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1.
Altern Ther Health Med ; 29(8): 733-737, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37708543

RESUMO

Objective: This study aimed to investigate the clinical features of angioimmunoblastic T-cell lymphoma (AITL) mimicking systemic lupus erythematosus (SLE) and raise awareness about AITL among rheumatologists in order to prevent misdiagnosis and missed diagnosis. The study reports on a case of AITL mimicking SLE and provides a literature review. Methods: Using key words as search terms, relevant articles published in PubMed before 2022-05 were searched, and their clinical characteristics were collected and analyzed. Results: The literature review retrieved six case reports, including four cases initially diagnosed with SLE and then with AITL. The other two case diagnoses were SLE and AITL, respectively. The two diseases are pathogenically associated and share some common features. The clinical manifestations of AITL are complex. The disease is closely associated with abnormal immune functions and is highly heterogeneous. Conclusion: Patients with AITL generally have a poor prognosis. Rarely do reported cases show AITL mimicking SLE. AITL should be considered during clinical practice to prevent missed diagnoses or misdiagnoses.


Assuntos
Linfadenopatia Imunoblástica , Lúpus Eritematoso Sistêmico , Linfoma de Células T , Humanos , Linfadenopatia Imunoblástica/diagnóstico , Linfadenopatia Imunoblástica/complicações , Linfadenopatia Imunoblástica/patologia , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/complicações , Linfoma de Células T/diagnóstico , Linfoma de Células T/complicações , Linfoma de Células T/patologia
2.
Altern Ther Health Med ; 29(8): 252-254, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37573597

RESUMO

Objective: Extranodal natural killer/T-cell lymphoma comprises less than 1% of all non-Hodgkin lymphomas. It is rare in Western countries but is common in East Asia and Central and South America. The pathological features are angiocentricity /angioinvasion and significant tissue necrosis. Case Presentation: A 72-year-old woman was diagnosed with primary breast extranodal natural killer/T-cell lymphoma. The patient presented with a painless right breast tumor and had uneven internal echo and strip blood flow signal on breast ultrasonography. After right breast tumor resection, the pathological diagnosis was extranodal natural killer/T-cell lymphoma. Despite receiving CHOP chemotherapy, the patient died of lymphoma and multiple organ dysfunction syndrome 27 months after diagnosis. Conclusion: Extranodal natural killer/T-cell lymphoma with breast tissue as the primary site is very rare. The disease is prone to misdiagnosis and missed diagnosis, and diagnosis by ultrasound is difficult, so pathological examination after biopsy is particularly important.


Assuntos
Neoplasias da Mama , Linfoma de Células T , Feminino , Humanos , Idoso , Células Matadoras Naturais/patologia , Linfoma de Células T/patologia , Neoplasias da Mama/diagnóstico por imagem
3.
Oxid Med Cell Longev ; 2021: 5529518, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34603598

RESUMO

T-cell malignancies are still difficult to treat due to a paucity of plans that target critical dependencies. Drug-induced cellular senescence provides a permanent cell cycle arrest during tumorigenesis and cancer development, particularly when combined with senolytics to promote apoptosis of senescent cells, which is an innovation for cancer therapy. Here, our research found that wogonin, a well-known natural flavonoid compound, not only had a potential to inhibit cell growth and proliferation but also induced cellular senescence in T-cell malignancies with nonlethal concentration. Transcription activity of senescence-suppression human telomerase reverse transcriptase (hTERT) and oncogenic C-MYC was suppressed in wogonin-induced senescent cells, resulting in the inhibition of telomerase activity. We also substantiated the occurrence of DNA damage during the wogonin-induced aging process. Results showed that wogonin increased the activity of senescence-associated ß-galactosidase (SA-ß-Gal) and activated the DNA damage response pathway mediated by p53. In addition, we found the upregulated expression of BCL-2 in senescent T-cell malignancies because of the antiapoptotic properties of senescent cells. Following up this result, we identified a BCL-2 inhibitor Navitoclax (ABT-263), which was highly effective in decreasing cell viability and inducing apoptotic cell death in wogonin-induced senescent cells. Thus, the "one-two punch" approach increased the sensibility of T-cell malignancies with low expression of BCL-2 to Navitoclax. In conclusion, our research revealed that wogonin possesses potential antitumor effects based on senescence induction, offering a better insight into the development of novel therapeutic methods for T-cell malignancies.


