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1.
Cancer Rep (Hoboken) ; 7(7): e2106, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38967112

RESUMO

BACKGROUND: Plasmacytoma of the skull base is a rare manifestation of plasma cell neoplasm with only a few cases documented in literature involving young adults. Plasmacytoma can be an isolated solitary lesion or a secondary manifestation of multiple myeloma (MM). In this study, we report the clinical and radiological characteristics, management, and outcomes of patients under the age of 40 who presented with skull base plasmacytoma and associated neurological manifestations. Additionally, we share our experience in treating a rare case of skull base plasmacytoma diagnosed during pregnancy, in which the patient exhibited a favorable response to myeloma treatment initiated after delivery. CASE SERIES: Four patients were identified, comprising one pregnant female and three male patients, with a median age of 36 years (range 33-37 years). The main presenting symptoms were headache, dizziness, and cranial nerve palsy. All patients received underwent systemic myeloma therapy and radiotherapy with three patients also underwent autologous stem cell transplantation (ASCT). Notably, all patients achieved complete remission. CONCLUSION: Skull base plasmacytoma represents a rare manifestation of plasma cell neoplasms, underscoring the importance of considering it in the differential diagnosis of skull base lesions to ensure early intervention and avoid potential serious complications. Throughout our series, the cornerstone of therapy involved radiotherapy, systemic myeloma therapy, and ASCT, all of which elicited a favorable response in every case.


Assuntos
Plasmocitoma , Neoplasias da Base do Crânio , Humanos , Masculino , Plasmocitoma/terapia , Plasmocitoma/patologia , Plasmocitoma/diagnóstico , Adulto , Feminino , Neoplasias da Base do Crânio/patologia , Neoplasias da Base do Crânio/terapia , Gravidez , Mieloma Múltiplo/terapia , Mieloma Múltiplo/patologia , Mieloma Múltiplo/diagnóstico , Transplante Autólogo , Resultado do Tratamento , Complicações Neoplásicas na Gravidez/patologia , Complicações Neoplásicas na Gravidez/terapia , Complicações Neoplásicas na Gravidez/diagnóstico , Imageamento por Ressonância Magnética
2.
Viral Immunol ; 37(4): 186-193, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38717821

RESUMO

Coronavirus disease 2019 (COVID-19) represented an international health risk. Variants of the interferon-induced transmembrane protein-3 (IFITM3) gene can increase the risk of developing severe viral infections. This cross-sectional study investigated the association between IFITM3 rs12252A>G single nucleotide polymorphism (SNP) and COVID-19 severity and mortality in 100 Egyptian patients. All participants were subjected to serum interleukin-6 (IL-6) determination by ELISA and IFITM3 rs12252 genotyping by real-time polymerase chain reaction. Of all participants, 85.0% had the IFITM3 rs12252 homozygous AA genotype, whereas 15.0% had the heterozygous AG genotype. None of our participants had the homozygous GG genotype. The IFITM3 rs12252A allele was found in 92.5% and the G allele in only 7.5%. There was no significant association (p > 0.05) between the IFITM3 rs12252 SNP and COVID-19 severity, intensive care unit (ICU) admission, or IL-6 serum levels. The heterozygous AG genotype frequency showed a significant increase among participants who died (32.0%) compared with those who had been cured (9.3%). The mutant G allele was associated with patients' death. Its frequency among cured participants was 8.5%, whereas in those who died was 24.2% (p = 0.024) with 3.429 odds ratio [95% confidence interval: 1.1-10.4]. In conclusion, this study revealed a significant association between the G allele variant of IFITM3 rs12252 and COVID-19 mortality. However, results were unable to establish a significant link between rs12252 polymorphism, disease severity, ICU admission, or serum IL-6 levels.


Assuntos
COVID-19 , Proteínas de Membrana , Proteínas de Ligação a RNA , SARS-CoV-2 , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Alelos , COVID-19/mortalidade , COVID-19/genética , Estudos Transversais , Egito , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Interleucina-6/sangue , Interleucina-6/genética , Proteínas de Membrana/genética , Polimorfismo de Nucleotídeo Único , Proteínas de Ligação a RNA/genética , SARS-CoV-2/patogenicidade , Índice de Gravidade de Doença
3.
Case Rep Oncol ; 17(1): 291-297, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38371169

RESUMO

Introduction: Multiple myeloma (MM) is a clonal neoplasm of plasma cells that may manifest as an extramedullary disease in rare cases. Case Report: In this case report, we present the rare occurrence of testicular relapse in a 39-year-old patient with IgA MM after 3 years of remission. We discuss the clinical course and management of this unusual presentation and provide a comprehensive literature review of testicular involvement by MM. Conclusion: Despite advances in MM treatment, relapse remains common, highlighting the importance of careful follow-up and timely detection of disease recurrence at atypical sites. This case highlights the need for further research to standardize the diagnosis and treatment of testicular MM.

