Background: We assessed the real-life clinical impact of bone health management in patients with ... more Background: We assessed the real-life clinical impact of bone health management in patients with breast cancer (BC) receiving adjuvant endocrine therapy at an Italian Osteoncology Center. Methods: Pre- and post-menopausal women undergoing adjuvant endocrine therapy for early-stage BC who came to our institute for their first bone health evaluation from January 2011 to June 2016 were considered in this retrospective observational study. Results: 1125 pre- and post-menopausal early-stage BC patients (209 and 916, respectively) were evaluated. Median age was 61 years (range 26–88). In the pre-menopausal group, spinal x-ray revealed that 10 patients (4.7%) had a morphometric vertebral fracture. Higher age (OR: 1.14; 95% CI: 1.01–1.29) and bone mineral density (BMD) ≤ −2.5 (OR: 14.45; 95% CI: 1.70–122.67) were associated with a higher risk of bone fracture. The overall frequency of bone fracture was 17.6% (n = 161) in post-menopausal patients and a lower risk for bone fractures was assoc...
The Italian Sarcoma Group performed this retrospective analysis of patients with advanced soft ti... more The Italian Sarcoma Group performed this retrospective analysis of patients with advanced soft tissue sarcoma, pretreated with ≥1 anthracycline-based treatment, and treated with trabectedin every three weeks. Primary endpoint was to describe real-life use of trabectedin across Italy. Secondary endpoints included objective response rate (ORR) and safety. Overall, 512 patients from 20 Italian centers were evaluated. Leiomyosarcoma (37.7%)/liposarcoma (30.3%) were the most prevalent histological types (abbreviated as L-sarcoma). Patients received a median of four trabectedin cycles (range: 1–40), mostly as a second-line treatment (~60% of patients). The ORR was 13.7% superior (p < 0.0001) in patients with L-sarcoma compared with patients with non-L-sarcoma (16.6% vs. 9.0%). Median progression-free survival (PFS) was 5.1 months, whereas median overall survival (OS) was 21.6 months. Significantly better PFS and OS were observed in patients with L-sarcoma, those with objective response...
Head and neck cancers (HNCs) represent the sixth most widespread malignancy worldwide. Surgery, r... more Head and neck cancers (HNCs) represent the sixth most widespread malignancy worldwide. Surgery, radiotherapy, chemotherapeutic and immunotherapeutic drugs represent the main clinical approaches for HNC patients. Moreover, HNCs are characterised by an elevated mutational load; however, specific genetic mutations or biomarkers have not yet been found. In this scenario, personalised medicine is showing its efficacy. To study the reliability and the effects of personalised treatments, preclinical research can take advantage of next-generation sequencing and innovative technologies that have been developed to obtain genomic and multi-omic profiles to drive personalised treatments. The crosstalk between malignant and healthy components, as well as interactions with extracellular matrices, are important features which are responsible for treatment failure. Preclinical research has constantly implemented in vitro and in vivo models to mimic the natural tumour microenvironment. Among them, 3...
Giant cell tumor of bone (GCTB) and desmoplastic fibroma (DF) are bone sarcomas with intermediate... more Giant cell tumor of bone (GCTB) and desmoplastic fibroma (DF) are bone sarcomas with intermediate malignant behavior and unpredictable prognosis. These locally aggressive neoplasms exhibit a predilection for the long bone or mandible of young adults, causing a severe bone resorption. In particular, the tumor stromal cells of these lesions are responsible for the recruiting of multinucleated giant cells which ultimately lead to bone disruption. In this regard, the underlying pathological mechanism of osteoclastogenesis processes in GCTB and DF is still poorly understood. Although current therapeutic strategy involves surgery, radiotherapy and chemotherapy, the benefit of the latter is still debated. Thus, in order to shed light on these poorly investigated diseases, we focused on the molecular biology of GCTB and DF. The expression of bone-vicious-cycle- and neoangiogenesis-related genes was investigated. Moreover, combining patient-derived primary cultures with 2D and 3D culture pla...