Assuntos
Antineoplásicos/farmacologia , Senescência Celular/efeitos dos fármacos , Proteína Supressora de Tumor p53/metabolismo , Compostos de Anilina/farmacologia , Antineoplásicos/uso terapêutico , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Medicamentos de Ervas Chinesas/uso terapêutico , Flavanonas/farmacologia , Flavanonas/uso terapêutico , Heterocromatina/efeitos dos fármacos , Heterocromatina/genética , Heterocromatina/metabolismo , Humanos , Linfoma de Células T/tratamento farmacológico , Linfoma de Células T/patologia , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Sulfonamidas/farmacologia , Proteína Supressora de Tumor p53/antagonistas & inibidores , Proteína Supressora de Tumor p53/genética
4.
J Pharmacol Sci ; 147(3): 260-270, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34507635

RESUMO

Sesamin is a lignan compound in plants that has various pharmacological effects, including reducing diabetes-associated injuries, regulating fatty acid and cholesterol metabolism, and exerting antiinflammatory and antitumour effects. Previous studies have reported that sesamin can inhibit the proliferation of several types of tumour cells and exert antitumour effects. However, the antitumour effect of sesamin on T-cell lymphoma is still unknown. In this study, we selected a T-cell lymphoma mouse model to investigate the mechanism of sesamin against T-cell lymphoma via programmed cell death in vivo and in vitro. We found that sesamin could significantly inhibit the growth of EL4 cells in a tumour-bearing mouse model. Sesamin markedly inhibited the proliferation of EL4 cells by inducing apoptosis, pyroptosis and autophagy. Autophagy occurred earlier than apoptosis and pyroptosis in EL4 cells after sesamin treatment. Blocking autophagy inhibited apoptosis and pyroptosis in EL4 cells after sesamin treatment. Taken together, these results suggested that sesamin promoted apoptosis and pyroptosis via autophagy to enhance antitumour effects on murine T-cell lymphoma. This study expands our knowledge of the pharmacological effects of sesamin on T-cell lymphoma, and provides a theoretical basis for the development of new antitumour drugs and treatments for T-cell lymphoma.


Assuntos
Antineoplásicos , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Dioxóis/farmacologia , Dioxóis/uso terapêutico , Lignanas/farmacologia , Lignanas/uso terapêutico , Linfoma de Células T/tratamento farmacológico , Linfoma de Células T/patologia , Fitoterapia , Piroptose/efeitos dos fármacos , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Camundongos Endogâmicos BALB C , Estimulação Química
5.
Oncogene ; 40(13): 2339-2354, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33664451

RESUMO

Most of the drugs currently prescribed for cancer treatment are riddled with substantial side effects. In order to develop more effective and specific strategies to treat cancer, it is of importance to understand the biology of drug targets, particularly the newly emerging ones. A comprehensive evaluation of these targets will benefit drug development with increased likelihood for success in clinical trials. The folate-mediated one-carbon (1C) metabolism pathway has drawn renewed attention as it is often hyperactivated in cancer and inhibition of this pathway displays promise in developing anticancer treatment with fewer side effects. Here, we systematically review individual enzymes in the 1C pathway and their compartmentalization to mitochondria and cytosol. Based on these insight, we conclude that (1) except the known 1C targets (DHFR, GART, and TYMS), MTHFD2 emerges as good drug target, especially for treating hematopoietic cancers such as CLL, AML, and T-cell lymphoma; (2) SHMT2 and MTHFD1L are potential drug targets; and (3) MTHFD2L and ALDH1L2 should not be considered as drug targets. We highlight MTHFD2 as an excellent therapeutic target and SHMT2 as a complementary target based on structural/biochemical considerations and up-to-date inhibitor development, which underscores the perspectives of their therapeutic potential.


Assuntos
Linfoma de Células T/tratamento farmacológico , Redes e Vias Metabólicas/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Carbono/metabolismo , Ácido Fólico/genética , Ácido Fólico/metabolismo , Humanos , Linfoma de Células T/metabolismo , Linfoma de Células T/patologia , Mitocôndrias/genética , Mitocôndrias/metabolismo , Neoplasias/metabolismo
6.
Cancer Invest ; 39(4): 333-348, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33474992

RESUMO

This study investigates the anticancer potential of methanolic extract of A. subulatum dry fruits (MEAS) in Dalton's Lymphoma Ascites (DLA) cells in vitro and on DLA induced ascitic and solid tumor-bearing mice. MEAS induced apoptosis in DLA cells and MEAS administration effectively reduced tumor burden, and increased life span via modulating pro-inflammatory cytokines and regulating NF-κB pathway. MEAS seemed to be much safer than the standard drug cyclophosphamide, as the latter was associated with adverse effects such as body weight loss, depletion of hemoglobin level and hepatotoxicity, suggesting A. subulatum as a potential nutraceutical against cancer.