4.
Front Pediatr ; 11: 1150179, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37152306

RESUMO

Background: Autoimmune lymphoproliferative syndrome (ALPS) is a rare disease characterized by defective FAS signaling, which results in chronic, nonmalignant lymphoproliferation and autoimmunity accompanied by increased numbers of "double-negative" T-cells (DNTs) (T-cell receptor αß+ CD4-CD8-) and an increased risk of developing malignancies later in life. Case presentation: We herein report a case of a newborn boy with a novel germline homozygous variant identified in the FAS gene, exon 9, c.775del, which was considered pathogenic. The consequence of this sequence change was the creation of a premature translational stop signal p.(lle259*), associated with a severe clinical phenotype of ALPS-FAS. The elder brother of the proband was also affected by ALPS and has been found to have the same FAS homozygous variant associated with a severe clinical phenotype of ALPS-FAS, whereas the unaffected parents are heterozygous carriers of this variant. This new variant has not previously been described in population databases (gnomAD and ExAC) or in patients with FAS-related conditions. Treatment with sirolimus effectively improved the patient clinical manifestations with obvious reduction in the percentage of DNTs. Conclusion: We described a new ALPS-FAS clinical phenotype-associated germline FAS homozygous pathogenic variant, exon 9, c.775del, that produces a premature translational stop signal p.(lle259*). Sirolimus significantly reduced DNTs and substantially relieved the patient's clinical symptoms.

5.
Clin Case Rep ; 11(5): e5908, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37234472

RESUMO

Chronic myeloid leukemia (CML) is a myeloproliferative disorder due to translocation between chromosomes (9, 22), known as the "Philadelphia chromosome." In 2016, the World health organization (WHO) introduced a new clinical entity of de novo acute myeloid leukemia (AML). Both diseases share some commonalities, therefore, create a challenge to diagnose.

6.
Egypt J Immunol ; 30(2): 47-58, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37031397

RESUMO

Mesenchymal stem cells (MSCs) and hepatocytes are considered valuable candidates for cell-based therapy. The use of free zoonotic media, as purified platelets derived growth factors (L-GF) and human platelet lysate (hPL), instead of using fetal bovine serum (FBS) to support the growth and proliferation of these cells could be used as a promising therapeutic tool in hepatic regeneration. This study aimed to evaluate the usage of purified platelet derived growth factors and platelet lysate in both MSCs and hepatocyte cultures and to compare them with the usage of FBS. MSCs and hepatocytes were cultured in growth media supplemented with L-GF or hPL and compared them to their culture in growth media supplemented with FBS. Cells were subjected to population doubling (PD) and generation time (GT) calculations. The best result for MSCs was that obtained by using 10% hPL or 10% FBS with the highest cell count, highest viability and shortest incubation time needed to reach confluency compared to supplementation with 10%, 20% or 30% L-GF. As for hepatocyte culture, the use of 10% FBS for supplementation of media used for hepatic cell proliferation showed better performance regarding cell count, viability, and incubation time to reach confluency compared to the use of either hPL or L-GF. In conclusion, our study showed that 10% hPL had the best results in MSCs culture which suggests that hPL could be a better alternative for the development of xenofree stem cell culture that can be used for many clinical applications. On the other hand, 10% FBS showed the best results in hepatocyte culture.


