placeholder
and
and

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Proceed order?

Export
Filter
Document type
Language
Year
  • 1
    Language: English
    In: The lancet oncology, 2015, Vol.16 (1), p.98-107
    Description: Summary Background Results of previous study showed promising but short-lived activity of sorafenib in the treatment of patients with unresectable advanced and metastatic osteosarcoma. This treatment failure has been attributed to the mTOR pathway and might therefore be overcome with the addition of mTOR inhibitors. We aimed to investigate the activity of sorafenib in combination with everolimus in patients with inoperable high-grade osteosarcoma progressing after standard treatment. Methods We did this non-randomised phase 2 trial in three Italian Sarcoma Group centres. We enrolled adults (≥18 years) with relapsed or unresectable osteosarcoma progressing after standard treatment (methotrexate, cisplatin, and doxorubicin, with or without ifosfamide). Patients received 800 mg sorafenib plus 5 mg everolimus once a day until disease progression or unacceptable toxic effects. The primary endpoint was 6 month progression-free survival (PFS). All analyses were intention-to-treat. This trial is registered with ClinicalTrials.gov , number NCT01804374. Findings We enrolled 38 patients between June 16, 2011, and June 4, 2013. 17 (45%; 95% CI 28–61) of 38 patients were progression free at 6 months. Toxic effects led to dose reductions, or short interruptions, or both in 25 (66%) of 38 patients and permanent discontinuation for two (5%) patients. The most common grade 3–4 adverse events were lymphopenia and hypophosphataemia each in six (16%) patients, hand and foot syndrome in five (13%), thrombocytopenia in four (11%), and fatigue, oral mucositis, diarrhoea, and anaemia each in two (5%). One patient (3%) had a grade 3 pneumothorax that required trans-thoracic drainage, and that recurred at the time of disease progression. This was reported as a serious adverse event related to the study drugs in both instances. No other serious adverse events were reported during the trial. There were no treatment-related deaths. Interpretation Although the combination of sorafenib and everolimus showed activity as a further-line treatment for patients with advanced or unresectable osteosarcoma, it did not attain the prespecified target of 6 month PFS of 50% or greater. Funding Italian Sarcoma Group.
    Subject(s): Hematology, Oncology and Palliative Medicine ; Niacinamide - analogs & derivatives ; Osteosarcoma - drug therapy ; TOR Serine-Threonine Kinases - metabolism ; Humans ; Middle Aged ; Antineoplastic Combined Chemotherapy Protocols - adverse effects ; Male ; Bone Neoplasms - pathology ; TOR Serine-Threonine Kinases - antagonists & inhibitors ; Young Adult ; Neoplasm Grading ; Time Factors ; Adult ; Female ; Bone Neoplasms - drug therapy ; Everolimus ; Sirolimus - analogs & derivatives ; Bone Neoplasms - enzymology ; Osteosarcoma - enzymology ; Kaplan-Meier Estimate ; Treatment Outcome ; Disease Progression ; Niacinamide - administration & dosage ; Disease-Free Survival ; Sirolimus - administration & dosage ; Phenylurea Compounds - administration & dosage ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Adolescent ; Intention to Treat Analysis ; Italy ; Osteosarcoma - secondary ; Antimitotic agents ; Chemotherapy ; Osteosarcoma ; Stem cells ; Clinical trials ; Product development ; Antineoplastic agents ; Standards ; Cancer ; Index Medicus
    ISSN: 1470-2045
    E-ISSN: 1474-5488
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 2
    Language: English
    In: Technology in Cancer Research & Treatment, 2019-07-19, Vol.18, p.1533033819840000-1533033819840000