Assuntos
Amomum , Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Ascite/tratamento farmacológico , Linfoma de Células T/tratamento farmacológico , Extratos Vegetais/farmacologia , Amomum/química , Animais , Antineoplásicos Alquilantes/farmacologia , Antineoplásicos Fitogênicos/isolamento & purificação , Ascite/sangue , Ascite/patologia , Linhagem Celular Tumoral , Ciclofosfamida/farmacologia , Citocinas/sangue , Mediadores da Inflamação/sangue , Mediadores da Inflamação/metabolismo , Linfoma de Células T/sangue , Linfoma de Células T/patologia , Masculino , Camundongos Endogâmicos BALB C , Extratos Vegetais/isolamento & purificação , Transdução de Sinais , Carga Tumoral/efeitos dos fármacos
7.
Anticancer Res ; 40(9): 4921-4928, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32878780

RESUMO

BACKGROUND/AIM: Phenothiazines constitute a versatile family of compounds in terms of biological activity, which have also gained a considerable attention in cancer research. MATERIALS AND METHODS: Three phenothiazines (promethazine, chlorpromazine and thioridazine) have been tested in combination with 11 active selenocompounds against MDR (ABCB1-overexpressing) mouse T-lymphoma cells to investigate their activity as combination chemotherapy and as antitumor adjuvants in vitro with a checkerboard combination assay. RESULTS: Seven selenocompounds showed toxicity on mouse embryonic fibroblasts, while three showed selectivity towards tumor cells. Two compounds showed synergism with all tested phenothiazines in low concentration ranges (1.46-11.25 µM). Thioridazine was the most potent among the three phenothiazines. CONCLUSION: Phenothiazines belonging to different generations showed different levels of adjuvant activities. All the tested phenothiazines are already approved medicines with known pharmacological and toxicity profiles, therefore, their use as adjuvants in cancer may be considered as a potential drug repurposing strategy.


Assuntos
Antineoplásicos/farmacologia , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Compostos Organosselênicos/farmacologia , Fenotiazinas/farmacologia , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Resistência a Múltiplos Medicamentos/genética , Resistencia a Medicamentos Antineoplásicos/genética , Sinergismo Farmacológico , Linfoma de Células T/tratamento farmacológico , Linfoma de Células T/patologia , Camundongos , Estrutura Molecular , Compostos Organosselênicos/síntese química , Compostos Organosselênicos/química , Fenotiazinas/síntese química , Fenotiazinas/química
8.
Skinmed ; 17(6): 406-408, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31904333

RESUMO

A 51-year-old white woman with a past medical history significant for steroid-dependent ulcerative colitis, rheumatoid arthritis, and diabetes mellitus presented to the hospital with fever and painful, erythematous subcutaneous nodules on the medical aspects of both thighs. Histopathologic examination showed features suggestive of an abscess, but her condition failed to improve with intravenous broad-spectrum antibiotics. Molecular studies detected T cell receptor-ß gene rearrangements. The lesions later exhibited signs of necrosis, requiring multiple debridements as well as therapy with hyperbaric oxygen. She was later referred to the MD Anderson Cancer Center for evaluation for possible subcutaneous panniculitis-like T cell lymphoma.


Assuntos
Dermatite/diagnóstico , Granuloma/diagnóstico , Linfoma de Células T/diagnóstico , Paniculite/diagnóstico , Desbridamento/métodos , Dermatite/patologia , Dermatite/terapia , Diagnóstico Diferencial , Feminino , Granuloma/patologia , Granuloma/terapia , Humanos , Oxigenoterapia Hiperbárica , Linfoma de Células T/patologia , Pessoa de Meia-Idade , Necrose , Paniculite/patologia , Paniculite/terapia , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/patologia
9.
Nat Commun ; 9(1): 2024, 2018 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-29789628