Assuntos
Células-Tronco Mesenquimais , Fator de Crescimento Derivado de Plaquetas , Humanos , Fator de Crescimento Derivado de Plaquetas/metabolismo , Diferenciação Celular , Células Cultivadas , Plaquetas , Meios de Cultura/metabolismo , Cirrose Hepática , Hepatócitos
7.
Technol Cancer Res Treat ; 21: 15330338221086396, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35341409

RESUMO

Objectives: This study aims to assess the value of FLT-PET as a non-invasive tool to differentiate between patients with ET and Pre-PMF. This study is a pilot study to have a proof of concept only. Methods: This is a prospective, interventional study where a total of 12 patients were included. Each patient underwent FLT PET imaging as well as bone marrow examination (gold standard). In addition, semi-quantitative (SUVmax and SUVmean) measurements of FLT uptake in the liver, spleen, and Lspine, SUVmean, as well as the Total Lesion Glycolysis (TLG) of the Lspine were performed. Results from the two patient cohorts were compared using = Kruskal-Wallis statistical test. A P-value of <.05 is considered to be statistically significant. Results: The differences in FLT SUVmax and SUVmean measurements in the three organs (liver, spleen, and LSpine) between the ET and Pre-PMF patients were not statistically significant (P > .05). In contrast, TLG measurements in the LSpine were statistically different (P = .013), and therefore, compared to gold standard bone marrow results, TLG can separate ET and Pre-PMF patients. Conclusion: This study is a proof of concept about the potential to discriminate between ET and pre-PMF patients in a non-invasive way. TLG of the LSpine in FLT PET images is a potential quantitative parameter to distinguish between ET and pre-PMF patients.


Assuntos
Mielofibrose Primária , Trombocitemia Essencial , Medula Óssea/diagnóstico por imagem , Medula Óssea/patologia , Didesoxinucleosídeos , Humanos , Projetos Piloto , Tomografia por Emissão de Pósitrons , Mielofibrose Primária/diagnóstico por imagem , Mielofibrose Primária/patologia , Estudos Prospectivos , Trombocitemia Essencial/diagnóstico por imagem , Trombocitemia Essencial/patologia
8.
J Hematol ; 11(1): 21-28, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35356636

RESUMO

Herein, we describe the clinicopathologic and genetic characteristics of the first report of simultaneous bone marrow involvement by classical hairy cell leukemia (HCL) and leukemic non-nodal variant of mantle cell lymphoma (L-NN-MCL) with t(11;14)(q13;q32) with BRAF mutation and deletion of TP53. A 40-year-old asymptomatic man was investigated for incidental neutropenia and thrombocytopenia. Flow cytometry showed two distinct monotypic B-cell populations: one expressed CD19 (bright), CD20 (bright), FMC7, CD103, CD25, CD11c, CD123, and IgD (bright) and showed kappa light chain restriction (bright), consistent with HCL and the other kappa-restricted CD5/CD10-negative B-cell population with distinctive immunophenotypic features. The bone marrow biopsy is infiltrated by an abnormal B-lymphoid infiltrate with different patterns of infiltration in different marrow areas. Fluorescence in situ hybridization (FISH) analysis revealed a CCND1/IGH rearrangement, t(11;14)(q13;q32), and deletion of TP53. The BRAF V600E missense mutation was detected by quantitative real-time polymerase chain reaction (PCR). The diagnosis of a composite B-cell neoplasm was composed of HCL together with a second CD5/CD10-negative monotypic B-cell population, with CCND1/IGH fusion, favoring the 2016 WHO new category of L-NN-MCL (CD5/SOX11-negative). Treatment with cladribine and rituximab normalized the blood counts within 6 weeks without significant side effects. L-NN-MCL is one of the smoldering MCL subtypes, recently listed in WHO 2016 as a separate variant, with a particular set of unique features and a less aggressive clinical course compared to classical MCL. To date, the clinicopathological features (including the bone marrow findings) of L-NN-MCL have not been sufficiently characterized in the literature. We describe the first report of synchronous presentation of HCL and L-NN-MCL. This case represents a real challenge from the biologic, diagnostic and therapeutic point of views, due to extremely rare combination of two distinct uncommon B-cell neoplasms. The study of composite lymphomas offers the opportunity to evaluate the etiology and the clonal interrelationship involved in the pathogenesis/evolution of lymphomas.

