RESUMEN
Background: Zinc (Zn), an essential micronutrient, regulates and maintains neurological functions. However, both Zn deficiency and excess can cause oxidative stress and neurodegenerative diseases. As previously reported, immunoglobulin G (IgG) can modulate oxidative stress in various disorders. Aims: This study aimed to investigate whether IgG treatment can alleviate oxidative stress caused by Zn0 on microglia in vitro. Study Design: In vitro study. Methods: The feasibility of Zn0 treatment was evaluated using the MTS assay. Oxidative stress following treatment with Zn0, either alone or with IgG supplementation, was determined with dihydrorhodamine 123 staining. Flow cytometry was employed to ascertain the intracellular protein levels of TRIM21, PINK, PARKIN, MFN2, Beclin-1, and active LC3B. Results: In silico screening confirmed the association between Zn0 cytotoxicity and apoptosis. Furthermore, oxidative stress was identified as a critical mechanism that underlies Zn0 neurotoxicity. The in silico analysis revealed that Zn can interact with the constant region of the Ig heavy chain, suggesting a potential role for IgG in alleviating Zn0-induced cytotoxicity. Experimental findings supported this hypothesis, as IgG administration significantly reduced Zn0-induced mitochondrial stress in a dose-dependent manner. The upregulation of PINK1 levels by Zn0 exposure suggests that mitochondrial injury promotes mitophagy. Interestingly, Zn0 decreased TRIM21 levels, which is reversed by IgG administration. Conclusion: These findings elucidate the cellular responses to Zn0 and highlight the potential use of intravenous immunoglobulin in mitigating the adverse effects of acute Zn0 exposure.
RESUMEN
BACKGROUND: Peripheral blood-derived hematopoietic stem cells (HSCs) are widely used for various adult stem cell transplants. To obtain sufficient HSCs from healthy volunteer donors during the apheresis process and ensure that the donors are exposed to fewer apheresis-related side effects, calculation methods have been developed for the prediction of processed blood volume or CD34+ count. However, there is no consensus on a formula to predict the volume of blood to be processed or the number of stem cells to be obtained. OBJECTIVE: This study aimed to estimate the predicted blood volume and CD34+ cell counts using collection efficiency (CE)-based formulas and evaluate their accuracy compared to the actual CD34+ cell counts. It also seeks to identify the factors that affect CE. METHODS: Data from 397 healthy, unrelated stem cell donors were retrospectively analyzed. An algorithm using four different CE2 metrics (1st quartile, mean, 3rd quartile, and median) was developed to predict the volume of blood to be processed using the Spectra Optia continuous mononuclear cell collection procedure. RESULTS: When employing the mean CE2 algorithm, the results revealed a strong correlation (r = .894, p < .001) between predicted and actual CD34+ values. The study also identified strong associations between pre-apheresis CD34+, pre-apheresis leukocyte count, the use of two doses of G-CSF, and low CE2. CONCLUSION: These findings suggest that the mean CE2 algorithm could be a potent, straightforward, and accurate tool for predicting CD34+ stem cell counts in healthy allogeneic stem cell donors and potentially optimizing stem cell collection procedures.
RESUMEN
Despite advances in cancer treatment, hepatocellular carcinoma (HCC), the most common form of liver cancer, remains a major public health problem worldwide. The immune microenvironment plays a critical role in regulating tumor progression and resistance to therapy, and in HCC, the tumor microenvironment (TME) is characterized by an abundance of immunosuppressive cells and signals that facilitate immune evasion and metastasis. Recently, anti-cancer immunotherapies, therapeutic interventions designed to modulate the immune system to recognize and eliminate cancer, have become an important cornerstone of cancer therapy. Immunotherapy has demonstrated the ability to improve survival and provide durable cancer control in certain groups of HCC patients, while reducing adverse side effects. These findings represent a significant step toward improving cancer treatment outcomes. As demonstrated in clinical trials, the administration of immune checkpoint inhibitors (ICIs), particularly in combination with anti-angiogenic agents and tyrosine kinase inhibitors, has prolonged survival in a subset of patients with HCC, providing an alternative for patients who progress on first-line therapy. In this review, we aimed to provide an overview of HCC and the role of the immune system in its development, and to summarize the findings of clinical trials involving ICIs, either as monotherapies or in combination with other agents in the treatment of the disease. Challenges and considerations regarding the administration of ICIs in the treatment of HCC are also outlined.
Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamiento farmacológico , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Neoplasias Hepáticas/tratamiento farmacológico , Inmunoterapia , Inhibidores de la Angiogénesis , Microambiente TumoralRESUMEN
INTRODUCTION: Following major developments in cancer immunotherapy, treatments targeting immune checkpoint proteins (ICP) gained interest in breast cancer, though studies mostly focus on patients with metastatic disease as well as patients nonresponsive to the conventional treatments. Herein, we aimed to investigate the levels of ICP in tumor stroma and tumor infiltrating lymphocytes, and tumor tissue prior to neoadjuvant chemotherapy administration to evaluate the relationship between ICP levels, clinicopathological parameters, and NAC response. MATERIALS AND METHODS: This study was conducted with 51 patients where PD-1, PD-L1, CTLA-4, TIM-3, CD24 and CD44 levels were investigated in CD45+ cells while CD326, CD24, CD44 and PD-L1 protein expression levels were investigated in CD45- population. In addition, CD44 and CD24 levels were evaluated in the tumor stroma. TIL levels were investigated according to the TILS Working Group. Treatment responses after NAC were evaluated according to the MD Anderson RCB score. RESULTS: Our results revealed positive correlation between CTLA-4 and CD44 expression in cases with high TIL levels as well as TIL levels and CTLA-4 expression in cases with partial response. Similarly, positive correlation was detected between TIM3 and PD-L1 levels in cases with good response. In addition, a negative correlation between TILs after NAC and PD-1/PD-L1 expression in lymphocytes in cases with partial complete response. CONCLUSIONS: Our study provides preliminary data about the correlation between ICP and clinicopathological status and NAC response in breast cancer, in addition to underlining the requirement for further research to determine their potential as therapeutic targets.
Asunto(s)
Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/patología , Proteínas de Punto de Control Inmunitario/uso terapéutico , Antígeno B7-H1/metabolismo , Antígeno CTLA-4/uso terapéutico , Terapia Neoadyuvante , Receptor de Muerte Celular Programada 1/uso terapéutico , PronósticoRESUMEN
PURPOSE: This study aimed to assess the significance of immunophenotyping and serum cytokines in predicting the clinical progression of acute biliary pancreatitis (ABP). MATERIALS AND METHODS: Cytokine levels, T-helper, cytotoxic T, natural killer (NK) cells, monocytes, HLA-DR, and PD-1, as well as PDL-1 immune checkpoints, were measured in ABP patients at the time of diagnosis and compared with results from healthy volunteers. The study also compared leukocyte counts, hematocrit, immunophenotyping results, cytokine statuses, and PD-1, PDL-1 expression between healthy volunteers and ABP subgroups categorized by pancreatitis severity. RESULTS: The study included 65 ABP patients and 20 healthy volunteers. Significant differences were observed between groups in hematocrit, leukocyte counts, total monocytes, lymphocytes, CD3+ total T cells, CD4+ Th cells, PD-1 expression on CD4+ and CD8+T lymphocytes, HLA-DR expression on CD14+ monocytes, NK cells, PD-L1 expression on CD14+ monocytes, classical and intermediate monocytes, as well as levels of IL-6, IL-8, IL-10, IL-18, and IL-33 cytokines. Moderate correlations were found with lymphocyte counts, PD-1+CD4+ cells, PD-L1+CD14+ cells, and strong correlations with HLA-DR+CD14+ cells. Hematocrit, CD3+ total T cells, NK cells, CD4+PD-1 + T cells, and CD8+PD-1 + T cells showed independent associations with the severity of ABP. Lymphocyte counts, CD14+HLA-DR+ cells, CD14+PD-L1+ cells, CD4+PD-1 + T cells, classical, and intermediate monocytes exhibited the highest Area Under the Curve rates in determining organ failure. CONCLUSIONS: Hematocrit, lymphocyte counts, CD14+HLA-DR+ cells, CD14+PD-L1+ cells, and intermediate monocytes emerged as parameters most closely associated with the severity and these parameters could be useful in predicting the severity of ABP.