Background: Giant cell tumors of bone (GCTB) are osteolytic tumors. Denosumab, a RANK-L inhibitor... more Background: Giant cell tumors of bone (GCTB) are osteolytic tumors. Denosumab, a RANK-L inhibitor, is approved for GCTB. Data on serum bone turnover marker (sBTM) changes are lacking. We present a phase II correlative study on sBTMs in GCTB patients treated with denosumab. Methods: All GCTB patients receiving denosumab within a multicentre, open-label, phase 2 study were enrolled. Serum levels of carboxyterminal-crosslinked-telopeptide of type I collagen (s-CTX), alkaline phosphatase (ALP), bone-alkaline phosphatase (bALP), parathyroid hormone (sPTH), and osteocalcin (OCN) were prospectively assessed (baseline, T0, 3 months, T1, 6 months, T2). The primary endpoint was assessment of sBTM changes after denosumab; the secondary endpoints were disease-free survival (DFS) and sBTM correlation. Results: In 54 cases, sBTMs decreased during denosumab treatment except for sPTH. With a median follow-up of 59 months, 3-year DFS was 65% (%CI 52–79), with a significantly worse outcome for patien...
In the clinical management of solid tumors, the possibility to successfully couple the regenerati... more In the clinical management of solid tumors, the possibility to successfully couple the regeneration of injured tissues with the elimination of residual tumor cells left after surgery could open doors to new therapeutic strategies. In this work, we present a composite hydrogel–electrospun nanofiber scaffold, showing a modular architecture for the delivery of two pharmaceutics with distinct release profiles, that is potentially suitable for local therapy and post-surgical treatment of solid soft tumors. The composite was obtained by coupling gelatin hydrogels to poly(ethylene oxide)/poly(butylene terephthalate) block copolymer nanofibers. Results of the scaffolds’ characterization, together with the analysis of gelatin and drug release kinetics, displayed the possibility to modulate the device architecture to control the release kinetics of the drugs, also providing evidence of their activity. In vitro analyses were also performed using a human epithelioid sarcoma cell line. Furthermo...
located on the World Wide Web at: The online version of this article, along with updated informat... more located on the World Wide Web at: The online version of this article, along with updated information and services, is
Adult rhabdomyosarcoma (RMS) represents an uncommon entity with an incidence of less than 3% of a... more Adult rhabdomyosarcoma (RMS) represents an uncommon entity with an incidence of less than 3% of all soft tissue sarcomas (STS). Consequently, the natural history and the clinical management of this disease are infrequently reported. In order to fill this gap, we investigated the molecular biology of an adult RMS case series. The expression of epithelial mesenchymal transition-related gene and chemoresistance-related gene panels were evaluated. Moreover, taking advantage of our STS translational model combining patient-derived primary culture and 3D-scaffold, the pharmacological profile of an adult head and neck sclerosing RMS was assessed. Furthermore, NGS, microsatellite instability, and in silico analyses were carried out. RT-PCR identified the upregulation of CDH1, SLUG, MMP9, RAB22a, S100P, and LAPTM4b, representing promising biomarkers for this disease. Pharmacological profiling showed the highest sensitivity with anthracycline-based regimen in both 2D and 3D culture systems. N...
Bone is one of the most common sites for cancer metastasis. Bone tissue is composed by different ... more Bone is one of the most common sites for cancer metastasis. Bone tissue is composed by different kinds of cells that coexist in a coordinated balance. Due to the complexity of bone, it is impossible to capture the intricate interactions between cells under either physiological or pathological conditions. Hence, a variety of in vivo and in vitro approaches have been developed. Various models of tumor–bone diseases are routinely used to provide valuable information on the relationship between metastatic cancer cells and the bone tissue. Ideally, when modeling the metastasis of human cancers to bone, models would replicate the intra-tumor heterogeneity, as well as the genetic and phenotypic changes that occur with human cancers; such models would be scalable and reproducible to allow high-throughput investigation. Despite the continuous progress, there is still a lack of solid, amenable, and affordable models that are able to fully recapitulate the biological processes happening in viv...
