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1.
Carbohydr Polym ; 259: 117696, 2021 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-33673985

RESUMEN

Doxorubicin (DOX), an anthracycline drug, is widely used for the treatment of several cancers like osteosarcoma, cervical carcinoma, breast cancer, etc. DOX lacks target specificity; thereby it also affects normal cells thus resulting in several side-effects. A drug delivery system (DDS) can be used to deliver the drug in a controlled and sustained manner at a targeted site within the body. Various DDS like nanoemulsions, polymeric nanoparticles, and liposomes are used for loading DOX. Alginate, a polysaccharide is widely used for fabricating DDS due to its biodegradable and bio-compatible properties. Alginates, in combination with other biomaterials, have been extensively used as a novel drug delivery carrier for DOX. Alginate provides a platform for drug delivery in different forms like hydrogels, nanogels, nanoparticles, microparticles, graphene oxide systems, magnetic systems, etc. Herein, we briefly describe alginate in combination with other materials as a nanocarrier for targeted delivery of DOX for anti-cancer treatment.


Asunto(s)
Alginatos/química , Antibióticos Antineoplásicos/química , Doxorrubicina/química , Portadores de Fármacos/química , Animales , Antibióticos Antineoplásicos/metabolismo , Antibióticos Antineoplásicos/farmacología , Antibióticos Antineoplásicos/uso terapéutico , Supervivencia Celular/efectos de los fármacos , Doxorrubicina/metabolismo , Doxorrubicina/farmacología , Doxorrubicina/uso terapéutico , Humanos , Hidrogeles/química , Nanogeles/química , Neoplasias/tratamiento farmacológico , Neoplasias/patología
2.
Int J Nanomedicine ; 16: 2219-2236, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33762822

RESUMEN

Introduction: In this paper, we have designed and formulated, a novel synthesis of doxorubicin (DOX) loaded bimetallic gold nanorods in which gold salt (HAuCl4) is chelated with anthracycline (DOX), diacid polyethylene-glycol (PEG-COOH) and gadolinium salt (GdCl3 * 6 H2O) to form DOX IN-Gd-AuNRs compared with DOX ON-Gd-AuNRs in which the drug was grafted onto the bimetallic pegylated nanoparticle surface by electrostatic adsorption. Material and Method: The physical and chemical evaluation was performed by spectroscopic analytical techniques (Raman spectroscopy, UV-Visible and transmission electron microscopy (TEM)). Magnetic features at 7T were also measured. Photothermal abilities were assessed. Cytotoxicity studies on MIA PaCa-2, human pancreatic carcinoma and TIB-75 hepatocytes cell lines were carried out to evaluate their biocompatibility and showed a 320 fold higher efficiency for DOX after encapsulation. Results: Exhaustive physicochemical characterization studies were conducted showing a mid size of 20 to 40 nm diameters obtained with low polydispersity, efficient synthesis using seed mediated synthesis with chelation reaction with high scale-up, long duration stability, specific doxorubicin release with acidic pH, strong photothermal abilities at 808 nm in the NIR transparency window, strong magnetic r1 relaxivities for positive MRI, well adapted for image guided therapy and therapeutical purpose in biological tissues. Conclusion: In this paper, we have developed a novel theranostic nanoparticle composed of gadolinium complexes to gold ions, with a PEG biopolymer matrix conjugated with antitumoral doxorubicin, providing multifunctional therapeutic features. Particularly, these nano conjugates enhanced the cytotoxicity toward tumoral MIAPaCa-2 cells by a factor of 320 compared to doxorubicin alone. Moreover, MRI T1 features at 7T enables interesting positive contrast for bioimaging and their adapted size for potential passive targeting to tumors by Enhanced Permeability Retention. Given these encouraging antitumoral and imaging properties, this bimetallic theranostic nanomaterial system represents a veritable promise as a therapeutic entity in the field of medicinal applications.


Asunto(s)
Doxorrubicina/uso terapéutico , Gadolinio/química , Oro/química , Nanotubos/química , Nanomedicina Teranóstica , Animales , Antibióticos Antineoplásicos/farmacología , Antibióticos Antineoplásicos/uso terapéutico , Muerte Celular/efectos de los fármacos , Línea Celular Tumoral , Doxorrubicina/farmacología , Liberación de Fármacos , Endocitosis , Humanos , Concentración 50 Inhibidora , Imagen por Resonancia Magnética , Ratones , Nanotubos/ultraestructura , Neoplasias/tratamiento farmacológico , Espectrofotometría Ultravioleta
3.
Front Immunol ; 12: 627186, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33613575

RESUMEN

After the COVID-19 outbreak, non-evidence based guidelines were published to advise clinicians on the adjustment of oncological treatment during this pandemic. As immune checkpoint inhibitors directly affect the immune system, concerns have arisen about the safety of immunotherapy during this pandemic. However, data on the immune response in oncology patients treated with immunotherapy are still lacking. Here, we present the adaptive immune response in a SARS-CoV-2 infected patient who was treated with immune checkpoint inhibitors for advanced renal cell cancer. To evaluate the immune response in this patient, the number of T cells and their major subsets were measured according to expression of markers for co-signalling, maturation, and chemotaxis at baseline, during therapy, and during the SARS-CoV-2 infection. In addition, plasma samples were analyzed for IgM and IgG antibodies and the ability of these antibodies to neutralise SARS-CoV-2. Despite several risk factors for an impaired immune response to SARS-CoV-2, both T- and B-cell responses were observed. Moreover, after treatment with immune checkpoint inhibitors, a sufficient cellular and humoral immune response was achieved in this SARS-CoV-2 infected patient. These findings warrant renewed discussion on withholding of immune checkpoint inhibitors during an ongoing COVID-19 pandemic.


