Cancer Go to Health Professional Version Key Points Renal ...

  12. Cadmium and renal cancer

    International Nuclear Information System (INIS)

    Il'yasova, Dora; Schwartz, Gary G.

    2005-01-01

    Background: Rates of renal cancer have increased steadily during the past two decades, and these increases are not explicable solely by advances in imaging modalities. Cadmium, a widespread environmental pollutant, is a carcinogen that accumulates in the kidney cortex and is a cause of end-stage renal disease. Several observations suggest that cadmium may be a cause of renal cancer. Methods: We performed a systematic review of the literature on cadmium and renal cancer using MEDLINE for the years 1966-2003. We reviewed seven epidemiological and eleven clinical studies. Results: Despite different methodologies, three large epidemiologic studies indicate that occupational exposure to cadmium is associated with increased risk renal cancer, with odds ratios varying from 1.2 to 5.0. Six of seven studies that compared the cadmium content of kidneys from patients with kidney cancer to that of patients without kidney cancer found lower concentrations of cadmium in renal cancer tissues. Conclusions: Exposure to cadmium appears to be associated with renal cancer, although this conclusion is tempered by the inability of studies to assess cumulative cadmium exposure from all sources including smoking and diet. The paradoxical findings of lower cadmium content in kidney tissues from patients with renal cancer may be caused by dilution of cadmium in rapidly dividing cells. This and other methodological problems limit the interpretation of studies of cadmium in clinical samples. Whether cadmium is a cause of renal cancer may be answered more definitively by future studies that employ biomarkers of cadmium exposure, such as cadmium levels in blood and urine

  13. Plasmablastic myeloma presenting as rapidly progressive renal failure in a young adult

    Directory of Open Access Journals (Sweden)

    M Srija

    2014-01-01

    Full Text Available Multiple myeloma (MM is a condition where there is malignant proliferation of plasma cells. There is a strong correlation with age, peaking at 60-70 years. The clinical course in adolescents and young individuals is generally indolent and the survival is longer. We report a case of a 28-year-old male, who was diagnosed to have plasmablastic myeloma, an atypical variant of MM with a poor prognosis, presenting as rapidly progressive renal failure. He was given induction chemotherapy and then underwent autologous peripheral blood stem cell transplantation.

  14. Measuring the frailty index of multiple myeloma cancer patients

    DEFF Research Database (Denmark)

    Corradini, Andrea; Bøgelund Hansen, Martin; Savic, Toma

    2016-01-01

    We report on a responsive web-based application that we have been developing for the cancer hospital in Vejle, Denmark. The application administers and handles systematic frailty scoring of patients with multiple myeloma and helps doctors make a more efficient and effective treatment choice. The ...

  15. Cancer - renal pelvis or ureter

    Science.gov (United States)

    ... ureter; Kidney cancer - renal pelvis; Ureter cancer Images Kidney anatomy References National Cancer Institute website. Transitional cell cancer (kidney/ureter) treatment (PDQ) - health professional version. www.cancer. ...

  16. An Application for Measuring Frailty of Myeloma Cancer Patients

    DEFF Research Database (Denmark)

    Corradini, Andrea; Bøgelund Hansen, Martin; Savic, Toma

    2016-01-01

    In this paper, we report on a responsive web-based application that we have been developing for the cancer hospital in the city of Vejle, Denmark. The application administers and handles systematic frailty scoring of patients with multiple myeloma (bone marrow cancer) and thereby helps the doctor...... make a more efficient and more effective treatment choice. The application is currently being tested with a small number of patients and is to replace the frailty measurement system used until now, which is usually done by the doctor on a per patient basis.......In this paper, we report on a responsive web-based application that we have been developing for the cancer hospital in the city of Vejle, Denmark. The application administers and handles systematic frailty scoring of patients with multiple myeloma (bone marrow cancer) and thereby helps the doctor...

  17. Acute gouty arthritis and rapidly progressive renal failure as manifestation of multiple myeloma: clinical case description

    Directory of Open Access Journals (Sweden)

    O.V. Gudym

    2017-08-01

    Full Text Available The article describes a clinical case of multiple myeloma in 78-year-old man, its clinical onset was as an acute attack of gout. The patient was admitted to hospital due to the development of the first acute attack of gout. The attack was characterized by polyarthricular joint lesion of the upper and lower extremities, pronounced inflammatory reaction, insufficient response to the use of non-steroidal anti-inflammatory drugs, and a high level of hyperuricemia. The serum uric acid concentration ranged from 636 to 712 μmol/l. The study of the synovial fluid of the inflamed knee joint made it possible to reveal uric acid crystals and to confirm the diagnosis of acute gouty arthritis. Simultaneously, the patient had significant renal impairment: creatinine was 574 μmol/l, urea — 39.9 mmol/l, glomerular filtration rate according to CKD-EPI — 8 ml/min. The daily proteinuria was 1.8 g. A retrospective assessment of laboratory parameters allowed to reveal completely normal indicators of renal function 6 months ago. Considering the development of acute gouty arthritis, its polyarticular nature, persistent course, rapid involvement of new joints, high uric acid levels during an acute attack exceeding 600 μmol/l (10 mg/dL, rapid development of renal failure within 6 months until the terminal stage, it was suggested the secondary nature of gout on the background of kidney damage by another pathological process. Further clinical, laboratory and instrumental studies allowed verifying multiple myeloma with renal damage. Bence Jones protein in the urine was not detected, there was also no evidence of hyperproteinemia. However, pain in the spine, ribs and chest was the basis for carrying out an X-ray study of the bones of the skeleton. Changes in the skeleton typical for multiple myeloma have been identified. Myelogram showed a high content of plasma cells (21.1 %, electrophoresis of blood proteins showed a high M-gradient (30.42 %, and a cytochemical

  18. Metastatic Breast Cancer or Multiple Myeloma? Camouflage by Lytic Lesions

    Directory of Open Access Journals (Sweden)

    Bruce Hough

    2010-01-01

    Full Text Available We report a case of a female with stage I infiltrating ductal carcinoma who received adjuvant therapy including trastuzumab. One year later she developed lytic lesions and was retreated with trastuzumab that was held after she developed symptomatic heart failure. Lytic lesions were attributed to relapse of breast cancer, and cardiac failure attributed to prior trastuzumab therapy. After complications necessitated multiple hospitalizations, a further workup revealed that the lytic lesions were not metastatic breast cancer but multiple myeloma. Her advanced multiple myeloma was associated with systemic amyloidosis involving gut and heart, which ultimately led to her demise. This report addresses the pitfalls of overlapping symptoms and the question of which patients with suspected metastatic disease should undergo a biopsy.

  19. Effects of iodinated contrast media on renal function in patients with multiple myeloma

    International Nuclear Information System (INIS)

    Jacob, H.M.

    1980-01-01

    Case histories of 89 patients with definite myoloma of the years 1959 to 1974 were investigated in a retrospective study. 41 intravenous urographies were carried out in 31 of these patients. There was no correlation between deterioration of the renal function and contrast medium application. Relevant literature on the subject has been compiled. By 1979, 19 case studies and 5 general studies had been published which have been summarized in tables in the present study. Analyses of these case histories have shown that acute renal failure was often due to other causes and not to contrast medium application. If these cases are left out of account 8 cases remain in which lethal renal failure occurred after intravenous urography of myeloma patients. The diiodinated contrast media formerly used was less well tolerated than the present triiodinated contrast media. Further risk factors were dehydratation and/or abdominal compression. Both measures are no longer employed in intravenous urography. (orig./MG) [de

  20. General Information about Renal Cell Cancer

    Science.gov (United States)

    ... Tumors Treatment Genetics of Kidney Cancer Research Renal Cell Cancer Treatment (PDQ®)–Patient Version General Information About Renal Cell Cancer Go to Health Professional Version Key Points Renal ...

  1. Treatment Option Overview (Renal Cell Cancer)

    Science.gov (United States)

    ... Tumors Treatment Genetics of Kidney Cancer Research Renal Cell Cancer Treatment (PDQ®)–Patient Version General Information About Renal Cell Cancer Go to Health Professional Version Key Points Renal ...

  2. Thirteen treated of acute renal failure secondary to multiple myeloma with high cut off filters.

    Science.gov (United States)

    Berni Wennekers, Ana; Martín Azara, María Pilar; Dourdil Sahun, Victoria; Bergasa Liberal, Beatriz; Ruiz Laiglesia, José Esteban; Vernet Perna, Patricia; Alvarez Lipe, Rafael

    2016-01-01

    Multiple myeloma (MM) is a haematological tumour that is characterised by uncontrolled proliferation of plasma cells and a significant volume of serum free light chains (sFLCs), which can cause acute renal failure due to intratubular precipitation, resulting in cast nephropathy. Acute renal failure is a complication that can arise in more than 20% of patients with multiple myeloma, half of which will require dialysis. We report our experience with 13 patients who were treated with dialysis using high cut off filters (HCO) between July 2011 and February 2015. A total of 6 consecutive 6-hour sessions were performed using a 2.1 m(2) HCO filter (Theralite® by Gambro®). Afterwards, further 6-hour sessions were continued on alternate days. A total of 151 sessions were conducted, with an average of 11.6 sessions per patient (range 6-27). The treatment proved to be effective in removing both kappa and lambda sFLCs, resulting in a 93.7% fall in sFLCs by the end of treatment. The average reduction was 57.7% per dialysis session. 10 out of the 13 cases recovered sufficient renal function to become independent of dialysis. There were no major changes in albumin levels using an infusion protocol of 2 50-mL vials of 20% albumin at the end of the dialysis session. Combination treatment with chemotherapy and long dialysis with HCO filters was effective in reducing the sFLC levels and recovering sufficient renal function in 77% of cases. With HCO filters, significant cost savings are achieved, contrary to what was previously believed. Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

  3. Cancer Associated Fibroblasts and Tumor Growth: Focus on Multiple Myeloma

    International Nuclear Information System (INIS)

    De Veirman, Kim; Rao, Luigia; De Bruyne, Elke; Menu, Eline; Van Valckenborgh, Els; Van Riet, Ivan; Frassanito, Maria Antonia; Di Marzo, Lucia; Vacca, Angelo; Vanderkerken, Karin

    2014-01-01

    Cancer associated fibroblasts (CAFs) comprise a heterogeneous population that resides within the tumor microenvironment. They actively participate in tumor growth and metastasis by production of cytokines and chemokines, and the release of pro-inflammatory and pro-angiogenic factors, creating a more supportive microenvironment. The aim of the current review is to summarize the origin and characteristics of CAFs, and to describe the role of CAFs in tumor progression and metastasis. Furthermore, we focus on the presence of CAFs in hypoxic conditions in relation to multiple myeloma disease

  4. Cancer Associated Fibroblasts and Tumor Growth: Focus on Multiple Myeloma

    Energy Technology Data Exchange (ETDEWEB)

    De Veirman, Kim, E-mail: kdeveirm@vub.ac.be [Department of Hematology and Immunology, Myeloma Center Brussels, Vrije Universiteit Brussel (VUB), Brussels 1090 (Belgium); Rao, Luigia [Department of Hematology and Immunology, Myeloma Center Brussels, Vrije Universiteit Brussel (VUB), Brussels 1090 (Belgium); Department of Biomedical Sciences and Human Oncology, Section of Internal Medicine, University of Bari Medical School, Bari I-70124 (Italy); De Bruyne, Elke; Menu, Eline; Van Valckenborgh, Els [Department of Hematology and Immunology, Myeloma Center Brussels, Vrije Universiteit Brussel (VUB), Brussels 1090 (Belgium); Van Riet, Ivan [Department of Hematology and Immunology, Myeloma Center Brussels, Vrije Universiteit Brussel (VUB), Brussels 1090 (Belgium); Stem Cell Laboratory, Division of Clinical Hematology, Universitair Ziekenhuis Brussel (UZ Brussel), Brussels 1090 (Belgium); Frassanito, Maria Antonia [Department of Biomedical Sciences and Human Oncology, Section of General Pathology, University of Bari Medical School, Bari I-70124 (Italy); Di Marzo, Lucia; Vacca, Angelo [Department of Biomedical Sciences and Human Oncology, Section of Internal Medicine, University of Bari Medical School, Bari I-70124 (Italy); Vanderkerken, Karin, E-mail: kdeveirm@vub.ac.be [Department of Hematology and Immunology, Myeloma Center Brussels, Vrije Universiteit Brussel (VUB), Brussels 1090 (Belgium)

    2014-06-27

    Cancer associated fibroblasts (CAFs) comprise a heterogeneous population that resides within the tumor microenvironment. They actively participate in tumor growth and metastasis by production of cytokines and chemokines, and the release of pro-inflammatory and pro-angiogenic factors, creating a more supportive microenvironment. The aim of the current review is to summarize the origin and characteristics of CAFs, and to describe the role of CAFs in tumor progression and metastasis. Furthermore, we focus on the presence of CAFs in hypoxic conditions in relation to multiple myeloma disease.

  5. [Expert consensus for the diagnosis and treatment of patients with renal impairment of multiple myeloma].

    Science.gov (United States)

    2017-11-01

    Renal impairment (RI) is a common complication of multiple myeloma (MM), which is presented as chronic kidney disease (CKD) or acute kidney injury (AKI). The typical pathological feature is cast nephropathy. Presently international system staging (ISS) is used in evaluating MM. Although the classic Durie-Salmon staging system could be still used in clinical practice, it may miss out some patients with renal impairment. For evaluations of RI in MM patients with CKD, it's recommended to assess the estimated glomerular filtration rate (eGFR) by creatinine based formula CKD-epidemiology collaboration (EPI) or modification of diet in renal disease(MDRD) and to stage the renal injuries according to 2013 Kidney Disease Improving Global Outcomes (KDIGO) CKD guidelines. For MM patients with AKI, KDIGO AKI guidelines is recommended for evaluation. Renal biopsy is not a routine procedure in all MM patients. It's necessary for patients presenting with glomerular injuries such as albuminuria > 1 g/24 h to eliminate immunoglobulin associated amyloidosis (AL) and monoclonal immunoglobulin deposition disease (MIDD). The effective treatment of MM can reduce serum light chain concentration and improve renal function. The basis of the RI treatment in MM is bortizomib-based regimen, which does not require dosage adjustment in patients with dialysis or renal insufficiency. Thalidomide and lenalidomide are two major immunomodulators in MM treatment. Thalidomide can be used effectively in RI patients without dosage adjustment while lenalidomide should be used cautiously in patients with mild or moderate RI with dosage adjustment and serum toxicity surveillance. High-dose therapy (HDT) and autologous peripheral blood stem cell transplantation (APBSCT) can be therapeutical options for RI patients younger than 65 y, and they should be considered more prudently in patients with severe renal insufficiency (GFRhydration (at least 3 litres of fluid intake a day or 2 L·m(-2)·d(-1)) and

  6. Drugs Approved for Kidney (Renal Cell) Cancer

    Science.gov (United States)

    ... Your Treatment Research Drugs Approved for Kidney (Renal Cell) Cancer This page lists cancer drugs approved by the ... not listed here. Drugs Approved for Kidney (Renal Cell) Cancer Afinitor (Everolimus) Aldesleukin Avastin (Bevacizumab) Axitinib Bevacizumab Cabometyx ( ...

  7. An Unpredicted Side Effect of Bisphosphonates in a Patient with Chronic Renal Failure Due to Multiple Myeloma: Reversible Parkinsonism

    Directory of Open Access Journals (Sweden)

    Barış İşak

    2010-09-01

    Full Text Available In this report, we present a unique case in which the chemotherapeutic agent, i.e., zoledronic acid, deepened the hypocalcemia on the basis of chronic renal failure secondary to multiple myeloma and caused parkinsonism episodes. An 80-year-old female patient, who had been diagnosed as multiple myeloma and had been administered bisphosphonate therapy monthly for six months, was ad¬mitted to our emergency room with two parkinsonism episodes. Low serum calcium levels accompanied parkinsonism symptoms, which subsided with calcium replacement therapy in both episodes. Imaging did not reveal any pathology in the basal ganglia. The fact that the patient was cured both times with calcium replacement suggests that hypocalcemia was the actual cause. This can be interpreted as a unique case, reflecting the reversible functional impairment due to metabolic side effects of a chemotherapeutic agent rather than destructive changes in the basal ganglia.

  8. An Unpredicted Side Effect of Bisphosphonates in a Patient with Chronic Renal Failure Due to Multiple Myeloma: Reversible Parkinsonism

    Directory of Open Access Journals (Sweden)

    Barış İşak

    2010-09-01

    Full Text Available In this report, we present a unique case in which the chemotherapeutic agent, i.e., zoledronic acid, deepened the hypocalcemia on the basis of chronic renal failure secondary to multiple myeloma and caused parkinsonism episodes. An 80-year-old female patient, who had been diagnosed as multiple myeloma and had been administered bisphosphonate therapy monthly for six months, was ad¬mitted to our emergency room with two parkinsonism episodes. Low serum calcium levels accompanied parkinsonism symptoms, which subsided with calcium replacement therapy in both episodes. Imaging did not reveal any pathology in the basal ganglia. The fact that the patient was cured both times with calcium replacement suggests that hypocalcemia was the actual cause. This can be interpreted as a unique case, reflecting the reversible functional impairment due to metabolic side effects of a chemotherapeutic agent rather than destructive changes in the basal ganglia

  9. Potential for all-trans retinoic acid (tretinoin) to enhance interferon-alpha treatment response in chronic myelogenous leukemia, melanoma, myeloma and renal cell carcinoma.

    Science.gov (United States)

    Kast, Richard E

    2008-10-01

    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.

  10. Population pharmacokinetics of pomalidomide in patients with relapsed or refractory multiple myeloma with various degrees of impaired renal function.

    Science.gov (United States)

    Li, Yan; Wang, Xiaomin; O'Mara, Edward; Dimopoulos, Meletios A; Sonneveld, Pieter; Weisel, Katja C; Matous, Jeffrey; Siegel, David S; Shah, Jatin J; Kueenburg, Elisabeth; Sternas, Lars; Cavanaugh, Chloe; Zaki, Mohamed; Palmisano, Maria; Zhou, Simon

    2017-01-01

    Pomalidomide is an immunomodulatory drug for treatment of relapsed or refractory multiple myeloma (rrMM) in patients who often have comorbid renal conditions. To assess the impact of renal impairment on pomalidomide exposure, a population pharmacokinetics (PPK) model of pomalidomide in rrMM patients with various degrees of impaired renal function was developed. Intensive and sparse pomalidomide concentration data collected from two clinical studies in rrMM patients with normal renal function, moderately impaired renal function, severely impaired renal function not requiring dialysis, and with severely impaired renal function requiring dialysis were pooled over the dose range of 2 to 4 mg, to assess specifically the influence of the impaired renal function as a categorical variable and a continuous variable on pomalidomide clearance and plasma exposure. In addition, pomalidomide concentration data collected on dialysis days from both the withdrawal (arterial) side and from the returning (venous) side of the dialyzer, from rrMM patients with severely impaired renal function requiring dialysis, were used to assess the extent to which dialysis contributes to the removal of pomalidomide from blood circulation. PPK analyses demonstrated that moderate to severe renal impairment not requiring dialysis has no influence on pomalidomide clearance or plasma exposure, as compared to those patients with normal renal function, while pomalidomide exposure increased approximately 35% in patients with severe renal impairment requiring dialysis on nondialysis days. In addition, dialysis increased total body pomalidomide clearance from 5 L/h to 12 L/h, indicating that dialysis will significantly remove pomalidomide from the blood circulation. Thus, pomalidomide should be administered post-dialysis on the days of dialysis.

  11. The risk of renal disease is increased in lambda myeloma with bone marrow amyloid deposits

    Directory of Open Access Journals (Sweden)

    Kozlowski P

    2017-03-01

    Full Text Available Piotr Kozlowski,1 Scott Montgomery,2–4 Rahel Befekadu,5 Victoria Hahn-Strömberg6 1Department of Medicine, School of Medical Sciences, Örebro University, Örebro, Sweden; 2Clinical Epidemiology and Biostatistics, School of Medical Sciences, Örebro University, Örebro, Sweden; 3Clinical Epidemiology Unit, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden; 4Department of Epidemiology and Public Health, University College London, London, UK; 5Department of Transfusion Medicine, School of Medical Sciences, Örebro University, Örebro, Sweden; 6Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden Background: Light chain amyloidosis (AL is a rare deposition disease and is present in 10–15% of patients with myeloma (MM. In contrast to symptomatic AL in MM, presence of bone marrow (BM amyloid deposits (AD in MM is not connected to kidney damage. Renal AD but not BM-AD occur mostly in MM with lambda paraprotein (lambda MM. Methods: We investigated amyloid presence in BM clots taken at diagnosis in 84 patients with symptomatic MM and compared disease characteristics in MM with kappa paraprotein (kappa MM/lambda MM with and without BM-AD. Results: Lambda MM with BM-AD was compared with kappa MM without BM-AD, kappa MM with BM-AD, and lambda MM without BM-AD: lambda MM with BM-AD patients had a significantly higher mean creatinine level (4.23 mg/dL vs 1.69, 1.14, and 1.28 mg/dL, respectively and a higher proportion presented with severe kidney failure (6/11 [55%] vs 6/32 [19%], 1/22 [5%], and 3/19 [16%], respectively. Proteinuria was more common in lambda MM with BM-AD patients compared with kappa MM without BM-AD patients (8/11 [73%] vs 5/32 [16%], respectively. Conclusion: Kidney damage was more common in lambda MM with BM-AD indicating presence of renal AD. Keywords: plasma cells, neoplasms, amyloidosis, renal insufficiency, proteinuria

  12. Impact of Autologous Stem Cell Transplantation on Blood Pressure and Renal Function in Multiple Myeloma Patients.

    Science.gov (United States)

    Balsam, Leah; Saad, Chadi; Arsene, Camelia; Fogel, Joshua

    2017-01-01

    Autologous stem cell transplantation (ASCT) reverses kidney failure in one-third of multiple myeloma (MM) patients, which may lead to blood pressure (BP) improvement. We evaluate the long term impact of ASCT on BP and renal function in MM patients. We studied 192 MM patients that underwent ASCT. We compared BP readings and glomerular filtration rate (GFR) at 4 weeks before ASCT, on day of ASCT and post-ASCT at 30, 100 and 180 days. Mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) on day of ASCT and at both 30 and 100 days post-ASCT was significantly lower as compared to pre-ASCT SBP and DBP. There was a significantly higher mean GFR at day of ASCT and 30 days post-ASCT and significantly lower mean GFR at 180 days post-ASCT as compared to pre-ASCT. White patients had similar patterns to the total group for SBP, DBP, and GFR except for SBP which was still significantly lower and GFR which was not significantly different at 180 days. African-American patients showed no significant reductions in the mean values of SBP and DBP and no significant increases for GFR in follow-up after day of ASCT. Furthermore, the mean value of GFR was significantly lower at 180 days post-ASCT. ASCT in MM patients had a positive impact on SBP and DBP and GFR but the impact was minimal for African-American patients. We recommend that clinicians consider closer follow-up of BP and kidney function and more intense therapy in African-Americans with MM. Copyright © 2017 National Medical Association. Published by Elsevier Inc. All rights reserved.

  13. Long-term outcome of patients with multiple [corrected] myeloma-related advanced renal failure following auto-SCT.

    Science.gov (United States)

    Glavey, S V; Gertz, M A; Dispenzieri, A; Kumar, S; Buadi, F; Lacy, M; Hayman, S R; Kapoor, P; Dingli, D; McCurdy, A; Hogan, W J; Gastineau, D A; Leung, N

    2013-11-01

    Renal failure commonly complicates multiple myeloma (MM) and is associated with reduced survival. It is not clear whether auto-SCT results in improved renal function or attainment of independence from dialysis in patients with advanced renal impairment due to MM. We conducted a retrospective cohort study of all patients who underwent auto-SCT for MM complicated by advanced renal failure at our institution over a 10-year period (2000-2010). We aimed to assess the association between auto-SCT and renal outcome in patients with serum creatinine (SCr) over 3 mg/dL, attributable to MM, including those who were dialysis dependent. Thirty patients (2.8% of all auto-SCT patients) met inclusion criteria. Fourteen of 15 patients who were dialysis dependent before auto-SCT remained dialysis dependent in the long term despite hematological response (HR). Of the remaining 15 patients with SCr >3 mg/dL, an improvement in glomerular filtration rate (GFR) from 15 to 19.4 mL/min/1.73 m(2) was noted post auto-SCT (P=0.035); however, neither HR post auto-SCT or pre-existing renal function were independently associated with renal outcome. Auto-SCT was not associated with independence from dialysis in patients with renal failure due to MM at our institution. Although auto-SCT was associated with an improvement in GFR in patients with SCr >3 mg/dL, this improvement was not related to HR.

  14. EARLY APPLICATION OF HIGH CUT-OFF HAEMODYALISIS FOR DE-NOVO MYELOMA NEPHROPATHY IS ASSOCIATED WITH LONG-TERM DIALYSIS-INDEPENDENCY AND RENAL RECOVERY

    Directory of Open Access Journals (Sweden)

    Alhossain A. Khalafallah

    2013-01-01

    Full Text Available Background Multiple myeloma (MM is a haematological malignancy associated with kidney injury resulting from cast nephropathy, which can be caused by monoclonal free light chains (FLC. It has been demonstrated that reduction of FLC can lead to a higher proportion of patients recovering renal function with a better outcome, especially if extended high cut-off haemodialysis (HCO-HD combined with chemotherapy is used. Patients and Methods In this study, four cases of MM nephropathy were treated with HCO-HD and chemotherapy at a single institution during the period from August 2009 to August 2011. All of the patients presented with acute renal failure and high serum FLC. All patients underwent a bone marrow biopsy to confirm the diagnosis of MM, according to the WHO criteria. Three patients had de-novo MM and one patient had relapsed light chain myeloma disease. All patients underwent HCO-HD concomitantly with specific myeloma therapy once the diagnosis or relapse of MM was established. Results After a median follow up of 26 months, (range, 13-36 our data showed that all patients had a significant decrease in serum FLC through HCO-HD, proving the effectiveness of HCO-HD in managing MM. De-novo MM patients restored their renal function and achieved low-level FLC early on the treatment and become dialysis-independent. One patient with relapsed myeloma remained dialysis dependant. Conclusion Our study suggests that if myeloma nephropathy associated with light-chain disease, HCO-HD should be initiated as early as possible. At the same time a specific MM treatment should be initiated to gain control of the disease and salvage the kidneys in order to achieve dialysis-independency. Further trials to confirm our results are warranted. Key Words: Multiple myeloma, renal failure, High cut-off haemodialysis, chemotherapy, outcome.

  15. Multiple myeloma presenting as CEA-producing rectal cancer.

    Science.gov (United States)

    Talamo, Giampaolo; Barochia, Amitkumar; Zangari, Maurizio; Loughran, Thomas P

    2010-03-31

    We report the case of a 57-year-old patient with multiple myeloma, characterized by extramedullary involvement of the rectum at presentation. Malignant plasma cells were found to produce carcinoembryonic antigen (CEA), a tumor antigen more commonly associated with rectal adenocarcinomas.

  16. Multiple myeloma presenting as CEA-producing rectal cancer

    Directory of Open Access Journals (Sweden)

    Giampaolo Talamo

    2010-03-01

    Full Text Available We report the case of a 57-year old patient with multiple myeloma, characterized by extramedullary involvement of the rectum at presentation. Malignant plasma cells were found to produce carcinoembryonic antigen (CEA, a tumor antigen more commonly associated with rectal adenocarcinomas.

  17. Multiple myeloma, leukemia, and breast cancer among the US radium dial workers

    International Nuclear Information System (INIS)

    Stebbings, J.H.; Lucas, H.F.; Stehney, A.F.

    1984-01-01

    The relationships of radium exposure to mortality from multiple myeloma, leukemia, and breast cancer were studied in three cohorts of female dial workers defined by year of first employment. A three-fold excess risk of multiple myeloma occurred in the pre-1930 cohort; however, analyses of body burdens and durations of employment suggest that external radiation was more likely to have been responsible than was internal radium. Leukemia incidence and mortality have not been elevated overall among the female dial workers, either in the pre-1930 or the post-1930 cohorts, but cases have tended to occur early and in subjects with higher body burdens of radium. Extensive analyses of breast cancer data have uncovered several observations weighing against a causal interpretation of the association between radium body burdens and breast cancer

  18. Pathogenesis of Renal Failure in Multiple Myeloma: Any Role of Contrast Media?

    Directory of Open Access Journals (Sweden)

    Michele Mussap

    2014-01-01

    Full Text Available The spectrum of kidney disease-associated monoclonal immunoglobulin and plasma cell malignancies is remarkably broad and encompasses nearly all nephropathologic entities. Multiple myeloma with kidney impairment at presentation is a medical emergency since the recovery of kidney function is associated with survival benefits. In most cases, kidney impairment may be the first clinical manifestation of malignant plasma cell dyscrasias like multiple myeloma and light chain amyloidosis. Multiple myeloma per se cannot be considered a main risk factor for developing acute kidney injury following intravascular administration of iodinated contrast media. The risk is increased by comorbidities such as chronic kidney disease, diabetes, hypercalcemia, dehydration, and use of nephrotoxic drugs. Before the administration of contrast media, the current recommended laboratory tests for assessing kidney function are serum creatinine measurement and the estimation of glomerular filtration rate by using the CKD-EPI equation. The assessment of Bence Jones proteinuria is unnecessary for evaluating the risk of kidney failure in patients with multiple myeloma, since this test cannot be considered a surrogate biomarker of kidney function.

  19. Pathogenesis of Renal Failure in Multiple Myeloma: Any Role of Contrast Media?

    Science.gov (United States)

    Mussap, Michele; Merlini, Giampaolo

    2014-01-01

    The spectrum of kidney disease-associated monoclonal immunoglobulin and plasma cell malignancies is remarkably broad and encompasses nearly all nephropathologic entities. Multiple myeloma with kidney impairment at presentation is a medical emergency since the recovery of kidney function is associated with survival benefits. In most cases, kidney impairment may be the first clinical manifestation of malignant plasma cell dyscrasias like multiple myeloma and light chain amyloidosis. Multiple myeloma per se cannot be considered a main risk factor for developing acute kidney injury following intravascular administration of iodinated contrast media. The risk is increased by comorbidities such as chronic kidney disease, diabetes, hypercalcemia, dehydration, and use of nephrotoxic drugs. Before the administration of contrast media, the current recommended laboratory tests for assessing kidney function are serum creatinine measurement and the estimation of glomerular filtration rate by using the CKD-EPI equation. The assessment of Bence Jones proteinuria is unnecessary for evaluating the risk of kidney failure in patients with multiple myeloma, since this test cannot be considered a surrogate biomarker of kidney function. PMID:24877060

  20. [Kidney function and renal cancer surgery].

    Science.gov (United States)

    Izzedine, Hassan; Méjean, Arnaud; Escudier, Bernard

    2014-02-01

    Although radical nephrectomy is still practiced in many patients with large renal tumors, oncology and nephrology arguments for kidney-sparing approach for small renal masses has taken over this first. Indeed, partial nephrectomy provides equivalent oncologic results while preserving renal function and thereby limit morbidity and cardiovascular mortality related to chronic kidney disease. In addition, patients who develop kidney cancer often have medical comorbidities that may affect renal function, such as diabetes and hypertension. Histological examination of renal tissue adjacent to the tumor showed significant pathological changes in the majority of patients. For elderly patients or patients with comorbidities, active surveillance allows kidney-sparing approach with extremely low rates of progression and metastasis of cancer disease. Despite these significant advances in understanding for the treatment of small renal masses, partial nephrectomy remains underused. Better management must take into account the preservation of renal function in order to increase overall survival. A strategy for the systematic evaluation of renal function in patients with CR, with multidisciplinary staff (nephrologist urologist and oncologist), is therefore highly desirable.

  1. Multiple myeloma, leukemia, and breast cancer among the US radium dial workers

    International Nuclear Information System (INIS)

    Stebbings, J.H.; Lucas, H.F.; Stehney, A.F.

    1983-01-01

    The relationships of radium exposure to mortality from multiple myeloma, leukemia, and breast cancer were studied in three cohorts of female dial workers defined by year of first employment. Mortality was compared with that expected from US white female rates, with and without adjustment for local mortality rates. Dose-response relationships of these cancers to systemic intake of radium were determined in workers whose body burdens had been measured in vivo since 1955. Incident cases of multiple myeloma occurred in the pre-1930 cohort; however, analyses of body burdens and durations of employment suggest that external radiation was more likely to have been responsible than was internal radium. Leukemia incidence and mortality have not been elevated overall among the female dial workers, either in the pre-1930 or the post-1930 cohorts, but cases have tended to occur early and in subjects with higher body burdens. Extensive analyses of breast cancer data have uncovered several observations weighing against a causal interpretation of the association between radium and breast cancer

  2. Prostate cancer in renal transplant recipients

    Directory of Open Access Journals (Sweden)

    Benjamin A. Sherer

    Full Text Available ABSTRACT As patients with end-stage renal disease are receiving renal allografts at older ages, the number of male renal transplant recipients (RTRs being diagnosed with prostate cancer (CaP is increasing. Historically, the literature regarding the management of CaP in RTR's is limited to case reports and small case series. To date, there are no standardized guidelines for screening or management of CaP in these complex patients. To better understand the unique characteristics of CaP in the renal transplant population, we performed a literature review of PubMed, without date limitations, using a combination of search terms including prostate cancer, end stage renal disease, renal transplantation, prostate cancer screening, prostate specific antigen kinetics, immuno-suppression, prostatectomy, and radiation therapy. Of special note, teams facilitating the care of these complex patients must carefully and meticulously consider the altered anatomy for surgical and radiotherapeutic planning. Active surveillance, though gaining popularity in the general low risk prostate cancer population, needs further study in this group, as does the management of advance disease. This review provides a comprehensive and contemporary understanding of the incidence, screening measures, risk stratification, and treatment options for CaP in RTRs.

  3. Coexisting multiple myeloma, lymphoma, and non-small cell lung cancer: a case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Khade P

    2017-11-01

    Full Text Available Parth Khade, Srinivas Devarakonda Department of Internal Medicine, Louisiana State University Health, Shreveport, LA, USA Abstract: Multiple myeloma is a plasma cell dyscrasia characterized by neoplastic proliferation of plasma cells, producing a monoclonal immunoglobulin. Small lymphocytic lymphoma (SLL is a neoplasm consisting of monoclonal B-cell lymphocyte proliferation. We present an extremely rare case of coexisting multiple myeloma, SLL, and squamous cell carcinoma of the lung in a 74-year-old female patient. She initially presented with a midline mass with pain in the lumbar area. Debulking surgery was performed, and pathology showed plasmacytoma. Further evaluation revealed coexistent IgG kappa myeloma. Imaging revealed extensive abdominal lymphadenopathy, and mesenteric lymph node biopsy confirmed the presence of SLL. The patient was also found to have a mass in the left lower lobe of the lung; biopsy showed squamous cell carcinoma. This patient was treated with lenalidomide and dexamethasone for multiple myeloma, and stereotactic body radiotherapy for limited stage lung cancer. Due to the more indolent course of SLL, watchful waiting was applied. Keywords: coexisting, multiple myeloma, lung cancer, non-Hodgkin’s lymphoma

  4. Genetics Home Reference: hereditary leiomyomatosis and renal cell cancer

    Science.gov (United States)

    ... Home Health Conditions HLRCC Hereditary leiomyomatosis and renal cell cancer Printable PDF Open All Close All Enable Javascript ... expand/collapse boxes. Description Hereditary leiomyomatosis and renal cell cancer ( HLRCC ) is a disorder in which affected individuals ...

  5. Incidence and outcome of patients starting renal replacement therapy for end-stage renal disease due to multiple myeloma or light-chain deposit disease: an ERA-EDTA Registry study

    DEFF Research Database (Denmark)

    Tsakiris, D.J.; Stel, V.S.; Finne, P.

    2010-01-01

    Background. Information on demographics and survival of patients starting renal replacement therapy (RRT) for end-stage renal disease (ESRD) due to multiple myeloma (MM) or light-chain deposit disease (LCDD) is scarce. The aim of this study was to describe the incidence, characteristics, causes...... causes (non-MM) was observed overtime. Patient survival on RRT was examined, unadjusted and adjusted for age and gender. Results. Of the 159 637 patients on RRT, 2453 (1.54%) had MM or LCDD. The incidence of RRT for ESRD due to MM or LCDD, adjusted for age and gender, increased from 0.70 pmp in 1986...

  6. Breast cancer metastatic to the kidney with renal vein involvement.

    Science.gov (United States)

    Nasu, Hatsuko; Miura, Katsutoshi; Baba, Megumi; Nagata, Masao; Yoshida, Masayuki; Ogura, Hiroyuki; Takehara, Yasuo; Sakahara, Harumi

    2015-02-01

    The common sites of breast cancer metastases include bones, lung, brain, and liver. Renal metastasis from the breast is rare. We report a case of breast cancer metastatic to the kidney with extension into the renal vein. A 40-year-old woman had undergone left mastectomy for breast cancer at the age of 38. A gastric tumor, which was later proved to be metastasis from breast cancer, was detected by endoscopy. Computed tomography performed for further examination of the gastric tumor revealed a large left renal tumor with extension into the left renal vein. It mimicked a primary renal tumor. Percutaneous biopsy of the renal tumor confirmed metastasis from breast cancer. Surgical intervention of the stomach and the kidney was avoided, and she was treated with systemic chemotherapy. Breast cancer metastatic to the kidney may present a solitary renal mass with extension into the renal vein, which mimics a primary renal tumor.

  7. Lung Cancer in Renal Transplant Recipients

    Directory of Open Access Journals (Sweden)

    Jozicic Mirela

    2016-06-01

    Full Text Available Introduction. Although the incidence of malignancy has increased after solid organ transplantation, data on lung cancer in this group of patients is scarce. The aim of this study was to determine clinical characteristics and outcome of patients who developed lung cancer after renal transplantation. Methods. Among a cohort of 1658 patients who received a transplant at our institution and were followedup between 1973 and 2014, five patients developed lung cancer. We analyzed risk factors, transplantation characteristics, treatment options and survival. Results. Lung cancer was diagnosed in 5 patients (0.3%. Time to diagnosis after the transplant procedure ranged from 26 to 156 months (mean 115 months. All of them had a smoking history. Tumors were classified as IIB (20%, IIIA (40%, and IV (40%. Histological types included adenocarcinoma (80% and there was one case of sarcomatoid carcinoma (20%. One patient had concomitant thyroid papillary carcinoma. Radiotherapy was applied in 2 patients, 2 underwent chemotherapy (erlotinib and combination of carboplatinum and etopozide in one patient each, and 2 died within one month after the diagnosis from disseminated malignant disease. Patients with stage IIIA survived 14 and 24 months after the diagnosis. The patient with sarcomatoid cancer underwent thoracotomy with a complete resection, lost his graft function and died 7 months after the diagnosis. Conclusion. Lung cancer is relatively rare malignancy in renal transplant recipients, but associated with high mortality. Smoking is a significant risk factor, thus smoking cessation should be promoted among renal transplant recipients, as well as regular screening for lung cancer.

  8. Large Population-Based Study Reveals Disparities in Myeloma Precursor Disease | Center for Cancer Research

    Science.gov (United States)

    Multiple myeloma (MM) is a cancer of plasma cells, which are antibody-producing white blood cells. Patients with MM have a characteristic excess of monoclonal antibodies, so called M proteins, in their serum, urine, or both and plasma cell infiltration into their bone marrow at multiple sites. African Americans are more than twice as likely as whites to develop MM, but the reason for this higher prevalence is not entirely clear. Since MM is nearly always preceded by the premalignant condition monoclonal gammopathy of undetermined significance (MGUS), Ola Landgren, M.D., Ph.D., a Senior Investigator in CCR’s Lymphoid Malignancies Branch, and colleagues from NCI’s Division of Cancer Epidemiology and Genetics, the Mayo Clinic, and the Centers for Disease Control and Prevention (CDC), wanted to determine whether there were also disparities in MGUS prevalence or in biomarkers associated with a high risk of MGUS progression to MM.

  9. Renal cancer in kidney transplanted patients.

    Science.gov (United States)

    Frascà, Giovanni M; Sandrini, Silvio; Cosmai, Laura; Porta, Camillo; Asch, William; Santoni, Matteo; Salviani, Chiara; D'Errico, Antonia; Malvi, Deborah; Balestra, Emilio; Gallieni, Maurizio

    2015-12-01

    Renal cancer occurs more frequently in renal transplanted patients than in the general population, affecting native kidneys in 90% of cases and the graft in 10 %. In addition to general risk factors, malignancy susceptibility may be influenced by immunosuppressive therapy, the use of calcineurin inhibitors (CNI) as compared with mammalian target of rapamycin inhibitors, and the length of dialysis treatment. Acquired cystic kidney disease may increase the risk for renal cancer after transplantation, while autosomal dominant polycystic kidney disease does not seem to predispose to cancer development. Annual ultrasound evaluation seems appropriate in patients with congenital or acquired cystic disease or even a single cyst in native kidneys, and every 2 years in patients older than 60 years if they were on dialysis for more than 5 years before transplantation. Immunosuppression should be lowered in patients who develop renal cancer, by reduction or withdrawal of CNI. Although more evidence is still needed, it seems reasonable to shift patients from CNI to everolimus or sirolimus if not already treated with one of these drugs, with due caution in subjects with chronic allograft nephropathy.

  10. Osteoclast nuclei of myeloma patients show chromosome translocations specific for the myeloma cell clone: a new type of cancer-host partnership?

    DEFF Research Database (Denmark)

    Levin Andersen, Thomas; Boissy, Patrice; Sondergaard, T E

    2007-01-01

    through fusion between myeloma cells and osteoclasts. In conclusion, malignant cells contribute significantly to the formation of bone-resorbing osteoclasts in multiple myeloma. Osteoclast-myeloma clone hybrids reflect a previously unrecognized mechanism of bone destruction in which malignant cells...

  11. Renal cancer in recipients of kidney transplant

    Directory of Open Access Journals (Sweden)

    Prajwal Dhakal

    2017-03-01

    Full Text Available The aim of our study is to determine characteristics and outcomes of kidney cancer in renal transplant recipients. MEDLINE ® database was searched in June 2015 to identify cases of kidney cancer in renal transplant recipients. We include also a new case. Descriptive statistics were used for analysis. Forty-eight (48 recipients reported in 25 papers met the eligibility criteria. The median age was 47 years (range 9-66; 27% were females. Chronic glomerulonephritis, cystic kidney disease and hypertension were common indications for renal transplant. Among donors 24% were females and the median age was 52.5 years (17- 73; 62% of kidney cancers were donor-derived. The median interval between transplant and cancer diagnosis was shorter for cancer of recipient versus donor origin (150 vs. 210 days. Clear cell carcinoma was diagnosed in 17%. 25% had metastasis at diagnosis. Kidney explantation or excision was done in 90% and 84% of cases with and without metastasis respectively. The median survival was 72 months. Actuarial 1-year and 5-year survival rates were 73.4% and 55.1% respectively. Among the recipients from 7 donors who subsequently developed malignancy, 57% were dead within a year. Kidney transplant recipients have a small risk of kidney cancer, which affects younger patients and occurs within a year of transplant, likely due to immunosuppression. Whether the use of older donors may increase the likelihood needs further investigation. The presence of metastasis, explantation or excision of affected kidney and development of cancer in donors predict outcomes. The results may guide patient education and informed decision-making.

  12. Metastasis Targeted Therapies in Renal Cell Cancer

    OpenAIRE

    K. Fehmi Narter; Bora Özveren

    2018-01-01

    Metastatic renal cell cancer is a malignant disease and its treatment has been not been described clearly yet. These patients are generally symptomatic and resistant to current treatment modalities. Radiotherapy, chemotherapy, and hormonal therapy are not curative in many of these patients. A multimodal approach consisting of cytoreductive nephrectomy, systemic therapy (immunotherapy or targeted molecules), and metastasectomy has been shown to be hopeful in prolonging the survival and improvi...

  13. Impact of High-Cut-Off Dialysis on Renal Recovery in Dialysis-Dependent Multiple Myeloma Patients: Results from a Case-Control Study.

    Directory of Open Access Journals (Sweden)

    Hans U Gerth

    Full Text Available High-cut-off hemodialysis (HCO-HD can effectively reduce high concentrations of circulating serum free light chains (sFLC in patients with dialysis-dependent acute kidney injury (AKI due to multiple myeloma (MM. Therefore, the aim of this study was to analyze renal recovery in a retrospective single-center cohort of dialysis-dependent MM patients treated with either conventional HD (conv. HD or HCO-HD.The final cohort consisted of 59 patients treated with HCO-HD (n = 42 or conv. HD (n = 17. A sustained sFLC response was detected in a significantly higher proportion of HCO-HD patients (83.3% compared with conv. HD patients (29.4%; p = 0.007. The median duration of sFLC required to reach values <1000 mg/l was 14.5 days in the HCO-HD group and 36 days in the conv. HD group. The corresponding rates of renal recovery were 64.3% and 29.4%, respectively (chi-squared test, p = 0.014. Multivariate regression and decision tree analysis (recursive partitioning revealed HCO-HD (adjusted odds ratio [OR] 6.1 [95% confidence interval (CI 1.5-24.5], p = 0.011 and low initial uric acid values (adjusted OR 1.3 [95%CI 1.0-1.7], p = 0.045 as independent and paramount variables associated with a favorable renal outcome.In summary, the results from this retrospective case-control study suggest in addition to novel agent-based chemotherapy a benefit of HCO-HD in sFLC removal and renal outcome in dialysis-dependent AKI secondary to MM. This finding was especially pertinent in patients with low initial uric acid values, resulting in a promising renal recovery rate of 71.9%. Further prospective studies are warranted.

  14. Genetics of Kidney Cancer (Renal Cell Cancer) (PDQ®)—Health Professional Version

    Science.gov (United States)

    Genetics of Kidney Cancer (Renal Cell) includes the hereditary cancer syndromes von Hippel-Lindau disease, hereditary leiomyomatosis and renal cell cancer, Birt-Hogg-Dubé syndrome, and hereditary papillary renal carcinoma. Get comprehensive information on these syndromes in this clinician summary.

  15. Treatment of advanced rectal cancer after renal transplantation

    Institute of Scientific and Technical Information of China (English)

    Hai-Yi Liu; Xiao-Bo Liang; Yao-Ping Li; Yi Feng; Dong-Bo Liu; Wen-Da Wang

    2011-01-01

    Renal transplantation is a standard procedure for end-stage renal disease today. Due to immunosuppressive drugs and increasing survival time after renal trans-plantation, patients with transplanted kidneys carry an increased risk of developing malignant tumors. In this case report, 3 patients with advanced rectal can-cer after renal transplantation for renal failure were treated with anterior resection or abdominoperineal resection plus total mesorectal excision, followed by adjuvant chemotherapy. One patient eventually died of metastasized cancer 31 mo after therapy, although his organ grafts functioned well until his death. The other 2 patients were well during the 8 and 21 mo follow-up periods after rectal resection. We therefore strongly argue that patients with advanced rectal cancer should receive standard oncology treatment, including opera-tion and adjuvant treatment after renal transplantation. Colorectal cancer screening in such patients appears justified.

  16. Synchronous colon and renal cancer - case report

    International Nuclear Information System (INIS)

    Luczynska, E.; Pawlik, T.; Aniol, J.; Chwalibog, A.

    2008-01-01

    Primary cancer may occur synchronously in two different organs. We present an example of pathologically proven, coexistent renal and colony double malignant tumors. A 59 year old man, was admitted to the Institute of Oncology due to left renal lesion, discovered during a routine abdominal ultrasound examination. The CT exam was performed before surgery. The CT scans reveled a second abnormality, presenting irregular shaped and thickened to 20 mm intestinal wall within a patient's large bowel. As a next diagnostic step a CT-colonoscopy was undertaken, which confirmed the presence of an exophytic sigmoid lesion, eccentrically affecting the colonic wall and protruding into the lumen moderately narrowing it, placed about 50 cm from the external rectal sphincter. Patient underwent simultaneous radical left nephrectomy and sigmoidectomy. Both tumors were confirmed in pathologic evaluation, reveling renal clear cell carcinoma (Fuhrman G II) and colonic adenocarcinoma (Astler-Coller B2). Preoperative careful imaging studies reveled neoplastic tumors in two different organs, allowing for radical resection at the same surgical procedure. (author)

  17. Analysis of renal impairment in MM-003, a phase III study of pomalidomide + low - dose dexamethasone versus high - dose dexamethasone in refractory or relapsed and refractory multiple myeloma

    Science.gov (United States)

    Weisel, Katja C.; Dimopoulos, Meletios A.; Moreau, Philippe; Lacy, Martha Q.; Song, Kevin W.; Delforge, Michel; Karlin, Lionel; Goldschmidt, Hartmut; Banos, Anne; Oriol, Albert; Alegre, Adrian; Chen, Christine; Cavo, Michele; Garderet, Laurent; Ivanova, Valentina; Martinez-Lopez, Joaquin; Knop, Stefan; Yu, Xin; Hong, Kevin; Sternas, Lars; Jacques, Christian; Zaki, Mohamed H.; Miguel, Jesus San

    2016-01-01

    Pomalidomide + low-dose dexamethasone is effective and well tolerated for refractory or relapsed and refractory multiple myeloma after bortezomib and lenalidomide failure. The phase III trial MM-003 compared pomalidomide + low-dose dexamethasone with high-dose dexamethasone. This subanalysis grouped patients by baseline creatinine clearance ≥ 30 − < 60 mL/min (n=93, pomalidomide + low-dose dexamethasone; n=56, high-dose dexamethasone) or ≥ 60 mL/min (n=205, pomalidomide + low-dose dexamethasone; n=93, high-dose dexamethasone). Median progression-free survival was similar for both subgroups and favored pomalidomide + low-dose dexamethasone versus high-dose dexamethasone: 4.0 versus 1.9 months in the group with baseline creatinine clearance ≥ 30 − < 60 mL/min (P<0.001) and 4.0 versus 2.0 months in the group with baseline creatinine clearance ≥ 60 mL/min (P<0.001). Median overall survival for pomalidomide + low-dose dexamethasone versus high-dose dexamethasone was 10.4 versus 4.9 months (P=0.030) and 15.5 versus 9.2 months (P=0.133), respectively. Improved renal function, defined as an increase in creatinine clearance from < 60 to ≥ 60 mL/min, was similar in pomalidomide + low-dose dexamethasone and high-dose dexamethasone patients (42% and 47%, respectively). Improvement in progression-free and overall survival in these patients was comparable with that in patients without renal impairment. There was no increase in discontinuations of therapy, dose modifications, and adverse events in patients with moderate renal impairment. Pomalidomide at a starting dose of 4 mg + low-dose dexamethasone is well tolerated in patients with refractory or relapsed and refractory multiple myeloma, and of comparable efficacy if moderate renal impairment is present. This trial was registered with clinicaltrials.gov identifier 01311687 and EudraCT identifier 2010-019820-30. PMID:27081177

  18. The database of the Danish Renal Cancer Group

    DEFF Research Database (Denmark)

    Petersen, Astrid Christine; Søgaard, Mette; Mehnert, Frank

    2016-01-01

    AIM OF THE DATABASE: The main purpose of the database of the Danish Renal Cancer Group (DaRenCaData) is to improve the quality of renal cancer treatment in Denmark and secondarily to conduct observational research. STUDY POPULATION: DaRenCaData includes all Danish patients with a first......-time diagnosis of renal cancer in the Danish National Pathology Registry since August 1, 2010. MAIN VARIABLES: DaRenCaData holds data on demographic characteristics, treatments, and pathology collected through linkage to central registries and online registration of a few clinical key variables. Eight quality...... indicators have been selected for monitoring treatment quality and outcome after renal cancer. DESCRIPTIVE DATA: The incidence of renal cancer in Denmark has increased from 12.7 per 100,000 population-years in 2010-2011 to 15.9 per 100,000 population-years in 2014-2015. A total of 3,977 Danish patients...

  19. Lenalidomide at the dose of 25 mg every other day in patients affected by multiple myeloma and renal failure: a real-life experience.

    Science.gov (United States)

    Cerchione, Claudio; Nappi, Davide; Pareto, Anna E; Romano, Alessandra; Martinelli, Vincenzo; Picardi, Marco; Pane, Fabrizio; Catalano, Lucio

    2018-04-01

    Renal impairment (RI) is a relevant complication of patients affected by multiple myeloma (MM); it can be present in up to 30-35% of newly diagnosed MM and is linked to a poor outcome. However, early recognition and early treatment with novel agents can overcome the negative impact of RI and even reverse kidney damage in most cases. Lenalidomide, available as an oral compound, is an immunomodulatory drug with both antiproliferative and immunomodulatory activity that is largely used in the management of MM. Dose reduction is mandatory in RI; however, there is no theoretical assumption against the possibility that protracting the time of full standard doses can be equally effective and tolerated by patients requiring reduced doses. In this report, we describe our retrospective experience, in 18 patients, with the administration of lenalidomide 25 mg every other day for patients with MM and RI. The overall response ratio was 66.5%. More than half (61.1%) of the patients had a renal response. The median progression-free survival was 8 months (range: 3-18 months). No serious adverse event occurred during treatment, and it was never necessary to disrupt or delay treatment for toxicity. These preliminary observations point to a significant therapeutic effect of lenalidomide, at the dose of 25 mg every other day for 21 days, with logistic and economic advantages. However, these results should be validated by controlled studies involving larger numbers of patients.

  20. PET/CT in renal, bladder and testicular cancer

    Science.gov (United States)

    Bouchelouche, Kirsten; Physician, Chief; Choyke, Peter L.

    2015-01-01

    Imaging plays an important role in the clinical management of cancer patients. Hybrid imaging with PET/CT is having a broad impact in oncology, and in recent years PET/CT is beginning to have an impact in uro-oncology as well. In both bladder and renal cancer there is a need to study the efficacy of other tracers than F-18 fluorodeoxyglucose (FDG), particularly tracers with only limited renal excretion. Thus, new tracers are being introduced in these malignancies. This review focuses on the clinical role of FDG and other PET agents in renal, bladder and testicular cancer. PMID:26099672

  1. End Stage and Chronic Kidney Disease: Associations with Renal Cancer

    International Nuclear Information System (INIS)

    Russo, Paul

    2012-01-01

    There is a well known association between end stage renal disease and the development of kidney cancer in the native kidney of patients requiring renal replacement therapy. There is now emerging evidence that lesser degrees of renal insufficiency (chronic kidney disease, CKD) are also associated with an increased likelihood of cancer in general and kidney cancer in particular. Nephropathological changes are commonly observed in the non-tumor bearing portions of kidney resected at the time of partial and radical nephrectomy (RN). In addition, patients with renal cancer are more likely to have CKD at the time of diagnosis and treatment than the general population. The exact mechanism by which renal insufficiency transforms normal kidney cells into tumor cells is not known. Possible mechanisms include uremic immune inhibition or increased exposure to circulating toxins not adequately cleared by the kidneys. Surgeons managing kidney tumors must have an increased awareness of their patient’s renal functional status as they plan their resection. Kidney sparing approaches, including partial nephrectomy (PN) or active surveillance in older and morbidly ill patients, can prevent CKD or delay the further decline in renal function which is well documented with RN. Despite emerging evidence that PN provides equivalent local tumor control to RN while at the same time preventing CKD, this operation remains under utilized in the United States and abroad. Increased awareness of the bi directional relationship between kidney function and kidney cancer is essential in the contemporary management of kidney cancer.

  2. Myeov (myeloma overexpressed gene) drives colon cancer cell migration and is regulated by PGE2

    LENUS (Irish Health Repository)

    Lawlor, Garrett

    2010-06-22

    Abstract Introduction We have previously reported that Myeov (MYEloma OVerexpressed gene) expression is enhanced in colorectal cancer (CRC) and that it promotes CRC cell proliferation and invasion. The role of Myeov in CRC migration is unclear. ProstaglandinE2 (PGE 2) is a known factor in promoting CRC carcinogenesis. The role of PGE 2 in modulating Myeov expression has also not been defined. Aim To assess the role of Myeov expression in CRC cell migration and to evaluate the role of PGE 2 in Myeov bioactivity. Methods siRNA mediated Myeov knockdown was achieved in T84 CRC cells. Knockdown was assessed using quantitative real time PCR. The effect of knockdown on CRC cell migration was assessed using a scratch wound healing assay. Separately, T84 cells were treated with PGE 2 (0.00025 μ M, 0.1 μ M and 1 μ M) from 30 min to 3 hours and the effect on Myeov gene expression was assessed using real time PCR. Results Myeov knockdown resulted in a significant reduction in CRC cell migration, observable as early as 12 hours (P < 0.05) with a 39% reduction compared to control at 36 hours (p < 0.01). Myeov expression was enhanced after treatment with PGE 2, with the greatest effect seen at 60 mins for all 3 PGE 2 doses. This response was dose dependent with a 290%, 550% & 1,000% increase in Myeov expression for 0.00025 μ M, 0.1 μ M and 1 μ M PGE 2 respectively. Conclusion In addition to promoting CRC proliferation and invasion, our findings indicate that Myeov stimulates CRC cell migration, and its expression may be PGE 2 dependant.

  3. MYEOV (myeloma overexpressed gene) drives colon cancer cell migration and is regulated by PGE2.

    LENUS (Irish Health Repository)

    Lawlor, Garrett

    2010-01-01

    INTRODUCTION: We have previously reported that Myeov (MYEloma OVerexpressed gene) expression is enhanced in colorectal cancer (CRC) and that it promotes CRC cell proliferation and invasion. The role of Myeov in CRC migration is unclear. ProstaglandinE2 (PGE 2) is a known factor in promoting CRC carcinogenesis. The role of PGE 2 in modulating Myeov expression has also not been defined. AIM: To assess the role of Myeov expression in CRC cell migration and to evaluate the role of PGE 2 in Myeov bioactivity. METHODS: siRNA mediated Myeov knockdown was achieved in T84 CRC cells. Knockdown was assessed using quantitative real time PCR. The effect of knockdown on CRC cell migration was assessed using a scratch wound healing assay. Separately, T84 cells were treated with PGE 2 (0.00025 micro M, 0.1 micro M and 1 micro M) from 30 min to 3 hours and the effect on Myeov gene expression was assessed using real time PCR. RESULTS: Myeov knockdown resulted in a significant reduction in CRC cell migration, observable as early as 12 hours (P < 0.05) with a 39% reduction compared to control at 36 hours (p < 0.01). Myeov expression was enhanced after treatment with PGE 2, with the greatest effect seen at 60 mins for all 3 PGE 2 doses. This response was dose dependent with a 290%, 550% & 1,000% increase in Myeov expression for 0.00025 micro M, 0.1 micro M and 1 micro M PGE 2 respectively. CONCLUSION: In addition to promoting CRC proliferation and invasion, our findings indicate that Myeov stimulates CRC cell migration, and its expression may be PGE 2 dependant.

  4. PROGNOSTIC FACTORS OF SURVIVAL IN RENAL CANCER

    Directory of Open Access Journals (Sweden)

    A. V. Seriogin

    2014-08-01

    Full Text Available The purpose of the study was to reveal the independent anatomic, histological, and clinical factors of cancer-specific survival in patients with renal-cell carcinoma (RCC. For this, the authors retrospectively analyzed their experience with radical surgical treatments in 73 RCC patients operated on at the Department of Urology and Surgical Andrology, Russian Medical Academy of Postgraduate Education, from January 1, 1999 to December 31, 2004; their outcomes have become known by the present time. There was a statistically significant correlation of cancer-specific survival with its parameters, such as pathological stage of a tumor, its maximum pathological size, differentiation grade, involvement of regional lymph nodes, venous tumor thrombosis, level of thrombocytosis, and degree of the clinical symptoms of the disease. Multivariate analysis of survival in RCC in relation to the prognostic factors could reveal odd ratios for the limit values of significant prognostic factors. The statistically significant prognostic values established in the present study, as well as the molecular factors the implication of which is being now investigated can become in future an effective addition to the TNM staging system to define indications for certain treatments and to predict survival in RCC  

  5. PROGNOSTIC FACTORS OF SURVIVAL IN RENAL CANCER

    Directory of Open Access Journals (Sweden)

    A. V. Seriogin

    2009-01-01

    Full Text Available The purpose of the study was to reveal the independent anatomic, histological, and clinical factors of cancer-specific survival in patients with renal-cell carcinoma (RCC. For this, the authors retrospectively analyzed their experience with radical surgical treatments in 73 RCC patients operated on at the Department of Urology and Surgical Andrology, Russian Medical Academy of Postgraduate Education, from January 1, 1999 to December 31, 2004; their outcomes have become known by the present time. There was a statistically significant correlation of cancer-specific survival with its parameters, such as pathological stage of a tumor, its maximum pathological size, differentiation grade, involvement of regional lymph nodes, venous tumor thrombosis, level of thrombocytosis, and degree of the clinical symptoms of the disease. Multivariate analysis of survival in RCC in relation to the prognostic factors could reveal odd ratios for the limit values of significant prognostic factors. The statistically significant prognostic values established in the present study, as well as the molecular factors the implication of which is being now investigated can become in future an effective addition to the TNM staging system to define indications for certain treatments and to predict survival in RCC  

  6. BRAFV600 mutations in solid tumors, other than metastatic melanoma and papillary thyroid cancer, or multiple myeloma: a screening study

    Directory of Open Access Journals (Sweden)

    Cohn AL

    2017-02-01

    Full Text Available Allen L Cohn,1 Bann-Mo Day,2 Sarang Abhyankar,3 Edward McKenna,2 Todd Riehl,4 Igor Puzanov5 1Medical Research, Rocky Mountain Cancer Centers, Denver, CO, 2US Medical Affairs, 3Global Safety and Risk Management, 4Product Development Oncology, Genentech, Inc., South San Francisco, CA, 5Melanoma Section, Division of Hematology-Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA Background: Mutations in the BRAF gene have been implicated in several human cancers. The objective of this screening study was to identify patients with solid tumors (other than metastatic melanoma or papillary thyroid cancer or multiple myeloma harboring activating BRAFV600 mutations for enrollment in a vemurafenib clinical study.Methods: Formalin-fixed, paraffin-embedded tumor samples were collected and sent to a central laboratory to identify activating BRAFV600 mutations by bidirectional direct Sanger sequencing.Results: Overall incidence of BRAFV600E mutation in evaluable patients (n=548 was 3% (95% confidence interval [CI], 1.7–4.7: 11% in colorectal tumors (n=75, 6% in biliary tract tumors (n=16, 3% in non-small cell lung cancers (n=71, 2% in other types of solid tumors (n=180, and 3% in multiple myeloma (n=31. There were no BRAFV600 mutations in this cohort of patients with ovarian tumors (n=68, breast cancer (n=86, or prostate cancer (n=21.Conclusion: This multicenter, national screening study confirms previously reported incidences of BRAFV600 mutations from single-center studies. Patients identified with BRAFV600 mutations were potentially eligible for enrollment in the VE-BASKET study. Keywords: genetic testing, proto-oncogene proteins B-raf, PLX4032

  7. Epidemiologic characteristics and risk factors for renal cell cancer

    Directory of Open Access Journals (Sweden)

    Loren Lipworth

    2009-04-01

    Full Text Available Loren Lipworth1,2, Robert E Tarone1,2, Lars Lund2,3, Joseph K McLaughlin1,21International Epidemiology Institute, Rockville, MD, USA; 2Department of Medicine (JKM, RET and Preventive Medicine (LL, Vanderbilt University Medical Center and Vanderbilt-Ingram Cancer Center, Nashville, TN, USA; 3Department of Urology, Viborg Hospital, Viborg, DenmarkAbstract: Incidence rates of renal cell cancer, which accounts for 85% of kidney cancers, have been rising in the United States and in most European countries for several decades. Family history is associated with a two- to four-fold increase in risk, but the major forms of inherited predisposition together account for less than 4% of renal cell cancers. Cigarette smoking, obesity, and hypertension are the most consistently established risk factors. Analgesics have not been convincingly linked with renal cell cancer risk. A reduced risk of renal cell cancer among statin users has been hypothesized but has not been adequately studied. A possible protective effect of fruit and vegetable consumption is the only moderately consistently reported dietary finding, and, with the exception of a positive association with parity, evidence for a role of hormonal or reproductive factors in the etiology of renal cell cancer in humans is limited. A recent hypothesis that moderate levels of alcohol consumption may be protective for renal cell cancer is not strongly supported by epidemiologic results, which are inconsistent with respect to the categories of alcohol consumption and the amount of alcohol intake reportedly associated with decreased risk. For occupational factors, the weight of the evidence does not provide consistent support for the hypotheses that renal cell cancer may be caused by asbestos, gasoline, or trichloroethylene exposure. The established determinants of renal cell cancer, cigarette smoking, obesity, and hypertension, account for less than half of these cancers. Novel epidemiologic approaches

  8. Synchronous triple urogenital cancer (renal cancer, bladder cancer, prostatic cancer). A case report

    Energy Technology Data Exchange (ETDEWEB)

    Takada, Tsuyoshi; Honda, Masahito; Momohara, Chikahiro; Komori, Kazuhiko; Fujioka, Hideki [Osaka Police Hospital (Japan)

    2002-04-01

    A case of synchronous triple urogenital cancer, which was comprised of renal cell carcinoma of the left kidney, transitional cell carcinoma of the urinary bladder, and adenocarcinoma of the prostate, is reported. A 72-year-old Japanese male patient was referred to our outpatient clinic with the complaint of asymptomatic hematuria. At that time, his serum of level of PSA was elevated to 20 ng/ml. Cystourethroscopy showed a papillary bladder tumor and coagula through the left urinary orifice. Ultrasonography, computed tomography and magnetic resonance imaging showed a mass lesion measuring about 6 cm by 5 cm in the left kidney. Angiography showed a hypervascular lesion measuring about 6 cm by 5 cm at the same site. Double cancer, consisting of renal cell carcinoma and transitional cell carcinoma of the urinary bladder, was suspected and we performed left total nephroureterectomy, hilar lymphadenectomy, and transurethral rection of the bladder tumor, one month later. At the same time, we performed a biopsy of the prostate. Histological diagnosis was renal cell carcinoma, clear cell carcinoma and transitional cell carcinoma of urinary bladder. Histological diagnosis of the prostate biopsy was moderately differentiated adenocarcinoma. Since this case fulfilled the criteria of Warren and Gates, it was classified as synchronous triple urogenital cancer. A review of the literature revealed 17 authentic cases of triple urogenital cancer, of which 14 and 10 cases were reported as a combination of renal cancer, bladder cancer and prostatic cancer, in the world and in Japan, respectively. Furthermore, he had been exposed to the atomic bomb explosion in Hiroshima in 1945. This carcinogenic precursor may be related to the development of the triple cancer. (author)

  9. Synchronous triple urogenital cancer (renal cancer, bladder cancer, prostatic cancer). A case report

    International Nuclear Information System (INIS)

    Takada, Tsuyoshi; Honda, Masahito; Momohara, Chikahiro; Komori, Kazuhiko; Fujioka, Hideki

    2002-01-01

    A case of synchronous triple urogenital cancer, which was comprised of renal cell carcinoma of the left kidney, transitional cell carcinoma of the urinary bladder, and adenocarcinoma of the prostate, is reported. A 72-year-old Japanese male patient was referred to our outpatient clinic with the complaint of asymptomatic hematuria. At that time, his serum of level of PSA was elevated to 20 ng/ml. Cystourethroscopy showed a papillary bladder tumor and coagula through the left urinary orifice. Ultrasonography, computed tomography and magnetic resonance imaging showed a mass lesion measuring about 6 cm by 5 cm in the left kidney. Angiography showed a hypervascular lesion measuring about 6 cm by 5 cm at the same site. Double cancer, consisting of renal cell carcinoma and transitional cell carcinoma of the urinary bladder, was suspected and we performed left total nephroureterectomy, hilar lymphadenectomy, and transurethral rection of the bladder tumor, one month later. At the same time, we performed a biopsy of the prostate. Histological diagnosis was renal cell carcinoma, clear cell carcinoma and transitional cell carcinoma of urinary bladder. Histological diagnosis of the prostate biopsy was moderately differentiated adenocarcinoma. Since this case fulfilled the criteria of Warren and Gates, it was classified as synchronous triple urogenital cancer. A review of the literature revealed 17 authentic cases of triple urogenital cancer, of which 14 and 10 cases were reported as a combination of renal cancer, bladder cancer and prostatic cancer, in the world and in Japan, respectively. Furthermore, he had been exposed to the atomic bomb explosion in Hiroshima in 1945. This carcinogenic precursor may be related to the development of the triple cancer. (author)

  10. Skin Manifestation of Unsuspecting Prostate Cancer Detected by {sup 18}F-FDG PET/CT Performed To Assess Underlying Multiple Myeloma

    Energy Technology Data Exchange (ETDEWEB)

    AbAziz, Aini; Mahaletchumy, Thanuja; Chung, Junekey [Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur (Malaysia)

    2013-12-15

    Skin metastases from either prostate adenocarcinoma or multiple myeloma rarely occur. We report the case of a 73-year-old man with multiple myeloma who presented with multiple subcutaneous nodules 3 years after his initial diagnosis. Fluorine-18 fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) imaging was suggestive of a concomitant second primary from the prostate. This case highlights not only a rare initial manifestation of prostate cancer, but also the role of 18F-FDG-PET/CT in detecting a clinically unsuspected second malignancy. It potentially corroborates the possible association of both diseases, as has been reported before.

  11. Diagnosis of renal cell cancer by dynamic MRI

    International Nuclear Information System (INIS)

    Togami, Izumi; Kitagawa, Takahiro; Katoh, Katsuya

    1992-01-01

    Dynamic MRI was performed in 15 cases (16 lesions) of renal cell cancer. The enhanced pattern of the tumor was mainly evaluated and findings were compared with these of dynamic CT and renal angiography. Enhanced patterns on dynamic MRI and dynamic CT were similar, but each phase on dynamic MRI tended to be prolonged compared with dynamic CT. Many hypervascular tumors on renal angiography had prominent enhancement in an early phase on dynamic MRI, but there was no prominent enhancement in cases with tumor thrombi in the renal vein or IVC. All hypovascular tumors were enhanced to some degree without exception on dynamic MRI. Dynamic MRI is considered to be useful for the evaluation of the characterization, especially vascularity, of renal cell cancer, but we should pay attention to the differential diagnosis from other tumor in atypical cases because its enhanced patterns are various on dynamic MRI. (author)

  12. Renal Metastasis from Primary Cervical Cancer: A Case Report

    International Nuclear Information System (INIS)

    Jeon, Seong Woo; Kim, See Hyung; Kwon, Sun Young

    2013-01-01

    Metastasis of malignant tumors to the kidney is clinically rare and often discovered by autopsy. Primary lymphoma and lung cancer are known that can metastasize to the kidney. Other malignant tumor metastasis to the kidney is very unusual. Primary cervical cancer metastasis to adjacent pelvic organs and lymph nodes are well known followed by abdominal solid organs such as the liver and adrenal glands. However, reported primary cervical cancer metastasis to the kidney is extremely rare and mostly appeared as bilateral multiple renal masses. We report here on a rare case of unilateral single renal metastasis from primary cervical cancer after concur- rent chemoradiotherapy.

  13. Multiple myeloma.

    LENUS (Irish Health Repository)

    Collins, Conor D

    2012-02-01

    Advances in the imaging and treatment of multiple myeloma have occurred over the past decade. This article summarises the current status and highlights how an understanding of both is necessary for optimum management.

  14. Multiple myeloma: diagnosis and treatment.

    Science.gov (United States)

    Nau, Konrad C; Lewis, William D

    2008-10-01

    Multiple myeloma, the most common bone malignancy, is occurring with increasing frequency in older persons. Typical symptoms are bone pain, malaise, anemia, renal insufficiency, and hypercalcemia. Incidental discovery on comprehensive laboratory panels is common. The disease is diagnosed with serum or urine protein electrophoresis or immunofixation and bone marrow aspirate analysis. Skeletal radiographs are important in staging multiple myeloma and revealing lytic lesions, vertebral compression fractures, and osteoporosis. Magnetic resonance imaging and positron emission tomography or computed tomography are emerging as useful tools in the evaluation of patients with myeloma; magnetic resonance imaging is preferred for evaluating acute spinal compression. Nuclear bone scans and dual energy x-ray absorptiometry have no role in the diagnosis and staging of myeloma. The differential diagnosis of monoclonal gammopathies includes monoclonal gammopathy of uncertain significance, smoldering (asymptomatic) and symptomatic multiple myeloma, amyloidosis, B-cell non-Hodgkin lymphoma, Waldenström macroglobulinemia, and rare plasma cell leukemia and heavy chain diseases. Patients with monoclonal gammopathy of uncertain significance or smoldering multiple myeloma should be followed closely, but not treated. Symptomatic multiple myeloma is treated with chemotherapy followed by autologous stem cell transplantation, if possible. Melphalan, prednisolone, dexamethasone, vincristine, doxorubicin, bortezomib, and thalidomide and its analogue lenalidomide have been used successfully. It is important that family physicians recognize and appropriately treat multiple myeloma complications. Bone pain is treated with opiates, bisphosphonates, radiotherapy, vertebroplasty, or kyphoplasty; nephrotoxic nonsteroidal anti-inflammatory drugs should be avoided. Hypercalcemia is treated with isotonic saline infusions, steroids, furosemide, or bisphosphonates. Because of susceptibility to infections

  15. Involvement of multiple myeloma cell-derived exosomes in osteoclast differentiation

    OpenAIRE

    Raimondi, Lavinia; De Luca, Angela; Amodio, Nicola; Manno, Mauro; Raccosta, Samuele; Taverna, Simona; Bellavia, Daniele; Naselli, Flores; Fontana, Simona; Schillaci, Odessa; Giardino, Roberto; Fini, Milena; Tassone, Pierfrancesco; Santoro, Alessandra; De Leo, Giacomo

    2015-01-01

    Bone disease is the most frequent complication in multiple myeloma (MM) resulting in osteolytic lesions, bone pain, hypercalcemia and renal failure. In MM bone disease the perfect balance between bone-resorbing osteoclasts (OCs) and bone-forming osteoblasts (OBs) activity is lost in favour of OCs, thus resulting in skeletal disorders. Since exosomes have been described for their functional role in cancer progression, we here investigate whether MM cell-derived exosomes may be involved in OCs ...

