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Biodegradable blends based on plasticized poly(lactic acid) PLA and thermoplastic starch (TPS) have been obtained. The influence of the PLA plasticizer as a compatibility agent has been studied by using two different plasticizers such as neat oligomeric lactic acid (OLA) and functionalized with maleic acid (mOLA). In particular, the morphological, thermal, and mechanical properties have been studied as well as the shape memory ability of the melt-processed materials. Therefore, the influence of the interaction between different plasticizers and the PLA matrix as well as the compatibility between the two polymeric phases on the thermally-activated shape memory properties have been studied. It is very interesting to use the same additive able to act as both plasticizer and compatibilizer, decreasing the glass transition temperature of PLA to a temperature close to the physiological one, obtaining a material suitable for potential biomedical applications. In particular, we obtain that OLA-plasticized blend (oPLA/TPS) show very good thermally-activated capability at 45 °C and 50% deformation, while the blend obtained by using maleic OLA (moPLA/TPS) did not show shape memory behavior at 45 °C and 50% deformation. This fact is due to their morphological changes and the loss of two well-distinguished phases, one acting as fixed phase and the other one acting as switching phase to typically obtain shape memory response. Therefore, the thermally-activated shape memory results show that it is very important to make a balance between plasticizer and compatibilizer, considering the need of two well-established phases to obtain shape memory response.
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Emerging evidence indicates that chemoresistance is closely related to altered metabolism in cancer. Here, we hypothesized that distinct metabolic gene expression profiling (GEP) signatures might be correlated with outcome and with specific fluorodeoxyglucose positron emission tomography (FDG-PET) radiomic profiles in diffuse large B-cell lymphoma (DLBCL). We retrospectively analyzed a discovery cohort of 48 consecutive patients with DLBCL treated at our center with standard first-line chemoimmunotherapy by performing targeted GEP (T-GEP)- and FDG-PET radiomic analyses on the same target lesions at baseline. T-GEP-based metabolic profiling identified a 6-gene signature independently associated with outcomes in univariate and multivariate analyses. This signature included genes regulating mitochondrial oxidative metabolism (SCL25A1, PDK4, PDPR) that were upregulated and was inversely associated with genes involved in hypoxia and glycolysis (MAP2K1, HIF1A, GBE1) that were downregulated. These data were validated in 2 large publicly available cohorts. By integrating FDG-PET radiomics and T-GEP, we identified a radiometabolic signature (RadSig) including 4 radiomic features (histo kurtosis, histo energy, shape sphericity, and neighboring gray level dependence matrix contrast), significantly associated with the metabolic GEP-based signature (r = 0.43, P = .0027) and with progression-free survival (P = .028). These results were confirmed using different target lesions, an alternative segmentation method, and were validated in an independent cohort of 64 patients. RadSig retained independent prognostic value in relation to the International Prognostic Index score and metabolic tumor volume (MTV). Integration of RadSig and MTV further refined prognostic stratification. This study provides the proof of principle for the use of FDG-PET radiomics as a tool for noninvasive assessment of cancer metabolism and prognostic stratification in DLBCL.
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Fluordesoxiglucose F18 , Linfoma Difuso de Grandes Células B , Humanos , Estudos Retrospectivos , Tomografia por Emissão de Pósitrons/métodos , Linfoma Difuso de Grandes Células B/patologia , Perfilação da Expressão GênicaRESUMO
BACKGROUND: The immune response to breast implants after COVID-19 disease or COVID-19 vaccine administration includes acute inflammatory manifestations, capsular contracture and seroma. Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a very rare tumor in which numerous up-regulated pro-inflammatory immunological pathways activate a T cell lymphoproliferative disorder. METHODS: The first reported case of a BIA-ALCL hidden mass clinically manifesting with inflammatory signs after SARS-CoV-2 infection and vaccinations is here described. RESULTS: Complete capsulectomy and adjuvant chemotherapy were performed and immediately after the surgical procedure local inflammatory signs disappeared; no evidence of disease was present 1 year later. CONCLUSIONS: Immunological stimulation by COVID-19 disease and vaccines may highlight some rare clinical manifestations of BIA-ALCL; persistent inflammatory symptomatology over breast implants should be investigated using second-level imaging. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
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Implante Mamário , Implantes de Mama , Neoplasias da Mama , COVID-19 , Linfoma Anaplásico de Células Grandes , Humanos , Feminino , Linfoma Anaplásico de Células Grandes/patologia , Vacinas contra COVID-19 , Neoplasias da Mama/cirurgia , Mastectomia , SARS-CoV-2 , Implante Mamário/métodos , Imunização , VacinaçãoRESUMO
Chitin nanofibrils (CN) can be obtained from crustaceans and fungal sources and can be used for preparing coatings for bioplastic films, that are fundamental for developing a safe and sustainable biodegradable food packaging. Coatings with different concentrations of CN from shrimps were applied on different bioplastic substrates, like Poly (butylene succinate-co-adipate)/Poly(3-hydroxybutyrate-co-3-hydroxyvalerate (PBSA/PHBV) blend, Polybutylene succinate (PBS), and Polybutylene adipate terephthalate/Poly(lactic acid) (PBAT/PLA) blend, but the adhesion to the substrates was scarce. On the contrary, the fungal-based CN showed a better adhesion. Additionally, it was found that the use of an additive based on oligomeric lactic acid was useful to prepare a coating with an improved adhesion to bioplastics. The gas barrier properties to oxygen and water vapour of coated and un-coated films were measured, revealing an improvement of these properties thanks to applied coatings, especially towards the oxygen. Antimicrobial properties and biodegradation capacity were also evaluated revealing an antibacterial effect of the coatings that did not significantly interfere with their biodegradability. The results are discussed and interpreted considering the correlation between composition and macromolecular structures with the observed functional properties.