Asunto(s)
Antibióticos Antineoplásicos/uso terapéutico , Linfocitos B/inmunología , Carcinoma de Células Renales/diagnóstico , Inmunoterapia/métodos , Ipilimumab/uso terapéutico , Neoplasias Renales/diagnóstico , Nivolumab/uso terapéutico , Linfocitos T/inmunología , Anticuerpos Antivirales/sangre , Carcinoma de Células Renales/tratamiento farmacológico , Células Cultivadas , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Neoplasias Renales/tratamiento farmacológico , Activación de Linfocitos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias
4.
J Oncol Pharm Pract ; 27(2): 464-469, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33620259

RESUMEN

INTRODUCTION: Synchronous detection of multiple myeloma and acute myeloid leukemia in a single patient is a rare coincidence. Treatment of these patients is still unclear, mostly based on acute myeloid leukemia strategies combined with bortezomib. CASE REPORT: A 72-year-old male with no medical history was investigated for pancytopenia. On medical examination, he was complicated with a wide and severe skin infection on arm. On examination of bone marrow aspirate, 25% myeloblasts infiltration and additional 10% plasma cells were seen. Acute myeloid leukemia was diagnosed and plasma cell proliferation was attributed to reactive plasmacytosis due to skin infection. However, flowcytometric studies and immunohistochemical examination revealed two different cell populations with 30-40% atypical plasma cells and >20% myeloblasts. Serum M-protein detected by serum electrophoresis test and immunofixation test revealed a monoclonal IgG lambda band. He was diagnosed with concurrent acute myeloid leukemia and multiple myeloma without history of chemotherapy.Management and outcome: The patient was initially treated with bortezomib and dexamethasone for the myeloma. Subsequently, azacitidine was administered subcutaneously for the acute myeloid leukemia treatment. The tru-cut biopsy of the lesion on his arm revealed suppurative inflammatory findings and no malign cells detected. Antibiotherapy was started according to susceptibility. He expired after three months of survival. DISCUSSION: The synchronous occurrence of these two different clonal hematological malignancies is rare in hematology practice. Patient-based prospective studies and case series are needed to guide diagnosis and treatment strategies. Furthermore, this report highlights the importance of ruling out reactive plasmacytosis in patients with hematological malignancy who developed severe infections.


Asunto(s)
Leucemia Mieloide Aguda/diagnóstico , Mieloma Múltiple/diagnóstico , Anciano , Antibióticos Antineoplásicos/uso terapéutico , Antineoplásicos/uso terapéutico , Antineoplásicos Hormonales/uso terapéutico , Brazo/patología , Azacitidina/uso terapéutico , Biopsia , Médula Ósea/patología , Bortezomib/uso terapéutico , Dexametasona/uso terapéutico , Resultado Fatal , Células Precursoras de Granulocitos/patología , Humanos , Leucemia Mieloide Aguda/complicaciones , Leucemia Mieloide Aguda/tratamiento farmacológico , Masculino , Mieloma Múltiple/complicaciones , Mieloma Múltiple/tratamiento farmacológico , Proteínas de Mieloma , Necrosis
5.
Medicine (Baltimore) ; 100(3): e24139, 2021 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-33546027

RESUMEN

ABSTRACT: To evaluate the efficacy and safety of plasma rich in growth factors (PRGF) in photorefractive keratectomy (PRK) versus Mitomycin C (MMC).This is a comparative, longitudinal and retrospective case-control study (MMC vs PRGF), in patients with a spherical correction from -0.25 to -8.00 D and cylinder correction from -0.25 to -3.00. The uncorrected distance visual acuity (UDVA), refractive efficacy and safety indices, and changes in endothelial cell density were evaluated. The predictability was assessed with the postoperative manifest spherical equivalent.Forty-four patients (72 eyes) were treated with MMC and twenty-five patients (45 eyes) with PRGF. The final UDVA (LogMar) in MMC was 0.029 ±â€Š0.065 and in PRGF it was 0.028 ±â€Š0.048 (p = 0.383). The efficacy index for MMC was 0.98 ±â€Š0.10 and 1.10 ±â€Š0.46 for patients treated with PRGF (p = 0.062). The safety index for MMC was 1.03 ±â€Š0.11 and 1.12 ±â€Š0.46 (p = 0.158) for PRGF group. The change percentage of endothelial cell density was 0.9 ±â€Š11.6 for MMC and 4.3 ±â€Š13.1 for PRGF (p = 0.593). The predictability for MMC was 92.1% and for the PRGF was 91.9% (p = 0.976). Hyperemia, eye pain and superficial keratitis were observed in 11.1% of the MMC group; no adverse events were observed with the PRGF.The use of PRGF in PRK surgery is as effective as MMC. The PRGF shows a better safety profile than MMC for its intraoperative use in PRK.