    Description: Background: Primary and recurrent giant cell tumor of bone is typically benign; however, rarely giant cell tumor of bone can undergo malignant transformation. Malignancy in giant cell tumor of bone may be primary (adjacent to benign giant cell tumor of bone at first diagnosis) or secondary (at the site of previously treated giant cell tumor of bone). Malignant giant cell tumor of bone has a poor prognosis; it is important to distinguish malignant from benign lesions to facilitate appropriate management. The true incidence of malignant giant cell tumor of bone is not known, probably owing to inaccurate diagnosis and inconsistent nomenclature. We have analyzed current data to provide a robust estimate of the incidence of malignancy in giant cell tumor of bone. Methods: A literature search was performed to source published reports of primary and secondary cases of malignant giant cell tumor of bone. Studies that reported a denominator were used to estimate the incidence of malignancy. Results: We identified 4 large series of patients with malignant giant cell tumor of bone that provided data on 2315 patients with giant cell tumor of bone. Across these studies, the cumulative incidence of malignancy was 4.0%; the cumulative incidence of primary malignancy was 1.6% compared with 2.4% for secondary malignancy. Our analyses confirmed that most malignant giant cell tumor of bone is secondary and occurs following radiation. In addition, data from 8 small series showed that 4.8% of patients with giant cell tumor of bone who received radiation therapy developed secondary malignancy. Conclusions: Malignant giant cell tumor of bone is rare, and its identification is hindered by a lack of clear diagnostic criteria. For optimal care of patients with giant cell tumor of bone, we recommend: comprehensive histologic sampling to ensure accurate diagnoses; watchful follow-up, particularly for patients treated with radiation; and timely treatment of local recurrence.
    Subject(s): Index Medicus
    ISSN: 1533-0346
    E-ISSN: 1533-0338
    Source: PubMed Central
    Source: ProQuest Central
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 3
    Article
    Article
    2020
    ISSN: 2072-6694 
    Language: English
    In: Cancers, 2020-11-01, Vol.12 (11), p.1
    Description: Primary malignant bone tumors are infrequent cancers. More than 90% of these neoplasms are classified as osteosarcomas, Ewing sarcomas or chondrosarcomas, and their clinical presentation, diagnosis, and treatment principles are well-established. The entities described in this article, are ultra-rare varieties of bone sarcomas, and there clinical and histological characteristics are not well known. Therefore, they are very difficult to be diagnosed and there is a lot of uncertainty on their treatment. Because of their rarity, it is also extremely difficult to perform clinical research on these cancers. This article creates more awareness of these very rare bone tumors. It explains how to recognize and diagnose each entity and it summarizes the medical scientific literature that is available on these cancers. Increasing awareness and clinical research for these cancers are key elements to improve the prognosis for patients with these diseases in the long term. Rare primary malignant bone sarcomas (RPMBS), other than osteosarcoma, chondrosarcoma, chordoma, and Ewing sarcoma, account for about 5-10% of primary bone tumors and represent a major diagnostic challenge. These tumors include spindle cell and round cell sarcoma entities, hemangiopericytoma-like and vascular tumors. Additionally, several history pes, traditionally described in the soft tissues, such as myxofibrosarcoma, synovial sarcoma, and malignant peripheral nerve sheath tumor of bone, have been reported in patients with primary bone tumors. While wide surgical resection is the mainstay of local treatment, systemic therapy of these rare entities is controversial. Patients with undifferentiated spindle cell or pleomorphic high-grade tumors of bone, are usually treated with osteosarcoma-like chemotherapy, while patients with round cell and undifferentiated round cell tumors (URCTs), may respond to sarcoma treatment regimens for Ewing sarcoma patients. Studies on analogies and differences among these ultra-rare tumors have seldom been reported. This review describes relevance, clinical aspects, diagnostic procedures, staging, treatment recommendations, and current research in this composite tumor group. Keywords: bone tumor; sarcoma; rare tumor; molecular diagnostic; chemotherapy; spindle cells sarcoma; round cells sarcoma; vascular sarcoma; CIC-DUX4; BCOR-CCNH3
