scholarly journals Near-infrared autofluorescence spectroscopy of in vivo soft tissue sarcomas

2015 ◽  
Vol 40 (23) ◽  
pp. 5498 ◽  
Author(s):  
John Quan Nguyen ◽  
Zain Gowani ◽  
Maggie O’Connor ◽  
Isaac Pence ◽  
The-Quyen Nguyen ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Near Infrared ◽  
Soft Tissue Sarcomas ◽  
Autofluorescence Spectroscopy

scholarly journals LRRC15 Targeting in Soft-Tissue Sarcomas: Biological and Clinical Implications

Cancers ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 757 ◽  
Author(s):  
Eytan Ben-Ami ◽  
Raul Perret ◽  
Ying Huang ◽  
Félicie Courgeon ◽  
Prafulla C. Gokhale ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Stromal Cells ◽  
Soft Tissue Sarcomas ◽  
Antibody Drug Conjugate ◽  
Drug Conjugate ◽  
In Vivo Experiments ◽  
Patient Derived Xenograft ◽  
Pdx Models ◽  
Antibody Drug

Background: LRRC15 is a member of the LRR (leucine-rich repeat) superfamily present on tumor-associated fibroblasts (CAFs) and stromal cells. The expression of LRRC15 is upregulated by the pro-inflammatory cytokine TGFβ. ABBV-085 is a monomethyl auristatin E (MMAE)-containing antibody-drug conjugate (ADC) designed to target LRRC15, and which has shown significant anti-tumor activity in several tumor models. This is the first focused examination of LRRC15 expression and ABBV-085 activity in soft-tissue sarcomas (STS). Methods: We analyzed the LRRC15 expression profile by immunohistochemistry in 711 STS cases, covering a broad spectrum of STS histologies and sub-classifications. In vivo experiments were carried out by using LRRC15-positive and LRRC15-negative patient-derived xenograft (PDX) models of STS. Results: In contrast to patterns observed in epithelial tumors, LRRC15 was expressed not only by stromal cells but also by cancer cells in multiple subsets of STS with significant variations noted between histological subtypes. Overexpression of LRRC15 is positively correlated with grade and independently associated with adverse outcome. ABBV-085 has robust preclinical efficacy against LRRC15 positive STS patient-derived xenograft (PDX) models. Conclusion: We provide the first preclinical evidence that LRRC15 targeting with an antibody-drug conjugate is a promising strategy in LRRC15-positive STS. ABBV-085 is being evaluated in an ongoing clinical trial in STS and other malignancies.

In vivo proton magnetic resonance spectroscopic (PMRS) evaluation: Emerging tool to solve the diagnostic dilemma in soft tissue sarcoma management

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 10020-10020
Author(s):  
M. Kar ◽  
S. S. Deo ◽  
V. Kumar ◽  
U. Sharma ◽  
N. R. Jagannathan ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Predictive Value ◽  
Proton Magnetic Resonance ◽  
Soft Tissue Sarcomas ◽  
Soft Tissue Tumour ◽  
Malignant Soft Tissue ◽  
Choline Peak

10020 Objective: Presently grade is the most important factor used to decide the soft tissue sarcoma management. But it is always very difficult to assign a pathologic grade because of discordance rate is 30–40%, even among experienced sarcoma oncopathologists. Again histopathology has the disadvantages of being invasive, subjective and insensitive to tumour heterogeneity. This emphasizes the need for an objective and accurate assessment of histologic type and grade of sarcoma. The aim of this study is to evaluate the correlation of in vivo proton magnetic resonance spectroscopic findings with histopathological features and validate its diagnostic efficacy in management of different types of soft tissue sarcomas. Methods: PMRS Study was performed at 1.5Tesla MRI machine with a surface coil appropriate for the location of the lesions in 25 patients. Single-voxel (SVS) study has been done in 10 cases and chemical shift imaging (CSI) study characterised the heterogeneity of the tumor in 15 cases by using point - resolved spectroscopic sequence (PRESS) with echo time TR=2,000 / TE = 30, 135 & 270 msec. The choline peak, identified at 3.2 ppm in spectra was considered as significant which shows the activity of the tumour. MRS results and histopathologic findings were correlated and P < 0.001, considered being significant. Results: Choline peak was found in 17 out of 17 patients with malignant soft tissue tumours where as three patient with benign and five treated malignant soft tissue tumour patients with no residual disease did not show any choline. In vivo spectroscopy here shows sensitivity, specificity, positive predictive value, negative predictive value and accuracy of 100% each. Conclusion: Choline peak in MRS study can predict the grade, margin status (especially CSI) and tumour activity in recurrent and / or residual soft tissue sarcoma. Most important findings here was that without using any contrast medium in study the choline peak in CSI spectroscopic evaluation could show the tumor activity at the margin of the tumor which is very important point for evaluation of residual or recurrent or completion of the surgical excision of the tumor A major study should be done to validate its efficacy for routine use in oncology. [Table: see text]

scholarly journals GSK3-beta as a candidate therapeutic target in soft tissue sarcomas