  16. Triiodothyronine regulates cell growth and survival in renal cell cancer.

    Science.gov (United States)

    Czarnecka, Anna M; Matak, Damian; Szymanski, Lukasz; Czarnecka, Karolina H; Lewicki, Slawomir; Zdanowski, Robert; Brzezianska-Lasota, Ewa; Szczylik, Cezary

    2016-10-01

    Triiodothyronine plays an important role in the regulation of kidney cell growth, differentiation and metabolism. Patients with renal cell cancer who develop hypothyreosis during tyrosine kinase inhibitor (TKI) treatment have statistically longer survival. In this study, we developed cell based model of triiodothyronine (T3) analysis in RCC and we show the different effects of T3 on renal cell cancer (RCC) cell growth response and expression of the thyroid hormone receptor in human renal cell cancer cell lines from primary and metastatic tumors along with human kidney cancer stem cells. Wild-type thyroid hormone receptor is ubiquitously expressed in human renal cancer cell lines, but normalized against healthy renal proximal tube cell expression its level is upregulated in Caki-2, RCC6, SKRC-42, SKRC-45 cell lines. On the contrary the mRNA level in the 769-P, ACHN, HKCSC, and HEK293 cells is significantly decreased. The TRβ protein was abundant in the cytoplasm of the 786-O, Caki-2, RCC6, and SKRC-45 cells and in the nucleus of SKRC-42, ACHN, 769-P and cancer stem cells. T3 has promoting effect on the cell proliferation of HKCSC, Caki-2, ASE, ACHN, SK-RC-42, SMKT-R2, Caki-1, 786-0, and SK-RC-45 cells. Tyrosine kinase inhibitor, sunitinib, directly inhibits proliferation of RCC cells, while thyroid hormone receptor antagonist 1-850 (CAS 251310‑57-3) has less significant inhibitory impact. T3 stimulation does not abrogate inhibitory effect of sunitinib. Renal cancer tumor cells hypostimulated with T3 may be more responsive to tyrosine kinase inhibition. Moreover, some tumors may be considered as T3-independent and present aggressive phenotype with thyroid hormone receptor activated independently from the ligand. On the contrary proliferation induced by deregulated VHL and or c-Met pathways may transgress normal T3 mediated regulation of the cell cycle.

  17. Is retention of zoledronic acid onto bone different in multiple myeloma and breast cancer patients with bone metastasis?

    DEFF Research Database (Denmark)

    Søe, Kent; Plesner, Torben; Jakobsen, Erik H

    2013-01-01

    Zoledronic acid (Zol) is used to treat bone disease in both multiple myeloma (MM) and breast cancer patients with bone metastasis (BC). However, bones of MM and BC patients show a difference in retention of the bisphosphonate used for bone scintigraphy. Therefore, we hypothesized that disease...... of Zol correlated with bone-specific alkaline phosphatase (bALP) levels in BC (p = 0.001), and with CTX/bALP in Zol naive MM patients (p = 0.012). Especially in BC patients, WBrt correlated with age (p = 0.014) independently of kidney function. In MM patients WBrt was found to primarily correlate...... with the extent of bone disease (p = 0.028). Multivariate linear regression analyses of the entire cohort pointed out that WBrt of Zol was best predicted by age (p ...

  18. Drugs Approved for Multiple Myeloma

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for multiple myeloma and other plasma cell neoplasms. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters. The drug names link to NCI's Cancer Drug Information summaries.

  19. Primary cardiac lymphoma in a patient with concomitant renal cancer.

    Science.gov (United States)

    Severino, Davide; Santos, Beatriz; Costa, Cátia; Durão, David; Alves, Miguel; Monteiro, Isabel; Pitta, Luz; Leal, Margarida

    2015-12-01

    Primary cardiac lymphoma is defined as non-Hodgkin lymphoma involving the heart and/or pericardium. It is a rare cancer that primarily affects the right heart and in particular the right atrium. By contrast, renal cell carcinoma is a relatively common cancer, which in rare circumstances can metastasize to the heart. It is now known that there is an association between non-Hodgkin lymphoma and renal cell carcinoma, although the underlying mechanisms are not fully understood. The authors present a case of primary cardiac non-Hodgkin lymphoma in a patient with concomitant renal cell carcinoma and explore the possible reasons for this association. Copyright © 2015 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

  20. Apoptotic Effect of Anti myeloma Polyclonal Antibodies on The Growth of Myeloma Cells

    International Nuclear Information System (INIS)

    Abd El-Ghany, I.Y.; El-Kolaly, M.T.; Moustafa, K.A.; El-Shershaby, H.M.; Sayed, A.A.; Borai, I.H.; El-Lahloby, N.M.

    2013-01-01

    Multiple myeloma (MM) is a malignancy characterized by proliferation of plasma cells. Cancer immunotherapy is a major branch of biological therapy that utilizes living cells and their products. The aim of this study is to produce and evaluate the antiproliferative effect of anti myeloma polyclonal antibodies (with and without labelling with radioactive isotopes) against the growth of myeloma cells. The production of polyclonal antibodies (PAb) was generated by immunizing five healthy female mature white New-Zealand rabbits with myeloma cells (SP2/OR) through primary injection and five booster doses. The preparation of labelled anti myeloma antibodies was carried out using chloramine-T method and it was purified using PD-10 chromatographic column. The results obtained revealed that anti myeloma polyclonal antibodies inhibited proliferation and induced apoptosis of myeloma cell lines in vitro and induced apoptosis after serial intraperitoneal injection of PAb in ascites bearing mice in vivo. The present study suggested that the effect of labelled anti myeloma antibodies on myeloma cells growth inhibition was more effective than that of anti myeloma antibodies without labelling which is due to the cytotoxic effect of ionizing radiation. Apoptosis triggered by PAb was confirmed by flow cytometry, caspase -8 and -9 and β2-microglobulin.

  1. Targeted therapy of multiple myeloma.

    Science.gov (United States)

    Dolloff, Nathan G; Talamo, Giampaolo

    2013-01-01

    Multiple myeloma (MM) is a plasma cell malignancy and the second most common hematologic cancer. MM is characterized by the accumulation of malignant plasma cells within the bone marrow, and presents clinically with a broad range of symptoms, including hypercalcemia, renal insufficiency, anemia, and lytic bone lesions. MM is a heterogeneous disease associated with genomic instability, where patients may express multiple genetic abnormalities that affect several oncogenic pathways. Commonly detected genetic aberrations are translocations involving immunoglobulin heavy chain (IgH) switch regions (chromosome 14q32) and oncogenes such as c-maf [t(14:16)], cyclin D1 [t(11:14)], and FGFR3/MMSET [t(4:14)]. Advances in the basic understanding of MM and the development of novel agents, such as the immunomodulatory drugs (IMiDs) thalidomide and lenalidomide and the proteasome inhibitor bortezomib, have increased therapeutic response rates and prolonged patient survival. Despite these advances MM remains incurable in the majority of patients, and it is therefore critical to identify additional therapeutic strategies and targets for its treatment. In this chapter, we review the underlying genetic components of MM and discuss the results of recent clinical trials that demonstrate the effectiveness of targeted agents in the management of MM. In addition, we discuss experimental therapies that are currently in clinical development along with their molecular rationale in the treatment of MM.

  2. Multiple myeloma

    International Nuclear Information System (INIS)

    Sohn, Jeong Ick; Ha, Choon Ho; Choi, Karp Shik

    1994-01-01

    Multiple myeloma is a malignant plasma cell tumor that is thought to originate proliferation of a single clone of abnormal plasma cell resulting production of a whole monoclonal paraprotein. The authors experienced a case of multiple myeloma with severe mandibular osteolytic lesions in 46-year-old female. As a result of careful analysis of clinical, radiological, histopathological features, and laboratory findings, we diagnosed it as multiple myeloma, and the following results were obtained. 1. Main clinical symptoms were intermittent dull pain on the mandibular body area, abnormal sensation of lip and pain due to the fracture on the right clavicle. 2. Laboratory findings revealed M-spike, reversed serum albumin-globulin ratio, markedly elevated ESR and hypercalcemia. 3. Radiographically, multiple osteolytic punched-out radiolucencies were evident on the skull, zygoma, jaw bones, ribs, clavicle and upper extremities. Enlarged liver and increased uptakes on the lesional sites in RN scan were also observed. 4. Histopathologically, markedly hypercellular marrow with sheets of plasmoblasts and megakaryocytes were also observed.

  3. Hypercalcaemia : myeloma

    International Nuclear Information System (INIS)

    Naude, F; Venter, E.K.; Meyer, B.J.

    2004-01-01

    Full text: Introduction: A hypercalcaemic patient was referred to the Department of Nuclear Medicine to localise a parathyroid adenoma pre-operatively. Instead of an adenoma, multiple myeloma was diagnosed - comprimed histologically. Conclusion: Many conditions are associated with hypercalcaemia. Principal causes are primary hyperparathyroidism, advanced secondary hyperparathyroidism, milk alkali syndrome, vitamin D intoxication, Vit A intoxication, thiazide diuretic treatment, malignancy. Primary hyperparathyroidism (pHPT) is the most common cause in ambulatory adult patients, and malignancy the leading cause in hospitalised patients. Radioscintigraphic imaging of the parathyroids is one of the procedures used to localise the site of parathyroid adenomas. Currently 99mTc-sestamibi is the radioactive agent of choice. Hypercalcaemia is a relative frequent phenomenon in many malignant disorders, but seems to be insufficiently recognised. Various patterns of 99mTc-sestamibi uptake in the bone marrow of multiple myeloma patients have been reported: normal (negative), focal. diffuse and combined focal and diffuse. Diffuse and/or focal 99mTc-sestamibi uptake in the bone marrow is almost diagnostic of multiple myeloma. The distribution and intensity of 99mTc-sestamibi uptake are related to both the clinical status and stage of the disease, and can be used to estimate the success of therapy; a negative sestamibi study in patients receiving therapy indicates remission. (author)

  4. NCI collaborates with Multiple Myeloma Research Foundation

    Science.gov (United States)

    The National Cancer Institute (NCI) announced a collaboration with the Multiple Myeloma Research Foundation (MMRF) to incorporate MMRF's wealth of genomic and clinical data on the disease into the NCI Genomic Data Commons (GDC), a publicly available datab

  5. Hereditary leiomyomatosis and renal cell cancer presenting as metastatic kidney cancer at 18 years of age : implications for surveillance

    NARCIS (Netherlands)

    van Spaendonck-Zwarts, Karin Y.; Badeloe, Sadhanna; Oosting, Sjoukje F.; Hovenga, Sjoerd; Semmelink, Harry J. F.; van Moorselaar, R. Jeroen A.; van Waesberghe, Jan Hein; Mensenkamp, Arjen R.; Menko, Fred H.

    Hereditary leiomyomatosis and renal cell cancer (HLRCC) is an autosomal dominant syndrome characterized by skin piloleiomyomas, uterine leiomyomas and papillary type 2 renal cancer caused by germline mutations in the fumarate hydratase (FH) gene. Previously, we proposed renal imaging for FH mutation

  6. Two cases of cisplatin-induced permanent renal failure following neoadjuvant chemotherapy for esophageal cancer.

    Science.gov (United States)

    Sasaki, Tomohiko; Motoyama, Satoru; Komatsuda, Atsushi; Shibata, Hiroyuki; Sato, Yusuke; Yoshino, Kei; Wakita, Akiyuki; Saito, Hajime; Anbai, Akira; Jin, Mario; Minamiya, Yoshihiro

    2016-01-01

    We experienced two esophageal cancer patients who developed severe acute renal failure after neoadjuvant chemotherapy with cisplatin and 5-fluorourasil. After administration of cisplatin, their serum creatinine increased gradually until they required hemodialysis and their renal failure was permanent. In both cases, renal biopsy examination indicated partial recovery of the proximal tubule, but renal function did not recover. After these events, one patient underwent definitive radiotherapy and the other underwent esophagectomy for their esophageal cancers, while continuing dialysis. Both patients are alive without cancer recurrence. In these two cases of cisplatin-induced renal failure, renal biopsy examination showed only slight disorder of proximal tubules and tendency to recover. Although cisplatin-related nephrotoxicity is a well-recognized complication, there have been few reports of renal failure requiring hemodialysis in cancer patients. In this report, we present their clinical courses and the pathological findings of cisplatin-related renal failure. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  7. Local recurrences after laparoscopic resections for renal parenchymal cancer

    Directory of Open Access Journals (Sweden)

    Yu. G. Alyaev

    2017-01-01

    Full Text Available Introduction. Renal cancer constitutes 2–3 % of all tumors of the human body. Annually worldwide renal cancer morbidity increases by 2 %, about 90 % of cases are localized in the parenchyma.  Currently, treatment of localized forms of kidney cancer increasingly  incorporates kidney-preserving technologies.The objective is to evaluate the rate and causes of local renal cancer recurrence after laparoscopic resections of the organ for treatment of localized renal parenchymal cancer.Materials and methods. Retrospective analysis of 459 laparoscopic resections performed between June of 2011 to May of 2017 at the R. M. Fronstein Urology Clinic of the I. M. Sechenov First Moscow State Medical University of the Ministry of Health of Russia was performed.Results. Of 459 patients who underwent endoscopic surgical kidney resections with video, 399 patients were diagnosed with renal cancer during planned histological examination, among them 3 (0.75 %  patients had local recurrence. All patients were operated on with  laparoscopic access, in 1 case the surgery was complicated by  intraoperative bleeding which required conversion to nephrectomy. At the time of primary surgery, all patients with cancer recurrence were diagnosed with stage Т1b. Clear cell renal cell  carcinoma was verified in all patients by morphological examination,  and malignancy grade (nuclear differentiation per the Furman  grading system was 2 (in 2 patients and 3 (in 1 patient. In 2  patients, local recurrence was diagnosed 6 months after the surgery, in 1 patient – 12 months after the surgery. One case of local  recurrence in the area of previous resection was detected, in 1 case  dissemination of the process through paranephric tissue (apart from local recurrence was observed, and 1 case of recurrence in the bed of the removed kidney was diagnosed. All patients underwent repeat surgery in the clinic: 2 patients were operated on laparoscopically, 1  patient

  8. Polycystic kidney disease and cancer after renal transplantation.

    Science.gov (United States)

    Wetmore, James B; Calvet, James P; Yu, Alan S L; Lynch, Charles F; Wang, Connie J; Kasiske, Bertram L; Engels, Eric A

    2014-10-01

    Autosomal dominant polycystic kidney disease (ADPKD), the most common form of polycystic kidney disease (PKD), is a disorder with characteristics of neoplasia. However, it is not known whether renal transplant recipients with PKD have an increased risk of cancer. Data from the Scientific Registry of Transplant Recipients, which contains information on all solid organ transplant recipients in the United States, were linked to 15 population-based cancer registries in the United States. For PKD recipients, we compared overall cancer risk with that in the general population. We also compared cancer incidence in PKD versus non-PKD renal transplant recipients using Poisson regression, and we determined incidence rate ratios (IRRs) adjusted for age, sex, race/ethnicity, dialysis duration, and time since transplantation. The study included 10,166 kidney recipients with PKD and 107,339 without PKD. Cancer incidence in PKD recipients was 1233.6 per 100,000 person-years, 48% higher than expected in the general population (standardized incidence ratio, 1.48; 95% confidence interval [95% CI], 1.37 to 1.60), whereas cancer incidence in non-PKD recipients was 1119.1 per 100,000 person-years. The unadjusted incidence was higher in PKD than in non-PKD recipients (IRR, 1.10; 95% CI, 1.01 to 1.20). However, PKD recipients were older (median age at transplantation, 51 years versus 45 years for non-PKD recipients), and after multivariable adjustment, cancer incidence was lower in PKD recipients than in others (IRR, 0.84; 95% CI, 0.77 to 0.91). The reason for the lower cancer risk in PKD recipients is not known but may relate to biologic characteristics of ADPKD or to cancer risk behaviors associated with ADPKD. Copyright © 2014 by the American Society of Nephrology.

  9. Multiple Myeloma

    African Journals Online (AJOL)

    proteinuria was also a poor prognostic finding,. but only because of its association with renal failure. Patients with. Bence-Jones protcinur;a and normal renal ... chemotherapy. The mean time which elapsed before the criteria of response were achieved, was 7 months. Five ad- ditional patients who are at present being ...

  10. Feature selection and classification of MAQC-II breast cancer and multiple myeloma microarray gene expression data.

    Directory of Open Access Journals (Sweden)

    Qingzhong Liu

    Full Text Available Microarray data has a high dimension of variables but available datasets usually have only a small number of samples, thereby making the study of such datasets interesting and challenging. In the task of analyzing microarray data for the purpose of, e.g., predicting gene-disease association, feature selection is very important because it provides a way to handle the high dimensionality by exploiting information redundancy induced by associations among genetic markers. Judicious feature selection in microarray data analysis can result in significant reduction of cost while maintaining or improving the classification or prediction accuracy of learning machines that are employed to sort out the datasets. In this paper, we propose a gene selection method called Recursive Feature Addition (RFA, which combines supervised learning and statistical similarity measures. We compare our method with the following gene selection methods: Support Vector Machine Recursive Feature Elimination (SVMRFE, Leave-One-Out Calculation Sequential Forward Selection (LOOCSFS, Gradient based Leave-one-out Gene Selection (GLGS. To evaluate the performance of these gene selection methods, we employ several popular learning classifiers on the MicroArray Quality Control phase II on predictive modeling (MAQC-II breast cancer dataset and the MAQC-II multiple myeloma dataset. Experimental results show that gene selection is strictly paired with learning classifier. Overall, our approach outperforms other compared methods. The biological functional analysis based on the MAQC-II breast cancer dataset convinced us to apply our method for phenotype prediction. Additionally, learning classifiers also play important roles in the classification of microarray data and our experimental results indicate that the Nearest Mean Scale Classifier (NMSC is a good choice due to its prediction reliability and its stability across the three performance measurements: Testing accuracy, MCC values, and

  11. Long-Term Lithium Use and Risk of Renal and Upper Urinary Tract Cancers

    DEFF Research Database (Denmark)

    Pottegård, Anton; Hallas, Jesper; Jensen, Boye L

    2015-01-01

    Lithium induces proliferation in the epithelium of renal collecting ducts. A recent small-scale cohort study reported a strong association between use of lithium and increased risk of renal neoplasia. We therefore conducted a large-scale pharmacoepidemiologic study of the association between long...... stratified by stage and subtype of upper urinary tract cancer revealed slight but nonsignificant increases in the ORs for localized disease (OR, 1.6; 95% CI, 0.8-3.0) and for renal pelvis/ureter cancers (OR, 1.7; 95% CI, 0.5-5.4). In conclusion, in our nationwide case-control study, use of lithium......-term use of lithium and risk of upper urinary tract cancer, including renal cell cancer and cancers of the renal pelvis or ureter. We identified all histologically verified upper urinary tract cancer cases in Denmark between 2000 and 2012 from the Danish Cancer Registry. A total of 6477 cases were matched...

  12. Cellular immune responses against CT7 (MAGE-C1) and humoral responses against other cancer-testis antigens in multiple myeloma patients.

    Science.gov (United States)

    Lendvai, Nikoletta; Gnjatic, Sacha; Ritter, Erika; Mangone, Michael; Austin, Wayne; Reyner, Karina; Jayabalan, David; Niesvizky, Ruben; Jagannath, Sundar; Bhardwaj, Nina; Chen-Kiang, Selina; Old, Lloyd J; Cho, Hearn Jay

    2010-01-29

    The type I melanoma antigen gene (MAGE) proteins CT7 (MAGE-C1) and MAGE-A3 are commonly expressed in multiple myeloma (MM), and their expression correlates with increased plasma cell proliferation and poor clinical outcome. They belong to the cancer-testis antigen (CTAg) group of tumor-associated proteins, some of which elicit spontaneous immune responses in cancer patients. CT7 and MAGE-A3 are promising antigenic targets for therapeutic tumor vaccines in myeloma; therefore, it is critical to determine if they are immunogenic in MM patients. We analyzed cellular and humoral immune responses against CTAgs in patients with plasma cell dyscrasias: MM, monoclonal gammopathy of undetermined significance (MGUS), and Waldenström's macroglobulinemia (WM). Bone marrow lymphocytes from two of four untreated MM patients exhibited CT7-specific cellular immune responses as measured by an autologous cellular immunity assay, the first such immune response to CT7 to be reported in cancer patients. Sera from 24 patients were screened by ELISA for humoral immune responses to CTAgs. Two patients with MM demonstrated positive titers, one for MAGE-A1 and the other for SSX1. These data demonstrate that CTAgs, particularly CT7, are immunogenic in MM patients and merit further exploration as targets of immunological therapy in MM.

  13. Breast Cancer with Synchronous Renal Cell Carcinoma: A Rare Presentation.

    Science.gov (United States)

    Arjunan, Ravi; Kumar, Durgesh; Kumar, K V Veerendra; Premlatha, C S

    2016-10-01

    Primary cancer arising from multiple organs is a well known fact. Synchronous tumours have been most commonly associated with kidney cancer. Bladder, prostate, colorectal and lung cancer are the most common synchronous primaries with Renal Cell Carcinoma (RCC) identified till date. We found metachronous tumours of breast with RCC in literature search which included both metastatic tumours as well second primaries. Overall, 25 cases of metastatic breast tumours and eight cases of second primary in previously treated RCC have been reported in the literature. Here, we are reporting a case of synchronous presentation of carcinoma breast with RCC which is very rare because most of the multiple malignancies reported in the literature are metastatic tumours or metachronous breast malignancy with RCC.

  14. Fibroblast growth factor receptor 3 interacts with and activates TGFβ-activated kinase 1 tyrosine phosphorylation and NFκB signaling in multiple myeloma and bladder cancer.

    Directory of Open Access Journals (Sweden)

    Lisa Salazar

    Full Text Available Cancer is a major public health problem worldwide. In the United States alone, 1 in 4 deaths is due to cancer and for 2013 a total of 1,660,290 new cancer cases and 580,350 cancer-related deaths are projected. Comprehensive profiling of multiple cancer genomes has revealed a highly complex genetic landscape in which a large number of altered genes, varying from tumor to tumor, impact core biological pathways and processes. This has implications for therapeutic targeting of signaling networks in the development of treatments for specific cancers. The NFκB transcription factor is constitutively active in a number of hematologic and solid tumors, and many signaling pathways implicated in cancer are likely connected to NFκB activation. A critical mediator of NFκB activity is TGFβ-activated kinase 1 (TAK1. Here, we identify TAK1 as a novel interacting protein and target of fibroblast growth factor receptor 3 (FGFR3 tyrosine kinase activity. We further demonstrate that activating mutations in FGFR3 associated with both multiple myeloma and bladder cancer can modulate expression of genes that regulate NFκB signaling, and promote both NFκB transcriptional activity and cell adhesion in a manner dependent on TAK1 expression in both cancer cell types. Our findings suggest TAK1 as a potential therapeutic target for FGFR3-associated cancers, and other malignancies in which TAK1 contributes to constitutive NFκB activation.

  15. A POX on Renal Cancer Cells | Center for Cancer Research

    Science.gov (United States)

    Proline oxidase, or POX, is an enzyme responsible for metabolizing the amino acid proline. POX contributes to the regulation of cell death that occurs when cellular systems malfunction, a process called apoptosis. Previous studies have determined that levels of POX are reduced in several types of human cancer. Likewise, many cancer cells become resistant to apoptosis, suggesting a link between POX and cancer cell survival.

  16. Economic and clinical impact of multiple myeloma to managed care.

    Science.gov (United States)

    Cook, Richard

    2008-09-01

    Because of the development of novel agents such as immunomodulators, proteasome inhibitors, and bisphosphonates, the standards of care for the multiple myeloma (MM) patient have changed. The costs associated with current and emerging therapies, as well as supportive care, are significant and pose a tremendous financial burden to both patients and managed care. To review the economic impact of MM and to weigh the advantages and disadvantages of current treatments in bringing value for prolonged life versus the cost of treatment. This chapter will also discuss the need for thorough data review and pharmacoeconomic analyses to determine the most cost-effective therapies. Although MM accounts for only a small percentage of all cancer types, the costs associated with treating and managing it are among the highest. Recent developments in diagnosing, treating, and managing myeloma have led to novel treatment strategies. Immunomodulators, proteasome inhibitors, and bisphosphonates are improving response rates and preserving quality of life. However, these agents are not replacing older treatment modalities, but being used in addition to them. Intensive chemotherapy, stem cell transplantation, and supportive care are all important components in achieving treatment goals. Costs associated with stem cell transplants and complications of the disease add to the economic burden of myeloma. Additional costs for routine diagnostics to measure the progression of the disease or response to treatment need to be considered. Complications (e.g., lytic bone disease, infection, anemia, and renal failure) also add to morbidity and mortality, thus increasing the burden to the patient and the health care system as a whole. Financial and time constraints of caregivers must also be considered, as well as the added administrative burdens to health care providers. New standards of care in the treatment and management of myeloma are likely to lead to significant increases in costs. Although

  17. Multiple myeloma

    Science.gov (United States)

    ... may have bone pain, most often in the ribs or back. The cancer cells can weaken bones. As a result: You may develop broken bones (bone fractures) just from doing normal activities. If cancer grows ...

  18. Agricultural Exposures, Multiple Myeloma Etiology: Profile of Jonathan Hofmann

    Science.gov (United States)

    Tenure-track investigator Jonathan Hofmann, Ph.D., M.P.H., has established a research program in the Occupational and Environmental Epidemiology Branch focused on the role of agricultural exposures in the etiology of multiple myeloma and other cancers, and on understanding the biological mechanisms that influence the development and progression of multiple myeloma.

  19. Recent Advances in the Pathogenesis and Management of Cast Nephropathy (Myeloma Kidney

    Directory of Open Access Journals (Sweden)

    Stephanie Stringer

    2011-01-01

    Full Text Available Multiple myeloma is an incurable plasma cell malignancy that is often accompanied by renal failure; there are a number of potential causes of this, of which cast nephropathy is the most important. Renal failure is highly significant in myeloma, as patient survival can be stratified by the severity of the renal impairment. Consequently, there is an ongoing focus on the pathological basis of cast nephropathy and the optimal treatment regimens in this setting, including effective chemotherapy regimens to reduce light chain production and emerging extracorporeal techniques to remove circulating light chains. This paper bridges recent advances in the pathogenesis and management of cast nephropathy in multiple myeloma.

  20. Incidental renal tumours on low-dose CT lung cancer screening exams.

    Science.gov (United States)

    Pinsky, Paul F; Dunn, Barbara; Gierada, David; Nath, P Hrudaya; Munden, Reginald; Berland, Lincoln; Kramer, Barnett S

    2017-06-01

    Introduction Renal cancer incidence has increased markedly in the United States in recent decades, largely due to incidentally detected tumours from computed tomography imaging. Here, we analyze the potential for low-dose computed tomography lung cancer screening to detect renal cancer. Methods The National Lung Screening Trial randomized subjects to three annual screens with either low-dose computed tomography or chest X-ray. Eligibility criteria included 30 + pack-years, current smoking or quit within 15 years, and age 55-74. Subjects were followed for seven years. Low-dose computed tomography screening forms collected information on lung cancer and non-lung cancer abnormalities, including abnormalities below the diaphragm. A reader study was performed on a sample of National Lung Screening Trial low-dose computed tomography images assessing presence of abnormalities below the diaphragms and abnormalities suspicious for renal cancer. Results There were 26,722 and 26,732 subjects enrolled in the low-dose computed tomography and chest X-ray arms, respectively, and there were 104 and 85 renal cancer cases diagnosed, respectively (relative risk = 1.22, 95% CI: 0.9-1.5). From 75,126 low-dose computed tomography screens, there were 46 renal cancer diagnoses within one year. Abnormalities below the diaphragm rates were 39.1% in screens with renal cancer versus 4.1% in screens without (P cancer cases versus 13% of non-cases had abnormalities below the diaphragms; 55% of cases and 0.8% of non-cases had a finding suspicious for renal cancer (P cancers. The benefits to harms tradeoff of incidental detection of renal tumours on low-dose computed tomography is unknown.

  1. Recent advances in multiple myeloma: a Korean perspective.

    Science.gov (United States)

    Hong, Junshik; Lee, Jae Hoon

    2016-09-01

    Epidemiologically, multiple myeloma (MM) is a malignant disorder of plasma cells with a higher incidence among Western populations than among Asians. However, there is growing evidence of a recent increase in the age-standardized incidence rate (ASR) of MM in Asian countries, particularly Korea. Application of novel agents has resulted in significant improvement of treatment outcomes, and the advances are ongoing with the recent introduction and U.S. Food and Drug Administration's approval of newer agents, including carfilzomib, ixazomib, elotuzumab, and daratumumab. In concert with the technical advances in the cytogenetic and molecular diagnostics of MM, modifications of its diagnosis and staging system have been attempted for better risk stratification. The modified diagnostic criteria from the International Myeloma Working Group in 2014 enabled a strategy of more active treatment for some patients with smoldering MM, with an ultra-high risk of progression, and fine-tuned the definition of end-organ damage, known as CRAB (hypercalcemia, renal insufficiency, anemia, and bone lesions). Considering Korea's trend of aging at an unprecedented rate, we can expect that the ASR of MM will maintain a gradual increase for many years to come; therefore, MM will be a cancer of critical importance from both medical and socioeconomic perspectives in Korea.

  2. Continuous renal replacement therapy for acute renal failure in patients with cancer: a well-tolerated adjunct treatment

    Directory of Open Access Journals (Sweden)

    Rebecca Fischler

    2016-08-01

    Full Text Available Abstract Introduction – Acute renal failure (ARF has a poor prognosis in patients with cancer requiring intensive care unit (ICU admission. Our aim is finding prognostic factors for hospital mortality in patients with cancer with ARF requiring renal replacement therapy (RRT. Methods – In this retrospective study, all patients with cancer with ARF treated with continuous venovenous filtration (CVVHDF in the ICU of the Institut Jules Bordet, between January 1st 2003 and December 31st 2012, were included in the study.Results – 103 patients are assessed: men/women 69/34, median age 62 years, solid/haematologic tumours 68/35, median SAPS II 56. Mortality rate was 63%. Seven patients required chronic renal dialysis. After multivariate analysis, two variables were statistically associated with hospital mortality : more than one organ failure (including kidney (OR 5.918 ; 95% CI 2.184 – 16.038 ; p<0,001 and low albumin level (OR 3.341; 95% CI 1.229 – 9.077; p=0,02. Only minor complications related to CVVHDF have been documented.Conclusions – Despite the poor prognosis associated with ARF, CVVHDF is an effective and tolerable renal replacement technique in patients with cancer admitted to the ICU. Multiple organ failure and hypoalbuminemia, two independent prognostic factors for hospital mortality have to be considered when deciding for introducing RRT.

  3. Semiinvasive Aspergillosis Case Coexisting to Metastatic Renal Cell Cancer

    Directory of Open Access Journals (Sweden)

    Hatice Kilic

    2013-10-01

    Full Text Available Chronic necrotizing pulmonary aspergillosis (CNPA is defined as an cavity or mass lesion in the lung due to invasion of lung tissue by a fungus of the Aspergillosis species. It was described also as semiinvasive aspergillosis. Semiinvasive pulmonary aspergillosis is generally seen in patients with primer immunocompromised and it can be fatal in the event of late diagnose. We present 60 years old patient who had had renal cell cancer admitted to hospital with metastatic nodules in his chest X-ray and Thorax computed tomography. We have seen yellow colour of bronchial secretion in his bronchoscopy. Multipl mantar hyphae by A. Fumigatus was detected in his bronchial lavage cytology. Itrakonazol was administred to this patient. We review to this cases due to a semiinvasive aspergillosis was detected randomly when this case who had not both symptomatic and clinical sign by Aspergillosis is investigated.

  4. End Stage and Chronic Kidney Disease:Associations with Renal Cancer

    Directory of Open Access Journals (Sweden)

    Paul eRusso

    2012-04-01

    Full Text Available There is a well known association between end stage renal disease and the development of kidney cancer in the native kidney of patients requiring renal replacement therapy. There is now emerging evidence that lesser degrees of renal insufficiency (chronic kidney disease, CKD are also associated with an increased likelihood of cancer in general and kidney cancer in particular. Nephro pathological changes are commonly observed in the non tumor bearing portions of kidney resected at the time of partial and radical nephrectomy. In addition, patients with renal cancer are more likely to have CKD at the time of diagnosis and treatment than the general population. The exact mechanism by which renal insufficiency transforms normal kidney cells into tumor cells is not known. Possible mechanisms include uremic immune inhibition or increased exposure to circulating toxins not adequately cleared by the kidneys. Surgeons managing kidney tumors must have an increased awareness of their patient’s renal functional status as they plan their resection. Kidney sparing approaches, including partial nephrectomy or active surveillance in older and morbidly ill patients, can prevent CKD or delay the further decline in renal function which is well documented with radical nephrectomy. Despite emerging evidence that partial nephrectomy provides equivalent local tumor control to radical nephrectomy while at the same time preventing CKD, this operation remains under utilized in the United States and abroad. Increased awareness of the bi directional relationship between kidney function and kidney cancer is essential in the contemporary management of kidney cancer.

  5. State-of-the-Art Management of Complications of Myeloma and Its Treatment

    Directory of Open Access Journals (Sweden)

    Monique A. Hartley-Brown

    2010-01-01

    Full Text Available Multiple myeloma is an incurable disease, although patient survival has increased with the availability of novel agents. Both multiple myeloma and its therapies often affect the renal, immune, skeletal, hematologic, and nervous systems. The resulting organ dysfunctions often impair the quality of life of affected patients, complicate and limit subsequent therapies, and may result in significant mortality. Research on the treatment of complications of multiple myeloma has been limited; hence, preventative and management strategies for patients with these complications are heterogeneous and often based on anecdotal experience. In this paper, we review the effects of myeloma and the novel therapies on organ systems and suggest management strategies.

  6. Stages of Plasma Cell Neoplasms (Including Multiple Myeloma)

    Science.gov (United States)

    ... cancer treatment is also called biotherapy or immunotherapy. Immunomodulators are a type of biologic therapy. Thalidomide , lenalidomide , and pomalidomide are immunomodulators used to treat multiple myeloma and other plasma ...

  7. Treatment Options for Plasma Cell Neoplasms (Including Multiple Myeloma)

    Science.gov (United States)

    ... cancer treatment is also called biotherapy or immunotherapy. Immunomodulators are a type of biologic therapy. Thalidomide , lenalidomide , and pomalidomide are immunomodulators used to treat multiple myeloma and other plasma ...

  8. Multiple Myeloma: Patient Handbook

    Science.gov (United States)

    ... information about myeloma in a caring and compassionate man- ner. IMF InfoLine specialists can be reached at InfoLine@myeloma.org, or 800-452-CURE (2873) or 818-487-7455. Terms and definitions Albumin (ALB): Simple water-soluble protein that is ...

  9. Recurrent renal cancer in Birt–Hogg–Dubé syndrome: A case report

    Directory of Open Access Journals (Sweden)

    Hammad Ather

    2018-01-01

    Conclusion: In conclusion, it is important to identify this rare syndrome at early stages. Diagnosis for the patients with a positive family history for renal cell cancer and pneumothorax should be considered. FLCN sequencing should also be taken into account in patients and their families because incidence of renal cancer in BHD patients is very high and detection at early stages can prevent its metastasis.

  10. Tc-99m MIBI imaging for secondary skeletal involvement in breast and prostate cancers and multiple myeloma

    International Nuclear Information System (INIS)

    Zehra, F.; Haq, S.; Fatmi, S.; Safaqat, S.

    2004-01-01

    Objective:The Objective of the study was to evaluate the role of Tc-99m MIBI whole body imaging in assessing secondary osseous involvement in patients with malignancy of breast, prostate or multiple myeloma. In this study a total of 41 patients were included. Out of these 18 had breast carcinoma, 12 had prostate carcinoma and 11 were diagnosed cases of multiple myeloma. All patients had their whole body MIBI imaging done which was compared with MDP bone scan by employing some other diagnostic modality (plain radiographs, CT scan, MRI scan or histopathological evidence) to confirm the lesions detected by either of the scans. The results of all the studies were evaluated qualitatively by assessing the number of lesions visually by three experienced nuclear physicians. Quantitative analysis of the lesions was also done, by calculating the lesion to normal uptake ratio, to augment the findings of visual assessment and for statistical analysis. Results: Results obtained in this study by MIBI and MDP imaging varied significantly among different groups and subgroups of patients depending on the primary malignancy and stage of therapy. However results obtained by imaging of patients within a group and subgroup were consistent with each other. MIBI scan showed a sensitivity of 99% in cases of multiple myeloma, where MDP scan was only 16% sensitive. In case of pre-therapy patients of breast and prostate carcinoma, the sensitivity of MIBI scan came out to be 80% and 74% respectively. In patients who were on chemo/radiotherapy MIBI scan was 54% sensitive in patients with breast carcinoma and 38% sensitive in patients with prostate carcinoma. MDP scan showed a sensitivity of 100% in all the groups. The positive predictive value of MIBI scan came out to be 100% but that of MDP was 42-76% in different groups. It is therefore concluded that the most significant role of MIBI imaging is in detection of bone metastases secondary to breast and prostate carcinoma in pre

  11. CUTANEOUS INVOLVEMENT IN MULTIPLE MYELOMA AT AN UNUSUAL SITE: A RARE CASE REPORT

    Directory of Open Access Journals (Sweden)

    Lohit Kumar

    2015-05-01

    Full Text Available Multiple myeloma is a rare cancer. According to the most recent data from the Surveillance, Epidemiology, and End Results (SEER program, multiple myeloma is the second most common haematological malignancy in the U.S. (after non - Hodgkin lymphoma, constitutes 1% of all cancers and constitutes 2% of all cancer deaths. Cutaneous involvement of multiple myeloma during treatment period is uncommon with fewer described in literature. Moreover, metastatic cutaneous involvement at the sole of the foot during treatment period of a IgA kappa type multiple myeloma patient followed by death has not encountered in literature. We have reported such a case

  12. musculoskeletal presentation of multiple myeloma at general

    African Journals Online (AJOL)

    2014-09-01

    Sep 1, 2014 ... Results: A total of 62 patients were diagnosed with multiple myeloma, 63% were female. ... Conclusion: Presence of bone pain and anaemia should alert the clinician to investigate along the ... not found to fall among the ten most common cancers ..... Dugan LO, Dugan DA, Dugan WM Jr. Back pain: the.

  13. Cancers as wounds that do not heal: differences and similarities between renal regeneration/repair and renal cell carcinoma.

    Science.gov (United States)

    Riss, Joseph; Khanna, Chand; Koo, Seongjoon; Chandramouli, Gadisetti V R; Yang, Howard H; Hu, Ying; Kleiner, David E; Rosenwald, Andreas; Schaefer, Carl F; Ben-Sasson, Shmuel A; Yang, Liming; Powell, John; Kane, David W; Star, Robert A; Aprelikova, Olga; Bauer, Kristin; Vasselli, James R; Maranchie, Jodi K; Kohn, Kurt W; Buetow, Ken H; Linehan, W Marston; Weinstein, John N; Lee, Maxwell P; Klausner, Richard D; Barrett, J Carl

    2006-07-15

    Cancers have been described as wounds that do not heal, suggesting that the two share common features. By comparing microarray data from a model of renal regeneration and repair (RRR) with reported gene expression in renal cell carcinoma (RCC), we asked whether those two processes do, in fact, share molecular features and regulatory mechanisms. The majority (77%) of the genes expressed in RRR and RCC were concordantly regulated, whereas only 23% were discordant (i.e., changed in opposite directions). The orchestrated processes of regeneration, involving cell proliferation and immune response, were reflected in the concordant genes. The discordant gene signature revealed processes (e.g., morphogenesis and glycolysis) and pathways (e.g., hypoxia-inducible factor and insulin-like growth factor-I) that reflect the intrinsic pathologic nature of RCC. This is the first study that compares gene expression patterns in RCC and RRR. It does so, in particular, with relation to the hypothesis that RCC resembles the wound healing processes seen in RRR. However, careful attention to the genes that are regulated in the discordant direction provides new insights into the critical differences between renal carcinogenesis and wound healing. The observations reported here provide a conceptual framework for further efforts to understand the biology and to develop more effective diagnostic biomarkers and therapeutic strategies for renal tumors and renal ischemia.

  14. Clustering of cancer among families of cases with Hodgkin Lymphoma (HL, Multiple Myeloma (MM, Non-Hodgkin's Lymphoma (NHL, Soft Tissue Sarcoma (STS and control subjects

    Directory of Open Access Journals (Sweden)

    Karunanayake Chandima P

    2009-02-01

    Full Text Available Abstract Background A positive family history of chronic diseases including cancer can be used as an index of genetic and shared environmental influences. The tumours studied have several putative risk factors in common including occupational exposure to certain pesticides and a positive family history of cancer. Methods We conducted population-based studies of Hodgkin lymphoma (HL, Multiple Myeloma (MM, non-Hodgkin's Lymphoma (NHL, and Soft Tissue Sarcoma (STS among male incident case and control subjects in six Canadian provinces. The postal questionnaire was used to collect personal demographic data, a medical history, a lifetime occupational history, smoking pattern, and the information on family history of cancer. The family history of cancer was restricted to first degree relatives and included relationship to the index subjects and the types of tumours diagnosed among relatives. The information was collected on 1528 cases (HL (n = 316, MM (n = 342, NHL (n = 513, STS (n = 357 and 1506 age ± 2 years and province of residence matched control subjects. Conditional logistic regression analyses adjusted for the matching variables were conducted. Results We found that most families were cancer free, and a minority included two or more affected relatives. HL [(ORadj (95% CI 1.79 (1.33, 2.42], MM (1.38(1.07, 1.78, NHL (1.43 (1.15, 1.77, and STS cases (1.30(1.00, 1.68 had higher incidence of cancer if any first degree relative was affected with cancer compared to control families. Constructing mutually exclusive categories combining "family history of cancer" (yes, no and "pesticide exposure ≥10 hours per year" (yes, no indicated that a positive family history was important for HL (2.25(1.61, 3.15, and for the combination of the two exposures increased risk for MM (1.69(1.14,2.51. Also, a positive family history of cancer both with (1.72 (1.21, 2.45 and without pesticide exposure (1.43(1.12, 1.83 increased risk of NHL. Conclusion HL, MM, NHL

  15. Timing the Landmark Events in the Evolution of Clear Cell Renal Cell Cancer: TRACERx Renal

    DEFF Research Database (Denmark)

    Mitchell, Thomas J.; Turajlic, Samra; Rowan, Andrew

    2018-01-01

    Clear cell renal cell carcinoma (ccRCC) is characterized by near-universal loss of the short arm of chromosome 3, deleting several tumor suppressor genes. We analyzed whole genomes from 95 biopsies across 33 patients with clear cell renal cell carcinoma. We find hotspots of point mutations in the...

  16. Understanding familial and non-familial renal cell cancer.

    Science.gov (United States)

    Bodmer, Daniëlle; van den Hurk, Wilhelmina; van Groningen, Jan J M; Eleveld, Marc J; Martens, Gerard J M; Weterman, Marian A J; van Kessel, Ad Geurts

    2002-10-01

    Molecular genetic analysis of familial and non-familial cases of conventional renal cell carcinoma (RCC) revealed a critical role(s) for multiple genes on human chromosome 3. For some of these genes, e.g. VHL, such a role has been firmly established, whereas for others, definite confirmation is still pending. Additionally, a novel role for constitutional chromosome 3 translocations as risk factors for conventional RCC development is rapidly emerging. Also, several candidate loci have been mapped to other chromosomes in both familial and non-familial RCCs of distinct histologic subtypes. The MET gene on chromosome 7, for example, was found to be involved in both forms of papillary RCC. A PRCC-TFE3 fusion gene is typically encountered in t(X;1)-positive non-familial papillary RCCs and results in abrogation of the cell cycle mitotic spindle checkpoint in a dominant-negative fashion, thus leading to RCC. Together, these data turn human RCC into a model system in which different aspects of both familial and non-familial syndromes may act as novel paradigms for cancer development.

  17. Body Composition in Relation to Clinical Outcomes in Renal Cell Cancer

    NARCIS (Netherlands)

    Vrieling, Alina; Kampman, Ellen; Knijnenburg, Nathalja C.; Mulders, Peter F.; Sedelaar, J.P.M.; Baracos, Vickie E.; Kiemeney, Lambertus A.

    2016-01-01

    Context: Several studies suggest that body composition (ie, body proportions of muscle and fat defined by computed tomography) is associated with clinical outcomes of several cancer types, including renal cell cancer (RCC). Objective: To conduct a systematic review and meta-analysis of the evidence

  18. [Molecular biology of renal cancer: bases for genetic directed therapy in advanced disease].

    Science.gov (United States)

    Maroto Rey, José Pablo; Cillán Narvaez, Elena

    2013-06-01

    There has been expansion of therapeutic options in the management of metastatic renal cell carcinoma due to a better knowledge of the molecular biology of kidney cancers. There are different tumors grouped under the term renal cell carcinoma, being clear cell cancer the most frequent and accounting for 80% of kidney tumors. Mutations in the Von Hippel-Lindau gene can be identified in up to 80% of sporadic clear cell cancer, linking a genetically inheritable disease where vascular tumors are frequent, with renal cell cancer. Other histologic types present specific alterations in molecular pathways, like c-MET in papillary type I tumors, and Fumarase Hydratase in papillary type II tumors. Identification of the molecular alteration for a specific tumor may offer an opportunity for treatment selection based on biomarkers, and, in the future, for developing an engineering designed genetic treatment.

  19. Young Adult and Usual Adult Body Mass Index and Multiple Myeloma Risk: A Pooled Analysis in the International Multiple Myeloma Consortium (IMMC).

    Science.gov (United States)

    Birmann, Brenda M; Andreotti, Gabriella; De Roos, Anneclaire J; Camp, Nicola J; Chiu, Brian C H; Spinelli, John J; Becker, Nikolaus; Benhaim-Luzon, Véronique; Bhatti, Parveen; Boffetta, Paolo; Brennan, Paul; Brown, Elizabeth E; Cocco, Pierluigi; Costas, Laura; Cozen, Wendy; de Sanjosé, Silvia; Foretová, Lenka; Giles, Graham G; Maynadié, Marc; Moysich, Kirsten; Nieters, Alexandra; Staines, Anthony; Tricot, Guido; Weisenburger, Dennis; Zhang, Yawei; Baris, Dalsu; Purdue, Mark P

    2017-06-01

    Background: Multiple myeloma risk increases with higher adult body mass index (BMI). Emerging evidence also supports an association of young adult BMI with multiple myeloma. We undertook a pooled analysis of eight case-control studies to further evaluate anthropometric multiple myeloma risk factors, including young adult BMI. Methods: We conducted multivariable logistic regression analysis of usual adult anthropometric measures of 2,318 multiple myeloma cases and 9,609 controls, and of young adult BMI (age 25 or 30 years) for 1,164 cases and 3,629 controls. Results: In the pooled sample, multiple myeloma risk was positively associated with usual adult BMI; risk increased 9% per 5-kg/m 2 increase in BMI [OR, 1.09; 95% confidence interval (CI), 1.04-1.14; P = 0.007]. We observed significant heterogeneity by study design ( P = 0.04), noting the BMI-multiple myeloma association only for population-based studies ( P trend = 0.0003). Young adult BMI was also positively associated with multiple myeloma (per 5-kg/m 2 ; OR, 1.2; 95% CI, 1.1-1.3; P = 0.0002). Furthermore, we observed strong evidence of interaction between younger and usual adult BMI ( P interaction adult BMI may increase multiple myeloma risk and suggest that healthy BMI maintenance throughout life may confer an added benefit of multiple myeloma prevention. Cancer Epidemiol Biomarkers Prev; 26(6); 876-85. ©2017 AACR . ©2017 American Association for Cancer Research.

  20. Cerebral metastases from multiple myeloma

    International Nuclear Information System (INIS)

    Norum, J.; Wist, E.; Dahl, I.M.; University Hospital, Tromsoe

    1991-01-01

    The authors report a patient with multiple intracerebral lesions from myeloma. The case also demonstrates that myeloma is a radiosensitive tumour and that radiotherapy is important to keep in mind when intracranial lesions are revealed. (orig.)

  1. Renal donors with prostate cancer, no longer a reason to decline.

    Science.gov (United States)

    Dholakia, S; Johns, R; Muirhead, L; Papalois, V; Crane, J

    2016-01-01

    To fully assess the true risk of prostate cancer transmission in during renal transplantation. A full review of all existing literature relevant to the topic. There has not been a single documented case of transmission of prostate cancer during renal transplant. Prostate cancer in deceased organ donors has an incidence estimated between 3% and 18.5% and over 100 transplants have been performed using organs from donor with proven prostate cancer without issue. Transmission of prostate cancer through kidney transplantation seems very unlikely. The risks of remaining on the waiting list are outweighed by a transmission risk and the potential benefit makes the case to have clear guidelines about donor prostate malignancy when accepting potential organs. Copyright © 2015. Published by Elsevier Inc.

  2. Melanotic Xp11 Translocation Renal Cancer Managed With Radical Nephrectomy and IVC Tumor Thrombectomy

    Directory of Open Access Journals (Sweden)

    Iyad S. Khourdaji

    2017-01-01

    Full Text Available Melanotic Xp11 translocation renal cancer is a rarely observed neoplasm primarily affecting adolescents and young adults. Given the paucity of data describing this malignancy, its natural history and subsequent long-term management are not well understood. We report a case of melanotic Xp11 translocation with tumor thrombus extension managed with radical nephrectomy and inferior vena cava (IVC tumor thrombectomy. To our knowledge, this is the first case report to describe use of conventional tumor thrombectomy techniques in a patient with melanotic Xp11 translocation renal cancer.

  3. Specific immunotherapy in renal cancer: a systematic review.

    Science.gov (United States)

    Hirbod-Mobarakeh, Armin; Gordan, Hesam Addin; Zahiri, Zahra; Mirshahvalad, Mohammad; Hosseinverdi, Sima; Rini, Brian I; Rezaei, Nima

    2017-02-01

    Renal cell cancer (RCC) is the tenth most common malignancy in adults. In recent years, several approaches of active and passive immunotherapy have been studied extensively in clinical trials of patients with RCC. The aim of this systematic review was to assess the clinical efficacy of various approaches of specific immunotherapy in patients with RCC. We searched Medline, Scopus, CENTRAL, TRIP, DART, OpenGrey and ProQuest without any language filter through to 9 October 2015. One author reviewed search results for irrelevant and duplicate studies and two other authors independently extracted data from the studies. We collated study findings and calculated a weighted treatment effect across studies using Review Manager (version 5.3. Copenhagen: The Nordic Cochrane Centre, the Cochrane Collaboration). We identified 14 controlled studies with 4013 RCC patients after excluding irrelevant and duplicate studies from 11,319 references retrieved from a literature search. Overall, five autologous tumor cell vaccines, one peptide-based vaccine, one virus-based vaccine and one dendritic cell (DC)-based vaccine were studied in nine controlled studies of active specific immunotherapies. A total of three passive immunotherapies including autologous cytokine-induced killer (CIK) cells, auto lymphocyte therapy (ALT) and autologous lymphokine-activated killer (LAK) cells were studied in four controlled studies. The clinical efficacy of tumor lysate-pulsed DCs, with CIK cells was studied in one controlled trial concurrently. The overall quality of studies was fair. Meta-analysis of seven studies showed that patients undergoing specific immunotherapy had significantly higher overall survival (OS) than those in the control group [hazard ratio (HR) = 0.72; 95% confidence interval (CI) = 0.58-0.89, p = 0.003]. In addition, a meta-analysis of four studies showed that there was a significant difference in progression-free survival (PFS) between patients undergoing specific immunotherapy

  4. Immunomodulation of multiple myeloma.

    Science.gov (United States)

    Tohnya, Tanyifor M; Figg, William D

    2004-11-01

    Multiple myeloma is a multi-process disease, and these different processes are responsible for the reduced sensitivity to chemotherapy and radiotherapy, hence the relapse and refractory nature of multiple myeloma. Emphasis is now placed on the hypothesis that myeloma cell growth, inhibition of apoptosis and drug resistance are dependent on immunomodulatory cytokines such as IL-6 and pro-angiogenic factors such as VEGF. In addition to its anti-angiogenic effects, the immunomodulatory properties of thalidomide make it a possible therapy for patients with advanced multiple myeloma. This has lead to the clinical development of a number of immunomodulatory thalidomide analogues (IMiDs) which are more potent and have less side effects than the parent drug, thalidomide. In the August 15(th) issue of Journal of Clinical Oncology, Schey SA et al. suggested that an IMiD (CC-4047) maybe efficacious due to T-cell co-stimulation, and safe in patients with relapsed or refractory multiple myeloma. This article demonstrates a supporting role for IMiDs as immunomodulatory adjuvant therapy.

  5. Imaging features of renal complications after crizotinib treatment for non–small-cell lung cancer: a case report

    Directory of Open Access Journals (Sweden)

    Wan Ying Chan, MBBS

    2016-09-01

    Full Text Available Crizotinib has been approved for the treatment of advanced ALK-positive non–small cell lung cancer. Its use is associated with the development of complex renal cysts. However, there is limited literature regarding imaging features of renal cystic disease during crizotinib therapy and its complications or progression. Here, we describe a case of a patient with ALK-positive advanced non–small cell lung cancer who developed complex renal cyst during crizotinib treatment. The renal cyst is complicated by infection and abscess formation. Subsequent renal biopsy, antibiotics treatment, and open drainage of loculated renal abscess showed no malignant cells and contributed to the diagnosis. The imaging features should be recognized as renal cystic disease of crizotinib treatment and not to be mistaken as new metastasis and disease progression.

  6. [Association of Kaposi sarcoma--multiple myeloma. A new case].

    Science.gov (United States)

    Cohen, J D; Thomas, E; Garnier, N; Hellier, I; Durand, L; Guilhou, J J; Baldet, P; Blotman, F

    2000-11-01

    Kaposi's disease is an angiogenic multifocal cancer process that has several forms, namely Mediterranean, African, HIV-associated, and secondary to a preexisting immunodepressive state (hematological disorder, corticosteroid therapy, immunodepressive treatment). Whatever its form, Kaposi's sarcoma is probably associated with a chronic viral human herpes type 8 infection (HHV8). This virus has been implicated in the pathogenesis of multiple myeloma (17 cases recorded to date). In the present study, a further case of Kaposi's sarcoma associated with multiple myeloma has been reported. However, Epstein-Barr virus, cytomegalovirus, hepatitis B and C, HIV and HHV8 serologies were negative. Radiotherapy on the lower limbs was initiated. It is concluded that HHV8 does not appear to play a pathogenic role in cases of multiple myeloma, given the rarity of the association between Kaposi's sarcoma/multiple myeloma/HHV8.

  7. Pleural Effusion in Multiple Myeloma.

    Science.gov (United States)

    Wang, Zhuo; Xia, Guoguang; Lan, Ling; Liu, Fayong; Wang, Yanxun; Liu, Baoyue; Ding, Yi; Dai, Li; Zhang, Yunjian

    2016-01-01

    Pleural effusion is rarely observed in patients with multiple myeloma (MM). Myeloma cell infiltration or invasion to the pleura is very rare. This study aimed to investigate the clinical characteristics of pleural effusion in patients with MM. We retrospectively reviewed the medical records of patients diagnosed with pleural effusion, MM, and pleural effusion with MM between 2004 and 2014 at Beijing Jishuitan Hospital. The present study included patients with pleural effusion who underwent cytological, bacteriological, biochemical and other testing. The cytopathology of abnormal pleural effusion cells was not diagnostic, thus flow cytometry was performed. MM was defined using the diagnosis standard of NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) 2014 for MM. This study included 3,480 pleural effusion patients and 319 MM patients. There were 34 patients with both MM and pleural effusion (17 men and 17 women). The average age was 63 years (range, 48-84 years). Pleural effusion with MM was caused by congestive heart disease, chronic renal failure, hypoalbuminemia, pulmonary infarctions, cirrhosis, pulmonary arterial hypertension, parapneumonic effusion, tuberculous pleural effusion, and myelomatous pleural effusion (MPE). The diagnosis of MPE was confirmed by the detection of myeloma cells in the pleural fluid using flow cytometric analyses. There were only 2 MPE cases in our study. The first MPE case was a woman. The first clinical manifestation was pleural effusion, and the diagnosis was non-secretory MM, DSS stage IIIA (Durie-Salmon staging system); ISS stage I (the International Staging System). The second MPE case was a man who was diagnosed with MM IgA-κ, DSS stage IIIA; ISS stage II. The detection rate of MPE was very low. MPE tended to present with yellow exudates and the lack of physical and chemical characteristics. Furthermore, patients with MPE exhibited many yellow nodules on the pleura. These nodules were lobulated and had abundant

  8. PET/CT and MR imaging in myeloma

    Energy Technology Data Exchange (ETDEWEB)

    Mulligan, Michael E. [University of Maryland Medical Center, Department of Radiology, Baltimore, MD (United States); Badros, Ashraf Z. [University of Maryland, Department of Medicine, Marlene and Stewart Greenebaum Cancer Center, Baltimore, MD (United States)

    2007-01-15

    Myeloma is the most common primary bone malignancy. It accounts for 10% of all hematological malignancies and 1% of all cancers. In the United States, there are an estimated 16,000 new cases and over 11,000 deaths yearly due to myeloma. Plasma cell dyscrasias manifest themselves in a variety of forms that range from MGUS (monoclonal gammopathy of undetermined significance) and smoldering myeloma that require no therapy, to the ''malignant'' form of multiple myeloma. The role of imaging in the management of myeloma includes: an assessment of the extent of intramedullary bone disease, detection of any extramedullary foci, and severity of the disease at presentation; the identification and characterization of complications; subsequent assessment of disease status. This review will focus on the use of PET/CT and MR imaging for myeloma patients at the time of initial diagnosis and for follow-up management, based on current reports in the literature and our practice at the Marlene and Stewart Greenebaum Cancer Center, University of Maryland Medical Center in Baltimore, USA. (orig.)

  9. Hereditary Kidney Cancer Syndromes and Surgical Management of the Small Renal Mass.

    Science.gov (United States)

    Nguyen, Kevin A; Syed, Jamil S; Shuch, Brian

    2017-05-01

    The management of patients with hereditary kidney cancers presents unique challenges to clinicians. In addition to an earlier age of onset compared with patients with sporadic kidney cancer, those with hereditary kidney cancer syndromes often present with bilateral and/or multifocal renal tumors and are at risk for multiple de novo lesions. This population of patients may also present with extrarenal manifestations, which adds an additional layer of complexity. Physicians who manage these patients should be familiar with the underlying clinical characteristics of each hereditary kidney cancer syndrome and the suggested surgical approaches and recommendations of genetic testing for at-risk individuals. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Immunological Dysregulation in Multiple Myeloma Microenvironment

    OpenAIRE

    Romano, Alessandra; Conticello, Concetta; Cavalli, Maide; Vetro, Calogero; La Fauci, Alessia; Parrinello, Nunziatina Laura; Di Raimondo, Francesco

    2014-01-01

    Multiple Myeloma (MM) is a systemic hematologic disease due to uncontrolled proliferation of monoclonal plasma cells (PC) in bone marrow (BM). Emerging in other solid and liquid cancers, the host immune system and the microenvironment have a pivotal role for PC growth, proliferation, survival, migration, and resistance to drugs and are responsible for some clinical manifestations of MM. In MM, microenvironment is represented by the cellular component of a normal bone marrow together with extr...

  11. Understanding familial and non-familial renal cell cancer

    NARCIS (Netherlands)

    Bodmer, Daniëlle; van den Hurk, Wilhelmina; van Groningen, Jan J. M.; Eleveld, Marc J.; Martens, Gerard J. M.; Weterman, Marian A. J.; van Kessel, Ad Geurts

    2002-01-01

    Molecular genetic analysis of familial and non-familial cases of conventional renal cell carcinoma (RCC) revealed a critical role(s) for multiple genes on human chromosome 3. For some of these genes, e.g. VHL, such a role has been firmly established, whereas for others, definite confirmation is

  12. Understanding familial and non-familial renal cell cancer.

    NARCIS (Netherlands)

    Bodmer, D.; Hurk, W.H. van den; Groningen, J.J.M. van; Eleveld, M.J.; Martens, G.J.M.; Weterman, M.A.J.; Geurts van Kessel, A.H.M.

    2002-01-01

    Molecular genetic analysis of familial and non-familial cases of conventional renal cell carcinoma (RCC) revealed a critical role(s) for multiple genes on human chromosome 3. For some of these genes, e.g. VHL, such a role has been firmly established, whereas for others, definite confirmation is

  13. The role of radiation therapy in multimodality treatment for renal-cell cancer

    International Nuclear Information System (INIS)

    Semikoz, N.G.; Kudryashov, O.G.; Ponomar'ov, V.V.; Osipenkov, R.A.; Anyishchenko, A.O.; Kudryashova, S.M.

    2011-01-01

    The authors report the results of multimodality treatment for renal-cell cancer (pT any, N any, M0) using pre- operative large-fraction irradiation. Our findings demonstrate that radiation therapy does not aggravate the conditions for surgery and improves long-term results. The data about efficacy of multimodality treatment (palliative nephrectomy with radiation therapy) in patients with primary metastatic kidney cancer T any, N any, M1) are also reported.

  14. The Cancer Genome Atlas Comprehensive Molecular Characterization of Renal Cell Carcinoma

    NARCIS (Netherlands)

    Ricketts, Christopher J.; De Cubas, Aguirre A.; Fan, Huihui; Smith, Christof C.; Lang, Martin; Reznik, Ed; Bowlby, Reanne; Gibb, Ewan A.; Akbani, Rehan; Beroukhim, Rameen; Bottaro, Donald P.; Choueiri, Toni K.; Gibbs, Richard A.; Godwin, Andrew K.; Haake, Scott; Hakimi, A. Ari; Henske, Elizabeth P.; Hsieh, James J.; Ho, Thai H.; Kanchi, Rupa S.; Krishnan, Bhavani; Kwaitkowski, David J.; Lui, Wembin; Merino, Maria J.; Mills, Gordon B.; Myers, Jerome; Nickerson, Michael L.; Reuter, Victor E.; Schmidt, Laura S.; Shelley, Carl Simon; Shen, Hui; Shuch, Brian; Signoretti, Sabina; Srinivasan, Ramaprasad; Tamboli, Pheroze; Thomas, George; Vincent, Benjamin G.; Vocke, Cathy D.; Wheeler, David A.; Yang, Lixing; Kim, William T.; Robertson, A. Gordon; Caesar-Johnson, Samantha J.; Demchok, John A.; Felau, Ina; Kasapi, Melpomeni; Ferguson, Martin L.; Hutter, Carolyn M.; Sofia, Heidi J.; Tarnuzzer, Roy; Wang, Zhining; Yang, Liming; Zenklusen, Jean C.; Zhang, Jiashan (Julia); Chudamani, Sudha; Liu, Jia; Lolla, Laxmi; Naresh, Rashi; Pihl, Todd; Sun, Qiang; Wan, Yunhu; Wu, Ye; Cho, Juok; DeFreitas, Timothy; Frazer, Scott; Gehlenborg, Nils; Getz, Gad; Heiman, David I.; Kim, Jaegil; Lawrence, Michael S.; Lin, Pei; Meier, Sam; Noble, Michael S.; Saksena, Gordon; Voet, Doug; Zhang, Hailei; Bernard, Brady; Chambwe, Nyasha; Dhankani, Varsha; Knijnenburg, Theo; Kramer, Roger; Leinonen, Kalle; Liu, Yuexin; Miller, Michael; Reynolds, Sheila; Shmulevich, Ilya; Thorsson, Vesteinn; Zhang, Wei; Akbani, Rehan; Broom, Bradley M.; Hegde, Apurva M.; Ju, Zhenlin; Kanchi, Rupa S.; Korkut, Anil; Li, Jun; Liang, Han; Ling, Shiyun; Liu, Wenbin; Lu, Yiling; Mills, Gordon B.; Ng, Kwok Shing; Rao, Arvind; Ryan, Michael; Wang, Jing; Weinstein, John N.; Zhang, Jiexin; Abeshouse, Adam; Armenia, Joshua; Chakravarty, Debyani; Chatila, Walid K.; de Bruijn, Ino; Gao, Jianjiong; Gross, Benjamin E.; Heins, Zachary J.; Kundra, Ritika; La, Konnor; Ladanyi, Marc; Luna, Augustin; Nissan, Moriah G.; Ochoa, Angelica; Phillips, Sarah M.; Reznik, Ed; Sanchez-Vega, Francisco; Sander, Chris; Schultz, Nikolaus; Sheridan, Robert; Sumer, S. Onur; Sun, Yichao; Taylor, Barry S.; Wang, Jioajiao; Zhang, Hongxin; Anur, Pavana; Peto, Myron; Spellman, Paul; Benz, Christopher; Stuart, Joshua M.; Wong, Christopher K.; Yau, Christina; Hayes, D. Neil; Parker, Joel S.; Wilkerson, Matthew D.; Ally, Adrian; Balasundaram, Miruna; Bowlby, Reanne; Brooks, Denise; Carlsen, Rebecca; Chuah, Eric; Dhalla, Noreen; Holt, Robert; Jones, Steven J.M.; Kasaian, Katayoon; Lee, Darlene; Ma, Yussanne; Marra, Marco A.; Mayo, Michael; Moore, Richard A.; Mungall, Andrew J.; Mungall, Karen; Robertson, A. Gordon; Sadeghi, Sara; Schein, Jacqueline E.; Sipahimalani, Payal; Tam, Angela; Thiessen, Nina; Tse, Kane; Wong, Tina; Berger, Ashton C.; Beroukhim, Rameen; Cherniack, Andrew D.; Cibulskis, Carrie; Gabriel, Stacey B.; Gao, Galen F.; Ha, Gavin; Meyerson, Matthew; Schumacher, Steven E.; Shih, Juliann; Kucherlapati, Melanie H.; Kucherlapati, Raju S.; Baylin, Stephen; Cope, Leslie; Danilova, Ludmila; Bootwalla, Moiz S.; Lai, Phillip H.; Maglinte, Dennis T.; Van Den Berg, David J.; Weisenberger, Daniel J.; Auman, J. Todd; Balu, Saianand; Bodenheimer, Tom; Fan, Cheng; Hoadley, Katherine A.; Hoyle, Alan P.; Jefferys, Stuart R.; Jones, Corbin D.; Meng, Shaowu; Mieczkowski, Piotr A.; Mose, Lisle E.; Perou, Amy H.; Perou, Charles M.; Roach, Jeffrey; Shi, Yan; Simons, Janae V.; Skelly, Tara; Soloway, Matthew G.; Tan, Donghui; Veluvolu, Umadevi; Fan, Huihui; Hinoue, Toshinori; Laird, Peter W.; Shen, Hui; Zhou, Wanding; Bellair, Michelle; Chang, Kyle; Covington, Kyle; Creighton, Chad J.; Dinh, Huyen; Doddapaneni, Harsha Vardhan; Donehower, Lawrence A.; Drummond, Jennifer; Gibbs, Richard A.; Glenn, Robert; Hale, Walker; Han, Yi; Hu, Jianhong; Korchina, Viktoriya; Lee, Sandra; Lewis, Lora; Li, Wei; Liu, Xiuping; Morgan, Margaret; Morton, Donna; Muzny, Donna; Santibanez, Jireh; Sheth, Margi; Shinbrot, Eve; Wang, Linghua; Wang, Min; Wheeler, David A.; Xi, Liu; Zhao, Fengmei; Hess, Julian; Appelbaum, Elizabeth L.; Bailey, Matthew; Cordes, Matthew G.; Ding, Li; Fronick, Catrina C.; Fulton, Lucinda A.; Fulton, Robert S.; Kandoth, Cyriac; Mardis, Elaine R.; McLellan, Michael D.; Miller, Christopher A.; Schmidt, Heather K.; Wilson, Richard K.; Crain, Daniel; Curley, Erin; Gardner, Johanna; Lau, Kevin; Mallery, David; Morris, Scott; Paulauskis, Joseph; Penny, Robert; Shelton, Candace; Shelton, Troy; Sherman, Mark; Thompson, Eric; Yena, Peggy; Bowen, Jay; Gastier-Foster, Julie M.; Gerken, Mark; Leraas, Kristen M.; Lichtenberg, Tara M.; Ramirez, Nilsa C.; Wise, Lisa; Zmuda, Erik; Corcoran, Niall; Costello, Tony; Hovens, Christopher; Carvalho, Andre L.; de Carvalho, Ana C.; Fregnani, José H.; Longatto-Filho, Adhemar; Reis, Rui M.; Scapulatempo-Neto, Cristovam; Silveira, Henrique C.S.; Vidal, Daniel O.; Burnette, Andrew; Eschbacher, Jennifer; Hermes, Beth; Noss, Ardene; Singh, Rosy; Anderson, Matthew L.; Castro, Patricia D.; Ittmann, Michael; Huntsman, David; Kohl, Bernard; Le, Xuan; Thorp, Richard; Andry, Chris; Duffy, Elizabeth R.; Lyadov, Vladimir; Paklina, Oxana; Setdikova, Galiya; Shabunin, Alexey; Tavobilov, Mikhail; McPherson, Christopher; Warnick, Ronald; Berkowitz, Ross; Cramer, Daniel; Feltmate, Colleen; Horowitz, Neil; Kibel, Adam; Muto, Michael; Raut, Chandrajit P.; Malykh, Andrei; Barnholtz-Sloan, Jill S.; Barrett, Wendi; Devine, Karen; Fulop, Jordonna; Ostrom, Quinn T.; Shimmel, Kristen; Wolinsky, Yingli; Sloan, Andrew E.; De Rose, Agostino; Giuliante, Felice; Goodman, Marc; Karlan, Beth Y.; Hagedorn, Curt H.; Eckman, John; Harr, Jodi; Myers, Jerome; Tucker, Kelinda; Zach, Leigh Anne; Deyarmin, Brenda; Hu, Hai; Kvecher, Leonid; Larson, Caroline; Mural, Richard J.; Somiari, Stella; Vicha, Ales; Zelinka, Tomas; Bennett, Joseph; Iacocca, Mary; Rabeno, Brenda; Swanson, Patricia; Latour, Mathieu; Lacombe, Louis; Têtu, Bernard; Bergeron, Alain; McGraw, Mary; Staugaitis, Susan M.; Chabot, John; Hibshoosh, Hanina; Sepulveda, Antonia; Su, Tao; Wang, Timothy; Potapova, Olga; Voronina, Olga; Desjardins, Laurence; Mariani, Odette; Roman-Roman, Sergio; Sastre, Xavier; Stern, Marc Henri; Cheng, Feixiong; Signoretti, Sabina; Berchuck, Andrew; Bigner, Darell; Lipp, Eric; Marks, Jeffrey; McCall, Shannon; McLendon, Roger; Secord, Angeles; Sharp, Alexis; Behera, Madhusmita; Brat, Daniel J.; Chen, Amy; Delman, Keith; Force, Seth; Khuri, Fadlo; Magliocca, Kelly; Maithel, Shishir; Olson, Jeffrey J.; Owonikoko, Taofeek; Pickens, Alan; Ramalingam, Suresh; Shin, Dong M.; Sica, Gabriel; Van Meir, Erwin G.; Zhang, Hongzheng; Eijckenboom, Wil; Gillis, Ad; Korpershoek, Esther; Looijenga, Leendert; Oosterhuis, Wolter; Stoop, Hans; van Kessel, Kim E.; Zwarthoff, Ellen C.; Calatozzolo, Chiara; Cuppini, Lucia; Cuzzubbo, Stefania; DiMeco, Francesco; Finocchiaro, Gaetano; Mattei, Luca; Perin, Alessandro; Pollo, Bianca; Chen, Chu; Houck, John; Lohavanichbutr, Pawadee; Hartmann, Arndt; Stoehr, Christine; Stoehr, Robert; Taubert, Helge; Wach, Sven; Wullich, Bernd; Kycler, Witold; Murawa, Dawid; Wiznerowicz, Maciej; Chung, Ki; Edenfield, W. Jeffrey; Martin, Julie; Baudin, Eric; Bubley, Glenn; Bueno, Raphael; De Rienzo, Assunta; Richards, William G.; Kalkanis, Steven; Mikkelsen, Tom; Noushmehr, Houtan; Scarpace, Lisa; Girard, Nicolas; Aymerich, Marta; Campo, Elias; Giné, Eva; Guillermo, Armando López; Van Bang, Nguyen; Hanh, Phan Thi; Phu, Bui Duc; Tang, Yufang; Colman, Howard; Evason, Kimberley; Dottino, Peter R.; Martignetti, John A.; Gabra, Hani; Juhl, Hartmut; Akeredolu, Teniola; Stepa, Serghei; Hoon, Dave; Ahn, Keunsoo; Kang, Koo Jeong; Beuschlein, Felix; Breggia, Anne; Birrer, Michael; Bell, Debra; Borad, Mitesh; Bryce, Alan H.; Castle, Erik; Chandan, Vishal; Cheville, John; Copland, John A.; Farnell, Michael; Flotte, Thomas; Giama, Nasra; Ho, Thai; Kendrick, Michael; Kocher, Jean Pierre; Kopp, Karla; Moser, Catherine; Nagorney, David; O'Brien, Daniel; O'Neill, Brian Patrick; Patel, Tushar; Petersen, Gloria; Que, Florencia; Rivera, Michael; Roberts, Lewis; Smallridge, Robert; Smyrk, Thomas; Stanton, Melissa; Thompson, R. Houston; Torbenson, Michael; Yang, Ju Dong; Zhang, Lizhi; Brimo, Fadi; Ajani, Jaffer A.; Gonzalez, Ana Maria Angulo; Behrens, Carmen; Bondaruk, Jolanta; Broaddus, Russell; Czerniak, Bogdan; Esmaeli, Bita; Fujimoto, Junya; Gershenwald, Jeffrey; Guo, Charles; Lazar, Alexander J.; Logothetis, Christopher; Meric-Bernstam, Funda; Moran, Cesar; Ramondetta, Lois; Rice, David; Sood, Anil; Tamboli, Pheroze; Thompson, Timothy; Troncoso, Patricia; Tsao, Anne; Wistuba, Ignacio; Carter, Candace; Haydu, Lauren; Hersey, Peter; Jakrot, Valerie; Kakavand, Hojabr; Kefford, Richard; Lee, Kenneth; Long, Georgina; Mann, Graham; Quinn, Michael; Saw, Robyn; Scolyer, Richard; Shannon, Kerwin; Spillane, Andrew; Stretch, onathan; Synott, Maria; Thompson, John; Wilmott, James; Al-Ahmadie, Hikmat; Chan, Timothy A.; Ghossein, Ronald; Gopalan, Anuradha; Levine, Douglas A.; Reuter, Victor; Singer, Samuel; Singh, Bhuvanesh; Tien, Nguyen Viet; Broudy, Thomas; Mirsaidi, Cyrus; Nair, Praveen; Drwiega, Paul; Miller, Judy; Smith, Jennifer; Zaren, Howard; Park, Joong Won; Hung, Nguyen Phi; Kebebew, Electron; Linehan, W. Marston; Metwalli, Adam R.; Pacak, Karel; Pinto, Peter A.; Schiffman, Mark; Schmidt, Laura S.; Vocke, Cathy D.; Wentzensen, Nicolas; Worrell, Robert; Yang, Hannah; Moncrieff, Marc; Goparaju, Chandra; Melamed, Jonathan; Pass, Harvey; Botnariuc, Natalia; Caraman, Irina; Cernat, Mircea; Chemencedji, Inga; Clipca, Adrian; Doruc, Serghei; Gorincioi, Ghenadie; Mura, Sergiu; Pirtac, Maria; Stancul, Irina; Tcaciuc, Diana; Albert, Monique; Alexopoulou, Iakovina; Arnaout, Angel; Bartlett, John; Engel, Jay; Gilbert, Sebastien; Parfitt, Jeremy; Sekhon, Harman; Thomas, George; Rassl, Doris M.; Rintoul, Robert C.; Bifulco, Carlo; Tamakawa, Raina; Urba, Walter; Hayward, Nicholas; Timmers, Henri; Antenucci, Anna; Facciolo, Francesco; Grazi, Gianluca; Marino, Mirella; Merola, Roberta; de Krijger, Ronald; Gimenez-Roqueplo, Anne Paule; Piché, Alain; Chevalier, Simone; McKercher, Ginette; Birsoy, Kivanc; Barnett, Gene; Brewer, Cathy; Farver, Carol; Naska, Theresa; Pennell, Nathan A.; Raymond, Daniel; Schilero, Cathy; Smolenski, Kathy; Williams, Felicia; Morrison, Carl; Borgia, Jeffrey A.; Liptay, Michael J.; Pool, Mark; Seder, Christopher W.; Junker, Kerstin; Omberg, Larsson; Dinkin, Mikhail; Manikhas, George; Alvaro, Domenico; Bragazzi, Maria Consiglia; Cardinale, Vincenzo; Carpino, Guido; Gaudio, Eugenio; Chesla, David; Cottingham, Sandra; Dubina, Michael; Moiseenko, Fedor; Dhanasekaran, Renumathy; Becker, Karl Friedrich; Janssen, Klaus Peter; Slotta-Huspenina, Julia; Abdel-Rahman, Mohamed H.; Aziz, Dina; Bell, Sue; Cebulla, Colleen M.; Davis, Amy; Duell, Rebecca; Elder, J. Bradley; Hilty, Joe; Kumar, Bahavna; Lang, James; Lehman, Norman L.; Mandt, Randy; Nguyen, Phuong; Pilarski, Robert; Rai, Karan; Schoenfield, Lynn; Senecal, Kelly; Wakely, Paul; Hansen, Paul; Lechan, Ronald; Powers, James; Tischler, Arthur; Grizzle, William E.; Sexton, Katherine C.; Kastl, Alison; Henderson, Joel; Porten, Sima; Waldmann, Jens; Fassnacht, Martin; Asa, Sylvia L.; Schadendorf, Dirk; Couce, Marta; Graefen, Markus; Huland, Hartwig; Sauter, Guido; Schlomm, Thorsten; Simon, Ronald; Tennstedt, Pierre; Olabode, Oluwole; Nelson, Mark; Bathe, Oliver; Carroll, Peter R.; Chan, June M.; Disaia, Philip; Glenn, Pat; Kelley, Robin K.; Landen, Charles N.; Phillips, Joanna; Prados, Michael; Simko, Jeffry; Smith-McCune, Karen; VandenBerg, Scott; Roggin, Kevin; Fehrenbach, Ashley; Kendler, Ady; Sifri, Suzanne; Steele, Ruth; Jimeno, Antonio; Carey, Francis; Forgie, Ian; Mannelli, Massimo; Carney, Michael; Hernandez, Brenda; Campos, Benito; Herold-Mende, Christel; Jungk, Christin; Unterberg, Andreas; von Deimling, Andreas; Bossler, Aaron; Galbraith, Joseph; Jacobus, Laura; Knudson, Michael; Knutson, Tina; Ma, Deqin; Milhem, Mohammed; Sigmund, Rita; Godwin, Andrew K.; Madan, Rashna; Rosenthal, Howard G.; Adebamowo, Clement; Adebamowo, Sally N.; Boussioutas, Alex; Beer, David; Giordano, Thomas; Mes-Masson, Anne Marie; Saad, Fred; Bocklage, Therese; Landrum, Lisa; Mannel, Robert; Moore, Kathleen; Moxley, Katherine; Postier, Russel; Walker, Joan; Zuna, Rosemary; Feldman, Michael; Valdivieso, Federico; Dhir, Rajiv; Luketich, James; Pinero, Edna M.Mora; Quintero-Aguilo, Mario; Carlotti, Carlos Gilberto; Dos Santos, Jose Sebastião; Kemp, Rafael; Sankarankuty, Ajith; Tirapelli, Daniela; Catto, James; Agnew, Kathy; Swisher, Elizabeth; Creaney, Jenette; Robinson, Bruce; Shelley, Carl Simon; Godwin, Eryn M.; Kendall, Sara; Shipman, Cassaundra; Bradford, Carol; Carey, Thomas; Haddad, Andrea; Moyer, Jeffey; Peterson, Lisa; Prince, Mark; Rozek, Laura; Wolf, Gregory; Bowman, Rayleen; Fong, Kwun M.; Yang, Ian; Korst, Robert; Rathmell, W. Kimryn; Fantacone-Campbell, J. Leigh; Hooke, Jeffrey A.; Kovatich, Albert J.; Shriver, Craig D.; DiPersio, John; Drake, Bettina; Govindan, Ramaswamy; Heath, Sharon; Ley, Timothy; Van Tine, Brian; Westervelt, Peter; Rubin, Mark A.; Lee, Jung Il; Aredes, Natália D.; Mariamidze, Armaz; Spellman, Paul T.; Rathmell, W. Kimryn; Linehan, W. Marston

    2018-01-01

    Renal cell carcinoma (RCC) is not a single disease, but several histologically defined cancers with different genetic drivers, clinical courses, and therapeutic responses. The current study evaluated 843 RCC from the three major histologic subtypes, including 488 clear cell RCC, 274 papillary RCC,

  15. Metastasis is promoted by a bioenergetic switch: New targets for progressive renal cell cancer

    NARCIS (Netherlands)

    Langbein, Sigrun; Frederiks, Wilma M.; zur Hansen, Axel; Popa, Juljane; Lehmann, Jan; Weiss, Christel; Alken, Peter; Coy, Johannes F.