RESUMO

T- and NK-cell lymphomas (TCL) are a heterogenous group of lymphoid malignancies with poor prognosis. In contrast to B-cell and myeloid malignancies, there are few preclinical models of TCLs, which has hampered the development of effective therapeutics. Here we establish and characterize preclinical models of TCL. We identify multiple vulnerabilities that are targetable with currently available agents (e.g., inhibitors of JAK2 or IKZF1) and demonstrate proof-of-principle for biomarker-driven therapies using patient-derived xenografts (PDXs). We show that MDM2 and MDMX are targetable vulnerabilities within TP53-wild-type TCLs. ALRN-6924, a stapled peptide that blocks interactions between p53 and both MDM2 and MDMX has potent in vitro activity and superior in vivo activity across 8 different PDX models compared to the standard-of-care agent romidepsin. ALRN-6924 induced a complete remission in a patient with TP53-wild-type angioimmunoblastic T-cell lymphoma, demonstrating the potential for rapid translation of discoveries from subtype-specific preclinical models.


Assuntos
Antineoplásicos/farmacologia , Regulação Neoplásica da Expressão Gênica , Linfoma Extranodal de Células T-NK/tratamento farmacológico , Linfoma de Células T/tratamento farmacológico , Proteínas Nucleares/genética , Peptídeos/farmacologia , Proteínas Proto-Oncogênicas c-mdm2/genética , Proteínas Proto-Oncogênicas/genética , Proteína Supressora de Tumor p53/genética , Animais , Proteínas de Ciclo Celular , Depsipeptídeos/farmacologia , Avaliação Pré-Clínica de Medicamentos , Humanos , Fator de Transcrição Ikaros/antagonistas & inibidores , Fator de Transcrição Ikaros/genética , Fator de Transcrição Ikaros/metabolismo , Imidazolinas/farmacologia , Janus Quinase 2/antagonistas & inibidores , Janus Quinase 2/genética , Janus Quinase 2/metabolismo , Linfoma Extranodal de Células T-NK/genética , Linfoma Extranodal de Células T-NK/metabolismo , Linfoma Extranodal de Células T-NK/patologia , Linfoma de Células T/genética , Linfoma de Células T/metabolismo , Linfoma de Células T/patologia , Camundongos , Proteínas Nucleares/antagonistas & inibidores , Proteínas Nucleares/metabolismo , Ligação Proteica/efeitos dos fármacos , Proteínas Proto-Oncogênicas/antagonistas & inibidores , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Proto-Oncogênicas c-mdm2/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Indução de Remissão , Transdução de Sinais , Proteína Supressora de Tumor p53/antagonistas & inibidores , Proteína Supressora de Tumor p53/metabolismo , Sequenciamento do Exoma , Ensaios Antitumorais Modelo de Xenoenxerto
10.
Expert Opin Drug Discov ; 12(8): 859-873, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28641053

RESUMO

INTRODUCTION: Romidepsin is a potent and selective inhibitor of histone deacetylases (HDCAi). It is also the only bicyclic inhibitor to undergo clinical assessment and is considered a promising drug for the treatment of T-cell lymphomas. The cellular action of romidepsin results in enhanced histone acetylation, as well as the acetylation of other nuclear or cytoplasmic proteins, influencing cell cycle, apoptosis, and angiogenesis. In phase II studies involving patients with relapsed or refractory of cutaneous T-cell lymphoma (CTCL) and peripheral T-cell lymphoma (PTCL), romidepsin produced overall response rates (ORR) of 34-35% and 25-38%, with complete response (CR) rates of 6% and 15-18%, respectively. Areas covered: This review summarizes the development of romidepsin, the mechanisms behind its antineoplastic action and its pharmacology. It also covers its pharmacokinetic and pharmacodynamic properties, as well as the preclinical and clinical data on its activity in T-cell lymphoma. Expert opinion: Since there are only few effective therapies available for T-cell lymphomas, romidepsin is a valuable option for relapsed/refractory patients with both CTCL and PTCL. It's also generally well tolerated, and gives potentially durable responses for patients with advanced and symptomatic disease. Combinations of romidepsin with other antineoplastic agents may also further improve drug response and outcomes in T-cell lymphoma.