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
S. Verbeke ◽  
R. Perret ◽  
V. Chaire ◽  
E. Richard ◽  
V. Velasco ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Glycogen Synthase ◽  
Treatment Options ◽  
Soft Tissue Sarcomas ◽  
Prognostic Impact ◽  
Gene And Protein Expression ◽  
Apoptosis Protein ◽  
Rare Malignancy ◽  
Gsk 3Β

AbstractSoft tissue sarcoma (STS) is a predominantly fatal rare malignancy with inadequate treatment options. Glycogen synthase kinase 3β (GSK-3β) is an emerging target in human malignancies. Its therapeutic relevance in STS is unknown. We analyzed the prognostic impact of GSK-3β gene and protein expression in two independent cohorts of patients with STS. We then treated STS cell lines and mice xenografts with a novel GSK-3 inhibitor 9-ING-41 alone or in combination with chemotherapy. We demonstrated that 9-ING-41 treatment induced significant STS cells apoptosis and was synergistic in vivo when combined with chemotherapy. Mechanistically, 9-ING-41 induces significant apoptosis of STS cells via suppression of NF-κB-mediated X-linked inhibitor of apoptosis protein (XIAP) expression. These data support the inclusion of patients with STS in clinical studies of 9-ING-41 alone and in combination with chemotherapy.

scholarly journals Assessment of Efficiency and Safety of Apatinib in Advanced Bone and Soft Tissue Sarcomas: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 11 ◽  
Author(s):  
Zuoyao Long ◽  
Mengquan Huang ◽  
Kaituo Liu ◽  
Minghui Li ◽  
Jing Li ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Adverse Events ◽  
Fixed Effects ◽  
Meta Analysis ◽  
Soft Tissue Sarcomas ◽  
Progression Free Survival ◽  
Cochrane Library

BackgroundPrevious studies, both in vitro and in vivo, have established that apatinib has anti-tumor properties. However, insufficient empirical evidence of the efficacy and safety of apatinib has been published for bone and soft tissue sarcoma, the reported results differing widely. Here, we conducted a meta-analysis to assess the efficacy and toxicity of apatinib for the treatment of bone and soft tissue sarcoma.MethodsPubmed, Medline, Web of Science, ScienceDirect, Ovid, Embase, Cochrane Library, Scopus, Vip (China), Cnki (China), Wanfang (China), and CBM (China) databases and literature from conferences were searched for studies of apatinib for the treatment of bone and soft tissue sarcomas, published from the inception of each database to Sep 1, 2020, without language restrictions. Primary outcomes were efficacy and toxicity of apatinib for the treatment of bone and soft tissue sarcoma, including treatment response, progression-free survival (PFS), and the incidence of adverse events. After extraction of data and methodological quality evaluation, random or fixed-effects models, as appropriate, were selected to calculate pooled effect estimates using R software (Version 3.4.1).ResultsA total of 21 studies with 827 participants were included in the present meta-analysis. The mean MINORS score was 10.48 ± 1.75 (range: 7-13), indicating evidence of moderate quality. Pooled outcomes indicated that overall response rate (ORR) and disease control rate (DCR) were 23.85% (95% CI: 18.47%-30.21%) and 79.16% (95% CI: 73.78%-83.68%), respectively. Median PFS ranged from 3.5 to 13.1 months, with a mean of 7.08 ± 2.98 months. Furthermore, the rates of PFS (PFR) after 1, 6, and 12 months were 99.31%, 44.90%, and 14.31%, respectively. Drug-related toxicity appears to be common in patients administered apatinib, for which hand-foot syndrome (41.13%), hypertension (36.15%), and fatigue (20.52%) ranked the top three most common adverse events. However, the incidence of grade 3-4 adverse events was relatively low and manageable.ConclusionsBased on the best evidence currently available, apatinib demonstrates promising clinical efficacy and an acceptable safety profile for the treatment of advanced bone and soft tissue sarcoma, although additional high-quality clinical studies are required to further define its properties and toxicity.