    Subject(s): molecular diagnostic ; sarcoma ; rare tumor ; chemotherapy ; bone tumor ; spindle cells sarcoma
    ISSN: 2072-6694
    E-ISSN: 2072-6694
    Source: Academic Search Ultimate
    Source: PubMed Central
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 4
    Language: English
    In: Journal of clinical oncology, 2012-06-10, Vol.30 (17), p.2112-2118
    Description: We compared two chemotherapy regimens that included methotrexate (MTX), cisplatin (CDP), and doxorubicin (ADM) with or without ifosfamide (IFO) in patients with nonmetastatic osteosarcoma of the extremity. Patients age ≤ 40 years randomly received regimens with the same cumulative doses of drugs (ADM 420 mg/m(2), MTX 120 g/m(2), CDP 600 mg/m(2), and IFO 30 g/m(2)) but with different durations (arm A, 44 weeks; arm B, 34 weeks). IFO was given postoperatively when pathologic response to MTX-CDP-ADM was poor (arm A) or given in the primary phase of chemotherapy with MTX-CDP-ADM (arm B). End points of the study included pathologic response to preoperative chemotherapy, toxicity, and survival. Given the feasibility of accrual, the statistical plan only permitted detection of a 15% difference in 5-year overall survival (OS). From April 2001 to December 2006, 246 patients were enrolled. Two hundred thirty patients (94%) underwent limb salvage surgery (arm A, 92%; arm B, 96%; P = .5). Chemotherapy-induced necrosis was good in 45% of patients (48% in arm A, 42% in arm B; P = .3). Four patients died of treatment-related toxicity (arm A, n = 1; arm B, n = 3). A significantly higher incidence of hematologic toxicity was reported in arm B. With a median follow-up of 66 months (range, 1 to 104 months), 5-year OS and event-free survival (EFS) rates were not significantly different between arm A and arm B, with OS being 73% (95% CI, 65% to 81%) in arm A and 74% (95% CI, 66% to 82%) in arm B and EFS being 64% (95% CI, 56% to 73%) in arm A and 55% (95% CI, 46% to 64%) in arm B. IFO added to MTX, CDP, and ADM from the preoperative phase does not improve the good responder rate and increases hematologic toxicity. IFO should only be considered in patients who have a poor histologic response to MTX, CDP, and ADM.
    Subject(s): Biological and medical sciences ; Medical sciences ; Diseases of the osteoarticular system ; Tumors of striated muscle and skeleton ; Tumors ; Osteosarcoma - drug therapy ; Femur - pathology ; Humans ; Child, Preschool ; Male ; Tibia - pathology ; Cisplatin - administration & dosage ; Humerus - pathology ; Disease-Free Survival ; Ifosfamide - administration & dosage ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Chemotherapy, Adjuvant - methods ; Adolescent ; Adult ; Female ; Methotrexate - administration & dosage ; Bone Neoplasms - drug therapy ; Child ; Doxorubicin - administration & dosage
    ISSN: 0732-183X
    E-ISSN: 1527-7755
    Source: Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 5
    Language: English
    In: Histopathology, 2016-10, Vol.69 (4), p.624-634
    Description: Aims Round‐cell sarcomas lacking specific translocations represent a diagnostic challenge. The aim of this study was to describe seven cases of CIC–DUX4 fusion‐positive sarcomas, including the first reported example arising primarily in bone. Methods and results Patients ranged in age from 15 years to 44 years (median: 33 years). Six cases arose from the soft tissues, and one from the iliac bone. Morphologically, all cases showed an undifferentiated round‐cell population with greater atypia and pleomorphism than Ewing sarcoma. Immunohistochemically, all tumours showed focal and weak positivity for CD99, and five of seven showed nuclear and/or cytoplasmic positivity for Wilms tumour 1. Five patients had lung metastases at presentation. All patients received chemotherapy according to Ewing sarcoma protocols. All but one patient (the one with a bone tumour) died of disease after a mean of 14.5 months from the diagnosis (range: 8–20 months). Conclusions Our series confirms that CIC–DUX4 fusion‐positive sarcomas are aggressive tumours with an adverse prognosis, and with clinical, histological and genetic differences from Ewing sarcoma. The best therapeutic approach needs to be investigated.