    2008-01-01

    Targeted therapies have demonstrated clinical benefit with limited impact on long-term disease specific survival in the treatment of renal cell cancer (RCC). New opportunities for the treatment of tumors that are resistant or have relapsed, are needed. Increased anaerobic glucose fermentation to

  16. Tumor infiltrating lymphocyte therapy for ovarian cancer and renal cell carcinoma

    DEFF Research Database (Denmark)

    Andersen, Rikke; Donia, Marco; Westergaard, Marie Christine Wulff

    2015-01-01

    stimulated the interest in developing this approach for other indications. Here, we summarize the early clinical data in the field of adoptive cell transfer therapy (ACT) using tumor-infiltrating lymphocytes for patients with renal cell carcinoma (RCC) and ovarian cancer (OC). In addition we describe...

  17. Cost utility analysis of everolimus in the treatment of metastatic renal cell cancer in the Netherlands

    NARCIS (Netherlands)

    Mihajlović, J.; Minović, I.; Bruinsma, A.; Postma, M.J.

    2013-01-01

    Objectives: Metastatic renal cell cancer (mRCC) is becoming an important part of Dutch health care expenditure due to expensive pharmaceutical options for disease control and lack of adequate prevention methods. New targeted therapeutics, such as sunitinib, sorafenib and everolimus, have recently

  18. Renal Cancer Biomarkers | NCI Technology Transfer Center | TTC

    Science.gov (United States)

    The National Cancer Institute's Laboratory of Proteomics and Analytical Technologies is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize diagnostic, therapeutic and prognostic cancer biomarkers from clinical specimens.

  19. Adjuvant therapy for locally advanced renal cell cancer: A systematic review with meta-analysis

    Directory of Open Access Journals (Sweden)

    Lima Carmen SP

    2011-03-01

    Full Text Available Abstract Background Many adjuvant trials have been undertaken in an attempt to reduce the risk of recurrence among patients who undergo surgical resection for locally advanced renal cancer. However, no clear benefit has been identified to date. This systematic review was conducted to examine the exact role of adjuvant therapy in renal cancer setting. Methods Randomized controlled trials were searched comparing adjuvant therapy (chemotherapy, vaccine, immunotherapy, biochemotherapy versus no active treatment after surgery among renal cell cancer patients. Outcomes were overall survival (OS, disease-free survival (DFS, and severe toxicities. Risk ratios (RR, hazard ratios (HR and 95% confidence intervals were calculated using a fixed-effects meta-analysis. Heterogeneity was measured by I2. Different strategies of adjuvant treatment were evaluated separately. Results Ten studies (2,609 patients were included. Adjuvant therapy provided no benefits in terms of OS (HR 1.07; 95%CI 0.89 to 1.28; P = 0.48 I2 = 0% or DFS (HR 1.03; 95%CI 0.87 to 1.21; P = 0.77 I2 = 15% when compared to no treatment. No subgroup analysis (immunotherapy, vaccines, biochemotherapy and hormone therapy had relevant results. Toxicity evaluation depicted a significantly higher frequency of serious adverse events in the adjuvant group. Conclusions This analysis provided no support for the hypothesis that the agents studied provide any clinical benefit for renal cancer patients although they increase the risk of toxic effects. Randomized trials are underway to test targeted therapies, which might open a new therapeutic frontier. Until these trials yield results, no adjuvant therapy can be recommended for patients who undergo surgical resection for renal cell cancer.

  20. Monoclonal antibodies in myeloma

    DEFF Research Database (Denmark)

    Sondergeld, P.; van de Donk, N. W. C. J.; Richardson, P. G.

    2015-01-01

    The development of monoclonal antibodies (mAbs) for the treatment of disease goes back to the vision of Paul Ehrlich in the late 19th century; however, the first successful treatment with a mAb was not until 1982, in a lymphoma patient. In multiple myeloma, mAbs are a very recent and exciting add...

  1. Multiple myeloma in a captive lion (Panthera leo

    Directory of Open Access Journals (Sweden)

    Adrian S.W. Tordiffe

    2013-09-01

    Full Text Available Multiple myeloma is a rare, systemic proliferation of neoplastic plasma cells. A case was reported in an 11-year-old male captive lion (Panthera leo at the National Zoological Gardens of South Africa, Pretoria. The classic features of symptomatic multiple myeloma were all evident in this case; namely osteolytic lesions, monoclonal gammopathy in the serum with excretion of monoclonal proteins in the urine, neoplastic plasma cells in the bone marrow and associated renal failure and anaemia. In addition, similar to the common pattern of this disease in domestic felids, at least three extramedullary tumours were found and several organs were infiltrated by neoplastic plasma cells. The cytoplasm of approximately 50%of the neoplastic round cells, including a few giant myeloma cells, stained weakly to strongly using immunohistochemical stains for B-lymphocytes (CD79a. The normal haematological parameters and lack of any osteolytic lesions in the lion at the time of the first evaluation suggest that the primary neoplastic cells could have originated from one of the extramedullary tumour sites. Only two cases of multiple myeloma have previously been reported in captive wild felids. To the authors’ knowledge, there are no case reports of multiple myeloma in lions.

  2. Renal Toxicity of Adjuvant Chemoradiotherapy With Cisplatin in Gastric Cancer

    International Nuclear Information System (INIS)

    Welz, Stefan; Hehr, Thomas; Kollmannsberger, Christian; Bokemeyer, Carsten; Belka, Claus; Budach, Wilfried

    2007-01-01

    Purpose: Adjuvant, 5-fluorouracil (5-FU)-based chemoradiotherapy for completely resected high-risk gastric adenocarcinoma has been shown to improve survival in a randomized Intergroup trial. However, the results still showed an unsatisfactory outcome. On the basis of previously reported results of a Phase II trial using a more aggressive, cisplatin-containing chemoradiotherapy schedule, we investigated the effects of this approach on long-term renal function. Patients and Methods: Between December 2000 and September 2003, 27 patients were treated at Tuebingen University in a Phase II multicenter trial investigating adjuvant chemoradiotherapy. The adjuvant chemoradiotherapy consisted of two cycles of adjuvant 5-FU, folinic acid, cisplatin (200 mg/m 2 ), and paclitaxel before and after radiotherapy (45 Gy in 1.8-Gy fractions) with daily concomitant 5-FU (225 mg/m 2 /24 h). A dose constraint of ≤12 Gy for 37.5% of the functional volume of both kidneys was used. Renal function was assessed by the changes in creatinine and creatinine clearance during follow-up. Results: The prescribed 45 Gy was administered to 100% of the patients, and the cumulative cisplatin dose was 200 mg/m 2 in 74% of all patients. In 89%, the constraints concerning the renal absorbed doses were met. The median follow-up for the creatinine and clearance values was 30 and 26 months, respectively. The creatinine values tended to worsen over time without reaching critical levels. We were unable to demonstrate a significant dose-response relationship for renal damage in the tested dose range. Conclusions: Using a dose constraint of ≤12 Gy for 37.5% of the functional volume of both kidneys appears to be safe at a median follow-up of 2 years for a cumulative cisplatin dose of 200 mg/m 2 administered before and after simultaneous 5-FU and radiotherapy

  3. Inhibition of fatty acid metabolism reduces human myeloma cells proliferation.

    Directory of Open Access Journals (Sweden)

    José Manuel Tirado-Vélez

    Full Text Available Multiple myeloma is a haematological malignancy characterized by the clonal proliferation of plasma cells. It has been proposed that targeting cancer cell metabolism would provide a new selective anticancer therapeutic strategy. In this work, we tested the hypothesis that inhibition of β-oxidation and de novo fatty acid synthesis would reduce cell proliferation in human myeloma cells. We evaluated the effect of etomoxir and orlistat on fatty acid metabolism, glucose metabolism, cell cycle distribution, proliferation, cell death and expression of G1/S phase regulatory proteins in myeloma cells. Etomoxir and orlistat inhibited β-oxidation and de novo fatty acid synthesis respectively in myeloma cells, without altering significantly glucose metabolism. These effects were associated with reduced cell viability and cell cycle arrest in G0/G1. Specifically, etomoxir and orlistat reduced by 40-70% myeloma cells proliferation. The combination of etomoxir and orlistat resulted in an additive inhibitory effect on cell proliferation. Orlistat induced apoptosis and sensitized RPMI-8226 cells to apoptosis induction by bortezomib, whereas apoptosis was not altered by etomoxir. Finally, the inhibitory effect of both drugs on cell proliferation was associated with reduced p21 protein levels and phosphorylation levels of retinoblastoma protein. In conclusion, inhibition of fatty acid metabolism represents a potential therapeutic approach to treat human multiple myeloma.

  4. Culture in embryonic kidney serum and xeno-free media as renal cell carcinoma and renal cell carcinoma cancer stem cells research model.

    Science.gov (United States)

    Krawczyk, Krzysztof M; Matak, Damian; Szymanski, Lukasz; Szczylik, Cezary; Porta, Camillo; Czarnecka, Anna M

    2018-04-01

    The use of fetal bovine serum hinders obtaining reproducible experimental results and should also be removed in hormone and growth factor studies. In particular hormones found in FBS act globally on cancer cell physiology and influence transcriptome and metabolome. The aim of our study was to develop a renal carcinoma serum free culture model optimized for (embryonal) renal cells in order to select the best study model for downstream auto-, para- or endocrine research. Secondary aim was to verify renal carcinoma stem cell culture for this application. In the study, we have cultured renal cell carcinoma primary tumour cell line (786-0) as well as human kidney cancer stem cells in standard 2D monolayer cultures in Roswell Park Memorial Institute Medium or Dulbecco's Modified Eagle's Medium and Complete Human Kidney Cancer Stem Cell Medium, respectively. Serum-free, animal-component free Human Embryonic Kidney 293 media were tested. Our results revealed that xeno-free embryonal renal cells optimized culture media provide a useful tool in RCC cancer biology research and at the same time enable effective growth of RCC. We propose bio-mimic RCC cell culture model with specific serum-free and xeno-free medium that promote RCC cell viability.

  5. Renal function and symptoms/adverse effects in opioid-treated patients with cancer

    DEFF Research Database (Denmark)

    Kurita, G P; Lundström, S; Sjøgren, P

    2015-01-01

    BACKGROUND: Renal impairment and the risk of toxicity caused by accumulation of opioids and/or active metabolites is an under-investigated issue. This study aimed at analysing if symptoms/adverse effects in opioid-treated patients with cancer were associated with renal function. METHODS: Cross...... loss of appetite (P = 0.04). No other significant associations were found. CONCLUSION: Only severe constipation and loss of appetite were associated with low GFR in patients treated with morphine. Oxycodone and fentanyl, in relation to the symptoms studied, seem to be safe as used and titrated...

  6. Quantitative promoter methylation analysis of multiple cancer-related genes in renal cell tumors

    Directory of Open Access Journals (Sweden)

    Oliveira Jorge

    2007-07-01

    Full Text Available Abstract Background Aberrant promoter hypermethylation of cancer-associated genes occurs frequently during carcinogenesis and may serve as a cancer biomarker. In this study we aimed at defining a quantitative gene promoter methylation panel that might identify the most prevalent types of renal cell tumors. Methods A panel of 18 gene promoters was assessed by quantitative methylation-specific PCR (QMSP in 85 primarily resected renal tumors representing the four major histologic subtypes (52 clear cell (ccRCC, 13 papillary (pRCC, 10 chromophobe (chRCC, and 10 oncocytomas and 62 paired normal tissue samples. After genomic DNA isolation and sodium bisulfite modification, methylation levels were determined and correlated with standard clinicopathological parameters. Results Significant differences in methylation levels among the four subtypes of renal tumors were found for CDH1 (p = 0.0007, PTGS2 (p = 0.002, and RASSF1A (p = 0.0001. CDH1 hypermethylation levels were significantly higher in ccRCC compared to chRCC and oncocytoma (p = 0.00016 and p = 0.0034, respectively, whereas PTGS2 methylation levels were significantly higher in ccRCC compared to pRCC (p = 0.004. RASSF1A methylation levels were significantly higher in pRCC than in normal tissue (p = 0.035. In pRCC, CDH1 and RASSF1A methylation levels were inversely correlated with tumor stage (p = 0.031 and nuclear grade (p = 0.022, respectively. Conclusion The major subtypes of renal epithelial neoplasms display differential aberrant CDH1, PTGS2, and RASSF1A promoter methylation levels. This gene panel might contribute to a more accurate discrimination among common renal tumors, improving preoperative assessment and therapeutic decision-making in patients harboring suspicious renal masses.

  7. Quantitative promoter methylation analysis of multiple cancer-related genes in renal cell tumors

    International Nuclear Information System (INIS)

    Costa, Vera L; Henrique, Rui; Ribeiro, Franclim R; Pinto, Mafalda; Oliveira, Jorge; Lobo, Francisco; Teixeira, Manuel R; Jerónimo, Carmen

    2007-01-01

    Aberrant promoter hypermethylation of cancer-associated genes occurs frequently during carcinogenesis and may serve as a cancer biomarker. In this study we aimed at defining a quantitative gene promoter methylation panel that might identify the most prevalent types of renal cell tumors. A panel of 18 gene promoters was assessed by quantitative methylation-specific PCR (QMSP) in 85 primarily resected renal tumors representing the four major histologic subtypes (52 clear cell (ccRCC), 13 papillary (pRCC), 10 chromophobe (chRCC), and 10 oncocytomas) and 62 paired normal tissue samples. After genomic DNA isolation and sodium bisulfite modification, methylation levels were determined and correlated with standard clinicopathological parameters. Significant differences in methylation levels among the four subtypes of renal tumors were found for CDH1 (p = 0.0007), PTGS2 (p = 0.002), and RASSF1A (p = 0.0001). CDH1 hypermethylation levels were significantly higher in ccRCC compared to chRCC and oncocytoma (p = 0.00016 and p = 0.0034, respectively), whereas PTGS2 methylation levels were significantly higher in ccRCC compared to pRCC (p = 0.004). RASSF1A methylation levels were significantly higher in pRCC than in normal tissue (p = 0.035). In pRCC, CDH1 and RASSF1A methylation levels were inversely correlated with tumor stage (p = 0.031) and nuclear grade (p = 0.022), respectively. The major subtypes of renal epithelial neoplasms display differential aberrant CDH1, PTGS2, and RASSF1A promoter methylation levels. This gene panel might contribute to a more accurate discrimination among common renal tumors, improving preoperative assessment and therapeutic decision-making in patients harboring suspicious renal masses

  8. Hypophosphatemic osteomalacia: an unusual clinical presentation of multiple myeloma.

    Science.gov (United States)

    Reyskens, M; Sleurs, K; Verresen, L; Janssen, M; van den Bergh, J; van den Berg, J; Geusens, P

    2015-07-01

    An unusual case of a 75-year-old man is presented who had multiple stress fractures due to adult onset hypophosphatemic osteomalacia, which was the result of Fanconi syndrome, with light chain cast proximal tubulopathy due to multiple myeloma. A 75-year-old man presented with diffuse pain and muscle weakness. He had multiple stress fractures, low serum phosphate, decreased renal tubular reabsorption of phosphate, and normal PTH and FGF23, indicating adult onset hypophosphatemic osteomalacia. Phosphate supplements with calcitriol resulted in clinical recovery and healing of stress fractures. Because of proteinuria, a renal biopsy was performed that revealed Fanconi syndrome with light chain cast proximal tubulopathy and light kappa chains were found in serum and urine. A bone biopsy confirmed the diagnosis of multiple myeloma, and treatment with chemotherapy resulted in cytological and clinical recovery.

  9. Xenobiotic Metabolizing Gene Variants and Renal Cell Cancer: A Multicenter Study

    Energy Technology Data Exchange (ETDEWEB)

    Heck, Julia E. [International Agency for Research on Cancer, Lyon (France); Department of Epidemiology, School of Public Health, University of California Los Angeles, Los Angeles, CA (United States); Moore, Lee E. [Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD (United States); Lee, Yuan-Chin A. [International Agency for Research on Cancer, Lyon (France); Department of Epidemiology, School of Public Health, University of California Los Angeles, Los Angeles, CA (United States); McKay, James D. [International Agency for Research on Cancer, Lyon (France); Hung, Rayjean J. [Samuel Lunenfeld Research Institute of Mount Sinai Hospital, Toronto, ON (Canada); Karami, Sara [Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD (United States); Gaborieau, Valérie [International Agency for Research on Cancer, Lyon (France); Szeszenia-Dabrowska, Neonila [Department of Epidemiology, Institute of Occupational Medicine, Lodz (Poland); Zaridze, David G. [Cancer Research Centre, Institute of Carcinogenesis, Moscow (Russian Federation); Mukeriya, Anush [Cancer Research Centre, Department of Epidemiology, Moscow (Russian Federation); Mates, Dana [Institute of Public Health, Bucharest (Romania); Foretova, Lenka [Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Brno (Czech Republic); Janout, Vladimir; Kollárová, Helena [Department of Preventive Medicine, Faculty of Medicine, Palacky University, Olomouc (Czech Republic); Bencko, Vladimir [First Faculty of Medicine, Institute of Hygiene and Epidemiology, Charles University in Prague, Prague, Czech Republic (Czech Republic); Rothman, Nathaniel [Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD (United States); Brennan, Paul [International Agency for Research on Cancer, Lyon (France); Chow, Wong-Ho [Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD (United States); Boffetta, Paolo, E-mail: paolo.boffetta@mssm.edu [International Prevention Research Institute, Lyon (France); Tisch Cancer Institute, Mt. Sinai School of Medicine, New York, NY (United States)

    2012-02-20

    Background: The countries of Central and Eastern Europe have among the highest worldwide rates of renal cell cancer (RCC). Few studies have examined whether genetic variation in xenobiotic metabolic pathway genes may modify risk for this cancer. Methods: The Central and Eastern Europe Renal Cell Cancer study was a hospital-based case–control study conducted between 1998 and 2003 across seven centers in Central and Eastern Europe. Detailed data were collected from 874 cases and 2053 controls on demographics, work history, and occupational exposure to chemical agents. Genes [cytochrome P-450 family, N-acetyltransferases, NAD(P)H:quinone oxidoreductase I (NQO1), microsomal epoxide hydrolase (mEH), catechol-O-methyltransferase (COMT), uridine diphosphate-glucuronosyltransferase (UGT)] were selected for the present analysis based on their putative role in xenobiotic metabolism. Haplotypes were calculated using fastPhase. Odds ratios and 95% confidence intervals were estimated by unconditional logistic regression adjusted for country of residence, age, sex, smoking, alcohol intake, obesity, and hypertension. Results: We observed an increased risk of RCC with one SNP. After adjustment for multiple comparisons it did not remain significant. Neither NAT1 nor NAT2 slow acetylation was associated with disease. Conclusion: We observed no association between this pathway and renal cell cancer.

  10. Xenobiotic Metabolizing Gene Variants and Renal Cell Cancer: A Multicenter Study

    International Nuclear Information System (INIS)

    Heck, Julia E.; Moore, Lee E.; Lee, Yuan-Chin A.; McKay, James D.; Hung, Rayjean J.; Karami, Sara; Gaborieau, Valérie; Szeszenia-Dabrowska, Neonila; Zaridze, David G.; Mukeriya, Anush; Mates, Dana; Foretova, Lenka; Janout, Vladimir; Kollárová, Helena; Bencko, Vladimir; Rothman, Nathaniel; Brennan, Paul; Chow, Wong-Ho; Boffetta, Paolo

    2012-01-01

    Background: The countries of Central and Eastern Europe have among the highest worldwide rates of renal cell cancer (RCC). Few studies have examined whether genetic variation in xenobiotic metabolic pathway genes may modify risk for this cancer. Methods: The Central and Eastern Europe Renal Cell Cancer study was a hospital-based case–control study conducted between 1998 and 2003 across seven centers in Central and Eastern Europe. Detailed data were collected from 874 cases and 2053 controls on demographics, work history, and occupational exposure to chemical agents. Genes [cytochrome P-450 family, N-acetyltransferases, NAD(P)H:quinone oxidoreductase I (NQO1), microsomal epoxide hydrolase (mEH), catechol-O-methyltransferase (COMT), uridine diphosphate-glucuronosyltransferase (UGT)] were selected for the present analysis based on their putative role in xenobiotic metabolism. Haplotypes were calculated using fastPhase. Odds ratios and 95% confidence intervals were estimated by unconditional logistic regression adjusted for country of residence, age, sex, smoking, alcohol intake, obesity, and hypertension. Results: We observed an increased risk of RCC with one SNP. After adjustment for multiple comparisons it did not remain significant. Neither NAT1 nor NAT2 slow acetylation was associated with disease. Conclusion: We observed no association between this pathway and renal cell cancer.

  11. (131)I treatment in Differentiated Thyroid Cancer and End-Stage Renal Disease.

    Science.gov (United States)

    Ortega, A J M; Vázquez, R G; Cuenca, J I C; Brocca, M A M; Castilla, J; Martínez, J M M; González, E N

    2016-01-01

    Radioiodine (RAI) is a cornerstone in the treatment of Differentiated Thyroid Cancer (DTC). In patients on haemodialysis due to End-Stage Renal Disease (ESRD), it must be used cautiously, considering the renal clearance of this radionuclide. Also, the safety of the procedure and subsequent long-term outcome is still not well defined. In 2001, we described a dosimetric method and short-term results in three patients, with a good safety profile. We hypothesize that our method is safe in a long-term scenario without compromising the prognosis of both renal and thyroid disease. Descriptive-retrospective study. A systematic search was carried out using our clinical database from 2000 to 2014. DTC and radioiodine treatment while on haemodialysis. peritoneal dialysis. Final sample n=9 patients (n=5 males), age 48 years (median age 51 years males, 67 years female group); n=8 papillary thyroid cancer, n=1 follicular thyroid cancer; n=5 lymph node invasion; n=1 metastatic disease. Median RAI dose administered on haemodialysis 100mCi. 7.5 years after radioiodine treatment on haemodialysis, n=7 deemed free of thyroid disease, n=1 persistent non-localised disease. No complications related to the procedure or other target organs were registered. After 3.25 years, n=4 patients underwent successful renal transplantation; n=4 patients did not meet transplantation criteria due to other conditions unrelated to the thyroid disease or its treatment. One patient died due to ischemic cardiomyopathy (free of thyroid disease). Radioiodine treatment during haemodialysis is a long-term, safe procedure without worsening prognosis of either renal or thyroid disease. Copyright © 2015 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

  12. Plasma cell morphology in multiple myeloma and related disorders.

    Science.gov (United States)

    Ribourtout, B; Zandecki, M

    2015-06-01

    to malignant changes of PC but are related to abnormal synthesis, trafficking, or excretion of the immunoglobulin that is stored in excess within the cytoplasm. Occurrence of crystalline inclusions within PC may be the first anomaly leading to the diagnosis of adult Fanconi syndrome. After a historical perspective, the authors report on the various morphological aspects of PC that may occur in multiple myeloma and related disorders, and discuss about their clinical and pathophysiological significance. Today, morphological identification and accurate determination of % PC within bone marrow remain ancillary criteria for the diagnosis of MM and help for the diagnosis of rare renal disorders. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  13. Multiple myeloma and plasmacytomas

    International Nuclear Information System (INIS)

    Mill, W.B.; Wasserman, T.H.

    1987-01-01

    Radiation therapy is the primary modality of treatment in the management of solitary plasmacytomas. The dose of radiation recommended is 5500 to 6000 cGy in 6 to 8 weeks. Disseminated myeloma is primarily treated with chemotherapy, which frequently includes melphalan and prednisone. Other drugs that are active in this disease are cyclophophamide, vincristine, procarbazine, BCNU, and doxorubicin. Adjuvant radiation therapy is indicated for painful bone lesions, for prevention and treatment of pathologic features of long bones, for spinal cord compression, and to relieve pressure from soft tissue masses. Myeloma is a relatively radiosensitive tumor requiring only 1000 to 2000 cGy in 1 to 2 weeks to relieve most painful lesions

  14. Curability of Multiple Myeloma

    Directory of Open Access Journals (Sweden)

    Raymond Alexanian

    2012-01-01

    Full Text Available Among 792 patients with multiple myeloma treated from 1987 to 2010 and assessed after 18 months, there were 167 patients with complete remission. For those 60 patients treated between 1987–1998 and with long followup, the latest relapse occurred after 11.8 years, so that 13 patients have remained in sustained complete remission for longer than 12 years (range 12–22 years. These results suggest that 3% of all patients treated during that period may be cured of multiple myeloma. In addition to immunofixation, more sensitive techniques for the detection of residual disease should be applied more consistently in patients with apparent complete remission in order to identify those with potential cure.

  15. Introduction: multiple myeloma.

    Science.gov (United States)

    Cook, Richard

    2008-09-01

    Multiple myeloma (MM) is the most common type of primary bone tumor, affecting approximately 50,000 patients in the United States. Although it is currently not curable, recent advancements in treatment are bringing myeloma closer to becoming a chronic disease instead of a terminal illness. To better understand the prevalence of MM as well as provide an overview of the costs associated with treatment. The goals of treatment in MM include eradicating all evidence of disease, controlling disease to prevent damage to target organs, preserving normal function and quality of life, relieving pain, and managing myeloma that is in remission. To achieve these goals, treatment must be individually tailored for each patient based on the patient's age, overall health status, symptoms, and laboratory test results. Advancements in the understanding of the pathogenesis of myeloma and the role of genetic mutations are leading to a new standard of treatment. Advancements in diagnostic technology, such as cytogenetic testing, are also being used to tailor treatment for each individual to work toward achieving better response rates, longer periods of remission, and improved quality of life. Increased costs associated with the improved therapies being used to treat MM, and the comorbid conditions associated with the disease, present a challenge to managed care. Health plans and formulary decision makers need to better understand the complexity of therapy to best use resources. The economic burden to the patient must also be considered when developing treatment strategies. Better understanding of the pathophysiology of MM, including the role of cytogenetics, is leading to the development and use of novel agents and treatment options. Head-to-head studies comparing treatments must be performed to best balance the costs associated with treatment and the benefits of improved survival rates and maintaining quality of life.

  16. The association of lifetime physical inactivity with bladder and renal cancer risk: A hospital-based case-control analysis.

    Science.gov (United States)

    Cannioto, Rikki; Etter, John Lewis; Guterman, Lauren Beryl; Joseph, Janine M; Gulati, Nicholas R; Schmitt, Kristina L; LaMonte, Michael J; Nagy, Ryan; Minlikeeva, Albina; Szender, James Brian; Moysich, Kirsten B

    2017-08-01

    Recreational physical inactivity has been gaining recognition as an independent epidemiological exposure of interest in relation to cancer endpoints due to evidence suggesting that it may associate with cancer independent of obesity. In the current analyses, we examined the associations of lifetime recreational physical inactivity with renal and bladder cancer risk. In this hospital-based case-control study, we identified N=160 renal cancer patients, N=208 bladder cancer patients, and N=766 age frequency-matched controls without cancer. Participants self-reporting never participating in any regular/weekly recreational physical activity throughout their lifetime were classified as physically inactive. Utilizing unconditional multivariable logistic regression analyses, we estimated odds ratios and 95% confidence intervals to represent the associations between lifetime physical inactivity and renal and bladder cancer risk. In multivariable logistic regression models, we observed significant positive associations between lifetime recreational physical inactivity and renal cancer and bladder cancer risk: odds ratio=1.77 (95% CI: 1.10-2.85) and odds ratio=1.73 (95% CI: 1.13-2.63), respectively. Similar associations also persisted among individuals who were not obese for both renal and bladder cancer: odds ratio=1.75 (95% CI: 1.03-2.98) and odds ratio=1.70 (95% CI: 1.08-2.69), respectively. In this case-control study, we observed evidence of a positive association between renal and bladder cancer with lifetime recreational physical inactivity. These data add to the growing body of evidence suggesting that physical inactivity may be an important independent risk factor for cancer. However, additional studies using a larger sample and prospectively collected data are needed to substantiate the current findings. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Multiple myeloma: 45 cases

    International Nuclear Information System (INIS)

    Yang, Hee Chul; Suh, Jin Suck; Park, Chang Yun

    1990-01-01

    We evaluated 45 cases of multiple myelomas retrospectively confirmed in Severance Hospital from the period of 1983-1989. In order to assess the radiologic features of the multiple myeloma and to assist in possible early diagnosis and treatment. The result were as follows: 1. IgG(41%) was the most common immunoglobulin type secreted followed by light chain(36%). IgA(19%) and IgD(2%). Two percent of the patients had non-secretory type. 89% of patients were in their stage III of the disease. 2. Among the 45 patients, 96% had abnormal plain radiographic findings with average number of 4.5 lesions. Common sites were the spine, rib, skull, pelvis, and humerus in descending orders. The findings were localized or diffuse osteolytic bone destruction(85%). osteoporosis(49%), pathologic fracture and endosteal scalloping(55%). Osteoporosis was more prominent in stage III than stage II. 3. Both plain X-ray and radioisotope study was available for comparison in 28 patients. Concordance between the two studies were 44%, lesions detected only on plain X-ray film were 51%, and lesions detected only on the radioisotope were 5%. The plain radiography was able to detect only 54% of bone lesions confirmed by bone marrow biopsy. With the above results, accurate evaluation of bone lesions in multiple myeloma may be difficult with radiologic studies only. But familiarity with these radiologic findings of the this disease entity is necessary for early suspicion of the disease, thus for early diagnosis and treatment

  18. Tracking Cancer Evolution Reveals Constrained Routes to Metastases: TRACERx Renal.

    Science.gov (United States)

    Turajlic, Samra; Xu, Hang; Litchfield, Kevin; Rowan, Andrew; Chambers, Tim; Lopez, Jose I; Nicol, David; O'Brien, Tim; Larkin, James; Horswell, Stuart; Stares, Mark; Au, Lewis; Jamal-Hanjani, Mariam; Challacombe, Ben; Chandra, Ashish; Hazell, Steve; Eichler-Jonsson, Claudia; Soultati, Aspasia; Chowdhury, Simon; Rudman, Sarah; Lynch, Joanna; Fernando, Archana; Stamp, Gordon; Nye, Emma; Jabbar, Faiz; Spain, Lavinia; Lall, Sharanpreet; Guarch, Rosa; Falzon, Mary; Proctor, Ian; Pickering, Lisa; Gore, Martin; Watkins, Thomas B K; Ward, Sophia; Stewart, Aengus; DiNatale, Renzo; Becerra, Maria F; Reznik, Ed; Hsieh, James J; Richmond, Todd A; Mayhew, George F; Hill, Samantha M; McNally, Catherine D; Jones, Carol; Rosenbaum, Heidi; Stanislaw, Stacey; Burgess, Daniel L; Alexander, Nelson R; Swanton, Charles

    2018-04-19

    Clear-cell renal cell carcinoma (ccRCC) exhibits a broad range of metastatic phenotypes that have not been systematically studied to date. Here, we analyzed 575 primary and 335 metastatic biopsies across 100 patients with metastatic ccRCC, including two cases sampledat post-mortem. Metastatic competence was afforded by chromosome complexity, and we identify 9p loss as a highly selected event driving metastasis and ccRCC-related mortality (p = 0.0014). Distinct patterns of metastatic dissemination were observed, including rapid progression to multiple tissue sites seeded by primary tumors of monoclonal structure. By contrast, we observed attenuated progression in cases characterized by high primary tumor heterogeneity, with metastatic competence acquired gradually and initial progression to solitary metastasis. Finally, we observed early divergence of primitive ancestral clones and protracted latency of up to two decades as a feature of pancreatic metastases. Crown Copyright © 2018. Published by Elsevier Inc. All rights reserved.

  19. Sunitinib treatment in patients with advanced renal cell cancer: the Brazilian National Cancer Institute (INCA) experience.

    Science.gov (United States)

    Coelho, Rafael Corrêa; Reinert, Tomás; Campos, Franz; Peixoto, Fábio Affonso; de Andrade, Carlos Augusto; Castro, Thalita; Herchenhorn, Daniel

    2016-01-01

    The aim of this study was to assess the impact of sunitinib treatment in a non-screened group of patients with metastatic renal cell cancer (mRCC) treated by the Brazilian Unified Health System (SUS) at a single reference institution. Retrospective cohort study, which evaluated patients with mRCC who received sunitinib between May 2010 and December 2013. Fifty-eight patients were eligible. Most patients were male 41 (71%), with a median age of 58 years. Nephrectomy was performed in 41 (71%) patients with a median interval of 16 months between the surgery and initiation of sunitinib. The most prevalent histological subtype was clear cell carcinoma, present in 52 (91.2%) patients. In 50 patients (86%), sunitinib was the first line of systemic treatment. The main adverse effects were fatigue (57%), hypothyroidism (43%), mucositis (33%) and diarrhea (29%). Grade 3 and 4 adverse effects were infrequent: fatigue (12%), hypertension (12%), thrombocytopenia (7%), neutropenia (5%) and hand-foot syndrome (5%). Forty percent of patients achieved a partial response and 35% stable disease, with a disease control rate of 75%. Median progression free survival was 7.6 months and median overall survival was 14.1 months. Sunitinib treatment was active in the majority of patients, especially those with low and intermediate risk by MSKCC score, with manageable toxicity. Survival rates were inferior in this non-screened population with mRCC treated in the SUS. Copyright© by the International Brazilian Journal of Urology.

  20. Sunitinib treatment in patients with advanced renal cell cancer: the Brazilian National Cancer Institute (INCA experience

    Directory of Open Access Journals (Sweden)

    Rafael Corrêa Coelho

    Full Text Available ABSTRACT Purpose: The aim of this study was to assess the impact of sunitinib treatment in a non-screened group of patients with metastatic renal cell cancer (mRCC treated by the Brazilian Unified Health System (SUS at a single reference institution. Material and Methods: Retrospective cohort study, which evaluated patients with mRCC who received sunitinib between May 2010 and December 2013. Results: Fifty-eight patients were eligible. Most patients were male 41 (71%, with a median age of 58 years. Nephrectomy was performed in 41 (71% patients with a median interval of 16 months between the surgery and initiation of sunitinib. The most prevalent histological subtype was clear cell carcinoma, present in 52 (91.2% patients. In 50 patients (86%, sunitinib was the first line of systemic treatment. The main adverse effects were fatigue (57%, hypothyroidism (43%, mucositis (33% and diarrhea (29%. Grade 3 and 4 adverse effects were infrequent: fatigue (12%, hypertension (12%, thrombocytopenia (7%, neutropenia (5% and hand-foot syndrome (5%. Forty percent of patients achieved a partial response and 35% stable disease, with a disease control rate of 75%. Median progression free survival was 7.6 months and median overall survival was 14.1 months. Conclusion: Sunitinib treatment was active in the majority of patients, especially those with low and intermediate risk by MSKCC score, with manageable toxicity. Survival rates were inferior in this non-screened population with mRCC treated in the SUS.

  1. An update on current management of advanced renal cell cancer, biomarkers, and future directions

    OpenAIRE

    Zhi, Wanqing Iris; Kim, Jenny J.

    2014-01-01

    In the past decade, metastatic renal cell carcinoma (mRCC) treatment underwent significant advancement that resulted in an unprecedented improvement in the prognosis of this disease. This review will provide an updated review of currently approved treatment options, namely antiangiogenic and immunotherapy, as well as treatment guideline recommended by the National Comprehensive Cancer Network (NCCN). We will summarize studies ongoing in determining prognostic and predictive biomarkers in maxi...

  2. The Cancer Genome Atlas Comprehensive Molecular Characterization of Renal Cell Carcinoma

    OpenAIRE

    Christopher J. Ricketts; Aguirre A. De Cubas; Huihui Fan; Christof C. Smith; Martin Lang; Ed Reznik; Reanne Bowlby; Ewan A. Gibb; Rehan Akbani; Rameen Beroukhim; Donald P. Bottaro; Toni K. Choueiri; Richard A. Gibbs; Andrew K. Godwin; Scott Haake

    2018-01-01

    Summary: Renal cell carcinoma (RCC) is not a single disease, but several histologically defined cancers with different genetic drivers, clinical courses, and therapeutic responses. The current study evaluated 843 RCC from the three major histologic subtypes, including 488 clear cell RCC, 274 papillary RCC, and 81 chromophobe RCC. Comprehensive genomic and phenotypic analysis of the RCC subtypes reveals distinctive features of each subtype that provide the foundation for the development of sub...

  3. Imaging of multiple myeloma and related monoclonal plasma cell diseases. An update

    International Nuclear Information System (INIS)

    Weber, Marc-Andre; Delorme, Stefan; Hillengass, Jens

    2014-01-01

    Multiple myeloma is a hematologic disorder characterized by the infiltration and proliferation of monoclonal plasma cells mainly in the bone marrow. The main symptoms are hypercalcemia, renal impairment, cytopenia/anemia and bone disease - summarized as CRAB-criteria. Symptomatic multiple myeloma is consistently preceded by asymptomatic premalignant stages called monoclonal gammopathy of undetermined significance and smoldering multiple myeloma. Staging of multiple myeloma is based on the measurement of the monoclonal protein in serum and urine as well as the assessment of impairment of hematopoiesis, renal function and mineralized bone. In the last decade the development of novel therapeutic agents has led to an increase in response rates and survival time of patients with multiple myeloma, which further stresses the value of response assessment by imaging. Cross sectional imaging like MRI and CT is currently replacing conventional radiological surveys in the initial work-up and follow-up of patients with monoclonal plasma cell diseases. The added value of MRI is to improve initial staging by unraveling a diffuse infiltration of bone marrow by plasma cells, a focal pattern or a combination of both. Furthermore, a complete remission of myeloma confirmed by MRI and CT goes along with a better prognosis compared to a complete response based only on serological parameters.

  4. Metformin Elicits Antitumor Effects and Downregulates the Histone Methyltransferase Multiple Myeloma SET Domain (MMSET) in Prostate Cancer Cells.

    Science.gov (United States)

    White-Al Habeeb, Nicole M A; Garcia, Julia; Fleshner, Neil; Bapat, Bharati

    2016-12-01

    This study explored the biological effects of metformin on prostate cancer (PCa) cells and determined molecular pathways and epigenetic regulators implicated in its mechanism of action. We performed mRNA expression profiling in 22Rv1 cells following 2.5 mM and 5 mM metformin treatment. Genes significantly modified by metformin treatment were ranked based on altered expression, involvement with cancer-related processes, and reported dysregulation in PCa. The effects of the top ranked gene, MMSET, on the proliferative and invasive capabilities of PCa cells were investigated via siRNA knockdown alone and also combined with metformin treatment. Metformin treatment decreased cell growth of PCa cell line 22Rv1 and stalled cells at the G1/S checkpoint in a time- and dose-dependent manner, resulting in increased cells in G1 (P prostate epithelium-derived cell-line RWPE-1, and its expression was decreased upon metformin treatment. siRNA-mediated knockdown of MMSET showed decreased cellular migration and invasion in DU-145 cells. MMSET knockdown in combination with metformin treatment resulted in further reduction in the capacity of PCa cells to migrate and invade. These data suggest MMSET may play a role in the inhibitory effect of metformin on PCa and could serve as a potential novel therapeutic target for PCa. Prostate 76:1507-1518, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  5. Nivolumab-Induced Encephalitis in Hereditary Leiomyomatosis and Renal Cell Cancer Syndrome

    Directory of Open Access Journals (Sweden)

    Benjamin Chaucer

    2018-01-01

    Full Text Available The treatment of cancer is a rapidly evolving field. As more chemotherapeutic agents become available, reporting the side effects of these agents in clinical practice becomes increasingly important. Nivolumab is one of the chemotherapeutic agents commonly used for treatment of renal cell carcinoma, metastatic melanoma, and metastatic non-small cell lung cancer. While common side effects are known and well documented, encephalitis is documented as an extremely rare side effect. We present the case of an extremely rare side effect to a common chemotherapeutic agent.

  6. Renal cancer and pneumothorax risk in Birt-Hogg-Dubé syndrome; an analysis of 115 FLCN mutation carriers from 35 BHD families

    NARCIS (Netherlands)

    Houweling, A. C.; Gijezen, L. M.; Jonker, M. A.; van Doorn, M. B. A.; Oldenburg, R. A.; van Spaendonck-Zwarts, K. Y.; Leter, E. M.; van Os, T. A.; van Grieken, N. C. T.; Jaspars, E. H.; de Jong, M. M.; Bongers, E. M. H. F.; Johannesma, P. C.; Postmus, P. E.; van Moorselaar, R. J. A.; van Waesberghe, J-H T. M.; Starink, T. M.; van Steensel, M. A. M.; Gille, J. J. P.; Menko, F. H.

    2011-01-01

    Birt-Hogg-Dubé (BHD) syndrome is an autosomal dominant condition caused by germline FLCN mutations, and characterised by fibrofolliculomas, pneumothorax and renal cancer. The renal cancer risk, cancer phenotype and pneumothorax risk of BHD have not yet been fully clarified. The main focus of this

  7. Renal cancer and pneumothorax risk in Birt-Hogg-Dube syndrome; an analysis of 115 FLCN mutation carriers from 35 BHD families

    NARCIS (Netherlands)

    Houweling, A. C.; Gijezen, L. M.; Jonker, M. A.; van Doorn, M. B. A.; Oldenburg, R. A.; van Spaendonck-Zwarts, K. Y.; Leter, E. M.; van Os, T. A.; van Grieken, N. C. T.; Jaspars, E. H.; de Jong, M. M.; Johannesma, P. C.; Postmus, P. E.; van Moorselaar, R. J. A.; van Waesberghe, J-H T. M.; Starink, T. M.; van Steensel, M. A. M.; Gille, J. J. P.; Menko, F. H.; Bongers, Ernie M. H. F.

    2011-01-01

    BACKGROUND: Birt-Hogg-Dube (BHD) syndrome is an autosomal dominant condition caused by germline FLCN mutations, and characterised by fibrofolliculomas, pneumothorax and renal cancer. The renal cancer risk, cancer phenotype and pneumothorax risk of BHD have not yet been fully clarified. The main

  8. Physiological antioxidant system and oxidative stress in stomach cancer patients with normal renal and hepatic function

    Directory of Open Access Journals (Sweden)

    E Prabhakar Reddy

    2010-04-01

    Full Text Available Role of free radicals has been proposed in the pathogenesis of many diseases. Gastric cancer is a common disease worldwide, and leading cause of cancer death in India. Severe oxidative stress produces reactive oxygen species (ROS and induces uncontrolled lipid peroxidation. Albumin, uric acid (UA and Bilirubin are important physiological antioxidants. We aimed to evaluate and assess the role of oxidative stress (OS and physiological antioxidant system in stomach cancer patients. Lipid peroxidation measured as plasma Thio Barbituric Acid Reactive substances (TBARS, was found to be elevated significantly (p=0.001 in stomach cancer compared to controls along with a decrease in plasma physiological antioxidant system. The documented results were due to increased lipid peroxidation and involvement of physiological antioxidants in scavenging free radicals but not because of impaired hepatic and renal functions.

  9. Plasma Cell Neoplasms (Including Multiple Myeloma)—Patient Version

    Science.gov (United States)

    Plasma cell neoplasms occur when abnormal plasma cells form cancerous tumors. When there is only one tumor, the disease is called a plasmacytoma. When there are multiple tumors, it is called multiple myeloma. Start here to find information on plasma cell neoplasms treatment, research, and statistics.

  10. Multiple myeloma in Nigeria: An insight to the clinical, laboratory ...

    African Journals Online (AJOL)

    The average percentage of bone marrow plasmacytosis at diagnosis ... of autologous stem cell transplantation (ASCT) for white, black, and ... Hospital Cancer Registry and Data Collation Institute. .... Figure 1: (a) Kaplan‑Meier survival curve for all myeloma patients, (b) Kaplan‑Meier survival curve for the different sexes b a ...

  11. An analysis of growth, differentiation and apoptosis genes with risk of renal cancer.

    Directory of Open Access Journals (Sweden)

    Linda M Dong

    2009-03-01

    Full Text Available We conducted a case-control study of renal cancer (987 cases and 1298 controls in Central and Eastern Europe and analyzed genomic DNA for 319 tagging single-nucleotide polymorphisms (SNPs in 21 genes involved in cellular growth, differentiation and apoptosis using an Illumina Oligo Pool All (OPA. A haplotype-based method (sliding window analysis of consecutive SNPs was used to identify chromosome regions of interest that remained significant at a false discovery rate of 10%. Subsequently, risk estimates were generated for regions with a high level of signal and individual SNPs by unconditional logistic regression adjusting for age, gender and study center. Three regions containing genes associated with renal cancer were identified: caspase 1/5/4/12(CASP 1/5/4/12, epidermal growth factor receptor (EGFR, and insulin-like growth factor binding protein-3 (IGFBP3. We observed that individuals with CASP1/5/4/12 haplotype (spanning area upstream of CASP1 through exon 2 of CASP5 GGGCTCAGT were at higher risk of renal cancer compared to individuals with the most common haplotype (OR:1.40, 95% CI:1.10-1.78, p-value = 0.007. Analysis of EGFR revealed three strong signals within intron 1, particularly a region centered around rs759158 with a global p = 0.006 (GGG: OR:1.26, 95% CI:1.04-1.53 and ATG: OR:1.55, 95% CI:1.14-2.11. A region in IGFBP3 was also associated with increased risk (global p = 0.04. In addition, the number of statistically significant (p-value<0.05 SNP associations observed within these three genes was higher than would be expected by chance on a gene level. To our knowledge, this is the first study to evaluate these genes in relation to renal cancer and there is need to replicate and extend our findings. The specific regions associated with risk may have particular relevance for gene function and/or carcinogenesis. In conclusion, our evaluation has identified common genetic variants in CASP1, CASP5, EGFR, and IGFBP3 that could be

  12. Stereotactic body radiotherapy for renal cell cancer and pancreatic cancer. Literature review and practice recommendations of the DEGRO Working Group on Stereotactic Radiotherapy

    International Nuclear Information System (INIS)

    Panje, Cedric; Andratschke, Nikolaus; Guckenberger, Matthias; Brunner, Thomas B.; Niyazi, Maximilian

    2016-01-01

    This report of the Working Group on Stereotactic Radiotherapy of the German Society of Radiation Oncology (DEGRO) aims to provide a literature review and practice recommendations for stereotactic body radiotherapy (SBRT) of primary renal cell cancer and primary pancreatic cancer. A literature search on SBRT for both renal cancer and pancreatic cancer was performed with focus on prospective trials and technical aspects for clinical implementation. Data on renal and pancreatic SBRT are limited, but show promising rates of local control for both treatment sites. For pancreatic cancer, fractionated SBRT should be preferred to single-dose treatment to reduce the risk of gastrointestinal toxicity. Motion-compensation strategies and image guidance are paramount for safe SBRT delivery in both tumor entities. SBRT for renal cancer and pancreatic cancer have been successfully evaluated in phase I and phase II trials. Pancreatic SBRT should be practiced carefully and only within prospective protocols due to the risk of severe gastrointestinal toxicity. SBRT for primary renal cell cancer appears a viable option for medically inoperable patients but future research needs to better define patient selection criteria and the detailed practice of SBRT. (orig.) [de

  13. Destabilization of Akt Promotes the Death of Myeloma Cell Lines

    Directory of Open Access Journals (Sweden)

    Yanan Zhang

    2014-01-01

    Full Text Available Constitutive activation of Akt is believed to be an oncogenic signal in multiple myeloma and is associated with poor patient prognosis and resistance to available treatment. The stability of Akt proteins is regulated by phosphorylating the highly conserved turn motif (TM of these proteins and the chaperone protein HSP90. In this study we investigate the antitumor effects of inhibiting mTORC2 plus HSP90 in myeloma cell lines. We show that chronic exposure of cells to rapamycin can inhibit mTORC2 pathway, and AKT will be destabilized by administration of the HSP90 inhibitor 17-allylamino-geldanamycin (17-AAG. Finally, we show that the rapamycin synergizes with 17-AAG and inhibits myeloma cells growth and promotes cell death to a greater extent than either drug alone. Our studies provide a clinical rationale of use mTOR inhibitors and chaperone protein inhibitors in combination regimens for the treatment of human blood cancers.

  14. Epidemiological profile of nonmelanoma skin cancer in renal transplant recipients: experience of a referral center*

    Science.gov (United States)

    Ferreira, Flávia Regina; Ogawa, Marilia Marufuji; Nascimento, Luiz Fernando Costa; Tomimori, Jane

    2014-01-01

    BACKGROUND Nonmelanoma skin cancer is the most common form of cancer in humans and also the malignant disease that is increasingly common among kidney transplant recipients. OBJECTIVE To determine the epidemiological characteristics of renal transplant recipients with nonmelanoma skin cancer seen at a referral transplantation center. METHODS Cross-sectional descriptive study with renal transplant recipients presenting nonmelanoma skin cancer, treated at a transplantation referral center between 08/01/2004 and 08/31/2009. Analyzed variables were: gender, age, skin phototype, occupational and recreational sun exposure, use of photoprotection, personal and family history of non-melanoma skin cancer, clinical type and location, time between transplantation and the appearance of the first nonmelanoma skin cancer, occurrence of viral warts, timing of transplantation, type of donor, cause of kidney failure, previous transplants, comorbidities, pre-transplant dialysis, type and duration of dialysis. RESULTS 64 subjects were included. Males - 71.9%; low skin phototypes (up to Fitzpatrick III) - 89%; mean age - 57.0 years - and mean age at transplant - 47.3 years; sun exposure - 67.2% occupational - and 64.1% recreational; photoprotection - 78.2% (although only 34.4% in a regular manner); squamous cell carcinoma - 67.2%; squamous cell carcinoma/basal cell carcinoma ratio - 2:1; personal history of nonmelanoma skin cancer - 25% - and family history - 10.9%; location at photoexposed area - 98.4%; average latency time between transplantation and first nonmelanoma skin cancer appearance - 78.3 months; viral warts (HPV) after transplant - 53.1%; average timing of transplantation - 115.5 months; living donor - 64.1%; triple regimen (antirejection) - 73.2%; comorbidities - 92.2%; pre-transplant dialysis - 98.4%; hemodialysis - 71.7%; average duration of dialysis - 39.1 months; previous transplants - 3.1%; hypertension as cause of renal failure - 46.9%. CONCLUSION This study allowed

  15. Radiation induced esophageal adenocarcinoma in a woman previously treated for breast cancer and renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Raissouni Soundouss

    2012-08-01

    Full Text Available Abstract Background Secondary radiation-induced cancers are rare but well-documented as long-term side effects of radiation in large populations of breast cancer survivors. Multiple neoplasms are rare. We report a case of esophageal adenocarcinoma in a patient treated previously for breast cancer and clear cell carcinoma of the kidney. Case presentation A 56 year-old non smoking woman, with no alcohol intake and no familial history of cancer; followed in the National Institute of Oncology of Rabat Morocco since 1999 for breast carcinoma, presented on consultation on January 2011 with dysphagia. Breast cancer was treated with modified radical mastectomy, 6 courses of chemotherapy based on CMF regimen and radiotherapy to breast, inner mammary chain and to pelvis as castration. Less than a year later, a renal right mass was discovered incidentally. Enlarged nephrectomy realized and showed renal cell carcinoma. A local and metastatic breast cancer recurrence occurred in 2007. Patient had 2 lines of chemotherapy and 2 lines of hormonotherapy with Letrozole and Tamoxifen assuring a stable disease. On January 2011, the patient presented dysphagia. Oesogastric endoscopy showed middle esophagus stenosing mass. Biopsy revealed adenocarcinoma. No evidence of metastasis was noticed on computed tomography and breast disease was controlled. Palliative brachytherapy to esophagus was delivered. Patient presented dysphagia due to progressive disease 4 months later. Jejunostomy was proposed but the patient refused any treatment. She died on July 2011. Conclusion We present here a multiple neoplasm in a patient with no known family history of cancers. Esophageal carcinoma is most likely induced by radiation. However the presence of a third malignancy suggests the presence of genetic disorders.

  16. Radiation induced esophageal adenocarcinoma in a woman previously treated for breast cancer and renal cell carcinoma.

    Science.gov (United States)

    Raissouni, Soundouss; Raissouni, Ferdaous; Rais, Ghizlane; Aitelhaj, Meryem; Lkhoyaali, Siham; Latib, Rachida; Mohtaram, Amina; Rais, Fadoua; Mrabti, Hind; Kabbaj, Nawal; Amrani, Naima; Errihani, Hassan

    2012-08-09

    Secondary radiation-induced cancers are rare but well-documented as long-term side effects of radiation in large populations of breast cancer survivors. Multiple neoplasms are rare. We report a case of esophageal adenocarcinoma in a patient treated previously for breast cancer and clear cell carcinoma of the kidney. A 56 year-old non smoking woman, with no alcohol intake and no familial history of cancer; followed in the National Institute of Oncology of Rabat Morocco since 1999 for breast carcinoma, presented on consultation on January 2011 with dysphagia. Breast cancer was treated with modified radical mastectomy, 6 courses of chemotherapy based on CMF regimen and radiotherapy to breast, inner mammary chain and to pelvis as castration. Less than a year later, a renal right mass was discovered incidentally. Enlarged nephrectomy realized and showed renal cell carcinoma. A local and metastatic breast cancer recurrence occurred in 2007. Patient had 2 lines of chemotherapy and 2 lines of hormonotherapy with Letrozole and Tamoxifen assuring a stable disease. On January 2011, the patient presented dysphagia. Oesogastric endoscopy showed middle esophagus stenosing mass. Biopsy revealed adenocarcinoma. No evidence of metastasis was noticed on computed tomography and breast disease was controlled. Palliative brachytherapy to esophagus was delivered. Patient presented dysphagia due to progressive disease 4 months later. Jejunostomy was proposed but the patient refused any treatment. She died on July 2011. We present here a multiple neoplasm in a patient with no known family history of cancers. Esophageal carcinoma is most likely induced by radiation. However the presence of a third malignancy suggests the presence of genetic disorders.

  17. Comprehensive evaluation of one-carbon metabolism pathway gene variants and renal cell cancer risk.

    Directory of Open Access Journals (Sweden)

    Todd M Gibson

    Full Text Available Folate and one-carbon metabolism are linked to cancer risk through their integral role in DNA synthesis and methylation. Variation in one-carbon metabolism genes, particularly MTHFR, has been associated with risk of a number of cancers in epidemiologic studies, but little is known regarding renal cancer.Tag single nucleotide polymorphisms (SNPs selected to produce high genomic coverage of 13 gene regions of one-carbon metabolism (ALDH1L1, BHMT, CBS, FOLR1, MTHFR, MTR, MTRR, SHMT1, SLC19A1, TYMS and the closely associated glutathione synthesis pathway (CTH, GGH, GSS were genotyped for 777 renal cell carcinoma (RCC cases and 1,035 controls in the Central and Eastern European Renal Cancer case-control study. Associations of individual SNPs (n = 163 with RCC risk were calculated using unconditional logistic regression adjusted for age, sex and study center. Minimum p-value permutation (Min-P tests were used to identify gene regions associated with risk, and haplotypes were evaluated within these genes.The strongest associations with RCC risk were observed for SLC19A1 (P(min-P = 0.03 and MTHFR (P(min-P = 0.13. A haplotype consisting of four SNPs in SLC19A1 (rs12483553, rs2838950, rs2838951, and rs17004785 was associated with a 37% increased risk (p = 0.02, and exploratory stratified analysis suggested the association was only significant among those in the lowest tertile of vegetable intake.To our knowledge, this is the first study to comprehensively examine variation in one-carbon metabolism genes in relation to RCC risk. We identified a novel association with SLC19A1, which is important for transport of folate into cells. Replication in other populations is required to confirm these findings.

  18. The natural history of renal function after surgical management of renal cell carcinoma: Results from the Canadian Kidney Cancer Information System.

    Science.gov (United States)

    Mason, Ross; Kapoor, Anil; Liu, Zhihui; Saarela, Olli; Tanguay, Simon; Jewett, Michael; Finelli, Antonio; Lacombe, Louis; Kawakami, Jun; Moore, Ronald; Morash, Christopher; Black, Peter; Rendon, Ricardo A

    2016-11-01

    Patients who undergo surgical management of renal cell carcinoma (RCC) are at risk for chronic kidney disease and its sequelae. This study describes the natural history of renal function after radical and partial nephrectomy and explores factors associated with postoperative decline in renal function. This is a multi-institutional cohort study of patients in the Canadian Kidney Cancer Information System who underwent partial or radical nephrectomy for RCC. Estimated glomerular filtration rate (eGFR) and stage of chronic kidney disease were determined preoperatively and at 3, 12, and 24 months postoperatively. Linear regression was used to determine the association between postoperative eGFR and type of surgery (radical vs. partial), duration of ischemia, ischemia type (warm vs. cold), and tumor size. With a median follow-up of 26 months, 1,379 patients were identified from the Canadian Kidney Cancer Information System database including 665 and 714 who underwent partial and radical nephrectomy, respectively. Patients undergoing radical nephrectomy had a lower eGFR (mean = 19ml/min/1.73m 2 lower) at 3, 12, and 24 months postoperatively (Prenal function occurred early and remained stable throughout follow-up. A lower preoperative eGFR and increasing age were also associated with a lower postoperative eGFR (P0.05). Severe renal failure (eGFRrenal function remains stable in patients undergoing surgery for RCC. Patients undergoing radical nephrectomy have a greater long-term reduction in renal function compared with those undergoing partial nephrectomy. Ischemia duration and type are not predictive of postoperative renal function when adhering to generally short ischemia durations. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Therapeutic advancements in multiple myeloma

    Directory of Open Access Journals (Sweden)

    Alessandro eGozzetti

    2014-09-01

    Full Text Available Multiple myeloma survival has significantly improved in latest years, due to a broad spectrum of novel agents available for treatment. The introduction of thalidomide, bortezomib and lenalidomide together with autologous stem cell transplantation has dramatically prolonged complete remissions rate, progression free survivals resulting ultimately in prolonged survivals in myeloma patients. Moreover, novel strategies of treatment such as consolidation and maintenance are being used to implement responses. A number of new drugs such as carfilzomib and pomalidomide are already in clinical practice, and new kids on the block are entering, making the future of myeloma patients brighter.

  20. Identify multiple myeloma stem cells: Utopia?

    Science.gov (United States)

    Saltarella, Ilaria; Lamanuzzi, Aurelia; Reale, Antonia; Vacca, Angelo; Ria, Roberto

    2015-01-26

    Multiple myeloma (MM) is a hematologic malignancy of monoclonal plasma cells which remains incurable despite recent advances in therapies. The presence of cancer stem cells (CSCs) has been demonstrated in many solid and hematologic tumors, so the idea of CSCs has been proposed for MM, even if MM CSCs have not been define yet. The existence of myeloma CSCs with clonotypic B and clonotypic non B cells was postulated by many groups. This review aims to focus on these distinct clonotypic subpopulations and on their ability to develop and sustain MM. The bone marrow microenvironment provides to MM CSCs self-renewal, survival and drug resistance thanks to the presence of normal and cancer stem cell niches. The niches and CSCs interact each other through adhesion molecules and the interplay between ligands and receptors activates stemness signaling (Hedgehog, Wnt and Notch pathways). MM CSCs are also supposed to be responsible for drug resistance that happens in three steps from the initial cancer cell homing microenvironment-mediated to development of microenvironment-independent drug resistance. In this review, we will underline all these aspects of MM CSCs.

  1. Combined Adjuvant Radiochemotherapy With IMRT/XELOX Improves Outcome With Low Renal Toxicity in Gastric Cancer

    International Nuclear Information System (INIS)

    Boda-Heggemann, Judit; Hofheinz, Ralf-Dieter; Weiss, Christel; Mennemeyer, Philipp; Mai, Sabine K.; Hermes, Petra; Wertz, Hansjoerg; Post, Stefan; Massner, Bernd; Hieber, Udo; Hochhaus, Andreas; Wenz, Frederik; Lohr, Frank

    2009-01-01

    Objectives: Adjuvant radiochemotherapy improves survival of patients with advanced gastric cancer. We assessed in two sequential cohorts whether improved radiotherapy technique (IMRT) together with intensified chemotherapy improves outcome vs. conventional three-dimensional conformal radiotherapy (3D-CRT) and standard chemotherapy in these patients while maintaining or reducing renal toxicity. Materials and Methods: Sixty consecutive patients treated for gastric cancer either with 3D-CRT (n = 27) and IMRT (n = 33) were evaluated. More than 70% had undergone D2 resection. Although there was a slight imbalance in R0 status between cohorts, N+ status was balanced. Chemotherapy consisted predominantly of 5-fluorouracil/folinic acid (n = 36) in the earlier cohort and mostly of oxaliplatin/capecitabine (XELOX, n = 24) in the later cohort. Primary end points were overall survival (OS), disease-free survival (DFS), and renal toxicity based on creatinine levels. Results: Median follow-up (FU) of all patients in the 3D-CRT group was 18 months and in the IMRT group 22 months (median FU of surviving patients 67 months in the 3D-CRT group and 25 months in the IMRT group). Overall median survival (and DFS) were 18 (13) months in the 3D-CRT group and both not reached in the IMRT group (p = 0.0492 and 0.0216). Actuarial 2-year survival was 37% and 67% in the 3D-CRT and IMRT groups, respectively. No late renal toxicity >Grade 2 (LENT-SOMA scale) was observed in either cohort. Conclusion: When comparing sequentially treated patient cohorts with similar characteristics, OS and DFS improved with the use of IMRT and intensified chemotherapy without signs of increased renal toxicity.

  2. The Cancer Genome Atlas Comprehensive Molecular Characterization of Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Christopher J. Ricketts

    2018-04-01

    Full Text Available Summary: Renal cell carcinoma (RCC is not a single disease, but several histologically defined cancers with different genetic drivers, clinical courses, and therapeutic responses. The current study evaluated 843 RCC from the three major histologic subtypes, including 488 clear cell RCC, 274 papillary RCC, and 81 chromophobe RCC. Comprehensive genomic and phenotypic analysis of the RCC subtypes reveals distinctive features of each subtype that provide the foundation for the development of subtype-specific therapeutic and management strategies for patients affected with these cancers. Somatic alteration of BAP1, PBRM1, and PTEN and altered metabolic pathways correlated with subtype-specific decreased survival, while CDKN2A alteration, increased DNA hypermethylation, and increases in the immune-related Th2 gene expression signature correlated with decreased survival within all major histologic subtypes. CIMP-RCC demonstrated an increased immune signature, and a uniform and distinct metabolic expression pattern identified a subset of metabolically divergent (MD ChRCC that associated with extremely poor survival. : Ricketts et al. find distinctive features of each RCC subtype, providing the foundation for development of subtype-specific therapeutic and management strategies. Somatic alteration of BAP1, PBRM1, and metabolic pathways correlates with subtype-specific decreased survival, while CDKN2A alteration, DNA hypermethylation, and Th2 immune signature correlate with decreased survival within all subtypes. Keywords: clear cell renal cell carcinoma, papillary renal cell carcinoma, chromophobe renal cell carcinoma, CDKN2A, DNA hypermethylation, immune signature, chromatin remodeling, TCGA, PanCanAtlas

  3. The renal handling of sodium and water is not affected by the standard-dose cisplatin treatment for testicular cancer

    DEFF Research Database (Denmark)

    Daugaard, G; Strandgaard, S; Holstein-Rathlou, N H

    1987-01-01

    Renal clearances of 51Cr-EDTA, lithium, sodium and potassium were measured before and after each of four consecutive treatment series with cisplatin in 15 men with testicular cancer. Since lithium is reabsorbed like sodium and water in the proximal tubules, but not reabsorbed to any measurable...... and all other parameters of glomerular filtration and renal sodium handling remained normal throughout the study (with the exception of a fall in fractional sodium excretion after the first treatment series). Plasma magnesium declined during all four treatment periods, signifying renal magnesium wasting....

  4. Osteosclerotic Myeloma with Peripheral Neuropathy

    African Journals Online (AJOL)

    diagnosis of myeloma should, in future, be suspected in these circumstances. ... moved towards the midline, and involved the lower thoracic region of his back for 18 .... further treatment, took his own discharge and has been lost to follow-up.

  5. Case report 383: Multiple myeloma

    International Nuclear Information System (INIS)

    Kouwenberg, J.J.; Simons, A.J.

    1986-01-01

    A unique and obviously extremely rare example of multiple myeloma has been presented, affecting the peripheral appendicular skeleton and not the hematopoietic system of the axial skeleton, radiologically and probably pathologically. Only one other similar case has been described. The radiological features were confirmed by the pathological studies: a biopsy specimen obtained from a large osteolytic lesion in a patella showed the typical stigma of multiple myeloma; a biopsy from the iliac creast showed no abnormality. (orig./SHA)

  6. radiochemical studies on the growth of myeloma cells

    International Nuclear Information System (INIS)

    Elshershaby, H.M.M.

    2008-01-01

    cancer is a disease of unregulated cell growth. humans of all ages develop cancer, and a wide variety of organs are affected. multiple myeloma is a cancer in which antibody-producing plasma cells grow in an uncontrolled and invasive (malignant) manner. melphalan (DNA cross-linker), is one of the most widely used and effective drugs in the treatment of multiple myeloma. thalidomide as an immunomodulatory agent is clinically useful in a number of cancers. antitumor activity may be related to a number of known properties, including antitumor necrosis factor (TNF)-α and T-cell costimulatory and antiangiogenic effect. however, it may also involve direct antitumor effects. radiotherapy is an important modality in the treatment of cancer. the aim of radiotherapy is to deliver radiation doses and schedules that kill cancer cells, while preserving normal tissue function. the aim of these studies was to evaluate the therapeutic effects of some chemical substances (chemotherapy)such as melphalan and thalidomide and γ-radiation (radiotherapy)on the growth of myeloma cells. also some confirmatory tests such as β2-microglobulin, caspases enzymes 8 and 9 and flow cytometric analyses were performed for the obtained optimum doses.

  7. Whole body MR in patients with multiple myeloma

    International Nuclear Information System (INIS)

    Piekarek, A.; Sosnowski, P.; Nowicki, A.; Komarnicki, M.

    2009-01-01

    Background: Multiple myeloma is a cancer of plasma cells which leads to bone marrow infiltration. Aim: Whole-body MR is the most sensitive imaging method available to detect multiple myeloma lesions. Ma terial and methods: MR scans were performed in 100 patients with multiple myeloma who were receiving treatment in the Haematology Clinic in Poznan in the years 2005 - 2006. Whole-body MR scans were performed with general coil 1.0 T in STIR sequences and T1 sequences, in coronal and sagittal planes with scanning area covering the head, neck, trunk and the limbs (FOV for specific regions was 36 -48 cm). The bone lesions were classified as focal (monofocal/multifocal lesions), infiltrative, mixed and 'salt and pepper' type. Depending on the size of the lesions the patients were included in one of three groups according to Salmon-Durie Plus classification. Results: Four main types of multiple myeloma were distinguished based on MR scans: focal (48 patients; monofocal in 10 patients), infiltrative (17 patients), mixed type (19 patients) and 'salt and pepper' type (4 patients). The remaining 12 patients had no multiple myeloma lesions in the bone marrow. Additionally, in 18% of patients a soft tissue mass could be observed. According to Salmon-Durie Plus categorisation 27 subjects were classified as having stage I, 16 patients stage and 57 patients stage III disease. In 12% of patients MR data changed the disease staging. Conclusions: WB MR is a sensitive and effective diagnostic method with an important impact on staging and further treatment of multiple myeloma. (authors)

  8. Annexin A2 and cancer

    DEFF Research Database (Denmark)

    Christensen, Maria V; Høgdall, Claus K; Jochumsen, Kirsten M

    2018-01-01

    Annexin A2 is a 36-kDa protein interfering with multiple cellular processes especially in cancer progression. The present review aimed to show the relations between Annexin A2 and cancer. A systematic search for studies investigating cancer and Annexin A2 expression was conducted using Pub......Med. Acute lymphoblastic leukaemia, acute promyelocytic leukaemia, clear cell renal cell carcinoma, breast, cervical, colorectal, endometrial, gastric cancer, glioblastoma, hepatocellular carcinoma, lung, multiple myeloma, oesophageal squamous cell carcinoma, ovarian cancer, pancreatic duct adenocarcinoma......, prostate cancer and urothelial carcinoma were evaluated. Annexin A2 expression correlates with resistance to treatment, binding to the bone marrow, histological grade and type, TNM-stage and shortened overall survival. The regulation of Annexin A2 is of interest due to its potential as target for a more...