10.
Am J Case Rep ; 22: e933398, 2021 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-34413281

RESUMO

BACKGROUND Amyloid light-chain (AL) amyloidosis is a disease that results in systemic amyloid deposition, which may present with multi-organ dysfunction. It carries a poor prognosis at the time of diagnosis. CASE REPORT A 37-year-old patient with a history of Wolff-Parkinson-White syndrome and thyroiditis presented with syncope and hypovolemia. ECG showed non-specific T wave inversions in the lateral leads with no signs of ischemia. Laboratory investigations revealed deranged coagulation parameters with prolonged prothrombin time (PT) and activated partial thromboplastin time (aPTT) and follow-up factor assays revealed severe factor X deficiency. A transthoracic echocardiogram and subsequent cardiac MRI showed signs of cardiac amyloidosis. Bone marrow biopsy was consistent with AL amyloidosis, demonstrating period acid-Schiff (PAS)-positive adipose deposits and interstitial infiltration by clusters of lambda restricted plasma cells with aberrant expression of CD 56 and CD 117.The patient was treated with bortezomib, cyclophosphamide, and dexamethasone, but died early during his treatment due to cardiac arrest, suspected to be secondary to conduction abnormalities caused by cardiac infiltration. CONCLUSIONS This case represents a novel pattern of disease in AL amyloidosis with cardiac, thyroid, and hematological involvement as a result of systemic amyloid deposition.Our report highlights the need for physicians to be aware of cardiac amyloidosis-related complications and the morbidity and mortality associated with concurrent hematological involvement in these cases.


Assuntos
Amiloidose , Deficiência do Fator X , Insuficiência Cardíaca , Amiloidose de Cadeia Leve de Imunoglobulina , Síndromes de Pré-Excitação , Adulto , Amiloidose/complicações , Amiloidose/diagnóstico , Humanos , Amiloidose de Cadeia Leve de Imunoglobulina/complicações , Amiloidose de Cadeia Leve de Imunoglobulina/diagnóstico
11.
Mediterr J Hematol Infect Dis ; 13(1): e2021043, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34276912

RESUMO

BACKGROUND: Plasma cell neoplasms can show aberrant expression of different lineage-related antigens; however, co-expression of T-cell-associated markers on malignant plasma cells is extremely rare. MATERIAL AND METHODS: This report describes clinicopathologic characteristics of three myeloma patients with emergent plasmablastic morphology and aberrant acquisition of T-cell-associated markers diagnosed in our center. An extensive literature search for similar cases was conducted, and the relevant pathologic, clinical, and prognostic characteristics were summarized. RESULTS: A total of 22 cases of plasma cell neoplasm (including the three cases reported here) showed aberrant co-expression of T-cell markers. We found an evident association between aberrant expression of T-cell markers on malignant plasma cells and extramedullary involvement, aggressive morphologic features, high proliferative index ki67 >90%, aggressive clinical course, an adverse outcome, and short survival. DISCUSSION & CONCLUSION: Due to the rarity of this aberrant phenotype and scarcity of the published data, the precise causative mechanism and its clinical implications have not yet been elucidated.

12.
Nanomaterials (Basel) ; 11(2)2021 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-33546151

RESUMO

Annona muricata is one of the most important traditional medicinal plants which contains numerous chemicals that exhibit various pharmacological properties. In this study, silver nanoparticles were prepared using A. muricata peel extract as a reducing agent and the effect was enhanced through A. muricata like pharmaceutical activity. AgNPs formation was confirmed by color changes, UV-visible spectroscopy, SEM, DLS, and XRD. The anti-proliferative activity of AgNPs against THP-1, AMJ-13, and HBL cell lines was studied. Apoptotic markers were tested using AO/EtBr staining assay, cell cycle phases using flowcytometry, and the expression of P53. Autophagy takes an essential part in controlling inflammasome activation by primary bone marrow-derived macrophages (BMDMs). We report novel functions for AgNPs-affected autophagy, represented by the control of the release of IL-1ß, caspase-1, adaptor protein apoptosis-associated speck-like protein containing a CARD (ASC), and NLRP3 in BMDMs following treatment with LPS+ATP. The current study revealed that the AgNPs inhibited THP-1 and AMJ-13 cell proliferation. Meanwhile, the AgNPs significantly increased autophagy and reduced IL-1b and NLRP3 levels in both in vivo and in vitro models. The secretion of IL-1ß was reduced whereas the degradation of NLRP3 inflammasome was enhanced. These findings propose that AgNPs apply an anti-proliferative activity against THP-1 and AMJ-13 cells through the stimulation of apoptosis via mitochondrial damage and induction of p53 protein pathway. In addition, AgNP-induced autophagy reduced the levels of IL-1ß and NLRP3 inflammasome activation. This indicated that the AgNPs augment autophagy controlled by the IL-1ß pathway via two different novel mechanisms. The first one is regulating activation of the IL-1 ß, caspae-1, and ASC, while the second is NLRP3 targeting for lysosomal degradation. Overall, this study suggests that AgNPs could be a potent therapy for various types of cancer and an alternative treatment for preventing inflammation via enhancing autophagy.