Bone health impairment is a frequent detrimental consequence of the high bone tropism of prostate... more Bone health impairment is a frequent detrimental consequence of the high bone tropism of prostate cancer (PCa) cells. It is further worsened by administration of androgen-deprivation therapy (ADT), the current standard of care in the management of advanced PCa, through a rapid and dramatic increase in bone turnover and body mass changes. As a result, patients may experience substantial pain and poor quality of life (QoL) and have an increased risk of death. Notwithstanding the importance of this issue, however, bone health preservation is not yet a widespread clinical goal in daily practice.To address this urgent unmet need, following a thorough discussion of available data and sharing of their clinical practice experience, a panel of Italian experts in the field of bone health and metabolism formulated a number of practical advices for optimising the monitoring and treatment of bone health in men undergoing ADT during all phases of the disease. The rationale behind the venture was ...
Myxofibrosarcoma (MFS) belongs to the group of sarcoma tumors, which represent only 1% of the tot... more Myxofibrosarcoma (MFS) belongs to the group of sarcoma tumors, which represent only 1% of the totality of adult tumors worldwide. Thus, given the rare nature of this cancer, this makes the availability of MFS cell lines difficult. In an attempt to partially fill this gap, we immortalized a primary culture of MFS (IM-MFS-1) and compared the cell morphology with patient's tumor tissue. IM-MFS-1 was genetically characterized through a Comparative Genomic Hybridization (CGH) array and the mesenchymal phenotype was evaluated using Polymerase chain reaction (PCR) and immunofluorescence staining. Drug sensitivity for MFS therapies was monitored over time in cultures. We confirmed the conservation of the patient's tumor cell morphology and of the mesenchymal phenotype. Conversely, the synthesis and expression of CD109, a TGFβ co-receptor used to facilitate the diagnosis of high-grade MFS diagnosis, was maintained constant until high cancer cell line passages. The CGH array revealed ...
The use of patient-derived primary cell cultures in cancer preclinical assays has increased in re... more The use of patient-derived primary cell cultures in cancer preclinical assays has increased in recent years. The management of resected tumor tissue remains complex and a number of parameters must be respected to obtain complete sample digestion and optimal vitality yield. We provide an overview of the benefits of correct primary cell culture management using different preclinical methodologies, and describe the pros and cons of this model with respect to other kinds of samples. One important advantage is that the heterogeneity of the cell populations composing a primary culture partially reproduces the tumor microenvironment and crosstalk between malignant and healthy cells, neither of which is possible with cell lines. Moreover, the use of patient-derived specimens in innovative preclinical technologies, such as 3D systems or bioreactors, represents an important opportunity to improve the translational value of the results obtained. In vivo models could further our understanding o...
International journal of molecular sciences, Jan 8, 2017
Undifferentiated pleomorphic sarcoma (UPS) is an aggressive mesenchymal neoplasm with no specific... more Undifferentiated pleomorphic sarcoma (UPS) is an aggressive mesenchymal neoplasm with no specific line of differentiation. Eribulin, a novel synthetic microtubule inhibitor, has shown anticancer activity in several tumors, including soft tissue sarcomas (STS). We investigated the molecular biology of UPS, and the mechanisms of action of this innovative microtubule-depolymerizing drug. A primary culture from a patient with UPS was established and characterized in terms of gene expression. The activity of eribulin was also compared with that of other drugs currently used for STS treatment, including trabectedin. Finally, Western blot analysis was performed to better elucidate the activity of eribulin. Our results showed an upregulation of epithelial mesenchymal transition-related genes, and a downregulation of epithelial markers. Furthermore, genes involved in chemoresistance were upregulated. Pharmacological analysis confirmed limited sensitivity to chemotherapy. Interestingly, eribu...
