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European Journal of Nuclear Medicine... Sep 2022Fibroblast activation protein (FAP) is a membrane-bound protease that has limited expression in normal adult tissues but is highly expressed in the tumor...
PURPOSE
Fibroblast activation protein (FAP) is a membrane-bound protease that has limited expression in normal adult tissues but is highly expressed in the tumor microenvironment of many solid cancers. FAP-2286 is a FAP-binding peptide coupled to a radionuclide chelator that is currently being investigated in patients as an imaging and therapeutic agent. The potency, selectivity, and efficacy of FAP-2286 were evaluated in preclinical studies.
METHODS
FAP expression analysis was performed by immunohistochemistry and autoradiography on primary human cancer specimens. FAP-2286 was assessed in biochemical and cellular assays and in in vivo imaging and efficacy studies, and was further evaluated against FAPI-46, a small molecule-based FAP-targeting agent.
RESULTS
Immunohistochemistry confirmed elevated levels of FAP expression in multiple tumor types including pancreatic, breast, and sarcoma, which correlated with FAP binding by FAP-2286 autoradiography. FAP-2286 and its metal complexes demonstrated high affinity to FAP recombinant protein and cell surface FAP expressed on fibroblasts. Biodistribution studies in mice showed rapid and persistent uptake of Ga-FAP-2286, In-FAP-2286, and Lu-FAP-2286 in FAP-positive tumors, with renal clearance and minimal uptake in normal tissues. Lu-FAP-2286 exhibited antitumor activity in FAP-expressing HEK293 tumors and sarcoma patient-derived xenografts, with no significant weight loss. In addition, FAP-2286 maintained longer tumor retention and suppression in comparison to FAPI-46.
CONCLUSION
In preclinical models, radiolabeled FAP-2286 demonstrated high tumor uptake and retention, as well as potent efficacy in FAP-positive tumors. These results support clinical development of Ga-FAP-2286 for imaging and Lu-FAP-2286 for therapeutic use in a broad spectrum of FAP-positive tumors.
Topics: Adult; Animals; Cell Line, Tumor; Fibroblasts; Gallium Radioisotopes; HEK293 Cells; Humans; Mice; Radionuclide Imaging; Sarcoma; Tissue Distribution; Tumor Microenvironment
PubMed: 35608703
DOI: 10.1007/s00259-022-05842-5 -
Journal of Veterinary Internal Medicine 2006Primary renal tumors are diagnosed uncommonly in dogs.
BACKGROUND
Primary renal tumors are diagnosed uncommonly in dogs.
HYPOTHESIS
Signs and survival will differ among different categories of primary renal tumors.
ANIMALS
Data were collected from the medical records of 82 dogs with primary renal tumors diagnosed by examination of tissue obtained by ultrasound-guided biopsy, needle aspiration, surgery, or at postmortem examination.
METHODS
This was a multi-institutional, retrospective study.
RESULTS
Forty-nine dogs had carcinomas, 28 had sarcomas, and 5 had nephroblastomas. The dogs were geriatric (mean 8.1 years; range: 1-17) with a weight of 24.9 kg (range: 4.5-80). Tumors occurred with equal frequency in each kidney with 4% occurring bilaterally. Initial signs included one or more of hematuria, inappetance, lethargy. weight loss, or a palpable abdominal mass. Pain was reported more frequently in dogs with sarcomas (5/28). The most common hematologic abnormalities were neutrophilia (22/63), anemia (21/64), and thrombocytopenia (6/68). Polycythemia was present in 3 dogs and resolved with treatment. Hematuria (28/49), pyuria (26/49), proteinuria (24/50), and isosthenuria (20/56) were the most frequently observed abnormalities on urinalysis. Pulmonary metastases were noted on thoracic radiographs in 16% of dogs at diagnosis. Seventy-seven percent of dogs had metastatic disease at the time of death. Median survival for dogs with carcinomas was 16 months (range 0-59 months), for dogs with sarcomas 9 months (range 0-70 months), and for dogs with nephroblastomas 6 months (range 0-6 months).
CONCLUSIONS AND CLINICAL IMPORTANCE
Primary renal tumors in dogs are generally highly malignant with surgery being the only treatment that improves survival.
Topics: Animals; Carcinoma; Dog Diseases; Dogs; Female; Kidney Neoplasms; Male; Retrospective Studies; Sarcoma; Statistics, Nonparametric; Survival Analysis; Wilms Tumor
PubMed: 17063709
DOI: 10.1892/0891-6640(2006)20[1155:prnod]2.0.co;2 -
Molecular Cancer Aug 2023Traditional radiotherapy and chemotherapy have been intensively studied for their role in the treatment of tumours. However, these therapies often cause side effects for...
