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https://www.readbyqxmd.com/read/28424409/clinical-genomic-profiling-to-identify-actionable-alterations-for-investigational-therapies-in-patients-with-diverse-sarcomas
#1
Roman Groisberg, David S Hong, Vijaykumar Holla, Filip Janku, Sarina Piha-Paul, Vinod Ravi, Robert Benjamin, Shreyas Kumar Patel, Neeta Somaiah, Anthony Conley, Siraj M Ali, Alexa B Schrock, Jeffrey S Ross, Philip J Stephens, Vincent A Miller, Shiraj Sen, Cynthia Herzog, Funda Meric-Bernstam, Vivek Subbiah
BACKGROUND: There are currently no United States Food and Drug Administration approved molecularly matched therapies for sarcomas except gastrointestinal stromal tumors. Complicating this is the extreme diversity, heterogeneity, and rarity of these neoplasms. Few therapeutic options exist for relapsed and refractory sarcomas. In clinical practice many oncologists refer patients for genomic profiling hoping for guidance on treatment options after standard therapy. However, a systematic analysis of actionable mutations has yet to be completed...
April 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423517/next-generation-sequencing-of-extraskeletal-myxoid-chondrosarcoma
#2
Elizabeth J Davis, Yi-Mi Wu, Dan Robinson, Scott M Schuetze, Laurence H Baker, Jyoti Athanikar, Xuhong Cao, Lakshmi P Kunju, Arul M Chinnaiyan, Rashmi Chugh
Extraskeletal myxoid chondrosarcoma (EMC) is an indolent translocation-associated soft tissue sarcoma with a high propensity for metastases. Using a clinical sequencing approach, we genomically profiled patients with metastatic EMC to elucidate the molecular biology and identify potentially actionable mutations. We also evaluated potential predictive factors of benefit to sunitinib, a multi-targeted tyrosine kinase inhibitor with reported activity in a subset of EMC patients. Between January 31, 2012 and April 15, 2016, six patients with EMC participated in the clinical sequencing research study...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28405501/pdl1-expression-is-a-poor-prognosis-factor-in-soft-tissue-sarcomas
#3
François Bertucci, Pascal Finetti, Delphine Perrot, Agnès Leroux, Françoise Collin, Axel Le Cesne, Jean-Michel Coindre, Jean-Yves Blay, Daniel Birnbaum, Emilie Mamessier
Soft-tissue sarcomas (STS) are a group of rare, heterogeneous, and aggressive tumors, with high metastatic risk and relatively few efficient systemic therapies. In the quest for new treatments, the immune system represents an attractive therapeutic target. Recently, PD1/PDL1 inhibitors showed very promising results in patients with solid tumors. PDL1 expression has been rarely studied in STS, in small series only, by using immunohistochemistry (IHC), and with non-concordant prognostic implications. Here, we have analyzed PDL1 mRNA expression in 758 clinical STS samples retrospectively profiled using DNA microarrays and RNAseq, and searched for correlations with clinicopathological variables including metastasis-free survival (MFS) after surgery...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28404975/mdm2-antagonists-synergize-with-pi3k-mtor-inhibition-in-well-differentiated-dedifferentiated-liposarcomas
#4
Audrey Laroche, Vanessa Chaire, Marie-Paule Algeo, Marie Karanian, Benjamin Fourneaux, Antoine Italiano
BACKGROUND: Well-differentiated/dedifferentiated liposarcoma (WDLPS/DDLPS) are characterized by a consistent amplification of the MDM2 gene. The PI3K/AKT/mTOR pathway has been suggested to play also an important role in their tumorigenesis. Our goal was to determine whether combined MDM2 and PI3K/AKT/mTOR targeting is associated with higher anti-tumor activity than single agent alone in preclinical models of WDLPS/DDLPS. METHODS: WDLPS/DDLPS cells were exposed to RG7388 (MDM2 antagonist) and BEZ235 (PI3K/mTOR dual inhibitor) after which apoptosis and signaling/survival pathway perturbations were monitored by flow cytometry and Western blot analysis...
March 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28399901/activity-of-trabectedin-and-the-parp-inhibitor-rucaparib-in-soft-tissue-sarcomas
#5
Audrey Laroche, Vanessa Chaire, François Le Loarer, Marie-Paule Algéo, Christophe Rey, Kevin Tran, Carlo Lucchesi, Antoine Italiano
BACKGROUND: Trabectedin has recently been approved in the USA and in Europe for advanced soft-tissue sarcoma patients who have been treated with anthracycline-based chemotherapy without success. The mechanism of action of trabectedin depends on the status of both the nucleotide excision repair (NER) and homologous recombination (HR) DNA repair pathways. Trabectedin results in DNA double-strand breaks. We hypothesized that PARP-1 inhibition is able to perpetuate trabectedin-induced DNA damage...