Assuntos
Antibióticos Antineoplásicos/uso terapêutico , Depsipeptídeos/uso terapêutico , Linfoma de Células T/tratamento farmacológico , Animais , Antibióticos Antineoplásicos/efeitos adversos , Antibióticos Antineoplásicos/farmacologia , Depsipeptídeos/efeitos adversos , Depsipeptídeos/farmacologia , Desenho de Fármacos , Avaliação Pré-Clínica de Medicamentos/métodos , Inibidores de Histona Desacetilases/efeitos adversos , Inibidores de Histona Desacetilases/farmacologia , Inibidores de Histona Desacetilases/uso terapêutico , Humanos , Linfoma de Células T/patologia , Resultado do Tratamento
11.
Eur J Med Chem ; 128: 247-257, 2017 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-28189906

RESUMO

Dregamine (1) and tabernaemontanine (2), two epimeric monoterpene indole alkaloids isolated in large amount from the roots of the African plant Tabernaemontana elegans, were derivatized, yielding ten imine derivatives, as previously described (3-12). In the present study, aiming at increasing the pool of analogues for establishing structure-activity relationships (SAR), compounds 1 and 2 were further submitted to several chemical transformations, yielding thirteen new derivatives (13-25). Their structures were assigned by spectroscopic methods, including 1D and 2D NMR experiments. Compounds 1-25 were evaluated for their effects on the reversion of multidrug resistance (MDR) in cancer cells mediated by P-glycoprotein (P-gp/ABCB1), through combination of functional and chemosensitivity assays, using a human ABCB1-transfected mouse T-lymphoma cell model. SAR analysis showed that different substituents at C-3 and at the indole nitrogen led to different ABCB1 modulatory effects. When compared to the parent compounds, a remarkable enhancement in MDR reversal activity was found for derivatives sharing a new aromatic moiety. Thus, the strongest ability as MDR reversers, and a manifold activity when compared to verapamil, was found for compound 8, the epimeric compounds 9 and 10, and compound 15, bearing pyrazine, bromo-pyridine, and methoxybenzyloxycarbonyl moieties, respectively. In drug combination assays, all compounds tested were revealed to interact synergistically with doxorubicin. Collectively, the results indicate that some of these derivatives may be promising leads for overcoming MDR in cancer.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Alcaloides Indólicos/farmacologia , Linfoma de Células T/tratamento farmacológico , Monoterpenos/farmacologia , Extratos Vegetais/farmacologia , Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Animais , Doxorrubicina/farmacologia , Humanos , Linfoma de Células T/metabolismo , Linfoma de Células T/patologia , Camundongos , Raízes de Plantas/química , Relação Estrutura-Atividade , Tabernaemontana/química
12.
PLoS One ; 11(8): e0160686, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27494022

RESUMO

Phosphatidylinositol 3 kinase-protein kinase B (PI3K-AKT) pathway has been considered as major drug target site due to its frequent activation in cancer. AKT regulates the activity of various targets to promote tumorigenesis and metastasis. Accumulation of reactive oxygen species (ROS) has been linked to oxidative stress and regulation of signaling pathways for metabolic adaptation of tumor microenvironment. Hydrogen peroxide (H2O2) in this context is used as ROS source for oxidative stress preconditioning. Antioxidants are commonly considered to be beneficial to reduce detrimental effects of ROS and are recommended as dietary supplements. Quercetin, a ubiquitous bioactive flavonoid is a dietary component which has attracted much of interest due to its potential health-promoting effects. Present study is aimed to analyze PI3K-AKT signaling pathway in H2O2 exposed Dalton's lymphoma ascite (DLA) cells. Further, regulation of PI3K-AKT pathway by quercetin as well as PI-103, an inhibitor of PI3K was analyzed. Exposure of H2O2 (1mM H2O2 for 30min) to DLA cells caused ROS accumulation and resulted in increased phosphorylation of PI3K and downstream proteins PDK1 and AKT (Ser-473 and Thr-308), cell survival factors BAD and ERK1/2, as well as TNFR1. However, level of tumor suppressor PTEN was declined. Both PI-103 & quercetin suppressed the enhanced level of ROS and significantly down-regulated phosphorylation of AKT, PDK1, BAD and level of TNFR1 as well as increased the level of PTEN in H2O2 induced lymphoma cells. The overall result suggests that quercetin and PI3K inhibitor PI-103 attenuate PI3K-AKT pathway in a similar mechanism.