Asunto(s)
Transfusión de Sangre Autóloga/métodos , Opacidad de la Córnea/prevención & control , Péptidos y Proteínas de Señalización Intercelular/administración & dosificación , Queratectomía Fotorrefractiva , Complicaciones Posoperatorias/prevención & control , Adulto , Anciano , Antibióticos Antineoplásicos/uso terapéutico , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Mitomicina/uso terapéutico , Soluciones Oftálmicas , Estudios Retrospectivos , Adulto Joven
6.
Medicine (Baltimore) ; 100(6): e24703, 2021 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-33578607

RESUMEN

RATIONALE: The abnormal expression of B-cell lymphoma-2 (Bcl-2) family members is often associated with the progression of the disease. Bcl-2 inhibitors (eg, venetoclax) were first reported to inhibit the proliferation of malignant lymphocytes and have a significant effect on patients with chronic lymphoblastic leukemia, but research on myeloid tumors is relatively delayed. Venetoclax was approved in 2018 for the treatment of acute myeloid leukemia (AML) patients who were not suitable for high-dose chemotherapy. The approval of venetoclax is an advance in the treatment of hematological tumors. PATIENT CONCERNS: Here we report a 64-year-old male with an increased white blood cell (WBC) count (39.0 × 109/L) and lymphocyte count (30.6 × 109/L) on physical examination in July 2014. The patients were diagnosed with chronic lymphocytic leukemia (CLL) through bone marrow (BM) smears and immunophenotyping without any cytogenetic or molecular abnormalities. Chlorambucil was prescribed, WBC was stable between 15 × 109/L and 25 × 109/L in the past 6 years. He came to the hospital again in May 2020 and complained of fatigue for 2 weeks. WBC (16.7 × 109/L) and lymphocyte (14.76 × 109/L) counts were increased, hemoglobin (HGB) and platelet (PLT) were decreased in peripheral blood, which indicated the progression of the disease. DIAGNOSES: The patient was diagnosed as secondary AML after CLL based on the clinical and laboratory findings. INTERVENTIONS: He achieved a morphological complete remission in both AML and CLL without any adverse reactions after one course of venetoclax monotherapy. OUTCOMES: He received standard daunorubicin and cytarabine combined with venetoclax as consolidation therapy and is now ready for allogeneic-hematopoietic stem cell transplantation. LESSONS: Our case presents a challenge to traditional treatment. New drugs such as venetoclax have shown outstanding effects in this respect. High expression of Bcl-2 can identify the responders of venetoclax. These findings should be validated in future clinical trials. We fully believe that in the near future, the comprehensive use of targeted drugs with different mechanisms will not only improve the quality of life of patients, but also completely change the prognosis of patients with recurrent and refractory hematological malignancies.


Asunto(s)
Leucemia Linfocítica Crónica de Células B/complicaciones , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/etiología , Antibióticos Antineoplásicos/administración & dosificación , Antibióticos Antineoplásicos/uso terapéutico , Antimetabolitos Antineoplásicos/administración & dosificación , Antimetabolitos Antineoplásicos/uso terapéutico , Antineoplásicos/administración & dosificación , Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Compuestos Bicíclicos Heterocíclicos con Puentes/administración & dosificación , Compuestos Bicíclicos Heterocíclicos con Puentes/uso terapéutico , Citarabina/administración & dosificación , Citarabina/uso terapéutico , Daunorrubicina/administración & dosificación , Daunorrubicina/uso terapéutico , Progresión de la Enfermedad , Trasplante de Células Madre Hematopoyéticas/normas , Humanos , Inmunofenotipificación/métodos , Leucemia Linfocítica Crónica de Células B/patología , Leucemia Mieloide Aguda/patología , Recuento de Leucocitos , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Inducción de Remisión , Sulfonamidas/administración & dosificación , Sulfonamidas/uso terapéutico , Resultado del Tratamiento
7.
ACS Appl Mater Interfaces ; 13(3): 3605-3621, 2021 Jan 27.
Artículo en Inglés | MEDLINE | ID: mdl-33449625