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The role and regulation of innate immune cells is poorly understood in B-cell non-Hodgkin lymphoma (NHL). As natural killer (NK) cells, helper innate lymphoid cells (ILCs) are lymphocytes endowed with either anti- or pro-tumour activity and involved in inflammatory processes. In our ex vivo analysis of NK cells and ILCs from NHL patients, we observed that, in comparison to healthy donors (HD), the frequency of the cytotoxic subset of NK cells, the CD16+ NK, decreased in patients' peripheral blood. In general, circulating NK cells showed a pro-tumorigenic phenotype, while ILCs displayed a more activated/cytotoxic phenotype. Conversely, at the tumour site, in patients' lymph nodes, ILCs showed a low expression of granzyme.In vitromixed lymphocyte-tumour cell cultures with HD PBMCs and NHL cell lines demonstrated that ILC cytotoxic potential was lowered by the presence of tumour cells but, in the absence of T regulatory cells (Tregs), their cytolytic potential was recovered. Our data shed novel light on dysfunctional innate immunity in NHL. We suggest a new mechanism of tumour immuno-escape based on the reduction of cell cytotoxicity involving ILCs and likely controlled by Tregs.
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Antineoplásicos , Linfoma não Hodgkin , Neoplasias , Humanos , Evasão Tumoral , Imunidade Inata , Linfócitos , Células Matadoras Naturais , Neoplasias/patologia , Linfoma não Hodgkin/patologiaRESUMO
The role of macrophages (Mo) and their prognostic impact in diffuse large B-cell lymphomas (DLBCL) remain controversial. By regulating the lipid metabolism, Liver-X-Receptors (LXRs) control Mo polarization/inflammatory response, and their pharmacological modulation is under clinical investigation to treat human cancers, including lymphomas. Herein, we surveyed the role of LXRs in DLBCL for prognostic purposes. Comparing bulk tumors with purified malignant and normal B-cells, we found an intriguing association of NR1H3, encoding for the LXR-α isoform, with the tumor microenvironment (TME). CIBERSORTx-based purification on large DLBCL datasets revealed a high expression of the receptor transcript in M1-like pro-inflammatory Mo. By determining an expression cut-off of NR1H3, we used digital measurement to validate its prognostic capacity on two large independent on-trial and real-world cohorts. Independently of classical prognosticators, NR1H3high patients displayed longer survival compared with NR1H3low cases and a high-resolution Mo GEP dissection suggested a remarkable transcriptional divergence between subgroups. Overall, our findings indicate NR1H3 as a Mo-related biomarker identifying patients at higher risk and prompt future preclinical studies investigating its mouldability for therapeutic purposes.
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Linfoma Difuso de Grandes Células B , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/genética , Microambiente Tumoral , Receptores X do Fígado/genéticaRESUMO
In this work, the thermally-activated shape memory behavior of poly(lactic acid)-based electrospun fibers (PLA-based efibers) reinforced with different amounts of magnesium oxide (MgO) nanoparticles (NPs) was studied at different temperatures. In particular, MgO NPs were added at different concentrations, such as 0.1, 0.5, 1 and 3 wt%, with respect to the PLA matrix. The glass-transition temperature of PLA-based efibers was modulated by adding a 20 wt% of oligomer lactic acid as plasticizer. Once the plasticized PLA-based efibers were obtained and basically characterized in term of morphology as well as thermal and mechanical properties, thermo-mechanical cycles were carried out at 60 °C and 45 °C in order to study their thermally-activated shape memory response, demonstrating that their crystalline nature strongly affects their shape memory behavior. Importantly, we found that the plastificant effect in the mechanical response of the reinforced plasticized PLA efibers is balanced with the reinforcing effect of the MgO NPs, obtaining the same mechanical response of neat PLA fibers. Finally, both the strain recovery and strain fixity ratios of each of the plasticized PLA-based efibers were calculated, obtaining excellent thermally-activated shape memory response at 45 °C, demonstrating that 1 wt% MgO nanoparticles was the best concentration for the plasticized system.