Detection of MSC-like cells in soft tissue sarcoma cell lines and primary tumors

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 11000-11000
Author(s):  
S. Wirths ◽  
E. Malenke ◽  
T. Wiesner ◽  
H. Buehring ◽  
J. Hartmann ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Cell Lines ◽  
Primary Tumor ◽  
Growth Factor Receptor ◽  
Soft Tissue Sarcomas ◽  
Proliferative Capacity ◽  
Differentiation Potential ◽  
Primary Tumors

11000 Background: Soft tissue sarcomas (STS) are a heterogeneous group of mesodermal tumors hypothetically originating from mesenchymal stem cells (MSC). While the expression profile of bone marrow derived MSCs and their in vitro differentiation potential have been examined extensively, knowledge regarding the in vivo counterparts of MSC is still evolving. We hypothesized that MSC-like cells within STS could represent sarcoma initiating cells. Methods: To target rare human cell populations including MSCs, an exclusive antibody panel was developed. The target antigens include platelet-derived growth factor receptor-β (CD140b), HER-2/erbB2 (CD340), TNFRSF16 (CD217), frizzled-4 (CD344), the recently described W8B2 antigen, as well as several surface antigens identified by novel antibodies. To define the expression pattern of MSC-markers in STS, both cell lines and primary tumor samples in suspension and in snap frozen sections were investigated. To reveal functional differences between identified rare tumor populations single cell proliferation kinetics were investigated after FACS-sorting. Results: All cell lines und primary tumor samples revealed expression of selected markers. Antigens identifying subpopulations within all sarcoma samples investigated, were selected for functional studies. These included frizzled-4, TNFRSF16, W5C5 and W8B2. Liposarcoma (SW872), leiomyosarcoma (SK-LMS) and fibrosarcoma (HT1080) cell lines enclosed subpopulations with differential expression of above markers and by FACS based limiting dilution it was demonstrated that only fractions of viable cells contained proliferative capacity. Cells lacking expression of CD271 had lower proliferative capacity compared to mock sorted HT1080 or SK-LMS, while CD271+ SW872 had significantly higher proliferation. The antigen defined by W5C5 identified cells with high proliferative capacity compared to control in SW872 and SK-LMS and its lack in HT1080 identified a subpopulation with largely reduced proliferation. Conclusions: Subpopulations within STS cell lines and primary sarcoma tissue express novel MSC-markers and display increased proliferative capacity, potentially reflecting the existence of sarcoma initiating cells. No significant financial relationships to disclose.

scholarly journals Candidate Biomarkers for Specific Intraoperative Near-Infrared Imaging of Soft Tissue Sarcomas: A Systematic Review

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 557
Author(s):  
Zeger Rijs ◽  
A. Naweed Shifai ◽  
Sarah E. Bosma ◽  
Peter J. K. Kuppen ◽  
Alexander L. Vahrmeijer ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Cell Surface ◽  
Near Infrared ◽  
Infrared Imaging ◽  
Tumor Resection ◽  
Soft Tissue Sarcomas ◽  
Complete Tumor Resection ◽  
Nirf Imaging ◽  
Pubmed Search ◽  
Complete Tumor

Surgery is the mainstay of treatment for localized soft tissue sarcomas (STS). The curative treatment highly depends on complete tumor resection, as positive margins are associated with local recurrence (LR) and prognosis. However, determining the tumor margin during surgery is challenging. Real-time tumor-specific imaging can facilitate complete resection by visualizing tumor tissue during surgery. Unfortunately, STS specific tracers are presently not clinically available. In this review, STS-associated cell surface-expressed biomarkers, which are currently already clinically targeted with monoclonal antibodies for therapeutic purposes, are evaluated for their use in near-infrared fluorescence (NIRF) imaging of STS. Clinically targeted biomarkers in STS were extracted from clinical trial registers and a PubMed search was performed. Data on biomarker characteristics, sample size, percentage of biomarker-positive STS samples, pattern of biomarker expression, biomarker internalization features, and previous applications of the biomarker in imaging were extracted. The biomarkers were ranked utilizing a previously described scoring system. Eleven cell surface-expressed biomarkers were identified from which 7 were selected as potential biomarkers for NIRF imaging: TEM1, VEGFR-1, EGFR, VEGFR-2, IGF-1R, PDGFRα, and CD40. Promising biomarkers in common and aggressive STS subtypes are TEM1 for myxofibrosarcoma, TEM1, and PDGFRα for undifferentiated soft tissue sarcoma and EGFR for synovial sarcoma.

scholarly journals Bcl-xL inhibition enhances Dinaciclib-induced cell death in soft-tissue sarcomas