Assuntos
Furanos/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Peróxido de Hidrogênio/farmacologia , Linfoma de Células T/tratamento farmacológico , Fosfatidilinositol 3-Quinase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Piridinas/farmacologia , Pirimidinas/farmacologia , Quercetina/farmacologia , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Humanos , Linfoma de Células T/metabolismo , Linfoma de Células T/patologia , Oxidantes/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Inibidores de Fosfoinositídeo-3 Quinase , Fosforilação/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Células Tumorais Cultivadas
13.
Asian Pac J Cancer Prev ; 17(4): 2083-7, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27221899

RESUMO

A new compound namely (13-(3,3-dihydroxypropyl)-1,6-dihydroxy-3,4-dihydro-1H-isochromen-8(5H)-one (1) was isolated from an ethyl acetate extract of the borne fungi Screlotium rolfsii. Its chemical structure was elucidated by spectroscopic analysis. Screlotiumol 1 were evaluated for their effects on the reversion of multidrug resistant (MDR) mediated by P-glycoprotein (P-gp) of the soil borne fungi. The multidrug resistant P-glycoprotein is a target for chemotherapeutic drugs in cancer cells. In the present study rhodamine-123 exclusion screening test on human mdr1 gene transfected mouse gene transfected L5178 and L5178Y mouse T-cell lymphoma which showed excellent MDR reversing effect in a dose dependent manner against mouse T-lymphoma cell line. Moreover, molecular docking studies of compound-1 also showed better results as compared with the standard. Therefore the preliminary results obtained from this study suggest that screlotiumol 1 could be used as a potential agent for the treatment of cancer.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Benzopiranos/química , Benzopiranos/farmacologia , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Fungos/química , Linfoma de Células T/tratamento farmacológico , Extratos Vegetais/farmacologia , Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Acetatos/metabolismo , Animais , Antineoplásicos/isolamento & purificação , Benzopiranos/isolamento & purificação , Humanos , Linfoma de Células T/patologia , Camundongos , Simulação de Acoplamento Molecular , Microbiologia do Solo , Células Tumorais Cultivadas
14.
Asian Pac J Cancer Prev ; 17(4): 2311-4, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27221936

RESUMO

Pistagremic acid (PA) is a bioactive triterpenoid isolated from various parts of Pistacia integerrima plants. The aim of this research was to investigate PA for reversion of multidrug resistant (MDR) mediated by P-glycoprotein using rhodamine-123 exclusion study on a multidrug resistant human ABCB1 (ATP-binding cassette, sub-family B, member 1) gene-transfected mouse T-lymphoma cell line in vitro. Results were similar to those with verapamil as a positive control. Docking studies of PA and standard Rhodamine123 were carried out against a P-gp crystal structure which showed satisfactory results. Actually, PA cannot bind exactly where co-crystallized ligand of P-gp is already present. However, the docking study predicted that if a compound gives a lesser score then it may have some potency. The docking scores of PA and Rhodamine were similar. Therefore, we can conclude that there are certain important chemical features of PA which are responsible for the inhibiting potency of P-gp.


Assuntos
Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Linfoma de Células T/tratamento farmacológico , Pistacia/química , Extratos Vegetais/farmacologia , Triterpenos/farmacologia , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Animais , Humanos , Linfoma de Células T/metabolismo , Linfoma de Células T/patologia , Camundongos , Estrutura Molecular , Extratos Vegetais/química , Células Tumorais Cultivadas
15.
Anticancer Res ; 35(11): 5915-9, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26504015

RESUMO

Efflux pump inhibitors are attractive compounds that reverse multidrug resistance (MDR) in cancer cells. In the present study, 10 phosphorus ylides (P-ylides) were compared based on their MDR-reverting activity in human ATP-binding cassette sub-family B member 1 (ABCB1; P-glycoprotein) gene-transfected L5178Y mouse T-lymphoma cells. Among them, three P-ylides, Ph3P=C(COCF3)COPh, Ph3P=C(COC2F5)COPh and Ph3P=C(COC3F7)COPh were identified as selectively modulating the ABCB1 pump. These compounds, with low cytotoxicity against mouse T-lymphoma cells, exhibited more potency than the positive control ABCB1 inhibitor verapamil.