Asunto(s)
Monocitos , Pancreatitis , Humanos , Receptor de Muerte Celular Programada 1/metabolismo , Antígeno B7-H1/metabolismo , Antígenos HLA-DR/metabolismo , Linfocitos T CD4-Positivos , Citocinas/metabolismo , PronósticoRESUMEN
BACKGROUND: T cell immunoglobulin and mucin-domain containing-3 (TIM-3) is a cell surface molecule that was first discovered on T cells. However, recent studies revealed that it is also highly expressed in acute myeloid leukemia (AML) cells and it is related to AML progression. As, Glutamine appears to play a prominent role in malignant tumor progression, especially in their myeloid group, therefore, in this study we aimed to evaluate the relation between TIM-3/Galectin-9 axis and glutamine metabolism in two types of AML cell lines, HL-60 and THP-1. METHODS: Cell lines were cultured in RPMI 1640 which supplemented with 10% FBS and 1% antibiotics. 24, 48, and 72 h after addition of recombinant Galectin-9 (Gal-9), RT-qPCR analysis, RP-HPLC and gas chromatography techniques were performed to evaluate the expression of glutaminase (GLS), glutamate dehydrogenase (GDH) enzymes, concentration of metabolites; Glutamate (Glu) and alpha-ketoglutarate (α-KG) in glutaminolysis pathway, respectively. Western blotting and MTT assay were used to detect expression of mammalian target of rapamycin complex (mTORC) as signaling factor, GLS protein and cell proliferation rate, respectively. RESULTS: The most mRNA expression of GLS and GDH in HL-60 cells was seen at 72 h after Gal-9 treatment (p = 0.001, p = 0.0001) and in THP-1 cell line was observed at 24 h after Gal-9 addition (p = 0.001, p = 0.0001). The most mTORC and GLS protein expression in HL-60 and THP-1 cells was observed at 72 and 24 h after Gal-9 treatment (p = 0.0001), respectively. MTT assay revealed that Gal-9 could promote cell proliferation rate in both cell lines (p = 0.001). Glu concentration in HL-60 and α-KG concentration in both HL-60 (p = 0.03) and THP-1 (p = 0.0001) cell lines had a decreasing trend. But, Glu concentration had an increasing trend in THP-1 cell line (p = 0.0001). CONCLUSION: Taken together, this study suggests TIM-3/Gal-9 interaction could promote glutamine metabolism in HL-60 and THP-1 cells and resulting in AML development.
Asunto(s)
Glutamina , Leucemia Mieloide Aguda , Humanos , Ácido Glutámico , Receptor 2 Celular del Virus de la Hepatitis A , Células HL-60RESUMEN
This review aims to summarize the latest evidence about the role of innate and adaptive immunity in Amyotrophic Lateral Sclerosis (ALS). ALS is a devastating neurodegenerative disease affecting upper and lower motor neurons, which involves essential cells of the immune system that play a basic role in innate or adaptive immunity, that can be neurotoxic or neuroprotective for neurons. However, distinguishing between the sole neurotoxic or neuroprotective function of certain cells such as astrocytes can be challenging due to intricate nature of these cells, the complexity of the microenvironment and the contextual factors. In this review, in regard to innate immunity we focus on the involvement of monocytes/macrophages, microglia, the complement, NK cells, neutrophils, mast cells, and astrocytes, while regarding adaptive immunity, in addition to humoral immunity the most important features and roles of T and B cells are highlighted, specifically different subsets of CD4+ as well as CD8+ T cells. The role of autoantibodies and cytokines is also discussed in distinct sections of this review.
RESUMEN
Acute myeloid leukemia (AML) arises from the cells of myeloid lineage and is the most frequent leukemia type in adulthood accounting for about 80% of all cases. The most common treatment strategy for the treatment of AML includes chemotherapy, in rare cases radiotherapy and stem cell and bone marrow transplantation are considered. Immune checkpoint proteins involve in the negative regulation of immune cells, leading to an escape from immune surveillance, in turn, causing failure of tumor cell elimination. Immune checkpoint inhibitors (ICIs) target the negative regulation of the immune cells and support the immune system in terms of anti-tumor immunity. Bone marrow microenvironment (BMM) bears various blood cell lineages and the interactions between these lineages and the noncellular components of BMM are considered important for AML development and progression. Administration of ICIs for the AML treatment may be a promising option by regulating BMM. In this review, we summarize the current treatment options in AML treatment and discuss the possible application of ICIs in AML treatment from the perspective of the regulation of BMM.