  9. Safe and tolerable one-hour pamidronate infusion for multiple myeloma patients

    Directory of Open Access Journals (Sweden)

    Dimitrios Chantzichristos

    2008-09-01

    Full Text Available Dimitrios Chantzichristos, Andréasson Björn, Johansson PeterDepartment of Internal Medicine, Uddevalla Hospital, Uddevalla, SwedenBackground: Once a month, patients with multiple myeloma received an infusion of bisphosphonates, principally to reduce osteoclastic bone resorption. Recommended infusion time for pamidronate is 2 hours in the US and 4 hours in Europe because of its potential nephrotoxicity. From 2003, a 90 mg infusion of pamidronate was provided over 1 hour to patients with no pre-existing renal impairment, in the Daily Care Unit at Uddevalla Hospital.Method: Retrospective analysis of the renal deterioration, serum calcium, and adverse effects in patients with multiple myeloma treated with 1-hour pamidronate 90 mg infusion from January 2003 to April 2007.Results: Seventy-nine patients provided valuable data. A total number of 846 infusions were given and the median number of infusion to each patient was 11. Significant creatinine elevation was seen in 7 patients (8.9%, after 19 infusions (2.2%. Renal deterioration occurred in 5 of these 7 patients, which was related to progress of the myeloma or opportunistic infections. Prevalence of infusion-related events was 0.8% and the mean total S-Ca was 0.05 mmol/L lower than the baseline.Conclusion: Few events of renal deterioration, hypocalcemia, or other adverse effects resulted from a 1-hour pamidronate 90 mg infusion for multiple myeloma patients with no pre-existing renal impairment.Keywords: bisphosphonates, pamidronate, multiple myeloma, infusion time

  10. Prognostic factors in urothelial renal pelvis and ureter tumors: a multicenter rare cancer network study

    International Nuclear Information System (INIS)

    Ozsahin, M.; Zouhair, A.; Villa, S.; Storme, G.; Chauvet, B.; Taussky, D.; Houtte, P. van; Ries, G.; Bontemps, P.; Coucke, P.; Mirimanoff, R.O.

    1997-01-01

    Purpose: To assess the prognostic factors and the outcome in patients with transitional-cell carcinoma of the renal pelvis and/or ureter. Materials and Methods: A series of 138 patients treated between 1971 and 1996 for transitional-cell carcinoma of the renal pelvis and/or ureter was collected in a retrospective multicenter study of the Rare Cancer Network. Twelve patients with distant metastases were excluded from the statistical evaluation. In the remaining 126 patients, median age was 66 years (range: 41-87). The male to female ratio was 2.5 ((90(36))). All but 3 patients underwent a radical surgery: nephroureterectomy (n = 71), nephroureterectomy and lymphadenectomy (n = 20), nephroureterectomy and partial bladder resection or transurethral resection (n = 20), nephrectomy (n = 8), and ureterectomy (n = 4). There were 6 stage pTa, 22 pT1, 17 pT2, 37 pT3, 37 pT4, and 7 pTx tumors. The pN-stage distribution was as follows: 69 pN0, 8 pN1, 14 pN2, 4 pN3, and 31 pNx. Sixty-one percent (n = 77) of the tumors were located in the renal pelvis, and 21% (n = 27) in the ureter. Renal pelvis and ureter localization was present together in 22 (17%) patients. There were 4 grade 1, 37 grade 2, 42 grade 3 tumors (grade was not registered in 43). Following surgery, microscopic (n = 16) or macroscopic (n = 17) tumor rest was detected in 33 patients. Postoperative radiotherapy was given in 45 (36%) patients with a median total dose of 50 Gy (range: 20-66) in median 25 fractions (range: 4-33). Adjuvant systemic chemotherapy was administered in 12 (10%) patients. The median follow-up period was 39 months (range: 5-220). Results: In a median period of 9 months (range: 1-141), 66% (n = 81) of the patients relapsed (local in 34, locoregional in 7, regional in 16, and distant in 24). The 5- and 10-year overall survival (Kaplan-Meier product-limit estimates) was respectively 29% (± 5) and 19% (± 5) in all patients. In univariate analyses (logrank test), statistically significant

  11. Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of renal cell carcinoma.

    Science.gov (United States)

    Rini, Brian I; McDermott, David F; Hammers, Hans; Bro, William; Bukowski, Ronald M; Faba, Bernard; Faba, Jo; Figlin, Robert A; Hutson, Thomas; Jonasch, Eric; Joseph, Richard W; Leibovich, Bradley C; Olencki, Thomas; Pantuck, Allan J; Quinn, David I; Seery, Virginia; Voss, Martin H; Wood, Christopher G; Wood, Laura S; Atkins, Michael B

    2016-01-01

    Immunotherapy has produced durable clinical benefit in patients with metastatic renal cell cancer (RCC). In the past, patients treated with interferon-alpha (IFN) and interleukin-2 (IL-2) have achieved complete responses, many of which have lasted for multiple decades. More recently, a large number of new agents have been approved for RCC, several of which attack tumor angiogenesis by inhibiting vascular endothelial growth factors (VEGF) and VEGF receptors (VEGFR), as well as tumor metabolism, inhibiting the mammalian target of rapamycin (mTOR). Additionally, a new class of immunotherapy agents, immune checkpoint inhibitors, is emerging and will play a significant role in the treatment of patients with RCC. Therefore, the Society for Immunotherapy of Cancer (SITC) convened a Task Force, which met to consider the current role of approved immunotherapy agents in RCC, to provide guidance to practicing clinicians by developing consensus recommendations and to set the stage for future immunotherapeutic developments in RCC.

  12. [Management of side effects of targeted therapies in renal cancer: stomatological side effects (mucositis, epistaxis)].

    Science.gov (United States)

    Agbo-Godeau, Scarlette; Nicolas-Virelizier, Emmanuelle; Scotté, Florian

    2011-01-01

    The advent of targeted therapies in the treatment of renal cancer has shown different types of lesions of the oral cavity, which appear to be specific to the drug classes used (mTOR inhibitors, anti-angiogenic agents and conventional cytotoxic drugs). Before starting treatment with targeted therapy, it is essential to have an oral and a dental examination. The treatment of mucositis induced by targeted therapies is based on bicarbonate-based mouthwash, with the optional addition of an antifungal or a local antiseptic. It is possible to use topical or systemic analgesics for the pain. Dietary advice for patients is also useful. Most cases of epistaxis caused by anti-angiogenics stop spontaneously and require no medical intervention. Regular application of an emollient can be used to prevent the formation of scabs. Copyright © 2011 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

  13. The selective Aurora B kinase inhibitor AZD1152 is a potential new treatment for multiple myeloma.

    Science.gov (United States)

    Evans, Robert P; Naber, Claudia; Steffler, Tara; Checkland, Tamara; Maxwell, Christopher A; Keats, Jonathan J; Belch, Andrew R; Pilarski, Linda M; Lai, Raymond; Reiman, Tony

    2008-02-01

    Aurora kinases are potential targets for cancer therapy. Previous studies have validated Aurora kinase A as a therapeutic target in multiple myeloma (MM), and have demonstrated in vitro anti-myeloma effects of small molecule Aurora kinase inhibitors that inhibit both Aurora A and B. This study demonstrated that Aurora B kinase was strongly expressed in myeloma cell lines and primary plasma cells. The selective Aurora B inhibitor AZD1152-induced apoptotic death in myeloma cell lines at nanomolar concentrations, with a cell cycle phenotype consistent with that reported previously for Aurora B inhibition. In some cases, AZD1152 in combination with dexamethasone showed increased anti-myeloma activity compared with the use of either agent alone. AZD1152 was active against sorted CD138(+) BM plasma cells from myeloma patients but also, as expected, was toxic to CD138(-) marrow cells from the same patients. In a murine myeloma xenograft model, AZD1152-inhibited tumour growth at well-tolerated doses and induced cell death in established tumours, with associated mild, transient leucopenia. AZD1152 shows promise in these preclinical studies as a novel treatment for MM.

  14. VHL-dependent regulation of a β-dystroglycan glycoform and glycogene expression in renal cancer.

    Science.gov (United States)

    Aggelis, Vassilis; Craven, Rachel A; Peng, Jianhe; Harnden, Patricia; Schaffer, Lana; Hernandez, Gilberto E; Head, Steven R; Maher, Eamonn R; Tonge, Robert; Selby, Peter J; Banks, Rosamonde E

    2013-11-01

    Identification of novel biomarkers and targets in renal cell carcinoma (RCC) remains a priority and one cellular compartment that is a rich potential source of such molecules is the plasma membrane. A shotgun proteomic analysis of cell surface proteins enriched by cell surface biotinylation and avidin affinity chromatography was explored using the UMRC2- renal cancer cell line, which lacks von Hippel-Lindau (VHL) tumour suppressor gene function, to determine whether proteins of interest could be detected. Of the 814 proteins identified ~22% were plasma membrane or membrane-associated, including several with known associations with cancer. This included β-dystroglycan, the transmembrane subunit of the DAG1 gene product. VHL-dependent changes in the form of β-dystroglycan were detected in UMRC2-/+VHL transfectants. Deglycosylation experiments showed that this was due to differential sialylation. Analysis of normal kidney cortex and conventional RCC tissues showed that a similar change also occurred in vivo. Investigation of the expression of genes involved in glycosylation in UMRC2-/+VHL cells using a focussed microarray highlighted a number of enzymes involved in sialylation; upregulation of bifunctional UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) was validated in UMRC2- cells compared with their +VHL counterparts and also found in conventional RCC tissue. These results implicate VHL in the regulation of glycosylation and raise interesting questions regarding the extent and importance of such changes in RCC.

  15. Ebselen inhibits QSOX1 enzymatic activity and suppresses invasion of pancreatic and renal cancer cell lines.

    Science.gov (United States)

    Hanavan, Paul D; Borges, Chad R; Katchman, Benjamin A; Faigel, Douglas O; Ho, Thai H; Ma, Chen-Ting; Sergienko, Eduard A; Meurice, Nathalie; Petit, Joachim L; Lake, Douglas F

    2015-07-30

    Quiescin sulfhydryl oxidase 1 (QSOX1) is a highly conserved disulfide bond-generating enzyme that is overexpressed in diverse tumor types. Its enzymatic activity promotes the growth and invasion of tumor cells and alters extracellular matrix composition. In a nude mouse-human tumor xenograft model, tumors containing shRNA for QSOX1 grew significantly more slowly than controls, suggesting that QSOX1 supports a proliferative phenotype in vivo. High throughput screening experiments identified ebselen as an in vitro inhibitor of QSOX1 enzymatic activity. Ebselen treatment of pancreatic and renal cancer cell lines stalled tumor growth and inhibited invasion through Matrigel in vitro. Daily oral treatment with ebselen resulted in a 58% reduction in tumor growth in mice bearing human pancreatic tumor xenografts compared to controls. Mass spectrometric analysis of ebselen-treated QSOX1 mechanistically revealed that C165 and C237 of QSOX1 covalently bound to ebselen. This report details the anti-neoplastic properties of ebselen in pancreatic and renal cancer cell lines. The results here offer a "proof-of-principle" that enzymatic inhibition of QSOX1 may have clinical relevancy.

  16. Adverse renal effects of anaplastic lymphoma kinase inhibitors and the response to alectinib of an ALK+ lung cancer patient with renal dysfunction

    Directory of Open Access Journals (Sweden)

    Shimada M

    2017-06-01

    Full Text Available Midori Shimada,1,2 Minoru Fukuda,2,3 Masaaki Fukuda,2 Takeshi Kitazaki,2 Kohji Hashiguchi,2 Takaya Ikeda,1 Hiroyuki Yamaguchi,1 Katsumi Nakatomi,1 Kazuto Ashizawa,3 Hiroshi Mukae1 1Department of Respiratory Medicine, Unit of Translational Medicine, Nagasaki University Graduate School of Biomedical Sciences, 2Department of Respiratory Medicine, Japanese Red Cross Nagasaki Genbaku Hospital, 3Clinical Oncology Center, Nagasaki University Hospital, Nagasaki, Japan Abstract: A 62-year-old female patient with renal dysfunction and pulmonary adenocarcinoma developed postoperative recurrence and received carboplatin/pemetrexed and maintenance pemetrexed. As an anaplastic lymphoma kinase (ALK gene translocation was identified, the therapy was changed to crizotinib. However, the patient’s blood creatinine level increased, and her physical status worsened. Alectinib also induced exacerbation of renal dysfunction but was controlled by dose reduction of 140 mg twice daily for 2 weeks treatment and 2 weeks break were repeated, and exhibited a partial response for 16 months. Here, we describe the case in which alectinib treatment had beneficial clinical effects on ALK-positive lung adenocarcinoma, which controlled the adverse renal effects by dose reduction and drug breaks. Keywords: lung cancer, ALK, renal dysfunction, alectinib

  17. TGF-β1 targets a microRNA network that regulates cellular adhesion and migration in renal cancer.

    Science.gov (United States)

    Bogusławska, Joanna; Rodzik, Katarzyna; Popławski, Piotr; Kędzierska, Hanna; Rybicka, Beata; Sokół, Elżbieta; Tański, Zbigniew; Piekiełko-Witkowska, Agnieszka

    2018-01-01

    In our previous study we found altered expression of 19 adhesion-related genes in renal tumors. In this study we hypothesized that disturbed expression of adhesion-related genes could be caused by microRNAs: short, non-coding RNAs that regulate gene expression. Here, we found that expression of 24 microRNAs predicted to target adhesion-related genes was disturbed in renal tumors and correlated with expression of their predicted targets. miR-25-3p, miR-30a-5p, miR-328 and miR-363-3p directly targeted adhesion-related genes, including COL5A1, COL11A1, ITGA5, MMP16 and THBS2. miR-363-3p and miR-328 inhibited proliferation of renal cancer cells, while miR-25-3p inhibited adhesion, promoted proliferation and migration of renal cancer cells. TGF-β1 influenced the expression of miR-25-3p, miR-30a-5p, and miR-328. The analyzed microRNAs, their target genes and TGF-β1 formed a network of strong correlations in tissue samples from renal cancer patients. The expression signature of microRNAs linked with TGF-β1 levels correlated with poor survival of renal cancer patients. The results of our study suggest that TGF-β1 coordinates the expression of microRNA network that regulates cellular adhesion in cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Total-Body Irradiation and Fludarabine Phosphate Followed by Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies or Kidney Cancer

    Science.gov (United States)

    2017-12-11

    Adult Acute Myeloid Leukemia in Remission; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Myelodysplastic Syndrome; Childhood Renal Cell Carcinoma; Chronic Myelomonocytic Leukemia; Clear Cell Renal Cell Carcinoma; de Novo Myelodysplastic Syndrome; Metastatic Renal Cell Cancer; Previously Treated Myelodysplastic Syndrome; Progression of Multiple Myeloma or Plasma Cell Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult Non-Hodgkin Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Non-Hodgkin Lymphoma; Refractory Anemia; Refractory Anemia With Ringed Sideroblasts; Refractory Childhood Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Renal Medullary Carcinoma; Type 1 Papillary Renal Cell Carcinoma; Type 2 Papillary Renal Cell Carcinoma; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

  19. Renal transplantation across the donor-specific antibody barrier: Graft outcome and cancer risk after desensitization therapy.

    Science.gov (United States)

    Yang, Ching-Yao; Lee, Chih-Yuan; Yeh, Chi-Chuan; Tsai, Meng-Kun

    2016-06-01

    Desensitization regimens including use of intravenous immune globulin and rituximab have been reported to overcome renal transplant hyperacute rejection. A retrospective case-control study was performed to assess the results and complications of renal transplantation with desensitization therapy for donor-specific antibody (DSA) in a transplant center in Asia, where donor exchange was usually not allowed. Between January 2007 and December 2013, 22 patients with DSA received live-donor renal transplantation after desensitization (DSA group). During the same period, the DSA group was compared to the NSA group (152 renal transplants) who had no specific antibody to the donors (66 from deceased donors and 86 from living relatives). Rejection, renal function, graft and patient survival rates, infection, and cancer incidence were reviewed and analyzed from medical records. The DSA group (46.8%) had significantly higher acute rejection rates than the NSA group (13.7%) at the 1-year follow-up. The estimated renal function, 5-year graft, and patient survival rates were comparable between the groups. The DSA group (19.6%) had significantly higher 5-year de novo cancer incidence than the NSA group (8.5%; p = 0.028); three patients of the DSA group developed urothelial carcinoma 17.0 ± 3.0 months after transplantation. By using stepwise Cox regression analysis, desensitization therapy was identified as the sole independent risk factor for post-transplant urothelial carcinoma. When compared to renal transplantation without DSA, desensitization therapy for DSA resulted in equivalent renal transplant outcome but potentially increased risk of urothelial carcinoma after transplantation. Copyright © 2015. Published by Elsevier B.V.

  20. Cytotoxic effect of the Her-2/Her-1 inhibitor PKI-166 on renal cancer cells expressing the connexin 32 gene.

    Science.gov (United States)

    Fujimoto, Eriko; Yano, Tomohiro; Sato, Hiromi; Hagiwara, Kiyokazu; Yamasaki, Hiroshi; Shirai, Sumiko; Fukumoto, Keiko; Hagiwara, Hiromi; Negishi, Etsuko; Ueno, Koichi

    2005-02-01

    We have reported that connexin (Cx) 32 acts as a tumor suppressor gene in renal cancer cells partly due to Her-2 inactivation. Here, we determined if a Her-2/Her-1 inhibitor (PKI-166) can enhance the tumor-suppressive effect of Cx32 in Caki-2 cells from human renal cell carcinoma. The expression of Cx32 in Caki-2 cells was required for PKI-166-induced cytotoxic effect at lower doses. The cyctotoxicity was dependent on the occurrence of apoptosis and partly mediated by Cx32-driven gap junction intercellular communications. These results suggest that PKI-166 further supports the tumor-suppressive effect of the Cx32 gene in renal cancer cells through the induction of apoptosis.

  1. Zoledronic acid use in patients with bone metastases from renal cell carcinoma or bladder cancer.

    Science.gov (United States)

    Saad, Fred; Eastham, James A

    2010-06-01

    Approximately 30% of patients with renal cell carcinoma (RCC) and 40% of patients with bladder cancer develop bone metastases that can disrupt normal bone homeostasis and place patients at risk for potentially life-limiting skeletal-related events (SREs). In the absence of bone-directed therapies, patients with RCC may experience up to four SREs per year. In patients with bone metastases from RCC or bladder cancer, zoledronic acid (ZOL) significantly reduced the risk of SREs compared with placebo. In addition to its bone-protective effects, preclinical and early clinical evidence indicates that ZOL prevents tumor progression. For example, retrospective subset analysis in patients with RCC indicated that ZOL extended time to disease progression and demonstrated a trend toward improved overall survival compared with placebo. Additionally, a study in patients with bone metastases from bladder cancer demonstrated that ZOL improved 1-year overall survival compared with placebo. Bone metastases place a heavy burden on patients with RCC or bladder cancer, and early, continuous treatment with ZOL may provide anticancer benefits in addition to important patient quality of life. 2010. Published by Elsevier Inc.

  2. Preclinical studies in support of defibrotide for the treatment of multiple myeloma and other neoplasias.

    Science.gov (United States)

    Mitsiades, Constantine S; Rouleau, Cecile; Echart, Cinara; Menon, Krishna; Teicher, Beverly; Distaso, Maria; Palumbo, Antonio; Boccadoro, Mario; Anderson, Kenneth C; Iacobelli, Massimo; Richardson, Paul G

    2009-02-15

    Defibrotide, an orally bioavailable polydisperse oligonucleotide, has promising activity in hepatic veno-occlusive disease, a stem cell transplantation-related toxicity characterized by microangiopathy. The antithrombotic properties of defibrotide and its minimal hemorrhagic risk could serve for treatment of cancer-associated thrombotic complications. Given its cytoprotective effect on endothelium, we investigated whether defibrotide protects tumor cells from cytotoxic antitumor agents. Further, given its antiadhesive properties, we evaluated whether defibrotide modulates the protection conferred to multiple myeloma cells by bone marrow stromal cells. Defibrotide lacks significant single-agent in vitro cytotoxicity on multiple myeloma or solid tumor cells and does not attenuate their in vitro response to dexamethasone, bortezomib, immunomodulatory thalidomide derivatives, and conventional chemotherapeutics, including melphalan and cyclophosphamide. Importantly, defibrotide enhances in vivo chemosensitivity of multiple myeloma and mammary carcinoma xenografts in animal models. In cocultures of multiple myeloma cells with bone marrow stromal cells in vitro, defibrotide enhances the multiple myeloma cell sensitivity to melphalan and dexamethasone, and decreases multiple myeloma-bone marrow stromal cell adhesion and its sequelae, including nuclear factor-kappaB activation in multiple myeloma and bone marrow stromal cells, and associated cytokine production. Moreover, defibrotide inhibits expression and/or function of key mediators of multiple myeloma interaction with bone marrow stromal cell and endothelium, including heparanase, angiogenic cytokines, and adhesion molecules. Defibrotide's in vivo chemosensitizing properties and lack of direct in vitro activity against tumor cells suggest that it favorably modulates antitumor interactions between bone marrow stromal cells and endothelia in the tumor microenvironment. These data support clinical studies of defibrotide in

  3. Prospective study on late renal toxicity following postoperative chemoradiotherapy in gastric cancer

    International Nuclear Information System (INIS)

    Jansen, Edwin; Saunders, Mark P.; Boot, Henk; Oppedijk, Vera; Dubbelman, Ria; Porritt, Bridget; Cats, Annemieke; Stroom, Joep; Valdes Olmos, Renato; Bartelink, Harry; Verheij, Marcel

    2007-01-01

    Purpose: Postoperative chemoradiotherapy in gastric cancer improves locoregional control and survival. Reports on late toxicity, however, have been scarce thus far. Because renal toxicity is one of the most serious late complications in upper abdominal radiotherapy, we prospectively analyzed kidney function in patients who underwent postoperative chemoradiotherapy for gastric cancer. Patients and Methods: In 44 patients, Tc 99m -thiatide renography was performed before and at regular intervals after postoperative chemoradiotherapy. The left-to-right (L/R) ratio was used as an index of the relative kidney function. Mean L/R values were calculated for four follow-up time intervals. For all patients, kidney V 20 (percentage of the volume of the kidney that received more than 20 Gy) and mean dose of both kidneys were retrieved from the three-dimensional dose-volume histograms. Results: We observed a progressive decrease in left renal function of 11% (p = 0.012) after 6 months, up to 52% (p 18 months. The V 20 (left kidney) and mean left kidney dose were identified as parameters associated with decreased kidney function. Mean serum creatinine was increased from 74.6 μmol/L before treatment to 86.1 μmol/L at 1 year after chemoradiotherapy (p < 0.001). In patients with a follow-up of 18-28 months, one case of severe renovascular hypertension was observed. Conclusion: A progressive relative functional impairment of the left kidney in patients after postoperative chemoradiotherapy for gastric cancer is demonstrated. To optimize the survival benefit that can be established with adjuvant regimens, strategies to minimize the dose to the kidneys and other critical organs should be explored

  4. Expression of Genes Involved in Cellular Adhesion and Extracellular Matrix Remodeling Correlates with Poor Survival of Patients with Renal Cancer.

    Science.gov (United States)

    Boguslawska, Joanna; Kedzierska, Hanna; Poplawski, Piotr; Rybicka, Beata; Tanski, Zbigniew; Piekielko-Witkowska, Agnieszka

    2016-06-01

    Renal cell carcinoma is the most common highly metastatic kidney malignancy. Adhesion has a crucial role in the metastatic process. TGF (transforming growth factor)-β1 is a pleiotropic cytokine that influences cancerous transformation. We hypothesized that 1) changes in the expression of adhesion related genes may influence survival rate of patients with renal cell carcinoma and 2) TGF-β1 may contribute to changed expression of adhesion related genes. Two-step quantitative real-time polymerase chain reaction arrays were used to analyze the expression of adhesion related genes in 77 tumors and matched pair controls. The prognostic significance of genes was evaluated in TCGA (The Cancer Genome Atlas) data on 468 patients with renal cell carcinoma. Quantitative real-time polymerase chain reaction and Western blot were applied for TGF-β1 analysis. TGF-β1 mediated regulation of gene expression was analyzed by TGF-β1 supplementation of Caki-2 cells and quantitative real-time polymerase chain reaction. The expression of 19 genes related to adhesion and extracellular matrix remodeling was statistically significantly disturbed in renal cell carcinoma compared with controls. The 10-gene expression signature (COL1A1, COL5A1, COL11A1, FN1, ICAM1, ITGAL, ITGAM, ITGB2, THBS2 and TIMP1) correlated with poor survival (HR 2.85, p = 5.7e-10). TGF-β1 expression was 22 times higher in renal cell carcinoma than in controls (p adhesion and extracellular matrix remodeling develops early during renal cell carcinoma carcinogenesis and correlates with poor survival. TGF-β1 contributes to changed expression of extracellular matrix and adhesion related genes. Bioinformatic analysis performed on a broad panel of cancers of nonkidney origin suggests that disturbed expression of genes related to extracellular matrix and adhesion may be a universal feature of cancerous progression. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All

  5. Opposite prognostic roles of HIF1β and HIF2β expressions in bone metastatic clear cell renal cell cancer

    DEFF Research Database (Denmark)

    Szendroi, Attila; Szász, A. Marcell; Kardos, Magdolna

    2016-01-01

    BACKGROUND: Prognostic markers of bone metastatic clear cell renal cell cancer (ccRCC) are poorly established. We tested prognostic value of HIF1β/HIF2β and their selected target genes in primary tumors and corresponding bone metastases. RESULTS: Expression of HIF2β was lower in mRCC both at m...

  6. Immunomodulatory effects of intravenous bis-1 f(ab')(2) administration in renal-cell cancer-patients

    NARCIS (Netherlands)

    Janssen, R. A. J.; Kroesen, B. J.; Mesander, G.; Sleijfer, D. T.; The, T. Hauw; Mulder, N. H.; de Leij, L

    We report the immunomodulatory effects of an intravenous treatment with F(ab')(2) fragments of the bispecific monoclonal antibody BIS-1 during subcutaneous recombinant interleukin 2 (rIL-2) therapy of renal cell cancer (RCC) patients. BIS-1 is directed against both the CD3 antigen on T cells and the

  7. Cryotherapy for renal-cell cancer: diagnosis, treatment, and contrast-enhanced ultrasonography for follow-up

    NARCIS (Netherlands)

    Wink, M. H.; Lagerveld, B. W.; Laguna, M. P.; de la Rosette, J. J. M. C. H.; Wijkstra, H.

    2006-01-01

    Cryotherapy is a curative treatment option for patients with small ( <4 cm) renal-cell cancers. For the followup of ablated lesions, imaging is the only available method, but the best tool has not yet been determined. The method selected should be able to determine the presence or absence of

  8. Meat and fish consumption and the risk of renal cell carcinoma in the European prospective investigation into cancer and nutrition

    NARCIS (Netherlands)

    Rohrmann, Sabine; Linseisen, Jakob; Overvad, Kim; Wurtz, Anne Mette Lund; Roswall, Nina; Tjonneland, Anne; Boutron-Ruault, Marie-Christine; Racine, Antoine; Bastide, Nadia; Palli, Domenico; Agnoli, Claudia; Panico, Salvatore; Tumino, Rosario; Sacerdote, Carlotta; Weikert, Steffen; Steffen, Annika; Kuehn, Tilman; Li, Kuanrong; Khaw, Kay-Tee; Wareham, Nicholas J.; Bradbury, Kathryn E.; Peppa, Eleni; Trichopoulou, Antonia; Trichopoulos, Dimitrios; Bueno-de-Mesquita, H. Bas; Peeters, Petra H. M.; Hjartaker, Anette; Skeie, Guri; Weiderpass, Elisabete; Jakszyn, Paula; Dorronsoro, Miren; Barricarte, Aurelio; Santiuste de Pablos, Carmen; Molina-Montes, Esther; Alonso de la Torre, Ramon; Ericson, Ulrika; Sonestedt, Emily; Johansson, Mattias; Ljungberg, Borje; Freisling, Heinz; Romieu, Isabelle; Cross, Amanda J.; Vergnaud, Anne-Claire; Riboli, Elio; Boeing, Heiner

    2015-01-01

    Renal cell cancer (RCC) incidence varies worldwide with a higher incidence in developed countries and lifestyle is likely to contribute to the development of this disease. We examined whether meat and fish consumption were related to the risk of RCC in the European Prospective Investigation into

  9. Bortezomib in the management of multiple myeloma

    Directory of Open Access Journals (Sweden)

    Jacob P Laubach

    2009-09-01

    Full Text Available Jacob P Laubach, Constantine S Mitsiades, Teru Hideshima, Robert Schlossman, Dharminder Chauhan, Nikhil Munshi, Irene Ghobrial, Nicole Carreau, Kenneth C Anderson, Paul G RichardsonDepartment of Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts, USAAbstract: Multiple myeloma (MM is a B-cell malignancy characterized by clonal expansion of plasma cells within the bone marrow, the presence of a serum and/or urine monoclonal protein, lytic bone lesions, and anemia. On a cellular level, the disease is characterized by complex interactions between tumor cells and the surrounding bone marrow microenvironment. Understanding of the relationship between malignant plasma cells and the microenvironment has sparked ongoing efforts to develop targeted therapeutic agents for treatment of this disease. The successful development of the first-in-class small-molecule proteasome inhibitor bortezomib occurred as a result of these efforts. This review focuses on the rationale for bortezomib therapy in the treatment of patients with newly diagnosed and relapsed MM, important treatment-related side effects, and future directions for use of bortezomib and other, emerging proteasome inhibitors.Keywords: multiple myeloma, bortezomib, stem cell transplantation, peripheral neuropathy

  10. sup(99m)Tc-DMSA renal scintigraphy in renal failure due to various renal diseases

    Energy Technology Data Exchange (ETDEWEB)

    Hosokawa, S; Daijo, K; Okabe, T; Kawamura, J; Hara, A [Kyoto Univ. (Japan). Hospital

    1979-08-01

    Renal contours in renal failure were studied by means of sup(99m)Tc-dimercaptosuccinic acid (DMSA) renoscintigraphy. Renal cortical images were obtained even in renal failure cases. Causes of renal failure were chronic glomerulonephritis in 7, bilateral renal tuberculosis in 2, chronic pyelonephritis in 3, bilateral renal calculi in 3, diabetic nephropathy in 2, polycystic kidney disease in 2 and stomach cancer in 1.

  11. sup(99m)Tc-DMSA renal scintigraphy in renal failure due to various renal diseases

    International Nuclear Information System (INIS)

    Hosokawa, Shin-ichi; Daijo, Kazuyuki; Okabe, Tatsushiro; Kawamura, Juichi; Hara, Akira

    1979-01-01

    Renal contours in renal failure were studied by means of sup(99m)Tc-dimercaptosuccinic acid (DMSA) renoscintigraphy. Renal cortical images were obtained even in renal failure cases. Causes of renal failure were chronic glomerulonephritis in 7, bilateral renal tuberculosis in 2, chronic pyelonephritis in 3, bilateral renal calculi in 3, diabetic nephropathy in 2, polycystic kidney disease in 2 and stomach cancer in 1. (author)

  12. Resveratrol inhibits myeloma cell growth, prevents osteoclast formation, and promotes osteoblast differentiation

    DEFF Research Database (Denmark)

    Boissy, Patrice; Andersen, Thomas L; Abdallah, Basem M

    2005-01-01

    , a challenge for treating multiple myeloma is discovering drugs targeting not only myeloma cells but also osteoclasts and osteoblasts. Because resveratrol (trans-3,4',5-trihydroxystilbene) is reported to display antitumor activities on a variety of human cancer cells, we investigated the effects...... of this natural compound on myeloma and bone cells. We found that resveratrol reduces dose-dependently the growth of myeloma cell lines (RPMI 8226 and OPM-2) by a mechanism involving cell apoptosis. In cultures of human primary monocytes, resveratrol inhibits dose-dependently receptor activator of nuclear factor......RNA and cell surface protein levels and a decrease of NFATc1 stimulation and NF-kappaB nuclear translocation, whereas the gene expression of c-fms, CD14, and CD11a is up-regulated. Finally, resveratrol promotes dose-dependently the expression of osteoblast markers like osteocalcin and osteopontin in human bone...

  13. Body-mounted robotic instrument guide for image-guided cryotherapy of renal cancer

    Science.gov (United States)

    Hata, Nobuhiko; Song, Sang-Eun; Olubiyi, Olutayo; Arimitsu, Yasumichi; Fujimoto, Kosuke; Kato, Takahisa; Tuncali, Kemal; Tani, Soichiro; Tokuda, Junichi

    2016-01-01

    Purpose: Image-guided cryotherapy of renal cancer is an emerging alternative to surgical nephrectomy, particularly for those who cannot sustain the physical burden of surgery. It is well known that the outcome of this therapy depends on the accurate placement of the cryotherapy probe. Therefore, a robotic instrument guide may help physicians aim the cryotherapy probe precisely to maximize the efficacy of the treatment and avoid damage to critical surrounding structures. The objective of this paper was to propose a robotic instrument guide for orienting cryotherapy probes in image-guided cryotherapy of renal cancers. The authors propose a body-mounted robotic guide that is expected to be less susceptible to guidance errors caused by the patient’s whole body motion. Methods: Keeping the device’s minimal footprint in mind, the authors developed and validated a body-mounted, robotic instrument guide that can maintain the geometrical relationship between the device and the patient’s body, even in the presence of the patient’s frequent body motions. The guide can orient the cryotherapy probe with the skin incision point as the remote-center-of-motion. The authors’ validation studies included an evaluation of the mechanical accuracy and position repeatability of the robotic instrument guide. The authors also performed a mock MRI-guided cryotherapy procedure with a phantom to compare the advantage of robotically assisted probe replacements over a free-hand approach, by introducing organ motions to investigate their effects on the accurate placement of the cryotherapy probe. Measurements collected for performance analysis included accuracy and time taken for probe placements. Multivariate analysis was performed to assess if either or both organ motion and the robotic guide impacted these measurements. Results: The mechanical accuracy and position repeatability of the probe placement using the robotic instrument guide were 0.3 and 0.1 mm, respectively, at a depth

  14. Structural transition of kidney cystatin in dimethylnitrosamine-induced renal cancer in rats: identification as a novel biomarker for kidney cancer and prognosis.

    Science.gov (United States)

    Shamsi, Anas; Ahmed, Azaj; Bano, Bilqees

    2017-04-01

    In our study, renal cancer is induced in rats making use of dimethylnitrosamine (DMN). G1 - Group 1 were control rats and G2 - Group 2 rats were given a single intra-peritoneal injection of DMN of 50 mg/kg body weight resulting in 100% incidences of renal tumors after 12 months. SEM and histopathology confirmed the presence of renal cancer in the DMN-treated rats. Making use of ammonium sulfate precipitation and gel filtration chromatography on Sephacryl S-100HR column, a thiol protease inhibitor was isolated from kidney of control rats known as Rat kidney Cystatin (RKC) as well as from kidney of cancerous rat called as Cancerous Rat Kidney Cystatin (CRKC). Both these inhibitors were characterized, and interestingly, it was found that CRKC showed greater anti-papain activity and also it was stable in a broad pH and temperature range thus implying that CRKC is more stable as compared to RKC. UV and fluorescence spectroscopy point out in structural difference between RKC and CRKC which was further confirmed by Circular dichroism (CD) and FTIR spectroscopy. Our study clearly showed that kidney cystatin is structurally modified in the case of renal cancer and performs its role in a more efficacious manner.

  15. Palliative radiotherapy for multiple myeloma

    International Nuclear Information System (INIS)

    Furusawa, Mitsuhiro; Baba, Yuji; Murakami, Ryuji; Yokoyama, Toshimi; Nishimura, Ryuichi; Uozumi, Hideaki; Takada, Chitose; Takahashi, Mutsumasa

    1995-01-01

    This study reviews the experience of palliative radiotherapy to patients with multiple myeloma to define the optimal dose for pain relief. The records of 31 patients (66 sites) with multiple myeloma irradiated for palliation at Kumamoto University hospital between 1985 and 1994 were reviewed. Total dose ranged from 8 to 50 Gy, with a mean of 32.2 Gy. Symptoms included pain (78.1%), neurological abnormalities (28.1%), and palpable masses (34.3%). Symptomatic remission was obtained in 45 of 46 evaluable sites (97.8%). Complete remission of symptoms were obtained in 28.3%, and partial remission in 69.6%. According to fraction size, there was no significant difference between 3-5 Gy and 1.8-2 Gy. The incidence of complete remission increased when a total dose of more than 20 Gy was given. When the quality of life is considered, hypofractionation was recommended for the palliative radiation therapy of multiple myeloma. (author)

  16. Skeletal surveys in multiple myeloma

    International Nuclear Information System (INIS)

    Sebes, J.I.; Niell, H.B.; Palmieri, G.M.A.; Reidy, T.J.

    1986-01-01

    Thirty-three patients with multiple myeloma were studied with serial skeletal surveys, serum immunoglobulin levels, and postabsorptive urinary hydroxyproline (Spot-HYPRO) determinations. Twenty receiving chemotherapy were also followed with skeletal surveys in order to evaluate bone response to treatment. A close association was found between skeletal findings and changes in immunoglubulin levels with positive correlation in 71% of the patients. A similar association was found between skeletal disease and Spot-HYPRO level changes in 65%. Five of 12 patients (42%) with partial or complete clinical response to chemotherapy, demonstrated improvement in the appearance of skeletal lesions. Positive correlation between the roentgenographic changes and clinical markers of myeloma as well as therapeutic response, indicates that skeletal surveys are useful and effective in monitoring patients with multiple myeloma. (orig.)

  17. Case Report: Multiple Myeloma with Gangrene of Extremities

    Directory of Open Access Journals (Sweden)

    N Gharahi

    2009-07-01

    Full Text Available Introduction: Multiple myeloma represents a malignant proliferation of plasma cells derived from a single clone and it results in bone pain or fracture, renal failure, susceptibility to infections, anemia and hypercalcemia. The hyper viscosity syndrome is rare. Cryoglobulins are immunoglubulins that precipitate at temperatures less than 37degrees Celsius. Monoclonal cryoglobulins are usually present along with a specific hematologic disorder and are often asymptomatic. We report a second case of multiple myeloma with gangrene of all four extremities. Case: The Patient was a 77 year–old farmer with a 2 weeks history of coldness, pain and discoloration of the fingers of both the extremities which had extended to the mid forearm and shin regions. It was accompanied by skin erosions of the lower extremities, dark spots on the ear auricles and discoloration of the tip of the nose. On physical examination, quadrigangrene associated with ischemia of the auricles and tip of nose was seen. Serum proteins electrophoresis demonstrated monoclonal gammopathy and serum was positive for cryoglobulin, Bone marrow study showed neoplastic plasma cells infiltration. The patient was diagnosed as cryoglobulinemia based on multiple myeloma and treated accordingly.

  18. Potential genetic anticipation in hereditary leiomyomatosis-renal cell cancer (HLRCC).

    Science.gov (United States)

    Wong, Mei Hua; Tan, Chuen Seng; Lee, Soo Chin; Yong, Yvonne; Ooi, Aik Seng; Ngeow, Joanne; Tan, Min Han

    2014-06-01

    Hereditary leiomyomatosis-renal cell cancer (HLRCC) is an autosomal dominant disorder characterised by cutaneous leiomyomas, symptomatic uterine leiomyomas and aggressive type II papillary renal cell carcinoma. It is caused by heterozygous mutations in the fumarate hydratase (FH) gene on chromosome 1q43. We present evidence of genetic anticipation in HLRCC syndrome. A comprehensive literature review was performed to determine the potential for genetic anticipation in HLRCC syndrome. The normal random effects model was used to evaluate for genetic anticipation to ensure reduction in bias. A total of 11 FH kindreds with available multi-generational data were identified for analysis. The mean difference in age at diagnosis of RCC between the first and second generation was -18.6 years (95 % CI -26.6 to -10.6, p anticipation for uterine leiomyomas was observed (p = 0.349). We report preliminary evidence of genetic anticipation of RCC in HLRCC syndrome. Additional clinical validation is important to confirm this observation, which may have practical implications on counseling and timing of surveillance initiation. Exploration of the underlying mechanisms of anticipation in HLRCC would be of considerable biological interest.

  19. Open Partial Nephrectomy in Renal Cancer: A Feasible Gold Standard Technique in All Hospitals

    Directory of Open Access Journals (Sweden)

    J. M. Cozar

    2008-01-01

    Full Text Available Introduction. Partial nephrectomy (PN is playing an increasingly important role in localized renal cell carcinoma (RCC as a true alternative to radical nephrectomy. With the greater experience and expertise of surgical teams, it has become an alternative to radical nephrectomy in young patients when the tumor diameter is 4 cm or less in almost all hospitals since cancer-specific survival outcomes are similar to those obtained with radical nephrectomy. Materials and Methods. The authors comment on their own experience and review the literature, reporting current indications and outcomes including complications. The surgical technique of open partial nephrectomy is outlined. Conclusions. Nowadays, open PN is the gold standard technique to treat small renal masses, and all nonablative techniques must pass the test of time to be compared to PN. It is not ethical for patients to undergo radical surgery just because the urologists involved do not have adequate experience with PN. Patients should be involved in the final treatment decision and, when appropriate, referred to specialized centers with experience in open or laparoscopic partial nephrectomies.

  20. Multiple myeloma with extramedullary disease.

    Science.gov (United States)

    Oriol, Albert

    2011-11-01

    Plasmacytoma is a tumor mass consisting of atypical plasma cells. Incidence of plasmacytomas associated with multiple myeloma range from 7% to 17% at diagnosis and from 6% to 20% during the course of the disease. In both situations, occurrence of extramedullary disease has been consistently associated with a poorer prognosis of myeloma. Extramedullary relapse or progression occurs in a variety of clinical circumstances and settings, and therefore requires individualization of treatment. Alkylating agents, bortezomib, and immunomodulatory drugs, along with corticoids, have been used to treat extramedullary relapse but, because of the relatively low frequency or detection rate of extramedullary relapse, no efficacy data are available from controlled studies in this setting.

  1. Inequalities in reported cancer patient experience by socio-demographic characteristic and cancer site: evidence from respondents to the English Cancer Patient Experience Survey.

    Science.gov (United States)

    Saunders, C L; Abel, G A; Lyratzopoulos, G

    2015-01-01

    Patient experience is a critical dimension of cancer care quality. Understanding variation in experience among patients with different cancers and characteristics is an important first step for designing targeted improvement interventions. We analysed data from the 2011/2012 English Cancer Patient Experience Survey (n = 69,086) using logistic regression to explore inequalities in care experience across 64 survey questions. We additionally calculated a summary measure of variation in patient experience by cancer, and explored inequalities between patients with cancers treated by the same specialist teams. We found that younger and very old, ethnic minority patients and women consistently reported worse experiences across questions. Patients with small intestine/rarer lower gastrointestinal, multiple myeloma and hepatobiliary cancers were most likely to report negative experiences whereas patients with breast, melanoma and testicular cancer were least likely (top-to-bottom odds ratio = 1.91, P patients with cancers treated by the same specialty for five of nine services (P patients with ovarian, multiple myeloma, anal, hepatobiliary and renal cancer reported notably worse experiences than patients with other gynaecological, haematological, gastrointestinal and urological malignancies respectively. Initiatives to improve cancer patient experience across oncology services may be suitably targeted on patients at higher risk of poorer experience. © 2014 The Authors. European Journal of Cancer Care published by John Wiley & Sons Ltd.

  2. Dynamic contrast-enhanced computed tomography as a potential biomarker in patients with metastatic renal cell carcinoma: preliminary results from the Danish Renal Cancer Group Study-1

    DEFF Research Database (Denmark)

    Mains, Jill Rachel; Donskov, Frede; Pedersen, Erik Morre

    2014-01-01

    OBJECTIVES: The aim of this study was to explore the impact of dynamic contrast-enhanced (DCE) computer tomography (CT) as a biomarker in metastatic renal cell carcinoma (mRCC). MATERIALS AND METHODS: Twelve patients with favorable or intermediate Memorial Sloan Kettering Cancer Center risk group...... blinded to treatment group. The DCE-CT scans were performed at baseline, at weeks 5 and 10, and thereafter every third month. Blood flow (BF; mL/min/100 mL), peak enhancement (Hounsfield units), time to peak (seconds), and blood volume (BV; mL/100 g) were calculated. Parameters for DCE-CT were correlated...

  3. The pituitary tumor transforming gene 1 (PTTG-1: An immunological target for multiple myeloma

    Directory of Open Access Journals (Sweden)

    Gagliano Nicoletta

    2008-04-01

    Full Text Available Abstract Background Multiple Myeloma is a cancer of B plasma cells, which produce non-specific antibodies and proliferate uncontrolled. Due to the potential relapse and non-specificity of current treatments, immunotherapy promises to be more specific and may induce long-term immunity in patients. The pituitary tumor transforming gene 1 (PTTG-1 has been shown to be a novel oncogene, expressed in the testis, thymus, colon, lung and placenta (undetectable in most other tissues. Furthermore, it is over expressed in many tumors such as the pituitary adenoma, breast, gastrointestinal cancers, leukemia, lymphoma, and lung cancer and it seems to be associated with tumorigenesis, angiogenesis and cancer progression. The purpose was to investigate the presence/rate of expression of PTTG-1 in multiple myeloma patients. Methods We analyzed the PTTG-1 expression at the transcriptional and the protein level, by PCR, immunocytochemical methods, Dot-blot and ELISA performed on patient's sera in 19 multiple myeloma patients, 6 different multiple myeloma cell lines and in normal human tissue. Results We did not find PTTG-1 presence in the normal human tissue panel, but PTTG-1 mRNA was detectable in 12 of the 19 patients, giving evidence of a 63% rate of expression (data confirmed by ELISA. Four of the 6 investigated cell lines (66.6% were positive for PTTG-1. Investigations of protein expression gave evidence of 26.3% cytoplasmic expression and 16% surface expression in the plasma cells of multiple myeloma patients. Protein presence was also confirmed by Dot-blot in both cell lines and patients. Conclusion We established PTTG-1's presence at both the transcriptional and protein levels. These data suggest that PTTG-1 is aberrantly expressed in multiple myeloma plasma cells, is highly immunogenic and is a suitable target for immunotherapy of multiple myeloma.

  4. Biological Therapy Following Chemotherapy and Peripheral Stem Cell Transplantation in Treating Patients With Cancer

    Science.gov (United States)

    2013-03-25

    Breast Cancer; Chronic Myeloproliferative Disorders; Gestational Trophoblastic Tumor; Kidney Cancer; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Neuroblastoma; Ovarian Cancer; Sarcoma; Testicular Germ Cell Tumor

  5. Thrombotic thrombocytopenic purpura and myoglobinuric acute renal failure following radiation therapy in a patient with polymyositis and cervical cancer

    International Nuclear Information System (INIS)

    Makino, Hirofumi; Nagake, Yoshio; Moriwaki, Kazuhiko; Hirakawa, Shuzo; Katayama, Takaaki; Yanai, Hiroyuki; Takahashi, Kiyoshi; Akagi, Tadaatsu; Ota, Zensuke

    1995-01-01

    A 73-year-old woman was admitted to receive radiation treatment for uterine cervical cancer, however a complex series of events ensued, leading to death. She developed an acute exacerbation of polymyositis complicated by thrombocytopenic purpura, rhabdomyolysis and acute renal failure. Radiation therapy may have produced an immune disturbance leading to the acute exacerbation of polymyositis. Auto-immune-mediated endothelial damage might have triggered a series of events leading to thrombotic thrombocytopenic purpura. Rhabdomyolysis seemed to be the main cause of acute renal failure. (author)

  6. Thrombotic thrombocytopenic purpura and myoglobinuric acute renal failure following radiation therapy in a patient with polymyositis and cervical cancer

    Energy Technology Data Exchange (ETDEWEB)

    Makino, Hirofumi; Nagake, Yoshio; Moriwaki, Kazuhiko; Hirakawa, Shuzo; Katayama, Takaaki; Yanai, Hiroyuki; Takahashi, Kiyoshi; Akagi, Tadaatsu; Ota, Zensuke [Okayama Univ. (Japan). School of Medicine

    1995-01-01

    A 73-year-old woman was admitted to receive radiation treatment for uterine cervical cancer, however a complex series of events ensued, leading to death. She developed an acute exacerbation of polymyositis complicated by thrombocytopenic purpura, rhabdomyolysis and acute renal failure. Radiation therapy may have produced an immune disturbance leading to the acute exacerbation of polymyositis. Auto-immune-mediated endothelial damage might have triggered a series of events leading to thrombotic thrombocytopenic purpura. Rhabdomyolysis seemed to be the main cause of acute renal failure. (author).

  7. Immunological dysregulation in multiple myeloma microenvironment.

    Science.gov (United States)

    Romano, Alessandra; Conticello, Concetta; Cavalli, Maide; Vetro, Calogero; La Fauci, Alessia; Parrinello, Nunziatina Laura; Di Raimondo, Francesco

    2014-01-01

    Multiple Myeloma (MM) is a systemic hematologic disease due to uncontrolled proliferation of monoclonal plasma cells (PC) in bone marrow (BM). Emerging in other solid and liquid cancers, the host immune system and the microenvironment have a pivotal role for PC growth, proliferation, survival, migration, and resistance to drugs and are responsible for some clinical manifestations of MM. In MM, microenvironment is represented by the cellular component of a normal bone marrow together with extracellular matrix proteins, adhesion molecules, cytokines, and growth factors produced by both stromal cells and PC themselves. All these components are able to protect PC from cytotoxic effect of chemo- and radiotherapy. This review is focused on the role of immunome to sustain MM progression, the emerging role of myeloid derived suppressor cells, and their potential clinical implications as novel therapeutic target.

  8. Immunological Dysregulation in Multiple Myeloma Microenvironment

    Directory of Open Access Journals (Sweden)

    Alessandra Romano

    2014-01-01

    Full Text Available Multiple Myeloma (MM is a systemic hematologic disease due to uncontrolled proliferation of monoclonal plasma cells (PC in bone marrow (BM. Emerging in other solid and liquid cancers, the host immune system and the microenvironment have a pivotal role for PC growth, proliferation, survival, migration, and resistance to drugs and are responsible for some clinical manifestations of MM. In MM, microenvironment is represented by the cellular component of a normal bone marrow together with extracellular matrix proteins, adhesion molecules, cytokines, and growth factors produced by both stromal cells and PC themselves. All these components are able to protect PC from cytotoxic effect of chemo- and radiotherapy. This review is focused on the role of immunome to sustain MM progression, the emerging role of myeloid derived suppressor cells, and their potential clinical implications as novel therapeutic target.

  9. What Is the Key to Improving Renal Transplant Recipients' Awareness of Skin Cancer Risk?

    Science.gov (United States)

    Borghi, Alessandro; Corazza, Monica; Battaglia, Yuri; Maietti, Elisa; Minghetti, Sara; Virgili, Annarosa

    2016-01-01

    Previous studies have shown poor compliance rates regarding sun protection among organ transplant recipients. The main objective of the present study was to assess the awareness among renal transplant recipients (RTRs) of their risk of non-melanoma skin cancer (NMSC) development and their sunscreen use. The influence of several potentially relevant variables was also assessed in order to identify possible weak points on which to concentrate efforts in this respect. A total of 132 RTRs (92 males and 40 females) were included. The following information was collected and elaborated: (a) demographics; (b) skin phototype; (c) educational level; (d) time elapsed since transplantation; (e) immunosuppressive treatments; (f) previous dermatological visits; (g) patients' awareness of their NMSC risk; (h) use of sunscreen; and (i) previous documented NMSCs or NMSCs found during the study visit. Overall, 65 patients (49.2%) expressed awareness of their susceptibility to skin cancers. A high educational level was the main factor associated with patients' awareness. Thirty-six RTRs (27.3%) reported using sunscreen regularly. High educational level and awareness of personal susceptibility to NMSC development were the most relevant factors associated with sun protection habits. The present study showed the low level of sunscreen use among RTRs and their scanty awareness of personal skin cancer risk. Since educational level has been found to be highly related to both awareness of cancer risk and adequate use of sunscreen among RTRs, it is necessary to improve the way education is delivered by dermatologists and nephrologists, especially to subjects with a low educational level. © 2017 S. Karger AG, Basel.

  10. A Rare Cause of Acute Kidney Injury in a Female Patient with Breast Cancer Presenting as Renal Colic

    Directory of Open Access Journals (Sweden)

    Roxana Jurubita

    2016-01-01

    Full Text Available Renal infarction is a rare cause of acute kidney injury which could lead to permanent loss of renal function. A prompt diagnosis is necessary in order to achieve a successful revascularization of the occluded artery. Given the rarity of the disease and the paucity of the reported cases in the previous literature a high index of suspicion must be maintained not only in the classical cardiac sources of systemic emboli (atrial fibrillation, dilated cardiomyopathy, or endocarditis, but also in the situations when a hypercoagulable state is presumed. The unspecific presenting symptoms often mask the true etiology of the patient’s complaints. We present here a rare case of renal infarction that occurred in the setting of a hypercoagulable state, in a female patient with a history of breast cancer and documented hepatic metastases.

  11. Renal cell tumors with clear cell histology and intact VHL and chromosome 3p: a histological review of tumors from the Cancer Genome Atlas database.

    Science.gov (United States)

    Favazza, Laura; Chitale, Dhananjay A; Barod, Ravi; Rogers, Craig G; Kalyana-Sundaram, Shanker; Palanisamy, Nallasivam; Gupta, Nilesh S; Williamson, Sean R

    2017-11-01

    Clear cell renal cell carcinoma is by far the most common form of kidney cancer; however, a number of histologically similar tumors are now recognized and considered distinct entities. The Cancer Genome Atlas published data set was queried (http://cbioportal.org) for clear cell renal cell carcinoma tumors lacking VHL gene mutation and chromosome 3p loss, for which whole-slide images were reviewed. Of the 418 tumors in the published Cancer Genome Atlas clear cell renal cell carcinoma database, 387 had VHL mutation, copy number loss for chromosome 3p, or both (93%). Of the remaining, 27/31 had whole-slide images for review. One had 3p loss based on karyotype but not sequencing, and three demonstrated VHL promoter hypermethylation. Nine could be reclassified as distinct or emerging entities: translocation renal cell carcinoma (n=3), TCEB1 mutant renal cell carcinoma (n=3), papillary renal cell carcinoma (n=2), and clear cell papillary renal cell carcinoma (n=1). Of the remaining, 6 had other clear cell renal cell carcinoma-associated gene alterations (PBRM1, SMARCA4, BAP1, SETD2), leaving 11 specimens, including 2 high-grade or sarcomatoid renal cell carcinomas and 2 with prominent fibromuscular stroma (not TCEB1 mutant). One of the remaining tumors exhibited gain of chromosome 7 but lacked histological features of papillary renal cell carcinoma. Two tumors previously reported to harbor TFE3 gene fusions also exhibited VHL mutation, chromosome 3p loss, and morphology indistinguishable from clear cell renal cell carcinoma, the significance of which is uncertain. In summary, almost all clear cell renal cell carcinomas harbor VHL mutation, 3p copy number loss, or both. Of tumors with clear cell histology that lack these alterations, a subset can now be reclassified as other entities. Further study will determine whether additional entities exist, based on distinct genetic pathways that may have implications for treatment.

  12. Phosphoinositide protein kinase PDPK1 is a crucial cell signaling mediator in multiple myeloma.

    Science.gov (United States)

    Chinen, Yoshiaki; Kuroda, Junya; Shimura, Yuji; Nagoshi, Hisao; Kiyota, Miki; Yamamoto-Sugitani, Mio; Mizutani, Shinsuke; Sakamoto, Natsumi; Ri, Masaki; Kawata, Eri; Kobayashi, Tsutomu; Matsumoto, Yosuke; Horiike, Shigeo; Iida, Shinsuke; Taniwaki, Masafumi

    2014-12-15

    Multiple myeloma is a cytogenetically/molecularly heterogeneous hematologic malignancy that remains mostly incurable, and the identification of a universal and relevant therapeutic target molecule is essential for the further development of therapeutic strategy. Herein, we identified that 3-phosphoinositide-dependent protein kinase 1 (PDPK1), a serine threonine kinase, is expressed and active in all eleven multiple myeloma-derived cell lines examined regardless of the type of cytogenetic abnormality, the mutation state of RAS and FGFR3 genes, or the activation state of ERK and AKT. Our results revealed that PDPK1 is a pivotal regulator of molecules that are essential for myelomagenesis, such as RSK2, AKT, c-MYC, IRF4, or cyclin Ds, and that PDPK1 inhibition caused the growth inhibition and the induction of apoptosis with the activation of BIM and BAD, and augmented the in vitro cytotoxic effects of antimyeloma agents in myeloma cells. In the clinical setting, PDPK1 was active in myeloma cells of approximately 90% of symptomatic patients at diagnosis, and the smaller population of patients with multiple myeloma exhibiting myeloma cells without active PDPK1 showed a significantly less frequent proportion of the disease stage III by the International Staging System and a significantly more favorable prognosis, including the longer overall survival period and the longer progression-free survival period by bortezomib treatment, than patients with active PDPK1, suggesting that PDPK1 activation accelerates the disease progression and the resistance to treatment in multiple myeloma. Our study demonstrates that PDPK1 is a potent and a universally targetable signaling mediator in multiple myeloma regardless of the types of cytogenetic/molecular profiles. ©2014 American Association for Cancer Research.

  13. Immunogenic Chemotherapy Sensitizes Renal Cancer to Immune Checkpoint Blockade Therapy in Preclinical Models.

    Science.gov (United States)

    Cui, Shujin

    2017-07-11

    BACKGROUND Renal cell carcinoma (RCC) is among the most common malignant cancers of males worldwide. For advanced RCC patients, there still is no effective therapy. Immune checkpoint blockade therapies have shown benefits for many cancers, but previous clinical trials of immune checkpoint blockade therapies in RCC patients achieved only modest results. MATERIAL AND METHODS We explored the effects of combining chemotherapy with immune checkpoint blockade therapy in RCC xenograft mouse models. We also studied the potential mechanisms by which chemotherapy might enhance the efficacy of immune checkpoint blockade therapy, both in vitro and in vivo. RESULTS Our results showed that many commonly used chemotherapy agents can induce immunogenic marker release in RCC cell lines. Importantly, the RCC xenograft mouse model mice who received the combination treatment of 5-fluorouracil (5-FU) and anti-programmed cell death-ligand 1 (PD-L1) antibodies (Abs) had longer survival times compared to those who received 5-FU or anti-PD-L1 Abs alone. Also, increased key cytokines that promote tumor immunity, such as IL-2, IFN-γ, and TNF-α, as well as tumor-infiltrating cytotoxic T cells, were also increased after the combination treatment. CONCLUSIONS We conclude that 5-FU can sensitize RCC to anti-PD-L1 treatment by releasing the immune suppression in the tumor microenvironment.

  14. IgM myeloma: A multicenter retrospective study of 134 patients.

    Science.gov (United States)

    Castillo, Jorge J; Jurczyszyn, Artur; Brozova, Lucie; Crusoe, Edvan; Czepiel, Jacek; Davila, Julio; Dispenzieri, Angela; Eveillard, Marion; Fiala, Mark A; Ghobrial, Irene M; Gozzetti, Alessandro; Gustine, Joshua N; Hajek, Roman; Hungria, Vania; Jarkovsky, Jiri; Jayabalan, David; Laubach, Jacob P; Lewicka, Barbara; Maisnar, Vladimir; Manasanch, Elisabet E; Moreau, Philippe; Morgan, Elizabeth A; Nahi, Hareth; Niesvizky, Ruben; Paba-Prada, Claudia; Pika, Tomas; Pour, Ludek; Reagan, John L; Richardson, Paul G; Shah, Jatin; Spicka, Ivan; Vij, Ravi; Waszczuk-Gajda, Anna; Gertz, Morie A

    2017-08-01

    IgM myeloma is a rare hematologic malignancy for which the clinicopathological features and patient outcomes have not been extensively studied. We carried out a multicenter retrospective study in patients with diagnosis of IgM myeloma defined by >10% marrow involvement by monoclonal plasma cells, presence of an IgM monoclonal paraproteinemia of any size, and anemia, renal dysfunction, hypercalcemia, lytic lesions and/or t(11;14) identified by FISH. A total of 134 patients from 20 centers were included in this analysis. The median age at diagnosis was 65.5 years with a male predominance (68%). Anemia, renal dysfunction, elevated calcium and skeletal lytic lesions were found in 37, 43, 19, and 70%, respectively. The median serum IgM level was 2,895 mg dL -1 with 19% of patients presenting with levels >6,000 mg dL -1 . International Staging System (ISS) stages 1, 2, and 3 were seen in 40 (33%), 54 (44%), and 29 (24%) of patients, respectively. The malignant cells expressed CD20 (58%) and cyclin D1 (67%), and t(11;14) was the most common cytogenetic finding (39%). The median overall survival (OS) was 61 months. Higher ISS score was associated with worse survival (P = 0.02). Patients with IgM myeloma present with similar characteristics and outcomes as patients with more common myeloma subtypes. © 2017 Wiley Periodicals, Inc.

  15. Evaluation of anticancer effects of a novel proteasome inhibitor (Velcade), interferon (alpha-interferon) and anti myeloma antibodies on the growth of myeloma cells

    International Nuclear Information System (INIS)

    El shershaby, H.M.M.

    2013-01-01

    Cancer is an abnormal growth of cells caused by multiple changes in gene expression leading to deregulated balance of cell proliferation and cell death and ultimately evolving into a population of cells that can invade tissues and metastasize to distant sites, causing significant morbidity. Multiple myeloma (MM) is characterized by the accumulation of malignant plasma cells in the bone marrow leading to impaired hematopoiesis and bone diseases, which includes mainly lytic lesions, pathological fractures, hypercalcaemia and osteoporosis. Chemotherapy is the systemic treatment of cancer with anticancer drugs. Chemotherapy uses powerful drugs that work by slowing or stopping the cancer cells from growing, spreading or multiplying to other parts of the body. Extensive studies were run all over the world during the last years to discovery some new drugs which possess anticancer effect with less toxicity and have the ability to increase the survival time. In the current study Bortezomib was employed as chemotherapeutic drug for the treatment of myeloma cells where a variable dose of Bortezomib (5, 10,20,30,50 and 100 nM/ml) were used for treatment of myeloma cells in vitro. The results obtained indicated that the T.C/ml was decreased by increasing the drug conc. compared to that of control group. These results illustrated the effect of Bortezomib on the growth of myeloma cells, where the myeloma cell division was decreased while the older cells were deteriorated so that the T.C/ml were decreased. Also the viability of myeloma cells were significantly decreased after 72 hours of addition at drug concentration 20, 30, 50 and 100 nM/ml).

  16. Evolutionary Dynamics of Tumor-Stroma Interactions in Multiple Myeloma.

    Directory of Open Access Journals (Sweden)

    Javad Salimi Sartakhti

    Full Text Available Cancer cells and stromal cells cooperate by exchanging diffusible factors that sustain tumor growth, a form of frequency-dependent selection that can be studied in the framework of evolutionary game theory. In the case of multiple myeloma, three types of cells (malignant plasma cells, osteoblasts and osteoclasts exchange growth factors with different effects, and tumor-stroma interactions have been analysed using a model of cooperation with pairwise interactions. Here we show that a model in which growth factors have autocrine and paracrine effects on multiple cells, a more realistic assumption for tumor-stroma interactions, leads to different results, with implications for disease progression and treatment. In particular, the model reveals that reducing the number of malignant plasma cells below a critical threshold can lead to their extinction and thus to restore a healthy balance between osteoclast and osteoblast, a result in line with current therapies against multiple myeloma.

  17. Healthcare resource use and costs associated with chronic kidney disease in US private insurance patients with multiple myeloma.

    Science.gov (United States)

    Bhowmik, Debajyoti; Song, Xue; Intorcia, Michele; Kent, Shia T; Shi, Nianwen

    2018-01-01

    Objectives Within a median 1.2 years after patients have an initial diagnosis with multiple myeloma, up to 61% were diagnosed with renal impairment and 50% were diagnosed with chronic kidney disease. This study estimated economic burden associated with chronic kidney disease in multiple myeloma patients in the US. Methods In this retrospective cohort study, patients ≥18 years old with ≥1 inpatient or ≥ 2 outpatient multiple myeloma diagnoses between 1 January 2008 and 31 March 2015 were identified from MarketScan® Commercial and Medicare Supplemental Databases. Chronic kidney disease patients had ≥1 diagnosis of chronic kidney disease Stages 1-5 (first chronic kidney disease diagnosis date = index date) on or after the first multiple myeloma diagnosis, and were propensity score matched 1:1 to multiple myeloma patients without chronic kidney disease, end-stage renal disease, dialysis, or other type of chronically impaired renal function. All patients had ≥six-month continuous enrollment prior to index date and were followed for ≥one month from index date until the earliest of inpatient death, end of continuous enrollment, or end of the study period (30 September 2015). The per-patient per-year healthcare resource utilization and costs were measured during follow-up. Costs were total reimbursed amount in 2016 US dollars. Results A total of 2541 multiple myeloma patients with chronic kidney disease stages 1-5 and 2541 matched controls met the study criteria and were respectively 69.3 and 69.6 years, 54.5% and 55.3% men, and had 572.2 and 533.4 mean days of follow up. Compared to controls, chronic kidney disease patients had significantly (all P chronic kidney disease, end-stage renal disease, or dialysis had $78,455 ( P chronic kidney disease in patients with multiple myeloma was estimated to be between $34,754 and $78,455 per-patient per-year. Given its substantial clinical and economic impact, preservation of renal function is important in

  18. Genetic variants and multiple myeloma risk

    DEFF Research Database (Denmark)

    Martino, Alessandro; Campa, Daniele; Jurczyszyn, Artur

    2014-01-01

    BACKGROUND: Genetic background plays a role in multiple myeloma susceptibility. Several single-nucleotide polymorphisms (SNP) associated with genetic susceptibility to multiple myeloma were identified in the last years, but only a few of them were validated in independent studies. METHODS...... with multiple myeloma risk (P value range, 0.055-0.981), possibly with the exception of the SNP rs2227667 (SERPINE1) in women. CONCLUSIONS: We can exclude that the selected polymorphisms are major multiple myeloma risk factors. IMPACT: Independent validation studies are crucial to identify true genetic risk...

  19. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... Cancer Research Common Cancer Types Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer ... Genomics Research Research on Causes of Cancer Cancer Diagnosis Research Cancer Prevention Research Screening & Early Detection Cancer ...

  20. Involvement of multiple myeloma cell-derived exosomes in osteoclast differentiation

    Science.gov (United States)

    Raimondi, Lavinia; De Luca, Angela; Amodio, Nicola; Manno, Mauro; Raccosta, Samuele; Taverna, Simona; Bellavia, Daniele; Naselli, Flores; Fontana, Simona; Schillaci, Odessa; Giardino, Roberto; Fini, Milena; Tassone, Pierfrancesco; Santoro, Alessandra; De Leo, Giacomo; Giavaresi, Gianluca; Alessandro, Riccardo

    2015-01-01

    Bone disease is the most frequent complication in multiple myeloma (MM) resulting in osteolytic lesions, bone pain, hypercalcemia and renal failure. In MM bone disease the perfect balance between bone-resorbing osteoclasts (OCs) and bone-forming osteoblasts (OBs) activity is lost in favour of OCs, thus resulting in skeletal disorders. Since exosomes have been described for their functional role in cancer progression, we here investigate whether MM cell-derived exosomes may be involved in OCs differentiation. We show that MM cells produce exosomes which are actively internalized by Raw264.7 cell line, a cellular model of osteoclast formation. MM cell-derived exosomes positively modulate pre-osteoclast migration, through the increasing of CXCR4 expression and trigger a survival pathway. MM cell-derived exosomes play a significant pro-differentiative role in murine Raw264.7 cells and human primary osteoclasts, inducing the expression of osteoclast markers such as Cathepsin K (CTSK), Matrix Metalloproteinases 9 (MMP9) and Tartrate-resistant Acid Phosphatase (TRAP). Pre-osteoclast treated with MM cell-derived exosomes differentiate in multinuclear OCs able to excavate authentic resorption lacunae. Similar results were obtained with exosomes derived from MM patient's sera. Our data indicate that MM-exosomes modulate OCs function and differentiation. Further studies are needed to identify the OCs activating factors transported by MM cell-derived exosomes. PMID:25944696

  1. Beyond the CRAB symptoms: a study of presenting clinical manifestations of multiple myeloma.

    Science.gov (United States)

    Talamo, Giampaolo; Farooq, Umar; Zangari, Maurizio; Liao, Jason; Dolloff, Nathan G; Loughran, Thomas P; Epner, Elliot

    2010-12-01

    Although the typical clinical manifestations of multiple myeloma (MM) are summarized by the CRAB symptoms (hypercalcemia, renal insufficiency, anemia, and bone lesions), a significant proportion of patients with MM present with a variety of other clinical manifestations. We conducted a study evaluating the presenting symptoms that led to the diagnosis of MM. We conducted a retrospective review of 170 consecutive patients with MM seen at the Penn State Hershey Cancer Institute. Among patients with symptomatic MM, 74% presented with CRAB symptoms, 20% presented with non-CRAB manifestations, and 6% had both clinical features. Ten categories of non-CRAB manifestations were found, in order of decreasing frequency: neuropathy (because of spinal cord compression, nerve root compression, or peripheral neuropathy), extramedullary involvement, hyperviscosity syndrome, concomitant amyloidosis (eg, nephrotic syndrome or cardiopathy), hemorrhage/coagulopathy, systemic symptoms (eg, fever or weight loss), primary plasma cell leukemia, infections, cryoglobulinemia, and secondary gout. Kaplan-Meier estimates of survival in patients with non-CRAB manifestations did not show a significant difference from the survival of patients presenting with CRAB symptoms. Presenting symptoms of MM may be grouped in a total of 14 categories, 4 for the CRAB and 10 for the less common non-CRAB features. Grouped together, non-CRAB manifestations do not appear to confer a negative effect on the prognosis of patients with MM.

  2. Iodine-based contrast media, multiple myeloma and monoclonal gammopathies: literature review and ESUR Contrast Media Safety Committee guidelines.

    Science.gov (United States)

    Stacul, Fulvio; Bertolotto, Michele; Thomsen, Henrik S; Pozzato, Gabriele; Ugolini, Donatella; Bellin, Marie-France; Bongartz, Georg; Clement, Olivier; Heinz-Peer, Gertraud; van der Molen, Aart; Reimer, Peter; Webb, Judith A W

    2018-02-01

    Many radiologists and clinicians still consider multiple myeloma (MM) and monoclonal gammopathies (MG) a contraindication for using iodine-based contrast media. The ESUR Contrast Media Safety Committee performed a systematic review of the incidence of post-contrast acute kidney injury (PC-AKI) in these patients. A systematic search in Medline and Scopus databases was performed for renal function deterioration studies in patients with MM or MG following administration of iodine-based contrast media. Data collection and analysis were performed according to the PRISMA statement 2009. Eligibility criteria and methods of analysis were specified in advance. Cohort and case-control studies reporting changes in renal function were included. Thirteen studies were selected that reported 824 iodine-based contrast medium administrations in 642 patients with MM or MG, in which 12 unconfounded cases of PC-AKI were found (1.6 %). The majority of patients had intravenous urography with high osmolality ionic contrast media after preparatory dehydration and purgation. MM and MG alone are not risk factors for PC-AKI. However, the risk of PC-AKI may become significant in dehydrated patients with impaired renal function. Hypercalcaemia may increase the risk of kidney damage, and should be corrected before contrast medium administration. Assessment for Bence-Jones proteinuria is not necessary. • Monoclonal gammopathies including multiple myeloma are a large spectrum of disorders. • In monoclonal gammopathy with normal renal function, PC-AKI risk is not increased. • Renal function is often reduced in myeloma, increasing the risk of PC-AKI. • Correction of hypercalcaemia is necessary in myeloma before iodine-based contrast medium administration. • Bence-Jones proteinuria assessment in myeloma is unnecessary before iodine-based contrast medium administration.