13.
Artif Cells Nanomed Biotechnol ; 49(1): 48-60, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33403879

RESUMO

Nanoparticles (NPs) have biological activities like antibacterial, antifungal, drug delivery, immunomodulation and antitumor activities. The aim of the current study was to investigate some of biomedical applications of silver NP synthesis using extracts from leaves of Eriobotrya japonica. Colour changes, UV-visible spectroscopy, SEM, zeta potential, dynamic light scattering, FTIR and XRD were used to confirm AgNPs formation. The UV-vis spectrum absorption band was observed at almost 430 nm. The SEM image shows quasi-spherical shape of AgNPs. The zeta potential demonstrated the negative surface charge of NPs. FTIR results showed the functional groups of AgNPs. Crystalline nature of AgNPs was confirmed by XRD pattern. MTT assay was used to study the anti-proliferative activity against MCF-7 and HeLa cells. Apoptosis was tested using a DNA-fragmentation test, and expression of P53. AgNPs inhibited the proliferation of MCF-7 and HeLa cells, and reduced inflammation. Treatment with AgNPs significantly decreased allergic disorder. AgNPs stimulated the phagocytosis process in BMDMs. The results suggested that AgNPs could be a promising therapy for future and preventing inflammation, reduce allergic disorders and prevent bacterial infection through the up-regulation of phagocytosis. Hence, future work such as developed and improved NPs as adjuvants, immune-modulating substances and nano-drug delivery system is needed.


Assuntos
Antineoplásicos , Proliferação de Células/efeitos dos fármacos , Eriobotrya/química , Química Verde , Hipersensibilidade , Nanopartículas Metálicas , Neoplasias , Extratos Vegetais/química , Prata , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Células HeLa , Humanos , Hipersensibilidade/tratamento farmacológico , Hipersensibilidade/metabolismo , Hipersensibilidade/patologia , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Inflamação/patologia , Células MCF-7 , Masculino , Nanopartículas Metálicas/química , Nanopartículas Metálicas/uso terapêutico , Camundongos , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Neoplasias/patologia , Fagocitose , Prata/química , Prata/farmacologia
14.
Int J Lab Hematol ; 43(3): 515-525, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33314668

RESUMO

INTRODUCTION: Lymphoid enhancer-binding factor 1 (LEF-1) overexpression has been recently remarkably reported in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and has shown utility in distinguishing CLL/SLL from other B-cell lymphomas. CLL has a well-defined immunophenotype, yet, some cases of CLL demonstrate atypical morphology/ phenotype reflected by low Matutes score (atypical CLL). Till date, LEF1 expression has not been systematically studied in cases of CLL with atypical features. METHODS: In this study, LEF-1 expression was assessed by two different techniques, (immunohistochemistry and flow cytometry), to investigate the expression profile of LEF-1 in cases of CLL/SLL, in comparison with other low-grade B-lymphomas and CLL with atypical features, including atypical immunophenotype and CLL with increased prolymphocytes or morphologically atypical cells. RESULTS: We found that LEF-1 expression is downregulated in CLL with atypical immunophenotype/features compared to classic CLL; Chi-Square P < .0001. The ratio for LEF-1 expression in malignant B-cells/NK (by flow cytometry) in CLL/SLL with classic immunophenotype was higher than atypical CLL and is significantly higher in other small B-cell lymphomas (P < .01). Absence of LEF-1 expression in CLL/SLL is correlated (P < .05) with downregulation of CD5, CD23, CD200, expression of FMC7, brighter expression of CD79b, brighter expression of surface light chain, increased prolymphocytes and lower Matutes score. CONCLUSION: As downregulation of LEF-1 expression is well correlated with atypical CLL, we suggest adding LEF-1 to Matutes score as a beneficial marker to differentiate classic from atypical CLL LEF-1 could also serve as a potential prognostic indicator for CLL clinical course.