Asunto(s)
Médula Ósea , Leucemia Mieloide Aguda , Humanos , Médula Ósea/metabolismo , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/metabolismo , Leucemia Mieloide Aguda/terapia , Trasplante de Médula Ósea , Células Madre Neoplásicas , Microambiente TumoralRESUMEN
Background: Various studies have reported the effects of testosterone on different cell types, yet bone marrow-derived mesenchymal stem cells' cellular responses to testosterone remain unknown. Aims: To investigate the effects of testosterone propionate, an oil-soluble short-acting form of testosterone, on human bone marrow-derived mesenchymal stem cells' proliferation and viability after 24 hours of incubation. We also investigated the impact of testosterone propionate on bone marrow-derived mesenchymal stem cell's polarization and cytotoxicity on K562 leukemia cell line. Study Design: In vitro study. Methods: We expanded commercially available bone marrow derived mesenchymal stem cells in vitro and treated them with testosterone propionate at concentrations ranging from 10-6-10-10 M for 24 hours. Ideal concentration was determined by evaluating cellular viability and proliferation with Annexin V/Propidium Iodide assay and carboxyfluorescein succinimidyl ester staining. The characteristic features of bone marrow-derived mesenchymal stem cells were evaluated by immunophenotyping and investigating their differentiation capacities. Bone marrow-derived mesenchymal stem cells' cytotoxic properties upon testosterone propionate treatment were determined by co-culturing the cells with K562 cells and with confocal imaging investigating polarization. Results: Testosterone propionate promoted proliferation and maintained the viability of bone marrow-derived mesenchymal stem at 10-8 M concentration. Further evaluations were conducted with the determined dose. The results showed that, apart from promoting mesenchymal stem cells' polarization and increasing their cytotoxicity on K562 cells, testosterone propionate did not alter differentiation capacities of bone marrow-derived mesenchymal stem cells and certain cell surface markers, but led to a significant increase in HLA-DR expression. Conclusion: The findings reveal that testosterone propionate promotes the proliferation and survival of bone marrow-derived mesenchymal stem cells in a dose-dependent manner without hampering their differentiation capacities, induces their polarization to the pro-inflammatory phenotype, and increases their cytotoxicity on the K562 cell line.
Asunto(s)
Células Madre Mesenquimatosas , Neoplasias , Propionato de Testosterona , Humanos , Propionato de Testosterona/metabolismo , Propionato de Testosterona/farmacología , Células Madre Mesenquimatosas/metabolismo , Diferenciación Celular/fisiología , Neoplasias/metabolismo , Proliferación CelularRESUMEN
Mammalian target of rapamycin (mTOR) is an important serine/threonine kinase that plays a critical role in several processes including cell cycle, protein synthesis, and energy metabolism. Due to its multiple roles and general dysregulation in cancer, the mTOR pathway is an important target in cancer therapy. However, studies on mTOR activity in seminoma are limited. Therefore, our aim was to investigate the expression of mTOR signaling pathway proteins in the TCam-2 cell line after rapamycin treatment. TCam-2 cells were treated with different concentrations of rapamycin (control (no rapamycin treatment), 4 nM, 20 nM, 100 nM, 500 nM, and 1000 nM rapamycin) for 48 h and 72 h. mTOR, p-mTOR, P70S6K, p-P70S6K, proliferating cell nuclear antigen (PCNA), and caspase-3 expression levels were analyzed by western blot. Apotosis and cell cycle were analyzed by flow cytometry. After 48 h of rapamycin administration, mTOR activity was significantly decreased at 1000 nM (p < 0.05). In addition, P70S6K acitivity significantly decreased in groups at all rapamycin concentrations (***p < 0.001, ****p < 0.0001). After 72 h of rapamycin administration, mTOR pathway activity were significantly decreased at 100, 500, and 1000 nM rapamycin-treated groups (p < 0.05). Moreover, P70S6K expression decreased in all treatment groups (****p < 0.0001). Caspase-3 expression were similar in all groups. While PCNA expression tended to decrease at 48 h in a dose-dependent manner, this decrease was not significant. We detected decreased PCNA expression at 1000 nM rapamycin at 72 h (p < 0.05). The rate of apoptosis increased especially at 1000 nM rapamycin at 72 h (***p < 0.001). On the other hand, according to the results of the cell cycle experiment, G1 phase arrest was detected at all rapamycin doses at 48 and 72 h (***p < 0.001). Our study indicated that 1000 nM rapamycin may inhibit TCam-2 seminoma cells growth by halting cell proliferation through inhibition of G1-S transition. Therefore, we believe that the findings obtained will contribute to the development of new treatment approaches for seminoma patients in the future and in the process of restoring testicular functions and preserving fertility.