  3. Chemosensitization of Human Renal Cell Cancer Using Antisense Oligonucleotides Targeting the Antiapoptotic Gene Clusterin

    Directory of Open Access Journals (Sweden)

    Tobias Zellweger

    2001-01-01

    Full Text Available BACKGROUND: Renal cell cancer (RCC is a chemoresistant disease with no active chemotherapeutic agent achieving objective response rates higher than 15%. Clusterin is a cell survival gene that increases in human renal tubular epithelial cells after various states of injury and disease. Downregulation of clusterin, using antisense oligonucleotides (ASO, has recently been shown to increase chemosensitivity in several prostate cancer models. The objectives in this study were to evaluate clusterin expression levels in human RCC and normal kidney tissue, and to test whether clusterin ASO could also enhance chemosensitivity in human RCC Caki-2 cells both in vitro and in vivo. METHODS: Immunohistochemical staining was used to characterize clusterin expression in 67 RCC and normal kidney tissues obtained from radical nephrectomy specimens. Northern blot analysis was used to assess changes in clusterin mRNA expression after ASO and paclitaxel treatment. The effects of combined clusterin ASO and paclitaxel treatment on Caki-2 cell growth was examined using an MTT assay. Athymic mice bearing Caki-2 tumors were treated with clusterin ASO alone, clusterin ASO plus paclitaxel, and mismatch control oligonucleotides plus paclitaxel, over a period of 28 days with measurement of tumor volumes once weekly over 8 weeks. RESULTS: Immunohistochemistry of normal and malignant kidney tissue sections of 67 patients demonstrated positive clusterin staining for almost all RCC (98% and an overexpression, compared to normal tissue, in a majority of RCC (69%. Clusterin ASO, but not mismatch control oligonucleotides, decreased clusterin mRNA expression in Caki-2 cells in a dosedependent and sequence-specific manner. Pretreatment of Caki-2 cells with clusterin ASO significantly enhanced chemosensitivity to paclitaxel in vitro. Characteristic apoptotic DNA laddering was observed after combined treatment with ASO plus paclitaxel, but not with either agent alone. In vivo

  4. Stereotactic body radiotherapy for renal cell cancer and pancreatic cancer. Literature review and practice recommendations of the DEGRO Working Group on Stereotactic Radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Panje, Cedric; Andratschke, Nikolaus; Guckenberger, Matthias [Zurich University Hospital, Department of Radiation Oncology, Zurich (Switzerland); Brunner, Thomas B. [Freiburg University Hospital, Department of Radiation Oncology, Freiburg (Germany); Niyazi, Maximilian [University of Munich, Department of Radiation Oncology, Munich (Germany)

    2016-12-15

    This report of the Working Group on Stereotactic Radiotherapy of the German Society of Radiation Oncology (DEGRO) aims to provide a literature review and practice recommendations for stereotactic body radiotherapy (SBRT) of primary renal cell cancer and primary pancreatic cancer. A literature search on SBRT for both renal cancer and pancreatic cancer was performed with focus on prospective trials and technical aspects for clinical implementation. Data on renal and pancreatic SBRT are limited, but show promising rates of local control for both treatment sites. For pancreatic cancer, fractionated SBRT should be preferred to single-dose treatment to reduce the risk of gastrointestinal toxicity. Motion-compensation strategies and image guidance are paramount for safe SBRT delivery in both tumor entities. SBRT for renal cancer and pancreatic cancer have been successfully evaluated in phase I and phase II trials. Pancreatic SBRT should be practiced carefully and only within prospective protocols due to the risk of severe gastrointestinal toxicity. SBRT for primary renal cell cancer appears a viable option for medically inoperable patients but future research needs to better define patient selection criteria and the detailed practice of SBRT. (orig.) [German] Die Arbeitsgruppe ''Stereotaktische Radiotherapie'' der Deutschen Gesellschaft fuer Radioonkologie (DEGRO) legt eine Zusammenfassung der aktuellen Literatur und daraus resultierende Empfehlungen zur Durchfuehrung der stereotaktischen Strahlentherapie (SBRT) beim Nierenzellkarzinom und beim Pankreaskarzinom vor. Es erfolgte eine Literaturrecherche zur Evidenz der SBRT beim Nierenzell- und Pankreaskarzinom, wobei der Schwerpunkt auf prospektive Studien und technische Aspekte fuer die klinische Umsetzung gelegt wurde. Fuer die SBRT beim Pankreaskarzinom und Nierenzellkarzinom sind bisher nur wenige Studien veroeffentlicht worden, die jedoch konsistent eine hohe Rate an lokaler Tumorkontrolle

  5. Tetraspanin 7 (TSPAN7) expression is upregulated in multiple myeloma patients and inhibits myeloma tumour development in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Cheong, Chee Man [Myeloma Research Laboratory, School of Medical Sciences, University of Adelaide, and South Australian Health and Medical Research Institute (SAHMRI), Adelaide 5000, SA (Australia); Chow, Annie W.S. [Myeloma Research Laboratory, School of Medical Sciences, University of Adelaide, and South Australian Health and Medical Research Institute (SAHMRI), Adelaide 5000, SA (Australia); Department of Haematology, SA Pathology, Adelaide 5000, SA (Australia); Fitter, Stephen [Myeloma Research Laboratory, School of Medical Sciences, University of Adelaide, and South Australian Health and Medical Research Institute (SAHMRI), Adelaide 5000, SA (Australia); Hewett, Duncan R. [Myeloma Research Laboratory, School of Medical Sciences, University of Adelaide, and South Australian Health and Medical Research Institute (SAHMRI), Adelaide 5000, SA (Australia); School of Medicine, University of Adelaide, Adelaide 5005, SA (Australia); Martin, Sally K. [Myeloma Research Laboratory, School of Medical Sciences, University of Adelaide, and South Australian Health and Medical Research Institute (SAHMRI), Adelaide 5000, SA (Australia); Department of Haematology, SA Pathology, Adelaide 5000, SA (Australia); School of Medicine, University of Adelaide, Adelaide 5005, SA (Australia); Williams, Sharon A. [Myeloma Research Laboratory, School of Medical Sciences, University of Adelaide, and South Australian Health and Medical Research Institute (SAHMRI), Adelaide 5000, SA (Australia); To, L. Bik [Department of Haematology, SA Pathology, Adelaide 5000, SA (Australia); and others

    2015-03-01

    Background: Increased expression of the tetraspanin TSPAN7 has been observed in a number of cancers; however, it is unclear how TSPAN7 plays a role in cancer progression. Methods: We investigated the expression of TSPAN7 in the haematological malignancy multiple myleoma (MM) and assessed the consequences of TSPAN7 expression in the adhesion, migration and growth of MM plasma cells (PC) in vitro and in bone marrow (BM) homing and tumour growth in vivo. Finally, we characterised the association of TSPAN7 with cell surface partner molecules in vitro. Results: TSPAN7 was found to be highly expressed at the RNA and protein level in CD138{sup +} MM PC from approximately 50% of MM patients. TSPAN7 overexpression in the murine myeloma cell line 5TGM1 significantly reduced tumour burden in 5TGM1/KaLwRij mice 4 weeks after intravenous adminstration of 5TGM1 cells. While TSPAN7 overexpression did not affect cell proliferation in vitro, TSPAN7 increased 5TGM1 cell adhesion to BM stromal cells and transendothelial migration. In addition, TSPAN7 was found to associate with the molecular chaperone calnexin on the cell surface. Conclusion: These results suggest that elevated TSPAN7 may be associated with better outcomes for up to 50% of MM patients. - Highlights: • TSPAN7 expression is upregulated in newly-diagnosed patients with active multiple myeloma. • Overexpression of TSPAN7 inhibits myeloma tumour development in vivo. • TSPAN7 interacts with calnexin at the plasma membrane in a myeloma cell line.

  6. Synchronous Oligometastatic Non-Small Cell Lung Cancer and Isolated Renal Cell Carcinoma: A Case Report and Literature Review.

    Science.gov (United States)

    Nguyen, Timothy K; Louie, Alexander V

    2015-10-27

    A 58-year-old gentleman presenting with a progressive headache, visual disturbance, decreased appetite, and weight loss was found to have a localized clear cell carcinoma of the kidney and synchronous Stage IV non-small cell lung cancer with a solitary brain metastasis. This case illustrates the challenges in distinguishing between primary and metastatic disease in a patient with both renal cell carcinoma and lung cancer. We highlight the uncertainties in the diagnosis and management of this unique clinical scenario and the potential implications on prognosis.

  7. Bone morphogenetic protein-9 suppresses growth of myeloma cells by signaling through ALK2 but is inhibited by endoglin

    International Nuclear Information System (INIS)

    Olsen, O E; Wader, K F; Misund, K; Våtsveen, T K; Rø, T B; Mylin, A K; Turesson, I; Størdal, B F; Moen, S H; Standal, T; Waage, A; Sundan, A; Holien, T

    2014-01-01

    Multiple myeloma is a malignancy of plasma cells predominantly located in the bone marrow. A number of bone morphogenetic proteins (BMPs) induce apoptosis in myeloma cells in vitro, and with this study we add BMP-9 to the list. BMP-9 has been found in human serum at concentrations that inhibit cancer cell growth in vitro. We here show that the level of BMP-9 in serum was elevated in myeloma patients (median 176 pg/ml, range 8–809) compared with healthy controls (median 110 pg/ml, range 8–359). BMP-9 was also present in the bone marrow and was able to induce apoptosis in 4 out of 11 primary myeloma cell samples by signaling through ALK2. BMP-9-induced apoptosis in myeloma cells was associated with c-MYC downregulation. The effects of BMP-9 were counteracted by membrane-bound (CD105) or soluble endoglin present in the bone marrow microenvironment, suggesting a mechanism for how myeloma cells can evade the tumor suppressing activity of BMP-9 in multiple myeloma

  8. Induction of potent NK cell-dependent anti-myeloma cytotoxic T cells in response to combined mapatumumab and bortezomib.

    Science.gov (United States)

    Neeson, Paul J; Hsu, Andy K; Chen, Yin R; Halse, Heloise M; Loh, Joanna; Cordy, Reece; Fielding, Kate; Davis, Joanne; Noske, Josh; Davenport, Alex J; Lindqvist-Gigg, Camilla A; Humphreys, Robin; Tai, Tsin; Prince, H Miles; Trapani, Joseph A; Smyth, Mark J; Ritchie, David S

    2015-09-01

    There is increasing evidence that some cancer therapies can promote tumor immunogenicity to boost the endogenous antitumor immune response. In this study, we used the novel combination of agonistic anti-TRAIL-R1 antibody (mapatumumab, Mapa) with low dose bortezomib (LDB) for this purpose. The combination induced profound myeloma cell apoptosis, greatly enhanced the uptake of myeloma cell apoptotic bodies by dendritic cell (DC) and induced anti-myeloma cytotoxicity by both CD8 + T cells and NK cells. Cytotoxic lymphocyte expansion was detected within 24 h of commencing therapy and was maximized when myeloma-pulsed DC were co-treated with low dose bortezomib and mapatumumab (LDB+Mapa) in the presence of NK cells. This study shows that Mapa has two distinct but connected modes of action against multiple myeloma (MM). First, when combined with LDB, Mapa produced powerful myeloma cell apoptosis; secondly, it promoted DC priming and an NK cell-mediated expansion of anti-myeloma cytotoxic lymphocyte (CTL). Overall, this study indicates that Mapa can be used to drive potent anti-MM immune responses.

  9. CDK2 phosphorylation of Smad2 disrupts TGF-beta transcriptional regulation in resistant primary bone marrow myeloma cells.

    Science.gov (United States)

    Baughn, Linda B; Di Liberto, Maurizio; Niesvizky, Ruben; Cho, Hearn J; Jayabalan, David; Lane, Joseph; Liu, Fang; Chen-Kiang, Selina

    2009-02-15

    Resistance to growth suppression by TGF-beta1 is common in cancer; however, mutations in this pathway are rare in hematopoietic malignancies. In multiple myeloma, a fatal cancer of plasma cells, malignant cells accumulate in the TGF-beta-rich bone marrow due to loss of both cell cycle and apoptotic controls. Herein we show that TGF-beta activates Smad2 but fails to induce cell cycle arrest or apoptosis in primary bone marrow myeloma and human myeloma cell lines due to its inability to activate G(1) cyclin-dependent kinase (CDK) inhibitors (p15(INK4b), p21(CIP1/WAF1), p27(KIP1), p57(KIP2)) or to repress c-myc and Bcl-2 transcription. Correlating with aberrant activation of CDKs, CDK-dependent phosphorylation of Smad2 on Thr(8) (pT8), a modification linked to impaired Smad activity, is elevated in primary bone marrow myeloma cells, even in asymptomatic monoclonal gammopathy of undetermined significance. Moreover, CDK2 is the predominant CDK that phosphorylates Smad2 on T8 in myeloma cells, leading to inhibition of Smad2-Smad4 association that precludes transcriptional regulation by Smad2. Our findings provide the first direct evidence that pT8 Smad2 couples dysregulation of CDK2 to TGF-beta resistance in primary cancer cells, and they suggest that disruption of Smad2 function by CDK2 phosphorylation acts as a mechanism for TGF-beta resistance in multiple myeloma.

  10. Emerging therapies in multiple myeloma.

    Science.gov (United States)

    El-Amm, Joelle; Tabbara, Imad A

    2015-06-01

    The treatment of multiple myeloma has evolved significantly over the past 2 decades due to the use of high-dose chemotherapy and autologous stem cell transplantation, and the subsequent introduction of the immunomodulatory agents (thalidomide and lenalidomide) and the proteasome inhibitor (bortezomib). The median overall survival of multiple myeloma patients has increased significantly with patients younger than age 50 years experiencing a 10-year survival rate of around 40%. However, despite the increased effectiveness of the first-line agents, the majority of patients will eventually relapse and become drug resistant. Promising novel therapies have recently emerged and are being used to treat relapsed and refractory patients. This review will cover the clinical data regarding these emergent therapies that include new generation of proteasome inhibitors (carfilzomib, ixazomib, oprozomib, and marizomib), immunomodulatory drugs (pomalidomide), monoclonal antibodies (elotuzumab and daratumumab), signal transduction modulator (perifosine), and histone deacetylase inhibitors (vorinostat and panobinostat).

  11. Renal cell cancer in Israel: sex and ethnic differences in incidence and mortality, 1980-2004.

    Science.gov (United States)

    Tarabeia, Jalal; Kaluski, Dorit Nitzan; Barchana, Micha; Dichtiar, Rita; Green, Manfred S

    2010-06-01

    The causes of renal cell cancer (RCC) remain largely unexplained. While the incidence is generally higher in men than in women, little has been reported on ethnic differences. We examine trends in RCC incidence and mortality rates among Israeli Arab and Jewish populations and compared with the rates in other countries. Age-adjusted RCC incidence and mortality rates in Israel, during 1980-2004, were calculated by sex and population group, using the National Cancer Registry. They were compared with the United States based on the Surveillance Epidemiology and End Results [SEER] program and the IARC database for international comparisons. While RCC incidence rates in Israel are similar to the United States and the European average, the rates are significantly higher among Israeli Jews than Arabs. Men are affected more than women. Incidence rates over the last 24 years have increased among all men and Jewish women, but not among Arab women. Among men, the incidence rate ratio for Jews to Arabs declined from 3.96 in 1980-1982 to 2.34 in 2001-2004, whereas for women there was no change. The mortality rates were higher among Jews than Arab and among men than women. There were no significant change in the mortality rates and rate ratios. Our findings demonstrate marked ethnic differences in RCC in Israel. The lower incidence among Arabs stands in contrast to the higher prevalence of potential risk factors for RCC in this population group. Genetic factors, diet and other lifestyle factors could play protective roles. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

  12. Pro-Tumorigenic Phosphorylation of p120 Catenin in Renal and Breast Cancer.

    Directory of Open Access Journals (Sweden)

    Antonis Kourtidis

    Full Text Available Altered protein expression and phosphorylation are common events during malignant transformation. These perturbations have been widely explored in the context of E-cadherin cell-cell adhesion complexes, which are central in the maintenance of the normal epithelial phenotype. A major component of these complexes is p120 catenin (p120, which binds and stabilizes E-cadherin to promote its adhesive and tumor suppressing function. However, p120 is also an essential mediator of pro-tumorigenic signals driven by oncogenes, such as Src, and can be phosphorylated at multiple sites. Although alterations in p120 expression have been extensively studied by immunohistochemistry (IHC in the context of tumor progression, little is known about the status and role of p120 phosphorylation in cancer. Here we show that tyrosine and threonine phosphorylation of p120 in two sites, Y228 and T916, is elevated in renal and breast tumor tissue samples. We also show that tyrosine phosphorylation of p120 at its N-terminus, including at the Y228 site is required for its pro-tumorigenic potential. In contrast, phosphorylation of p120 at T916 does not affect this p120 function. However, phosphorylation of p120 at T916 interferes with epitope recognition of the most commonly used p120 antibody, namely pp120. As a result, this antibody selectively underrepresents p120 levels in tumor tissues, where p120 is phosphorylated. Overall, our data support a role of p120 phosphorylation as a marker and mediator of tumor transformation. Importantly, they also argue that the level and localization of p120 in human cancer tissues immunostained with pp120 needs to be re-evaluated.

  13. Comparison of diagnostic protocols and the equivalent effective dose in renal cancer and herniated lumbar disc

    International Nuclear Information System (INIS)

    Ruiz Perez de Villar, M.J.; Vano Carruana, E.; Lanzos Gonbzalez, E.; Perez Torrubia, A.

    1994-01-01

    Renal cancer (RC) and herniated lumbar disc (HLD) were the two pathologies selected for the study of the diagnostic protocols applied in different centers to determine how their variability is reflected in the effective equivalent dose (EED) and establish the optimal radiological protocol for diagnostic purposes, while using the lowest possible dose. On the basis of 222 case histories, it was observed that the EED resulting from the diagnosis of HLD can vary as much as a factor of 3(6.2-18.9 mSv). Likewise, the EED related to the diagnosis of RC can be modified by a factor of 1.5(32.6-48.3 mSv), depending on the diagnostic protocol employed. It can be considered that the optimal protocol to reach a diagnosis of HLD includes chest x-ray, lumbar spine x-ray and lumbar CT scan, while that required for the diagnosis of RC involves chest x-ray, IVU, abdominal CT scan and digital subtraction angiography. The optimization of the study protocols-especially the reduction of the number of exposures, modernization and quality control of the equipment, among other aspects, can reduce the EED by a factor of 2. (Author)

  14. Predicting risk of nonmelanoma skin cancer and premalignant skin lesions in renal transplant recipients.

    Science.gov (United States)

    Urwin, Helen R; Jones, Peter W; Harden, Paul N; Ramsay, Helen M; Hawley, Carmel M; Nicol, David L; Fryer, Anthony A

    2009-06-15

    Nonmelanoma skin cancer (NMSC) and associated premalignant lesions represent a major complication after transplantation, particularly in areas with high ultraviolet radiation (UVR) exposure. The American Society of Transplantation has proposed annual NMSC screening for all renal transplant recipients. The aim of this study was to develop a predictive index (PI) that could be used in targeted screening. Data on patient demographics, UVR exposure, and other clinical parameters were collected on 398 adult recipients recruited from the Princess Alexandra Hospital, Brisbane. Structured interview, skin examination, biopsy of lesions, and review of medical/pathologic records were performed. Time to presentation with the first NMSC was assessed using Cox's regression models and Kaplan-Meier estimates used to assess detection of NMSC during screening. Stepwise selection identified age, outdoor UVR exposure, living in a hot climate, pretransplant NMSC, childhood sunburning, and skin type as predictors. The PI generated was used to allocate patients into three screening groups (6 months, 2 years, and 5 years). The survival curves of these groups were significantly different (PPI to enable development of targeted NMSC surveillance strategies.

  15. Radiological evaluation of response to treatment: Application to metastatic renal cancers receiving anti-angiogenic treatment

    International Nuclear Information System (INIS)

    Ammari, S.; Hernigou, A.; Grataloup, C.; Thiam, R.; Cuenod, C.A.; Siauve, N.; Fournier, L.S.; Oudard, S.; Medioni, J.

    2014-01-01

    Targeted therapies have considerably improved the prognosis of patients with metastatic renal cancer (mRCC) but there are no reliable response assessment criteria reflecting the clinical benefits, because there is no regression in size, or it is delayed. Such criteria would help early identification of non-responders, who would then benefit from a change of treatment, and would avoid their being subjected to unnecessary side effects related to the treatment. We will review the imaging techniques currently available for evaluating tumour response in mRCC patients, including the response evaluation criteria in solid tumours (RECIST), the Choi criteria, the modified Choi criteria, and the CT size and attenuation criteria (SACT). We will also discuss functional imaging techniques, which are based on the physiological characteristics of the tumours, such as perfusion CT, magnetic resonance imaging or ultrasound (DCE-CT, DCE-MRI, DCE-US), diffusion MRI, BOLD MRI and new positron emission tomography (PET) tracers. It is not possible at present to propose a unanimously acknowledged criterion for evaluating tumour response to targeted therapy. However, there is a real need for this according to oncologists and the pharmaceutical industry, and radiologists need to be involved in reflecting on the subject. (authors)

  16. Dose-dependent changes in renal 1H-/23Na MRI after adjuvant radiochemotherapy for gastric cancer

    International Nuclear Information System (INIS)

    Haneder, Stefan; Budjan, Johannes Michael; Schoenberg, Stefan Oswald; Konstandin, Simon; Schad, Lothar Rudi; Hofheinz, Ralf Dieter; Gramlich, Veronika; Wenz, Frederik; Lohr, Frank; Boda-Heggemann, Judit

    2015-01-01

    Combined radiochemotherapy (RCT) for gastric cancer with three-dimensional conformal radiotherapy (3D-CRT) results in ablative doses to the upper left kidney, while image-guided intensity-modulated radiotherapy (IG-IMRT) allows kidney sparing despite improved target coverage. Renal function in long-term gastric cancer survivors was evaluated with 3T functional magnetic resonance imaging (MRI) including diffusion-weighted imaging (DWI) and 23 Na imaging. Five healthy volunteers and 13 patients after radiotherapy were included: 11 x IG-IMRT; 1 x 3D-CRT; 1 x ''positive control'' with stereotactic body radiotherapy (SBRT) of a metastasis between the spleen/left kidney. Radiation doses were documented for the upper/middle/lower kidney subvolumes. Late toxicity was evaluated based on CTC criteria, questionnaire, and creatinine values. Morphological sequences, DWI images, and 23 Na images were acquired using a 1 H/ 23 Na-tuned body-coil before/after intravenous water load (WL). Statistics for [ 23 Na] (concentration) and apparent diffusion coefficient (ADC) values were calculated for upper/middle/lower renal subvolumes. Corticomedullary [ 23 Na] gradients and [ 23 Na] differences after WL were determined. No major morphological alteration was detected in any patient. Minor scars were observed in the cranial subvolume of the left kidney of the 3D-CRT and the whole kidney of the control SBRT patient. All participants presented a corticomedullary [ 23 Na] gradient. After WL, a significant physiological [ 23 Na] gradient decrease (p < 0.001) was observed in all HV and IG-IMRT patients. In the cranial left kidney of the 3D-CRT patient and the positive control SBRT patient, the decrease was nonsignificant (p = 0.01, p = 0.02). ADC values were altered nonsignificantly in all renal subvolumes (all participants). Renal subvolumes with doses ≥ 35 Gy showed a reduced change of the [ 23 Na] gradient after WL (p = 0.043). No participants showed clinical renal

  17. Oncological outcomes of laparoscopic radical nephrectomy for renal cancer Resultados oncológicos da nefrectomia radical laparoscópica no tratamento do carcinoma renal

    Directory of Open Access Journals (Sweden)

    Jose R. Colombo Jr.

    2007-01-01

    Full Text Available PURPOSE: To report the 5-year oncological outcomes of patients undergoing laparoscopic radical nephrectomy for renal cancer compared to a cohort of patients undergoing open radical nephrectomy. METHODS: We retrospectively analyzed the data of 88 patients undergoing radical nephrectomy for renal cell carcinoma prior to January 2000. Of these, 45 patients underwent laparoscopic radical nephrectomy, and 43 patients underwent open radical nephrectomy. Inclusion criteria comprised clinically organ-confined tumors of 15 cm or less in size without concomitant lymphadenopathy or vena cava thrombus. Oncological follow-up data were obtained from charts, radiological reports, and phone calls to patients or their families, and were calculated from the date of surgery to the date of last appointment with physician or date of death. RESULTS: All laparoscopic procedures were completed without open conversion. On comparing the laparoscopic radical nephrectomy and open radical nephrectomy groups, mean tumor size was 5. 8 vs 6.2 cm (P = . 44, mean blood loss was 183 vs 461 mL (P = . 004, and mean operative time was 2.8 vs 3.7 hrs (P OBJETIVO: Relatar os resultados oncológicos após 5 anos de seguimento em pacientes submetidos a nefrectomia radical laparoscópica para tratamento do câncer renal, comparando esses com os resultados obtidos com um grupo de pacientes submetidos a nefrectomia radical aberta. MÉTODOS: Foram analisadas retrospectivamente as informações obtidas de 88 pacientes submetidos a nefrectomia radical para o tratamento do carcinoma renal realizadas previamente a Janeiro de 2000. Destes pacientes, 45 foram tratados com nefrectomia radical laparoscópica e 43 com nefrectomia radical aberta. Foram incluídos pacientes com tumores localizados com tamanho máximo de 15 cm, sem adenopatia ou sinal de envolvimento de veia renal na avaliação radiologica pré-operatória. As informações sobre o seguimento dos pacientes foram obtidas a partir de

  18. Imaging of multiple myeloma and related monoclonal plasma cell diseases. An update; Bildgebung des multiplen Myeloms und verwandter monoklonaler Plasmazellerkrankungen. Ein Update

    Energy Technology Data Exchange (ETDEWEB)

    Weber, Marc-Andre [Universitaetsklinikum, Heidelberg (Germany). Abt. Diagnostische und Interventionelle Radiologie; Delorme, Stefan [Deutsches Krebsforschungszentrum, Heidelberg (Germany). Abt. Radiologie; Hillengass, Jens [Universitaetsklinikum, Heidelberg (Germany). Sektion Multiples Myelom

    2014-09-15

    Multiple myeloma is a hematologic disorder characterized by the infiltration and proliferation of monoclonal plasma cells mainly in the bone marrow. The main symptoms are hypercalcemia, renal impairment, cytopenia/anemia and bone disease - summarized as CRAB-criteria. Symptomatic multiple myeloma is consistently preceded by asymptomatic premalignant stages called monoclonal gammopathy of undetermined significance and smoldering multiple myeloma. Staging of multiple myeloma is based on the measurement of the monoclonal protein in serum and urine as well as the assessment of impairment of hematopoiesis, renal function and mineralized bone. In the last decade the development of novel therapeutic agents has led to an increase in response rates and survival time of patients with multiple myeloma, which further stresses the value of response assessment by imaging. Cross sectional imaging like MRI and CT is currently replacing conventional radiological surveys in the initial work-up and follow-up of patients with monoclonal plasma cell diseases. The added value of MRI is to improve initial staging by unraveling a diffuse infiltration of bone marrow by plasma cells, a focal pattern or a combination of both. Furthermore, a complete remission of myeloma confirmed by MRI and CT goes along with a better prognosis compared to a complete response based only on serological parameters.

  19. Immunoparesis in newly diagnosed Multiple Myeloma patients

    DEFF Research Database (Denmark)

    Sorrig, Rasmus; Klausen, Tobias W.; Salomo, Morten

    2017-01-01

    Immunoparesis (hypogammaglobulinemia) is associated to an unfavorable prognosis in newly diagnosed Multiple myeloma (MM) patients. However, this finding has not been validated in an unselected population-based cohort. We analyzed 2558 newly diagnosed MM patients in the Danish Multiple Myeloma...

  20. Respiration-induced movement correlation for synchronous noninvasive renal cancer surgery.

    Science.gov (United States)

    Abhilash, Rakkunedeth H; Chauhan, Sunita

    2012-07-01

    Noninvasive surgery (NIS), such as high-intensity focused ultrasound (HIFU)-based ablation or radiosurgery, is used for treating tumors and cancers in various parts of the body. The soft tissue targets (usually organs) deform and move as a result of physiological processes such as respiration. Moreover, other deformations induced during surgery by changes in patient position, changes in physical properties caused by repeated exposures and uncertainties resulting from cavitation also occur. In this paper, we present a correlation-based movement prediction technique to address respiration-induced movement of the urological organs while targeting through extracorporeal trans-abdominal route access. Among other organs, kidneys are worst affected during respiratory cycles, with significant three-dimensional displacements observed on the order of 20 mm. Remote access to renal targets such as renal carcinomas and cysts during noninvasive surgery, therefore, requires a tightly controlled real-time motion tracking and quantitative estimate for compensation routine to synchronize the energy source(s) for precise energy delivery to the intended regions. The correlation model finds a mapping between the movement patterns of external skin markers placed on the abdominal access window and the internal movement of the targeted kidney. The coarse estimate of position is then fine-tuned using the Adaptive Neuro-Fuzzy Inference System (ANFIS), thereby achieving a nonlinear mapping. The technical issues involved in this tracking scheme are threefold: the model must have sufficient accuracy in mapping the movement pattern; there must be an image-based tracking scheme to provide the organ position within allowable system latency; and the processing delay resulting from modeling and tracking must be within the achievable prediction horizon to accommodate the latency in the therapeutic delivery system. The concept was tested on ultrasound image sequences collected from 20 healthy

  1. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... Types Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer Leukemia Liver ... on Causes of Cancer Cancer Diagnosis Research Cancer Prevention Research Screening & Early Detection Cancer Treatment Research Cancer & ...

  2. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... Types Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer Leukemia Liver ... of Cancer Cancer Diagnosis Research Cancer Prevention Research Screening & Early Detection Cancer Treatment Research Cancer & Public Health ...

  3. LINE-1 methylation levels in leukocyte DNA and risk of renal cell cancer.

    Directory of Open Access Journals (Sweden)

    Linda M Liao

    Full Text Available Leukocyte global DNA methylation levels are currently being considered as biomarkers of cancer susceptibility and have been associated with risk of several cancers. In this study, we aimed to examine the association between long interspersed nuclear elements (LINE-1 methylation levels, as a biomarker of global DNA methylation in blood cell DNA, and renal cell cancer risk.LINE-1 methylation of bisulfite-converted genomic DNA isolated from leukocytes was quantified by pyrosequencing measured in triplicate, and averaged across 4 CpG sites. A total of 328 RCC cases and 654 controls frequency-matched(2∶1 on age(±5years, sex and study center, from a large case-control study conducted in Central and Eastern Europe were evaluated.LINE-1 methylation levels were significantly higher in RCC cases with a median of 81.97% (interquartile range[IQR]: 80.84-83.47 compared to 81.67% (IQR: 80.35-83.03 among controls (p = 0.003, Wilcoxon. Compared to the lowest LINE-1 methylation quartile(Q1, the adjusted ORs for increasing methylation quartiles were as follows: OR(Q2 = 1.84(1.20-2.81, OR(Q3 = 1.72(1.11-2.65 and OR(Q4 = 2.06(1.34-3.17, with a p-trend = 0.004. The association was stronger among current smokers (p-trend<0.001 than former or never smokers (p-interaction = 0.03. To eliminate the possibility of selection bias among controls, the relationship between LINE-1 methylation and smoking was evaluated and confirmed in a case-only analysis, as well.Higher levels of LINE-1 methylation appear to be positively associated with RCC risk, particularly among current smokers. Further investigations using both post- and pre-diagnostic genomic DNA is warranted to confirm findings and will be necessary to determine whether the observed differences occur prior to, or as a result of carcinogenesis.

  4. Paradoxical resistance of multiple myeloma to proteasome inhibitors by decreased levels of 19S proteasomal subunits

    DEFF Research Database (Denmark)

    Acosta-Alvear, Diego; Cho, Min Y; Wild, Thomas

    2015-01-01

    Hallmarks of cancer, including rapid growth and aneuploidy, can result in non-oncogene addiction to the proteostasis network that can be exploited clinically. The defining example is the exquisite sensitivity of multiple myeloma (MM) to 20S proteasome inhibitors, such as carfilzomib. However, MM...

  5. Everolimus: the first approved product for patients with advanced renal cell cancer after sunitinib and/or sorafenib

    Directory of Open Access Journals (Sweden)

    Chris Coppin

    2010-04-01

    Full Text Available Chris CoppinMedical Oncology, BC Cancer Agency and University of British Columbia, Vancouver, CanadaAbstract: Everolimus (RAD001, Afinitor® Novartis is the first oral inhibitor of mTOR (mammalian target of rapamycin to reach the oncology clinic. Everolimus 10 mg daily achieves complete inhibition of its target at below the maximum tolerable dose for most patients. A phase III randomized placebo-controlled trial has examined the impact of everolimus in patients with clear cell renal cancers and progressive disease on or within 6 months of the VEGFR tyrosine kinase inhibitors sunitinib and/or sorafenib. The primary endpoint of progression-free survival was increased from median 1.9 to 4.9 months (hazard ratio 0.33, P < 0.001 and 25% were still progression-free after 10 months of everolimus therapy. There was a delay in time to decline of performance status and trends to improvement in quality of life, disease-related symptoms, and overall survival despite crossover of the majority of patients assigned to placebo. In 2009, everolimus was approved in the US and Europe as the only validated option for this indication. Toxicities are usually mild to moderate and can be managed with dose reduction or interruption if necessary. Opportunistic infections and non-infectious pneumonitis are seen as a class effect. Management of common practical management issues are discussed. Clinical trials are in progress to examine additional roles for everolimus in renal cancer, alone and in combination with other agents.Keywords: everolimus, drug therapy, advanced renal cancer

  6. Kidney Cancer Risk Questionnaire

    Science.gov (United States)

    ... NCI Cancer Information A to Z Treatment Roles Cancer Types Bladder Brain/Spine Breast Cervical Colorectal Esophageal Gallbladder Head/Neck Kidney Leukemia Liver Lung Lymphoma Multiple Myeloma Ovarian Pancreatic ...

  7. Aurora A kinase RNAi and small molecule inhibition of Aurora kinases with VE-465 induce apoptotic death in multiple myeloma cells.

    Science.gov (United States)

    Evans, Robert; Naber, Claudia; Steffler, Tara; Checkland, Tamara; Keats, Jonathan; Maxwell, Christopher; Perry, Troy; Chau, Heidi; Belch, Andrew; Pilarski, Linda; Reiman, Tony

    2008-03-01

    The expression of RHAMM and other centrosome-associated genes are known to correlate with the extent of centrosome amplification in multiple myeloma, and with poor prognosis. RHAMM has a significant interaction with TPX2, a protein which regulates the localization and action of Aurora A kinase (AURKA) at the spindle poles. AURKA is known to be a central determinant of centrosome and spindle function and is a target for cancer therapy. Given these observations, we investigated the role of Aurora kinases as therapeutic targets in myeloma. Here we report that AURKA is expressed ubiquitously in myeloma, to varying degrees, in both cell lines and patients' bone marrow plasma cells. siRNA targeting AURKA induces apoptotic cell death in myeloma cell lines. The Aurora kinase inhibitor VE-465 also induces apoptosis and death in myeloma cell lines and primary myeloma plasma cells. The combination of VE-465 and dexamethasone improves cell killing compared with the use of either agent alone, even in cells resistant to the single agents. The phenotype of myeloma cells treated with VE-465 is consistent with published reports on the effects of Aurora kinase inhibition. Aurora kinase inhibitors should be pursued as potential treatments for myeloma.

  8. Cold atmospheric plasma as a potential tool for multiple myeloma treatment

    Science.gov (United States)

    Cui, Qingjie; Liu, Dingxin; Liu, Zhijie; Wang, Xiaohua; Yang, Yanjie; Feng, Miaojuan; Liang, Rong; Chen, Hailan; Ye, Kai; Kong, Michael G.

    2018-01-01

    Multiple myeloma (MM) is a fatal and incurable hematological malignancy thus new therapy need to be developed. Cold atmospheric plasma, a new technology that could generate various active species, could efficiently induce various tumor cells apoptosis. More details about the interaction of plasma and tumor cells need to be addressed before the application of gas plasma in clinical cancer treatment. In this study, we demonstrate that He+O2 plasma could efficiently induce myeloma cell apoptosis through the activation of CD95 and downstream caspase cascades. Extracellular and intracellular reactive oxygen species (ROS) accumulation is essential for CD95-mediated cell apoptosis in response to plasma treatment. Furthermore, p53 is shown to be a key transcription factor in activating CD95 and caspase cascades. More importantly, we demonstrate that CD95 expression is higher in tumor cells than in normal cells in both MM cell lines and MM clinical samples, which suggests that CD95 could be a favorable target for plasma treatment as it could selectively inactivate myeloma tumor cells. Our results illustrate the molecular details of plasma induced myeloma cell apoptosis and it shows that gas plasma could be a potential tool for myeloma therapy in the future. PMID:29719586

  9. MicroRNA Transfer Between Bone Marrow Adipose and Multiple Myeloma Cells.

    Science.gov (United States)

    Soley, Luna; Falank, Carolyne; Reagan, Michaela R

    2017-06-01

    Multiple myeloma remains an incurable disease, largely due to the tumor-supportive role of the bone marrow microenvironment. Bone marrow adipose tissue (BMAT) is one component of the fertile microenvironment which is believed to contribute to myeloma progression and drug resistance, as well as participate in a vicious cycle of osteolysis and tumor growth. MicroRNAs (miRNAs) have recently emerged as instrumental regulators of cellular processes that enable the development and dissemination of cancer. This review highlights the intersection between two emerging research fields and pursues the scientific and clinical implications of miRNA transfer between BMAT and myeloma cells. This review provides a concise and provocative summary of the evidence to support exosome-mediated transfer of tumor-supportive miRNAs. The work may prompt researchers to better elucidate the mechanisms by which this novel means of genetic communication between tumor cells and their environment could someday yield targeted therapeutics.

  10. Icotinib combined with rapamycin in a renal transplant recipient with epidermal growth factor receptor-mutated non-small cell lung cancer: A case report

    OpenAIRE

    ZHAO, QIONG; WANG, YINA; TANG, YEMIN; PENG, LING

    2013-01-01

    As kidney transplant recipients are at increased risk of developing cancer, regular monitoring should be undertaken to monitor the balance between immunosuppression and graft function and to identify malignancy. The present study reports the outcome of the treatment of adenocarcinoma of the lung (T1aN0M1a, stage IV) using the molecular-targeted therapy, icotinib, in a 66-year-old male renal transplant patient receiving rapamycin and prednisolone as ongoing renal immunosuppressive therapy. An ...

  11. [Multiple myeloma : What has been confirmed in therapy?

    Science.gov (United States)

    Baertsch, M-A; Goldschmidt, H

    2017-12-01

    Multiple myeloma (MM) is a malignancy of terminally differentiated B cells/plasma cells and is primarily located in the bone marrow. Symptomatic multiple myeloma typically presents with osteolyses, anemia, reduced renal function, and/or hypercalcemia. In the case of such MM-related end organ damage, urgent systemic treatment is indicated. In order to prevent end organ damage, current guidelines now recommend treatment initiation already when certain biomarkers are met. Current first-line treatment is based on proteasome inhibition and immunomodulation. Eligible patients still benefit from the addition of high-dose chemotherapy and autologous stem cell transplantation. Radiotherapy and orthopedic interventions play an important role in the treatment of localized skeletal complications. For relapsed MM, five novel agents have been approved in Europe during the last two years. These are second-generation proteasome inhibitors (carfilzomib, ixazomib) as well as first-in-class monoclonal antibodies (daratumumab, elotuzumab) and a histone deacetylase inhibitor (panobinostat). Triple combinations based on the established regimens lenalidomide/dexamethasone and bortezomib/dexamethasone plus one of the novel agents have been shown to significantly prolong progression-free survival. Median overall survival of patients with MM has doubled since the turn of the millennium.

  12. Dendritic-cell-based immunotherapy evokes potent anti-tumor immune responses in CD105+ human renal cancer stem cells.

    Science.gov (United States)

    Zhang, Xiao-Fei; Weng, De-Sheng; Pan, Ke; Zhou, Zi-Qi; Pan, Qiu-Zhong; Zhao, Jing-Jing; Tang, Yan; Jiang, Shan-Shan; Chen, Chang-Long; Li, Yong-Qiang; Zhang, Hong-Xia; Chang, Alfred E; Wicha, Max S; Zeng, Yi-Xin; Li, Qiao; Xia, Jian-Chuan

    2017-11-01

    Cancer stem cells (CSCs) are responsible for tumor initiation, progression, and resistance to therapeutic agents; they are usually less sensitive to conventional cancer therapies, and could cause tumor relapse. An ideal therapeutic strategy would therefore be to selectively target and destroy CSCs, thereby preventing tumor relapse. The aim of the present study was to evaluate the effectiveness of dendritic cells (DCs) pulsed with antigen derived from CD105+ human renal cell carcinoma (RCC) CSCs against renal cancer cells in vitro and in vivo. We identified "stem-like" characteristics of CD105+ cells in two human RCC cell lines: A498 and SK-RC-39. Loading with cell lysates did not change the characteristics of the DCs. However, DCs loaded with lysates derived from CD105+ CSCs induced more functionally specific active T cells and specific antibodies against CSCs, and clearly depressed the tumor growth in mice. Our results could form the basis for a novel strategy to improve the efficacy of DC-based immunotherapy for human RCC. © 2017 Wiley Periodicals, Inc.

  13. 3D element imaging using NSECT for the detection of renal cancer: a simulation study in MCNP

    Science.gov (United States)

    Viana, R. S.; Agasthya, G. A.; Yoriyaz, H.; Kapadia, A. J.

    2013-09-01

    This work describes a simulation study investigating the application of neutron stimulated emission computed tomography (NSECT) for noninvasive 3D imaging of renal cancer in vivo. Using MCNP5 simulations, we describe a method of diagnosing renal cancer in the body by mapping the 3D distribution of elements present in tumors using the NSECT technique. A human phantom containing the kidneys and other major organs was modeled in MCNP5. The element composition of each organ was based on values reported in literature. The two kidneys were modeled to contain elements reported in renal cell carcinoma (RCC) and healthy kidney tissue. Simulated NSECT scans were executed to determine the 3D element distribution of the phantom body. Elements specific to RCC and healthy kidney tissue were then analyzed to identify the locations of the diseased and healthy kidneys and generate tomographic images of the tumor. The extent of the RCC lesion inside the kidney was determined using 3D volume rendering. A similar procedure was used to generate images of each individual organ in the body. Six isotopes were studied in this work—32S, 12C, 23Na, 14N, 31P and 39K. The results demonstrated that through a single NSECT scan performed in vivo, it is possible to identify the location of the kidneys and other organs within the body, determine the extent of the tumor within the organ, and to quantify the differences between cancer and healthy tissue-related isotopes with p ≤ 0.05. All of the images demonstrated appropriate concentration changes between the organs, with some discrepancy observed in 31P, 39K and 23Na. The discrepancies were likely due to the low concentration of the elements in the tissue that were below the current detection sensitivity of the NSECT technique.

  14. 3D element imaging using NSECT for the detection of renal cancer: a simulation study in MCNP.

    Science.gov (United States)

    Viana, R S; Agasthya, G A; Yoriyaz, H; Kapadia, A J

    2013-09-07

    This work describes a simulation study investigating the application of neutron stimulated emission computed tomography (NSECT) for noninvasive 3D imaging of renal cancer in vivo. Using MCNP5 simulations, we describe a method of diagnosing renal cancer in the body by mapping the 3D distribution of elements present in tumors using the NSECT technique. A human phantom containing the kidneys and other major organs was modeled in MCNP5. The element composition of each organ was based on values reported in literature. The two kidneys were modeled to contain elements reported in renal cell carcinoma (RCC) and healthy kidney tissue. Simulated NSECT scans were executed to determine the 3D element distribution of the phantom body. Elements specific to RCC and healthy kidney tissue were then analyzed to identify the locations of the diseased and healthy kidneys and generate tomographic images of the tumor. The extent of the RCC lesion inside the kidney was determined using 3D volume rendering. A similar procedure was used to generate images of each individual organ in the body. Six isotopes were studied in this work - (32)S, (12)C, (23)Na, (14)N, (31)P and (39)K. The results demonstrated that through a single NSECT scan performed in vivo, it is possible to identify the location of the kidneys and other organs within the body, determine the extent of the tumor within the organ, and to quantify the differences between cancer and healthy tissue-related isotopes with p ≤ 0.05. All of the images demonstrated appropriate concentration changes between the organs, with some discrepancy observed in (31)P, (39)K and (23)Na. The discrepancies were likely due to the low concentration of the elements in the tissue that were below the current detection sensitivity of the NSECT technique.

  15. End-Stage Renal Disease From Cast Nephropathy in a Teenager With Neuroendocrine Carcinoma.

    Science.gov (United States)

    Butani, Lavjay; Ducore, Jonathan

    2016-07-01

    Cast nephropathy is the most common manifestation of renal injury in patients with multiple myeloma but is rarely reported in other conditions. We are reporting our experience in caring for a teenager with a metastatic neuroendocrine carcinoma who developed rapidly progressive kidney injury that advanced to end-stage renal disease. On renal biopsy extensive tubular necrosis and intratubular eosinophilic casts were noted. This previously unreported finding should prompt oncologists to closely monitor for such a complication in patients with secretory tumors. Whether early plasmapheresis could be of benefit, as has been tried in multiple myeloma, remains to be determined.

  16. Radiotherapy for solitary plasmacytoma and multiple myeloma

    International Nuclear Information System (INIS)

    Schmaus, M.C.; Neuhof, D.

    2014-01-01

    Solitary plasmacytoma and multiple myeloma require a differentiated radiotherapy. The irradiation for plasmacytoma with an adequate total dose (medullary 40-50 Gy or extramedullary 50-60 Gy) leads to a high degree of local control with a low rate of side effects. In cases of multiple myeloma radiotherapy will achieve effective palliation, both in terms of recalcification as well as reduction of neurological symptoms and analgesia. In terms of analgesia the rule is the higher the single dose fraction the faster the reduction of pain. As part of a conditioning treatment prior to stem cell transplantation radiotherapy contributes to the establishment of a graft versus myeloma effect (GVM). (orig.) [de

  17. Synchronous sigmoid and caecal cancers together with a primary renal cell carcinoma.

    LENUS (Irish Health Repository)

    Bhargava, A

    2012-06-01

    Multiple primary neoplasms, a common clinical entity, can be classified as synchronous or metachronous. Renal cell carcinoma, in particular, is associated with a high rate of multiple primary neoplasms.

  18. Free light chains of immunoglobulins in the diagnosis and prognosis of multiple myeloma

    Directory of Open Access Journals (Sweden)

    N. V. Lyubimova

    2017-01-01

    Full Text Available Background: Analysis of free light chains of immunoglobulins (FLC in the serum is an effective method in the diagnosis of multiple myeloma. Plasma cells produce two types of FLC: κand λ-FLC. FLC, which are not incorporated into monoclonal intact immunoglobulins, are released into circulation, and then are filtered and reabsorbed in kidneys depending on their molecular weight. Circulating FLC commonly form homodimers, known as Bence-Jones protein, which is a biomarker of Bence-Jones multiple myeloma. According to the international guidelines, the ratio κ/λ FLC is an important diagnostic criterion of multiple myeloma. Aim: To evaluate the diagnostic and prognostic value of serum FLC in multiple myeloma patients. Materials and methods: We examined 118 patients with multiple myeloma, admitted to the Department of Hemoblastosis Chemotherapy of N.N. Blokhin Russian Cancer Research Center from 2010 to 2016, and 68 healthy men and women. Serum concentrations of FLC were measured with an immunoturbidimetric method using the test-system Freelite Human Lambda and Freelite Human Kappa (Binding Site Inc.. Results: The levels of monoclonal κor λ-FLC in patients with G-, A-myeloma and Bence-Jones multiple myeloma were significantly higher than those in the control group (p < 0.005. The diagnostic sensitivity of quantification of FLC and their ratio was 87.3% and 89.8%, and in combination with the use of immune electrophoresis it was close to 100%. Analysis of progression free survival and overall survival showed significant differences (p < 0.04 between the groups of patients according their κ/λ FLC ratio. The basal value of κ/λ FLC ratio of less than 0.04 and more than 140 was a  predictor of unfavorable outcome. Conclusion: The inclusion of the determination of serum FLC into the assessment plan of patients with suspected monoclonal gammapathy makes it possible to increase diagnostic sensitivity of the available methods for paraprotein

  19. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer Leukemia Liver Cancer Lung Cancer Lymphoma Pancreatic Cancer Prostate ... Genomics Research Research on Causes of Cancer Cancer Diagnosis Research Cancer Prevention Research Screening & Early Detection Cancer ...

  20. Lung Cancer Prevention

    Science.gov (United States)

    ... Colorectal Cancer Kidney (Renal Cell) Cancer Leukemia Liver Cancer Lung Cancer Lymphoma Pancreatic Cancer Prostate Cancer Skin Cancer ... following PDQ summaries for more information about lung cancer: Lung Cancer Screening Non-Small Cell Lung Cancer Treatment ...

  1. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... Types Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer Leukemia Liver ... Genomics Research Research on Causes of Cancer Cancer Diagnosis Research Cancer Prevention Research Screening & Early Detection Cancer ...

  2. Synchronous malignant renal mass in patient with a Lung cancer: case report and literature review

    OpenAIRE

    Mazouz, Aicha; Amaadour, Lamiae; Souaf, Ihsane; El Fatemi, Hinde; Amarti, Afaf; Erraisse, Mohamed Ait; Oubelkacem, Essaadia; Bouhafa, Touria; Tahiri, Yassir; Tazi, Mohammed Fadl; Mellas, Soufiane; Arifi, Samia; Mellas, Nawfel

    2015-01-01

    The finding on imaging (computed tomography scan or magnetic resonance imaging) of synchronous malignant renal mass in patient with an active nonrenal malignancy without renal specific symptoms is not frequent and diagnostic evaluation can be challenging. We describe a 54-year-old Moroccan male former chronic smoker who presented to our hospital with dry cough and impairment of the performance status. The imaging found a tumor mass in the left upper lobe of the lung associated to mediastinal ...

  3. Sustained systemic response paralleled with ovarian metastasis progression by sunitinib in metastatic renal cell carcinoma: Is this an anti-angiogenic potentiation of cancer?

    Directory of Open Access Journals (Sweden)

    Uttam K Mete

    2015-01-01

    Full Text Available Metastatic renal cell cancer is associated with poor prognosis and survival and is resistant to conventional chemotherapy. Therapeutic targeting of molecular pathways for tumor angiogenesis and other specific activation mechanisms offers improved tumor response and prolonged survival. A 48-year-old, female patient presented with large right renal mass with features suggesting of renal cell cancer without metastasis on contrast enhanced computed tomography (CT. Right radical nephrectomy was done. After 9 months of surgery, she got metastasis in lung, liver and ovary. The patient received sunitinib via an expanded access program. After eight 6-week cycles of sunitinib, a reassessment CT scan confirmed an excellent partial response with the almost complete disappearance (90% of liver and lung metastasis but the adnexal mass had increased in size (>10 times and the possibility was thought of second malignancy. Excision of the mass performed. Histopathology of the mass depicted metastatic renal cell cancer. There is possibility of a ′site-specific anti-angiogenic potentiation mechanism′ of malignancy in relation to sunitinib based upon the preclinical studies, in reference to the index case. Regression of one site with concurrent progression is possible. The exact mechanism of site-specific response, especially organ specific progression by vascular endothelial growth factor inhibitors in metastatic renal cell cancer warrants further study.

  4. Lactobacillus in Preventing Infection in Patients Undergoing a Donor Stem Cell Transplant for Hematologic Cancer or Myelodysplastic Syndrome

    Science.gov (United States)

    2017-02-02

    Breast Cancer; Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms; Neuroblastoma; Ovarian Cancer; Testicular Germ Cell Tumor

  5. Antibody-Based Therapies in Multiple Myeloma

    Directory of Open Access Journals (Sweden)

    Yu-Tzu Tai

    2011-01-01

    Full Text Available The unmet need for improved multiple myeloma (MM therapy has stimulated clinical development of monoclonal antibodies (mAbs targeting either MM cells or cells of the bone marrow (BM microenvironment. In contrast to small-molecule inhibitors, therapeutic mAbs present the potential to specifically target tumor cells and directly induce an immune response to lyse tumor cells. Unique immune-effector mechanisms are only triggered by therapeutic mAbs but not by small molecule targeting agents. Although therapeutic murine mAbs or chimeric mAbs can cause immunogenicity, the advancement of genetic recombination for humanizing rodent mAbs has allowed large-scale production and designation of mAbs with better affinities, efficient selection, decreasing immunogenicity, and improved effector functions. These advancements of antibody engineering technologies have largely overcome the critical obstacle of antibody immunogenicity and enabled the development and subsequent Food and Drug Administration (FDA approval of therapeutic Abs for cancer and other diseases.

  6. Multiple Myeloma in a Patient with Acromegaly

    Directory of Open Access Journals (Sweden)

    Yu Mi Kang

    2015-03-01

    Full Text Available Acromegaly is a slowly progressing condition resulting from excess growth hormone (GH, generally caused by a GH-secreting pituitary adenoma. Cancer is the third most common cause of mortality in patients with acromegaly, and insulin-like growth factor 1 (IGF-1 is known to influence tumor formation by increasing cell proliferation and inhibiting apoptosis. Multiple myeloma (MM is a plasma cell neoplasm, and previous studies have suggested the possible role of IGF-1 in its development of MM. However, no cases of acromegaly accompanied with MM have been reported in Asia to date. We here report the case of a 58-year-old woman with acromegaly accompanied with MM who presented with longstanding acromegalic manifestations resulting from a GH-secreting pituitary adenoma and also exhibited anemia, a reversed albumin/globulin ratio, and plasmacytosis on bone marrow examination. Because IGF-1 has been suggested to play an important role in the development and progression of MM, the patient promptly underwent surgical removal of the pituitary adenoma via a transsphenoidal approach. Since there is currently no consensus on therapeutic guidelines and suggested prognosis for MM with acromegaly, long-term follow-up of such cases is needed.

  7. Restoration of type 1 iodothyronine deiodinase expression in renal cancer cells downregulates oncoproteins and affects key metabolic pathways as well as anti-oxidative system.

    Science.gov (United States)

    Popławski, Piotr; Wiśniewski, Jacek R; Rijntjes, Eddy; Richards, Keith; Rybicka, Beata; Köhrle, Josef; Piekiełko-Witkowska, Agnieszka

    2017-01-01

    Type 1 iodothyronine deiodinase (DIO1) contributes to deiodination of 3,5,3',5'-tetraiodo-L-thyronine (thyroxine, T4) yielding of 3,5,3'-triiodothyronine (T3), a powerful regulator of cell differentiation, proliferation, and metabolism. Our previous work showed that loss of DIO1 enhances proliferation and migration of renal cancer cells. However, the global effects of DIO1 expression in various tissues affected by cancer remain unknown. Here, the effects of stable DIO1 re-expression were analyzed on the proteome of renal cancer cells, followed by quantitative real-time PCR validation in two renal cancer-derived cell lines. DIO1-induced changes in intracellular concentrations of thyroid hormones were quantified by L-MS/MS and correlations between expression of DIO1 and potential target genes were determined in tissue samples from renal cancer patients. Stable re-expression of DIO1, resulted in 26 downregulated proteins while 59 proteins were overexpressed in renal cancer cells. The 'downregulated' group consisted mainly of oncoproteins (e.g. STAT3, ANPEP, TGFBI, TGM2) that promote proliferation, migration and invasion. Furthermore, DIO1 re-expression enhanced concentrations of two subunits of thyroid hormone transporter (SLC7A5, SLC3A2), enzymes of key pathways of cellular energy metabolism (e.g. TKT, NAMPT, IDH2), sex steroid metabolism and anti-oxidative response (AKR1C2, AKR1B10). DIO1 expression resulted in elevated intracellular concentration of T4. Expression of DIO1-affected genes strongly correlated with DIO1 transcript levels in tissue samples from renal cancer patients as well as with their poor survival. This first study addressing effects of deiodinase re-expression on proteome of cancer cells demonstrates that induced DIO1 re-expression in renal cancer robustly downregulates oncoproteins, affects key metabolic pathways, and triggers proteins involved in anti-oxidative protection. This data supports the notion that suppressed DIO1 expression and changes

  8. Restoration of type 1 iodothyronine deiodinase expression in renal cancer cells downregulates oncoproteins and affects key metabolic pathways as well as anti-oxidative system.

    Directory of Open Access Journals (Sweden)

    Piotr Popławski

    Full Text Available Type 1 iodothyronine deiodinase (DIO1 contributes to deiodination of 3,5,3',5'-tetraiodo-L-thyronine (thyroxine, T4 yielding of 3,5,3'-triiodothyronine (T3, a powerful regulator of cell differentiation, proliferation, and metabolism. Our previous work showed that loss of DIO1 enhances proliferation and migration of renal cancer cells. However, the global effects of DIO1 expression in various tissues affected by cancer remain unknown. Here, the effects of stable DIO1 re-expression were analyzed on the proteome of renal cancer cells, followed by quantitative real-time PCR validation in two renal cancer-derived cell lines. DIO1-induced changes in intracellular concentrations of thyroid hormones were quantified by L-MS/MS and correlations between expression of DIO1 and potential target genes were determined in tissue samples from renal cancer patients. Stable re-expression of DIO1, resulted in 26 downregulated proteins while 59 proteins were overexpressed in renal cancer cells. The 'downregulated' group consisted mainly of oncoproteins (e.g. STAT3, ANPEP, TGFBI, TGM2 that promote proliferation, migration and invasion. Furthermore, DIO1 re-expression enhanced concentrations of two subunits of thyroid hormone transporter (SLC7A5, SLC3A2, enzymes of key pathways of cellular energy metabolism (e.g. TKT, NAMPT, IDH2, sex steroid metabolism and anti-oxidative response (AKR1C2, AKR1B10. DIO1 expression resulted in elevated intracellular concentration of T4. Expression of DIO1-affected genes strongly correlated with DIO1 transcript levels in tissue samples from renal cancer patients as well as with their poor survival. This first study addressing effects of deiodinase re-expression on proteome of cancer cells demonstrates that induced DIO1 re-expression in renal cancer robustly downregulates oncoproteins, affects key metabolic pathways, and triggers proteins involved in anti-oxidative protection. This data supports the notion that suppressed DIO1 expression

  9. Cannabinoids synergize with carfilzomib, reducing multiple myeloma cells viability and migration

    OpenAIRE

    Nabissi, Massimo; Morelli, Maria Beatrice; Offidani, Massimo; Amantini, Consuelo; Gentili, Silvia; Soriani, Alessandra; Cardinali, Claudio; Leoni, Pietro; Santoni, Giorgio

    2016-01-01

    Several studies showed a potential anti-tumor role for cannabinoids, by modulating cell signaling pathways involved in cancer cell proliferation, chemo-resistance and migration. Cannabidiol (CBD) was previously noted in multiple myeloma (MM), both alone and in synergy with the proteasome inhibitor bortezomib, to induce cell death. In other type of human cancers, the combination of CBD with ?9-tetrahydrocannabinol (THC) was found to act synergistically with other chemotherapeutic drugs suggest...

  10. Monitoring multiple myeloma patients treated with daratumumab

    DEFF Research Database (Denmark)

    McCudden, Christopher; Axel, Amy E; Slaets, Dominique

    2016-01-01

    BACKGROUND: Monoclonal antibodies are promising anti-myeloma treatments. As immunoglobulins, monoclonal antibodies have the potential to be identified by serum protein electrophoresis (SPE) and immunofixation electrophoresis (IFE). Therapeutic antibody interference with standard clinical SPE and ...

  11. Heterogeneity in the multiple myeloma tumor clone

    NARCIS (Netherlands)

    Guikema, Jeroen E. J.; Hovenga, Sjoerd; Vellenga, Edo; Bos, Nicolaas A.

    2004-01-01

    Multiple Myeloma (MM) is a plasma cell malignancy which is characterized by a very heterogeneous disease outcome. Heterogeneity in plasma cell characteristics, including morphology, maturation status, immunophenotype and genetic abnormalities partly account for the variable disease outcome. Although

  12. Heterogeneity in the multiple myeloma tumor clone

    NARCIS (Netherlands)

    Guikema, JEJ; Hovenga, S; Vellenga, E; Bos, NA

    Multiple Myeloma ( MM) is a plasma cell malignancy which is characterized by a very heterogeneous disease outcome. Heterogeneity in plasma cell characteristics, including morphology, maturation status, immunophenotype and genetic abnormalities partly account for the variable disease outcome.

  13. CARs in the Lead Against Multiple Myeloma

    DEFF Research Database (Denmark)

    Ormhøj, Maria; Bedoya, Felipe; Frigault, Matthew J.

    2017-01-01

    The recent clinical success of CD19-directed chimeric antigen receptor (CAR) T cell therapy in chronic and acute leukemia has led to increased interest in broadening this technology to other hematological malignancies and solid tumors. Now, advances are being made using CAR T cell technology...... to target myeloma antigens such as B cell maturation antigen (BCMA), CD138, and kappa-light chain as well as CD19 on putative myeloma stem cells. To date, only a limited number of multiple myeloma patients have received CAR T cell therapy but preliminary results have been encouraging. In this review, we...... summarize the recently reported results of clinical trials conducted utilizing CAR T cell therapy in multiple myeloma (MM)....

  14. Histone deacetylase inhibitors in multiple myeloma

    Directory of Open Access Journals (Sweden)

    Sarah Deleu

    2009-06-01

    Full Text Available Novel drugs such as bortezomib and high dose chemotherapy combined with stem cell transplantation improved the outcome of multiple myeloma patients in the past decade. However, multiple myeloma often remains incurable due to the development of drug resistance governed by the bone marrow micro-environment. Therefore targeting new pathways to overcome this resistance is needed. Histone deacetylase (HDAC inhibitors represent a new class of anti-myeloma agents. Inhibiting HDACs results in histone hyperacetylation and alterations in chromatine structure, which, in turn, cause growth arrest differentiation and/or apoptosis in several tumor cells. Here we summarize the molecular actions of HDACi as a single agent or in combination with other drugs in different in vitro and in vivo myeloma models and in (preclinical trials.

  15. Titanocene–Gold Complexes Containing N-Heterocyclic Carbene Ligands Inhibit Growth of Prostate, Renal, and Colon Cancers in Vitro

    Science.gov (United States)

    2016-01-01

    We report on the synthesis, characterization, and stability studies of new titanocene complexes containing a methyl group and a carboxylate ligand (mba = −OC(O)-p-C6H4-S−) bound to gold(I)–N-heterocyclic carbene fragments through the thiolate group: [(η5-C5H5)2TiMe(μ-mba)Au(NHC)]. The cytotoxicities of the heterometallic compounds along with those of novel monometallic gold–N-heterocyclic carbene precursors [(NHC)Au(mbaH)] have been evaluated against renal, prostate, colon, and breast cancer cell lines. The highest activity and selectivity and a synergistic effect of the resulting heterometallic species was found for the prostate and colon cancer cell lines. The colocalization of both titanium and gold metals (1:1 ratio) in PC3 prostate cancer cells was demonstrated for the selected compound 5a, indicating the robustness of the heterometallic compound in vitro. We describe here preliminary mechanistic data involving studies on the interaction of selected mono- and bimetallic compounds with plasmid (pBR322) used as a model nucleic acid and the inhibition of thioredoxin reductase in PC3 prostate cancer cells. The heterometallic compounds, which are highly apoptotic, exhibit strong antimigratory effects on the prostate cancer cell line PC3. PMID:27182101

  16. Pazopanib in metastatic renal cancer: a “real-world” experience at National Cancer Institute “Fondazione G. Pascale”

    Directory of Open Access Journals (Sweden)

    Sabrina Chiara Cecere

    2016-08-01

    Full Text Available Pazopanib is an oral angiogenesis inhibitor, currently approved for treatment of metastatic renal cell carcinoma (mRCC and soft tissue sarcoma. The present study analyzed the outcomes of pazopanib in first-line treatment of mRCC, in a single Italian cancer center. In the light of the retrospective, observational nature and the unselected population, our experience can be defined a real-world study. The medical records of 38 mRCC patients treated with front-line pazopanib were retrospectively reviewed and analyzed. The progression free survival (PFS and the overall survival (OS were the primary endpoints, while secondary objectives included Objective Response Rate (ORR, Disease Control Rate (DCR, and treatment tolerability. Pazopanib achieved a median PFS (mPFS of 12.7 months (95% CI, 6.9-18.5 months. The median OS (mOS was 26.2 months (95% CI, 12.6-39.9 months; the observed ORR and DCR were 30.3% and 72.7%, respectively, with a median duration of response of 11 weeks. mPFS appeared not to be influenced by number of co-morbidities (3, gender, Fuhrman grade and age. Conversely, the ORR and the DCR positively affect the mPFS (HR=0.05 [95% CI, 0.05-055], p=0.01; HR=0.10 [95% CI, 0.02-0.43], p=0.002 respectively. A worse outcome was associated with a lower mPFS in patients with liver metastases (p= 0.2 and with a high tumor burden (number of metastatic sites 6 (p= 0.08. Worst OS was observed in patients age >70 years old (HR=6.91 [95% CI, 1.49-31.91], p=0.01. The treatment was well tolerated: no grade 4 adverse events, nor discontinuation due to toxicities was reported. Grade 3 hypertension affected positively the OS reaching the statistical significance (HR=0.22 [95% CI, 0.05-0.8], p=0.03 and thyroid dysfunction (hypo and hyperthyroidism seems to correlate with better outcome in terms of a longer mPFS (HR=0.12 [95% CI, 0.02-0.78], p=0.02. Our results are consistent with those reported in prospective phase III trials and the published retrospective

  17. [Diagnostic and evolutionary profile of multiple myeloma in Senegal: monocentric study conducted from 2005 to 2016].

    Science.gov (United States)

    Fall, Seynabou; Dieng, Fatma; Diouf, Coumba; Djiba, Boundia; Ndao, Awa Cheikh; Ndiaye, Fatou Samba Diago

    2017-01-01

    Accessibility to innovative multiple myeloma therapies is limited in sub-Saharan Africa. This study aimed to describe the diagnostic and evolutionary features observed during treatment of our patients with myeloma. We conducted a retrospective, descriptive, analytical study (2005 - 2016) of patients with myeloma included in the study based on International Myeloma Working Group (IMWG) Criteria (2003,2014) at the Hopital Aristide Le Dantec (Senegal). We collected data from 136 medical records (69 men, 67 women) of patients with an average age of 59 years ± 10.1 years, who were less than 65 years of age in 69.1% of cases. Tell-tale signs included bone pain (96.3%), renal failure (36.8%), infection (23.5%), pathological fracture (17.6%), spinal cord compression (16.9%) and malignant hypercalcaemia (16.2%). Isotopic antiglobulin test showed that anti-IgG could be detected in 61.3% of cases and Kappa in 65% of cases. Patients were classified stage III (59.4%) and I-II (40.6%)of the index staging system. The median survival of patients under conventional traitement (Méphalan-Prédnisone: 67.6%, innovative: 5.9%) was 20 months (1-78 months). Survival rates are better in the absence of neurological and infectious complications and for patients with score I-II of the index Staging System. In our study, multiple myeloma was frequently diagnosed before age 65, at advanced stage of tumor mass. Early detection and access to adequate therapies could improve overall survival.

  18. [Acute renal failure: a rare presentation of Addison's disease].

    Science.gov (United States)

    Salhi, Houda

    2016-01-01

    Addison's disease is a rare condition. Its onset of symptoms most often is nonspecific contributing to a diagnostic and therapeutic delay. Acute renal failure can be the first manifestation of this disease. We report the case of a patient with Addison's disease who was initially treated for acute renal failure due to multiple myeloma and whose diagnosis was adjusted thereafter. Patient's condition dramatically improved after treatment with intravenous rehydration; injectable hydrocortisone.

  19. Occupation, exposure to chemicals, sensitizing agents, and risk of multiple myeloma in Sweden.

    Science.gov (United States)

    Lope, Virginia; Pérez-Gómez, Beatriz; Aragonés, Nuria; López-Abente, Gonzalo; Gustavsson, Per; Plato, Nils; Zock, Jan-Paul; Pollán, Marina

    2008-11-01

    This study sought to identify occupations with high incidence of multiple myeloma and to investigate possible excess risk associated with occupational exposure to chemicals and sensitizing agents in Sweden. A historical cohort of 2,992,166 workers was followed up (1971--1989) through record linkage with the National Cancer and Death Registries. For each job category, age and period standardized incidence ratios and age and period adjusted relative risks of multiple myeloma were calculated using Poisson models. Exposure to chemicals and to sensitizing agents was also assessed using two job-exposure matrices. Men and women were analyzed separately. During follow-up, 3,127 and 1,282 myelomas were diagnosed in men and women, respectively. In men, excess risk was detected among working proprietors, agricultural, horticultural and forestry enterprisers, bakers and pastry cooks, dental technicians, stone cutters/carvers, and prison/reformatory officials. In women, this excess was observed among attendants in psychiatric care, metal workers, bakers and pastry cooks, and paper/paperboard product workers. Workers, particularly bakers and pastry cooks, exposed to high molecular weight sensitizing agents registered an excess risk of over 40% across the sexes. Occasional, although intense, exposure to pesticides was also associated with risk of myeloma in our cohort. Our study supports a possible etiologic role for farming and use of pesticides in myeloma risk. The high incidence found in both female and male bakers and pastry cooks has not been described previously. Further research is required to assess the influence of high molecular weight sensitizing agents on risk of multiple myeloma.

  20. Analysis of survival for patients with chronic kidney disease primarily related to renal cancer surgery.

    Science.gov (United States)

    Wu, Jitao; Suk-Ouichai, Chalairat; Dong, Wen; Antonio, Elvis Caraballo; Derweesh, Ithaar H; Lane, Brian R; Demirjian, Sevag; Li, Jianbo; Campbell, Steven C

    2018-01-01

    To evaluate predictors of long-term survival for patients with chronic kidney disease primarily due to surgery (CKD-S). Patients with CKD-S have generally good survival that approximates patients who do not have CKD even after renal cancer surgery (RCS), yet there may be heterogeneity within this cohort. From 1997 to 2008, 4 246 patients underwent RCS at our centre. The median (interquartile range [IQR]) follow-up was 9.4 (7.3-11.0) years. New baseline glomerular filtration rate (GFR) was defined as highest GFR between nadir and 6 weeks after RCS. We retrospectively evaluated three cohorts: no-CKD (new baseline GFR of ≥60 mL/min/1.73 m 2 ); CKD-S (new baseline GFR of cancer-related survival (NRCRS) for the CKD-S cohort. Kaplan-Meier analysis assessed the longitudinal impact of new baseline GFR (45-60 mL/min/1.73 m 2 vs <45 mL/min/1.73 m 2 ) and Cox regression evaluated relative impact of preoperative GFR, new baseline GFR, and relevant demographics/comorbidities. Of the 4 246 patients who underwent RCS, 931 had CKD-S and 1 113 had CKD-M/S, whilst 2 202 had no-CKD even after RCS. Partial/radical nephrectomy (PN/RN) was performed in 54%/46% of the patients, respectively. For CKD-S, 641 patients had a new baseline GFR of 45-60 mL/min/1.73 m 2 and 290 had a new baseline GFR of <45 mL/min/1.73 m 2 . Kaplan-Meier analysis showed significantly reduced NRCRS for patients with CKD-S with a GFR of <45 mL/min/1.73 m 2 compared to those with no-CKD or CKD-S with a GFR of 45-60 mL/min/1.73 m 2 (both P ≤ 0.004), and competing risk analysis confirmed this (P < 0.001). Age, gender, heart disease, and new baseline GFR were all associated independently with NRCRS for patients with CKD-S (all P ≤ 0.02). Our data suggest that CKD-S is heterogeneous, and patients with a reduced new baseline GFR have compromised survival, particularly if <45 mL/min/1.73 m 2 . Our findings may have implications regarding choice of PN/RN in patients at risk of developing

  1. Report from the European myeloma network on interphase FISH in multiple myeloma and related disorders

    NARCIS (Netherlands)

    F. Ross (F.); H. Avet-Loiseau; G. Ameye (Geneviève); N. Gutierrez (Norma); G. Liebisch (Gerhard); S. O'Connor (Sheila); K. Dalva (Klara); F. Fabris (Federica Margherita); A.M. Testi (Adele); M. Jarosova (M.); C. Hodkinson (Clare); A. Collin (Anna); G. Kerndrup (Gitte); P. Kuglik (Petr); D. Ladon (Dariusz); P. Bernasconi (Paolo); B. Maes (Bart); Z. Zemanova (Zuzana); K. Michalova (Kyra); L. Michau (Lucienne); K. Neben (Kai); N.E.U. Hermansen (N. Emil); K. Rack (Katrina); A. Rocci (Alberto); R. Protheroe (Rebecca); L. Chiecchio (Laura); H.A. Poirel (Hélène A); P. Sonneveld (Pieter); M. Nyegaard (M.); H.E. Johnsen (Hans)

    2012-01-01

    textabstractThe European Myeloma Network has organized two workshops on fluorescence in situ hybridization in multiple myeloma. The first aimed to identify specific indications and consensus technical approaches of current practice. A second workshop followed a quality control exercise in which 21

  2. Abnormal radiological features in a multiple myeloma patient: a case report and radiological review of myelomas

    DEFF Research Database (Denmark)

    Ghosh, Sujoy; Wadhwa, P; A, Kumar

    2011-01-01

    and porotic changes. Primary sclerotic manifestations are rare and occur in only 3% of cases. Although exceptional, multiple myeloma must be borne in mind in the presence of bone sclerosis. This report presents a patient with multiple myeloma with a sunburst/hair-on-end pattern on the radiograph and sclerotic...

  3. [Non-metastatic clear cell renal cancer: dependence of the tumour stage on clinico-anatomic and morphologic factors; prognostic value of macro- and karyometric characteristics].

    Science.gov (United States)

    Iurin, A G

    2010-01-01

    Non-metastatic clear-cell renal cancer: dependence of the tumour stage on clinico-anatomic and morphologic factors; prognostic value of macro- and karyometric characteristics Sankt Peterburg Pathology Bureau, Sankt Peterburg It was shown based on multivariate regression analysis that pT1a3bN0MO stages of non-metastatic clear-cell renal cancer significantly correlate not only with the tumor size and invasion into the fatty tissue and/or renal vein but also with the invasion into the renal capsule and with the mean maximum diameter and mean nucleus area of tumor cells. There was no correlation of clear-cell renal cancer stages with tumor proliferative activity, gene p53 mutation, oncosuppressor gene PTEN expression, fraction of tumour clear-cell component, and such clinical characteristics as patients' sex, age, and body mass index. Taking into account statistically significant differences between the patients' survival rates, the regression equations developed in this work may be used for the prediction of disease outcome.

  4. Renal transplantation across the donor-specific antibody barrier: Graft outcome and cancer risk after desensitization therapy

    Directory of Open Access Journals (Sweden)

    Ching-Yao Yang

    2016-06-01

    Conclusion: When compared to renal transplantation without DSA, desensitization therapy for DSA resulted in equivalent renal transplant outcome but potentially increased risk of urothelial carcinoma after transplantation.