April 11, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28386735/-erratum-to-isolated-limb-perfusion-for-liposarcoma-histopathological-response-and-subgroup-analysis-after-tnf-melphalan-based-ilp
#6
L E Podleska, B Schwindenhammer, F Grabellus, S Bauer, H-U Steinau, G Taeger
No abstract text is available yet for this article.
April 6, 2017: Der Chirurg; Zeitschrift Für Alle Gebiete der Operativen Medizen
https://www.readbyqxmd.com/read/28381318/well-differentiated-liposarcoma-in-a-bonnet-macaque-macaca-radiata
#7
Cynthia J Doane, Paula J Johnson, David G Besselsen
Here we describe the occurrence of a subcutaneous liposarcoma in a geriatric bonnet macaque (Macaca radiata). Clinical presentation was a rapidly growing, ulcerated, subcutaneous mass in the umbilical region of a 28-y-old intact female macaque. The mass was successfully removed through excisional biopsy, and histopathology provided a morphologic diagnosis of well-differentiated liposarcoma. The macaque recovered without complication and displayed no signs of recurrence for at least 18 mo after excision. To our knowledge, this case represents the first report of liposarcoma in a bonnet macaque...
March 1, 2017: Comparative Medicine
https://www.readbyqxmd.com/read/28377828/paravertebral-well-differentiated-liposarcoma-with-low-grade-osteosarcomatous-component-case-report-with-11-year-follow-up-radiological-pathological-and-genetic-data-and-literature-review
#8
Nicolas Macagno, Stéphane Fuentes, Gonzague de Pinieux, André Maues de Paula, Sébastien Salas, Jean-Camille Mattéi, Charlotte Dupuis, Romain Appay, Alain Aurias, Henry Dufour, Dominique Figarella-Branger, Corinne Bouvier
Despite being one of the most frequent soft-tissue sarcomas, well-differentiated liposarcoma has never been reported near the spine. The authors present the case of a 67-year-old man with progressive history of back pain. Physical examination revealed a mass located within the right paravertebral muscles. MR and CT imaging showed a heavily ossified central mass surrounded by a peripheral fatty component. No connection with the underlying bone was detected on imagery and during surgery. After surgical resection, histopathological examination revealed a tumor harboring combined features of well-differentiated liposarcoma and low-grade osteosarcoma...
2017: Case Reports in Pathology
https://www.readbyqxmd.com/read/28362929/metastatic-liposarcoma-of-the-skull-base-a-case-report-and-review-of-literature
#9
Nirmeen Zagzoog, Greta Ra, Alex Koziarz, John Provias, Doron Sommer, Saleh A Almenawer, Kesava Reddy
BACKGROUND AND IMPORTANCE: Myxoid liposarcoma is not an uncommon form of sarcoma. However, it usually affects the lower extremity long bones. Scapular involvement is extremely rare, as is a metastasis to the parasellar region. We present a case of liposarcoma of the skull base originating in the scapular region and metastasizing to the sellar and parasellar regions and provide a review of the pertinent literature. CLINICAL PRESENTATION: A 43-year-old female patient diagnosed with left scapular myxoid liposarcoma was treated with surgical resection...
April 1, 2017: Neurosurgery
https://www.readbyqxmd.com/read/28361070/primary-psoas-sarcoma-causing-malignant-psoas-syndrome-favourable-response-to-radiotherapy
#10
Thomas A McKay, Sarah Bishop, Michael J McKay
Malignant psoas syndrome (MPS) is an uncommon condition first described by Stevens et al. MPS is caused by malignant infiltration of the psoas muscle and adjacent nerves and is characterised by (fixed) flexion deformity of the ipsilateral hip and proximal lumbosacral plexopathy. It has previously been described in relation to metastatic carcinoma, melanoma and liposarcoma, as well as non-Hodgkins lymphoma. We present the case of a 68-year-old woman with a sarcoma arising in the left psoas muscle at the level of L4 who presented with symptoms of MPS...