Myxofibrosarcoma (MFS), formerly considered as a myxoid variant of malignant fibrous histiocytoma... more Myxofibrosarcoma (MFS), formerly considered as a myxoid variant of malignant fibrous histiocytoma, is the most common sarcoma of the extremities in adults and is characterized by a high frequency of local recurrence. The clinical behavior of MFS is unpredictable and the efficacy of chemotherapy is still not well documented. Furthermore, given the relatively recent recognition of MFS as a distinct pathologic entity its cellular and molecular biology has still not been extensively studied in patient-derived preclinical models. We examined the molecular biology and treatment outcomes of high-grade, patient-derived MFS primary cultures. A total of three patient-derived MFS primary cultures were analyzed. We evaluated the role of CD109 expression and also looked for a correlation between transforming growth factor-beta (TGF-β) expression and sensitivity of the primary cultures to different drugs. CD109 was a promising marker for the identification of more aggressive high-grade MFS and a ...
Patient-derived specimens are an invaluable resource to investigate tumor biology. However, in vi... more Patient-derived specimens are an invaluable resource to investigate tumor biology. However, in vivo studies on primary cultures are often limited by the small amount of material available, while conventional in vitro systems might alter the features and behavior that characterize cancer cells. We present our data obtained on primary dedifferentiated liposarcoma cells cultured in a 3D scaffold-based system and injected into a zebrafish model. Primary cells were characterized in vitro for their morphological features, sensitivity to drugs and biomarker expression, and in vivo for their engraftment and invasiveness abilities. The 3D culture showed a higher enrichment in cancer cells than the standard monolayer culture and a better preservation of liposarcoma-associated markers. We also successfully grafted primary cells into zebrafish, showing their local migratory and invasive abilities. Our work provides proof of concept of the ability of 3D cultures to maintain the original phenotyp...
Background: We assessed the real-life clinical impact of bone health management in patients with ... more Background: We assessed the real-life clinical impact of bone health management in patients with breast cancer (BC) receiving adjuvant endocrine therapy at an Italian Osteoncology Center. Methods: Pre- and post-menopausal women undergoing adjuvant endocrine therapy for early-stage BC who came to our institute for their first bone health evaluation from January 2011 to June 2016 were considered in this retrospective observational study. Results: 1125 pre- and post-menopausal early-stage BC patients (209 and 916, respectively) were evaluated. Median age was 61 years (range 26–88). In the pre-menopausal group, spinal x-ray revealed that 10 patients (4.7%) had a morphometric vertebral fracture. Higher age (OR: 1.14; 95% CI: 1.01–1.29) and bone mineral density (BMD) ≤ −2.5 (OR: 14.45; 95% CI: 1.70–122.67) were associated with a higher risk of bone fracture. The overall frequency of bone fracture was 17.6% (n = 161) in post-menopausal patients and a lower risk for bone fractures was assoc...
The Italian Sarcoma Group performed this retrospective analysis of patients with advanced soft ti... more The Italian Sarcoma Group performed this retrospective analysis of patients with advanced soft tissue sarcoma, pretreated with ≥1 anthracycline-based treatment, and treated with trabectedin every three weeks. Primary endpoint was to describe real-life use of trabectedin across Italy. Secondary endpoints included objective response rate (ORR) and safety. Overall, 512 patients from 20 Italian centers were evaluated. Leiomyosarcoma (37.7%)/liposarcoma (30.3%) were the most prevalent histological types (abbreviated as L-sarcoma). Patients received a median of four trabectedin cycles (range: 1–40), mostly as a second-line treatment (~60% of patients). The ORR was 13.7% superior (p < 0.0001) in patients with L-sarcoma compared with patients with non-L-sarcoma (16.6% vs. 9.0%). Median progression-free survival (PFS) was 5.1 months, whereas median overall survival (OS) was 21.6 months. Significantly better PFS and OS were observed in patients with L-sarcoma, those with objective response...