    Subject(s): Ewing sarcoma ; CIC ; round-cell sarcoma ; DUX4 ; round‐cell sarcoma ; Immunohistochemistry ; Biomarkers, Tumor - analysis ; Humans ; In Situ Hybridization, Fluorescence ; Male ; Bone Neoplasms - pathology ; Young Adult ; Oncogene Proteins, Fusion - genetics ; Sarcoma, Small Cell - genetics ; Adolescent ; Polymerase Chain Reaction ; Soft Tissue Neoplasms - pathology ; Adult ; Female ; Bone Neoplasms - genetics ; Sarcoma, Small Cell - pathology ; Soft Tissue Neoplasms - genetics ; Chemotherapy ; Sarcoma ; Analysis ; Cancer ; Index Medicus
    ISSN: 0309-0167
    E-ISSN: 1365-2559
    Source: Academic Search Ultimate
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 6
    Language: English
    In: Cancer, 2020-11-01, Vol.126 (21), p.4726-4734
    Description: Background Although elderly patients (≥70 years) represent 30% of new diagnoses of soft tissue sarcoma (STS), they are underrepresented in clinical trials and are often unfit to receive standard anthracycline‐based chemotherapy. Trabectedin is registered as a second‐line treatment for advanced STS and is characterized by a favorable safety profile. Methods The aim of this single‐arm, phase 2 study was to investigate trabectedin (scheduled dose, 1.3‐1.5 mg/m2) as a first‐line treatment in elderly patients with advanced stage STS who are inoperable and are unfit to receive standard anthracycline‐based chemotherapy. The coprimary endpoints were progression‐free survival at 3 months (PFS3) and the rate of clinically limiting toxicities (CLTs). We also conducted an ancillary study on pharmacokinetics. Results Twenty‐four patients (12 men and 12 women) with a median age of 79 years (interquartile range [IQR], 74‐83 years) were enrolled. The histological subtype was leiomyosarcoma in 46%, liposarcoma in 33%, and other histotypes in 21%. The median number of trabectedin courses was 4 (IQR, 3‐6), with 7 patients (29%) receiving ≥6 cycles. Eight patients (33%) required dose reductions. The most frequent grade 3/4 adverse events were neutropenia in 9 patients (38%), fatigue in 5 patients (21%), and aminotransferase elevation in 5 patients (21%). PFS3, median PFS, and overall survival were 71% (80% CI, 57%‐81%), 4 months, and 12 months, respectively. Ten patients (42% [80% CI, 28%‐57%]) experienced CLTs. Trabectedin Cmax, half‐life, clearance, and distribution volume were 1.28 ng/mL (standard deviation [SD], 0.58 ng/mL), 26.70 hours (SD, 9.09 hours), 39.98 L/h/m2 (SD, 14.08 L/h/m2), and 1460 L/m2 (SD, 561 L/m2), respectively. Conclusion Trabectedin can be administered safely to elderly patients with STS who are unfit to receive anthracyclines. Pharmacokinetics in the elderly population was superimposable to historical data. Trabectedin can be administered safely to patients who are elderly and are unfit to receive anthracyclines for the treatment of soft tissue sarcoma. The pharmacokinetics of trabectedin in the elderly population is superimposable to historical data.