Asunto(s)
Seminoma , Neoplasias Testiculares , Masculino , Humanos , Sirolimus/farmacología , Proteínas Quinasas S6 Ribosómicas 70-kDa/metabolismo , Proteínas Quinasas S6 Ribosómicas 70-kDa/farmacología , Antígeno Nuclear de Célula en Proliferación/metabolismo , Caspasa 3/metabolismo , Transducción de Señal , Seminoma/tratamiento farmacológico , Serina-Treonina Quinasas TOR/metabolismo , Proliferación Celular , Neoplasias Testiculares/tratamiento farmacológico , Apoptosis , Línea Celular TumoralRESUMEN
BACKGROUND/AIM: Lung transplantation is a life-saving procedure for patients with end-stage lung diseases. T-Cell receptor excision circle (TREC) is circular DNA produced during T-cell receptor gene rearrangement in the thymus and indicates naive T-cell migration from the thymus. Therefore, its levels represent thymic T-cell output. Post-transplant lymphocyte kinetics correlate with graft tolerance. The aim of this study was to investigate T-lymphocyte kinetics in the early recovery period after lung transplantation. For this purpose, copy numbers of TREC were determined in patients with a lung transplant. In addition, TREC copy numbers were evaluated according to age, diagnosis and the forced expiratory volume in 1 second (FEV1) of lung transplant patients. MATERIALS AND METHODS: Peripheral blood samples were taken from patients aged 23 to 59 years who underwent lung transplantation at the Thoracic Surgery Clinic, Kartal-Kosuyolu High Specialization Educational and Research Hospital. This study included peripheral blood samples from 11 lung transplant patients (comprising four with chronic obstructive pulmonary disease, three with idiopathic pulmonary fibrosis, one with cystic fibrosis, one with silicosis and two with bronchiectasis; three females in total). Samples were taken at three different timepoints: Before transplant, and 24 hours and 7 days post transplant. TREC copy numbers were analyzed with real time reverse transcriptase-polymerase chain reaction. RESULTS: Post-transplant TREC numbers and density values were higher compared to pre-transplant values, although these differences were statistically insignificant. TREC copy numbers were found to be significantly higher in patients younger than 45 years compared to patients older than 45 years. At 24 hours after the transplant, the average TREC copy number/peripheral blood mononuclear cells of the cases with an FEV1 value of or below 50% was found to be statistically significantly higher than that of cases with an FEV1 value above 50% (p=0.046). There was no statistically significant difference in TREC copy numbers between male and female patients or by diagnostic group. CONCLUSION: TREC copy numbers can be evaluated as a prognostic marker for lung transplantation. There is a need for multicenter studies with more patients.
Asunto(s)
Trasplante de Pulmón , Linfocitos T , Humanos , Masculino , Femenino , Reordenamiento Génico de Linfocito T , Leucocitos Mononucleares , Variaciones en el Número de Copia de ADN , Timo , Receptores de Antígenos de Linfocitos TRESUMEN
Cytotoxic activity-guided isolation studies on the underground parts of Valeriana sisymbriifolia Vahl. led to the isolation of 12 secondary metabolites including two undescribed iridoids, sisymbriifolivaltrate and sisymbriifolioside, and two unreported sesquiterpene lactones, sisymbriifolins A and B. Chemical structures of the isolates were established by extensive 1D and 2D NMR analyses as well as HR-ESI-MS. The in vitro cytotoxic activities of the extract, sub-fractions and isolates on lung (A549), breast (MCF7), gastric (HGC27) and prostate (PC3) cancer cell lines were evaluated by MTS assay. Sisymbriifolivaltrate, didrovaltrate, valtrate, 7-homovaltrate and 1-α-acevaltrate exhibited promising cytotoxic activity on MCF7 cell line with IC50 values ranging from 2.5 to 12.3 µM, while valtrate demonstrated the best cytotoxicity against A549 cells with the IC50 value of 7.5 µM. Valtrate and 7-homovaltrate were found to exert noteworthy cytotoxicity towards HGC27 cell line (IC50 values: 2.3 and 3.7 µM, respectively), whereas valtrate, 7-homovaltrate and 1-α-acevaltrate (IC50 values: 2.3-9.7 µM) were found to be potent cytotoxic against PC3 cells. Among the tested compounds, particularly valepotriate-type iridoids were found to be the main cytotoxic principles of V. sisymbriifolia.