Assuntos
Proliferação de Células/efeitos dos fármacos , Compostos Heterocíclicos/farmacologia , Hidrocarbonetos Fluorados/farmacologia , Linfoma de Células T/tratamento farmacológico , Linfoma de Células T/patologia , Fósforo/química , Subfamília B de Transportador de Cassetes de Ligação de ATP/antagonistas & inibidores , Animais , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Citometria de Fluxo , Compostos Heterocíclicos/química , Humanos , Hidrocarbonetos Fluorados/química , Camundongos , Células Tumorais Cultivadas , Vasodilatadores/farmacologia , Verapamil/farmacologia
16.
Molecules ; 20(1): 1731-50, 2015 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-25608858

RESUMO

Natural organosulfur compounds (OSCs) from Allium sativum L. display antioxidant and chemo-sensitization properties, including the in vitro inhibition of tumor cell proliferation through the induction of apoptosis. Garlic water- and oil-soluble allyl sulfur compounds show distinct properties and the capability to inhibit the proliferation of tumor cells. In the present study, we optimized a new protocol for the extraction of water-soluble compounds from garlic at low temperatures and the production of glutathionyl-OSC conjugates during the extraction. Spontaneously, Cys/GSH-mixed-disulfide conjugates are produced by in vivo metabolism of OSCs and represent active molecules able to affect cellular metabolism. Water-soluble extracts, with (GSGaWS) or without (GaWS) glutathione conjugates, were here produced and tested for their ability to release hydrogen sulfide (H2S), also in the presence of reductants and of thiosulfate:cyanide sulfurtransferase (TST) enzyme. Thus, the TST catalysis of the H2S-release from garlic OSCs and their conjugates has been investigated by molecular in vitro experiments. The antiproliferative properties of these extracts on the human T-cell lymphoma cell line, HuT 78, were observed and related to histone hyperacetylation and downregulation of GAPDH expression. Altogether, the results presented here pave the way for the production of a GSGaWS as new, slowly-releasing hydrogen sulfide extract for potential therapeutic applications.


Assuntos
Alho/química , Glutationa/metabolismo , Sulfeto de Hidrogênio/metabolismo , Compostos de Enxofre/uso terapêutico , Enxofre/metabolismo , Biocatálise/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Cromatografia de Fase Reversa , Temperatura Baixa , Humanos , Linfoma de Células T/patologia , Microscopia de Fluorescência , Peso Molecular , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Substâncias Redutoras/farmacologia , Solubilidade , Compostos de Enxofre/farmacologia , Tiorredoxinas/metabolismo , Tiossulfato Sulfurtransferase/antagonistas & inibidores , Tiossulfato Sulfurtransferase/metabolismo , Água/química
17.
Biomed Res Int ; 2014: 753451, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24959588

RESUMO

Dendrobium, a genus of orchid, was found to possess useful therapeutic activities like anticancer, hypoglycaemic, antimicrobial, immunomodulatory, hepatoprotective, antioxidant, and neuroprotective activities. The study was aimed to evaluate the anticancer property of the ethanolic extract of Dendrobium formosum on Dalton's lymphoma. In vitro cytotoxicity was determined by MTT assay, apoptosis was determined by fluorescence microscopy, and cell cycle progression was analysed using flow cytometry; in vivo antitumor activity was performed in Dalton's lymphoma bearing mice. The IC50 value of ethanolic extract was obtained at 350 µg/mL in Dalton's lymphoma cells. Fluorescence microscopy analysis showed significant increase in apoptotic cell death in dose- and time-dependent manner which was further confirmed through the resulting DNA fragmentation. Further, flow cytometry analysis showed that the ethanolic extract arrests the cells in G2/M phase of the cell cycle. The in vivo anticancer activity study illustrates significant increase in the survival time of Dalton's lymphoma bearing mice on treatment with ethanolic extract when compared to control. These results substantiate the antitumor properties of ethanolic extract of Dendrobium formosum and suggest an alternative in treatment of cancer. Further studies are required regarding the isolation and characterization of bioactive components along with the analysis of molecular mechanism involved.


Assuntos
Dendrobium/química , Linfoma de Células T/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Fragmentação do DNA/efeitos dos fármacos , Humanos , Técnicas In Vitro , Linfoma de Células T/patologia , Camundongos , Extratos Vegetais/química , Ensaios Antitumorais Modelo de Xenoenxerto
18.
Cancer ; 120(13): 1993-9, 2014 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-24706502