RESUMEN

Breast cancer is a major threat to health and lives of females. Biomimetic nanotechnology brought brighter hope for early diagnosis and treatment of breast cancer. Here, we proposed a platelet (PLT) membrane-derived strategy for enhanced photoacoustic (PA)/ultrasonic (US)/fluorescence (FL) multimodal imaging and augmented synergistic photothermal/chemotherapeutic efficacy in tumor cells. A PA imaging contrast and photothermal agent, nanocarbons (CNs), a chemotherapeutic and FL material, doxorubicin (DOX), and perfluoropentane (PFP) were coencapsulated into the poly(lactic-co-glycolic) acid (PLGA) skeletons. Then, the PLT membranes were coated onto the PLGA NPs, which were named as "nanoplatelets" (DOX-PFP-CNs@PLGA/PM NPs). The "nanoplatelets", which conserved the structural advantages and inherent properties of PLTs, could not only escape from phagocytosis of macrophages but also actively targeted tumor cells by the way of antigen-antibody interactions between P-selectin on the PM and CD44 receptors of the tumor cells. With CNs and DOX loaded in, these "nanoplatelets" could serve as an excellent contrast agent for PA/FL imaging. Under laser irradiation, the "nanoplatelets" could turn light energy into heat energy. The laser-triggered photothermal effect, on the one hand, could ablate the tumor cells immediately, and on the other hand, could initiate the optical droplet vaporization of PFP, which subsequently enhanced US imaging and promoted the discharge of encapsulated DOX from the "nanoplatelets" for remarkably strengthening photothermal therapeutic power in turn. In this work, as compared with the bare drug-loaded nanoparticles, the "nanoplatelets" exhibited much more accumulation in the tumor cells, demonstrating superior multimodal imaging capability and preferable synergistic therapeutic performance. In conclusion, the "nanoplatelets" could serve as contrast agents for US imaging and PA imaging to guide the therapy. What is more, the bioinspired PLT-derived, targeted, and nontoxic "nanoplatelets", which were exploited for multimodal PA/US/FL imaging-guided synergistic photothermal/chemo therapy, will be of great value to breast cancer theranostics in the days to come.


Asunto(s)
Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/terapia , Sistemas de Liberación de Medicamentos/métodos , Nanoestructuras/química , Animales , Antibióticos Antineoplásicos/administración & dosificación , Antibióticos Antineoplásicos/uso terapéutico , Materiales Biomiméticos/química , Biomimética , Neoplasias de la Mama/patología , Doxorrubicina/administración & dosificación , Doxorrubicina/uso terapéutico , Femenino , Fluorocarburos/administración & dosificación , Fluorocarburos/uso terapéutico , Células Endoteliales de la Vena Umbilical Humana , Humanos , Ratones , Ratones Endogámicos BALB C , Imagen Óptica/métodos , Técnicas Fotoacústicas/métodos , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Nanomedicina Teranóstica/métodos
8.
ACS Appl Mater Interfaces ; 13(4): 4861-4873, 2021 Feb 03.
Artículo en Inglés | MEDLINE | ID: mdl-33471499

RESUMEN

A combination treatment strategy that relies on the synergetic effects of different therapeutic approaches has been considered to be an effective method for cancer therapy. Herein, a chemotherapeutic drug (doxorubicin, Dox) and a manganese ion (Mn2+) were co-loaded into regenerated silk fibroin-based nanoparticles (NPs), followed by the surface conjugation of phycocyanin (PC) to construct tumor microenvironment-activated nanococktails. The resultant PC-Mn@Dox-NPs showed increased drug release rates by responding to various stimulating factors (acidic pH, hydrogen peroxide (H2O2), and glutathione), revealing that they could efficiently release the payloads (Dox and Mn2+) in tumor cells. The released Dox could not only inhibit the growth of tumor cells but also generated a large amount of H2O2. The elevated H2O2 was decomposed into the highly harmful hydroxyl radicals and oxygen through an Mn2+-mediated Fenton-like reaction. Furthermore, the generated oxygen participated in photodynamic therapy (PDT) and produced abundant singlet oxygen. Our investigations demonstrate that these PC-Mn@Dox-NPs exhibit multiple bioresponsibilities and favorable biosafety. By integrating Dox-induced chemotherapy, Mn2+-mediated chemodynamic therapy, and PC-based PDT via cascade reactions, PC-Mn@Dox-NPs achieved enhanced in vitro and in vivo anticancer efficacies compared to all the mono- or dual-therapeutic approaches. These findings reveal that PC-Mn@Dox-NPs can be exploited as a promising nanococktail for cascade reaction-mediated synergistic cancer treatment.


Asunto(s)
Antibióticos Antineoplásicos/administración & dosificación , Doxorrubicina/administración & dosificación , Manganeso/administración & dosificación , Neoplasias/tratamiento farmacológico , Fármacos Fotosensibilizantes/administración & dosificación , Ficocianina/administración & dosificación , Animales , Antibióticos Antineoplásicos/farmacología , Antibióticos Antineoplásicos/uso terapéutico , Bombyx/química , Cationes Bivalentes/administración & dosificación , Cationes Bivalentes/farmacología , Cationes Bivalentes/uso terapéutico , Línea Celular Tumoral , Doxorrubicina/farmacología , Doxorrubicina/uso terapéutico , Portadores de Fármacos/química , Fibroínas/química , Glutatión/metabolismo , Células Endoteliales de la Vena Umbilical Humana , Humanos , Concentración de Iones de Hidrógeno , Manganeso/farmacología , Manganeso/uso terapéutico , Ratones , Nanopartículas/química , Neoplasias/metabolismo , Neoplasias/patología , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Ficocianina/farmacología , Ficocianina/uso terapéutico , Microambiente Tumoral/efectos de los fármacos
9.
ACS Appl Mater Interfaces ; 13(2): 2256-2268, 2021 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-33423468