Head and neck cancers (HNCs) represent the sixth most widespread malignancy worldwide. Surgery, r... more Head and neck cancers (HNCs) represent the sixth most widespread malignancy worldwide. Surgery, radiotherapy, chemotherapeutic and immunotherapeutic drugs represent the main clinical approaches for HNC patients. Moreover, HNCs are characterised by an elevated mutational load; however, specific genetic mutations or biomarkers have not yet been found. In this scenario, personalised medicine is showing its efficacy. To study the reliability and the effects of personalised treatments, preclinical research can take advantage of next-generation sequencing and innovative technologies that have been developed to obtain genomic and multi-omic profiles to drive personalised treatments. The crosstalk between malignant and healthy components, as well as interactions with extracellular matrices, are important features which are responsible for treatment failure. Preclinical research has constantly implemented in vitro and in vivo models to mimic the natural tumour microenvironment. Among them, 3...
Giant cell tumor of bone (GCTB) and desmoplastic fibroma (DF) are bone sarcomas with intermediate... more Giant cell tumor of bone (GCTB) and desmoplastic fibroma (DF) are bone sarcomas with intermediate malignant behavior and unpredictable prognosis. These locally aggressive neoplasms exhibit a predilection for the long bone or mandible of young adults, causing a severe bone resorption. In particular, the tumor stromal cells of these lesions are responsible for the recruiting of multinucleated giant cells which ultimately lead to bone disruption. In this regard, the underlying pathological mechanism of osteoclastogenesis processes in GCTB and DF is still poorly understood. Although current therapeutic strategy involves surgery, radiotherapy and chemotherapy, the benefit of the latter is still debated. Thus, in order to shed light on these poorly investigated diseases, we focused on the molecular biology of GCTB and DF. The expression of bone-vicious-cycle- and neoangiogenesis-related genes was investigated. Moreover, combining patient-derived primary cultures with 2D and 3D culture pla...
Background: Giant cell tumors of bone (GCTB) are osteolytic tumors. Denosumab, a RANK-L inhibitor... more Background: Giant cell tumors of bone (GCTB) are osteolytic tumors. Denosumab, a RANK-L inhibitor, is approved for GCTB. Data on serum bone turnover marker (sBTM) changes are lacking. We present a phase II correlative study on sBTMs in GCTB patients treated with denosumab. Methods: All GCTB patients receiving denosumab within a multicentre, open-label, phase 2 study were enrolled. Serum levels of carboxyterminal-crosslinked-telopeptide of type I collagen (s-CTX), alkaline phosphatase (ALP), bone-alkaline phosphatase (bALP), parathyroid hormone (sPTH), and osteocalcin (OCN) were prospectively assessed (baseline, T0, 3 months, T1, 6 months, T2). The primary endpoint was assessment of sBTM changes after denosumab; the secondary endpoints were disease-free survival (DFS) and sBTM correlation. Results: In 54 cases, sBTMs decreased during denosumab treatment except for sPTH. With a median follow-up of 59 months, 3-year DFS was 65% (%CI 52–79), with a significantly worse outcome for patien...
In the clinical management of solid tumors, the possibility to successfully couple the regenerati... more In the clinical management of solid tumors, the possibility to successfully couple the regeneration of injured tissues with the elimination of residual tumor cells left after surgery could open doors to new therapeutic strategies. In this work, we present a composite hydrogel–electrospun nanofiber scaffold, showing a modular architecture for the delivery of two pharmaceutics with distinct release profiles, that is potentially suitable for local therapy and post-surgical treatment of solid soft tumors. The composite was obtained by coupling gelatin hydrogels to poly(ethylene oxide)/poly(butylene terephthalate) block copolymer nanofibers. Results of the scaffolds’ characterization, together with the analysis of gelatin and drug release kinetics, displayed the possibility to modulate the device architecture to control the release kinetics of the drugs, also providing evidence of their activity. In vitro analyses were also performed using a human epithelioid sarcoma cell line. Furthermo...