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T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL) is a rare and aggressive variant of diffuse large B-cell lymphoma (DLBCL) that usually affects young to middle-aged patients, with disseminated disease at presentation. The tumor microenvironment (TME) plays a key role in THRLBCL due to its peculiar cellular composition (<10% neoplastic B cells interspersed in a cytotoxic T-cell/histiocyte-rich background). A significant percentage of THRLBCL is refractory to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (RCHOP)-based regimens and to chimeric antigen receptor T-cell therapy; thus, the development of a specific therapeutic approach for these patients represents an unmet clinical need. To better understand the interaction of immune cells in THRLBCL TME and identify more promising therapeutic strategies, we compared the immune gene expression profiles of 12 THRLBCL and 10 DLBCL samples, and further corroborated our findings in an extended in silico set. Gene coexpression network analysis identified the predominant role of the programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) axis in the modulation of the immune response. Furthermore, the PD-1/PD-L1 activation was flanked by the overexpression of 48 genes related to the functional exhaustion of T cells. Globally, THRLBCL TME was highly interferon-inflamed and severely exhausted. The immune gene profiling findings strongly suggest that THRLBCL may be responsive to anti-PD-1 therapy but also allowed us to take a step forward in understanding THRLBCL TME. Of therapeutic relevance, we validated our results by immunohistochemistry, identifying a subset of TCF1+ (T cell-specific transcription factor 1, encoded by the TCF7 gene) progenitor exhausted T cells enriched in patients with THRLBCL. This subset of TCF1+ exhausted T cells correlates with good clinical response to immune checkpoint therapy and may improve prediction of anti-PD-1 response in patients with THRLBCL.
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Antígeno B7-H1 , Linfoma Difuso de Grandes Células B , Apoptose , Antígeno B7-H1/genética , Fator 1-alfa Nuclear de Hepatócito , Histiócitos/metabolismo , Histiócitos/patologia , Humanos , Ligantes , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/genética , Receptor de Morte Celular Programada 1 , Microambiente TumoralRESUMO
Abstract Introduction: Lymphomas arising from cardiac myxomas represent a particularly rare pathology, with only few cases reported in the literature. Case presentation: We report a complete excision of a malignant lymphoma arising from a cardiac myxoma in a 44-year-old female patient. The myxoma presented like a floating mass within the left atrium with a maximum diameter of 3.5 cm. The clinical post-operative period was uneventful and the patient was dismissed on the 6th post-operative day. Conclusion: This case reinforces the concept of radical excision of cardiac neoplasms.
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In this work, we report the development and characterization of polylactide (PLA) blends with improved toughness by the addition of 10 wt.% lactic acid oligomers (OLA) and assess the feasibility of reactive extrusion (REX) and injection moulding to obtain high impact resistant injection moulded parts. To improve PLA/OLA interactions, two approaches are carried out. On the one hand, reactive extrusion of PLA/OLA with different dicumyl peroxide (DCP) concentrations is evaluated and, on the other hand, the effect of maleinized linseed oil (MLO) is studied. The effect of DCP and MLO content used in the reactive extrusion process is evaluated in terms of mechanical, thermal, dynamic mechanical, wetting and colour properties, as well as the morphology of the obtained materials. The impact strength of neat PLA (39.3 kJ/m2) was slightly improved up to 42.4 kJ/m2 with 10 wt.% OLA. Nevertheless, reactive extrusion with 0.3 phr DCP (parts by weight of DCP per 100 parts by weight of PLA-OLA base blend 90:10) led to a noticeable higher impact strength of 51.7 kJ/m2, while the reactive extrusion with 6 phr MLO gave an even higher impact strength of 59.5 kJ/m2, thus giving evidence of the feasibility of these two approaches to overcome the intrinsic brittleness of PLA. Therefore, despite MLO being able to provide the highest impact strength, reactive extrusion with DCP led to high transparency, which could be an interesting feature in food packaging, for example. In any case, these two approaches represent environmentally friendly strategies to improve PLA toughness.