BACKGROUND
Traditional radiotherapy and chemotherapy have been intensively studied for their role in the treatment of tumours. However, these therapies often cause side effects for patients, which calls for the development of novel treatment options for tumours. B-cell lymphoma-2 (Bcl-2)/adenovirus E1B 19 kDa-interacting protein 3 (BNIP3) reportedly apoptosis-inducing effects in tumour cells and is associated with the progression and treatment of multiple tumours. Nevertheless, little is known about its potential role in tumour diagnosis and targeted therapy.
FINDINGS
The results of the study demonstrated that the interaction of BNIP3 with HDAC1 may affect the progression of breast invasive cancer (BRCA), sarcoma (SARC), kidney renal clear cell carcinoma (KIRC), and low-grade glioma (LGG). BNIP3 seemed to exert its effects in BRCA and SARC primarily through gene silencing and integrator complex, and in KIRC and LGG, mainly by affecting olfactory function, suggesting that targeted therapy can be developed based on the above signalling pathway and downstream molecules.
INTERPRETATION
BNIP3 has emerged as a promising therapeutic and diagnostic target for BRCA, SARC, KIRC, and LGG, providing new insights into tumour molecular therapies in the clinic.
Topics: Humans; Female; Prognosis; Biomarkers; Sarcoma; Breast Neoplasms; Glioma; Carcinoma, Renal Cell; Kidney Neoplasms; Membrane Proteins; Proto-Oncogene Proteins
PubMed: 37649051
DOI: 10.1186/s12943-023-01808-9 -
European Radiology Feb 2022To assess imaging features of primary renal sarcomas in order to better discriminate them from non-sarcoma renal tumors.
OBJECTIVES
To assess imaging features of primary renal sarcomas in order to better discriminate them from non-sarcoma renal tumors.
METHODS
Adult patients diagnosed with renal sarcomas from 1995 to 2018 were included from 11 European tertiary referral centers (Germany, Belgium, Turkey). Renal sarcomas were 1:4 compared to patients with non-sarcoma renal tumors. CT/MRI findings were assessed using 21 predefined imaging features. A random forest model was trained to predict "renal sarcoma vs. non-sarcoma renal tumors" based on demographics and imaging features.
RESULTS
n = 34 renal sarcomas were included and compared to n = 136 non-sarcoma renal tumors. Renal sarcomas manifested in younger patients (median 55 vs. 67 years, p < 0.01) and were more complex (high RENAL score complexity 79.4% vs. 25.7%, p < 0.01). Renal sarcomas were larger (median diameter 108 vs. 43 mm, p < 0.01) with irregular shape and ill-defined margins, and more frequently demonstrated invasion of the renal vein or inferior vena cava, tumor necrosis, direct invasion of adjacent organs, and contact to renal artery or vein, compared to non-sarcoma renal tumors (p < 0.05, each). The random forest algorithm yielded a median AUC = 93.8% to predict renal sarcoma histology, with sensitivity, specificity, and positive predictive value of 90.4%, 76.5%, and 93.9%, respectively. Tumor diameter and RENAL score were the most relevant imaging features for renal sarcoma identification.
CONCLUSION
Renal sarcomas are rare tumors commonly manifesting as large masses in young patients. A random forest model using demographics and imaging features shows good diagnostic accuracy for discrimination of renal sarcomas from non-sarcoma renal tumors, which might aid in clinical decision-making.
KEY POINTS
• Renal sarcomas commonly manifest in younger patients as large, complex renal masses. • Compared to non-sarcoma renal tumors, renal sarcomas more frequently demonstrated invasion of the renal vein or inferior vena cava, tumor necrosis, direct invasion of adjacent organs, and contact to renal artery or vein. • Using demographics and standardized imaging features, a random forest showed excellent diagnostic performance for discrimination of sarcoma vs. non-sarcoma renal tumors (AUC = 93.8%, sensitivity = 90.4%, specificity = 76.5%, and PPV = 93.9%).
Topics: Adult; Humans; Kidney Neoplasms; Magnetic Resonance Imaging; Sarcoma; Soft Tissue Neoplasms; Vena Cava, Inferior
PubMed: 34331576
DOI: 10.1007/s00330-021-08201-4 -
BMJ Case Reports Jul 2018An older male patient with a history of tachycardia treated with atenolol presented to an outside hospital on 22 February 2017 with acute right flank pain. He had a CT...