located on the World Wide Web at: The online version of this article, along with updated informat... more located on the World Wide Web at: The online version of this article, along with updated information and services, is
Adult rhabdomyosarcoma (RMS) represents an uncommon entity with an incidence of less than 3% of a... more Adult rhabdomyosarcoma (RMS) represents an uncommon entity with an incidence of less than 3% of all soft tissue sarcomas (STS). Consequently, the natural history and the clinical management of this disease are infrequently reported. In order to fill this gap, we investigated the molecular biology of an adult RMS case series. The expression of epithelial mesenchymal transition-related gene and chemoresistance-related gene panels were evaluated. Moreover, taking advantage of our STS translational model combining patient-derived primary culture and 3D-scaffold, the pharmacological profile of an adult head and neck sclerosing RMS was assessed. Furthermore, NGS, microsatellite instability, and in silico analyses were carried out. RT-PCR identified the upregulation of CDH1, SLUG, MMP9, RAB22a, S100P, and LAPTM4b, representing promising biomarkers for this disease. Pharmacological profiling showed the highest sensitivity with anthracycline-based regimen in both 2D and 3D culture systems. N...
Bone is one of the most common sites for cancer metastasis. Bone tissue is composed by different ... more Bone is one of the most common sites for cancer metastasis. Bone tissue is composed by different kinds of cells that coexist in a coordinated balance. Due to the complexity of bone, it is impossible to capture the intricate interactions between cells under either physiological or pathological conditions. Hence, a variety of in vivo and in vitro approaches have been developed. Various models of tumor–bone diseases are routinely used to provide valuable information on the relationship between metastatic cancer cells and the bone tissue. Ideally, when modeling the metastasis of human cancers to bone, models would replicate the intra-tumor heterogeneity, as well as the genetic and phenotypic changes that occur with human cancers; such models would be scalable and reproducible to allow high-throughput investigation. Despite the continuous progress, there is still a lack of solid, amenable, and affordable models that are able to fully recapitulate the biological processes happening in viv...
Bone health impairment is a frequent detrimental consequence of the high bone tropism of prostate... more Bone health impairment is a frequent detrimental consequence of the high bone tropism of prostate cancer (PCa) cells. It is further worsened by administration of androgen-deprivation therapy (ADT), the current standard of care in the management of advanced PCa, through a rapid and dramatic increase in bone turnover and body mass changes. As a result, patients may experience substantial pain and poor quality of life (QoL) and have an increased risk of death. Notwithstanding the importance of this issue, however, bone health preservation is not yet a widespread clinical goal in daily practice.To address this urgent unmet need, following a thorough discussion of available data and sharing of their clinical practice experience, a panel of Italian experts in the field of bone health and metabolism formulated a number of practical advices for optimising the monitoring and treatment of bone health in men undergoing ADT during all phases of the disease. The rationale behind the venture was ...
Myxofibrosarcoma (MFS) belongs to the group of sarcoma tumors, which represent only 1% of the tot... more Myxofibrosarcoma (MFS) belongs to the group of sarcoma tumors, which represent only 1% of the totality of adult tumors worldwide. Thus, given the rare nature of this cancer, this makes the availability of MFS cell lines difficult. In an attempt to partially fill this gap, we immortalized a primary culture of MFS (IM-MFS-1) and compared the cell morphology with patient's tumor tissue. IM-MFS-1 was genetically characterized through a Comparative Genomic Hybridization (CGH) array and the mesenchymal phenotype was evaluated using Polymerase chain reaction (PCR) and immunofluorescence staining. Drug sensitivity for MFS therapies was monitored over time in cultures. We confirmed the conservation of the patient's tumor cell morphology and of the mesenchymal phenotype. Conversely, the synthesis and expression of CD109, a TGFβ co-receptor used to facilitate the diagnosis of high-grade MFS diagnosis, was maintained constant until high cancer cell line passages. The CGH array revealed ...