  5. Treatment for Chronic Pain in Patients With Advanced Cancer

    Science.gov (United States)

    2016-11-25

    Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Pain; Precancerous/Nonmalignant Condition; Small Intestine Cancer; Unspecified Adult Solid Tumor, Protocol Specific

  6. The shaping and functional consequences of the dosage effect landscape in multiple myeloma.

    Science.gov (United States)

    Samur, Mehmet K; Shah, Parantu K; Wang, Xujun; Minvielle, Stéphane; Magrangeas, Florence; Avet-Loiseau, Hervé; Munshi, Nikhil C; Li, Cheng

    2013-10-02

    Multiple myeloma (MM) is a malignant proliferation of plasma B cells. Based on recurrent aneuploidy such as copy number alterations (CNAs), myeloma is divided into two subtypes with different CNA patterns and patient survival outcomes. How aneuploidy events arise, and whether they contribute to cancer cell evolution are actively studied. The large amount of transcriptomic changes resultant of CNAs (dosage effect) pose big challenges for identifying functional consequences of CNAs in myeloma in terms of specific driver genes and pathways. In this study, we hypothesize that gene-wise dosage effect varies as a result from complex regulatory networks that translate the impact of CNAs to gene expression, and studying this variation can provide insights into functional effects of CNAs. We propose gene-wise dosage effect score and genome-wide karyotype plot as tools to measure and visualize concordant copy number and expression changes across cancer samples. We find that dosage effect in myeloma is widespread yet variable, and it is correlated with gene expression level and CNA frequencies in different chromosomes. Our analysis suggests that despite the enrichment of differentially expressed genes between hyperdiploid MM and non-hyperdiploid MM in the trisomy chromosomes, the chromosomal proportion of dosage sensitive genes is higher in the non-trisomy chromosomes. Dosage-sensitive genes are enriched by genes with protein translation and localization functions, and dosage resistant genes are enriched by apoptosis genes. These results point to future studies on differential dosage sensitivity and resistance of pro- and anti-proliferation pathways and their variation across patients as therapeutic targets and prognosis markers. Our findings support the hypothesis that recurrent CNAs in myeloma are selected by their functional consequences. The novel dosage effect score defined in this work will facilitate integration of copy number and expression data for identifying driver

  7. Body Composition in Relation to Clinical Outcomes in Renal Cell Cancer: A Systematic Review and Meta-analysis.

    Science.gov (United States)

    Vrieling, Alina; Kampman, Ellen; Knijnenburg, Nathalja C; Mulders, Peter F; Sedelaar, J P Michiel; Baracos, Vickie E; Kiemeney, Lambertus A

    2016-12-04

    Several studies suggest that body composition (ie, body proportions of muscle and fat defined by computed tomography) is associated with clinical outcomes of several cancer types, including renal cell cancer (RCC). To conduct a systematic review and meta-analysis of the evidence on body composition in relation to clinical outcomes in RCC. Literature was reviewed through October 2016 using PubMed and Embase. We included studies investigating computed tomography-measured cross-sectional areas of visceral adipose tissue (VAT), perinephric fat, subcutaneous adipose tissue (SAT), skeletal muscle index (SMI), and skeletal muscle radiodensity (SMD) in relation to perioperative outcomes, treatment toxicity, and survival in RCC patients. We included 28 studies with a total of 6608 patients. Binary classification of body composition was used in most studies. In metastatic RCC (mRCC) patients treated with antiangiogenic drugs, dose-limiting toxicity was more frequent in patients with low versus high SMI (four studies, risk difference = 16%, 95% confidence interval [CI]: 2-31%, p = 0.03, I 2 = 26%). Low versus high SMI (six studies, hazard ratio = 1.48, 95% CI: 1.08-2.03, p = 0.02, I 2 = 28%) and SMD (four studies, HR = 1.56, 95% CI: 1.20-2.03, p = 0.0008, I 2 = 0%) were associated with an increased risk of overall mortality in mRCC. Low versus high VAT and perinephric fat were not consistently associated with perioperative outcomes and survival. No associations for SAT were found. Low SMI is associated with increased dose-limiting toxicity, and low SMI and SMD are associated with increased overall mortality in mRCC. The association of VAT, perinephric fat, and SAT with clinical outcomes needs further investigation, also in localized RCC. We reviewed studies assessing the association of body composition with clinical outcomes in renal cell cancer. We demonstrated higher risk of dose-limiting toxicity and overall mortality for metastatic renal cell cancer patients with low

  8. Temsirolimus Is Highly Effective as Third-Line Treatment in Chromophobe Renal Cell Cancer

    Directory of Open Access Journals (Sweden)

    Dimitrios Zardavas

    2011-01-01

    Full Text Available We report unexpectedly high efficacy of temsirolimus as third-line treatment in a patient with metastatic chromophobe renal cell carcinoma. After failure of two sequentially administered tyrosine kinase inhibitors, treatment with temsirolimus resulted in a prolonged partial remission of 14 months, and the response is still continuing. Up to now, no data from randomized clinical studies have been published addressing the question of efficacy of temsirolimus as third-line treatment after failure of tyrosine kinase inhibitors. The case presented here implies that temsirolimus could be a viable option for patients with metastatic chromophobe renal cell carcinoma.

  9. Isolated Late Metastasis of a Renal Cell Cancer Treated by Radical Distal Pancreatectomy

    Directory of Open Access Journals (Sweden)

    J. P. Barras

    1996-01-01

    Full Text Available A 53–year-old man underwent right nephrectomy for a locally advanced renal cell carcinoma with concomitant resection of a solitary metastasis in the right lung. Ten years later, he presented with haematochezia caused by a tumour in the tail of pancreas, invading the transverse colon and the greater curvature of the stomach. The tumour was radically resected, and histological examination revealed a solitary metastasis of the previous renal cell carcinoma. This case illustrates a rare indication for pancreatic resection because of pancreatic metastasis.

  10. The impact of repeated cycles of radioligand therapy using [{sup 177}Lu]Lu-PSMA-617 on renal function in patients with hormone refractory metastatic prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yordanova, Anna; Becker, Anja; Eppard, Elisabeth; Kuerpig, Stefan; Essler, Markus; Ahmadzadehfar, Hojjat [University Hospital Bonn, Department of Nuclear Medicine, Bonn (Germany); Fisang, Christian [University Hospital Bonn, Department of Urology, Bonn (Germany); Feldmann, Georg [University Hospital Bonn, Department of Internal Medicine, MED3, Bonn (Germany)

    2017-08-15

    [{sup 177}Lu]Lu-PSMA-617 is a well-tolerated therapy for the treatment of metastatic prostate cancer. However, because of the mainly renal excretion of the tracer, the kidneys are one of the most limiting organs. The purpose of this study was to examine the post-therapeutic changes in renal function over time and to identify risk factors for developing renal toxicity. We also tested the reliability of markers for renal function monitoring. Fifty-five patients with castrate-resistant metastatic prostate cancer treated with at least three cycles of [{sup 177}Lu]Lu-PSMA-617 were investigated. Renal function was assessed through laboratory tests (creatinine, GFR, cystatin C) and Tc-99 m-MAG3 measurements. Adverse events were classified according to the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. To identify risk factors for renal toxicity, we used Pearson's correlation coefficient and the corresponding p values. None of the 55 patients experienced severe nephrotoxicity (grade 3/4). In 14 patients (25%), we observed increased creatinine levels of CTC 1 or 2 . There were 16 cases of increased GFR (grade 1/2). At the baseline, only 14 patients had elevated cystatin C. However, post-therapeutic cystatin C was elevated in 32 patients (58%). A significant effect on renal function was found for age (p = 0.049), hypertension (p = 0.001) and pre-existing kidney disease (p = 0.001). The most reliable predictive markers of nephrotoxicity were TER-MAG3 and cystatin C. Renal toxicity in patients treated with [{sup 177}Lu]Lu-PSMA-617 was low. There was no (sub)acute grade 3 or 4 nephrotoxicity. (orig.)

  11. Contrast media induced acute renal failure in diabetics

    International Nuclear Information System (INIS)

    Rambausek, M.

    1985-01-01

    Dehydration, preexisting renal insufficiency, multiple myeloma and insulin-dependent diabetes mellitus are known risk factors for a radiocontrast medium induced acute renal failure. In 90% of patients with insulin-dependent diabetes mellitus, renal insufficiency and proteinuria, a further detoriation of renal function can be expected after i.v. administration of radiocontrast medium. Recent concepts on the genesis of acute renal failure after radiocontrast medium in multiple myeloma emphasize the role of tubular blocade (tubular precipitation of myeloma protein with contrast medium). In insulin-dependent diabetic patients we found altered carbohydrate composition of urinary Tamm Horsfall Protein (THP), with increased glucose and diminished N-acetyl-neuraminicacid content. This was paralleled by a difference in an in-vitro system of coprecipitation where THP of diabetes triggered more pronounced calcium dependent coprecipitation of contrast medium and albumin. These in-vitro findings might be important for the explanation of the genesis of radiocontrast medium-induced acute renal failure in insulin-dependent diabetes mellitus. (orig.) [de

  12. Positive findings on bone scan in multiple myeloma

    International Nuclear Information System (INIS)

    Lin Lin

    2004-01-01

    We report a case of multiple myeloma in which the CT only shows osteolytic lesions and MRI only shows compressive fractrue, but the scan shows some interesting imaging that make us to think of multiple myeloma. (authors)

  13. Successful use of combined high cut-off haemodialysis and bortezomib for acute kidney injury associated with myeloma cast nephropathy.

    LENUS (Irish Health Repository)

    Ward, F

    2012-05-01

    We present the case of a 58-year old female with de novo dialysis-dependent acute kidney injury (AKI) secondary to myeloma cast nephropathy. The patient underwent extended high cut-off haemodialysis (HCO-HD), in conjunction with bortezomib-based chemotherapy, and soon became dialysis independent with normal renal function. To our knowledge, this is the first time this treatment strategy has been employed successfully in an Irish centre.

  14. Adipose, Bone, and Myeloma: Contributions from the Microenvironment.

    Science.gov (United States)

    McDonald, Michelle M; Fairfield, Heather; Falank, Carolyne; Reagan, Michaela R

    2017-05-01

    Researchers globally are working towards finding a cure for multiple myeloma (MM), a destructive blood cancer diagnosed yearly in ~750,000 people worldwide (Podar et al. in Expert Opin Emerg Drugs 14:99-127, 2009). Although MM targets multiple organ systems, it is the devastating skeletal destruction experienced by over 90 % of patients that often most severely impacts patient morbidity, pain, and quality of life. Preventing bone disease is therefore a priority in MM treatment, and understanding how and why myeloma cells target the bone marrow (BM) is fundamental to this process. This review focuses on a key area of MM research: the contributions of the bone microenvironment to disease origins, progression, and drug resistance. We describe some of the key cell types in the BM niche: osteoclasts, osteoblasts, osteocytes, adipocytes, and mesenchymal stem cells. We then focus on how these key cellular players are, or could be, regulating a range of disease-related processes spanning MM growth, drug resistance, and bone disease (including osteolysis, fracture, and hypercalcemia). We summarize the literature regarding MM-bone cell and MM-adipocyte relationships and subsequent phenotypic changes or adaptations in MM cells, with the aim of providing a deeper understanding of how myeloma cells grow in the skeleton to cause bone destruction. We identify avenues and therapies that intervene in these networks to stop tumor growth and/or induce bone regeneration. Overall, we aim to illustrate how novel therapeutic target molecules, proteins, and cellular mediators may offer new avenues to attack this disease while reviewing currently utilized therapies.

  15. Effects of gemcitabine on renal function in patients with non-small cell lung cancer

    NARCIS (Netherlands)

    Gietema, JA; Groen, HJM; Meijer, S; Smit, EF

    Gemcitabine is a novel fluorine-substituted cytarabine (Ara-C) analogue with activity against a range of solid tumours. Besides dose-limiting haematological toxicity, renal side-effects were observed from phase I and II studies concerning elevations of serum creatinine, proteinuria and

  16. Skin cancer and (pre)malignancies of the female genital tract in renal transplant recipients.

    NARCIS (Netherlands)

    Meeuwis, K.A.P.; Rossum, M.M. van; Kerkhof, P.C.M. van de; Hoitsma, A.J.; Massuger, L.F.A.G.; Hullu, J.A. de

    2010-01-01

    SUMMARY: Immunosuppressive therapy in renal transplant recipients (RTRs) is associated with an increased risk for the development of (pre)malignancies involving the skin and the female lower genital tract. We assessed whether yearly cervical screening was performed and evaluated the development of

  17. Overall survival after immunotherapy, tyrosine kinase inhibitors and surgery in treatment of metastatic renal cell cancer

    DEFF Research Database (Denmark)

    de Lichtenberg, Trine Honnens; Hermann, Gregers G.; Rorth, Mikael

    2014-01-01

    Abstract Objective. The aim of this study was to evaluate overall survival (OS) after treatment of metastatic renal cell carcinoma (mRCC) following the introduction of tyrosine kinase inhibitors (TKIs) and mammalian target of rapamycin (mTOR) inhibitors. Material and methods. One-hundred and forty...

  18. European Association of Urology Guidelines for Clear Cell Renal Cancers That Are Resistant to Vascular Endothelial Growth Factor Receptor-Targeted Therapy

    NARCIS (Netherlands)

    Powles, Thomas; Staehler, Michael; Ljungberg, Börje; Bensalah, Karim; Canfield, Steven E; Dabestani, Saeed; Giles, Rachel H; Hofmann, Fabian; Hora, Milan; Kuczyk, Markus A; Lam, Thomas; Marconi, Lorenzo; Merseburger, Axel S; Volpe, Alessandro; Bex, Axel

    2016-01-01

    The European Association of Urology renal cancer guidelines panel recommends nivolumab and cabozantinib over the previous standard of care in patients who have failed one or more lines of vascular endothelial growth factor-targeted therapy. New data have recently become available showing a survival

  19. Expression of the vitamin D receptor, 25-hydroxylases, 1alpha-hydroxylase and 24-hydroxylase in the human kidney and renal clear cell cancer

    DEFF Research Database (Denmark)

    Blomberg Jensen, Martin; Andersen, Claus B.; Nielsen, John E

    2010-01-01

    The vitamin D receptor (VDR), CYP27B1 and CYP24A1 are expressed in the human kidney, but the segmental expression of the 25-hydroxylases is unknown. A comprehensive analysis of CYP2R1, CYP27A1, CYP27B1, VDR and CYP24A1 expression in normal kidney and renal clear cell cancer (CCc) would reveal...

  20. Preclinical renal cancer chemopreventive efficacy of geraniol by modulation of multiple molecular pathways

    International Nuclear Information System (INIS)

    Ahmad, Shiekh Tanveer; Arjumand, Wani; Seth, Amlesh; Nafees, Sana; Rashid, Summya; Ali, Nemat; Sultana, Sarwat

    2011-01-01

    Graphical abstract: Diagrammatic presentation of the hypothesis of the article in a concise manner. It reveals the chemopreventive efficacy of GOH possibly through the modulation of multiple molecular targets. GOH inhibits ROS generation, NFκB and PCNA expression thereby abrogating inflammation and proliferation of tubular cells of kidney. Whereas, GOH induces effector caspase-3 expression both through mitochondrial signalling pathway and death receptor signalling pathway. Highlights: → Geraniol modulates renal carcinogenesis in Wistar rats. → It abrogates Fe-NTA induced oxidative stress, inflammation and hyperproliferation. → Promotes apoptosis via induction of both mitochondrial and death receptor pathway. → Thus, inhibits renal carcinogenesis by modulating multiple molecular targets. -- Abstract: In the present study, we have evaluated the chemopreventive potential of geraniol (GOH), an acyclic monoterpene alcohol against ferric nitrilotriacetate (Fe-NTA) induced renal oxidative stress and carcinogenesis in Wistar rats. Chronic treatment of Fe-NTA induced oxidative stress, inflammation and cellular proliferation in Wistar rats. The chemopreventive efficacy of GOH was studied in terms of xenobiotic metabolizing enzyme activities, LPO, redox status, serum toxicity markers and the expression of putative nephrotoxicity biomarker Kim-1, tumor suppressor gene P53, inflammation, cell proliferation and apoptosis related genes in the kidney tissue. Oral administration of GOH at doses of 100 and 200 mg/kg b wt effectively suppressed renal oxidative stress and tumor incidence. Chemopreventive effects of GOH were associated with upregulation of xenobiotic metabolizing enzyme activities and down regulation of serum toxicity markers. GOH was able to down regulate expression of Kim-1, NFκB, PCNA, P53 along with induction of apoptosis. However, higher dose of GOH was more effective in modulating these multiple molecular targets both at transcriptional and protein

  1. Myeloma

    Science.gov (United States)

    ... Ways to Help Ways to Donate Volunteer Wills, Annuities & Planned Gifts Become a Social Ambassador Donate About ... Ways to Help Ways to Donate Volunteer Wills, Annuities & Planned Gifts Become a Social Ambassador Partners LLS ...

  2. Occupational risk factors for renal cell carcinoma: agent-specific results from a case-control study in Germany. MURC Study Group. Multicenter urothelial and renal cancer study.

    Science.gov (United States)

    Pesch, B; Haerting, J; Ranft, U; Klimpel, A; Oelschlägel, B; Schill, W

    2000-12-01

    This case-control study was conducted to estimate the renal cell cancer (RCC) risk for exposure to occupation-related agents, besides other suspected risk factors. In a population-based multicentre study, 935 incident RCC cases and 4298 controls matched for region, sex, and age were interviewed between 1991 and 1995 for their occupational history and lifestyle habits. Agent-specific exposure was expert-rated with two job-exposure matrices and a job task-exposure matrix. Conditional logistic regression was used to calculate smoking adjusted odds ratios (OR). Very long exposures in the chemical, rubber, and printing industries were associated with risk for RCC. Males considered as 'substantially exposed to organic solvents' showed a significant excess risk (OR = 1.6, 95% CI : 1.1-2.3). In females substantial exposure to solvents was also a significant risk factor (OR = 2.1, 95% CI : 1.0-4.4). Excess risks were shown for high exposure to cadmium (OR = 1.4, 95% CI : 1.1-1.8, in men, OR = 2.5, 95% CI : 1.2-5.3 in women), for substantial exposure to lead (OR = 1.5, 95% CI : 1.0-2.3, in men, OR = 2.6, 95% CI : 1.2-5.5, in women) and to solder fumes (OR = 1.5, 95% CI : 1.0-2.4, in men). In females, an excess risk for the task 'soldering, welding, milling' was found (OR = 3.0, 95% CI : 1.1-7.8). Exposure to paints, mineral oils, cutting fluids, benzene, polycyclic aromatic hydrocarbons, and asbestos showed an association with RCC development. Our results indicate that substantial exposure to metals and solvents may be nephrocarcinogenic. There is evidence for a gender-specific susceptibility of the kidneys.

  3. New Genetic Insights and Therapy in Multiple Myeloma

    NARCIS (Netherlands)

    K.L. Wu

    2007-01-01

    textabstractIn the last decade, several significant advances in myeloma therapy have occurred with the pace of change accelerated with the introduction of new anti-myeloma agents. The approach to the treatment of multiple myeloma has become more complex with an array of therapeutic options,

  4. A murine model of human myeloma bone disease

    NARCIS (Netherlands)

    Garrett, I.R.; Dallas, S.; Radl, J.; Mundy, G.R.

    1997-01-01

    Myeloma causes a devastating and unique form of osteolytic bone disease. Although osteoclast activation is responsible for bone destruction, the precise mechanisms by which myeloma cells increase osteoclast activity have not been defined. An animal model of human myeloma bone disease mould help in

  5. Immune resistance of Multiple Myeloma : the role of the microenvironment

    NARCIS (Netherlands)

    de Haart, SJ

    2017-01-01

    Immunotherapeutic strategies in Multiple Myeloma are under development. In this thesis we present a new perspective in optimizing immunotherapy in Multiple Myeloma patient. We propose that currently, immunotherapy is limited in efficacy through interactions of Multiple Myeloma cells with the bone

  6. Feasibility of similarity coefficient map for improving morphological evaluation of T2* weighted MRI for renal cancer

    International Nuclear Information System (INIS)

    Wang Hao-Yu; Bao Shang-Lian; Jiani Hu; Meng Li; Haacke, E. M.; Xie Yao-Qin; Chen Jie; Amy Yu; Wei Xin-Hua; Dai Yong-Ming

    2013-01-01

    The purpose of this paper is to investigate the feasibility of using a similarity coefficient map (SCM) in improving the morphological evaluation of T 2 * weighted (T 2 *W) magnatic resonance imaging (MRI) for renal cancer. Simulation studies and in vivo 12-echo T 2 *W experiments for renal cancers were performed for this purpose. The results of the first simulation study suggest that an SCM can reveal small structures which are hard to distinguish from the background tissue in T 2 *W images and the corresponding T 2 * map. The capability of improving the morphological evaluation is likely due to the improvement in the signal-to-noise ratio (SNR) and the carrier-to-noise ratio (CNR) by using the SCM technique. Compared with T 2 *W images, an SCM can improve the SNR by a factor ranging from 1.87 to 2.47. Compared with T 2 * maps, an SCM can improve the SNR by a factor ranging from 3.85 to 33.31. Compared with T 2 *W images, an SCM can improve the CNR by a factor ranging from 2.09 to 2.43. Compared with T 2 * maps, an SCM can improve the CNR by a factor ranging from 1.94 to 8.14. For a given noise level, the improvements of the SNR and the CNR depend mainly on the original SNRs and CNRs in T 2 *W images, respectively. In vivo experiments confirmed the results of the first simulation study. The results of the second simulation study suggest that more echoes are used to generate the SCM, and higher SNRs and CNRs can be achieved in SCMs. In conclusion, an SCM can provide improved morphological evaluation of T 2 *W MR images for renal cancer by unveiling fine structures which are ambiguous or invisible in the corresponding T 2 *W MR images and T 2 * maps. Furthermore, in practical applications, for a fixed total sampling time, one should increase the number of echoes as much as possible to achieve SCMs with better SNRs and CNRs

  7. Non-neoplastic parenchymal changes in kidney cancer and post-partial nephrectomy recovery of renal function.

    Science.gov (United States)

    Bazzi, Wassim M; Chen, Ling Y; Cordon, Billy H; Mashni, Joseph; Sjoberg, Daniel D; Bernstein, Melanie; Russo, Paul

    2015-09-01

    To explore the association of non-neoplastic parenchymal changes (nNPC) with patients' health and renal function recovery after partial nephrectomy (PN). This retrospective review identified 800 pT1a patients who underwent PN at Memorial Sloan Kettering Cancer Center from 2007 to 2012. Pathology reports were reviewed for nNPC graded as mild or severe: vascular sclerosis (VS), glomerulosclerosis (GS), and fibrosis/scarring. Correlations between nNPC and known preoperative predictors of renal function [age, sex, African-American race, estimated glomerular filtration rate (eGFR), American Society of Anesthesiologists (ASA) score, body mass index, coronary artery disease, and hypertension (HTN)] were assessed using Spearman's rank correlation (ρ). Multivariable linear regression, adjusted for the described known preoperative risk predictors, was performed to evaluate whether the parenchymal features were able to predict 6-month postoperative eGFR. In this study, 46 % of tumors had benign surrounding parenchyma. We noted statistically significant yet weak associations of VS with age (ρ = 0.19; p < 0.001), ASA (ρ = 0.09; p < 0.001), preoperative eGFR (ρ = -0.14; p < 0.001), and HTN (ρ = 0.14; p < 0.001). GS also significantly correlated with HTN, but the correlation was again small (ρ = 0.12; p < 0.001). After adjusting for known risk predictors, only GS was a significant predictor of 6-month postoperative eGFR. When compared with no GS, mild and severe GS were negatively associated with a decrease of 4.9 and 10.8 mL/min/1.73 m(2) in 6-month postoperative eGFR, respectively. Presence of VS and GS correlated with patients' baseline health, and presence of GS predicted postoperative renal function recovery.

  8. Pazopanib in Metastatic Renal Cancer: A “Real-World” Experience at National Cancer Institute “Fondazione G. Pascale”

    Science.gov (United States)

    Cecere, Sabrina C.; Rossetti, Sabrina; Cavaliere, Carla; Della Pepa, Chiara; Di Napoli, Marilena; Crispo, Anna; Iovane, Gelsomina; Piscitelli, Raffaele; Sorrentino, Domenico; Ciliberto, Gennaro; Maiolino, Piera; Muto, Paolo; Perdonà, Sisto; Berretta, Massimiliano; Pignata, Sandro; Facchini, Gaetano; D'Aniello, Carmine

    2016-01-01

    Pazopanib is an oral angiogenesis inhibitor, currently approved for treatment of metastatic renal cell carcinoma (mRCC) and soft tissue sarcoma. The present study analyzed the outcomes of pazopanib in first-line treatment of mRCC, in a single Italian cancer center. In the light of the retrospective, observational nature and the unselected population, our experience can be defined a “real-world” study. The medical records of 38 mRCC patients treated with front-line pazopanib were retrospectively reviewed and analyzed. The progression free survival (PFS) and the overall survival (OS) were the primary endpoints, while secondary objectives included objective response rate (ORR), disease control rate (DCR), and treatment tolerability. Pazopanib achieved a median PFS (mPFS) of 12.7 months (95% CI, 6.9–18.5 months). The median OS (mOS) was 26.2 months (95% CI, 12.6–39.9 months); the observed ORR and DCR were 30.3 and 72.7%, respectively, with a median duration of response of 11 weeks. mPFS appeared not to be influenced by number of co-morbidities (< 3 vs. ≥3), gender, Fuhrman grade and age. Conversely, the ORR and the DCR positively affect the mPFS (HR = 0.05 [95% CI, 0.05–0.55], p = 0.01; HR = 0.10 [95% CI, 0.02–0.43], p = 0.002, respectively). A worse outcome was associated with a lower mPFS in patients with liver metastases (p = 0.2) and with a high tumor burden (number of metastatic sites < 6 vs. ≥6) (p = 0.08). Worst OS was observed in patients aged ≥70 years old (HR = 6.91 [95% CI, 1.49–31.91], p = 0.01). The treatment was well-tolerated: no grade 4 adverse events, nor discontinuation due to toxicities was reported. Grade 3 hypertension affected positively the OS reaching the statistical significance (HR = 0.22 [95% CI, 0.05–0.8], p = 0.03). Thyroid dysfunction (hypo and hyperthyroidism) seems to correlate with better outcome in terms of a longer mPFS (HR = 0.12 [95% CI, 0.02–0.78], p = 0.02). Our results are consistent with those reported in

  9. An easy irradiation technique (partial half-beam) to reduce renal dose in radiotherapy of cervical cancer including paraaortic lymph nodes

    International Nuclear Information System (INIS)

    Vorwerk, H.; Wagner, D.; Christiansen, H.; Hess, C.F.; Hermann, R.M.

    2008-01-01

    Purpose: for radiation treatment of patients with cervical cancer and a high risk for paraaortic lymph node involvement, an easy three-dimensional (3-D) conformal irradiation technique (partial half-beam [PHB]) for protection of organs at risk, especially of renal tissue, was developed. Patients and methods: in five consecutive female patients a computed tomography scan was performed. Dose-volume histograms of the renal tissue and other organs at risk were analyzed for PHB, three other 3-D conformal techniques, and an intensity-modulated radiotherapy (IMRT) technique. Results: the PHB technique reduced the renal volume and volumes of other organs at risk exposed to radiation doses when comparing all patients to the other 3-D conformal techniques. With use of the IMRT technique more renal tissue volume received very low radiation doses (≤ 6.8 Gy) whereas the D 10 was lower than with the PHB technique. Conclusion: in female patients with cervical cancer and high risk for paraaortic lymph node involvement, the use of the PHB technique is recommended to reduce renal radiation exposure, if no IMRT technique should be applied. The PHB technique is very easily and fast applicable. (orig.)

  10. Review of the Interaction Between Body Composition and Clinical Outcomes in Metastatic Renal Cell Cancer Treated With Targeted Therapies

    Directory of Open Access Journals (Sweden)

    Steven M Yip

    2016-03-01

    Full Text Available Treatment of metastatic renal cell cancer (mRCC currently focuses on inhibition of the vascular endothelial growth factor pathway and the mammalian target of rapamycin (mTOR pathway. Obesity confers a higher risk of RCC. However, the influence of obesity on clinical outcomes in mRCC in the era of targeted therapy is less clear. This review focuses on the impact of body composition on targeted therapy outcomes in mRCC. The International Metastatic Renal Cell Carcinoma Database Consortium database has the largest series of patients evaluating the impact of body mass index (BMI on outcomes in mRCC patients treated with targeted therapy. Overall survival was significantly improved in overweight patients (BMI ≥ 25 kg/m2, and this observation was externally validated in patients who participated in Pfizer trials. In contrast, sarcopenia is consistently associated with increased toxicity to inhibitors of angiogenesis and mTOR. Strengthening patients with mRCC and sarcopenia, through a structured exercise program and dietary intervention, may improve outcomes in mRCC treated with targeted therapies. At the same time, the paradox of obesity being a risk factor for RCC while offering a better overall survival in response to targeted therapy needs to be further evaluated.

  11. Withanolides from Aeroponically Grown Physalis peruviana and Their Selective Cytotoxicity to Prostate Cancer and Renal Carcinoma Cells.

    Science.gov (United States)

    Xu, Ya-Ming; Wijeratne, E M Kithsiri; Babyak, Ashley L; Marks, Hanna R; Brooks, Alan D; Tewary, Poonam; Xuan, Li-Jiang; Wang, Wen-Qiong; Sayers, Thomas J; Gunatilaka, A A Leslie

    2017-07-28

    Investigation of aeroponically grown Physalis peruviana resulted in the isolation of 11 new withanolides, including perulactones I-L (1-4), 17-deoxy-23β-hydroxywithanolide E (5), 23β-hydroxywithanolide E (6), 4-deoxyphyperunolide A (7), 7β-hydroxywithanolide F (8), 7β-hydroxy-17-epi-withanolide K (9), 24,25-dihydro-23β,28-dihydroxywithanolide G (10), and 24,25-dihydrowithanolide E (11), together with 14 known withanolides (12-25). The structures of 1-11 were elucidated by the analysis of their spectroscopic data, and 12-25 were identified by comparison of their spectroscopic data with those reported. All withanolides were evaluated for their cytotoxic activity against a panel of tumor cell lines including LNCaP (androgen-sensitive human prostate adenocarcinoma), 22Rv1 (androgen-resistant human prostate adenocarcinoma), ACHN (human renal adenocarcinoma), M14 (human melanoma), SK-MEL-28 (human melanoma), and normal human foreskin fibroblast cells. Of these, the 17β-hydroxywithanolides (17-BHWs) 6, 8, 9, 11-13, 15, and 19-22 showed selective cytotoxic activity against the two prostate cancer cell lines LNCaP and 22Rv1, whereas 13 and 20 exhibited selective toxicity for the ACHN renal carcinoma cell line. These cytotoxicity data provide additional structure-activity relationship information for the 17-BHWs.

  12. A concise revised myeloma comorbidity index as a valid prognostic instrument in a large cohort of 801 multiple myeloma patients

    NARCIS (Netherlands)

    M. Engelhardt (Monika); Domm, A.-S. (Anne-Saskia); Dold, S.M. (Sandra Maria); G. Ihorst (Gabriele); Reinhardt, H. (Heike); Zober, A. (Alexander); Hieke, S. (Stefanie); Baayen, C. (Corine); Müller, S.J. (Stefan Jürgen); H. Einsele (Hermann); P. Sonneveld (Pieter); O. Landgren; M. Schumacher (M.); R. Wäsch (Ralph)

    2017-01-01

    textabstractWith growing numbers of elderly multiple myeloma patients, reliable tools to assess their vulnerability are required. The objective of the analysis herein was to develop and validate an easy to use myeloma risk score (revised Myeloma Comorbidity Index) that allows for risk prediction of

  13. Top Information Need Priorities of Older Adults Newly Diagnosed With Active Myeloma.

    Science.gov (United States)

    Tariman, Joseph D; Doorenbos, Ardith; Schepp, Karen G; Singhal, Seema; Berry, Donna L

    2015-01-01

    Prioritizing patients' information needs maximizes efficiency. This study examined the information sources and priorities in a sample of older adults newly diagnosed with symptomatic myeloma requiring immediate therapy. An association analysis of whether information needs were influenced by sociodemographic variables such as age, gender, education, marital status, and income was also conducted. The Information Needs Questionnaire (INQ) and an investigator-developed interview schedule were administered to 20 older adults diagnosed with symptomatic myeloma during a 30- to 45-minute semistructured interview. We found that older adults newly diagnosed with symptomatic myeloma have different priorities of information needs when compared with younger patients diagnosed with various types of cancer. The top three priorities related to treatment, prognosis, and self-care. Sociodemographic variables did not influence the priorities of information needs among older adults with symptomatic myeloma. The Internet, physicians, family, and friends were among the top sources of information. Advanced practitioners in oncology should support and identify interventions that can enhance patients' learning process from these sources. Well poised to assist patients in searching credible and reliable Internet sources, advanced practitioners in oncology can provide patient education about different treatments and the impact of such treatments on prognosis (e.g., overall survival and likelihood of cure).

  14. Impact of surgical volume on functional results and cardiospecific survival rates in patients with clinically localized renal cancer

    Directory of Open Access Journals (Sweden)

    M. I. Volkova

    2014-11-01

    . No relationship was found betwen cardiospecific survival and GFR in the late postoperative period.Conclusion. Kidney resection versus radical nephrectomy significantly increases the risk of severe ARD. The scope of surgical treatment for clinically localized renal cancer has not been found to affect cardiospecific survival.

  15. Impact of surgical volume on functional results and cardiospecific survival rates in patients with clinically localized renal cancer

    Directory of Open Access Journals (Sweden)

    M. I. Volkova

    2014-01-01

    . No relationship was found betwen cardiospecific survival and GFR in the late postoperative period.Conclusion. Kidney resection versus radical nephrectomy significantly increases the risk of severe ARD. The scope of surgical treatment for clinically localized renal cancer has not been found to affect cardiospecific survival.

  16. Nuclear expression of Lyn, a Src family kinase member, is associated with poor prognosis in renal cancer patients.

    Science.gov (United States)

    Roseweir, Antonia K; Qayyum, Tahir; Lim, Zhi; Hammond, Rachel; MacDonald, Alasdair I; Fraser, Sioban; Oades, Grenville M; Aitchison, Michael; Jones, Robert J; Edwards, Joanne

    2016-03-16

    8000 cases of renal cancer are diagnosed each year in the UK, with a five-year survival rate of 50%. Treatment options are limited; a potential therapeutic target is the Src family kinases (SFKs). SFKs have roles in multiple oncogenic processes and promote metastases in solid tumours. The aim of this study was to investigate SFKs as potential therapeutic targets for clear cell renal cell carcinoma (ccRCC). SFKs expression was assessed in a tissue microarray consisting of 192 ccRCC patients with full clinical follow-up. SFK inhibitors, dasatinib and saracatinib, were assessed in early ccRCC cell lines, 786-O and 769-P and a metastatic ccRCC cell line, ACHN (± Src) for effects on protein expression, apoptosis, proliferation and wound healing. High nuclear expression of Lyn and the downstream marker of activation, paxillin, were associated with decreased patient survival. Conversely, high cytoplasmic expression of other SFK members and downstream marker of activation, focal adhesion kinase (FAK) were associated with increased patient survival. Treatment of non-metastatic 786-O and 769-P cells with dasatinib, dose dependently reduced SFK activation, shown via SFK (Y(419)) and FAK (Y(861)) phosphorylation, with no effect in metastatic ACHN cells. Dasatinib also increased apoptosis, while decreasing proliferation and migration in 786-O and 769-P cell lines, both in the presence and absence of Src protein. Our data suggests that nuclear Lyn is a potential therapeutic target for ccRCC and dasatinib affects cellular functions associated with cancer progression via a Src kinase independent mechanism.

  17. Renal function and urological complications after radical hysterectomy with postoperative radiotherapy and platinum-based chemotherapy for cervical cancer.

    Science.gov (United States)

    Okadome, Masao; Saito, Toshiaki; Kitade, Shoko; Ariyoshi, Kazuya; Shimamoto, Kumi; Kawano, Hiroyuki; Minami, Kazuhito; Nakamura, Motonobu; Shimokawa, Mototsugu; Okushima, Kazuhiro; Kubo, Yuichiro; Kunitake, Naonobu

    2018-02-01

    We aimed to clarify renal functional changes long term and serious urological complications in women with cervical cancer who undergo radical hysterectomy followed by pelvic radiotherapy and/or platinum-based chemotherapy to treat the initial disease. Data on 380 women who underwent radical hysterectomy at the National Kyushu Cancer Center from January 1997 to December 2013 were reviewed. Main outcome measures were the estimated glomerular filtration rate (eGFR) and monitored abnormal urological findings. Postoperative eGFR was significantly lower than preoperative eGFR in 179 women with surgery alone and in 201 women with additional pelvic radiotherapy and/or chemotherapy (both P types of univariate analyses for eGFR reduction in women after treatment showed that older age, advanced stage, pelvic radiotherapy, and platinum-based chemotherapy were significant variables on both analyses. Two types of multivariate analyses showed that platinum-based chemotherapy or pelvic radiotherapy were associated with impaired renal function (odds ratio 1.96, 95% confidence interval 1.08-3.54 and odds ratio 2.85, 95% confidence interval 1.12-7.24, for the respective analyses). There was a higher rate of bladder wall thickening in women with pelvic radiotherapy had than those without it (17.4% vs. 2.7%, P chemotherapy and/or postoperative pelvic radiotherapy. Serious and life-threatening urological complications are rare, but surgeons should be aware of the possibility during the long follow-up. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  18. Coffee and Green Tea Consumption and Subsequent Risk of Malignant Lymphoma and Multiple Myeloma in Japan: The Japan Public Health Center-based Prospective Study.

    Science.gov (United States)

    Ugai, Tomotaka; Matsuo, Keitaro; Sawada, Norie; Iwasaki, Motoki; Yamaji, Taiki; Shimazu, Taichi; Sasazuki, Shizuka; Inoue, Manami; Kanda, Yoshinobu; Tsugane, Shoichiro

    2017-08-01

    Background: The aim of this study was to investigate the association of coffee and green tea consumption and the risk of malignant lymphoma and multiple myeloma in a large-scale population-based cohort study in Japan. Methods: In this analysis, a total of 95,807 Japanese subjects (45,937 men and 49,870 women; ages 40-69 years at baseline) of the Japan Public Health Center-based Prospective Study who completed a questionnaire about their coffee and green tea consumption were followed up until December 31, 2012, for an average of 18 years. HRs and 95% confidence intervals were estimated using a Cox regression model adjusted for potential confounders as a measure of association between the risk of malignant lymphoma and multiple myeloma associated with coffee and green tea consumption at baseline. Results: During the follow-up period, a total of 411 malignant lymphoma cases and 138 multiple myeloma cases were identified. Overall, our findings showed no significant association between coffee or green tea consumption and the risk of malignant lymphoma or multiple myeloma for both sexes. Conclusions: In this study, we observed no significant association between coffee or green tea consumption and the risk of malignant lymphoma or multiple myeloma. Impact: Our results do not support an association between coffee or green tea consumption and the risk of malignant lymphoma or multiple myeloma. Cancer Epidemiol Biomarkers Prev; 26(8); 1352-6. ©2017 AACR . ©2017 American Association for Cancer Research.

  19. The Danish National Multiple Myeloma Registry

    DEFF Research Database (Denmark)

    Gimsing, Peter; Holmström, Morten Orebo; Klausen, Tobias Wirenfelt

    2016-01-01

    AIM: The Danish National Multiple Myeloma Registry (DMMR) is a population-based clinical quality database established in January 2005. The primary aim of the database is to ensure that diagnosis and treatment of plasma cell dyscrasia are of uniform quality throughout the country. Another aim...... diagnosed patients with multiple myeloma (MM), smoldering MM, solitary plasmacytomas, and plasma cell leukemia in Denmark are registered annually; ~350 patients. Amyloid light-chain amyloidosis, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes syndrome......), monoclonal gammopathy of undetermined significance and monoclonal gammopathy of undetermined significance with polyneuropathy have been registered since 2014. MAIN VARIABLES: The main registered variables at diagnosis are patient demographics, baseline disease characteristics, myeloma-defining events...

  20. The Role of Immunotherapy in Multiple Myeloma

    Directory of Open Access Journals (Sweden)

    Mehmet Kocoglu

    2016-01-01

    Full Text Available Multiple myeloma is the second most common hematologic malignancy. The treatment of this disease has changed considerably over the last two decades with the introduction to the clinical practice of novel agents such as proteasome inhibitors and immunomodulatory drugs. Basic research efforts towards better understanding of normal and missing immune surveillence in myeloma have led to development of new strategies and therapies that require the engagement of the immune system. Many of these treatments are under clinical development and have already started providing encouraging results. We, for the second time in the last two decades, are about to witness another shift of the paradigm in the management of this ailment. This review will summarize the major approaches in myeloma immunotherapies.

  1. Smoldering multiple myeloma risk factors for progression

    DEFF Research Database (Denmark)

    Sørrig, Rasmus; Klausen, Tobias W; Salomo, Morten

    2016-01-01

    Several risk scores for disease progression in Smoldering Multiple Myeloma (SMM) patients have been proposed, however, all have been developed using single center registries. To examine risk factors for time to progression (TTP) to Multiple Myeloma (MM) for SMM we analyzed a nationwide population......-based cohort of 321 newly diagnosed SMM patients registered within the Danish Multiple Myeloma Registry between 2005 and 2014. Significant univariable risk factors for TTP were selected for multivariable Cox regression analyses. We found that both an M-protein ≥ 30g/l and immunoparesis significantly influenced......-high risk of transformation to MM. Using only immunoparesis and M-protein ≥ 30g/l, we created a scoring system to identify low, intermediate and high risk SMM. This first population-based study of SMM patients confirms that an M-protein ≥ 30g/l and immunoparesis remain important risk factors for progression...

  2. Hemibody irradiation in multiple myeloma

    International Nuclear Information System (INIS)

    Tobias, J.S.; Richards, J.D.M.; Blackman, G.M.; Joannides, T.; Trask, C.W.L.; Nathan, J.I.

    1985-01-01

    Eighteen patients with multiple myeloma were treated by hemibody irradiation using large single fractions, usually to a dose of 10 Gy (lower half) and 7.5 GY (upper half). All except one patient had previously been treated by multiple courses of conventional chemotherapy with melphalan and prednisone, and were considered to be resistant to further chemotherapy. In most cases, local field irradiation had also been given for symptomatic bone pain. Of the 13 patients who had symptoms at the start of hemibody irradiation, 11 improved sufficiently for their analgesia requirement to be reduced. In eight patients, there was a significant fall in circulating immunoglobulin but no patient with Bence-Jones proteinuria had complete resolution of this biochemical abnormality. Although thrombocytopenia and neutropenia were common, only two patients required platelet transfusion and the treatment was in general extremely well tolerated. Survival following hemibody irradiation was similar to the survival reported from the use of 'second-line' chemotherapy and we feel that hemibody irradiation is a more acceptable alternative for most patients. (orig.)

  3. The impact of comorbidity on mortality in multiple myeloma

    DEFF Research Database (Denmark)

    Gregersen, Henrik; Vangsted, Annette Juul; Abildgaard, Niels

    2017-01-01

    To describe the prevalence of comorbidity and its impact on survival in newly diagnosed multiple myeloma patients compared with population controls. Cases of newly diagnosed symptomatic multiple myeloma during the 2005-2012 period were identified in the Danish National Multiple Myeloma Registry....... For each myeloma patient, 10 members of the general population matched by age and sex were chosen from the national Civil Registration System. Data on comorbidity in the myeloma patients and the general population comparison cohort were collected by linkage to the Danish National Patient Registry (DNPR......). Cox proportional hazards regression models were used to evaluate the prognostic significance of comorbidity. The study included 2190 cases of multiple myeloma and 21,900 population controls. The comorbidity was increased in multiple myeloma patients compared with population controls, odds ratio (OR) 1...

  4. Up-regulation of hexokinaseII in myeloma cells: targeting myeloma cells with 3-bromopyruvate.

    Science.gov (United States)

    Nakano, Ayako; Miki, Hirokazu; Nakamura, Shingen; Harada, Takeshi; Oda, Asuka; Amou, Hiroe; Fujii, Shiro; Kagawa, Kumiko; Takeuchi, Kyoko; Ozaki, Shuji; Matsumoto, Toshio; Abe, Masahiro

    2012-02-01

    Hexokinase II (HKII), a key enzyme of glycolysis, is widely over-expressed in cancer cells. However, HKII levels and its roles in ATP production and ATP-dependent cellular process have not been well studied in hematopoietic malignant cells including multiple myeloma (MM) cells.We demonstrate herein that HKII is constitutively over-expressed in MM cells. 3-bromopyruvate (3BrPA), an inhibitor of HKII, promptly and substantially suppresses ATP production and induces cell death in MM cells. Interestingly, cocultures with osteoclasts (OCs) but not bone marrow stromal cells (BMSCs) enhanced the phosphorylation of Akt along with an increase in HKII levels and lactate production in MM cells. The enhancement of HKII levels and lactate production in MM cells by OCs were mostly abrogated by the PI3K inhibitor LY294002, suggesting activation of glycolysis in MM cells by OCs via the PI3K-Akt-HKII pathway. Although BMSCs and OCs stimulate MM cell growth and survival, 3BrPA induces cell death in MM cells even in cocultures with OCs as well as BMSCs. Furthermore, 3BrPA was able to diminish ATP-dependent ABC transporter activity to restore drug retention in MM cells in the presence of OCs. These results may underpin possible clinical application of 3BrPA in patients with MM.

  5. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer Leukemia Liver Cancer Lung ... need for different kinds of information about her colorectal cancer prognosis. Diving Out of the Dark View this ...

  6. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer Leukemia Liver Cancer ... need for different kinds of information about her colorectal cancer prognosis. Diving Out of the Dark View ...

  7. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer Leukemia Liver Cancer Lung ... need for different kinds of information about her colorectal cancer prognosis. Diving Out of the Dark View this ...

  8. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... Cancer Kidney (Renal Cell) Cancer Leukemia Liver Cancer Lung Cancer Lymphoma Pancreatic Cancer Prostate Cancer Skin Cancer Thyroid ... and where it is in your body The stage of the cancer, which refers to the size ...

  9. Stages of Endometrial Cancer

    Science.gov (United States)

    ... Common Cancer Types Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer ... cancer cells have places where hormones can attach ( receptors ), drugs , surgery, or radiation therapy is used to ...

  10. Technetium-99m Sestamibi in Multiple Myeloma

    International Nuclear Information System (INIS)

    Saber, R.A.

    2002-01-01

    Technetium-99m 2-methoxy - isobutyl - isonitrile (99mTc-MIBI) has been reported to be useful in evaluating patients with multiple myeloma. The aim of this study is to evaluate the role of technetium-99m sestamibi (99mTc-MIBI) scintigraphy in the diagnosis. staging and follow-up of patients with multiple myeloma. Methods and Materials: twenty-five consecutive patients with multiple myeloma were studied using 99mTc- MIBI. Of the 25 patients included in this study, 6 were in stage I, II in stage II and 8 in stage III. Anterior and posterior whole-body imaging were obtained 20 min after I.V. injection of 740 MBq of 99mTc-MIBI. Four different MIBI patterns could be described in our patients: physiological (P), diffuse (D), focal (F) and combined diffuse and focal (D+F). All patients in stages II and III as well as 3 patients in stage I were treated with chemotherapy (cyclophosphamide and prednisone) then 99mTc-MlBI scans were repeated after 6 courses. Results: in comparison to conventional X-ray skeletal survey, 99mTc-MIBI scans showed a higher number of myeloma bone disease at diagnosis. All patients with stage II and III multiple myeloma were positive with 99mTc-MlBl scans at diagnosis. The pattern of positive MIBI accumulation was diffuse in 13 (52%) patients, focal in 4 (16%) and combined focal and diffuse in 6 (24%) patients. The intensity of 99mTc-MIBI correlated with disease activity as determined by lactate dehydrogenase (LDH), number of plasma cells in bone marrow and serum electrophoresis. There was a direct correlation between 99mTc-MIBI scan result and clinical outcome of patients following 6 courses of chemotherapy. Sensitivity and specificity of 99mTc-MIBI scintigraphy in detecting myeloma bone lesions were 92% and 90% respectively. Conclusion: 99mTc-MIBI scintigraphy is a reliable method to evaluate bone marrow activity in patients with multiple myeloma and follow-up of myeloma bone lesions

  11. Genetic variations in multiple myeloma I

    DEFF Research Database (Denmark)

    Vangsted, A.; Klausen, T.W.; Vogel, Ulla Birgitte

    2012-01-01

    Few risk factors have been established for the plasma cell disorder multiple myeloma, but some of these like African American ethnicity and a family history of B-cell lymphoproliferative diseases suggest a genetic component for the disease. Genetic variation represents the genetic basis of variab......Few risk factors have been established for the plasma cell disorder multiple myeloma, but some of these like African American ethnicity and a family history of B-cell lymphoproliferative diseases suggest a genetic component for the disease. Genetic variation represents the genetic basis...

  12. Thymidine secretion by hybridoma and myeloma cells

    International Nuclear Information System (INIS)

    Spilsberg, Bjorn; Rise, Frode; Petersen, Dirk; Nissen-Meyer, Jon

    2006-01-01

    Secretion of thymidine appeared to be a common property of hybridoma and myeloma cells, but not of other cell types, which were tested. Of three hybridoma cell lines tested, all secreted thymidine in amounts resulting in the accumulation of thymidine to concentrations of 10-20 μM in the culture medium. Also three of five myeloma cell lines that were analyzed secrete thymidine, but none of the other cell types that were studied. Thymidine was purified to homogeneity (4 mg purified from 3 l of culture medium) and identified as such by nuclear magnetic resonance spectroscopy. The cells that secreted thymidine showed high resistance to the growth inhibitory effect of thymidine

  13. [IgE myeloma. Laboratory typing difficulties].

    Science.gov (United States)

    Bovone, Nora S; Fuente, María Cristina; Gastiazoro, Ana María; Alfonso, Graciela; Freitas, María Josefina

    2014-01-01

    The IgE multiple myeloma is a rare neoplasm of plasma cell accounting for 0.01% of all plasma cell dyscrasias. They are generally of more aggressive development and to date there are no more than 50 cases published in current literature. Laboratory studies are, in these cases, essential for the classification of the monoclonal component in serum and urine. The aim of this presentation is to report a patient diagnosed with IgE myeloma and to point out that the laboratory difficulties noted in these rare cases can lead to an erroneous report.

  14. Pre-clinical evaluation of CD38 chimeric antigen receptor engineered T cells for the treatment of multiple myeloma

    DEFF Research Database (Denmark)

    Drent, Esther; Groen, Richard W. J.; Noort, Willy A. Noort

    2016-01-01

    Adoptive transfer of chimeric antigen receptor-transduced T cells is a promising strategy for cancer immunotherapy. The CD38 molecule, with its high expression on multiple myeloma cells, appears a suitable target for antibody therapy. Prompted by this, we used three different CD38 antibody...... sequences to generate second-generation retroviral CD38- chimeric antigen receptor constructs with which we transduced T cells from healthy donors and multiple myeloma patients. We then evaluated the preclinical efficacy and safety of the transduced T cells. Irrespective of the donor and antibody sequence......, CD38-chimeric antigen receptor-transduced T cells proliferated, produced inflammatory cytokines and effectively lysed malignant cell lines and primary malignant cells from patients with acute myeloid leukemia and multi-drug resistant multiple myeloma in a cell-dose, and CD38-dependent manner, despite...

  15. Report of the European Myeloma Network on multiparametric flow cytometry in multiple myeloma and related disorders

    DEFF Research Database (Denmark)

    Rawstron, Andy C; Orfao, Alberto; Beksac, Meral

    2008-01-01

    The European Myeloma Network (EMN) organized two flow cytometry workshops. The first aimed to identify specific indications for flow cytometry in patients with monoclonal gammopathies, and consensus technical approaches through a questionnaire-based review of current practice in participating...

  16. Renal Cell Regulation and Cancer: Tumor Suppressor Networks and the Primary Cilium

    NARCIS (Netherlands)

    Klasson, TD

    2017-01-01

    Cancer affects a large number of people the world over. Cancer is a class of extremely complex diseases that arise from malfunctions in otherwise vital cellular processes, especially those that govern aspects of cellular functions like proliferation, apoptosis or the cell cycle. These processes are

  17. Acute renal failure secondary to drug-related crystalluria and/or drug reaction with eosinophilia and systemic symptom syndrome in a patient with metastatic lung cancer

    Directory of Open Access Journals (Sweden)

    Saime Paydas

    2017-01-01

    Full Text Available Drug reaction with eosinophilia and systemic symptoms (DRESS or drug-induced hypersensitivity is a severe adverse drug-induced reaction. Aromatic anticonvulsants, such as phenytoin, phenobarbital, and carbamazepine, and some drugs, can induce DRESS. Atypical crystalluria can be seen in patients treated with amoxycillin or some drugs and can cause acute renal failure. We describe a 66-year-old man who presented fever and rash and acute renal failure three days after starting amoxycillin. He was also using phenytoin because of cerebral metastatic lung cancer. Investigation revealed eosinophilia and atypical crystalluria. The diagnosis of DRESS syndrome was made, amoxicillin was stopped, and dose of phenytoin was reduced. No systemic corticosteroid therapy was prescribed. Symptoms began to resolve within three to four days. The aim of this paper is to highlight the importance of microscopic examination of urine in a case with acute renal failure and skin lesions to suspect DRESS syndrome.

  18. Renal Cell Cancer: What Can We Learn from Pre-Operative Studies?

    Energy Technology Data Exchange (ETDEWEB)

    Fisher, Rosalie; Larkin, James, E-mail: james.larkin@rmh.nhs.uk [Department of Medical Oncology, Royal Marsden Hospital, London (United Kingdom)

    2011-12-08

    Renal cell carcinoma (RCC) affects approximately 60,000 people in Europe and in the United States each year (Ferlay et al., 2007; Jemal et al., 2010), and is associated with high rates of morbidity and mortality. The incidence of RCC is rising, perhaps because of the widespread use of abdominal imaging, resulting in an increased detection of small renal masses, and surgical intervention for these (Hollingsworth et al., 2006; Falebita et al., 2009). Surgery remains an integral part of the management of RCC, and is the only curative treatment in patients with disease confined to the kidney and its regional vasculature and lymph nodes. However, about 30% of patients are diagnosed with metastatic renal cell carcinoma (mRCC) at presentation (Motzer et al., 1996) and a similar proportion will later develop metastases (Leibovich et al., 2003). Until 2007, a combination of cytoreductive nephrectomy (CN) and immunotherapy, usually interferon-α, was considered to be the standard of care for those patients presenting with mRCC deemed fit enough, although cytokine therapy was associated with modest benefits and much toxicity (Coppin et al., 2005). The basis for nephrectomy in the context of metastatic disease was provided by two similar prospective trials which randomized patients to CN plus interferon or interferon alone. Combined analysis of the two trials demonstrated a median survival of 13.6 months for surgery plus interferon, and 7.8 months for interferon alone (HR = 0.69, 95% CI = 0.55–0.87, p = 0.002; Flanigan et al., 2004). The simplest rationale for why CN might improve survival in mRCC is a reduction in overall tumor burden, thus delaying time to a lethal burden of disease; other theories include a decrease in the amount of tumor shedding and systemic signaling from the primary renal mass, effective palliation of pain, bleeding and paraneoplastic syndromes, and removal of a source of significant immunosuppression. The latter was proposed on the basis of reports

  19. Common variation at 1q24.1 (ALDH9A1 is a potential risk factor for renal cancer.

    Directory of Open Access Journals (Sweden)

    Marc Y R Henrion

    Full Text Available So far six susceptibility loci for renal cell carcinoma (RCC have been discovered by genome-wide association studies (GWAS. To identify additional RCC common risk loci, we performed a meta-analysis of published GWAS (totalling 2,215 cases and 8,566 controls of Western-European background with imputation using 1000 Genomes Project and UK10K Project data as reference panels and followed up the most significant association signals [22 single nucleotide polymorphisms (SNPs and 3 indels in eight genomic regions] in 383 cases and 2,189 controls from The Cancer Genome Atlas (TCGA. A combined analysis identified a promising susceptibility locus mapping to 1q24.1 marked by the imputed SNP rs3845536 (Pcombined =2.30x10-8. Specifically, the signal maps to intron 4 of the ALDH9A1 gene (aldehyde dehydrogenase 9 family, member A1. We further evaluated this potential signal in 2,461 cases and 5,081 controls from the International Agency for Research on Cancer (IARC GWAS of RCC cases and controls from multiple European regions. In contrast to earlier findings no association was shown in the IARC series (P=0.94; Pcombined =2.73x10-5. While variation at 1q24.1 represents a potential risk locus for RCC, future replication analyses are required to substantiate our observation.

  20. T cells in multiple myeloma display features of exhaustion and senescence at the tumor site

    Directory of Open Access Journals (Sweden)

    Claudia Zelle-Rieser

    2016-11-01

    Full Text Available Abstract Background Multiple myeloma is an incurable plasma cell malignancy that is mostly restricted to the bone marrow. Cancer-induced dysfunction of cytotoxic T cells at the tumor site may be responsible for immune evasion and therapeutical failure of immunotherapies. Therefore, enhanced knowledge about the actual status of T cells in myeloma bone marrow is urgently needed. Here, we assessed the expression of inhibitory molecules PD-1, CTLA-4, 2B4, CD160, senescence marker CD57, and CD28 on T cells of naive and treated myeloma patients in the bone marrow and peripheral blood and collected data on T cell subset distribution in both compartments. In addition, T cell function concerning proliferation and expression of T-bet, IL-2, IFNγ, and CD107a was investigated after in vitro stimulation by CD3/CD28. Finally, data was compared to healthy, age-matched donor T cells from both compartments. Methods Multicolor flow cytometry was utilized for the analyses of surface molecules, intracellular staining of cytokines was also performed by flow cytometry, and proliferation was assessed by 3H-thymidine incorporation. Statistical analyses were performed utilizing unpaired T test and Mann-Whitney U test. Results We observed enhanced T cell exhaustion and senescence especially at the tumor site. CD8+ T cells expressed several molecules associated with T cell exhaustion (PD-1, CTLA-4, 2B4, CD160 and T cell senescence (CD57, lack of CD28. This phenotype was associated with lower proliferative capacity and impaired function. Despite a high expression of the transcription factor T-bet, CD8+ T cells from the tumor site failed to produce IFNγ after CD3/CD28 in vitro restimulation and displayed a reduced ability to degranulate in response to T cell stimuli. Notably, the percentage of senescent CD57+CD28− CD8+ T cells was significantly lower in treated myeloma patients when compared to untreated patients. Conclusions T cells from the bone marrow of myeloma

  1. Cancer drug troglitazone stimulates the growth and response of renal cells to hypoxia inducible factors

    Energy Technology Data Exchange (ETDEWEB)

    Taub, Mary, E-mail: biochtau@buffalo.edu

    2016-03-11

    Troglitazone has been used to suppress the growth of a number of tumors through apoptosis and autophagy. However, previous in vitro studies have employed very high concentrations of troglitazone (≥10{sup −5} M) in order to elicit growth inhibitory effects. In this report, when employing lower concentrations of troglitazone in defined medium, troglitazone was observed to stimulate the growth of primary renal proximal tubule (RPT) cells. Rosiglitazone, like troglitazone, is a thiazolidinedione (TZD) that is known to activate Peroxisome Proliferator Activated Receptor Υ (PPARΥ). Notably, rosiglitazone also stimulates RPT cell growth, as does Υ-linolenic acids, another PPARΥ agonist. The PPARΥ antagonist GW9662 inhibited the growth stimulatory effect of troglitazone. In addition, troglitazone stimulated transcription by a PPAR Response Element/Luciferase construct. These results are consistent with the involvement of PPARΥ as a mediator of the growth stimulatory effect of troglitazone. In a number of tumor cells, the expression of hypoxia inducible factor (HIF) is increased, promoting the expression of HIF inducible genes, and vascularization. Troglitazone was observed to stimulate transcription by a HIF/luciferase construct. These observations indicate that troglitazone not only promotes growth, also the survival of RPT cells under conditions of hypoxia. - Highlights: • Troglitazone and rosiglitazone stimulate renal proximal tubule cell growth. • Troglitazone and linolenic acid stimulate growth via PPARϒ. • Linolenic acid stimulates growth in the presence of fatty acid free serum albumin. • Rosiglitazone stimulates transcription by a HRE luciferase construct.

  2. Cancer drug troglitazone stimulates the growth and response of renal cells to hypoxia inducible factors

    International Nuclear Information System (INIS)

    Taub, Mary

    2016-01-01

    Troglitazone has been used to suppress the growth of a number of tumors through apoptosis and autophagy. However, previous in vitro studies have employed very high concentrations of troglitazone (≥10"−"5 M) in order to elicit growth inhibitory effects. In this report, when employing lower concentrations of troglitazone in defined medium, troglitazone was observed to stimulate the growth of primary renal proximal tubule (RPT) cells. Rosiglitazone, like troglitazone, is a thiazolidinedione (TZD) that is known to activate Peroxisome Proliferator Activated Receptor Υ (PPARΥ). Notably, rosiglitazone also stimulates RPT cell growth, as does Υ-linolenic acids, another PPARΥ agonist. The PPARΥ antagonist GW9662 inhibited the growth stimulatory effect of troglitazone. In addition, troglitazone stimulated transcription by a PPAR Response Element/Luciferase construct. These results are consistent with the involvement of PPARΥ as a mediator of the growth stimulatory effect of troglitazone. In a number of tumor cells, the expression of hypoxia inducible factor (HIF) is increased, promoting the expression of HIF inducible genes, and vascularization. Troglitazone was observed to stimulate transcription by a HIF/luciferase construct. These observations indicate that troglitazone not only promotes growth, also the survival of RPT cells under conditions of hypoxia. - Highlights: • Troglitazone and rosiglitazone stimulate renal proximal tubule cell growth. • Troglitazone and linolenic acid stimulate growth via PPARϒ. • Linolenic acid stimulates growth in the presence of fatty acid free serum albumin. • Rosiglitazone stimulates transcription by a HRE luciferase construct.

  3. Unique protein expression signatures of survival time in kidney renal clear cell carcinoma through a pan-cancer screening.

    Science.gov (United States)

    Han, Guangchun; Zhao, Wei; Song, Xiaofeng; Kwok-Shing Ng, Patrick; Karam, Jose A; Jonasch, Eric; Mills, Gordon B; Zhao, Zhongming; Ding, Zhiyong; Jia, Peilin

    2017-10-03

    In 2016, it is estimated that there will be 62,700 new cases of kidney cancer in the United States, and 14,240 patients will die from the disease. Because the incidence of kidney renal clear cell carcinoma (KIRC), the most common type of kidney cancer, is expected to continue to increase in the US, there is an urgent need to find effective diagnostic biomarkers for KIRC that could help earlier detection of and customized treatment strategies for the disease. Accordingly, in this study we systematically investigated KIRC's prognostic biomarkers for survival using the reverse phase protein array (RPPA) data and the high throughput sequencing data from The Cancer Genome Atlas (TCGA). With comprehensive data available in TCGA, we systematically screened protein expression based survival biomarkers in 10 major cancer types, among which KIRC presented many protein prognostic biomarkers of survival time. This is in agreement with a previous report that expression level changes (mRNAs, microRNA and protein) may have a better performance for prognosis of KIRC. In this study, we also identified 52 prognostic genes for KIRC, many of which are involved in cell-cycle and cancer signaling, as well as 15 tumor-stage-specific prognostic biomarkers. Notably, we found fewer prognostic biomarkers for early-stage than for late-stage KIRC. Four biomarkers (the RPPA protein IDs: FASN, ACC1, Cyclin_B1 and Rad51) were found to be prognostic for survival based on both protein and mRNA expression data. Through pan-cancer screening, we found that many protein biomarkers were prognostic for patients' survival in KIRC. Stage-specific survival biomarkers in KIRC were also identified. Our study indicated that these protein biomarkers might have potential clinical value in terms of predicting survival in KIRC patients and developing individualized treatment strategies. Importantly, we found many biomarkers in KIRC at both the mRNA expression level and the protein expression level. These

  4. The role of epigenetics in the biology of multiple myeloma

    DEFF Research Database (Denmark)

    Dimopoulos, K; Gimsing, P; Grønbæk, K

    2014-01-01

    Several recent studies have highlighted the biological complexity of multiple myeloma (MM) that arises as a result of several disrupted cancer pathways. Apart from the central role of genetic abnormalities, epigenetic aberrations have also been shown to be important players in the development of MM......, and a lot of research during the past decades has focused on the ways DNA methylation, histone modifications and noncoding RNAs contribute to the pathobiology of MM. This has led to, apart from better understanding of the disease biology, the development of epigenetic drugs, such as histone deacetylase...... inhibitors that are already used in clinical trials in MM with promising results. This review will present the role of epigenetic abnormalities in MM and how these can affect specific pathways, and focus on the potential of novel 'epidrugs' as future treatment modalities for MM....

  5. General Information about Transitional Cell Cancer of the Renal Pelvis and Ureter

    Science.gov (United States)

    ... These cells can change shape and stretch without breaking apart. Transitional cell cancer starts in these cells. ... away. Extreme tiredness. Weight loss with no known reason. Painful or frequent urination. Tests that examine the ...

  6. Dose-dependent changes in renal {sup 1}H-/{sup 23}Na MRI after adjuvant radiochemotherapy for gastric cancer

    Energy Technology Data Exchange (ETDEWEB)

    Haneder, Stefan [University Medical Centre Mannheim, University of Heidelberg, Institute of Clinical Radiology and Nuclear Medicine, Mannheim (Germany); University Hospital of Cologne, Department of Radiology, Cologne (Germany); Budjan, Johannes Michael; Schoenberg, Stefan Oswald [University Medical Centre Mannheim, University of Heidelberg, Institute of Clinical Radiology and Nuclear Medicine, Mannheim (Germany); Konstandin, Simon; Schad, Lothar Rudi [University Medical Centre Mannheim, University of Heidelberg, Computer Assisted Clinical Medicine, Mannheim (Germany); Hofheinz, Ralf Dieter [University Medical Centre Mannheim, University of Heidelberg, III. Department of Internal Medicine, Mannheim (Germany); Gramlich, Veronika; Wenz, Frederik; Lohr, Frank; Boda-Heggemann, Judit [University Medical Centre Mannheim, Medical Faculty Mannheim - University of Heidelberg, Department of Radiation Oncology, Mannheim (Germany)

    2015-04-01

    Combined radiochemotherapy (RCT) for gastric cancer with three-dimensional conformal radiotherapy (3D-CRT) results in ablative doses to the upper left kidney, while image-guided intensity-modulated radiotherapy (IG-IMRT) allows kidney sparing despite improved target coverage. Renal function in long-term gastric cancer survivors was evaluated with 3T functional magnetic resonance imaging (MRI) including diffusion-weighted imaging (DWI) and {sup 23}Na imaging. Five healthy volunteers and 13 patients after radiotherapy were included: 11 x IG-IMRT; 1 x 3D-CRT; 1 x ''positive control'' with stereotactic body radiotherapy (SBRT) of a metastasis between the spleen/left kidney. Radiation doses were documented for the upper/middle/lower kidney subvolumes. Late toxicity was evaluated based on CTC criteria, questionnaire, and creatinine values. Morphological sequences, DWI images, and {sup 23}Na images were acquired using a {sup 1}H/{sup 23}Na-tuned body-coil before/after intravenous water load (WL). Statistics for [{sup 23}Na] (concentration) and apparent diffusion coefficient (ADC) values were calculated for upper/middle/lower renal subvolumes. Corticomedullary [{sup 23}Na] gradients and [{sup 23}Na] differences after WL were determined. No major morphological alteration was detected in any patient. Minor scars were observed in the cranial subvolume of the left kidney of the 3D-CRT and the whole kidney of the control SBRT patient. All participants presented a corticomedullary [{sup 23}Na] gradient. After WL, a significant physiological [{sup 23}Na] gradient decrease (p < 0.001) was observed in all HV and IG-IMRT patients. In the cranial left kidney of the 3D-CRT patient and the positive control SBRT patient, the decrease was nonsignificant (p = 0.01, p = 0.02). ADC values were altered nonsignificantly in all renal subvolumes (all participants). Renal subvolumes with doses ≥ 35 Gy showed a reduced change of the [{sup 23}Na] gradient after WL (p = 0

  7. Human Renal Normal, Tumoral, and Cancer Stem Cells Express Membrane-Bound Interleukin-15 Isoforms Displaying Different Functions

    Directory of Open Access Journals (Sweden)

    Sandy Azzi

    2015-06-01

    Full Text Available Intrarenal interleukin-15 (IL-15 participates to renal pathophysiology, but the role of its different membrane-bound isoforms remains to be elucidated. In this study, we reassess the biology of membrane-bound IL-15 (mb-IL-15 isoforms by comparing primary cultures of human renal proximal tubular epithelial cells (RPTEC to peritumoral (ptumTEC, tumoral (RCC, and cancer stem cells (CSC/CD105+. RPTEC express a 14 to 16 kDa mb-IL-15, whose existence has been assumed but never formally demonstrated and likely represents the isoform anchored at the cell membrane through the IL-15 receptor α (IL-15Rα chain, because it is sensitive to acidic treatment and is not competent to deliver a reverse signal. By contrast, ptumTEC, RCC, and CSC express a novel N-hyperglycosylated, short-lived transmembrane mb-IL-15 (tmb-IL-15 isoform around 27 kDa, resistant to acidic shock, delivering a reverse signal in response to its soluble receptor (sIL-15Rα. This reverse signal triggers the down-regulation of the tumor suppressor gene E-cadherin in ptumTEC and RCC but not in CSC/CD105+, where it promotes survival. Indeed, through the AKT pathway, tmb-IL-15 protects CSC/CD105+ from non-programmed cell death induced by serum starvation. Finally, both mb-IL-15 and tmb-IL-15 are sensitive to metalloproteases, and the cleaved tmb-IL-15 (25 kDa displays a powerful anti-apoptotic effect on human hematopoietic cells. Overall, our data indicate that both mb-IL-15 and tmb-IL-15 isoforms play a complex role in renal pathophysiology downregulating E-cadherin and favoring cell survival. Moreover, “apparently normal” ptumTEC cells, sharing different properties with RCC, could contribute to organize an enlarged peritumoral “preneoplastic” environment committed to favor tumor progression.

  8. Plasmacytoma Infiltrating Leiomyoma in Multiple Myeloma

    Science.gov (United States)

    2018-01-19

    REPORT TYPE 3. DATES COVERED (From - To) 01/19/2018 Poster 01/19/2018-01/21/2018 4. TITLE AND SUBTITLE Sa. CONTRACT NUMBER Plasmacytoma...Infiltrating Leiomyoma in Multiple Myeloma Sb. GRANT NUMBER Sc. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Sd. PROJECT NUMBER Capt Eden, Rina Se. TASK NUMBER Sf

  9. Myeloma cells suppress osteoblasts through sclerostin secretion

    Energy Technology Data Exchange (ETDEWEB)

    Colucci, S; Brunetti, G; Oranger, A [Department of Human Anatomy and Histology, University of Bari Medical School, Bari (Italy); Mori, G [Department of Biomedical Science, University of Foggia, Foggia (Italy); Sardone, F [Department of Human Anatomy and Histology, University of Bari Medical School, Bari (Italy); Specchia, G; Rinaldi, E; Curci, P; Liso, V [Department of Emergency and Organ Transplantation, Hematology Section, Bari University Medical School, Bari (Italy); Passeri, G [Department of Internal Medicine and Biomedical Sciences, Center for Metabolic Bone Diseases, University of Parma, Parma (Italy); Zallone, A [Department of Human Anatomy and Histology, University of Bari Medical School, Bari (Italy); Rizzi, R [Department of Emergency and Organ Transplantation, Hematology Section, Bari University Medical School, Bari (Italy); Grano, M [Department of Human Anatomy and Histology, University of Bari Medical School, Bari (Italy)

    2011-06-01

    Wingless-type (Wnt) signaling through the secretion of Wnt inhibitors Dickkopf1, soluble frizzled-related protein-2 and -3 has a key role in the decreased osteoblast (OB) activity associated with multiple myeloma (MM) bone disease. We provide evidence that another Wnt antagonist, sclerostin, an osteocyte-expressed negative regulator of bone formation, is expressed by myeloma cells, that is, human myeloma cell lines (HMCLs) and plasma cells (CD138+ cells) obtained from the bone marrow (BM) of a large number of MM patients with bone disease. We demonstrated that BM stromal cells (BMSCs), differentiated into OBs and co-cultured with HMCLs showed, compared with BMSCs alone, reduced expression of major osteoblastic-specific proteins, decreased mineralized nodule formation and attenuated the expression of members of the activator protein 1 transcription factor family (Fra-1, Fra-2 and Jun-D). Moreover, in the same co-culture system, the addition of neutralizing anti-sclerostin antibodies restored OB functions by inducing nuclear accumulation of β-catenin. We further demonstrated that the upregulation of receptor activator of nuclear factor κ-B ligand and the downregulation of osteoprotegerin in OBs were also sclerostin mediated. Our data indicated that sclerostin secretion by myeloma cells contribute to the suppression of bone formation in the osteolytic bone disease associated to MM.

  10. Implications of Heterogeneity in Multiple Myeloma

    Directory of Open Access Journals (Sweden)

    Sanjay de Mel

    2014-01-01

    Full Text Available Multiple myeloma is the second most common hematologic malignancy in the world. Despite improvement in outcome, the disease is still incurable for most patients. However, not all myeloma are the same. With the same treatment, some patients can have very long survival whereas others can have very short survival. This suggests that there is underlying heterogeneity in myeloma. Studies over the years have revealed multiple layers of heterogeneity. First, clinical parameters such as age and tumor burden could significantly affect outcome. At the genetic level, there are also significant heterogeneity ranging for chromosome numbers, genetic translocations, and genetic mutations. At the clonal level, there appears to be significant clonal heterogeneity with multiple clones coexisting in the same patient. At the cell differentiation level, there appears to be a hierarchy of clonally related cells that have different clonogenic potential and sensitivity to therapies. These levels of complexities present challenges in terms of treatment and prognostication as well as monitoring of treatment. However, if we can clearly delineate and dissect this heterogeneity, we may also be presented with unique opportunities for precision and personalized treatment of myeloma. Some proof of concepts of such approaches has been demonstrated.