Assuntos
Leucemia Linfocítica Crônica de Células B/diagnóstico , Fator 1 de Ligação ao Facilitador Linfoide/análise , Regulação para Baixo , Feminino , Citometria de Fluxo , Regulação Leucêmica da Expressão Gênica , Humanos , Imuno-Histoquímica , Leucemia Linfocítica Crônica de Células B/genética , Leucemia Linfocítica Crônica de Células B/patologia , Fator 1 de Ligação ao Facilitador Linfoide/genética , Masculino , Estudos Prospectivos , Estudos Retrospectivos
15.
Int J Nanomedicine ; 15: 9025-9047, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33235450

RESUMO

BACKGROUND: Linalool is a monoterpene compound with various potential therapeutic applications in several medical fields. Previous studies have indicated the activity of linalool against cell lines; however, its high level of toxicity restricts its use. The aim of this study was to design and manufacture compounds with a novel structure that can be used for loading linalool, to reduce its toxicity and improve its reachable ability. METHODS: We synthesized and characterized a new molecule for loading linalool onto gold nanoparticles (GNPs) capped with glutathione and conjugated with a CALNN peptide. Linalool was loaded onto the GNPs via the reaction of the surface groups of both linalool and the GNPs. Moreover, the target peptide could be loaded onto the surface of the GNPs via a chemical reaction. The cytotoxic effects of linalool-GNP (LG) and linalool-GNP-CALNN peptide (LGC) conjugates against ovarian cancer cells were investigated, as were the possible mechanisms underlying the induction of apoptosis. RESULTS: Our findings illustrated the significant antiproliferative effect of LG and LGC on SKOV-3 cells. The cytotoxicity assay demonstrated that LG and LGC were selectively toxic in cancer cells and induced apoptosis by activating caspase-8, the p53 protein, and various proteins involved in apoptosis. The present data demonstrated that LG and LGC have a high therapeutic potential and should be given particular consideration as anticancer drug-delivery systems, as LG and LGC were remarkably more cytotoxic against a cancer cell line than were linalool and GNPs alone. CONCLUSION: We concluded that LG and LGC are promising compounds that can be used for treating ovarian cancer (SKOV-3) cells via the induction of apoptosis through extrinsic and intrinsic pathways.


Assuntos
Monoterpenos Acíclicos/química , Apoptose , Glutationa/química , Ouro/química , Nanopartículas Metálicas/química , NF-kappa B/metabolismo , Peptídeos/farmacologia , Antineoplásicos/farmacologia , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Biomarcadores Tumorais/metabolismo , Caspase 8/genética , Caspase 8/metabolismo , Linhagem Celular Tumoral , Forma do Núcleo Celular/efeitos dos fármacos , Dano ao DNA , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Nanopartículas Metálicas/ultraestrutura , Mutagênicos/toxicidade , Transporte Proteico/efeitos dos fármacos , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/genética
16.
Case Rep Oncol ; 13(3): 1215-1226, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33173488

RESUMO

Lymphomas are presently categorized according to their origin from B or T lymphocytes. The co-expression of CD3 in B-cell lymphomas or CD20 in T-cell lymphomas has been rarely reported. Immature and less often mature lymphomas may incorporate the rearrangements of both B- and T-cell antigen receptor genes (dual genotype or bigenotype). Lymphoma cells with a sole genotype hardly concurrently express both B- and T-cell markers (biphenotypic lymphomas). We describe a 63-year-old female who was presented with obstructive jaundice and epigastric pain of 10 days. Initial CBC revealed 43×103/µL white blood cells, 11.2 g/dL hemoglobin, and 88x103/µL platelets. CT abdomen revealed hepatomegaly and suspected pancreatic mass with large retroperitoneal lymph nodal mass. Peripheral smear showed 56% lymphoid cells with blast morphology. The bone marrow (BM) aspirate smear was infiltrated by 83% immature-looking cells. BM biopsy showed interstitial to diffuse extensive infiltration by primitive-looking cells, positive for pan-B-cell antigens CD20, CD79, and PAX5 as well as the T-cell antigen CD4, CD5, CD3, while negative for all immaturity markers (CD34, TdT, and CD1a). In situ hybridization for Epstein-Barr virus (EBV)-encoded small RNA (EBER) was negative. Flow cytometry on BM aspirate showed an abnormal population (50%) expressing the B-cell antigens (CD19, CD20, CD79, CD22) and CD10, and showed lambda light chain restriction as well as the T-cell antigens cCD3 and CD4 with partial CD5. The analysis showed, also, another abnormal population of lambda restricted monotypic B cells (8%) with dimmer CD45 (blast gate) and showed the same immunophenotype (expressing the B-cell antigens), but negative for CD10, cCD3, CD5, and CD4. Conventional cytogenetic revealed complex karyotype. Molecular studies revealed rearrangements of the immunoglobulin heavy chain region consistent with a clonal B-cell population. TCR gene rearrangement analysis was equivocal concerning clonality but was not conclusive for clonal T-cell disease. Our final diagnosis was peripheral blood and BM involvement by EBV-negative high-grade lymphoid neoplasm (in leukemic phase with blast morphology) and an ambiguous immunophenotype with a differential diagnosis that may include the rare entity of bigenotypic lymphoma or an unusual case of high-grade B-cell lymphoma with aberrant expression of T-cell markers (biphenotypic lymphomas).