    Subject(s): pharmacokinetics ; advanced soft tissue sarcoma ; unfit patients ; elderly ; trabectedin
    ISSN: 0008-543X
    E-ISSN: 1097-0142
    Source: Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 7
    Language: English
    In: European journal of nuclear medicine and molecular imaging, 2017-02, Vol.44 (2), p.215-223
    Description: The histological response to neoadjuvant chemotherapy is an important prognostic factor in patients with osteosarcoma (OS) and Ewing sarcoma (EWS). The aim of this study was to assess baseline primary tumour FDG uptake on PET/CT, and serum values of alkaline phosphatase (ALP) and lactate dehydrogenase (LDH), to establish whether these factors are correlated with tumour necrosis and prognosis.Patients treated between 2009 and 2014 for localized EWS and OS, who underwent FDG PET/CT as part of their staging work-up, were included. The relationships between primary tumour SUVmax at baseline (SUV1), SUVmax after induction chemotherapy (SUV2), metabolic response calculated as [(SUV1 − SUV2)/SUV1)] × 100, LDH and ALP and tumour response/survival were analysed. A good response (GR) was defined as tumour necrosis 〉90 % in patients with OS, and grade II-III Picci necrosis (persitence of microscopic foci only or no viable tumor) in patients with Ewing sarcoma.The study included 77 patients, 45 with EWS and 32 with OS. A good histological response was achieved in 53 % of EWS patients, and 41 % of OS patients. The 3-year event-free survival (EFS) was 57 % in EWS patients and 48 % OS patients. The median SUV1 was 5.6 (range 0 – 17) in EWS patients and 7.9 (range 0 – 24) in OS patients (p = 0.006). In EWS patients the GR rate was 30 % in those with a high SUV1 (≥6) and 72 % in those with a lower SUV1 (p = 0.0004), and in OS patients the GR rate was 29 % in those with SUV1 ≥6 and 64 % in those with a lower SUV1 (p = 0.05). In the univariate analysis the 3-year EFS was significantly better in patients with a low ALP level (59 %) than in those with a high ALP level (22 %, p = 0.02) and in patients with a low LDH level (62 %) than in those with a high LDH level (37 %, p = 0.004). In EWS patients the 3-year EFS was 37 % in those with a high SUV1 and 75 % in those with a low SUV1 (p = 0.004), and in OS patients the 3-year EFS was 32 % in those with a high SUV1 and 66 % in those with a low SUV1 (p = 0.1). Histology, age and gender were not associated with survival. In the multivariate analysis, SUV1 was the only independent pretreatment prognostic factor to retain statistical significance (p = 0.017). SUV2 was assessed in 25 EWS patients: the median SUV2 was 1.9 (range 1 – 8). The GR rate was 20 % in patients with a high SUV2, and 67 % in those with a low SUV2 (p = 0.02). A good metabolic response (SUV reduction of ≥55 %) was associated with a 3-year EFS of 80 % and a poor metabolic response with a 3-year EFS of 20 % (p = 0.05). In the OS patients the median SUV2 was 2.7 (range 0 – 4.5). Neither SUV2 nor the metabolic response was associated with outcome in OS patients.FDG PET/CT is a useful and noninvasive tool for identifying patients who are more likely to be resistant to chemotherapy. If this finding is confirmed in a larger series, SUV1, SUV2 and metabolic response could be proposed as factors for stratifying EWS patients to identify those with high-grade localized bone EWS who would benefit from risk-adapted induction chemotherapy.