  11. New experimental model of multiple myeloma.

    Science.gov (United States)

    Telegin, G B; Kalinina, A R; Ponomarenko, N A; Ovsepyan, A A; Smirnov, S V; Tsybenko, V V; Homeriki, S G

    2001-06-01

    NSO/1 (P3x63Ay 8Ut) and SP20 myeloma cells were inoculated to BALB/c OlaHsd mice. NSO/1 cells allowed adequate stage-by-stage monitoring of tumor development. The adequacy of this model was confirmed in experiments with conventional cytostatics: prospidium and cytarabine caused necrosis of tumor cells and reduced animal mortality.

  12. The option value of innovative treatments for non-small cell lung cancer and renal cell carcinoma.

    Science.gov (United States)

    Thornton Snider, Julia; Batt, Katharine; Wu, Yanyu; Tebeka, Mahlet Gizaw; Seabury, Seth

    2017-10-01

    To develop a model of the option value a therapy provides by enabling patients to live to see subsequent innovations and to apply the model to the case of nivolumab in renal cell carcinoma (RCC) and non-small cell lung cancer (NSCLC). A model of the option value of nivolumab in RCC and NSCLC was developed and estimated. Data from the Surveillance, Epidemiology, and End Results (SEER) cancer registry and published clinical trial results were used to estimate survival curves for metastatic cancer patients with RCC, squamous NSCLC, or nonsquamous NSCLC. To estimate the conventional value of nivolumab, survival with the pre-nivolumab standard of care was compared with survival with nivolumab assuming no future innovation. To estimate the option value of nivolumab, long-term survival trends in RCC and squamous and nonsquamous NSCLC were measured in SEER to forecast mortality improvements that nivolumab patients may live to see. Compared with the previous standard of care, nivolumab extended life expectancy by 6.3 months in RCC, 7.5 months in squamous NSCLC, and 4.5 months in nonsquamous NSCLC, according to conventional methods. Accounting for expected future mortality trends, nivolumab patients are likely to gain an additional 1.2 months in RCC, 0.4 months in squamous NSCLC, and 0.5 months in nonsquamous NSCLC. These option values correspond to 18%, 5%, and 10% of the conventional value of nivolumab, respectively. Option value is important when valuing therapies like nivolumab that extend life in a rapidly evolving area of care.

  13. Improved overall survival after implementation of targeted therapy for patients with metastatic renal cell carcinoma: Results from the Danish Renal Cancer Group (DARENCA) study-2

    DEFF Research Database (Denmark)

    Sørensen, Anne V.; Donskov, Frede; Hermann, Gregers G.

    2014-01-01

    AbstractAim To evaluate the implementation of targeted therapy on overall survival (OS) in a complete national cohort of patients with metastatic renal cell carcinoma (mRCC). Methods All Danish patients with mRCC referred for first line treatment with immunotherapy, TKIs or mTOR-inhibitors between...

  14. Value of the free light chain analysis in the clinical evaluation of response in multiple myeloma patients receiving anti-myeloma therapy

    DEFF Research Database (Denmark)

    Toftmann Hansen, Charlotte; Pedersen, Per T.; Jensen, Bo Amdi

    Value of the free light chain analysis in the clinical evaluation of response in multiple myeloma patients receiving anti-myeloma therapy.......Value of the free light chain analysis in the clinical evaluation of response in multiple myeloma patients receiving anti-myeloma therapy....

  15. Recommendations from the Spanish Oncology Genitourinary Group for the treatment of metastatic renal cancer.

    Science.gov (United States)

    Bellmunt, Joaquim; Calvo, Emiliano; Castellano, Daniel; Climent, Miguel Angel; Esteban, Emilio; García del Muro, Xavier; González-Larriba, José Luis; Maroto, Pablo; Trigo, José Manuel

    2009-03-01

    For almost the last two decades, interleukin-2 and interferon-alpha have been the only systemic treatment options available for metastatic renal cell carcinoma. However, in recent years, five new targeted therapies namely sunitinib, sorafenib, temsirolimus, everolimus and bevacizumab have demonstrated clinical activity in these patients. With the availability of new targeted agents that are active in this disease, there is a need to continuously update the treatment algorithm of the disease. Due to the important advances obtained, the Spanish Oncology Genitourinary Group (SOGUG) has considered it would be useful to review the current status of the disease, including the genetic and molecular biology factors involved, the current predicting models for development of metastases as well as the role of surgery, radiotherapy and systemic therapies in the early- or late management of the disease. Based on this previous work, a treatment algorithm was developed.

  16. Fundamentals in the management of multiple myeloma.

    Science.gov (United States)

    Fadilah, S A W

    2010-09-01

    Progress in our understanding of multiple myeloma and its treatment has resulted in a more tailored approach to patient management, with different therapeutics regimens for different patient populations. The decision to initiate therapy depends primarily on the presence of symptoms which has to balance the chance of tumor clearance and against the risks of treatment related mortality. Selection of appropriate initial treatment should be based primarily on patient's characteristics (biologic age, co-morbidities), the disease characteristics (tumor burden and genetic risk profile) and the expected toxicity profile of the different regimens. When treatment begins, in younger transplant eligible patients the goal is to achieve high quality responses with intensive therapies as the quality of response appears to be important surrogates for long-term outcome. In the majority of myeloma patients in whom intensive treatment is not an option due to advanced age and co-morbidities, treatment should emphasize on optimal disease control to obtain symptomatic relief and to maintain a satisfactory quality of life. The introduction of novel agents has substantially changed the treatment paradigm of this otherwise incurable disease. The utilization of these drugs has moved from relapse setting to the front line setting and has benefited all patient groups. Because of these rapid developments and many treatment options we need good quality clinical studies to guide clinical practice in the management of patients with multiple myeloma. This review presents an update on current concepts of diagnosis and treatment of patients with multiple myeloma and provides recommendations on tailored therapies with particular reference to the local practice. The information presented herein may be used by the health care providers caring for myeloma patients as a guideline to counsel patients to understand their disease and the treatment better.

  17. Radical nephrectomy and regional lymph node dissection for locally advanced type 2 papillary renal cell carcinoma in an at-risk individual from a family with hereditary leiomyomatosis and renal cell cancer: a case report

    International Nuclear Information System (INIS)

    Kamai, Takao; Abe, Hideyuki; Arai, Kyoko; Murakami, Satoshi; Sakamoto, Setsu; Kaji, Yasushi; Yoshida, Ken-Ichiro

    2016-01-01

    Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is an autosomal dominant tumor susceptibility syndrome, and the disease-related gene has been identified as fumarate hydratase (fumarase, FH). HLRCC-associated kidney cancer is an aggressive tumor characterized by early metastasis to regional lymph nodes and distant organs. Since early diagnosis and provision of definitive therapy is thought to be the best way to reduce the tumor burden, it is widely accepted that germline testing and active surveillance for an at-risk individual from a family with HLRCC is very important. However, it still remains controversial how we should treat HLRCC-associated kidney cancer. We successfully treated the patient with locally advanced HLRCC-associated kidney cancer, who has received active surveillance because of at-risk individual, by radical nephrectomy and extended retroperitoneal lymph node dissection, and examined surgically resected samples from a molecular point of view. We recommended that 13 at-risk individuals from a family with HLRCC should receive active surveillance for early detection of renal cancer. A 48-year-old woman with a left renal tumor and involvement of multiple regional lymph nodes with high accumulation of fluorine-18-deoxyglucose on positron emission tomography was treated with axitinib as a neoadjuvant therapy. Preoperative axitinib induced the shrinkage of the tumor with decreased fluorine-18-deoxyglucose accumulation. Resected samples showed two thirds tumor tissue necrosis as well as high expression of serine/threonine kinase Akt and low expression of nuclear factor E2-related factor 2 (Nrf2) which activates anti-oxidant response and protects against oxidative stress in viable cancer cells. Targeted next-generation sequencing revealed that FH mutation and loss of the second allele were completely identical between blood and tumor samples, suggesting that FH mutation plays a direct role in FH-deficient RCC. She has remained well after radical

  18. Determinants of anxiety in patients with advanced somatic disease: differences and similarities between patients undergoing renal replacement therapies and patients suffering from cancer.

    Science.gov (United States)

    Janiszewska, Justyna; Lichodziejewska-Niemierko, Monika; Gołębiewska, Justyna; Majkowicz, Mikołaj; Rutkowski, Bolesław

    2013-10-01

    Anxiety is the most frequent emotional reaction to the chronic somatic disease. However, little is known about anxiety and coping strategies in patients with end-stage renal disease (ESRD) undergoing renal replacement therapies (RRTs). The purpose of the study was to assess the intensity and determinants of anxiety in patients treated with different RRTs in comparison with end-stage breast cancer patients and healthy controls. The study involved (1) ESRD patients undergoing different RRTs: 32 renal transplant recipients, 31 maintenance haemodialysis and 21 chronic peritoneal dialysis patients, (2) women with end-stage breast cancer (n = 25) and (3) healthy persons (n = 55). We used State-Trait Anxiety Inventory, Scale of Personal Religiousness, Mental Adjustment to Cancer Scale, Rotterdam Symptom Checklist with reference to medical history. The data thus obtained were analysed using the analysis of variance, the Tukey's HSD post hoc test and Spearman's rank correlation coefficient. Both ESRD and breast cancer patients revealed higher level of anxiety state and trait than healthy controls; however, there was no statistically significant difference found between both findings. There was a tendency towards higher levels of anxiety state in breast cancer patients when compared to ESRD patients undergoing the RRT treatment and for both groups non-constructive coping strategies correlated with the levels of anxiety state. With ESRD patients undergoing RRTs, the intensity of anxiety state did not depend on the mode of treatment but on the correlation between the levels of anxiety and the general quality of their life, psychological condition and social activity. In patients with advanced somatic disease (ESRD and end-stage breast cancer), non-constructive strategies of coping with the disease require further evaluation and possibly psychological support.

  19. Myeloma Cell Dynamics in Response to Treatment Supports a Model of Hierarchical Differentiation and Clonal Evolution.

    Science.gov (United States)

    Tang, Min; Zhao, Rui; van de Velde, Helgi; Tross, Jennifer G; Mitsiades, Constantine; Viselli, Suzanne; Neuwirth, Rachel; Esseltine, Dixie-Lee; Anderson, Kenneth; Ghobrial, Irene M; San Miguel, Jesús F; Richardson, Paul G; Tomasson, Michael H; Michor, Franziska

    2016-08-15

    Since the pioneering work of Salmon and Durie, quantitative measures of tumor burden in multiple myeloma have been used to make clinical predictions and model tumor growth. However, such quantitative analyses have not yet been performed on large datasets from trials using modern chemotherapy regimens. We analyzed a large set of tumor response data from three randomized controlled trials of bortezomib-based chemotherapy regimens (total sample size n = 1,469 patients) to establish and validate a novel mathematical model of multiple myeloma cell dynamics. Treatment dynamics in newly diagnosed patients were most consistent with a model postulating two tumor cell subpopulations, "progenitor cells" and "differentiated cells." Differential treatment responses were observed with significant tumoricidal effects on differentiated cells and less clear effects on progenitor cells. We validated this model using a second trial of newly diagnosed patients and a third trial of refractory patients. When applying our model to data of relapsed patients, we found that a hybrid model incorporating both a differentiation hierarchy and clonal evolution best explains the response patterns. The clinical data, together with mathematical modeling, suggest that bortezomib-based therapy exerts a selection pressure on myeloma cells that can shape the disease phenotype, thereby generating further inter-patient variability. This model may be a useful tool for improving our understanding of disease biology and the response to chemotherapy regimens. Clin Cancer Res; 22(16); 4206-14. ©2016 AACR. ©2016 American Association for Cancer Research.

  20. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer Leukemia Liver Cancer Lung Cancer Lymphoma Pancreatic ... grade, which refers to how abnormal the cancer cells look under a microscope. Grade provides clues about ...

  1. Inflammatory Breast Cancer

    Science.gov (United States)

    ... Common Cancer Types Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer ... white women. Inflammatory breast tumors are frequently hormone receptor negative, which means they cannot be treated with ...

  2. Stages of Rectal Cancer

    Science.gov (United States)

    ... Common Cancer Types Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer ... VEGF inhibitors and angiogenesis inhibitors . Epidermal growth factor receptor (EGFR) inhibitor therapy: EGFRs are proteins found on ...

  3. Stages of Colon Cancer

    Science.gov (United States)

    ... Common Cancer Types Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer ... VEGF inhibitors and angiogenesis inhibitors . Epidermal growth factor receptor (EGFR) inhibitor therapy: EGFRs are proteins found on ...

  4. Obesity and Cancer Risk

    Science.gov (United States)

    ... Common Cancer Types Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer ... hormone therapy and for tumors that express hormone receptors . Obesity is also a risk factor for breast ...

  5. Presence of Donor-Derived DNA in Semen Samples From Cancer Survivors Who Underwent Donor Stem Cell Transplant

    Science.gov (United States)

    2014-12-08

    Cancer Survivor; Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms; Neuroblastoma; Testicular Germ Cell Tumor

  6. Renal impairment and late toxicity in germ-cell cancer survivors

    DEFF Research Database (Denmark)

    Lauritsen, J.; Mortensen, M. S.; Kier, M. G. G.

    2015-01-01

    cohort of germ-cell cancer survivors. Patients and methods BEP-treated patients (N = 1206) were identified in the Danish DaTeCa database, and merged with national registers to identify late toxicity. GFR were measured (51Cr-EDTA clearance) before and after treatment and at 1, 3 and 5-year follow...

  7. FDG-PET as a predictive biomarker for therapy with everolimus in metastatic renal cell cancer

    International Nuclear Information System (INIS)

    Chen, James L; Appelbaum, Daniel E; Kocherginsky, Masha; Cowey, Charles L; Kimryn Rathmell, Wendy; McDermott, David F; Stadler, Walter M

    2013-01-01

    The mTOR (mammalian target of rapamycin) inhibitor, everolimus, affects tumor growth by targeting cellular metabolic proliferation pathways and delays renal cell carcinoma (RCC) progression. Preclinical evidence suggests that baseline elevated tumor glucose metabolism as quantified by FDG-PET ([ 18 F] fluorodeoxy-glucose positron emission tomography) may predict antitumor activity. Metastatic RCC (mRCC) patients refractory to vascular endothelial growth factor (VEGF) pathway inhibition were treated with standard dose everolimus. FDG-PET scans were obtained at baseline and 2 weeks; serial computed tomography (CT) scans were obtained at baseline and every 8 weeks. Maximum standardized uptake value (SUVmax) of the most FDG avid lesion, average SUVmax of all measured lesions and their corresponding 2-week relative changes were examined for association with 8-week change in tumor size. A total of 63 patients were enrolled; 50 were evaluable for the primary endpoint of which 48 had both PET scans. Patient characteristics included the following: 36 (72%) clear cell histology and median age 59 (range: 37–80). Median pre- and 2-week treatment average SUVmax were 6.6 (1–17.9) and 4.2 (1–13.9), respectively. Response evaluation criteria in solid tumors (RECIST)-based measurements demonstrated an average change in tumor burden of 0.2% (−32.7% to 35.9%) at 8 weeks. Relative change in average SUVmax was the best predictor of change in tumor burden (all evaluable P = 0.01; clear cell subtype P = 0.02), with modest correlation. Baseline average SUVmax was correlated with overall survival and progression-free survival (PFS) (P = 0.023; 0.020), but not with change in tumor burden. Everolimus therapy decreased SUVs on follow-up PET scans in mRCC patients, but changes were only modestly correlated with changes in tumor size. Thus, clinical use of FDG-PET-based biomarkers is challenged by high variability. In this phase II trial, FDG-PET was explored as a predictive biomarker

  8. MAGE-A inhibits apoptosis in proliferating myeloma cells through repression of Bax and maintenance of survivin.

    Science.gov (United States)

    Nardiello, Tricia; Jungbluth, Achim A; Mei, Anna; Diliberto, Maurizio; Huang, Xiangao; Dabrowski, Ania; Andrade, Valéria C C; Wasserstrum, Rebecca; Ely, Scott; Niesvizky, Ruben; Pearse, Roger; Coleman, Morton; Jayabalan, David S; Bhardwaj, Nina; Old, Lloyd J; Chen-Kiang, Selina; Cho, Hearn Jay

    2011-07-01

    The type I Melanoma Antigen GEnes (MAGEs) are commonly expressed in cancers, fueling speculation that they may be therapeutic targets with oncogenic potential. They form complexes with RING domain proteins that have E3 ubiquitin ligase activity and promote p53 degradation. MAGE-A3 was detected in tumor specimens from patients with multiple myeloma and its expression correlated with higher frequencies of Ki-67(+) malignant cells. In this report, we examine the mechanistic role of MAGE-A in promoting survival of proliferating multiple myeloma cells. The impact of MAGE-A3 expression on survival and proliferation in vivo was examined by immunohistochemical analysis in an independent set of tumor specimens segregated into two groups: newly diagnosed, untreated patients and patients who had relapsed after chemotherapy. The mechanisms of MAGE-A3 activity were investigated in vitro by silencing its expression by short hairpin RNA interference in myeloma cell lines and primary cells and assessing the resultant effects on proliferation and apoptosis. MAGE-A3 was detected in a significantly higher percentage of relapsed patients compared with newly diagnosed, establishing a novel correlation with progression of disease. Silencing of MAGE-A showed that it was dispensable for cell cycling, but was required for survival of proliferating myeloma cells. Loss of MAGE-A led to apoptosis mediated by p53-dependent activation of proapoptotic Bax expression and by reduction of survivin expression through both p53-dependent and -independent mechanisms. These data support a role for MAGE-A in the pathogenesis and progression of multiple myeloma by inhibiting apoptosis in proliferating myeloma cells through two novel mechanisms.

  9. Targeting CD38 with Daratumumab Monotherapy in Multiple Myeloma

    DEFF Research Database (Denmark)

    Lokhorst, Henk M; Plesner, Torben; Laubach, Jacob P

    2015-01-01

    BACKGROUND: Multiple myeloma cells uniformly overexpress CD38. We studied daratumumab, a CD38-targeting, human IgG1κ monoclonal antibody, in a phase 1-2 trial involving patients with relapsed myeloma or relapsed myeloma that was refractory to two or more prior lines of therapy. METHODS: In part 1...... interval [CI], 4.2 to 8.1), and 65% (95% CI, 28 to 86) of the patients who had a response did not have progression at 12 months. CONCLUSIONS: Daratumumab monotherapy had a favorable safety profile and encouraging efficacy in patients with heavily pretreated and refractory myeloma. (Funded by Janssen...

  10. Imaging spectrum in sclerotic myelomas: an experience of three cases

    International Nuclear Information System (INIS)

    Grover, S.B.; Dhar, A.

    2000-01-01

    The classic radiographic presentation of multiple myeloma is lytic skeletal lesions. Primary sclerotic manifestations are rare and occur only in 3 % of cases. The imaging spectrum in three cases of multiple myeloma with primary osteosclerosis is described. The first patient had spiculated sclerosis of the orbit, which is an uncommon site for myeloma. The second patient with POEMS syndrome had multiple, scattered, skeletal lesions with sclerotic margins. The third patient presented with a chest wall mass and had an expansile thick spiculated sclerosis in the rib. The wide imaging spectrum possible in sclerotic myelomas and their relevant differential diagnosis is emphasized. (orig.)

  11. Role of Radiation Therapy in the Management of Renal Cell Cancer

    International Nuclear Information System (INIS)

    Blanco, Angel I.; Teh, Bin S.; Amato, Robert J.

    2011-01-01

    Renal cell carcinoma (RCC) is traditionally considered to be radioresistant; therefore, conventional radiotherapy (RT) fraction sizes of 1.8 to 2 Gy are thought to have little role in the management of primary RCC, especially for curative disease. In the setting of metastatic RCC, conventionally fractionated RT has been an effective palliative treatment in 50% of patients. Recent technological advances in radiation oncology have led to the clinical implementation of image-guided radiotherapy, allowing biologically potent doses to the tumors intra- and extra-cranially. As predicted by radiobiologic modeling, favorable outcomes have been observed with highly hypofractionated schemes modeled after the experience with intracranial stereotactic radiosurgery (SRS) for RCC brain metastases with reported local control rates averaging 85%. At present, both primary and metastatic RCC tumors may be successfully treated using stereotactic approaches, which utilize steep dose gradients to maximally preserve function and avoid toxicity of adjacent organs including liver, uninvolved kidney, bowel, and spinal cord regions. Future endeavors will combine stereotactic body radiation therapy (SBRT) with novel targeted therapies, such as tyrosine kinase inhibitors and targeted rapamycin (mTOR) inhibitors, to maximize both local and systemic control

  12. Cost-Effectiveness of Pazopanib Versus Sunitinib for Renal Cancer in the United States.

    Science.gov (United States)

    Benedict, Agnes; Ramaswamy, Krishnan; Sandin, Rickard

    2015-09-01

    We write to comment on a recently published study by Delea et al. in the January 2015 issue of JMCP that evaluated the cost-effectiveness (CE) of sunitinib (SU) versus pazopanib (PAZ) as first-line treatment for metastatic renal cell carcinoma (mRCC) from a U.S. third-party payer perspective.1 This analysis was based on COMPARZ and PISCES, clinical trials that compared SU and PAZ2,3 and led the authors to conclude that PAZ is cost-effective (in fact, dominant, according to the base-case results) compared with SU. Such assessment of economic value is clearly important for deciding between therapies to ensure fair access; therefore, we welcome a comparative evaluation of SU and PAZ. However, we believe that some of the key assumptions and inputs used in the model by Delea et al. render their results and conclusions invalid.  Best practice requires that results from a health economic model should reflect the most likely outcomes based on sound methodology and robust evidence for its inputs, as recommended by the International Society of Pharmacoeconomics and Outcomes Research (ISPOR).4 Here, we focus on 2 key areas (utilities and survival modeling) where, in our view, the analysis by Delea et al. falls short of this standard, and a third area (treatment costs) where the basis for the data derived is unclear.

  13. Role of Radiation Therapy in the Management of Renal Cell Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Blanco, Angel I.; Teh, Bin S. [Department of Radiation Oncology, The Methodist Hospital, The Methodist Hospital Research Institute, Houston, TX 77030 (United States); Department of Radiation Oncology, The Methodist Hospital, Houston, TX 77030 (United States); Amato, Robert J., E-mail: Robert.amato@uth.tmc.edu [Division of Oncology, University of Texas Health Science Center at Houston, Memorial Hermann Cancer Center, Houston, TX 77030 (United States)

    2011-10-26

    Renal cell carcinoma (RCC) is traditionally considered to be radioresistant; therefore, conventional radiotherapy (RT) fraction sizes of 1.8 to 2 Gy are thought to have little role in the management of primary RCC, especially for curative disease. In the setting of metastatic RCC, conventionally fractionated RT has been an effective palliative treatment in 50% of patients. Recent technological advances in radiation oncology have led to the clinical implementation of image-guided radiotherapy, allowing biologically potent doses to the tumors intra- and extra-cranially. As predicted by radiobiologic modeling, favorable outcomes have been observed with highly hypofractionated schemes modeled after the experience with intracranial stereotactic radiosurgery (SRS) for RCC brain metastases with reported local control rates averaging 85%. At present, both primary and metastatic RCC tumors may be successfully treated using stereotactic approaches, which utilize steep dose gradients to maximally preserve function and avoid toxicity of adjacent organs including liver, uninvolved kidney, bowel, and spinal cord regions. Future endeavors will combine stereotactic body radiation therapy (SBRT) with novel targeted therapies, such as tyrosine kinase inhibitors and targeted rapamycin (mTOR) inhibitors, to maximize both local and systemic control.

  14. Targeting CXCR4 reverts the suppressive activity of T-regulatory cells in renal cancer.

    Science.gov (United States)

    Santagata, Sara; Napolitano, Maria; D'Alterio, Crescenzo; Desicato, Sonia; Maro, Salvatore Di; Marinelli, Luciana; Fragale, Alessandra; Buoncervello, Maria; Persico, Francesco; Gabriele, Lucia; Novellino, Ettore; Longo, Nicola; Pignata, Sandro; Perdonà, Sisto; Scala, Stefania

    2017-09-29

    With the intent to identify biomarkers in renal cell carcinoma (RCC) the functional status of T-regulatory cells (Tregs) was investigated in primary RCC. Tregs were isolated from tumoral-(TT), peritumoral tissue-(PT) and peripheral blood-(PB) of 42 primary RCC patients and function evaluated through effector T cells (Teff) proliferation, cytokines release and demethylation of Treg Specific Region (TSDR). The highest value of Tregs was detected in TT with the uppermost amount of effector-Tregs-(CD4 + CD25 hi FOXP3 hi CD45RA - ). PB-RCC Tregs efficiently suppress Teff proliferation compared to healthy donor (HD)-Tregs and, at the intrapatient evaluation, TT-derived Tregs were the most suppressive. Higher demethylation TSDR was detected in TT- and PB-RCC Tregs vs HD-Tregs ( P <0,001). CXCR4 is highly expressed on Tregs, thus we wished to modulate Tregs function through CXCR4 inhibition. CXCR4 antagonism, elicited by a new peptidic antagonist, Peptide-R29, efficiently reversed Tregs suppression of Teff proliferation. Thus Tregs functional evaluation precisely reflects Tregs status and may be a reliable biomarker of tumoral immune response. In addition, treatment with CXCR4 antagonist, impairing Tregs function, could improve the anticancer immune response, in combination with conventional therapy and/or immunotherapy such as checkpoints inhibitors.

  15. Curcumin enhances the radiosensitivity of renal cancer cells by suppressing NF-κB signaling pathway.

    Science.gov (United States)

    Li, Gang; Wang, Ziming; Chong, Tie; Yang, Jie; Li, Hongliang; Chen, Haiwen

    2017-10-01

    The radiation resistance of renal cell carcinoma (RCC) remains the primary obstacle to improve patient survival. This study aimed to investigate the effects of curcumin on the radiosensitivity of RCC cells. Human RCC cell (ACHN) was exposed to irradiation (IR) and/or curcumin treatment. Cell viability, DNA repair, cell cycle, and apoptosis, were evaluated by MTT, immunofluoresence staining and flow cytometry. Moreover, ACHN cells were xenografted into nude mice and subjected to IR and/or curcumin treatment. The expression of NF-κB signaling related proteins in ACHN cells and xenografts was detected by western blot analysis. The results showed that curcumin significantly increased radiosensitivity of ACHN cells by inhibiting the cell proliferation and DNA damage repair, causing cell cycle arrest at G2/M phase, inducing apoptosis in vitro, and suppressing the growth of xenografts in vivo. In addition, curcumin enhanced radiosensitivity was through markedly inhibiting IR-induced NF-κB signaling by modulating the related protein expressions including NF-κBP65, I-κB, VEGF, COX2, and Bcl-2 in ACHN cells, which was further strengthened by NF-κB inhibitor PDTC treatment. Thus, curcumin may confer radiosensitivity on RCC via inhibition of NF-κB activation and its downstream regulars, suggesting the potential application of curcumin as an adjuvant in radiotherapy of RCC. Copyright © 2017. Published by Elsevier Masson SAS.

  16. Markers of systemic inflammation predict survival in patients with advanced renal cell cancer.

    Science.gov (United States)

    Fox, P; Hudson, M; Brown, C; Lord, S; Gebski, V; De Souza, P; Lee, C K

    2013-07-09

    The host inflammatory response has a vital role in carcinogenesis and tumour progression. We examined the prognostic value of inflammatory markers (albumin, white-cell count and its components, and platelets) in pre-treated patients with advanced renal cell carcinoma (RCC). Using data from a randomised trial, multivariable proportional hazards models were generated to examine the impact of inflammatory markers and established prognostic factors (performance status, calcium, and haemoglobin) on overall survival (OS). We evaluated a new prognostic classification incorporating additional information from inflammatory markers. Of the 416 patients, 362 were included in the analysis. Elevated neutrophil counts, elevated platelet counts, and a high neutrophil-lymphocyte ratio were significant independent predictors for shorter OS in a model with established prognostic factors. The addition of inflammatory markers improves the discriminatory value of the prognostic classification as compared with established factors alone (C-statistic 0.673 vs 0.654, P=0.002 for the difference), with 25.8% (P=0.004) of patients more appropriately classified using the new classification. Markers of systemic inflammation contribute significantly to prognostic classification in addition to established factors for pre-treated patients with advanced RCC. Upon validation of these data in independent studies, stratification of patients using these markers in future clinical trials is recommended.

  17. Class I histone deacetylase inhibitor entinostat suppresses regulatory T cells and enhances immunotherapies in renal and prostate cancer models.

    Directory of Open Access Journals (Sweden)

    Li Shen

    Full Text Available Immunosuppressive factors such as regulatory T cells (Tregs limit the efficacy of immunotherapies. Histone deacetylase (HDAC inhibitors have been reported to have antitumor activity in different malignancies and immunomodulatory effects. Herein, we report the Tregs-targeting and immune-promoting effect of a class I specific HDAC inhibitor, entinostat, in combination with either IL-2 in a murine renal cell carcinoma (RENCA model or a survivin-based vaccine therapy (SurVaxM in a castration resistant prostate cancer (CR Myc-CaP model.RENCA or CR Myc-CaP tumors were implanted orthotopically or subcutaneously, respectively. Inoculated mice were randomized into four treatment groups: vehicle, entinostat, cytokine or vaccine, and combination. Tregs in the blood were assessed by FACS analysis. Real time quantitative PCR and Western blot analysis of isolated T cell subpopulations from spleen were performed to determine Foxp3 gene and protein expression. The suppressive function of Tregs was tested by T cell proliferation assay. Low dose (5 mg/kg entinostat reduced Foxp3 levels in Tregs and this was associated with enhanced tumor growth inhibition in combination with either IL-2 or a SurVaxM vaccine. Entinostat down-regulated Foxp3 expression transcriptionally and blocked Tregs suppressive function without affecting T effector cells (Teffs. In vitro low dose entinostat (0.5 µM induced STAT3 acetylation and a specific inhibitor of STAT3 partially rescued entinostat-induced down-regulation of Foxp3, suggesting that STAT3 signaling is involved in Foxp3 down-regulation by entinostat.These results demonstrate a novel immunomodulatory effect of class I HDAC inhibition and provide a rationale for the clinical testing of entinostat to enhance cancer immunotherapy.

  18. Kaempferol Inhibits the Invasion and Migration of Renal Cancer Cells through the Downregulation of AKT and FAK Pathways.

    Science.gov (United States)

    Hung, Tung-Wei; Chen, Pei-Ni; Wu, Hsu-Chen; Wu, Sheng-Wen; Tsai, Pao-Yu; Hsieh, Yih-Shou; Chang, Horng-Rong

    2017-01-01

    Kaempferol, which is isolated from several natural plants, is a polyphenol belonging to the subgroup of flavonoids. Kaempferol exhibits various pharmacological activities, including anti-inflammatory, antioxidant, antimicrobial, and anticancer activities. In this study, kaempferol can significantly inhibit the invasion and migration of 786-O renal cell carcinoma (RCC) without cytotoxicity. We examined the potential mechanisms underlying its anti-invasive activities on 786-O RCC cells. Western blot was performed, and the results showed that kaempferol attenuates the manifestation of metalloproteinase-2 (MMP-2) protein and activity. The inhibitive effect of kaempferol on MMP-2 may be attributed to the downregulation of phosphorylation of Akt and focal adhesion kinase (FAK). By examining the SCID mice model, we found that kaempferol can safely inhibit the metastasis of the 786-O RCC cells into the lungs by about 87.4% as compared to vehicle treated control animals. In addition, the lung tumor masses of mice pretreated with 2-10 mg/kg kaempferol were reduced about twofold to fourfold. These data suggested that kaempferol can play a promising role in tumor prevention and cancer metastasis inhibition.

  19. Dual energy CT allows for improved characterization of response to antiangiogenic treatment in patients with metastatic renal cell cancer

    Energy Technology Data Exchange (ETDEWEB)

    Hellbach, K.; Sterzik, A.; Sommer, W.; Karpitschka, M.; Hummel, N.; Ingrisch, M.; Graser, A. [Ludwig-Maximilians-University Hospital Munich, Department of Clinical Radiology, Muenchen (Germany); Casuscelli, J.; Staehler, Michael [Ludwig-Maximilians-University Hospital Munich, Department of Urology, Muenchen (Germany); Schlemmer, M. [Krankenhaus Barmherzige Brueder Muenchen, Department of Palliative Care, Muenchen (Germany)

    2017-06-15

    To evaluate the potential role of dual energy CT (DECT) to visualize antiangiogenic treatment effects in patients with metastatic renal cell cancer (mRCC) while treated with tyrosine-kinase inhibitors (TKI). 26 patients with mRCC underwent baseline and follow-up single-phase abdominal contrast enhanced DECT scans. Scans were performed immediately before and 10 weeks after start of treatment with TKI. Virtual non-enhanced (VNE) and colour coded iodine images were generated. 44 metastases were measured at the two time points. Hounsfield unit (HU) values for VNE and iodine density (ID) as well as iodine content (IC) in mg/ml of tissue were derived. These values were compared to the venous phase DECT density (CTD) of the lesions. Values before and after treatment were compared using a paired Student's t test. Between baseline and follow up, mean CTD and DECT-derived ID both showed a significant reduction (p < 0.005). The relative reduction measured in percent was significantly greater for ID than for CTD (49.8 ± 36,3 % vs. 29.5 ± 20.8 %, p < 0.005). IC was also significantly reduced under antiangiogenic treatment (p < 0.0001). Dual energy CT-based quantification of iodine content of mRCC metastases allows for significantly more sensitive and reproducible detection of antiangiogenic treatment effects. (orig.)

  20. Kidney (Renal Cell) Cancer—Health Professional Version

    Science.gov (United States)

    Kidney cancer has three main types. Renal cell cancer, or renal cell adenocarcinoma, forms in the tubules of the kidney. Transitional cell carcinoma forms in the renal pelvis and ureter. Wilms tumors are common in children. Find evidence-based information on kidney cancer treatment, research, genetics, and statistics.

  1. Hormone Therapy for Breast Cancer

    Science.gov (United States)

    ... Common Cancer Types Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer ... sensitive breast cancer cells contain proteins called hormone receptors that become activated when hormones bind to them. ...

  2. General Information About Endometrial Cancer

    Science.gov (United States)

    ... Common Cancer Types Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer ... cancer cells have places where hormones can attach ( receptors ), drugs , surgery, or radiation therapy is used to ...

  3. Treatment Option Overview (Endometrial Cancer)

    Science.gov (United States)

    ... Common Cancer Types Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer ... cancer cells have places where hormones can attach ( receptors ), drugs , surgery, or radiation therapy is used to ...

  4. Changes in causes of death and risk of cancer in Danish patients with autosomal dominant polycystic kidney disease and end-stage renal disease.

    Science.gov (United States)

    Orskov, Bjarne; Sørensen, Vibeke Rømming; Feldt-Rasmussen, Bo; Strandgaard, Svend

    2012-04-01

    With the improved prognosis in patients with autosomal dominant polycystic kidney disease (ADPKD), causes of death and the risk of cancer might have changed. This was investigated in a Danish population with ADPKD and end-stage renal disease (ESRD) between 1 January 1993 and 31 December 2008. Data were retrieved from three Danish national registries and a total of 823 patients were identified of which 431 had died during the study period. The 16 years were divided into two 8-year periods and the causes of death were divided into six categories: cancer, cardiovascular, cerebrovascular, infection, other and unknown. Cardiovascular disease was the major cause of death. A multivariate competing risk model comparing the two 8-year periods, adjusted for age at ESRD, gender and treatment modality, showed that deaths from cardiovascular disease decreased by 35% [hazard ratios (HR) 0.65, P=0.008] and deaths from cerebrovascular disease decreased by 69% (HR 0.31, P=0.0003) from the first to the second time period. There were no significant changes between the time periods in death from cancer, infection, other or unknown. From the first to the second 8-year interval, the prevalence of cancer increased by 35% (P=0.0002) while the cancer incidence was stable. In Danish patients with ADPKD and ESRD, there was a significant reduction in cardiovascular and cerebrovascular deaths from 1993 to 2008. The prevalence of cancer increased without significant change in cancer incidence or deaths from cancer.

  5. Validity of two recently-proposed prognostic grading indices for lung, gastro-intestinal, breast and renal cell cancer patients with radiosurgically-treated brain metastases.

    Science.gov (United States)

    Yamamoto, Masaaki; Serizawa, Toru; Sato, Yasunori; Kawabe, Takuya; Higuchi, Yoshinori; Nagano, Osamu; Barfod, Bierta E; Ono, Junichi; Kasuya, Hidetoshi; Urakawa, Yoichi

    2013-02-01

    We tested the validity of two prognostic indices for stereotactic radiosurgically (SRS)-treated patients with brain metastases (BMs) from five major original cancer categories. The two indices are Diagnosis-Specific Graded Prognostic Assessment (DS-GPA) and our Modified Recursive Partitioning Analysis (RPA). Forty-six hundred and eight BM patients underwent gamma knife SRS during the 1998-2011 period. Primary cancer categories were non-small cell lung cancer (NSCLC, 2827 patients), small cell lung cancer (SCLC, 460), gastro-intestinal cancer (GIC, 582), breast cancer (BC, 547) and renal cell cancer (RCC, 192). There were statistically significant survival differences among patients stratified into four groups based on the DS-GPA systems (p failed to reach statistical significance with this system. There were, however, statistically significant MST differences (p < 0.001) among the three groups without overlapping of 95 % CIs between any two pairs of groups with the Modified RPA system in all five categories. The DS-GPA system is applicable to our set of patients with NSCLC only. However, the Modified RPA system was shown to be applicable to patients with five primary cancer categories. This index should be considered when designing future clinical trials involving BM patients.

  6. Kidney (Renal Cell) Cancer—Patient Version

    Science.gov (United States)

    Kidney cancer can develop in adults and children. The main types of kidney cancer are renal cell cancer, transitional cell cancer, and Wilms tumor. Certain inherited conditions increase the risk of kidney cancer. Start here to find information on kidney cancer treatment, research, and statistics.

  7. Analysis of SNPs and haplotypes in vitamin D pathway genes and renal cancer risk.

    Directory of Open Access Journals (Sweden)

    Sara Karami

    2009-09-01

    Full Text Available In the kidney vitamin D is converted to its active form. Since vitamin D exerts its activity through binding to the nuclear vitamin D receptor (VDR, most genetic studies have primarily focused on variation within this gene. Therefore, analysis of genetic variation in VDR and other vitamin D pathway genes may provide insight into the role of vitamin D in renal cell carcinoma (RCC etiology. RCC cases (N = 777 and controls (N = 1,035 were genotyped to investigate the relationship between RCC risk and variation in eight target genes. Minimum-p-value permutation (Min-P tests were used to identify genes associated with risk. A three single nucleotide polymorphism (SNP sliding window was used to identify chromosomal regions with a False Discovery Rate of <10%, where subsequently, haplotype relative risks were computed in Haplostats. Min-P values showed that VDR (p-value = 0.02 and retinoid-X-receptor-alpha (RXRA (p-value = 0.10 were associated with RCC risk. Within VDR, three haplotypes across two chromosomal regions of interest were identified. The first region, located within intron 2, contained two haplotypes that increased RCC risk by approximately 25%. The second region included a haplotype (rs2239179, rs12717991 across intron 4 that increased risk among participants with the TC (OR = 1.31, 95% CI = 1.09-1.57 haplotype compared to participants with the common haplotype, TT. Across RXRA, one haplotype located 3' of the coding sequence (rs748964, rs3118523, increased RCC risk 35% among individuals with the variant haplotype compared to those with the most common haplotype. This study comprehensively evaluated genetic variation across eight vitamin D pathway genes in relation to RCC risk. We found increased risk associated with VDR and RXRA. Replication studies are warranted to confirm these findings.

  8. Biomarker-Based Phase II Trial of Savolitinib in Patients With Advanced Papillary Renal Cell Cancer.

    Science.gov (United States)

    Choueiri, Toni K; Plimack, Elizabeth; Arkenau, Hendrik-Tobias; Jonasch, Eric; Heng, Daniel Y C; Powles, Thomas; Frigault, Melanie M; Clark, Edwin A; Handzel, Amir A; Gardner, Humphrey; Morgan, Shethah; Albiges, Laurence; Pal, Sumanta Kumar

    2017-09-10

    Purpose Patients with advanced papillary renal cell carcinoma (PRCC) have limited therapeutic options. PRCC may involve activation of the MET pathway, for example, through gene amplification or mutations. Savolitinib (AZD6094, HMPL-504, volitinib) is a highly selective MET tyrosine kinase inhibitor. We report results of a single-arm, multicenter, phase II study evaluating the safety and efficacy of savolitinib in patients with PRCC according to MET status. Patients and Methods Patients with histologically confirmed locally advanced or metastatic PRCC were enrolled and received savolitinib 600 mg orally once daily. MET-driven PRCC was defined as any of the following: chromosome 7 copy gain, focal MET or HGF gene amplification, or MET kinase domain mutations. Efficacy was assessed according to MET status. Safety, toxicity, and patient-reported health-related quality-of-life outcomes were assessed in all patients. Results Of 109 patients treated, PRCC was MET driven in 44 (40%) and MET independent in 46 (42%); MET status was unknown in 19 (17%). MET-driven PRCC was strongly associated with response; there were eight confirmed partial responders with MET-driven disease (18%), but none with MET-independent disease ( P = .002). Median progression-free survival for patients with MET-driven and MET-independent PRCC was 6.2 months (95% CI, 4.1 to 7.0 months) and 1.4 months (95% CI, 1.4 to 2.7 months), respectively (hazard ratio, 0.33; 95% CI, 0.20 to 0.52; log-rank P < .001). The most frequent adverse events associated with savolitinib were nausea, fatigue, vomiting, and peripheral edema. Conclusion These data show activity and tolerability of savolitinib in the subgroup of patients with MET-driven PRCC. Furthermore, molecular characterization of MET status was more predictive of response to savolitinib than a classification based on pathology. These findings justify investigating savolitinib in MET-driven PRCC.

  9. Advancements in Nanomedicine for Multiple Myeloma.

    Science.gov (United States)

    Detappe, Alexandre; Bustoros, Mark; Mouhieddine, Tarek H; Ghoroghchian, P Peter

    2018-06-01

    In the past decades, considerable progress has been made in our understanding and treatment of multiple myeloma. Several challenges remain including our abilities to longitudinally image tumor responses to treatment, to combine various therapeutic agents with different mechanisms of action but with overlapping toxicities, and to efficiently harness the power of the immune system to augment remission and/or to induce permanent cures. Nanomedicine may help to address many of these outstanding issues, affording novel diagnostic capabilities and offering disruptive technologies that promise to revolutionize treatment. Here, we review recent developments and the future of nanomedicine for multiple myeloma, highlighting new considerations in nanoparticle designs that may help to augment active targeting, to facilitate longitudinal imaging, and to improve drug delivery. Copyright © 2018 Elsevier Ltd. All rights reserved.

  10. Multiple myeloma associated with acquired cutis laxa.

    Science.gov (United States)

    Cho, S Y; Maguire, R F

    1980-08-01

    Acquired cutis laxa is a rare disorder characterized by diffuse laxity of the skin and loss of connective tissue support with involvement of the lungs, gastrointestinal tract, pelvic organs, and aorta. The case report presented herein describes a forty-six year old woman with multiple myeloma and cutis laxa. Her history included several severe allergic reactions and the gradual development of lax skin, loss of connective tissue support throughout the body, and emphysema. At autopsy, multiple myeloma, diffuse laxity of the skin, and panacinar emphysema were found. The amount of elastic fiber in the skin, lungs, and aorta was decreased and showed abnormal fragmentation. Results of direct immunofluorescence study demonstrated IgG bound to dermal elastic fibers. Speculation regarding an immunologic etiology of the elastic tissue abnormality is presented herein.

  11. Report from the European Myeloma Network on interphase FISH in multiple myeloma and related disorders

    DEFF Research Database (Denmark)

    Ross, Fiona M; Avet-Loiseau, Hervé; Ameye, Geneviève

    2012-01-01

    The European Myeloma Network has organized two workshops on fluorescence in situ hybridization in multiple myeloma. The first aimed to identify specific indications and consensus technical approaches of current practice. A second workshop followed a quality control exercise in which 21 laboratories...... analyzed diagnostic cases of purified plasma cells for recurrent abnormalities. The summary report was discussed at the EHA Myeloma Scientific Working Group Meeting 2010. During the quality control exercise, there was acceptable agreement on more than 1,000 tests. The conclusions from the exercise were...... that the primary clinical applications for FISH analysis were for newly diagnosed cases of MM or frank relapse cases. A range of technical recommendations included: 1) material should be part of the first draw of the aspirate; 2) samples should be sent at suitable times to allow for the lengthy processing...

  12. Sexual dysfunction in multiple myeloma: survivorship care plan of the International Myeloma Foundation Nurse Leadership Board.

    Science.gov (United States)

    Richards, Tiffany A; Bertolotti, Page A; Doss, Deborah; McCullagh, Emily J

    2011-08-01

    The World Health Organization describes sexuality as a "central aspect of being human throughout life and encompasses sex, gender identities and roles, sexual orientation, eroticism, pleasure, intimacy, and reproduction. Sexuality is influenced by the interaction of biological, psychological, social, economic, political, cultural, ethical, legal, historical, religious, and spiritual factors." Currently, no research has been conducted regarding sexual dysfunction in patients with multiple myeloma; therefore, information related to the assessment and evaluation of sexual dysfunction is gleaned from other malignancies and diseases. In this article, members of the International Myeloma Foundation's Nurse Leadership Board discuss the definition, presentation, and causes of sexual dysfunction; provide recommendations for sexual assessment practices; and promote discussion among patients with multiple myeloma, their healthcare providers, and their partners.

  13. Accumulation of Tc99m-DMSA-3 in the spleen in a case of multiple myeloma with associated amyloidosis

    Directory of Open Access Journals (Sweden)

    Barai Sukanta

    2005-01-01

    Full Text Available We describe a case of a 58-year-old male with longstanding hypertension and Type 2 diabetes mellitus who developed sudden onset renal impairment. The first clue to the possible presence of amyloidosis in this case was provided by the radionuclide renal cortical scan performed with trivalent dimercapto succinic acid (Tc99m-DMSA-3, which revealed intense tracer uptake in the spleen suggesting amyloid deposit. Further workup to ascertain the cause of amyloidosis led to the diagnosis of multiple myeloma. We conclude that in cases of extra-renal or splenic accumulation of Tc99m-DMSA-3, a diagnosis of amyloidosis should be considered, in an appropriate clinical setting.

  14. Phase I-II study of everolimus and low-dose oral cyclophosphamide in patients with metastatic renal cell cancer

    International Nuclear Information System (INIS)

    Huijts, Charlotte M; Santegoets, Saskia J; Eertwegh, Alfons J van den; Pijpers, Laura S; Haanen, John B; Gruijl, Tanja D de; Verheul, Henk M; Vliet, Hans J van der

    2011-01-01

    For patients with metastatic renal cell cancer (mRCC) who progressed on vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitor therapy, the orally administered mammalian target of rapamycin (mTOR) inhibitor everolimus has been shown to prolong progression free survival. Intriguingly, inhibition of mTOR also promotes expansion of immunosuppressive regulatory T cells (Tregs) that can inhibit anti-tumor immune responses in a clinically relevant way in various tumor types including RCC. This study intends to investigate whether the antitumor efficacy of everolimus can be increased by preventing the detrimental everolimus induced expansion of Tregs using a metronomic schedule of cyclophosphamide. This phase I-II trial is a national multi-center study of different doses and schedules of low-dose oral cyclophosphamide in combination with a fixed dose of everolimus in patients with mRCC not amenable to or progressive after a VEGF-receptor tyrosine kinase inhibitor containing treatment regimen. In the phase I part of the study the optimal Treg-depleting dose and schedule of metronomic oral cyclophosphamide when given in combination with everolimus will be determined. In the phase II part of the study we will evaluate whether the percentage of patients progression free at 4 months of everolimus treatment can be increased from 50% to 70% by adding metronomic cyclophosphamide (in the dose and schedule determined in the phase I part). In addition to efficacy, we will perform extensive immune monitoring with a focus on the number, phenotype and function of Tregs, evaluate the safety and feasibility of the combination of everolimus and cyclophosphamide, perform monitoring of selected angiogenesis parameters and analyze everolimus and cyclophosphamide drug levels. This phase I-II study is designed to determine whether metronomic cyclophosphamide can be used to counter the mTOR inhibitor everolimus induced Treg expansion in patients with metastatic renal cell

  15. Phase I-II study of everolimus and low-dose oral cyclophosphamide in patients with metastatic renal cell cancer

    Directory of Open Access Journals (Sweden)

    Huijts Charlotte M

    2011-11-01

    Full Text Available Abstract Background For patients with metastatic renal cell cancer (mRCC who progressed on vascular endothelial growth factor (VEGF receptor tyrosine kinase inhibitor therapy, the orally administered mammalian target of rapamycin (mTOR inhibitor everolimus has been shown to prolong progression free survival. Intriguingly, inhibition of mTOR also promotes expansion of immunosuppressive regulatory T cells (Tregs that can inhibit anti-tumor immune responses in a clinically relevant way in various tumor types including RCC. This study intends to investigate whether the antitumor efficacy of everolimus can be increased by preventing the detrimental everolimus induced expansion of Tregs using a metronomic schedule of cyclophosphamide. Methods/design This phase I-II trial is a national multi-center study of different doses and schedules of low-dose oral cyclophosphamide in combination with a fixed dose of everolimus in patients with mRCC not amenable to or progressive after a VEGF-receptor tyrosine kinase inhibitor containing treatment regimen. In the phase I part of the study the optimal Treg-depleting dose and schedule of metronomic oral cyclophosphamide when given in combination with everolimus will be determined. In the phase II part of the study we will evaluate whether the percentage of patients progression free at 4 months of everolimus treatment can be increased from 50% to 70% by adding metronomic cyclophosphamide (in the dose and schedule determined in the phase I part. In addition to efficacy, we will perform extensive immune monitoring with a focus on the number, phenotype and function of Tregs, evaluate the safety and feasibility of the combination of everolimus and cyclophosphamide, perform monitoring of selected angiogenesis parameters and analyze everolimus and cyclophosphamide drug levels. Discussion This phase I-II study is designed to determine whether metronomic cyclophosphamide can be used to counter the mTOR inhibitor everolimus

  16. Bilateral renal metastasis of 261-265huerthle cell thyroid cancer with discordant uptake between I-131 sodium iodide and F-18 FDG

    Energy Technology Data Exchange (ETDEWEB)

    Claimon, Apichaya; Suh, Min Seok; Cheon, Gi Jeong; Lee, Dong Soo; Chung, June Key [Dept. of Nuclear Medicine, Seoul National University Hospital, Seoul (Korea, Republic of); Kim, E. Edmund [Dept. of Radiological Sciences, University of California, Irvine (United States)

    2017-09-15

    Renal metastasis of thyroid cancer is extremely rare. We report the case of a 62-year-old woman with Hürthle cell thyroid cancer (HCTC) with lungs, bones, and bilateral kidneys metastases. The renal metastatic lesions were clearly demonstrated by {sup 131}I whole body scan (WBS) with SPECT/CT. However, they exhibited false-negative results in {sup 18}F-FDG PET/CT, kidney ultrasonography, and contrast-enhanced CT scan. The findings imply that tumors have low glucose metabolism and are able to accumulate radioiodine, which is not commonly found in the relatively aggressive nature of HCTC. The patient received two sessions of 200 mCi {sup 131}I therapy within 6 months duration. There was complete treatment response as evaluated by the second post-therapeutic {sup 131}I SPECT/CT and serum thyroglobulin. To our knowledge, renal metastasis from HCTC with positive {sup 131}I but negative {sup 18}F-FDG uptake has not been reported in the literature. This case suggests that {sup 131}I SPECT/CT is useful for lesion localization and prediction of {sup 131}I therapy response.

  17. Icotinib combined with rapamycin in a renal transplant recipient with epidermal growth factor receptor-mutated non-small cell lung cancer: A case report.

    Science.gov (United States)

    Zhao, Qiong; Wang, Yina; Tang, Yemin; Peng, Ling

    2014-01-01

    As kidney transplant recipients are at increased risk of developing cancer, regular monitoring should be undertaken to monitor the balance between immunosuppression and graft function and to identify malignancy. The present study reports the outcome of the treatment of adenocarcinoma of the lung (T1aN0M1a, stage IV) using the molecular-targeted therapy, icotinib, in a 66-year-old male renal transplant patient receiving rapamycin and prednisolone as ongoing renal immunosuppressive therapy. An initial partial response to icotinib was achieved, and graft function remained good. However, the patient subsequently developed interstitial pneumonitis. The plasma concentrations of rapamycin and icotinib were within the normal ranges, which excluded the possibility of a pharmacokinetic drug interaction and indicated that the interstitial pneumonitis was likely to be associated with the side-effects of icotinib. Drug therapy was discontinued and the patient underwent a segmentectomy. Tacrolimus was administered for ongoing renal graft immunosuppression. To the best of our knowledge, this is the first report of the concomitant administration of icotinib and rapamycin in post-transplant de novo lung cancer. It is also the first report of interstitial pneumonitis associated with icotinib in a post-transplant patient.

  18. Multiple myeloma: radiology or bone scanning

    International Nuclear Information System (INIS)

    Leonard, R.C.F.; Owen, J.P.; Proctor, S.J.; Hamilton, P.J.

    1981-01-01

    A comparative study of radionuclide bone scanning and skeletal radiology in patients with multiple myeloma revealed four principal findings: (i) There were no cases of negative bone scans with positive skeletal radiographs. (ii) Lytic bone lesions were seriously underestimated by bone scans. (iii) Bone scans tended to pick up lesions in ribs missed on the skeletal surveys. (iv) Patients with bone pain were more likely to have positive bone scans and skeletal radiographs than asymptomatic patients. (author)

  19. Multiple myeloma presenting as mandibular pain

    LENUS (Irish Health Repository)

    Crowley, Miriam

    2016-10-01

    Introduction: Multiple myeloma (MM) is a systemic malignancy of plasma cells defined by monoclonal production of circulating immunoglobulins. Bone pain is a presenting feature in the majority of cases. Treatment may involve intravenous use of bisphosphonates, chemotherapy or haematopoietic stem cell transplantation. Here, we illustrate a first presentation of MM in a patient with mandibular pain and discuss radiographic, diagnostic and treatment challenges of orofacial issues in patients with MM.\\r\

  20. Clinicopathological features of plasmablastic multiple myeloma

    DEFF Research Database (Denmark)

    Møller, Hanne E H; Preiss, Birgitte S; Pedersen, Per

    2015-01-01

    Multiple myeloma (MM) is a common malignant hematological disease displaying considerable heterogeneity. Historical data indicate a prognostic significance of plasmablastic morphology, proliferation, and adverse cytogenetics, but there is little knowledge on the degree of interdependency......, which indicates that plasmablastic morphology reflects advanced and highly proliferative disease. However, plasmablastic morphology did not correlate with established adverse prognostic cytogenetics identified by FISH, for example, t(4;14), t(14;16) and del(17p)....

  1. Renal Osteodystrophy

    Directory of Open Access Journals (Sweden)

    Aynur Metin Terzibaşoğlu

    2004-12-01

    Full Text Available Chronic renal insufficiency is a functional definition which is characterized by irreversible and progressive decreasing in renal functions. This impairment is in collaboration with glomeruler filtration rate and serum creatinine levels. Besides this, different grades of bone metabolism disorders develop in chronic renal insufficiency. Pathologic changes in bone tissue due to loss of renal paranchyme is interrelated with calcium, phosphorus vitamine-D and parathyroid hormone. Clinically we can see high turnover bone disease, low turnover bone disease, osteomalacia, osteosclerosis and osteoporosis in renal osteodystropy. In this article we aimed to review pathology of bone metabolism disorders due to chronic renal insufficiency, clinic aspects and treatment approaches briefly.

  2. Radiotherapy in the treatment of multiple myeloma.

    Science.gov (United States)

    Bosch, A; Frias, Z

    1988-12-01

    Fifty-nine patients with multiple myeloma referred for treatment of painful bony lesions received irradiation to 95 local areas, and 16 of the 59 were irradiated using hemibody techniques. Pain relief was obtained in practically all of the irradiated regions. Most local areas were treated to doses of 3000 cGy in 10 to 15 fractions. Patients with generalized pain due to multiple site involvement were treated with single dose hemibody irradiation, to doses of 600 cGy to the upper hemibody, and of 800 cGy to the lower hemibody. This treatment was well tolerated and side effects minimal. Median survival from diagnosis was 30 months and the survival at 1, 3, and 5 years was 80%, 42%, and 12% respectively. Key articles on radiation therapy of multiple myeloma are reviewed and discussed. Since all patients eventually relapse after chemotherapy, the role of radiotherapy using present techniques should be fully evaluated and considered as an alternative in the primary treatment of multiple myeloma.

  3. Palliative radiation therapy for multiple myeloma

    International Nuclear Information System (INIS)

    Minowa, Yasushi; Sasai, Keisuke; Ishigaki, Takashi; Nagata, Yasushi; Hiraoka, Masahiro

    1996-01-01

    Radiation therapy is a useful palliative modality for refractory lesions of multiple myeloma. It has been reported that total doses of 10 to 20 Gy are usually adequate to obtain some degree of pain relief. However, there are many patients who need additional doses to obtain sufficient pain relief. In this study. we retrospectively analyzed the records of patients with multiple myeloma irradiated at our department, in an attempt to develop an effective treatment policy for this disease. Twenty-nine patients with 53 lesions were treated between 1968 and 1993. Total irradiation doses were 4 to 60 Gy (median 40 Gy) with daily fractions of 2 Gy or less, and 16 to 51 Gy (median 30 Gy) with daily fractions greater than 2 Gy. Evaluated were 59 symptoms, including pain (68%), neurological abnormalities (15%), and masses (28%). Symptomatic remission was obtained in 33 of 36 (92%) lesions with pain, 6 of 8 (75%) with neurological abnormalities, and 13 of 15 (87%) mass lesions. Pain was partially relieved at a median TDF of 34, and completely at a median TDF of 66 (equivalent to 40-42 Gy with daily fractions of 2 Gy). Radiation therapy is an effective and palliative treatment method for symptomatic multiple myeloma. However, the treatment seems to require higher radiation doses than those reported to obtain adequate relief of symptoms. (author)

  4. The Dynamics of Acute Renal Impairment Markers During a Surgery for Kidney Cancer

    Directory of Open Access Journals (Sweden)

    E. M. Frantsiyants

    2017-01-01

    Full Text Available The purpose of the study is to investigate the effect of epidural block on the functional state of the kidneys in patients with localized cancer during kidney resection under the conditions of warm ischemia.Materials and methods. We examined 45 patients (25 men and 20 women with a localized kidney cancer (T1N0M0 aged 56.5±8.7 years. All the patients underwent kidney resection performed under conditions of warm ischemia (15—20 minutes. Patients were divided into 2 groups: the main group (25 subjects in which the perioperative epidural block was applied and the reference group (20 patients without the epidural block. The following parameters were tested in blood and urine using the ELISA technique: cystatin C, L-FABP, KIM-1 , IL-18, and GFR. The test was carried out 1 hour prior to surgery, 20 minutes after the warm ischemia stage, and on Days 1 and 3. Based on the baseline cystatin С level, the patients in each group were divided into 2 subgroups: subgroup 1 —cystatin C is 1000 ng/ml and lower; subgroup 2 — more than 1000 ng/ml. The statistical processing of the findings was performed using the Statistica 6.0 software based on the t-test for two independent samples. Differences were considered to be statistically significant at P<0.05.Results. It has been demonstrated that functional parameters of kidneys were recovered to the baseline values by the 3rd day after the kidney resection under the warm ischemia due to perioperative epidural block. Impairment of the tubulointerstitium and glomerular apparatus were observed in the reference group. GFR values in the patients of the main group were within normal limits by Day 3, whereas in the patients of the GFR was lower by 38.8% as compared to the baseline (P<0.05.Conclusion. The use of the perioperative epidural block in patients with localized kidney cancer who underwent the organ resection under the warm ischemia demonstrated the nephroprotective effect, while maintaining the functional

  5. Non-invasive imaging provides spatiotemporal information on disease progression and response to therapy in a murine model of multiple myeloma.

    Directory of Open Access Journals (Sweden)

    Simone S Riedel

    Full Text Available Multiple myeloma (MM is a B-cell malignancy, where malignant plasma cells clonally expand in the bone marrow of older people, causing significant morbidity and mortality. Typical clinical symptoms include increased serum calcium levels, renal insufficiency, anemia, and bone lesions. With standard therapies, MM remains incurable; therefore, the development of new drugs or immune cell-based therapies is desirable. To advance the goal of finding a more effective treatment for MM, we aimed to develop a reliable preclinical MM mouse model applying sensitive and reproducible methods for monitoring of tumor growth and metastasis in response to therapy.A mouse model was created by intravenously injecting bone marrow-homing mouse myeloma cells (MOPC-315.BM that expressed luciferase into BALB/c wild type mice. The luciferase in the myeloma cells allowed in vivo tracking before and after melphalan treatment with bioluminescence imaging (BLI. Homing of MOPC-315.BM luciferase+ myeloma cells to specific tissues was examined by flow cytometry. Idiotype-specific myeloma protein serum levels were measured by ELISA. In vivo measurements were validated with histopathology.Strong bone marrow tropism and subsequent dissemination of MOPC-315.BM luciferase(+ cells in vivo closely mimicked the human disease. In vivo BLI and later histopathological analysis revealed that 12 days of melphalan treatment slowed tumor progression and reduced MM dissemination compared to untreated controls. MOPC-315.BM luciferase(+ cells expressed CXCR4 and high levels of CD44 and α4β1 in vitro which could explain the strong bone marrow tropism. The results showed that MOPC-315.BM cells dynamically regulated homing receptor expression and depended on interactions with surrounding cells.This study described a novel MM mouse model that facilitated convenient, reliable, and sensitive tracking of myeloma cells with whole body BLI in living animals. This model is highly suitable for monitoring

  6. Raman spectroscopy differentiates between sensitive and resistant multiple myeloma cell lines

    Science.gov (United States)

    Franco, Domenico; Trusso, Sebastiano; Fazio, Enza; Allegra, Alessandro; Musolino, Caterina; Speciale, Antonio; Cimino, Francesco; Saija, Antonella; Neri, Fortunato; Nicolò, Marco S.; Guglielmino, Salvatore P. P.

    2017-12-01

    Current methods for identifying neoplastic cells and discerning them from their normal counterparts are often nonspecific and biologically perturbing. Here, we show that single-cell micro-Raman spectroscopy can be used to discriminate between resistant and sensitive multiple myeloma cell lines based on their highly reproducible biomolecular spectral signatures. In order to demonstrate robustness of the proposed approach, we used two different cell lines of multiple myeloma, namely MM.1S and U266B1, and their counterparts MM.1R and U266/BTZ-R subtypes, resistant to dexamethasone and bortezomib, respectively. Then, micro-Raman spectroscopy provides an easily accurate and noninvasive method for cancer detection for both research and clinical environments. Characteristic peaks, mostly due to different DNA/RNA ratio, nucleic acids, lipids and protein concentrations, allow for discerning the sensitive and resistant subtypes. We also explored principal component analysis (PCA) for resistant cell identification and classification. Sensitive and resistant cells form distinct clusters that can be defined using just two principal components. The identification of drug-resistant cells by confocal micro-Raman spectroscopy is thus proposed as a clinical tool to assess the development of resistance to glucocorticoids and proteasome inhibitors in myeloma cells.

  7. Apoptotic effects of non-edible parts of Punica granatum on human multiple myeloma cells.

    Science.gov (United States)

    Kiraz, Yağmur; Neergheen-Bhujun, Vidushi S; Rummun, Nawraj; Baran, Yusuf

    2016-02-01

    Multiple myeloma is of great concern since existing therapies are unable to cure this clinical condition. Alternative therapeutic approaches are mandatory, and the use of plant extracts is considered interesting. Punica granatum and its derived products were suggested as potential anticancer agents due to the presence of bioactive compounds. Thus, polypenolic-rich extracts of the non-edible parts of P. granatum were investigated for their antiproliferative and apoptotic effects on U266 multiple myeloma cells. We demonstrated that there were dose-dependent decreases in the proliferation of U266 cells in response to P. granatum extracts. Also, exposure to the extracts triggered apoptosis with significant increases in loss of mitochondrial membrane potential in U266 cells exposed to the leaves and stem extracts, while the flower extract resulted in slight increases in loss of MMP. These results were confirmed by Annexin-V analysis. These results documented the cytotoxic and apoptotic effects of P. granatum extracts on human U266 multiple myeloma cells via disruption of mitochondrial membrane potential and increasing cell cycle arrest. The data suggest that the extracts can be envisaged in cancer chemoprevention and call for further exploration into the potential application of these plant parts.

  8. Synchronous Bone Metastasis From Multiple Myeloma and Prostate Adenocarcinoma as Initial Presentation of Coexistent Malignancies

    Directory of Open Access Journals (Sweden)

    Diego Andres Adrianzen Herrera

    2018-04-01

    Full Text Available The radiographic appearance of bone metastases is usually determined by tumor histology and can be osteolytic, osteoblastic, or mixed. We present a patient with coexistent bone metastasis from multiple myeloma and prostate adenocarcinoma who exhibited synchronous bone involvement of both histologies within the same bone lesion, a rare phenomenon that has not been previously reported and led to atypical radiographic findings. The radiograph of a 71-year-old man with thigh swelling and pain demonstrated a lytic femoral lesion. Magnetic resonance imaging (MRI confirmed a destructive process, but showed coexistent metaphyseal sclerosis. Multiple myeloma was suspected by demonstration of monoclonal gammopathy and confirmed by computed tomography (CT-guided biopsy. Incidentally, CT demonstrated areas of sclerosis corresponding to T2 hypointensity on MRI. Further studies revealed osteoblastic spinal metastasis, prostate enhancement on CT and prostate-specific antigen (PSA level of 90 ng/mL, concerning for concomitant prostate neoplasm. After endoprosthetic reconstruction, pathology of the femur identified both plasma cell neoplasm and metastatic prostate adenocarcinoma. An association between prostate cancer and multiple myeloma is hypothesized due to tumor microenvironment similarities and possible common genetic variations, however, coexisting bone metastases have never been reported. This unusual finding explains the discrepant imaging features in our patient and is evidenced that certain clinical situations merit contemplation of atypical presentations of common malignancies even if this leads to additional testing.

  9. Changes in causes of death and risk of cancer in Danish patients with autosomal dominant polycystic kidney didease and end-stage renal disease

    DEFF Research Database (Denmark)

    Ørskov, Bjarne; Sørensen, Vibeke Rømming; Feldt-Rasmussen, Bo Friis

    2012-01-01

    Abstract Background. With the improved prognosis in patients with autosomal dominant polycystic kidney disease (ADPKD), causes of death and the risk of cancer might have changed. This was investigated in a Danish population with ADPKD and end-stage renal disease (ESRD) between 1 January 1993 and 31...... December 2008. Methods. Data were retrieved from three Danish national registries and a total of 823 patients were identified of which 431 had died during the study period. The 16 years were divided into two 8-year periods and the causes of death were divided into six categories: cancer, cardiovascular...... (HR) 0.65, P = 0.008] and deaths from cerebrovascular disease decreased by 69% (HR 0.31, P = 0.0003) from the first to the second time period. There were no significant changes between the time periods in death from cancer, infection, other or unknown. From the first to the second 8-year interval...

  10. Bortezomib consolidation after autologous stem cell transplantation in multiple myeloma

    DEFF Research Database (Denmark)

    Mellqvist, Ulf-Henrik; Gimsing, Peter; Hjertner, Oyvind

    2013-01-01

    The Nordic Myeloma Study Group conducted an open randomized trial to compare bortezomib as consolidation therapy given after high-dose therapy and autologous stem cell transplantation (ASCT) with no consolidation in bortezomib-naive patients with newly diagnosed multiple myeloma. Overall, 370...

  11. Drug response prediction in high-risk multiple myeloma

    DEFF Research Database (Denmark)

    Vangsted, A J; Helm-Petersen, S; Cowland, J B

    2018-01-01

    from high-risk patients by GEP70 at diagnosis from Total Therapy 2 and 3A to predict the response by the DRP score of drugs used in the treatment of myeloma patients. The DRP score stratified patients further. High-risk myeloma with a predicted sensitivity to melphalan by the DRP score had a prolonged...

  12. Interleukin-6, a new target for therapy in multiple myeloma?

    NARCIS (Netherlands)

    van Oers, M. H.; van Zaanen, H. C.; Lokhorst, H. M.

    1993-01-01

    During the past few years much insight has been gained into the immunobiology of multiple myeloma. It has become evident that the growth of myeloma cells is regulated by cytokines, notably interleukin-6. In this paper a brief review is given of the evidence derived from in vitro as well as in vivo

  13. Bortezomib or high-dose dexamethasone for relapsed multiple myeloma

    NARCIS (Netherlands)

    P.G. Richardson (Paul Gerard); P. Sonneveld (Pieter); M.W. Schuster (Michael); D. Irwin (David); E.A. Stadtmauer (Edward); T. Facon (Thierry); J-L. Harousseau (Jean-Luc); D. Ben-Yehuda (Dina); S. Lonial (Sagar); H. Goldschmidt (Hartmut); D. Reece (Donna); J.F. San Miguel (Jesús Fernando); J. Bladé (Joan); M. Boccadoro (Mario); J. Cavenagh (Jamie); W. Dalton (William); A.L. Boral (Anthony); D.-L. Esseltine (Dixie-Lee); J.B. Porter (Jane); D. Schenkein (David); K.C. Anderson (Kenneth)

    2005-01-01

    textabstractBACKGROUND: This study compared bortezomib with high-dose dexamethasone in patients with relapsed multiple myeloma who had received one to three previous therapies. METHODS: We randomly assigned 669 patients with relapsed myeloma to receive either an intravenous bolus of bortezomib (1.3

  14. Novel human multiple myeloma cell line UHKT-893

    Czech Academy of Sciences Publication Activity Database

    Uherková, L.; Vančurová, I.; Vyhlídalová, I.; Pleschnerová, M.; Špička, I.; Mihalová, R.; Březinová, J.; Hodný, Zdeněk; Čermáková, K.; Polanská, V.; Marinov, I.; Jedelský, P.L.; Kuželová, K.; Stöckbauer, P.

    2013-01-01

    Roč. 37, č. 3 (2013), s. 320-326 ISSN 0145-2126 Institutional support: RVO:68378050 Keywords : human myeloma cell line * human multiple myeloma * plasma cell * IL-6 dependence * immunoglobulin * free light chain Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.692, year: 2013

  15. Renal venogram

    Science.gov (United States)

    ... be black. Other structures will be shades of gray. Veins are not normally seen in an x- ... Venogram - kidney; Renal vein thrombosis - venogram Images Kidney anatomy Kidney - blood and urine flow Renal veins References ...

  16. New developments in the management of relapsed/refractory multiple myeloma – the role of ixazomib

    Directory of Open Access Journals (Sweden)

    Richardson PG

    2017-08-01

    Full Text Available Paul G Richardson,1 Shaji Kumar,2 Jacob P Laubach,1 Claudia Paba-Prada,1 Neeraj Gupta,3 Deborah Berg,3 Helgi van de Velde,3 Philippe Moreau4 1Division of Hematologic Malignancy, Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Boston, MA, USA; 2Division of Hematology, Mayo Clinic, Rochester, MN, USA; 3Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Ltd, Cambridge, MA, USA; 4Hematology Department, University Hospital Hotel-Dieu, Nantes, France Abstract: Ixazomib is the first oral proteasome inhibitor to be approved, in combination with lenalidomide and dexamethasone, for the treatment of patients with multiple myeloma who have received at least one prior therapy. Approval was on the basis of results from the phase 3, double-blind, placebo-controlled TOURMALINE-MM1 study, which demonstrated a 35% improvement in progression-free survival with the all-oral combination of ixazomib plus lenalidomide–dexamethasone versus lenalidomide–dexamethasone alone (median: 20.6 vs 14.7 months; hazard ratio: 0.74, p=0.012; median follow-up 14.7 months. The addition of ixazomib to the lenalidomide–dexamethasone regimen was associated with limited additional toxicity and had no adverse impact on patient-reported quality of life. Common grade ≥3 adverse events with ixazomib include gastrointestinal adverse events, rash, and thrombocytopenia. Here, we review the efficacy, safety, pharmacokinetics, and patient-reported quality of life data seen with ixazomib, and discuss the role of this oral agent in the treatment of patients with relapsed/refractory multiple myeloma, including in patients with high-risk cytogenetic abnormalities and those with multiple prior therapies. Keywords: ixazomib, multiple myeloma, proteasome inhibitor, clinical, efficacy, tolerability, pharmacokinetics 

  17. Commentary on "The association between physical activity and renal cancer: systematic review and meta-analysis." Behrens G, Leitzmann MF, Department of Epidemiology and Preventive Medicine, Regensburg University Medical Center, Regensburg, Germany. Br J Cancer 2013; 108(4):798-811. [Epub 2013 Feb 14]. doi: 10.1038/bjc.2013.37.

    Science.gov (United States)

    Boorjian, Stephen

    2014-08-01

    Physical activity may decrease renal cancer risk by reducing obesity, blood pressure, insulin resistance, and lipid peroxidation. Despite plausible biologic mechanisms linking increased physical activity to decreased risk for renal cancer, few epidemiologic studies have been able to report a clear inverse association between physical activity and renal cancer, and no meta-analysis is available on the topic. We searched the literature using PubMed and Web of Knowledge to identify published non-ecologic epidemiologic studies quantifying the relationship between physical activity and renal cancer risk in individuals without a cancer history. Following the PRISMA guidelines, we conducted a systematic review and meta-analysis, including information from 19 studies based on a total of 2,327,322 subjects and 10,756 cases. The methodologic quality of the studies was examined using a comprehensive scoring system. Comparing high vs low levels of physical activity, we observed an inverse association between physical activity and renal cancer risk (summary relative risk (RR) from random-effects meta-analysis=0.88; 95% confidence interval (CI)=0.79-0.97). Summarising risk estimates from high-quality studies strengthened the inverse association between physical activity and renal cancer risk (RR=0.78; 95% CI=0.66-0.92). Effect modification by adiposity, hypertension, type 2 diabetes, smoking, gender, or geographic region was not observed. Our comprehensive meta-analysis provides strong support for an inverse relation of physical activity to renal cancer risk. Future high-quality studies are required to discern which specific types, intensities, frequencies, and durations of physical activity are needed for renal cancer risk reduction. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Anti-S1P Antibody as a Novel Therapeutic Strategy for VEGFR TKI-Resistant Renal Cancer.