March 2017: Annals of Translational Medicine
https://www.readbyqxmd.com/read/28359489/palpitations-and-a-left-ventricular-mass-an-odd-presentation-of-left-dominant-arrhythmogenic-cardiomyopathy
#11
Sandor Toledo, Elizabeth Grigoryan, Jacobo Kirsch, Edward B Savage
A 20-year-old woman presented with palpitations. Echocardiography demonstrated a left ventricular mass involving the posterolateral apical wall and protruding into the ventricular cavity. Evaluation with magnetic resonance imaging (MRI) suggested fatty consistency with all edges well defined except the medial, which was ill defined, raising concern for an invasive liposarcoma. Open core needle biopsy demonstrated mature adipocytes infiltrating the myocardium with extensive interstitial fibrosis. The diagnosis was left-dominant arrhythmogenic cardiomyopathy...
April 2017: Annals of Thoracic Surgery
https://www.readbyqxmd.com/read/28355977/three-patients-with-lower-extremity-tumors-referred-through-medical-channels-to-physical-therapists-a-description-of-clinical-reasoning-screening-and-collaborative-practice
#12
Seth Peterson, Thomas Denninger, Scott Porter
Study Design Resident's case problem. Background Although rare in the general population, bone and soft tissue tumors may be more frequently encountered in patients seeking physical therapy because of the propensity to mimic commonly treated musculoskeletal disorders. Screening for tumors requires the physical therapist be attentive to unexpected findings. The purpose of this paper was to describe the clinical reasoning and screening processes of physical therapists that facilitated the timely recognition of bone and soft tumors in 3 patients referred through medical channels...
March 29, 2017: Journal of Orthopaedic and Sports Physical Therapy
https://www.readbyqxmd.com/read/28352488/rare-case-of-a-well-differentiated-paratesticular-sarcoma-of-the-spermatic-cord-in-a-60-year-old-patient
#13
Marwen Benna, Semia Zarraâ, Asma Belaïd, Aziz Cherif, Lotfi Kochbati, Mohammed Chebil, Farouk Benna
Introduction. Liposarcomas are tumors that occur mostly in the retroperitoneum. Of all liposarcomas only 3 to 7% are found in the paratesticular region. The spermatic cord is the main site of origin in these cases. The patients ages range from 50 to 60 years. This malignant disease can result in a loss of fertility aside from life-threatening sequelae. Case. We present a case of a liposarcoma of the paratesticular region. A 60-year-old man was referred with a painless mass in the scrotum and the right inguinal region...
2017: Case Reports in Urology
https://www.readbyqxmd.com/read/28337832/retroperitoneal-dedifferentiated-liposarcoma-with-huge-cystic-degeneration-a-case-report
#14
Kazuyoshi Uchihashi, Atsuji Matsuyama, Eisuke Shiba, Yoshizo Kimura, Toshiro Ogata, Kei Yabuki, Hiroshi Harada, Chisachi Kubo, Yojiro Tsuda, Mao Jotatsu, Masanori Hisaoka
Prominent cyst formation is an unusual feature of liposarcoma. We report here a case of dedifferentiated liposarcoma with huge cystic change without preoperative chemo- or radiation therapy. The lesion arose in the retroperitoneum juxtaposed to the right kidney of a 67-year-old woman. She underwent a surgical removal of the retroperitoneal cyst. The cystic tumor contained 1600 mL of old bloody fluid, and its wall was composed of edematous, inflamed or sclerosing fibrous tissue with fatty tissue containing abundant atypical stromal cells, which were immunohistochemically positive for MDM2 and CDK4, and demonstrated MDM2 gene amplification by fluorescence in situ hybridization...
March 23, 2017: Pathology International
https://www.readbyqxmd.com/read/28331547/application-of-high-resolution-genomic-profiling-in-the-differential-diagnosis-of-liposarcoma
#15
Magdalena Koczkowska, Beata Stefania Lipska-Ziętkiewicz, Mariola Iliszko, Janusz Ryś, Markku Miettinen, Jerzy Lasota, Wojciech Biernat, Agnieszka Harazin-Lechowska, Anna Kruczak, Janusz Limon
BACKGROUND: Rarity and heterogeneity of liposarcomas (LPS) make their diagnosis difficult even for sarcoma-experts pathologists. The molecular mechanism underlying the development and progression of liposarcomas (LPS) remains only partially known. In order to identify and compare the genomic profiles, we analyzed array-based comparative genomic hybridization (array-CGH) profiles of 66 liposarcomas, including well-differentiated (WDLPS), dedifferentiated (DDLPS) and myxoid (MLPS) subtypes...