    Subject(s): Ewing sarcoma ; Neo-adjuvant chemotherapy ; Prognosis ; Medicine & Public Health ; Osteosarcoma ; Orthopedics ; Oncology ; PET-CT ; SUV1 ; Nuclear Medicine ; Imaging / Radiology ; Cardiology ; Bone Neoplasms - mortality ; Prevalence ; Bone Neoplasms - therapy ; Sarcoma, Ewing - therapy ; Humans ; Child, Preschool ; Male ; Sarcoma, Ewing - mortality ; Chemoradiotherapy, Adjuvant - mortality ; Sarcoma, Ewing - diagnostic imaging ; Young Adult ; Neoadjuvant Therapy - mortality ; Adult ; Female ; Radiopharmaceuticals ; Child ; Positron Emission Tomography Computed Tomography - statistics & numerical data ; Positron Emission Tomography Computed Tomography - methods ; Risk Assessment ; Bone Neoplasms - diagnostic imaging ; Risk Factors ; Survival Rate ; Treatment Outcome ; Adolescent ; Fluorodeoxyglucose F18 ; Italy - epidemiology ; Antimitotic agents ; Care and treatment ; Phosphatases ; PET imaging ; Sarcoma ; Analysis ; Adjuvant treatment ; Antineoplastic agents ; Cancer ; Index Medicus ; Original
    ISSN: 1619-7070
    E-ISSN: 1619-7089
    Source: Academic Search Ultimate
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 8
    Language: English
    In: Annals of surgical oncology, 2021-02, Vol.28 (2), p.1142-1150
    Description: Extraskeletal myxoid chondrosarcoma (EMC) is a rare sarcoma of uncertain origin, marked by specific chromosomal translocations involving the NR4A3 gene, and usually characterized by an indolent course. Surgery (with or without radiotherapy) is the treatment of choice in localized disease. The treatment for advanced disease remains uncertain. In order to better evaluate prognostic factors and outcome, a retrospective pooled analysis of patients with EMC treated at three Italian Sarcoma Group (ISG) referral centers was carried out. All patients with localized EMC surgically treated from 1989 to 2016 were identified. Diagnosis was centrally reviewed according to WHO 2013. Only patients with NR4A3 rearrangement were included. Sixty-seven patients were identified: 13 (20%) female, 54 (80%) male. Median age was 56 years (range 18-84). Numbers and type of translocation were: 50 (80%) NR4A3-EWS, 10 (16%) NR4A3-TAF15, 1 (2%) NR4A3-TCF12, and 1 (2%) NR4A3-TFG. Median follow-up was 55 months (range 2-312). Five- and ten-year overall survival rates were 94% (86-100 95%CI) and 84% (69-98 95%CI). Thirty-five (52%) patients relapsed: 9 had local recurrence (LR) and 26 had distant metastasis (5 with concomitant LR). The 5- and 10-year disease-free survival rates (DFS) were 51% (38-65 95%CI) and 20% (7-33 95%CI). Size of the primary tumor was significantly related to distant metastasis-free survival (DMFS) (p = 0.004). Patients carrying the NR4A3-EWS translocation had a trend in favor of better DFS (p = 0.08) and DMFS (p = 0.09) compared with the patients with NR4A3-TAF15. Prolonged survival can be expected in patients with EMC, in spite of a high rate of recurrence. Size is significantly associated with distant relapse. The type of NR4A3 translocation could influence outcome.
    Subject(s): Chondrosarcoma - surgery ; Sarcoma ; Humans ; Middle Aged ; Neoplasm Recurrence, Local ; Male ; Receptors, Thyroid Hormone ; Young Adult ; Receptors, Steroid ; Adolescent ; Aged, 80 and over ; Chondrosarcoma - genetics ; Adult ; Female ; Italy - epidemiology ; Aged ; Retrospective Studies ; Metastasis ; Diagnosis ; Analysis ; Index Medicus
    ISSN: 1068-9265
    E-ISSN: 1534-4681
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 9
    Language: English
    In: Frontiers in immunology, 2021, Vol.12, p.577766-577766
    Description: High-grade sarcomas are a heterogeneous group of aggressive tumors arising in bone and soft tissues. After relapse, treatment options are limited. The multi-targeted receptor tyrosine kinase inhibitors (TKIs) sunitinib and inhibitor of PD-1 (anti-PD-1) nivolumab have shown antitumor activity in selected subtypes. In this study, we examine the role of TKIs and PD-1 based therapy in cocultures of sarcoma. The human osteosarcoma (SaOS-2) and synovial sarcoma (SYO-1) cell lines were treated with sunitinib. After cell death and proliferation assessment, expression of PD-L1 was analyzed by flow cytometry. Sunitinib-treated sarcoma cells were cocultured with dendritic cells (DCs), and the phenotype of mature DCs was determined by flow cytometry. Mature DCs