RESUMO

BACKGROUND: T-cell lymphomas (TCLs) are uncommon in the United States. The accurate diagnosis of TCL is challenging and requires morphologic interpretation, immunophenotyping, and molecular techniques. The authors compared pathologic diagnoses at referring centers with diagnoses from expert hematopathology review to determine concordance rates and to characterize the usefulness of second-opinion pathology review for TCL. METHODS: Patients in the National Comprehensive Cancer Network non-Hodgkin lymphoma database with peripheral TCL, not otherwise specified (PTCL-NOS), angioimmunoblastic TCL (AITL), and anaplastic lymphoma kinase (ALK)-positive and ALK-negative anaplastic large cell lymphoma (ALCL) were eligible if they had prior tissue specimens examined at a referring institution. Pathologic concordance was evaluated using available pathology and diagnostic testing reports and provider progress notes. The etiology of discordance and the potential impact on treatment were examined. RESULTS: Among 131 eligible patients, 57 (44%) had concordant results, totaling 64% of the 89 patients who were referred with a final diagnosis. Thirty-two patients (24%) had discordant results, representing 36% of those who were referred with a final diagnosis. The rates of discordance among patients with of PTCL-NOS, AITL, ALK-negative ALCL, and ALK-positive ALCL were 19%, 33%, 34%, and 6%, respectively. In 14 patients (44% of discordant results), pathologic reclassification could have resulted in a different therapeutic strategy. Forty-two patients (32%) were referred for classification with a provisional diagnosis. CONCLUSIONS: In a large cohort of patients with TCL who were referred to National Comprehensive Cancer Network centers, the likelihood of a concordant final diagnosis at a referring institution was low. As current and future therapies target TCL subsets, these data suggest that patients with suspected TCLs would benefit from evaluation by an expert hematopathologist.


Assuntos
Biomarcadores Tumorais/análise , Linfoma de Células T/patologia , Receptores Proteína Tirosina Quinases/análise , Encaminhamento e Consulta , Atenção Secundária à Saúde , Adulto , Idoso , Quinase do Linfoma Anaplásico , Estudos de Coortes , Diagnóstico Diferencial , Linfoma de Células T Associado a Enteropatia/patologia , Feminino , Citometria de Fluxo , Humanos , Linfadenopatia Imunoblástica/patologia , Imuno-Histoquímica , Imunofenotipagem , Linfoma Difuso de Grandes Células B/patologia , Linfoma Anaplásico de Células Grandes/patologia , Linfoma de Célula do Manto/patologia , Linfoma de Células T/terapia , Masculino , Pessoa de Meia-Idade , Encaminhamento e Consulta/estatística & dados numéricos , Atenção Secundária à Saúde/estatística & dados numéricos , Estados Unidos
19.
J Comp Pathol ; 150(2-3): 336-40, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24650893

RESUMO

This report describes the pathological findings in an adult female short-beaked common dolphin (Delphinus delphis) stranded alive in the Canary Islands. Necropsy examination revealed the presence of a nodular neoplastic growth in the central nervous system (CNS) at the level of the thalamus. Microscopical examination revealed the mass to be a lymphoma and immunohistochemical labelling demonstrated a T-cell origin. No significant lesions were observed in other organs, including lymphoid organs. This is the first report of a primary T-cell lymphoma in the CNS in cetaceans.


Assuntos
Neoplasias do Sistema Nervoso Central/veterinária , Golfinhos Comuns , Linfoma de Células T/veterinária , Tálamo/patologia , Animais , Neoplasias do Sistema Nervoso Central/patologia , Feminino , Linfoma de Células T/patologia
20.
Artigo em Inglês | MEDLINE | ID: mdl-24311843

RESUMO

The objective of the study was to investigate the in-vivo anti-tumour activity of Spica prunellae extract, and to preliminarily explore the possible mechanism of in-vivo anti-tumour effect of Spica prunellae extract. Tumour inhibition rate and tumour apoptosis-related protein status were determined using the mice model of transplanted T lymphoma cell EL-4 tumour, and by immunohistochemical method. The results revealed that Spica prunellae extract showed certain tumour inhibitory effect, and compared with the model group. Tumour weight in Spica prunellae high-dose group was highly significantly different (P<0.01). Tumour weight in Spica prunellae medium-dose group was also significantly different (P<0.05) compared with the model group. Spica prunellae high-dose group enabled the high expression of Bcl-2 protein (47.54%) and low expression of Bax protein (13.14%). The study concluded that Spica prunellae extract has certain in vivo anti-tumour effect, which may be achieved through regulation of apoptosis related proteins.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Linfoma de Células T/tratamento farmacológico , Fitoterapia , Extratos Vegetais/uso terapêutico , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Prunella , Animais , Antineoplásicos Fitogênicos/farmacologia , Apoptose , Frutas , Linfoma de Células T/metabolismo , Linfoma de Células T/patologia , Camundongos , Camundongos Endogâmicos C57BL , Extratos Vegetais/farmacologia , Proteína X Associada a bcl-2/metabolismo
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