An older male patient with a history of tachycardia treated with atenolol presented to an outside hospital on 22 February 2017 with acute right flank pain. He had a CT scan which revealed a large right renal mass with acute haemorrhage. He was initially managed with interventional radiology guided embolism on 25 February 2017 due to the ongoing bleeding and haemodynamic instability. He was then transferred to our institution. He underwent right radical nephrectomy on 13 March 2017. His pathology revealed a 12.5×6×4.5 cm mass consistent with angiosarcoma of the right kidney with negative margins. Final pathology was pT2b with extension of the mass into the renal vein and perirenal adipose tissue. He was discharged soon after surgery. He was recommended to undergo adjuvant chemotherapy.
Topics: Aged; Chemotherapy, Adjuvant; Fatal Outcome; Flank Pain; Hemangiosarcoma; Humans; Image-Guided Biopsy; Kidney Neoplasms; Male; Nephrectomy; Renal Veins
PubMed: 30061122
DOI: 10.1136/bcr-2017-222672 -
Annals of Oncology : Official Journal... Sep 2013Renal Ewing's sarcoma/primitive neuroectodermal tumor (ES/PNET) is extremely rare. Clinical symptoms are nonspecific presenting abdominal pain, palpable mass, and...
BACKGROUND
Renal Ewing's sarcoma/primitive neuroectodermal tumor (ES/PNET) is extremely rare. Clinical symptoms are nonspecific presenting abdominal pain, palpable mass, and hematuria. Owing to advanced technology demonstrating the ES-specific EWS/ETS translocation, this differential diagnosis has become feasible.
PATIENTS AND METHODS
The German database of GPOH Ewing's sarcoma trials from 1980 to 2009 was searched for kidney as primary site. Twenty-four patients were identified and analyzed. The median time of observation was 3.71 years (range 0.27-8.75 years). Additionally, we carried out a Medline search for renal ES/PNET.
RESULTS
The median age was 24.9 years (range 11-60 years). In 37.5%, patients presented with primary metastases. Tumor thrombi in the adjacent renal vessels occurred in 56.2%. In 90.9%, rearrangements of t(11;22) were found. All patients received a combined chemotherapy according to the EURO-E.W.I.N.G.99 protocol. In accordance, local control consisted predominantly of combined modality surgery and radiation (47%). At 3 years, overall survival (OS) was 0.80 (SE = 0.09), and event-free survival (EFS) 0.66 (SE = 0.11).
CONCLUSIONS
ES/PNET should be considered in the differential diagnosis of renal tumors. Patients with renal ES/PNET respond to and benefit from conventional ES treatment according to ES study protocols. Therefore, an accurate diagnostic approach and a guideline-adapted therapy should be facilitated.
Topics: Adolescent; Adult; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Child; Clinical Trials as Topic; Combined Modality Therapy; Disease-Free Survival; Female; Humans; Kidney; Kidney Neoplasms; Male; Middle Aged; Neoplasm Metastasis; Neuroectodermal Tumors, Primitive; Sarcoma, Ewing; Survival; Young Adult
PubMed: 23761687
DOI: 10.1093/annonc/mdt215 -
Archives of Pathology & Laboratory... Jan 2020Clear cell sarcoma of the kidney is an uncommon malignant pediatric renal neoplasm that typically presents in the 2- to 3-year age group and has a propensity for... (Review)
Review
Clear cell sarcoma of the kidney is an uncommon malignant pediatric renal neoplasm that typically presents in the 2- to 3-year age group and has a propensity for aggressive behavior and late relapses. Histologically, this tumor exhibits a great diversity of morphologic patterns that can mimic most other pediatric renal neoplasms, often leading to confusion and misdiagnosis. Until recently, adjunct immunohistochemical and molecular genetic tests to support the diagnosis were lacking. The presence of internal tandem duplications in BCL-6 coreceptor () and a translocation t(10;17) creating the fusion gene have now been well accepted. Immunohistochemistry for BCOR has also been shown to be a sensitive and specific marker for clear cell sarcoma of the kidney in the context of pediatric renal tumors. Improved intensive chemotherapy regimens have influenced the clinical course of the disease, with late relapses now being less frequent and the brain having overtaken bone as the most common site of relapse.