2017: Molecular Cytogenetics
https://www.readbyqxmd.com/read/28324749/a-phase-i-study-of-sar405838-a-novel-human-double-minute-2-hdm2-antagonist-in-patients-with-solid-tumours
#16
Maja de Jonge, Vincent A de Weger, Mark A Dickson, Marlies Langenberg, Axel Le Cesne, Andrew J Wagner, Karl Hsu, Wei Zheng, Sandrine Macé, Gilles Tuffal, Koruth Thomas, Jan H M Schellens
PURPOSE: In tumours with wild-type TP53, the tumour-suppressive function of p53 is frequently inhibited by HDM2. This phase I, dose-escalating study investigated the maximum tolerated dose (MTD), safety, pharmacokinetics and pharmacodynamics of SAR405838, an HDM2 inhibitor, in patients with advanced solid tumours (NCT01636479). METHODS: In dose escalation, patients with any locally advanced/metastatic solid tumour with TP53 mutation prevalence below 40%, or documented as TP53 wild-type, were eligible...
March 16, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28322185/well-differentiated-liposarcoma-in-a-bonnet-macaque-macaca-radiata
#17
Cynthia J Doane Paula J Johnson And David G Besselsen
Here we describe the occurrence of a subcutaneous liposarcoma in a geriatric bonnet macaque (Macaca radiata). Clinicalpresentation was a rapidly growing, ulcerated, subcutaneous mass in the umbilical region of a 28-y-old intact female macaque. The mass was successfully removed through excisional biopsy, and histopathology provided a morphologic diagnosis of well-differentiated liposarcoma. The macaque recovered without complication and displayed no signs of recurrence for at least 18 mo after excision. To our knowledge, this case represents the first report of liposarcoma in a bonnet macaque...
March 20, 2017: Comparative Medicine
https://www.readbyqxmd.com/read/28300575/correlation-of-histological-grade-of-dedifferentiation-with-clinical-outcome-in-55-patients-with-dedifferentiated-liposarcomas
#18
Kossivi Dantey, Karen Schoedel, Oleksandr Yergiyev, David Bartlett, Uma N M Rao
In this study the histologic grade of dedifferentiated liposarcomas was correlated with outcome in surgically resected specimens in 55 patients over a 19-year period at the University of Pittsburgh Medical Center. The tumors were located in the retroperitoneum (N=34); the extremities and thigh (N=16), and the remainder involved the spermatic cord and head and neck. Most tumors were large (mean=21 cm.) Follow up was available in all 55 patients (median=36months). Forty-one tumors classified as high-grade dedifferentiated liposarcoma (HG-DDLPS) had mitotically active pleomorphic and spindle cells and foci of necrosis...
March 11, 2017: Human Pathology
https://www.readbyqxmd.com/read/28298998/condylar-intramedullary-intraosseous-lipoma-contribution-of-a-new-case-and-review-of-the-literature
#19
Alba Sanjuan, Alicia Dean, Blas Garcia, Francisco Alamillos, Elisa Roldan, Antonio Blanco
BACKGROUND: Lipoma is the most common benign tumour of the human body, being intraosseous involvement very rare. Just 1 to 4% of all cases of lipoma are located in the oral cavity, only 0.1% being intraosseous. The jaw is its most uncommon bone location. Etiology of intraosseous lipoma (IOL) is unknown, although several theories have been proposed. Usually asymptomatic, the symptoms, when present, will depend on its location and size. Its origin may be intraosseous or juxtacortical. A biopsy is essential for diagnosis, and definitive treatment involves resection or curettage of the lesion...
March 2017: Journal of Clinical and Experimental Dentistry
https://www.readbyqxmd.com/read/28291056/perspectives-on-low-grade-sarcomas-the-extraordinary-contributions-of-sharon-w-weiss-md
#20
Hope Hastings, John R Goldblum
Soft-tissue pathology encompasses a wide spectrum of neoplasms that represent some of the most challenging and problematic tumors in surgical pathology. Owing to the intensive work of dedicated pathologists, this once esoteric field has become increasingly well defined. In this review, Dr Sharon Weiss' monumental contributions to low-grade sarcomas, including low-grade fibromyxoid sarcoma/so-called hyalinizing spindle cell tumor, atypical lipomatous tumor/well-differentiated liposarcoma and dedifferentiated liposarcoma, epithelioid hemangioendothelioma, and dermatofibrosarcoma protuberans with fibrosarcomatous transformation will be discussed...
March 13, 2017: Advances in Anatomic Pathology
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