The use of patient-derived primary cell cultures in cancer preclinical assays has increased in re... more The use of patient-derived primary cell cultures in cancer preclinical assays has increased in recent years. The management of resected tumor tissue remains complex and a number of parameters must be respected to obtain complete sample digestion and optimal vitality yield. We provide an overview of the benefits of correct primary cell culture management using different preclinical methodologies, and describe the pros and cons of this model with respect to other kinds of samples. One important advantage is that the heterogeneity of the cell populations composing a primary culture partially reproduces the tumor microenvironment and crosstalk between malignant and healthy cells, neither of which is possible with cell lines. Moreover, the use of patient-derived specimens in innovative preclinical technologies, such as 3D systems or bioreactors, represents an important opportunity to improve the translational value of the results obtained. In vivo models could further our understanding o...
International journal of molecular sciences, Jan 8, 2017
Undifferentiated pleomorphic sarcoma (UPS) is an aggressive mesenchymal neoplasm with no specific... more Undifferentiated pleomorphic sarcoma (UPS) is an aggressive mesenchymal neoplasm with no specific line of differentiation. Eribulin, a novel synthetic microtubule inhibitor, has shown anticancer activity in several tumors, including soft tissue sarcomas (STS). We investigated the molecular biology of UPS, and the mechanisms of action of this innovative microtubule-depolymerizing drug. A primary culture from a patient with UPS was established and characterized in terms of gene expression. The activity of eribulin was also compared with that of other drugs currently used for STS treatment, including trabectedin. Finally, Western blot analysis was performed to better elucidate the activity of eribulin. Our results showed an upregulation of epithelial mesenchymal transition-related genes, and a downregulation of epithelial markers. Furthermore, genes involved in chemoresistance were upregulated. Pharmacological analysis confirmed limited sensitivity to chemotherapy. Interestingly, eribu...
Myxofibrosarcoma (MFS), formerly considered as a myxoid variant of malignant fibrous histiocytoma... more Myxofibrosarcoma (MFS), formerly considered as a myxoid variant of malignant fibrous histiocytoma, is the most common sarcoma of the extremities in adults and is characterized by a high frequency of local recurrence. The clinical behavior of MFS is unpredictable and the efficacy of chemotherapy is still not well documented. Furthermore, given the relatively recent recognition of MFS as a distinct pathologic entity its cellular and molecular biology has still not been extensively studied in patient-derived preclinical models. We examined the molecular biology and treatment outcomes of high-grade, patient-derived MFS primary cultures. A total of three patient-derived MFS primary cultures were analyzed. We evaluated the role of CD109 expression and also looked for a correlation between transforming growth factor-beta (TGF-β) expression and sensitivity of the primary cultures to different drugs. CD109 was a promising marker for the identification of more aggressive high-grade MFS and a ...
Patient-derived specimens are an invaluable resource to investigate tumor biology. However, in vi... more Patient-derived specimens are an invaluable resource to investigate tumor biology. However, in vivo studies on primary cultures are often limited by the small amount of material available, while conventional in vitro systems might alter the features and behavior that characterize cancer cells. We present our data obtained on primary dedifferentiated liposarcoma cells cultured in a 3D scaffold-based system and injected into a zebrafish model. Primary cells were characterized in vitro for their morphological features, sensitivity to drugs and biomarker expression, and in vivo for their engraftment and invasiveness abilities. The 3D culture showed a higher enrichment in cancer cells than the standard monolayer culture and a better preservation of liposarcoma-associated markers. We also successfully grafted primary cells into zebrafish, showing their local migratory and invasive abilities. Our work provides proof of concept of the ability of 3D cultures to maintain the original phenotyp...
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