Topics: Biomarkers, Tumor; Humans; Kidney Neoplasms; Sarcoma, Clear Cell
PubMed: 30917048
DOI: 10.5858/arpa.2018-0353-RS -
Archives of Pathology & Laboratory... Aug 2019Clear cell sarcoma of the kidney is the second most common primary renal malignancy in childhood. It is histologically diverse, making accurate diagnosis challenging in... (Review)
Review
Clear cell sarcoma of the kidney is the second most common primary renal malignancy in childhood. It is histologically diverse, making accurate diagnosis challenging in some cases. Recent molecular studies have uncovered exon 15 internal tandem duplications in most cases, and fusion in a few cases, with the remaining cases having other genetic mutations, including fusion and mutations. Although clear cell sarcoma of the kidney has no specific immunophenotype, several markers including cyclin D1, nerve growth factor receptor, and BCOR (BCL6 corepressor) have emerged as potential diagnostic aides. This review provides a concise account of recent advances in our understanding of clear cell sarcoma of the kidney to serve as a practical update for the practicing pathologist.
Topics: Biomarkers, Tumor; Child; Cyclin B; Diagnosis, Differential; Humans; Kidney; Kidney Neoplasms; Mutation; Proto-Oncogene Proteins; Repressor Proteins; Sarcoma, Clear Cell
PubMed: 30628851
DOI: 10.5858/arpa.2018-0045-RS -
Journal of Cardiovascular Pharmacology... Sep 2018Pazopanib is an approved treatment for renal cell carcinoma and a second-line treatment for nonadipocytic soft-tissue sarcoma. However, its clinical efficacy is limited... (Review)
Review
Pazopanib is an approved treatment for renal cell carcinoma and a second-line treatment for nonadipocytic soft-tissue sarcoma. However, its clinical efficacy is limited by its cardiovascular side effects. Pazopanib and other vascular endothelial growth factor receptor tyrosine kinase inhibitors have been associated with the development of hypertension, QT interval prolongation, and other cardiovascular events; however, these mechanisms are largely unknown. Gaining a deeper understanding of these mechanisms is essential for the development of appropriate surveillance strategies and possible diagnostic biomarkers to allow us to monitor patients and modulate therapy prior to significant cardiac insult. This approach will be vital in keeping patients on these life-saving therapies and may be applicable to other tyrosine kinase inhibitors as well. In this review, we provide a comprehensive overview of the preclinical and clinical side effects of pazopanib with a focus on the mechanisms responsible for its toxicity to the cardiovascular system.
Topics: Angiogenesis Inhibitors; Animals; Carcinoma, Renal Cell; Cardiovascular Diseases; Cardiovascular System; Humans; Indazoles; Kidney Neoplasms; Pyrimidines; Risk Assessment; Risk Factors; Sarcoma; Soft Tissue Neoplasms; Sulfonamides; Treatment Outcome
PubMed: 29706106
DOI: 10.1177/1074248418769612 -
Annals of the Royal College of Surgeons... May 2011The retroperitoneum can host a wide spectrum of pathologies, including a variety of rare benign tumours and malignant neoplasms that can be either primary or metastatic... (Review)
Review
INTRODUCTION
The retroperitoneum can host a wide spectrum of pathologies, including a variety of rare benign tumours and malignant neoplasms that can be either primary or metastatic lesions. Retroperitoneal tumours can cause a diagnostic dilemma and present several therapeutic challenges because of their rarity, relative late presentation and anatomical location, often in close relationship with several vital structures in the retroperitoneal space.
MATERIALS AND METHODS
A comprehensive literature search was conducted using PubMed. Relevant international articles published in the last ten years were assessed. The keywords for search purposes included: retroperitoneum, benign, sarcoma, neoplasm, diagnosis and surgery, radiotherapy, chemotherapy. The search was limited to articles published in English. All articles were read in full by the authors and selected for inclusion based on relevance to this article.
RESULTS
Tumours usually present late and cause symptoms or become palpable once they have reached a significant size. Retroperitoneal tumours are best evaluated with good quality cross-sectional imaging and preoperative histology by core needle biopsy is required when imaging is non-diagnostic. Sarcomas comprise a third of retroperitoneal tumours. Other retroperitoneal neoplasms include lymphomas and epithelial tumours or might represent metastatic disease from known or unknown primary sites. The most common benign pathologies encountered in the retroperitoneum include benign neurogenic tumours, paragangliomas, fibromatosis, renal angiomyolipomas and benign retroperitoneal lipomas.
CONCLUSIONS
Complete surgical resection is the only potential curative treatment modality for retroperitoneal sarcomas and is best performed in high-volume centres by a multidisciplinary sarcoma team. The ability completely to resect a retroperitoneal sarcoma and tumour grade remain the most important predictors of local recurrence and disease-specific survival.
Topics: Chemotherapy, Adjuvant; Humans; Neoplasm Recurrence, Local; Retroperitoneal Neoplasms; Sarcoma; Tomography, X-Ray Computed; Treatment Outcome
PubMed: 21944791
DOI: 10.1308/003588411X571944