Asunto(s)
Antineoplásicos , Valeriana , Animales , Valeriana/química , Iridoides/químicaRESUMEN
The aim of this study was to isolate the cytotoxic compounds from V.â alliariifolia via activity-guided isolation and to determine the mechanism of actions of the most potent ones. The crude EtOH extract as well as CHCl3 and AcOEt subextracts demonstrated remarkable cytotoxic activities against A549, MCF7, HGC27 and PC3 cancer cells. Sequential chromatographic separations on active subextracts yielded 14 secondary metabolites, including 11 iridoids (1-11) most of which belong to non-glycosidic ester iridoids, two phenylpropanoids (12 and 13) and one lignan (14). The chemical structures of purified compounds were elucidated by NMR and MS analysis. Among the isolates, 7-deisovaleroylvaltrate (3) was isolated for the first time as a natural product. According to the cytotoxic assay compounds, 2, 4-6 and 8 were found to be the potent cytotoxic compounds (IC50 <10â µM) against at least one of the tested cancer cell lines. Thus, 2, 4-6 and 8 were investigated for their effects on apoptotic, necrotic and autophagic pathways as well as cell cycle progression. They exerted anticancer activities by inducing different cell death mechanisms depending on the cancer cells. The results demonstrated that 2, 4-6 and 8 could be potential anticancer drug leads that deserve further inâ vivo and clinical studies on the way to discover novel natural compounds with anticancer properties.
Asunto(s)
Antineoplásicos , Lignanos , Valeriana , Valeriana/química , Iridoides/farmacología , Iridoides/química , Ésteres , Antineoplásicos/farmacología , Antineoplásicos/química , Muerte Celular , Extractos Vegetales/farmacología , Extractos Vegetales/químicaRESUMEN
Colorectal cancer ranks as the third most lethal cancer worldwide, resulting in over 1 million cases and 900â¯000 deaths per year. According to population-based studies, administration of long-term non-steroidal anti-inflammatory drugs (NSAIDs) was proven to reduce the risk of a subject developing colorectal cancer. In the present study, the anti-cancer activity of two different NSAIDs, sulindac- (Pc-1) or diclofenac-substituted (Pc-2) asymmetric silicon phthalocyanine derivatives, was evaluated in four different colorectal cancer cell lines bearing various carcinogenic mutations. In this context, the IC50 values of each compound after 24 and 48 h were determined on HCT116, SW480, LoVo, and HT29 cell lines, and the effects of the compounds on programmed cell death pathways apoptosis and autophagy, their impact on cell cycle progression, and the effect of NSAID moieties they bear on COX-1 and COX-2 proteins were analyzed. In addition, the photophysical and photochemical properties of a synthesized Pc derivative bearing axial diclofenac and triethylene glycol groups (Pc-2) have been investigated, and the compound has been characterized by using different analytical techniques. Our results indicated that both compounds inhibit COX protein expression levels, activate apoptosis in all cell lines, and lead to cell cycle arrest in the G2/M phase, depending on the COX expression profiles of the cell lines, indicating that NSAIDs can be coupled with Pc's to achieve increased anti-cancer activity, especially on cancer cells known to have high COX activity.
Asunto(s)
Neoplasias Colorrectales , Inhibidores de la Ciclooxigenasa , Antiinflamatorios no Esteroideos/farmacología , Neoplasias Colorrectales/tratamiento farmacológico , Inhibidores de la Ciclooxigenasa/farmacología , Diclofenaco/farmacología , Células HT29 , Humanos , Indoles , Compuestos de Organosilicio , Silicio/uso terapéuticoRESUMEN
The development of immune checkpoint inhibitors, the monoclonal antibodies that modulate the interaction between immune checkpoint molecules or their ligands on the immune cells or tumor tissue has revolutionized cancer treatment. While there are various studies proving their efficacy in hematological malignancies, there is also a body of accumulating evidence indicating that immune checkpoint inhibitors' clinical benefits are limited in such diseases. In addition, due to their regulatory nature that balances the immune responses, blockade of immune checkpoints may lead to toxic side effects and autoimmune responses, and even primary or acquired resistance mechanisms may restrict their success. Thus, the need for laboratory biomarkers to identify and monitor patient populations who are more likely respond to this type of therapy and the management of side effects seem critical. However, guidelines regarding the use of immune checkpoint inhibitors in hematological cancers and during follow-up are limited while there is no consensus on the laboratory parameters to be investigated for safety and efficacy of the treatment. This review aims to provide an insight into recent information on predictive and prognostic value of biomarkers and laboratory tests for the clinical follow up of hematological malignancies, with an emphasis on leukemia.