17.
Medicine (Baltimore) ; 99(45): e23088, 2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33157979

RESUMO

The objectives of this research project are to study in patients with primary myelofibrosis (PMF) and Essential Thrombocythemia (ET); (1) the uptake patterns of FLT-PET (FLT-PET) and its value in diagnosing, staging, and treatment response monitoring of malignant hematopoiesis, (2) compare imaging findings from FLT-PET with bone marrow biopsy (standard of care), and (3) associate FLT-PET uptake patterns with genetic makeup such as JAK2 (Janus kinase 2), CALR (Calreticulin), MPL (myeloproliferative leukemia protein), Triple negative disease, and allele burden.This trial is registered in ClinicalTrials.gov with number NCT03116542. Protocol version: Mar 2017.


Assuntos
Didesoxinucleosídeos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Mielofibrose Primária/diagnóstico por imagem , Trombocitemia Essencial/diagnóstico por imagem , Ensaios Clínicos Fase I como Assunto , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos
18.
Molecules ; 25(22)2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33233753

RESUMO

The main objective of the current study was the extraction, purification, and biochemical characterization of a protein protease inhibitor from Conyzadioscoridis. Antimicrobial potential and cytotoxic effects were also examined. The protease inhibitor was extracted in 0.1 M phosphate buffer (pH 6-7). Then, the protease inhibitor, named PDInhibitor, was purified using ammonium sulfate precipitation followed by filtration through a Sephadex G-50 column and had an apparent molecular weight of 25 kDa. The N-terminal sequence of PDInhibitor showed a high level of identity with those of the Kunitz family. PDInhibitor was found to be active at pH values ranging from 5.0 to 11.0, with maximal activity at pH 9.0. It was also fully active at 50 °C and maintained 90% of its stability at over 55 °C. The thermostability of the PDInhibitor was clearly enhanced by CaCl2 and sorbitol, whereas the presence of Ca2+ and Zn2+ ions, Sodium taurodeoxycholate (NaTDC), Sodium dodecyl sulfate (SDS), Dithiothreitol (DTT), and ß-ME dramatically improved the inhibitory activity. A remarkable affinity of the protease inhibitor with available important therapeutic proteases (elastase and trypsin) was observed. PDInhibitor also acted as a potent inhibitor of commercial proteases from Aspergillus oryzae and of Proteinase K. The inhibitor displayed potent antimicrobial activity against gram+ and gram- bacteria and against fungal strains. Interestingly, PDInhibitor affected several human cancer cell lines, namely HCT-116, MDA-MB-231, and Lovo. Thus, it can be considered a potentially powerful therapeutic agent.


Assuntos
Anti-Infecciosos/química , Anti-Infecciosos/isolamento & purificação , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Conyza/química , Inibidores de Proteases/química , Inibidores de Proteases/isolamento & purificação , Anti-Infecciosos/farmacologia , Antineoplásicos/farmacologia , Cromatografia em Gel , Estabilidade de Medicamentos , Eletroforese em Gel de Poliacrilamida , Humanos , Concentração de Íons de Hidrogênio , Testes de Sensibilidade Microbiana , Oxidantes/química , Oxidantes/farmacologia , Oxirredução/efeitos dos fármacos , Inibidores de Proteases/farmacologia , Solventes/química , Temperatura
20.
Case Rep Oncol ; 13(3): 1325-1329, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33250749

RESUMO

Selective immunoglobulin A (IgA) deficiency is one of many congenital immunodeficiencies. It is associated with several medical condition. It has been shown to be associated with some types of malignancies, some autoimmune disorders, and even with some infections. Here we report a young male with selective IgA deficiency who also tested positive for Helicobacter pylori and strongyloidiasis at the time when he was diagnosed with stomach adenocarcinoma. The presence of IgA deficiency with multiple etiological possibilities such as infections and cancer makes this case unusual.

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