RESUMEN

The aggressive progression of breast cancer is impacted significantly by the tumor microenvironment (TME). The current chemotherapy normally causes cytotoxicity to tumor cells, while does not effectively modulate the TME. Thus, the chemotherapy effect of breast cancer is usually dissatisfactory. In this study, a kind of hierarchically releasing bio-responsive nanoparticles (R(D)/H(S) NPs), constructed by ß-cyclodextrin-grafted heparin and pH-sensitive pseudorotaxane, were investigated to enhance the breast cancer chemotherapeutic efficacy through TME modulation. Doxorubicin (DOX) and transforming growth factor-ß (TGF-ß) receptor inhibitor (SB431542) loaded onto R(D)/H(S) NPs were released rapidly for the respective response to low pH in endosomes/lysosomes and heparanase (HPSE) in TME. Our results showed that R(D)/H(S) NPs effectively inhibited the formation of tumor-associated fibroblasts (TAFs) and reduced TGF-ß and collagen I secretion. Besides, the immunosuppressive microenvironment was effectively reversed into immunogenic, characterized by increased CD8+ and CD4+ T cell infiltration, which distinctly inhibited breast cancer metastasis. Therefore, R(D)/H(S) NPs remodeled the TME by downregulating TAFs, TGF-ß, and collagen I; activating the immune microenvironment; and then amplifying the chemotherapeutic efficacy of DOX.


Asunto(s)
Antibióticos Antineoplásicos/administración & dosificación , Benzamidas/administración & dosificación , Preparaciones de Acción Retardada/química , Dioxoles/administración & dosificación , Doxorrubicina/administración & dosificación , Factor de Crecimiento Transformador beta/antagonistas & inhibidores , Microambiente Tumoral/efectos de los fármacos , Células 3T3 , Animales , Antibióticos Antineoplásicos/uso terapéutico , Benzamidas/uso terapéutico , Fibroblastos Asociados al Cáncer/efectos de los fármacos , Línea Celular Tumoral , Dioxoles/uso terapéutico , Doxorrubicina/uso terapéutico , Femenino , Concentración de Iones de Hidrógeno , Ratones , Ratones Endogámicos BALB C , Nanopartículas/química , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Neoplasias/patología , Rotaxanos/química , Transducción de Señal/efectos de los fármacos , Factor de Crecimiento Transformador beta/metabolismo
10.
BMJ Case Rep ; 14(1)2021 Jan 11.
Artículo en Inglés | MEDLINE | ID: mdl-33431536

RESUMEN

Changes of the hepatic subcapsular blood flow with the early appearance of hypervascularity near the falciform ligament are rare radiologic findings. They present most frequently in cases of superior vena cava (SVC) obstruction and are related to the recruitment of the cavo-mammary-phrenic-hepatic-capsule-portal and the cavo-superficial-umbilical-portal pathways. We present the case of a 52-year-old female patient with an highly aggressive retroperitoneal liposarcoma with SVC obstruction caused by external compression due to a mediastinal metastatic mass. The patient exhibited no symptoms of SVC obstruction due to the collateral cavo-portal pathways.


Asunto(s)
Dolor Abdominal/etiología , Liposarcoma/diagnóstico , Neoplasias del Mediastino/diagnóstico , Cuidados Paliativos/legislación & jurisprudencia , Neoplasias Retroperitoneales/diagnóstico , Síndrome de la Vena Cava Superior/diagnóstico , Dolor Abdominal/diagnóstico , Antibióticos Antineoplásicos/uso terapéutico , Doxorrubicina/uso terapéutico , Resultado Fatal , Femenino , Humanos , Biopsia Guiada por Imagen , Liposarcoma/complicaciones , Liposarcoma/patología , Liposarcoma/terapia , Neoplasias del Mediastino/complicaciones , Neoplasias del Mediastino/secundario , Neoplasias del Mediastino/terapia , Persona de Mediana Edad , Invasividad Neoplásica , Neoplasias Retroperitoneales/complicaciones , Neoplasias Retroperitoneales/patología , Neoplasias Retroperitoneales/terapia , Síndrome de la Vena Cava Superior/etiología , Síndrome de la Vena Cava Superior/terapia , Tomografía Computarizada por Rayos X , Vena Cava Superior/diagnóstico por imagen
11.
Cancer Sci ; 112(3): 1225-1234, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33370472