were cultured with autologous T cells. PD-1 expression on T cells, their proliferation, T regulatory cell (Tregs) induction and IFN-γ production, before and after nivolumab exposure, were analyzed. Along with its anti-proliferative and direct pro-apoptotic effect on sarcoma cell lines, sunitinib prompted PD-L1 upregulation on sarcoma cells. Interestingly, sunitinib-treated sarcoma cells drive DCs to full maturation and increase their capacity to induce sarcoma-reactive T cells to produce IFN-γ. Conversely, no effect on T cell proliferation and T cell subpopulation composition was observed. Moreover, both bone and synovial sarcoma cell lines induced Tregs through DCs but sunitinib treatment completely abrogated Treg induction. Finally, sarcoma cell lines induced PD-1 upregulation on both effector T cells and Tregs when loaded into DCs, providing a rationale for using PD-1 blockade. Indeed, PD-1 blockade by nivolumab synergized with sunitinib in inducing IFN-γ-producing effector T cells. Taken together, our data indicate that the treatment of sarcoma cells with sunitinib can exert significant changes on immune cell subsets toward immune activation, leading to DC-based cross-priming of IFN-γ-producing effector T cells and reduced Treg induction. PD-1 blockade with nivolumab has a synergistic effect with sunitinib, supporting the use of TKI and anti-PD-1 approach in sarcomas, and perhaps in other cancers. DC-targeted drugs, including toll-like receptor 3 inhibitors and CD47 inhibitors, are under development and our preclinical model might help to better design their clinical application.
    Subject(s): Index Medicus ; sunitinib (PubChem CID: 5329102) ; synovial sarcoma ; immunomodulation ; nivolumab (PubChem SID: 178103907) ; tyrosine kinase inhibitor (TKI) ; osteosarcoma
    ISSN: 1664-3224
    E-ISSN: 1664-3224
    Source: PubMed Central
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 10
    Language: English
    In: BMC cancer, 2021-01-22, Vol.21 (1), p.89-89
    Description: Giant cell tumor of bone (GCTB) is a rare osteoclastogenic stromal tumor. GCTB can rarely undergo malignant transformation. This post hoc analysis evaluated and classified malignancies in patients with GCTB who received denosumab. This analysis was conducted on patients with pathologically confirmed GCTB and measurable active disease treated with denosumab 120 mg subcutaneously once every 4 weeks, with loading doses on study days 8 and 15, as part of a phase 2, open-label, multicenter study. We identified potential cases of malignancy related to GCTB through an independent multidisciplinary review or medical history, associated imaging or histopathologic reports, and disease course. The findings were summarized and no statistical analysis was performed. Twenty of five hundred twenty-six patients (3.8%) who received at least one dose of denosumab were misdiagnosed with GCTB that was later discovered to be malignancies: five primary malignant GCTB, five secondary malignant GCTB, four sarcomatous transformations, and six patients with other malignancies (giant cell-rich osteosarcoma, undifferentiated pleomorphic sarcoma, spindle cell sarcoma, osteogenic sarcoma, phosphaturic mesenchymal tumor of mixed connective tissue type, and fibrosarcoma/malignant fibrous histiocytoma). Many malignancies were present before denosumab was initiated (8 definitive cases, 7 likely cases), excluding potential involvement of denosumab in these cases. Signs associated with potential misdiagnoses of GCTB included poor mineralization with denosumab treatment, rapid relapse in pain, or a failure of the typical dramatic improvement in pain normally observed with denosumab. Although rare, GCTB can undergo malignant transformation, and rates in this study were consistent with previous reports. Signs of poor mineralization or lack of response to denosumab treatment may warrant close monitoring. clinicaltrials.gov , ( NCT00680992 ). Registered May 20, 2008.
    Subject(s): Usage ; Bone cancer ; Development and progression ; Denosumab ; Drug therapy ; Giant cell tumors ; Risk factors ; Index Medicus ; Giant cell tumor of bone ; RANK ligand ; Bone neoplasms
    ISSN: 1471-2407
    E-ISSN: 1471-2407
    Source: BioMedCentral Open Access
    Source: Academic Search Ultimate
    Source: PubMed Central
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...