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INTRODUCTION: Primary CNS lymphoma (PCNSL) has traditionally been treated with induction HD-MTX-based chemotherapy, followed by consolidation whole-brain radiotherapy. However, this approach is associated with significant neurocognitive complications, especially in older patients. Therefore, different consolidation protocols have been evaluated. High-dose chemotherapy followed by autologous stem cell transplantation (HD-ASCT) has the best long-term survival outcomes in younger patients. AREAS COVERED: In this review of the literature, we focus on the overall therapeutic strategy and advances in the management of the aggressive primary CNS B-cell lymphomas. EXPERT OPINION: In young and fit PCNSL patients, HD-ASCT is the preferred consolidation strategy to achieve long-term survivals. Older patients with good performance status should also be evaluated for MTX-based induction polychemotherapy followed by ASCT. However, management of PCNSL patients remains challenging, and new avenues with targeted therapies are under investigation. To date, ibrutinib, lenalidomide, and immune checkpoint inhibitors appearto be promising in PCNSL. However, as monotherapy, durable responses are less likely to be achieved. Unfortunately, when combined with chemoimmunotherapy, considerable toxicity and mortality have been reported. Clinical trials on these molecules are aiming to reduce toxicity and maintain responses. CAR-T-cell therapy has recently emerged as a further option. It has shown efficacy in patients with secondary CNS lymphoma, with few but encouraging results in primary CNSL.
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Neoplasias do Sistema Nervoso Central , Transplante de Células-Tronco Hematopoéticas , Linfoma de Células B , Linfoma , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias do Sistema Nervoso Central/terapia , Terapia Combinada , Humanos , Linfoma/terapia , Linfoma de Células B/tratamento farmacológico , Metotrexato/uso terapêutico , Transplante AutólogoRESUMO
The present work puts the Circular Bioeconomy's concept into action, originally valorizing residues of spent coffee grains from the beverage liquor coffee industry to develop green composite pieces of polylactide (PLA). The as-received spent coffee grains were first milled to obtain the so-called spent coffee grounds (SCGs) that were, thereafter, incorporated at 20 wt.% into PLA by extrusion. Finally, the resultant green composite pellets were shaped into pieces by injection molding. Moreover, two oligomers of lactic acid (OLAs), namely OLA2 and OLA2mal, the latter being functionalized with maleic anhydride (MAH), were added with SCGs during the extrusion process at 10 wt.%. The results show that, opposite to most claims published in the literature of green composites of PLA, the incorporation of the liquor waste derived SCGs increased the ductility of the pieces by approximately 280% mainly due to their high lipid content. Moreover, the simultaneous addition of OLA2 and OLA2mal further contributed to improve the tensile strength of the green composite pieces by nearly 36% and 60%, respectively. The higher performance of OLA2mal was ascribed to the chemical interaction achieved between the biopolyester and the lignocellulosic fillers by the MAH groups. The resultant green composite pieces are very promising as disposable food-serving utensils and tableware.
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INTRODUCTION: Lymphomas arising from cardiac myxomas represent a particularly rare pathology, with only few cases reported in the literature.Case presentation: We report a complete excision of a malignant lymphoma arising from a cardiac myxoma in a 44-year-old female patient. The myxoma presented like a floating mass within the left atrium with a maximum diameter of 3.5 cm. The clinical post-operative period was uneventful and the patient was dismissed on the 6th post-operative day. CONCLUSION: This case reinforces the concept of radical excision of cardiac neoplasms.
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Neoplasias Cardíacas , Linfoma , Mixoma , Adulto , Feminino , Átrios do Coração/patologia , Átrios do Coração/cirurgia , Neoplasias Cardíacas/diagnóstico por imagem , Neoplasias Cardíacas/patologia , Neoplasias Cardíacas/cirurgia , Humanos , Linfoma/diagnóstico por imagem , Linfoma/patologia , Linfoma/cirurgia , Mixoma/diagnóstico por imagem , Mixoma/patologia , Mixoma/cirurgiaRESUMO
Standard chemotherapies for diffuse large B-cell lymphoma (DLBCL), based on the induction of exogenous DNA damage and oxidative stress, are often less effective in the presence of increased MYC and BCL-2 levels, especially in the case of double hit (DH) lymphomas harboring rearrangements of the MYC and BCL-2 oncogenes, which enrich for a patient's population characterized by refractoriness to anthracycline-based chemotherapy. Here we hypothesized that adaptive mechanisms to MYC-induced replicative and oxidative stress, consisting in DNA damage response (DDR) activation and BCL-2 overexpression, could represent the biologic basis of the poor prognosis and chemoresistance observed in MYC/BCL-2-positive lymphoma. We first integrated targeted gene expression profiling (T-GEP), fluorescence in situ hybridization (FISH) analysis, and characterization of replicative and oxidative stress biomarkers in two independent DLBCL cohorts. The presence of oxidative DNA damage biomarkers identified a poor prognosis double expresser (DE)-DLBCL subset, characterized by relatively higher BCL-2 gene expression levels and enrichment for DH lymphomas. Based on these findings, we tested therapeutic strategies based on combined DDR and BCL-2 inhibition, confirming efficacy and synergistic interactions in in vitro and in vivo DH-DLBCL models. These data provide the rationale for precision-therapy strategies based on combined DDR and BCL-2 inhibition in DH or DE-DLBCL.