RESUMEN

We have previously identified receptor tyrosine kinase-like orphan receptor 1 (ROR1) as a direct transcriptional target of TTF-1/NKX2-1, a lineage-survival oncogene in lung adenocarcinoma. ROR1 sustains prosurvival signaling from multiple receptor tyrosine kinases including epidermal growth factor receptor, MET, and insulin-like growth factor 1 receptor in part by maintaining the caveolae structure as a scaffold protein of cavin-1 and caveolin-1. In this study, a high throughput screening of the natural product library containing 2560 compounds was undertaken using a cell-based FluoPPI assay detecting ROR1-cavin-1 interaction. As a result, geldanamycin (GA), a known inhibitor of heat shock protein 90 (HSP90), was identified as a potential inhibitor of ROR1. Geldanamycin, as well as two GA derivatives tested in the clinic, 17-allylamino-17-demethoxygeldanamycin (17-AAG) and 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG), decreased ROR1 protein expression. We found that ROR1 physically interacted with HSP90α, but not with other HSP90 paralogs, HSP90ß or GRP94. Geldanamycin in turn destabilized and degraded ROR1 protein in a dose- and time-dependent manner through the ubiquitin/proteasome pathway, resulting in a significant suppression of cell proliferation in lung adenocarcinoma cell lines, for which the kinase domain of ROR1, but not its kinase activity or N-glycosylation, was required. Our findings indicate that HSP90 is required to sustain expression of ROR1 crucial for lung adenosarcoma survival, suggesting that inhibition of HSP90 could be a promising therapeutic strategy in ROR1-positive lung adenocarcinoma.


Asunto(s)
Adenocarcinoma del Pulmón/tratamiento farmacológico , Antibióticos Antineoplásicos/farmacología , Proteínas HSP90 de Choque Térmico/antagonistas & inhibidores , Neoplasias Pulmonares/tratamiento farmacológico , Receptores Huérfanos Similares al Receptor Tirosina Quinasa/metabolismo , Adenocarcinoma del Pulmón/patología , Antibióticos Antineoplásicos/uso terapéutico , Benzoquinonas/farmacología , Benzoquinonas/uso terapéutico , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Técnicas de Silenciamiento del Gen , Proteínas HSP90 de Choque Térmico/genética , Proteínas HSP90 de Choque Térmico/metabolismo , Ensayos Analíticos de Alto Rendimiento , Humanos , Lactamas Macrocíclicas/farmacología , Lactamas Macrocíclicas/uso terapéutico , Neoplasias Pulmonares/patología , Complejo de la Endopetidasa Proteasomal/metabolismo , Proteolisis/efectos de los fármacos , Proteínas de Unión al ARN/metabolismo
12.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 5021-5024, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-33019114

RESUMEN

Thermosensitive liposomes (TSL) are nanoparticles that can encapsulate therapeutic drugs, and release those drugs when exposed to hyperthermic temperatures (>40 °C). Combined with localized hyperthermia, TSL enable focused drug delivery. In this study, we created a three-dimensional (3D) computer model for simulating delivery with TSL-encapsulated doxorubicin (TSL-Dox) to mouse tumors. A mouse hind limb was scanned by a 3D scanner and the resulting geometry was imported into finite element modeling software, with a virtual tumor added. Then, heating by a surface probe was simulated. Further, a drug delivery model was coupled to the heat transfer model to simulate drug delivery kinetics. For comparison, experimental studies in gel phantoms and in vivo fluorescence imaging studies in mice carrying lung tumor xenografts were performed. We report the tissue temperature profile, drug concentration profile and compare the experimental studies with the computer model. The thermistor produced very localized heating that resulted in highest drug delivery to regions near the probe. The average tumor temperature was 38.2˚C (range 34.4-43.4˚C), and produced an average tumor drug concentration of 11.8 µg/g (0.3-28.1 µg/g) after 15 min heating, and 25.6 µg/g (0.3-52 µg/g), after 60 min heating. The computer model reproduced the temperature profile compared to phantom experiments (mean error 0.71 °C, range 0.59-1.25 °C), as well as drug delivery profile as compared to in vivo studies. Our results suggest feasibility of using this approach to model drug delivery in preclinical studies with accurate model geometry.


Asunto(s)
Hipertermia Inducida , Liposomas , Animales , Antibióticos Antineoplásicos/uso terapéutico , Simulación por Computador , Sistemas de Liberación de Medicamentos , Ratones
13.
Zhonghua Zhong Liu Za Zhi ; 42(8): 617-623, 2020 Aug 23.
Artículo en Chino | MEDLINE | ID: mdl-32867451

RESUMEN

As a new type of anthracyclines, pegylated liposomal doxorubicin (PLD) is widely used in the treatment of a variety of malignant tumors, including soft tissue sarcoma, ovarian cancer, breast cancer, multiple myeloma, and so on. Compared with traditional anthracyclines, PLD can significantly decrease the incidences of adverse events such as cardiac toxicity and alopecia. However, the use of PLD will be accompanied with toxic side effects such as hand-foot syndrome, oral mucositis, and infusion reaction. This consensus will mainly focus on the mechanism, prevention and treatment of adverse events of PLD, in order to improve the therapeutic efficacy of PLD and life quality of patients.