2018 ◽  
Author(s):  
Santi Rello-Varona ◽  
Miriam Fuentes-Guirado ◽  
Roser López-Alemany ◽  
Aida Contreras-Pérez ◽  
Núria Mulet-Margalef ◽  
...  
Keyword(s):  
Cell Death ◽  
Protein Synthesis ◽  
Soft Tissue ◽  
Liver Toxicity ◽  
Soft Tissue Sarcomas ◽  
Mitochondrial Pathway ◽  
Chemotherapy Drugs ◽  
Model Drug

AbstractSoft-tissue sarcomas (STS) are an uncommon and heterogeneous group of malignancies that result in high mortality. Metastatic STS have very bad prognosis due to the lack of effective treatments. Dinaciclib is a model drug for the family of CDK inhibitors. Its main targets are cell cycle regulator CDK1 and protein synthesis controller CDK9. We present data supporting Dinaciclib ability to inactivate in vitro different STS models at nanomolar concentrations. Moreover, the different rhythms of cell death induction allow us to further study into the mechanism of action of the drug. Cell death was found to respond to the mitochondrial pathway of apoptosis. Anti-apoptotic Bcl-xL was identified as the key regulator of this process. Bcl-xL showed a slower decay curve after protein synthesis disruption that in tolerant cell lines was enough to delay apoptosis, as its action cannot be countered by the relative low levels of pro-apoptotic BH3 proteins BIM and PUMA. Combination of Dinaciclib with BH3-mimetics led to quick and massive apoptosis induction in vitro, but in vivo assessment was prevented due to liver toxicity. Additionally, Bcl-xL inhibitor A-1331852 also synergized with conventional chemotherapy drugs as Gemcitabine. Thus, Bcl-xL targeted therapy arises as a major opportunity to the treatment of STS.

A phase II study of intravenous (IV) wild-type reovirus (Reolysin) in the treatment of patients with bone and soft tissue sarcomas metastatic to the lung

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 10524-10524 ◽  
Author(s):  
A. C. Mita ◽  
K. Sankhala ◽  
J. Sarantopoulos ◽  
J. Carmona ◽  
S. Okuno ◽  
...  
Keyword(s):  
Side Effects ◽  
Soft Tissue ◽  
Phase Ii ◽  
Performance Status ◽  
Single Agent ◽  
Soft Tissue Sarcomas ◽  
In Vivo Studies ◽  
Open Label

10524 Background: Reolysin is a Dearing strain, naturally occurring, ubiquitous human reovirus. The PKR (double stranded RNA-activated protein kinase) is inhibited and therefore the virus replicates specifically in transformed cells possessing an activated Ras pathway producing lysis. In vitro and in vivo studies with Reolysin in sarcoma cell lines revealed significant antitumor activity. Methods: This phase II open-label, single agent study was designed to characterize the efficacy and safety of Reolysin given IV every 28 days in patients (pts) with bone or soft tissue sarcoma with lung metastasis using a Simon two-stage design. 38 pts were accrued to the first stage. If 1 or more pts experience clinical benefit (prolonged SD > 6 months, partial or complete response) up to 52 pts could be accrued. The agent will be considered active if 3 or more responses or prolonged SD are observed. Results: Since July 2007, 43 pts age 19–76 (median 49) were enrolled (20 female) and received a total of 141 cycles (range 1–18). All pts had performance status 1 (29 pts) or 0 (14 pts). 38 pts received prior chemotherapy, radiotherapy, biological agents or combinations for their metastatic disease, 15 pts received more than 3 chemotherapy regimens. The sarcoma subtypes included: synovial sarcoma (13 pts), osteosarcoma (7 pts), leiomyosarcoma (7 pts), MFH (5 pts), Ewing/PNET (1 pt), chordoma (1 pt), others (9 pts). Side effects were mild to moderate (grade 1–2) and included constitutional symptoms fever, chills, fatigue. Two pts experienced respiratory side effects (cough and dyspnea) and 2 pts had diarrhea. Hematological side effects included grade 2–3 neutropenia (6 pts) and grade 2 thrombocytopenia (2 pts). One patient experienced grade 2 AST elevation. 33 pts are evaluable for response to date: 14 pts (42%) had SD for 2+ months including 5 pts having SD for more than 6 months. Conclusions: Utilization of single agent reovirus for treatment of sarcoma is a novel and unique therapeutic approach to date. Reolysin is well tolerated and shows promise for the treatment of metastatic sarcoma. Primary efficacy goals have been met. Accrual is ongoing to a total of 52 pts. [Table: see text]

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