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Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Enzimas Reparadoras do DNA/antagonistas & inibidores , Regulação Leucêmica da Expressão Gênica/efeitos dos fármacos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Proteínas Proto-Oncogênicas c-bcl-2/antagonistas & inibidores , Sulfonamidas/farmacologia , Tiofenos/farmacologia , Ureia/análogos & derivados , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/farmacologia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Linfoma Difuso de Grandes Células B/metabolismo , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Taxa de Sobrevida , Ureia/farmacologia , Adulto JovemRESUMO
Peripheral T-cell lymphoma, not otherwise specified (PTCL_NOS) corresponds to about one fourth of mature T-cell tumors, which overall represent 10-12% of all lymphoid malignancies. This category comprises all T-cell neoplasms, which do not correspond to any of the distinct entities listed in the WHO (World Health Organization) Classification of Tumours of Haematopoietic and Lymphoid Tissues. In spite of the extreme variability of morphologic features and phenotypic profiles, gene expression profiling (GEP) studies have shown a signature that is distinct from that of all remaining PTCLs. GEP has also allowed the identification of subtypes provided with prognostic relevance. Conversely to GEP, next-generation sequencing (NGS) has so far been applied to a limited number of cases, providing some hints to better understand the pathobiology of PTCL_NOS. Although several pieces of information have emerged from pathological studies, PTCL_NOS still remains a tumor with a dismal prognosis. The usage of CHOEP (cyclophosphamide, doxorubicin, vincristine, prednisone, etoposide) followed by autologous stem cell transplantation may represent the best option, by curing about 50% of the patients whom such an approach can be applied to. Many new drugs have been proposed without achieving the expected results. Thus, the optimal treatment of PTCL_NOS remains unidentified.
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Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and highly aggressive hematologic malignancy originating from plasmacytoid dendritic cells (pDCs). The microRNA expression profile of BPDCN was compared to that of normal pDCs and the impact of miRNA dysregulation on the BPDCN transcriptional program was assessed. MiRNA and gene expression profiling data were integrated to obtain the BPDCN miRNA-regulatory network. The biological process mainly dysregulated by this network was predicted to be neurogenesis, a phenomenon raising growing interest in solid tumors. Neurogenesis was explored in BPDCN by querying different molecular sources (RNA sequencing, Chromatin immunoprecipitation-sequencing, and immunohistochemistry). It was shown that BPDCN cells upregulated neural mitogen genes possibly critical for tumor dissemination, expressed neuronal progenitor markers involved in cell migration, exchanged acetylcholine neurotransmitter, and overexpressed multiple neural receptors that may stimulate tumor proliferation, migration and cross-talk with the nervous system. Most neural genes upregulated in BPDCN are currently investigated as therapeutic targets.
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Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a rare and newly recognized subtype of T cell Non-Hodgkin Lymphoma (NHLs) associated with breast implants.The mechanism involved in the development of this kind of lymphoma is still uncertain.BIA-ALCL is generally an indolent disease localized to the breast implant and its capsule and effectively treated with capsulectomy alone without chemotherapy.Clinically, BIA-ALCL may typically present a sudden-onset breast-swelling secondary to periimplant effusion. The minority of BIA-ALCL patients present a more aggressive mass-forming subtype, for which systemic therapy is mandatory.Despite the number of cases has recently increased, BIA-ALCL remains a rare disease described mainly in several case reports and small case series.Breast imaging, including mammography, ultrasound and breast MRI are routinely used in the screening of breast cancer; however, guidelines for the imaging and pathological diagnosis of this disease have only recently been proposed and included in the 2019 National Comprehensive Cancer Network (NCCN) consensus guidelines for BIA-ALCL.The main purpose of this pictorial is to illustrate the MRI signs of BIA-ALCL and correlate them with the corresponding pathology features in order to improve the knowledge of the principals MRI features of this type of lymphoma.