Asunto(s)
Antibióticos Antineoplásicos/efectos adversos , Doxorrubicina/análogos & derivados , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/prevención & control , Síndrome Mano-Pie/complicaciones , Neoplasias/tratamiento farmacológico , Estomatitis/complicaciones , Antibióticos Antineoplásicos/uso terapéutico , Consenso , Doxorrubicina/efectos adversos , Doxorrubicina/uso terapéutico , Femenino , Humanos , Polietilenglicoles/efectos adversos , Polietilenglicoles/uso terapéutico , Guías de Práctica Clínica como Asunto
14.
Middle East Afr J Ophthalmol ; 27(2): 134-138, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32874049

RESUMEN

Nodular posterior scleritis represents a small percentage of all cases of posterior scleritis. Because of the scarcity of nodular posterior scleritis, it may be confused or even misdiagnosed as an intraocular tumor or posterior uveitis. Here, we are reporting a case of nodular posterior scleritis in a 25-year-old medically free male. Furthermore, we reviewed previously reported cases of nodular posterior scleritis. Our patient presented with a choroidal mass of about one disc diameter in size. In addition, the patient had exudative retinal detachment and chorioretinal folds. B scan ultrasonography showed subretinal fluid, macular nodular thickening and underlying echolucent area along with medium internal reflectivity on A scan. Fluorescein angiography revealed early pinpoint areas of hyperfluorescence and late pooling under the detached retina. Indocyanine green angiography demonstrated early diffuse hypofluorescence corresponding to the area of detachment and late multiple pinpoint spots of hyperfluorescence. After intravenous methylprednisolone 1 g for 3 days followed by a course of oral prednisolone along with mycophenolate mofetil, the patient experienced rapid recovery with improvement in vision and complete resolution of subretinal fluid. On further follow-up, the patient regained 20/20 vision. Nodular posterior scleritis is a rare unilateral disease with strong female predominance. Multimodal imaging should be employed to confirm the diagnosis. The disease must be diagnosed correctly to avoid any unnecessary diagnostic work-up and aggressive management. Most cases carry excellent prognosis with no recurrence.


Asunto(s)
Neoplasias de la Coroides/diagnóstico , Melanoma Amelanótico/diagnóstico , Desprendimiento de Retina/diagnóstico , Escleritis/diagnóstico , Administración Oral , Adulto , Antibióticos Antineoplásicos/uso terapéutico , Neoplasias de la Coroides/tratamiento farmacológico , Colorantes/administración & dosificación , Quimioterapia Combinada , Angiografía con Fluoresceína , Glucocorticoides/uso terapéutico , Humanos , Verde de Indocianina/administración & dosificación , Infusiones Intravenosas , Masculino , Melanoma Amelanótico/tratamiento farmacológico , Metilprednisolona/uso terapéutico , Imagen Multimodal , Ácido Micofenólico/uso terapéutico , Prednisolona/uso terapéutico , Desprendimiento de Retina/tratamiento farmacológico , Escleritis/tratamiento farmacológico , Tomografía de Coherencia Óptica
17.
Orv Hetil ; 161(26): 1094-1102, 2020 06.
Artículo en Húngaro | MEDLINE | ID: mdl-32541088

RESUMEN

INTRODUCTION: The incidence of dilated cardiomyopathy after anthracycline chemotherapy is mainly influenced by anthracycline cumulative dose. Previous researches showed doxorubicin treatment under cumulative dose of 450 mg/m2 associated with a low incidence of heart failure. Nowadays, doxorubicin is administered with a lower dose, the development of heart failure is largely determined by other factors. AIM: Our purpose was to identify the risk factors for heart failure due to doxorubicin therapy. METHOD: With the use of the Hungarian financial healthcare databases merged with the National Cancer Registry, we performed a retrospective study. All the patients having confirmation for breast carcinoma between 2004 and 2015 were enrolled. The subjects with a preceding period characterized by any chemotherapy or diagnoses suggesting heart failure were excluded. Heart failure outcome event was defined by the assignment of I50 diagnosis code at hospital discharge or in autopsy reports. STATISTICAL ANALYSIS: We used multivariate binary logistic regression to calculate odds ratios for heart failure. Besides the baseline characteristics, oncological state and cumulative doses of the chemotherapies were also taken into account. RESULTS: Among the analysed 3288, doxorubicin-treated patients, heart failure cumulative incidence was 6.2%. Doxorubicin cumulative dose over 400 mg/m2 increased the risk. The heart failure incidence was essentially influenced by age, even over 50 years the risk rose. Diabetes mellitus and the treatments with pyrimidine-analogues, carboplatin or bevacizumab were also associated with higher risk. CONCLUSION: By the integration of national financial and clinical databases, we could identify the risk factors for doxorubicin-associated heart failure. Orv Hetil. 2020; 161(26): 1094-1102.


Asunto(s)
Antibióticos Antineoplásicos/efectos adversos , Neoplasias de la Mama/tratamiento farmacológico , Doxorrubicina/efectos adversos , Insuficiencia Cardíaca/inducido químicamente , Antibióticos Antineoplásicos/uso terapéutico , Doxorrubicina/uso terapéutico , Femenino , Humanos , Hungría , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo
18.
J Am Acad Dermatol ; 83(2): 703-704, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32305443
19.
Biochem Pharmacol ; 177: 113986, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32330494