    Science.gov (United States)

    Zhang, Liang; Wang, Xiaoen; Bullock, Andrea J; Callea, Marcella; Shah, Harleen; Song, Jiaxi; Moreno, Kelli; Visentin, Barbara; Deutschman, Douglas; Alsop, David C; Atkins, Michael B; Mier, James W; Signoretti, Sabina; Bhasin, Manoj; Sabbadini, Roger A; Bhatt, Rupal S

    2015-04-15

    VEGFR2 tyrosine kinase inhibition (TKI) is a valuable treatment approach for patients with metastatic renal cell carcinoma (RCC). However, resistance to treatment is inevitable. Identification of novel targets could lead to better treatment for patients with TKI-naïve or -resistant RCC. In this study, we performed transcriptome analysis of VEGFR TKI-resistant tumors in a murine model and discovered that the SPHK-S1P pathway is upregulated at the time of resistance. We tested sphingosine-1-phosphate (S1P) pathway inhibition using an anti-S1P mAb (sphingomab), in two mouse xenograft models of RCC, and assessed tumor SPHK expression and S1P plasma levels in patients with metastatic RCC. Resistant tumors expressed several hypoxia-regulated genes. The SPHK1 pathway was among the most highly upregulated pathways that accompanied resistance to VEGFR TKI therapy. SPHK1 was expressed in human RCC, and the product of SPHK1 activity, S1P, was elevated in patients with metastatic RCC, suggesting that human RCC behavior could, in part, be due to overproduction of S1P. Sphingomab neutralization of extracellular S1P slowed tumor growth in both mouse models. Mice bearing tumors that had developed resistance to sunitinib treatment also exhibited tumor growth suppression with sphingomab. Sphingomab treatment led to a reduction in tumor blood flow as measured by MRI. Our findings suggest that S1P inhibition may be a novel therapeutic strategy in patients with treatment-naïve RCC and also in the setting of resistance to VEGFR TKI therapy. ©2015 American Association for Cancer Research.

  19. RNA interference-mediated silencing of speckle-type POZ protein promotes apoptosis of renal cell cancer cells.

    Science.gov (United States)

    Liu, Xiaoxia; Sun, Guiling; Sun, Xiuju

    2016-01-01

    This study aimed to investigate the effects of silencing the speckle-type POZ protein (SPOP) gene on renal cell cancer (RCC) cells and to explore its possible mechanism. The A498 and ACHN RCC cells were transfected with small interference RNA (siRNA)-SPOP by lipofection methods. The silencing efficiency was monitored by quantitative real-time polymerase chain reaction and Western blot. The effects of SPOP silencing on cell apoptosis, cell viability, colony formation ability, cell migration ability, and chemosensitivity to Sorafenib were assessed by flow cytometry, an MTT assay, a colony formation assay, a trans-well migration assay, and a CCK-8 assay, respectively. Its effects on the expression of several cytokines were determined by a protein microarray. Relevant signaling pathways were also analyzed. Compared with the control group, the cell apoptosis rate was significantly higher; the cell viability, the colony formation, and migration ability were significantly decreased in the siRNA-SPOP group. The protein microarray screening showed that the expression of vascular endothelial growth factor receptor, matrix metallopeptidase-9, vascular cell adhesion molecule-1, and stromal cell-derived factor-1 in the siRNA group was significantly decreased and that the expression of granulocyte-macrophage colony-stimulating factor and E-cadherin was significantly increased (Pmatrix organization signal pathway. SPOP gene silencing induced cell apoptosis, decreased cell viability, colony formation, and migration ability, and elevated the drug sensitivity in the RCC cells. A possible mechanism is that silencing SPOP induces the differential expression of E-cadherin, vascular endothelial growth factor receptor, matrix metallopeptidase-9, and vascular cell adhesion molecule, which are related to the integrin-mediated cell surface interactions and extracellular matrix organization signaling pathway.

  20. Feasibility of Cisplatin-Based Neoadjuvant Chemotherapy in Muscle-Invasive Bladder Cancer Patients With Diminished Renal Function.

    Science.gov (United States)

    Koshkin, Vadim S; Barata, Pedro C; Rybicki, Lisa A; Zahoor, Haris; Almassi, Nima; Redden, Alicia M; Fergany, Amr F; Kaouk, Jihad; Haber, Georges-Pascal; Stephenson, Andrew J; Ornstein, Moshe C; Gilligan, Timothy; Garcia, Jorge A; Rini, Brian I; Grivas, Petros

    2018-02-22

    Cisplatin-based neoadjuvant chemotherapy (NAC) before radical cystectomy is the standard of care in muscle-invasive bladder cancer. There are limited data regarding chemotherapy tolerability and outcomes for patients with low glomerular filtration rate (GFR) who receive cisplatin-based NAC. A retrospective analysis of patients who received cisplatin-based NAC at Cleveland Clinic (2005-2016) was undertaken. Patients with pre-NAC GFR < 60 mL/min by either Cockcroft-Gault (CG) or Modification of Diet in Renal Disease (MDRD) formula were compared to patients with GFR ≥ 60 mL/min for NAC tolerability, pathologic complete and partial response (pPR), and the ability to undergo radical cystectomy. Thirty patients with low GFR (34-59 mL/min) and 94 patients with normal GFR (≥ 60 mL/min) were identified. Low GFR patients were older (median, 71 vs. 65 years), but other demographic and transurethral resection of bladder tumor characteristics were comparable. Low GFR patients more frequently had early NAC discontinuation (30% vs. 13%), NAC modifications (delays, dose reduction, or discontinuation, 66% vs. 40%), and cisplatin-based NAC administered in split doses (37% vs. 16%). No differences in NAC tolerability or outcomes were noted among low GFR patients receiving split-dose versus standard regimens. No differences were noted between low and normal GFR patients in NAC cycles (median, 3 for each), cystectomy rates (93% for each), time to cystectomy, and GFR change from baseline to after NAC. Pathologic complete response was higher among normal GFR patients (24% vs. 14%). Patients with low GFR had more NAC discontinuations and modifications, but most completed planned NAC cycles. For carefully selected patients with GFR < 60 mL/min, cisplatin-based NAC remains a treatment option. Copyright © 2018 Elsevier Inc. All rights reserved.

  1. A case of multiple myeloma presenting as a bullous dermatosis

    Directory of Open Access Journals (Sweden)

    Gul Ulker

    2008-01-01

    Full Text Available Multiple myeloma is a malignant plasma cell proliferative disorder that produces a monoclonal immunoglobulin protein. The skin involvement and the development of bullous disease are rarely seen features in multiple myeloma. We present a 55-year-old man with a longstanding, large, tense bullous eruption and hypertrophic scars over his body accompanied recently with weight loss and fatique. He had no response to the previous treatments, which included oral glucocorticoids and dapsone. Histologic examination of the lesions revealed subepidermal bullae, while no immunoflourescence staining was observed. In a further detailed labarotory examination, multiple myeloma was detected. After the treatment of multiple myeloma with chemotherapy, the lesions regressed. Patients with longstanding, recurrent, unusual bullous eruption should be investigated for the development of multiple myeloma.

  2. Multiple myeloma of the jaw: A case report

    Directory of Open Access Journals (Sweden)

    Shubhasini A Raghavan

    2014-01-01

    Full Text Available Multiple myeloma is a systemic B-cell lymphoproliferative disease that causes osteolytic lesions in the vertebra, ribs, pelvic bone, skull and jaw. Rarely jaw lesions are seen as the first sign in multiple myeloma. This is a case report with follow up of a 57-year-old female patient, previously treated for osteoporosis, who presented with a swelling of the jaw. On radiographic examination, she was found to have osteolytic lesions in the mandible and skull bones. These conventional aids led to the diagnosis of multiple myeloma thereby proving that the osteoporotic lesions were a part of the spectrum of multiple myeloma. The patient underwent chemotherapy and is currently on follow-up. This case report emphasizes the importance of early diagnosis of multiple myeloma in the jaw using readily available technologies and illustrates the contribution that oral assessment can provide.

  3. [Management of side effects of targeted therapies in renal cancer: iatrogenic side effects].

    Science.gov (United States)

    Massard, Christophe; Patard, Jean-Jacques; Hermine, Olivier; Ravaud, Alain

    2011-01-01

    Since premedication of patients with an H1 antihistamine is recommended before the start of the intravenous infusion of temsirolimus, temsirolimus is to be used with caution in cases where there is a history of hypersensitivity to this class of antihistamines, or medical contra-indication for treatment with antihistamines. Comorbidities and co-medications must be taken into account in the prescription of targeted therapies. For sunitinib, sorafenib, and pazopanib: potential drug interactions are possible with inducers/inhibitors of CYP3A4, anti-hypertensive drugs, antidiabetic drugs, thyroid hormones, and anticoagulant treatments. The combination of bevacizumab and sunitinib is very toxic (microangiopathic haemolytic anaemia), and is contra-indicated unless part of a clinical trial. Screening, equilibration or treatment of hypothyroidism, anaemia, undernutrition, hypophosphatemia, hypomagnesaemia, sleep disorders, depression or other comorbidities, which may contribute to asthenia is recommended. In patients treated with sunitinib or pazopanib, a thyroid function test is recommended at the treatment centre as well as regular TSH assays. Copyright © 2011 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

  4. Development of a "Myeloma Risk Score" using a population-based registry on paraproteinemia and myeloma

    NARCIS (Netherlands)

    Ong, F; Hermans, J; Noordijk, E M; De Kieviet, W; Seelen, P J; Wijermans, P W; Kluin-Nelemans, J C

    1997-01-01

    Diagnostic systems for monoclonal gammopathies use bone marrow and X-ray examinations to exclude multiple myeloma (MM). Data from a population-based registry of unselected patients with paraproteinemia indicate that these tests are often done only when MM is suspected. We used 441 randomly selected

  5. Bortezomib: a novel therapy approved for multiple myeloma.

    Science.gov (United States)

    Richardson, Paul G; Anderson, Kenneth C

    2003-10-01

    Cellular homeostasis requires routine degradation of key regulatory proteins, including tumor suppressor gene products, transcription factors, cell-cycle proteins and their inhibitors, as well as damaged and misfolded proteins. A critical part of this process is mediated by the 26S proteasome, a multi-subunit enzyme found in the nucleus and cytoplasm of all eukaryotic cells. Because of its essential role in many cellular processes controlling growth and survival, the proteasome has been identified as a potential target for cancer therapy. Drugs known to inhibit proteasome activity have been shown to induce cell-cycle arrest and programmed cell death (apoptosis). The impact of this finding is heightened by research showing that cancer cells are more sensitive to the proapoptotic effects of proteasome inhibition than normal cells. Preclinical evidence using bortezomib, the only proteasome inhibitor to enter clinical trials, suggests that proteasome inhibition may be effective in the treatment of hematologic and solid malignancies by promoting apoptosis, retarding angiogenesis, and inhibiting tumor cell adhesion and production of growth factors by acting on molecules such as nuclear factor-kappaB. Further preclinical evidence suggests that the antitumor effects of cytotoxic chemotherapy or radiotherapy may be enhanced by the addition of a proteasome inhibitor. Bortezomib was recently approved for the treatment of multiple myeloma. It is currently being investigated, both as a single agent and in combination, in phase I and II trials in a variety of tumor types.

  6. Multiple Myeloma in the Very Old: An IASIA Conference Report

    Science.gov (United States)

    Shapiro, Gary R.; Ershler, William B.; Badros, Ashraf; Cohen, Harvey J.; Dispenzieri, Angela; Flores, Irene Q.; Kanapuru, Bindu; Jurivich, Donald; Longo, Dan L.; Nourbakhsh, Ali; Palumbo, Antonio; Walston, Jeremy; Yates, Jerome W.

    2014-01-01

    Multiple myeloma (MM) in patients aged greater than 80 years poses an increasingly common challenge for oncology providers. A multidisciplinary workshop was held in which MM-focused hematologists/oncologists, geriatricians, and associated health-care team members discussed the state of research for MM therapy, as well as themes from geriatric medicine that pertain directly to this patient population. A summary statement of our discussions is presented here, in which we highlight several topics. MM disproportionately affects senior adults, and demographic trends indicate that this trend will accelerate. Complex issues impact cancer in seniors, and although factors such as social environment, comorbidities, and frailty have been well characterized in nononcological geriatric medicine, these themes have been inadequately explored in cancers such as MM, despite their clear relevance to this field. Therapeutically, novel agents have improved survival for MM patients of all ages, but less so for seniors than younger patients for a variety of reasons. Lastly, both MM- and treatment-related symptoms and toxicities require special attention in senior adults. Existing research provides limited insight into how best to manage these often complex patients, who are often not reflected in typical clinical trial populations. We hence offer suggestions for clinical trials that address knowledge gaps in how to manage very old and/or frail patients with MM, given the complicated issues that often surround this patient population. PMID:24700806

  7. GWAS of 972 autologous stem cell recipients with multiple myeloma identifies 11 genetic variants associated with chemotherapy-induced oral mucositis

    DEFF Research Database (Denmark)

    Coleman, Elizabeth Ann; Lee, Jeannette Y; Erickson, Stephen W

    2015-01-01

    PURPOSE: High-dose chemotherapy and autologous stem cell transplant (ASCT) to treat multiple myeloma (MM) and other cancers carries the risk of oral mucositis (OM) with sequelae including impaired nutritional and fluid intake, pain, and infectious complications. As a result of these problems, can...

  8. Economic assessment of fidaxomicin for the treatment of Clostridium difficile infection (CDI) in special populations (patients with cancer, concomitant antibiotic treatment or renal impairment) in Spain.

    Science.gov (United States)

    Rubio-Terrés, C; Cobo Reinoso, J; Grau Cerrato, S; Mensa Pueyo, J; Salavert Lletí, M; Toledo, A; Anguita, P; Rubio-Rodríguez, D; Watt, M; Gani, R

    2015-11-01

    The objective of this paper was to assess the cost-utility of fidaxomicin versus vancomycin in the treatment of Clostridium difficile infection (CDI) in three specific CDI patient subgroups: those with cancer, treated with concomitant antibiotic therapy or with renal impairment. A Markov model with six health states was developed to assess the cost-utility of fidaxomicin versus vancomycin in the patient subgroups over a period of 1 year from initial infection. Cost and outcome data used to parameterise the model were taken from Spanish sources and published literature. The costs were from the Spanish hospital perspective, in Euros (€) and for 2013. For CDI patients with cancer, fidaxomicin was dominant versus vancomycin [gain of 0.016 quality-adjusted life-years (QALYs) and savings of €2,397 per patient]. At a cost-effectiveness threshold of €30,000 per QALY gained, the probability that fidaxomicin was cost-effective was 96 %. For CDI patients treated with concomitant antibiotic therapy, fidaxomicin was the dominant treatment versus vancomycin (gain of 0.014 QALYs and savings of €1,452 per patient), with a probability that fidaxomicin was cost-effective of 94 %. For CDI patients with renal impairment, fidaxomicin was also dominant versus vancomycin (gain of 0.013 QALYs and savings of €1,432 per patient), with a probability that fidaxomicin was cost-effective of 96 %. Over a 1-year time horizon, when fidaxomicin is compared to vancomycin in CDI patients with cancer, treated with concomitant antibiotic therapy or with renal impairment, the use of fidaxomicin would be expected to result in increased QALYs for patients and reduced overall costs.

  9. External radiation of brain metastases from renal carcinoma: a retrospective study of 119 patients from the M. D. Anderson Cancer Center

    International Nuclear Information System (INIS)

    Wronski, Marek; Maor, Moshe H.; Davis, Brian J.; Sawaya, Raymond; Levin, Victor A.

    1997-01-01

    Purpose: Approximately 10% of patients with metastatic renal cell carcinoma are diagnosed with brain metastases. Most of these patients receive palliative radiotherapy and die of progressive brain metastatic disease. This retrospective study examines the M. D. Anderson Cancer Center experience with such patients who received only whole brain radiation therapy (WBRT). Methods and Materials: Records of 200 patients with brain metastases from renal carcinoma who were treated at M. D. Anderson Cancer Center between 1976 and 1993 were reviewed. Of these patients, 119 received WBRT only and constitute the basis of this study. Different prognostic factors were analyzed. Results: Overall median survival time from diagnosis of the brain metastases was 4.4 months. Multiple brain tumors were treated in 70 patients (58.8%) who had a survival of 3.0 months compared with 4.4 months for patients having a single brain metastasis (p = 0.043). Among 117 patients the causes of death were neurologic in 90 (76%), systemic cancer in 19 (16%), and unknown in 9 (8%). Survival rates at 6 months, 1 year, and 2 years, were 33.6, 16.8, and 5.9%, respectively. Patients in whom brain metastases were diagnosed synchronously with a renal primary (n = 24) had a median survival time of 3.4 months compared with 3.2 months for those 95 who were diagnosed metachronously (p < 0.79, NS). In the Cox multivariate analysis of 13 possible prognostic factors, only a single brain metastasis (p = 0.0329), lack of distant metastases at the time of diagnosis (p = 0.0056), and tumor diameter ≤ 2 cm (p < 0.0016) were statistically significant. Conclusion: These unsatisfactory results with WBRT suggest that more aggressive approaches, such as surgery or radiosurgery should be applied whenever possible

  10. Adipokines, adiposity, and bone marrow adipocytes: Dangerous accomplices in multiple myeloma.

    Science.gov (United States)

    Morris, Emma V; Edwards, Claire M

    2018-06-26

    Obesity has become a global epidemic influencing the establishment and progression of a wide range of diseases, such as diabetes, cardiovascular disease, and cancer. In 2016, International Agency for Research on Cancer reported that obesity is now associated with 13 different cancers, one of which is multiple myeloma (MM), a destructive cancer of plasma cells that predominantly reside in the bone marrow. Obesity is the accumulation of excess body fat, which causes metabolic, endocrine, immunologic, and inflammatory-like changes. Obesity is usually associated with an increase in visceral and/or subcutaneous fat; however, an additional fat depot that also responds to diet-induced changes is bone marrow adipose tissue (BMAT). There have been several studies over the past few decades that have identified BMAT as a key driver in MM progression. Adipocytes secrete numerous adipokines, such as leptin, adiponectin, resistin, adipsin, and visfatin, which when secreted at normal controlled levels have protective properties. However, in obesity these levels of secretion change, coupled with an increase in adipocyte number and size causing a profound and lasting effect on the bone microenvironment, contributing to MM cell growth, survival, and migration as well as potentially fueling bone destruction. Obesity is a modifiable risk factor making it an attractive option for targeted therapy. This review discusses the link between obesity, monoclonal gammopathy of undetermined significance (a benign condition that precedes MM), and myeloma, and the contribution of key adipokines to disease establishment and progression. © 2018 Wiley Periodicals, Inc.

  11. IgD multiple myeloma: Clinical, biological features and prognostic value of the serum free light chain assay.

    Science.gov (United States)

    Djidjik, R; Lounici, Y; Chergeulaïne, K; Berkouk, Y; Mouhoub, S; Chaib, S; Belhani, M; Ghaffor, M

    2015-09-01

    IgD multiple myeloma (MM) is a rare subtype of myeloma, it affects less than 2% of patients with MM. To evaluate the clinical and prognostic attributes of serum free light chains (sFLCs) analysis, we examined 17 cases of IgD MM. From 1998 to 2012, we obtained 1250 monoclonal gammapathies including 590 multiple myeloma and 17 patients had IgD MM. With preponderance of men patients with a mean age at diagnosis of: 59±12years. Patients with IgD MM have a short survival (Median survival=9months). The presenting features included: bone pain (75%), lymphadenopathy (16%), hepatomegaly (25%), splenomegaly (8%), associated AL amyloidosis (6%), renal impairment function (82%), infections (47%), hypercalcemia (37%) and anemia (93%). Serum electrophoresis showed a subtle M-spike (Mean=13.22±10g/L) in all patients associated to a hypogammaglobulinemia. There was an over-representation of Lambda light chain (65%); high serum β2-microglobulin in 91% and Bence Jones proteinuria was identified in 71%. The median rate of sFLCs κ was 19.05mg/L and 296.75mg/L for sFLCs λ. sFLCR was abnormal in 93% of patients and it showed concordance between baseline sFLCR and the survival (P=0.034). The contribution of FLC assay is crucial for the prognosis of patients with IgD MM. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  12. Intratumoral Administration of Holmium-166 Acetylacetonate Microspheres : Antitumor Efficacy and Feasibility of Multimodality Imaging in Renal Cancer

    NARCIS (Netherlands)

    Bult, Wouter; Kroeze, Stephanie G. C.; Elschot, Mattijs; Seevinck, Peter R.; Beekman, Freek J.; de Jong, Hugo W. A. M.; Uges, Donald R. A.; Kosterink, Jos G. W.; Luijten, Peter R.; Hennink, Wim E.; Schip, Alfred D. van Het; Bosch, J. L. H. Ruud; Nijsen, J. Frank W.; Jans, Judith J. M.

    2013-01-01

    Purpose: The increasing incidence of small renal tumors in an aging population with comorbidities has stimulated the development of minimally invasive treatments. This study aimed to assess the efficacy and demonstrate feasibility of multimodality imaging of intratumoral administration of

  13. Induction of Apoptosis in Human Multiple Myeloma Cell Lines by Ebselen via Enhancing the Endogenous Reactive Oxygen Species Production

    OpenAIRE

    Zhang, Liang; Zhou, Liwei; Du, Jia; Li, Mengxia; Qian, Chengyuan; Cheng, Yi; Peng, Yang; Xie, Jiayin; Wang, Dong

    2014-01-01

    Ebselen a selenoorganic compound showing glutathione peroxidase like activity is an anti-inflammatory and antioxidative agent. Its cytoprotective activity has been investigated in recent years. However, experimental evidence also shows that ebselen causes cell death in several cancer cell types whose mechanism has not yet been elucidated. In this study, we examined the effect of ebselen on multiple myeloma (MM) cell lines in vitro. The results showed that ebselen significantly enhanced the pr...

  14. General Information about Rectal Cancer

    Science.gov (United States)

    ... Common Cancer Types Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer ... VEGF inhibitors and angiogenesis inhibitors . Epidermal growth factor receptor (EGFR) inhibitor therapy: EGFRs are proteins found on ...

  15. General Information about Colon Cancer

    Science.gov (United States)

    ... Common Cancer Types Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer ... VEGF inhibitors and angiogenesis inhibitors . Epidermal growth factor receptor (EGFR) inhibitor therapy: EGFRs are proteins found on ...

  16. Treatment Option Overview (Colon Cancer)

    Science.gov (United States)

    ... Common Cancer Types Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer ... VEGF inhibitors and angiogenesis inhibitors . Epidermal growth factor receptor (EGFR) inhibitor therapy: EGFRs are proteins found on ...

  17. Treatment Option Overview (Rectal Cancer)

    Science.gov (United States)

    ... Common Cancer Types Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer ... VEGF inhibitors and angiogenesis inhibitors . Epidermal growth factor receptor (EGFR) inhibitor therapy: EGFRs are proteins found on ...

  18. Treatment Option Overview (Breast Cancer)

    Science.gov (United States)

    ... Common Cancer Types Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer ... only hormone therapy after a hysterectomy . Selective estrogen receptor modulators (SERMs). Aromatase inhibitors . Less exposure of breast ...

  19. Hormone Therapy for Prostate Cancer

    Science.gov (United States)

    ... Common Cancer Types Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer ... compete with androgens for binding to the androgen receptor. By competing for binding to the androgen receptor, ...

  20. Renal perfusion scintiscan

    Science.gov (United States)

    ... Radionuclide renal perfusion scan; Perfusion scintiscan - renal; Scintiscan - renal perfusion Images Kidney anatomy Kidney - blood and urine flow Intravenous pyelogram References Rottenberg G, Andi AC. Renal ...

  1. A TAD better for myeloma therapy?

    Science.gov (United States)

    Giralt, Sergio

    2010-02-11

    In this issue of Blood, Lokhorst and colleagues report on the results of HOVON-50, a phase 3 randomized trial designed to evaluate the effects of thalidomide during induction treatment and as maintenance in patients with multiple myeloma. There were 556 patients randomly assigned either to 3 cycles of VAD or to TAD. All patients were to receive high-dose melphalan with autologous stem cell support followed by maintenance with interferon for the VAD arm or thalidomide for the TAD arm.(1) This study together with other randomized and nonrandomized trials establish a definitive role for thalidomide as induction therapy in conjunction with dexamethasone, anthracyclines, and alkylating agents.

  2. Von Hippel-Lindau (VHL inactivation in sporadic clear cell renal cancer: associations with germline VHL polymorphisms and etiologic risk factors.

    Directory of Open Access Journals (Sweden)

    Lee E Moore

    2011-10-01

    Full Text Available Renal tumor heterogeneity studies have utilized the von Hippel-Lindau VHL gene to classify disease into molecularly defined subtypes to examine associations with etiologic risk factors and prognosis. The aim of this study was to provide a comprehensive analysis of VHL inactivation in clear cell renal tumors (ccRCC and to evaluate relationships between VHL inactivation subgroups with renal cancer risk factors and VHL germline single nucleotide polymorphisms (SNPs. VHL genetic and epigenetic inactivation was examined among 507 sporadic RCC/470 ccRCC cases using endonuclease scanning and using bisulfite treatment and Sanger sequencing across 11 CpG sites within the VHL promoter. Case-only multivariate analyses were conducted to identify associations between alteration subtypes and risk factors. VHL inactivation, either through sequence alterations or promoter methylation in tumor DNA, was observed among 86.6% of ccRCC cases. Germline VHL SNPs and a haplotype were associated with promoter hypermethylation in tumor tissue (OR = 6.10; 95% CI: 2.28-16.35, p = 3.76E-4, p-global = 8E-5. Risk of having genetic VHL inactivation was inversely associated with smoking due to a higher proportion of wild-type ccRCC tumors [former: OR = 0.70 (0.20-1.31 and current: OR = 0.56 (0.32-0.99; P-trend = 0.04]. Alteration prevalence did not differ by histopathologic characteristics or occupational exposure to trichloroethylene. ccRCC cases with particular VHL germline polymorphisms were more likely to have VHL inactivation through promoter hypermethylation than through sequence alterations in tumor DNA, suggesting that the presence of these SNPs may represent an example of facilitated epigenetic variation (an inherited propensity towards epigenetic variation in renal tissue. A proportion of tumors from current smokers lacked VHL alterations and may represent a biologically distinct clinical entity from inactivated cases.

  3. Association between intracranial plasmacytoma and multiple myeloma: clinicopathological outcome study.

    Science.gov (United States)

    Schwartz, T H; Rhiew, R; Isaacson, S R; Orazi, A; Bruce, J N

    2001-11-01

    Intracranial plasmacytomas are rare lesions that can arise from the calvarium, dura, or cranial base and exhibit a benign course unless associated with myeloma. Attention has recently been focused on the role of the cell adhesion molecules CD56 and CD31 in the pathogenesis of myeloma. No such information is available for intracranial plasmacytomas and myeloma-associated lesions. We investigated the relationship between CD56 and CD31 expression, intracranial location, and progression to myeloma for a series of nine intracranial plasmacytomas (three dural, one calvarial, and five cranial base lesions). These parameters were also correlated with proliferation indices, as assessed by MIB-1 immunostaining of the histological sections. A single pathologist (AO) performed immunohistochemical analyses and reviewed all slides. Intracranial plasmacytomas presented more commonly in female patients (89%). The three dural lesions were CD56- and CD31-negative and exhibited MIB-1 staining of less than 10%; no patient developed myeloma or recurrence. Of the five cranial base lesions, three were CD56-positive, none was CD31-positive, and two exhibited MIB-1 labeling of more than 45%, with plasmablastic morphological features. Compared with other intracranial plasmacytomas, five of five patients with cranial base lesions developed bone marrow biopsy-proven myeloma (P myeloma soon after diagnosis. Both of the two highly proliferative plasmablastic lesions recurred, one after gross total resection without radiotherapy and the other after a biopsy and 2000-cGy radiotherapy. Among intracranial plasmacytomas, cranial base location was the strongest predictor of the development of multiple myeloma. Expression of the cell adhesion molecules CD31 and CD56 was not predictive of outcome. Extramedullary dural-based lesions were CD56-negative and were not associated with myeloma. A high proliferation index and plasmablastic morphological features were predictive of a short time to recurrence

  4. Changes in causes of death and risk of cancer in Danish patients with autosomal dominant polycystic kidney didease and end-stage renal disease

    DEFF Research Database (Denmark)

    Ørskov, Bjarne; Feldt-Rasmussen, Bo Friis; Strandgaard, Svend Valdemar

    2012-01-01

    Abstract Background. With the improved prognosis in patients with autosomal dominant polycystic kidney disease (ADPKD), causes of death and the risk of cancer might have changed. This was investigated in a Danish population with ADPKD and end-stage renal disease (ESRD) between 1 January 1993 and 31...... December 2008. Methods. Data were retrieved from three Danish national registries and a total of 823 patients were identified of which 431 had died during the study period. The 16 years were divided into two 8-year periods and the causes of death were divided into six categories: cancer, cardiovascular......, cerebrovascular, infection, other and unknown. Results. Cardiovascular disease was the major cause of death. A multivariate competing risk model comparing the two 8-year periods, adjusted for age at ESRD, gender and treatment modality, showed that deaths from cardiovascular disease decreased by 35% [hazard ratios...

  5. Radioablative therapy with Iodine-131 on a patient with thyroid cancer and chronic renal failure in hemodialysis first experience in Peru

    International Nuclear Information System (INIS)

    Apaza Veliz, D. G.; Herrera Vera, R. D.; Cardenas Abarca, C. A.; Oporto Gonzales, C. A.; Aguilar Ramírez, C.; Urquizo Baldomero, R. M.; Vega Ramírez, J. L.

    2016-01-01

    The Iodine-131 (I-131) is a radioisotope used as a standard treatment for radioablation of thyroid remnants. Among thyroid cancer patients, the ones undergoing hemodialysis represent a specific group. The dose of I-131 is given orally to these patients, part of it is absorbed by the thyroid remnants and the rest of it, largely not incorporated, is excreted primarily by renal excretion. The use of a high dose of radioactivity in the process, and the inability of excretion, represents a high risk of exposure to the patient, medical staff and hemodialysis equipment. This work describes the procedure applied on the radioablation therapy for thyroid cancer while receiving hemodialysis, minimizing the risks for the patient and the staff involved. This clinical procedure will establish the dosimetric measures, a plan on radiation protection and a treatment protocol for this specific type of patients.

  6. Post-radiational ureteric fibrosis with extrarenal renal failure as a rare complication after adjuvant treatment of gastric cancer - a case report

    International Nuclear Information System (INIS)

    Swieboda-Sadlej, A.; Staszewska-Skurczynska, M.; Piyush Vyas; Zurawinska, E.; Heleniak, H.; Kocik, J.; Danek, A.; Tragarz, E.

    2008-01-01

    The principles of chemoradiotherapy for treating patients with radically resected gastric cancer are not fully established. In many oncological centres patients with unfavourable prognostic factors who previously had radical gastrectomy are treated with Macdonald regimen which includes combined fluorouracil with radiotherapy. Statistics indicate that more then 30% patients treated with chemoradiotherapy suffer from serious complication. In this article we describe a case of a patient who developed ureteric fibrosis with consequent renal failure as a rare life threatening complication of Macdonald regimen. The patient received chemoradiotherapy because of unfavourable prognostic factors and good performance status however he was in advanced age and with other comorbidities. These data support the notion of the high toxicity of this regimen and suggest that selection of patients for this treatment should be done very carefully. This is discussed in the context of other available therapies in gastric cancer. (author)

  7. Radioablative therapy with Iodine-131 on a patient with thyroid cancer and chronic renal failure in hemodialysis first experience in Peru

    Energy Technology Data Exchange (ETDEWEB)

    Apaza Veliz, D. G., E-mail: dgav02@gmail.com [Hospital Nacional Carlos Alberto Seguin Escobedo, Servicio de Medicina Nuclear, Arequipa, Perú, Universidad Nacional de San Agustín de Arequipa, Escuela de Física, Arequipa (Peru); Herrera Vera, R. D.; Cardenas Abarca, C. A.; Oporto Gonzales, C. A.; Aguilar Ramírez, C.; Urquizo Baldomero, R. M. [Hospital Nacional Carlos Alberto Seguin Escobedo, Servicio de Medicina Nuclear, Arequipa (Peru); Vega Ramírez, J. L. [Universidad Nacional de San Agustín de Arequipa, Escuela de Física, Arequipa (Peru)

    2016-07-07

    The Iodine-131 (I-131) is a radioisotope used as a standard treatment for radioablation of thyroid remnants. Among thyroid cancer patients, the ones undergoing hemodialysis represent a specific group. The dose of I-131 is given orally to these patients, part of it is absorbed by the thyroid remnants and the rest of it, largely not incorporated, is excreted primarily by renal excretion. The use of a high dose of radioactivity in the process, and the inability of excretion, represents a high risk of exposure to the patient, medical staff and hemodialysis equipment. This work describes the procedure applied on the radioablation therapy for thyroid cancer while receiving hemodialysis, minimizing the risks for the patient and the staff involved. This clinical procedure will establish the dosimetric measures, a plan on radiation protection and a treatment protocol for this specific type of patients.

  8. Radioablative therapy with Iodine-131 on a patient with thyroid cancer and chronic renal failure in hemodialysis first experience in Peru

    Science.gov (United States)

    Apaza Veliz, D. G.; Herrera Vera, R. D.; Cardenas Abarca, C. A.; Oporto Gonzales, C. A.; Aguilar Ramírez, C.; Vega Ramírez, J. L.; Urquizo Baldomero, R. M.

    2016-07-01

    The Iodine-131 (I-131) is a radioisotope used as a standard treatment for radioablation of thyroid remnants. Among thyroid cancer patients, the ones undergoing hemodialysis represent a specific group. The dose of I-131 is given orally to these patients, part of it is absorbed by the thyroid remnants and the rest of it, largely not incorporated, is excreted primarily by renal excretion. The use of a high dose of radioactivity in the process, and the inability of excretion, represents a high risk of exposure to the patient, medical staff and hemodialysis equipment. This work describes the procedure applied on the radioablation therapy for thyroid cancer while receiving hemodialysis, minimizing the risks for the patient and the staff involved. This clinical procedure will establish the dosimetric measures, a plan on radiation protection and a treatment protocol for this specific type of patients.

  9. RNA interference-mediated silencing of speckle-type POZ protein promotes apoptosis of renal cell cancer cells

    Directory of Open Access Journals (Sweden)

    Liu X

    2016-04-01

    Full Text Available Xiaoxia Liu, Guiling Sun, Xiuju Sun Department of Nephrology, Affiliated Hospital of Weifang Medical University, Weifang, People’s Republic of China Abstract: This study aimed to investigate the effects of silencing the speckle-type POZ protein (SPOP gene on renal cell cancer (RCC cells and to explore its possible mechanism. The A498 and ACHN RCC cells were transfected with small interference RNA (siRNA-SPOP by lipofection methods. The silencing efficiency was monitored by quantitative real-time polymerase chain reaction and Western blot. The effects of SPOP silencing on cell apoptosis, cell viability, colony formation ability, cell migration ability, and chemosensitivity to Sorafenib were assessed by flow cytometry, an MTT assay, a colony formation assay, a trans-well migration assay, and a CCK-8 assay, respectively. Its effects on the expression of several cytokines were determined by a protein microarray. Relevant signaling pathways were also analyzed. Compared with the control group, the cell apoptosis rate was significantly higher; the cell viability, the colony formation, and migration ability were significantly decreased in the siRNA-SPOP group. The protein microarray screening showed that the expression of vascular endothelial growth factor receptor, matrix metallopeptidase-9, vascular cell adhesion molecule-1, and stromal cell-derived factor-1 in the siRNA group was significantly decreased and that the expression of granulocyte–macrophage colony-stimulating factor and E-cadherin was significantly increased (P<0.05. The relevant signaling pathways were the integrin-mediated cell surface interactions pathway and extracellular matrix organization signal pathway. SPOP gene silencing induced cell apoptosis, decreased cell viability, colony formation, and migration ability, and elevated the drug sensitivity in the RCC cells. A possible mechanism is that silencing SPOP induces the differential expression of E-cadherin, vascular endothelial

  10. Immunogenic Targets for Specific Immunotherapy in Multiple Myeloma

    Directory of Open Access Journals (Sweden)

    Lu Zhang

    2012-01-01

    Full Text Available Multiple myeloma remains an incurable disease although the prognosis has been improved by novel therapeutics and agents recently. Relapse occurs in the majority of patients and becomes fatal finally. Immunotherapy might be a powerful intervention to maintain a long-lasting control of minimal residual disease or to even eradicate disseminated tumor cells. Several tumor-associated antigens have been identified in patients with multiple myeloma. These antigens are expressed in a tumor-specific or tumor-restricted pattern, are able to elicit immune response, and thus could serve as targets for immunotherapy. This review discusses immunogenic antigens with therapeutic potential for multiple myeloma.

  11. The safety of CRT with high-dose cisplatin for head and neck cancers in a community hospital and the renal protection effect with magnesium

    International Nuclear Information System (INIS)

    Ariizumi, Yosuke; Takahashi, Ryosuke; Tateishi, Yumiko; Yamada, Masato

    2016-01-01

    To confirm the safety of CRT with cisplatin 100mg/m"2 for head and neck cancers in a community hospital in Japan and the renal protection effect with magnesium (Mg) supplementation. A retrospective review of 13 head and neck cancers (oropharynx, hypopharynx, and larynx) was conducted. The patients of the 80mgMg - group received CDDP 80mg/m"2 without Mg supplementation, and 100mgMg + group received CDDP 100mg/m"2 with Mg supplementation. Our hospital is a community hospital, therefore second and third administrations of CDDP are discontinued with a lower level of adverse effects than clinical trials. The total dose of CDDP and adverse effects of the two groups were compared. The grade 3 adverse effects were 5 (38%) with stomatitis, 3 (23%) with decreased white blood cell count, 1 (8%) with decreased platelet count, and 1 (8%) with febrile neutropenia. There was no grade 4 adverse effect. The proportion of patients who could receive 200mg/m"2 or more was higher (p = 0.0097) in the 100mgMg + group (7/7) than the 80mgMg - group (1/6). CRT with CDDP 100mg/m"2 at a community hospital in Japan is feasible, with reduction of renal toxicity by Mg supplementation. (author)

  12. A pilot study to assess feasibility of value based pricing in Cyprus through pharmacoeconomic modelling and assessment of its operational framework: sorafenib for second line renal cell cancer.

    Science.gov (United States)

    Petrou, Panagiotis; Talias, Michael A

    2014-01-01

    The continuing increase of pharmaceutical expenditure calls for new approaches to pricing and reimbursement of pharmaceuticals. Value based pricing of pharmaceuticals is emerging as a useful tool and possess theoretical attributes to help health system cope with rising pharmaceutical expenditure. To assess the feasibility of introducing a value-based pricing scheme of pharmaceuticals in Cyprus and explore the integrative framework. A probabilistic Markov chain Monte Carlo model was created to simulate progression of advanced renal cell cancer for comparison of sorafenib to standard best supportive care. Literature review was performed and efficacy data were transferred from a published landmark trial, while official pricelists and clinical guidelines from Cyprus Ministry of Health were utilised for cost calculation. Based on proposed willingness to pay threshold the maximum price of sorafenib for the indication of second line renal cell cancer was assessed. Sorafenib value based price was found to be significantly lower compared to its current reference price. Feasibility of Value Based Pricing is documented and pharmacoeconomic modelling can lead to robust results. Integration of value and affordability in the price are its main advantages which have to be weighed against lack of documentation for several theoretical parameters that influence outcome. Smaller countries such as Cyprus may experience adversities in establishing and sustaining essential structures for this scheme.

  13. Treatment Options by Stage (Endometrial Cancer)

    Science.gov (United States)

    ... Common Cancer Types Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer ... cancer cells have places where hormones can attach ( receptors ), drugs , surgery, or radiation therapy is used to ...

  14. Reproductive History and Breast Cancer Risk

    Science.gov (United States)

    ... Common Cancer Types Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer ... 4 ). This risk reduction is limited to hormone receptor –positive breast cancer; age at first full-term ...

  15. Novel agents in the treatment of multiple myeloma: a review about the future

    Directory of Open Access Journals (Sweden)

    Leonard Naymagon

    2016-06-01

    Full Text Available Abstract Multiple myeloma (MM is a disease that affects plasma cells and can lead to devastating clinical features such as anemia, lytic bone lesions, hypercalcemia, and renal disease. An enhanced understanding of MM disease mechanisms has led to new more targeted treatments. There is now a plethora of treatments available for MM. In this review article, our aim is to discuss many of the novel agents that are being studied or have recently been approved for the treatment of MM. These agents include the following: immunomodulators (pomalidomide, proteasome inhibitors (carfilzomib, marizomib, ixazomib, oprozomib, alkylating agents (bendamustine, AKT inhibitors (afuresertib, BTK inhibitors (ibrutinib, CDK inhibitors (dinaciclib, histone deacetylase inhibitors (panobinostat, rocilinostat, vorinostat, IL-6 inhibitors (siltuximab, kinesin spindle protein inhibitors (filanesib, monoclonal antibodies (daratumumab, elotuzumab, indatuximab, SAR650984, and phosphoinositide 3-kinase (PI3K inhibitors.

  16. Functional and clinical evaluation of renal injury in patients treated with adjuvant chemoradiotherapy for gastric cancer: Low dose and comorbidity considerations

    Directory of Open Access Journals (Sweden)

    Roman Ibrahimov

    2016-01-01

    Conclusion: Functional renal impairment without any clinical signs or symptoms can be observed in low doses after radiotherapy. Careful treatment planning and a detailed evaluation of the functional renal capacity before treatment may help to reduce late renal toxicity.

  17. Obesity as a Major Risk Factor for Cancer

    Directory of Open Access Journals (Sweden)

    Giovanni De Pergola

    2013-01-01

    Full Text Available The number of cancer cases caused by being obese is estimated to be 20% with the increased risk of malignancies being influenced by diet, weight change, and body fat distribution together with physical activity. Reports from the International Agency for Research into Cancer and the World Cancer Research Fund (WCRF have shown that the strongest evidence exists for an association of obesity with the following cancer types: endometrial, esophageal adenocarcinoma, colorectal, postmenopausal breast, prostate, and renal, whereas the less common malignancies are leukemia, non-Hodgkin’s lymphoma, multiple myeloma, malignant melanoma, and thyroid tumours. To be able to develop novel methods in prevention and treatment, we first must understand the underlying processes which link cancer to obesity. Four main systems have been identified as potential producers of cancer in obesity: insulin, insulin-like growth factor-I, sex steroids, and adipokines. Various novel candidate mechanisms have been proposed: chronic inflammation, oxidative stress, crosstalk between tumour cells and surrounding adipocytes, migrating adipose stromal cells, obesity-induced hypoxia, shared genetic susceptibility, and the functional defeat of immune function. Herein, we review the major pathogenic links between obesity and susceptibility to cancer.

  18. Imaging of renal metastases

    International Nuclear Information System (INIS)

    Bruneton, J.N.; Normand, F.; Balu-Maestro, C.; Rogopoulos, A.; Drouillard, J.; Laurent, F.

    1988-01-01

    Metastases are the most frequent malignant tumors of the kidney, but these lesions are of late onset in neoplastic disease. The 19 cases reported here were all investigated with various imaging techniques (CT 12 cases, ultrasonography 12 cases, urography 8 cases, angiography 2 cases, MRI 1 case). The most common primary malignancies were lung cancer, melanoma and cancer of the controlateral kidney. In this series, 8 of the lesions were solitary, and 9 were unilateral. Tumor vascularity was evaluated in 15 cases: 14 of these lesions were hypovascular. The differential diagnosis includes small cysts, lymphoma, bilateral renal cancer, multiple small abscesses and multiple small infarcts [fr

  19. THERAPY-RELATED MYELOID MALIGNANCIES IN MYELOMA

    Directory of Open Access Journals (Sweden)

    Xenofon Papanikolaou

    2011-10-01

    Full Text Available Therapy related myeloid malignancies are an increasingly recognized treatment complication in patients undergoing therapy for multiple myeloma. The main predisposing factors are the alkylating agents, topoisomerase II inhibitors and radiotherapy, but recently questions have been raised regarding the immunomodulatory agent lenalidomide. Little is known about the new antimyeloma agents in the context of therapy related myeloid malignanices. The duration of treatment and the time from diagnosis are the main contributing factors in alkylating induced myeloid malignancies which occur 5-10 years after treatment, chromosome 5 and 7 abnormalities being the characteristic finding. High dose therapy (HDT does not seem to be a major contributing factor per se in multiple myeloma. In a number of large published series, all the factors related with therapy-induced myelodysplasia were defined prior to HDT. Topoisomerase II inhibitors induce mainly acute leukemias which invariably correlate with dysregulation of the MLL gene. Radiotherapy causes therapy related myelodysplasia if applied in bone marrow producing areas, especially if combined with chemotherapy. Therapy related myeloid malignancies generally herald a poor prognosis. Karyotypic abnormalities seem to be the main prognostic factor. In all cases the risk for therapy related myeloid malignancies drops sharply by 10 years after the treatment.

  20. THERAPY-RELATED MYELOID MALIGNANCIES IN MYELOMA

    Directory of Open Access Journals (Sweden)

    Bart Barlogie

    2011-01-01

    Full Text Available

    Therapy related myeloid malignancies are an increasingly recognized treatment complication in patients undergoing therapy for multiple myeloma. The main predisposing factors are the alkylating agents, topoisomerase II inhibitors and radiotherapy, but recently questions have been raised regarding the immunomodulatory agent lenalidomide. Little is known about the new antimyeloma agents in the context of therapy related myeloid malignanices. The duration of treatment and the time from diagnosis are the main contributing factors in alkylating induced myeloid malignancies which occur 5-10 years after treatment, chromosome 5 and 7 abnormalities being the characteristic finding. High dose therapy (HDT does not seem to be a major contributing factor per se in multiple myeloma. In a number of large published series, all the factors related with therapy-induced myelodysplasia were defined prior to HDT. Topoisomerase II inhibitors induce mainly acute leukemias which invariably correlate with dysregulation of the MLL gene. Radiotherapy causes therapy related myelodysplasia if applied in bone marrow producing areas, especially if combined with chemotherapy. Therapy related myeloid malignancies generally herald a poor prognosis. Karyotypic abnormalities seem to be the main prognostic factor. In all cases the risk for therapy related myeloid malignancies drops sharply by 10 years after the treatment.

  1. Palliative radiotherapy in plasma cell myeloma

    International Nuclear Information System (INIS)

    Adamietz, I.A.; Schoeber, C.; Schulte, R.W.M.; Renner, K.; Peest, D.

    1991-01-01

    Pain symptoms caused by bone lesions of multiple myeloma can be relieved by a local irradiation treatment. To estimate the influence of systemic treatment on the palliative effect of local radiotherapy the records of 70 myeloma patients treated with chemotherapy combined with or followed by local irradiation were reviewed. The local response rate, defined as complete pain relief at the irradiated site, was 80 percent in patients receiving irradiation during chemotherapy (melphalan and prednisone) and this palliative effect endured 31.8+-3.6 months. If irradiation was started in the period without systemic treatment the local response rate was 39.6 percent and lasted 24.8+-17.9 months. In sites treated with more than one radiotherapy course 94 percent response after the 1st treatment, 56 percent after the 2nd and no response after the 3rd was achieved. The duration of local pain control was positively related to the applied radiation dose. It is concluded that irradiation during concomitant chemotherapy is superior to radiotherapy performed in a period without systemic treatment. Local long-term palliation can only be achieved by a sufficient high radiation dose. (author). 24 refs.; 2 figs.; 2 tabs

  2. Cyclic AMP induces apoptosis in multiple myeloma cells and inhibits tumor development in a mouse myeloma model

    International Nuclear Information System (INIS)

    Follin-Arbelet, Virginie; Hofgaard, Peter O; Hauglin, Harald; Naderi, Soheil; Sundan, Anders; Blomhoff, Rune; Bogen, Bjarne; Blomhoff, Heidi K

    2011-01-01

    Multiple myeloma is an incurable disease requiring the development of effective therapies which can be used clinically. We have elucidated the potential for manipulating the cAMP signaling pathway as a target for inhibiting the growth of multiple myeloma cells. As a model system, we primarily used the murine multiple myeloma cell line MOPC315 which can be grown both in vivo and in vitro. Human multiple myeloma cell lines U266, INA-6 and the B-cell precursor acute lymphoblastic leukemia cell line Reh were used only for in vitro studies. Cell death was assessed by flow cytometry and western blot analysis after treatment with cAMP elevating agents (forskolin, prostaglandin E2 and rolipram) and cAMP analogs. We followed tumor growth in vivo after forskolin treatment by imaging DsRed-labelled MOPC315 cells transplanted subcutaneously in BALB/c nude mice. In contrast to the effect on Reh cells, 50 μM forskolin more than tripled the death of MOPC315 cells after 24 h in vitro. Forskolin induced cell death to a similar extent in the human myeloma cell lines U266 and INA-6. cAMP-mediated cell death had all the typical hallmarks of apoptosis, including changes in the mitochondrial membrane potential and cleavage of caspase 3, caspase 9 and PARP. Forskolin also inhibited the growth of multiple myeloma cells in a mouse model in vivo. Elevation of intracellular levels of cAMP kills multiple myeloma cells in vitro and inhibits development of multiple myeloma in vivo. This strongly suggests that compounds activating the cAMP signaling pathway may be useful in the field of multiple myeloma

  3. The application of Gadopentate-Dimeneglumin has no impact on progression free and overall survival as well as renal function in patients with monoclonal plasma cell disorders if general precautions are taken

    Energy Technology Data Exchange (ETDEWEB)

    Hillengass, J. [University of Heidelberg, Department of Hematology, Oncology and Rheumatology, Heidelberg (Germany); German Cancer Research Center Heidelberg, Department of Radiology, Heidelberg (Germany); Stoll, J.; Wagner, B.; Goldschmidt, H. [University of Heidelberg, Department of Hematology, Oncology and Rheumatology, Heidelberg (Germany); Zechmann, C.M. [Rinecker Proton Therapy Center, Munich (Germany); Kunz, C.; Heiss, C. [German Cancer Research Center Heidelberg, Department of Biostatistics, Heidelberg (Germany); Sumkauskaite, M. [University of Heidelberg, Department of Radiology, Heidelberg (Germany); Moehler, T.M. [InVentiv Health Clinical, Wiesbaden (Germany); Schlemmer, H.P.; Delorme, S. [German Cancer Research Center Heidelberg, Department of Radiology, Heidelberg (Germany)

    2014-10-31

    The current analysis investigated the prognostic significance of gadopentetate dimeglumine on survival and renal function in patients with monoclonal plasma cell disorders. In this study 263 patients who had received gadopentetate dimeglumine within a prospective trial investigating dynamic contrast-enhanced magnetic resonance imaging (MRI) were compared with 335 patients who had undergone routine, unenhanced MRI. We found no significant prognostic impact of the application of contrast agent on progression-free survival in patients with either monoclonal gammopathy of undetermined significance, smouldering or symptomatic myeloma and no significant prognostic impact on overall survival in patients with symptomatic myeloma. Since renal impairment is a frequent complication of myeloma, and decreased renal function is associated with a higher risk of complications in patients receiving contrast agents, we evaluated the impact of contrast agent on renal function after 1 year. In the present analysis the only significant adverse impact on kidney function occurred in symptomatic myeloma patients who already had impaired renal parameters at baseline. Here, the renal function did not recover during therapy, whereas it did so in patients with normal or only slightly impaired renal function. If general recommendations are adhered to, gadopentetate dimeglumine can be safely applied in patients with monoclonal plasma cell disease. (orig.)

  4. RENAL CRYOABLATION

    Directory of Open Access Journals (Sweden)

    A. V. Govorov

    2012-01-01

    Full Text Available Renal cryoablation is an alternative minimally-invasive method of treatment for localized renal cell carcinoma. The main advantages of this methodology include visualization of the tumor and the forming of "ice ball" in real time, fewer complications compared with other methods of treatment of renal cell carcinoma, as well as the possibility of conducting cryotherapy in patients with concomitant pathology. Compared with other ablative technologies cryoablation has a low rate of repeat sessions and good intermediate oncological results. The studies of long-term oncological and functional results of renal cryoablation are presently under way.

  5. Identifying mRNA targets of microRNA dysregulated in cancer: with application to clear cell Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Liou Louis S

    2010-04-01

    Full Text Available Abstract Background MicroRNA regulate mRNA levels in a tissue specific way, either by inducing degradation of the transcript or by inhibiting translation or transcription. Putative mRNA targets of microRNA identified from seed sequence matches are available in many databases. However, such matches have a high false positive rate and cannot identify tissue specificity of regulation. Results We describe a simple method to identify direct mRNA targets of microRNA dysregulated in cancers from expression level measurements in patient matched tumor/normal samples. The word "direct" is used here in a strict sense to: a represent mRNA which have an exact seed sequence match to the microRNA in their 3'UTR, b the seed sequence match is strictly conserved across mouse, human, rat and dog genomes, c the mRNA and microRNA expression levels can distinguish tumor from normal with high significance and d the microRNA/mRNA expression levels are strongly and significantly anti-correlated in tumor and/or normal samples. We apply and validate the method using clear cell Renal Cell Carcinoma (ccRCC and matched normal kidney samples, limiting our analysis to mRNA targets which undergo degradation of the mRNA transcript because of a perfect seed sequence match. Dysregulated microRNA and mRNA are first identified by comparing their expression levels in tumor vs normal samples. Putative dysregulated microRNA/mRNA pairs are identified from these using seed sequence matches, requiring that the seed sequence be conserved in human/dog/rat/mouse genomes. These are further pruned by requiring a strong anti-correlation signature in tumor and/or normal samples. The method revealed many new regulations in ccRCC. For instance, loss of miR-149, miR-200c and mir-141 causes gain of function of oncogenes (KCNMA1, LOX, VEGFA and SEMA6A respectively and increased levels of miR-142-3p, miR-185, mir-34a, miR-224, miR-21 cause loss of function of tumor suppressors LRRC2, PTPN13, SFRP1

  6. Renal toxicity after total body irradiation

    International Nuclear Information System (INIS)

    Borg, Martin; Hughes, Timothy; Horvath, Noemi; Rice, Michael; Thomas, Anthony C.

    2002-01-01

    Purpose: To evaluate the incidence of renal dysfunction after total body irradiation (TBI). Methods and Materials: Between 1990 and 1997, 64 patients (median age 50 years) received TBI as part of the conditioning regimen before bone marrow transplantation (BMT). Five patients with abnormal renal function at the beginning of treatment or with incomplete data were excluded. All patients received a total of 12 Gy (6 fractions twice daily for 3 consecutive days) prescribed to the peak lung dose (corrected for lung transmission) at a dose rate of 7.5 cGy/min. Renal shielding was not used. Renal dysfunction was assessed on the basis of the serum creatinine levels measured at the start and end of TBI and at 6, 12, 18, and 24 months after completion of BMT. Cox proportional hazard analysis was used to evaluate the various factors known to affect renal function. Results: Only 4 patients had elevated serum creatinine levels at 12 months and subsequently only 2 of the 33 surviving patients had persistent elevated renal serum creatinine levels 24 months after BMT. A fifth patient developed proteinuria and mildly elevated serum creatinine levels at 2.5 years. In 2 patients, the elevation coincided with disease relapse and normalized once remission was achieved. In the third patient, the elevation in serum creatinine levels coincided with relapse of multiple myeloma and the presence of Bence-Jones proteinuria. The fourth patient was the only patient who developed chronic renal failure secondary to radiation nephritis at 2 years. The etiology of the fifth patient's rise in creatinine was unknown, but may have been secondary to radiation nephritis. On univariate analysis, but not on multivariate analysis, a significant correlation was found between TBI-related renal dysfunction and hypertension before and after BMT. Conclusion: A dose of 12 Gy at 2 Gy/fraction resulted in only 1 case of radiation nephritis in the 59 patients studied 24 months after the completion of TBI and BMT

  7. Spotlight on ixazomib: potential in the treatment of multiple myeloma

    Directory of Open Access Journals (Sweden)

    Muz B

    2016-01-01

    Full Text Available Barbara Muz,1 Rachel Nicole Ghazarian,1,2 Monica Ou,1,3 Micah John Luderer,1 Hubert Daniel Kusdono,1,2 Abdel Kareem Azab1 1Department of Radiation Oncology, Cancer Biology Division, Washington University in St Louis School of Medicine, 2Department of Pharmaceutical and Administrative Sciences, St Louis College of Pharmacy, 3Department of Biology, St Louis University, St Louis, MO, USA Abstract: Despite the significant therapeutic advances achieved with proteasome inhibitors (PIs such as bortezomib and carfilzomib in prolonging the survival of patients with multiple myeloma, the development of drug resistance, peripheral neuropathy, and pharmacokinetic limitations continue to pose major challenges when using these compounds. Ixazomib is a second-generation PI with improved activity over other PIs. Unlike bortezomib and carfilzomib, which are administered by injection, ixazomib is the first oral PI approved by US Food and Drug Administration. This review discusses the biochemical properties, mechanisms of action, preclinical efficacy, and clinical trial results leading to the US Food and Drug Administration approval of ixazomib. Keywords: proteasome inhibitor, oral administration, biological mechanism, clinical trials

  8. Illegitimate WNT signaling promotes proliferation of multiple myeloma cells

    Science.gov (United States)

    Derksen, Patrick W. B.; Tjin, Esther; Meijer, Helen P.; Klok, Melanie D.; Mac Gillavry, Harold D.; van Oers, Marinus H. J.; Lokhorst, Henk M.; Bloem, Andries C.; Clevers, Hans; Nusse, Roel; van der Neut, Ronald; Spaargaren, Marcel; Pals, Steven T.

    2004-01-01

    The unrestrained growth of tumor cells is generally attributed to mutations in essential growth control genes, but tumor cells are also influenced by signals from the environment. In multiple myeloma (MM), the factors and signals coming from the bone marrow microenvironment are possibly even essential for the growth of the tumor cells. As targets for intervention, these signals may be equally important as mutated oncogenes. Given their oncogenic potential, WNT signals form a class of paracrine growth factors that could act to influence MM cell growth. In this paper, we report that MM cells have hallmarks of active WNT signaling, whereas the cells have not undergone detectable mutations in WNT signaling genes such as adenomatous polyposis coli and β-catenin (CTNNB1). We show that the malignant MM plasma cells overexpress β-catenin, including its N-terminally unphosphorylated form, suggesting active β-catenin/T cell factor-mediated transcription. Further accumulation and nuclear localization of β-catenin, and/or increased cell proliferation, was achieved by stimulation of WNT signaling with either Wnt3a, LiCl, or the constitutively active S33Y mutant of β-catenin. In contrast, by blocking WNT signaling by dominant-negative T cell factor, we can interfere with the growth of MM cells. We therefore suggest that MM cells are dependent on an active WNT signal, which may have important implications for the management of this incurable form of cancer. PMID:15067127

  9. Dalteparin versus vitamin K antagonists for the prevention of recurrent venous thromboembolism in patients with cancer and renal impairment: a Canadian pharmacoeconomic analysis

    Directory of Open Access Journals (Sweden)

    Dranitsaris G

    2017-01-01

    Full Text Available George Dranitsaris,1 Lesley G Shane,2 Mark Crowther,3 Guillaume Feugere,4 Seth Woodruff2 1Health Economic and Outcomes Research, Augmentium Pharma Consulting Inc, Toronto, ON, Canada; 2Pfizer Inc, New York, NY, USA; 3McMaster University, Hamilton, ON, 4Pfizer Canada, Montreal, QC, Canada Background: Patients with cancer are at increased risk of venous thromboembolism (VTE and the risk is further elevated after a primary VTE. To reduce the risk of recurrent events, extended prophylaxis with vitamin K antagonists (VKA is available for use. However, in a large randomized trial (Comparison of Low-Molecular-Weight Heparin versus Oral Anticoagulant Therapy for the Prevention of Recurrent Venous Thromboembolism in Patients with Cancer [CLOT]; Lee et al, extended duration dalteparin reduced the relative risk of recurrent VTE by 52% compared to VKA (p=0.002. A recent subgroup analysis of patients with moderate-to-severe renal impairment also revealed lower absolute VTE rates with dalteparin (3% vs. 17%; p=0.011. To measure the economic value of dalteparin as an alternative to VKA, a patient-level cost utility analysis was conducted from a Canadian perspective. Methods: Resource use data captured during the CLOT trial were extracted and linked to 2015 Canadian unit cost estimates. Health state utilities were then measured using the Time-Trade-Off technique in 24 randomly selected members of the general Canadian public to estimate the gains in quality-adjusted life years (QALYs. Results: For the entire CLOT trial population (n=676, the dalteparin group had significantly higher mean costs compared to the VKA group ($Can5,771 vs. $Can2,569; p<0.001. However, the utility assessment revealed that 21 of 24 respondents (88% selected dalteparin over VKA, with an associated gain of 0.14 (95% confidence interval [CI]: 0.10–0.18 QALYs. When the incremental cost of dalteparin was combined with the QALY gain, dalteparin had a cost of $Can23,100 (95% CI: $Can19,200

  10. Renal cell karcinoma trial

    International Nuclear Information System (INIS)

    Werf-Messing, B. van der; Heul, R.O. van der; Ledeboer, R.C.

    1981-01-01

    A total of 174 patients underwent simple nephrectomy in case of clinically operable kidney cancer without demonstrable metastases. Of these 85 received preoperative irradiation to the kidney and the regional lymph nodes (3000-4000 rad in 3-4 weeks). Prognosis was not influenced by preoperative irradiation. The preoperatively assessable prognostic criteria were sex and sedimentation rate: ESR >= 30 and being male worsened prognosis. The clinical T-categories of the UICC were not related to prognosis. Of the microscopic examination of the nephrectomy specimen, renal vein invasion and to a lesser extent a low degree of differentiation appeared to worsen prognosis. The prognostic influence of the P-categories was caused by a higher incidence of renal vein involvement in case of higher P-category. The most important prognostic factors - ESR, renal vein involvement, and sex - were not interrelated. Elective chemotherapy, radiation therapy, and hormone therapy could be considered in certain high-risk groups. (orig.)

  11. A Meta-analysis of Multiple Myeloma Risk Regions in African and European Ancestry Populations Identifies Putatively Functional Loci.

    Science.gov (United States)

    Rand, Kristin A; Song, Chi; Dean, Eric; Serie, Daniel J; Curtin, Karen; Sheng, Xin; Hu, Donglei; Huff, Carol Ann; Bernal-Mizrachi, Leon; Tomasson, Michael H; Ailawadhi, Sikander; Singhal, Seema; Pawlish, Karen; Peters, Edward S; Bock, Cathryn H; Stram, Alex; Van Den Berg, David J; Edlund, Christopher K; Conti, David V; Zimmerman, Todd; Hwang, Amie E; Huntsman, Scott; Graff, John; Nooka, Ajay; Kong, Yinfei; Pregja, Silvana L; Berndt, Sonja I; Blot, William J; Carpten, John; Casey, Graham; Chu, Lisa; Diver, W Ryan; Stevens, Victoria L; Lieber, Michael R; Goodman, Phyllis J; Hennis, Anselm J M; Hsing, Ann W; Mehta, Jayesh; Kittles, Rick A; Kolb, Suzanne; Klein, Eric A; Leske, Cristina; Murphy, Adam B; Nemesure, Barbara; Neslund-Dudas, Christine; Strom, Sara S; Vij, Ravi; Rybicki, Benjamin A; Stanford, Janet L; Signorello, Lisa B; Witte, John S; Ambrosone, Christine B; Bhatti, Parveen; John, Esther M; Bernstein, Leslie; Zheng, Wei; Olshan, Andrew F; Hu, Jennifer J; Ziegler, Regina G; Nyante, Sarah J; Bandera, Elisa V; Birmann, Brenda M; Ingles, Sue A; Press, Michael F; Atanackovic, Djordje; Glenn, Martha J; Cannon-Albright, Lisa A; Jones, Brandt; Tricot, Guido; Martin, Thomas G; Kumar, Shaji K; Wolf, Jeffrey L; Deming Halverson, Sandra L; Rothman, Nathaniel; Brooks-Wilson, Angela R; Rajkumar, S Vincent; Kolonel, Laurence N; Chanock, Stephen J; Slager, Susan L; Severson, Richard K; Janakiraman, Nalini; Terebelo, Howard R; Brown, Elizabeth E; De Roos, Anneclaire J; Mohrbacher, Ann F; Colditz, Graham A; Giles, Graham G; Spinelli, John J; Chiu, Brian C; Munshi, Nikhil C; Anderson, Kenneth C; Levy, Joan; Zonder, Jeffrey A; Orlowski, Robert Z; Lonial, Sagar; Camp, Nicola J; Vachon, Celine M; Ziv, Elad; Stram, Daniel O; Hazelett, Dennis J; Haiman, Christopher A; Cozen, Wendy

    2016-12-01

    Genome-wide association studies (GWAS) in European populations have identified genetic risk variants associated with multiple myeloma. We performed association testing of common variation in eight regions in 1,318 patients with multiple myeloma and 1,480 controls of European ancestry and 1,305 patients with multiple myeloma and 7,078 controls of African ancestry and conducted a meta-analysis to localize the signals, with epigenetic annotation used to predict functionality. We found that variants in 7p15.3, 17p11.2, 22q13.1 were statistically significantly (P ancestry and persons of European ancestry, and the variant in 3p22.1 was associated in European ancestry only. In a combined African ancestry-European ancestry meta-analysis, variation in five regions (2p23.3, 3p22.1, 7p15.3, 17p11.2, 22q13.1) was statistically significantly associated with multiple myeloma risk. In 3p22.1, the correlated variants clustered within the gene body of ULK4 Correlated variants in 7p15.3 clustered around an enhancer at the 3' end of the CDCA7L transcription termination site. A missense variant at 17p11.2 (rs34562254, Pro251Leu, OR, 1.32; P = 2.93 × 10 -7 ) in TNFRSF13B encodes a lymphocyte-specific protein in the TNF receptor family that interacts with the NF-κB pathway. SNPs correlated with the index signal in 22q13.1 cluster around the promoter and enhancer regions of CBX7 CONCLUSIONS: We found that reported multiple myeloma susceptibility regions contain risk variants important across populations, supporting the use of multiple racial/ethnic groups with different underlying genetic architecture to enhance the localization and identification of putatively functional alleles. A subset of reported risk loci for multiple myeloma has consistent effects across populations and is likely to be functional. Cancer Epidemiol Biomarkers Prev; 25(12); 1609-18. ©2016 AACR. ©2016 American Association for Cancer Research.

  12. A novel option for reducing free light chains in myeloma kidney: supra-hemodiafiltration with endogenous reinfusion (HFR).

    Science.gov (United States)

    Pasquali, Sonia; Iannuzzella, Francesco; Corradini, Mattia; Mattei, Silvia; Bovino, Achiropita; Stefani, Alfredo; Palladino, Giuseppe; Caiazzo, Marialuisa

    2015-04-01

    In myeloma cast nephropathy, fast reduction of serum free light chain (FLC) levels correlates with renal recovery. Recently, extracorporeal treatments using filters with a high-molecular weight cut-off have been successfully used for FLC removal. However, using these new filters, high cost and elevated albumin leakage are common drawbacks. We studied a new and cheaper therapeutic approach with adsorbent resins to evaluate its efficacy. We treated four patients, affected by dialysis-dependent acute kidney injury (AKI) due to biopsy proven de novo FLC myeloma cast nephropathy. Each patient underwent bortezomib chemotherapy and extracorporeal treatment with the supra-hemodiafiltration with endogenous reinfusion (HFR) technique (Supra-HFR, Bellco Mirandola, Modena, Italy). Supra-HFR is a kind of hemodiafiltration that utilizes separated convection, diffusion and adsorption. The sorbent cartridge has a high affinity for FLC (both κ and λ) but is able to re-infuse albumin, avoiding the need for albumin perfusions. Supra HFR treatments (4 h each) were carried out for eight consecutive days and then every other day. All patients showed a significant reduction of serum FLC, whereas serum albumin concentration remained unchanged. Renal function recovered in three out of four patients. FLC removal with adsorbent resins represents an effective therapeutic strategy that does not require replacement with albumin .

  13. Interferon-alpha in the treatment of multiple myeloma

    DEFF Research Database (Denmark)

    Khoo, T.L.; Joshua, D.; Gibson, J.

    2011-01-01

    Interferons are soluble proteins produced naturally by cells in response to viruses. It has both anti-proliferative and immunomodulating properties and is one of the first examples of a biological response modifier use to treat the hematological malignancy multiple myeloma. Interferon has been used......-induction agent with other chemotherapy regimens, and as maintenance therapy after conventional chemotherapy or complete remission after autologous or allogeneic transplantation. Interferon as a single induction agent or co-induction agent with other chemotherapy agents appears only to have minimal benefit...... in myeloma. Its role as maintenance therapy in the plateau phase of myeloma also remains uncertain. More recently, the use of interferon must now compete with the "new drugs" - thalidomide, lenalidomide and bortezomib in myeloma treatment. Will there be a future role of interferon in the treatment...

  14. Continuous lenalidomide treatment for newly diagnosed multiple myeloma

    DEFF Research Database (Denmark)

    Palumbo, Antonio; Hajek, Roman; Delforge, Michel

    2012-01-01

    Lenalidomide has tumoricidal and immunomodulatory activity against multiple myeloma. This double-blind, multicenter, randomized study compared melphalan-prednisone-lenalidomide induction followed by lenalidomide maintenance (MPR-R) with melphalan-prednisone-lenalidomide (MPR) or melphalan-prednis...

  15. Concomitant HIV infection in newly diagnosed multiple myeloma ...

    African Journals Online (AJOL)

    RESEARCH ... To compare the presenting features of HIV-positive patients diagnosed with MM ..... Especially since recent publications are showing trends of .... 18. Agrawal S, Deshpande A. A unique presentation of multiple myeloma in an ...

  16. Osteoprotegerin is bound, internalized, and degraded by multiple myeloma cells

    DEFF Research Database (Denmark)

    Standal, Therese; Seidel, Carina; Hjertner, Øyvind

    2002-01-01

    Multiple myeloma (MM) is a hematologic malignancy characterized by accumulation of plasma cells in the bone marrow (BM). Bone destruction is a complication of the disease and is usually associated with severe morbidity. The balance between receptor activator of nuclear factor-kappaB (NF-kappaB......) ligand and osteoprotegerin (OPG) is of major importance in bone homeostasis. We have recently shown that serum OPG levels are lower in patients with myeloma than in healthy individuals. Here we show that myeloma cells can bind, internalize, and degrade OPG, thereby providing a possible explanation...... for the lower levels of OPG in the BM of patients with MM. This process is dependent on interaction of OPG with heparan sulfates on the myeloma cells. The results suggest a novel biologic mechanism for the bone disease associated with MM and that treatment of the bone disease with OPG lacking the heparin...

  17. Recombinant alpha-interferon as salvage therapy in multiple myeloma

    African Journals Online (AJOL)

    1989-08-05

    Aug 5, 1989 ... Ten patients with end-stage multiple myeloma refractory to conventional chemotherapy and ... malities and relief of pain using local radiotherapy. However, .... therapy programmes. However, the role of this agent remains.

  18. A Pictorial Review on Extraosseous Manifestations of Multiple Myelomas

    International Nuclear Information System (INIS)

    Seo, Jung Min; Lee, Kyung Soo; Yi, Chin A; Kim, Seong Hyun; Park, Byung Kwan; Han, Boo Kyung; Kim, Hyung Jin

    2011-01-01

    Extraosseous involvement of multiple myelomas can be seen clinically or radiologically in approximately 10-20% of patients at the time of initial diagnosis and may develop in an additional 15% of patients over the course of the disease. The condition can arise in any tissue of the body and its presence has been associated with more aggressive disease, a guarded prognosis, or high-dose chemotherapy. Imaging findings of extraosseous multiple myelomas are diverse. They usually show high enhancement on contrast-medium enhanced CT scans, exhibit iso-signal intensity on both T1- and T2- weighted images, and variable 18F-fluorine deoxyglucose (FDG) uptake at PET. The disease may simulate an infectious condition since it may be concurrent with underlying multiple myelomas per se or it may occur during myeloma treatment including stem cell transplantation.

  19. Maxillary Swelling as the First Evidence of Multiple Myeloma

    Directory of Open Access Journals (Sweden)

    Atsushi Kasamatsu

    2015-01-01

    Full Text Available Multiple myeloma is a malignant neoplasm of plasma cells characterized by proliferation of a single clone of abnormal immunoglobulin-secreting plasma cells. Since the amount of hemopoietic bone marrow is decreased in the maxilla, oral manifestations of multiple myeloma are less common in the maxilla than in the mandible. We report the case of 33-year-old Japanese man who presented with a mass in the right maxillary alveolar region. Computed tomography and magnetic resonance images showed a soft tissue mass in the right maxilla eroding the anterior and lateral walls of the maxillary sinus and extending into the buccal space. The biopsy results, imaging, and laboratory investigations led to the diagnosis of multiple myeloma. This case report suggests that oral surgeons and dentists should properly address oral manifestations as first indications of multiple myeloma.

  20. Maxillary Swelling as the First Evidence of Multiple Myeloma

    Science.gov (United States)

    Kasamatsu, Atsushi; Kimura, Yasushi; Tsujimura, Hideki; Kanazawa, Harusachi; Koide, Nao; Miyamoto, Isao; Endo-Sakamoto, Yosuke; Shiiba, Masashi; Tanzawa, Hideki; Uzawa, Katsuhiro

    2015-01-01

    Multiple myeloma is a malignant neoplasm of plasma cells characterized by proliferation of a single clone of abnormal immunoglobulin-secreting plasma cells. Since the amount of hemopoietic bone marrow is decreased in the maxilla, oral manifestations of multiple myeloma are less common in the maxilla than in the mandible. We report the case of 33-year-old Japanese man who presented with a mass in the right maxillary alveolar region. Computed tomography and magnetic resonance images showed a soft tissue mass in the right maxilla eroding the anterior and lateral walls of the maxillary sinus and extending into the buccal space. The biopsy results, imaging, and laboratory investigations led to the diagnosis of multiple myeloma. This case report suggests that oral surgeons and dentists should properly address oral manifestations as first indications of multiple myeloma. PMID:26640721