RESUMEN

Virotherpay is emerging as a promising strategy against cancer, and three oncolytic viruses (OVs) have gained approval in different countries for the treatment of several cancer types. Beyond the capability to selectively infect, replicate and lyse cancer cells, OVs act through a multitude of events, including modification of the tumour micro/macro-environment as well as a complex modulation of the anti-tumour immune response by activation of danger signals and immunogenic cell death pathways. Most OVs show limited effects, depending on the viral platform and the interactions with the host. OVs used as monotherapy only in a minority of patients elicited a full response. Better outcomes were obtained using OVs in combination with other treatments, such as immune therapy or chemotherapy, suggesting that the full potential of OVs can be unleashed in combination with other treatment modalities. Here, we report the main described combination of OVs with conventional chemotherapeutic agents: platinum salts, mitotic inhibitors, anthracyclines and other antibiotics, anti-metabolites, alkylating agents and topoisomerase inhibitors. Additionally, our work provides an overview of OV combination with targeted therapies: histone deacetylase inhibitors, kinase inhibitors, monoclonal antibodies, inhibitors of DNA repair, inhibitors of the proteasome complex and statins that demonstrated enhanced OV anti-neoplastic activity. Although further studies are required to assess the best combinations to translate the results in the clinic, it is clear that combined therapies, acting with complementary mechanisms of action might be useful to target cancer lesions resistant to currently available treatments.


Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Terapia Combinada/métodos , Inmunoterapia/métodos , Neoplasias/terapia , Viroterapia Oncolítica/métodos , Virus Oncolíticos/genética , Alquilantes/uso terapéutico , Antibióticos Antineoplásicos/uso terapéutico , Antimetabolitos Antineoplásicos/uso terapéutico , Antimitóticos/uso terapéutico , Inhibidores de Histona Desacetilasas/uso terapéutico , Humanos , Neoplasias/genética , Neoplasias/inmunología , Neoplasias/patología , Virus Oncolíticos/inmunología , Compuestos de Platino/uso terapéutico , Inhibidores de Proteínas Quinasas/uso terapéutico , Inhibidores de Topoisomerasa/uso terapéutico , Microambiente Tumoral/efectos de los fármacos , Microambiente Tumoral/genética , Microambiente Tumoral/inmunología
20.
Medicine (Baltimore) ; 99(15): e19741, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32282733

RESUMEN

INTRODUCTION: Immune-related adverse events (ir-AEs) are increasingly becoming a concern, as immune checkpoint inhibitors (ICIs) are used more frequently. Herein, we present a case of fulminant cytokine release syndrome (CRS) complicated by dermatomyositis after the combination therapy with ICIs. PATIENT CONCERNS: A 70-year-old male developed dermatomyositis during the course of treatment with two ICIs, nivolumab and ipilimumab. He was treated by steroid pulse therapy, but the effect was limited. Afterwards, he had acute-onset high fever, hypotension, respiratory failure, impaired consciousness, renal failure, and coagulation abnormality at the same time. C reactive protein (CRP), creatinine kinase (CK), D-dimer, and ferritin levels were considerably elevated: CRP, 24 mg/dL; CK, 40,500 U/L; D-dimer, 290 µg/mL; ferritin, 329,000 ng/mL. DIAGNOSIS: CRS induced by ICI combination therapy. INTERVENTIONS: Given that high fever and elevated CRP level indicated potential sepsis, an antibiotic was used until the confirmation of negative blood cultures. All the simultaneous acute symptoms were supposed to be CRS. He was admitted to the intensive care unit (ICU), and temporary intubation and hemodialysis were needed. Immunosuppressive therapy was reinforced by mycophenolate mofetil together with steroid, and plasma exchange was performed for the elimination of abnormal proteins. OUTCOMES: The patient's clinical symptoms and laboratory parameters gradually improved and he was discharged from the ICU in a month. CONCLUSION: Fulminant CRS can be induced by ICI combination therapy. As the initial symptoms of CRS resemble sepsis, it is important to consider CRS as a differential diagnosis and to initiate immunosuppressive therapy early when needed. In steroid-resistant cases, early introduction of other immunosuppressive therapy and plasma exchange can be effective.


Asunto(s)
Terapia Combinada/métodos , Síndrome de Liberación de Citoquinas/sangre , Síndrome de Liberación de Citoquinas/complicaciones , Dermatomiositis/etiología , Anciano , Antibióticos Antineoplásicos/administración & dosificación , Antibióticos Antineoplásicos/uso terapéutico , Antineoplásicos Inmunológicos/administración & dosificación , Antineoplásicos Inmunológicos/efectos adversos , Antineoplásicos Inmunológicos/uso terapéutico , Biomarcadores/sangre , Síndrome de Liberación de Citoquinas/tratamiento farmacológico , Dermatomiositis/sangre , Dermatomiositis/patología , Dermatomiositis/terapia , Diagnóstico Diferencial , Humanos , Factores Inmunológicos/administración & dosificación , Factores Inmunológicos/efectos adversos , Factores Inmunológicos/uso terapéutico , Ipilimumab/administración & dosificación , Ipilimumab/efectos adversos , Ipilimumab/uso terapéutico , Masculino , Ácido Micofenólico/administración & dosificación , Ácido Micofenólico/uso terapéutico , Nivolumab/administración & dosificación , Nivolumab/efectos adversos , Nivolumab/uso terapéutico , Intercambio Plasmático/métodos , Resultado del Tratamiento
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