RESUMEN
Background: This study aims to evaluate humoral immune system response by measuring copy numbers of kappa-deleting recombination excision circles (KREC) gene segment from B lymphocytes in patients with lung transplantation. Methods: Between September 2015 and November 2016, a total of 11 patients (8 males, 3 females; mean age: 45.4±12.0 years; range, 23 to 59 years) who underwent lung transplantation with different primary indications were included. The copy numbers of KREC gene segment were quantified using real-time polymerase chain reaction method in peripheral blood samples collected pre- and post-transplantation. The samples of the patients were compared with the KREC l evels i n deoxyribonucleic acid extracted from blood samples of healthy children. Results: There was no significant change in KREC levels between pre- and post-operation (p=0.594 and p=0.657), although the median values indicated that the highest increase in the KREC levels (7x105- 12x105; 85-170) was on Day 7 of transplantation. There was a positive correlation between the KREC levels (mL in blood) and lymphocytes at 24 h after transplantation (p=0.043) and between KREC copies per 106 of blood and age on Day 7. Conclusion: Our preliminary results suggest that KREC l evels a s an indicator of B lymphocyte production are elevated after lung transplantation. A prognostic algorithm by tracking B cell kinetics after post-transplantation for long-term follow-up can be developed following the confirmation of these preliminary results with more patient samples.
RESUMEN
The aim was to compare granulosa cell's (GCs) apoptosis rate with (group A) or without (group B) luteinising hormone (LH) supplementation in poor ovarian responders (PORs) during controlled ovarian stimulation (COS). After oocyte retrieval, the follicular fluid was analysed by cytoflowmetry. Primary outcomes were GCs apoptosis rate in terms of viability, early apoptosis, late apoptosis and necrosis. Secondary outcome was clinical pregnancy rate. The viability was 96.7{IQR: 8} and 83.5{IQR: 20} for groups A and B, respectively (p < .001). Late apoptosis rates were significantly lower in group A (median 1.5, {IQR: 3.1}) than group B (median 9.5, {IQR: 20.6}) (p < .001). Median early apoptosis rates were 1.4 {IQR: 2.9} and 5.2 {IQR: 6.5} for group A and B respectively (p = .04). No significant difference was observed in the clinical pregnancy rate. Although LH seems necessary in PORs to decrease late granulosa apoptosis rates, this does not improve clinical pregnancy rates.IMPACT STATEMENTWhat is already known on this subject? LH supplementation during COS has long been an issue in PORs to overcome the rFSH responsiveness due to the LH polymorphism. LH receptors have also been on GCs and their expression increases in preovulatory follicles. GCs apoptosis rates may show the oocyte quality and reproductive potential of oocyte retrieved and the requirement for LH supplementation.What do the results of this study add? The present study shows that LH supplementation during COS for PORs promotes the GC viability and reduces early/late apoptosis rates. Similarly, the number of MII oocytes was significantly higher in the LH regimen group. However, there was no significant difference in terms of clinical pregnancy rates.What are the implications of these findings for clinical practice and/or further research? The oocyte quality parameters such as higher GC viability and lower GC early/late apoptosis rates verify the LH supplementation in PORs during COS. However, the limited size of this study requires further multi-centre research in a larger cohort of patients. Results obtained with a sensitive and validated method will help clinicians to make better decisions in patient care.
Asunto(s)
Apoptosis/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Líquido Folicular/citología , Células de la Granulosa/efectos de los fármacos , Hormona Luteinizante/administración & dosificación , Adulto , Femenino , Humanos , Recuperación del Oocito/métodos , Inducción de la Ovulación/métodos , Embarazo , Índice de Embarazo , Estudios ProspectivosRESUMEN
BACKGROUND: The relationship between serum calcium (Ca) level to serum parathyroid hormone (PTH), phosphorus (P) levels and tissue properties of the parathyroid gland is unknown in primary hyperparathyroidism cases. Revealing this relationship may be useful for understanding the etiopathogenesis of primary hyperparathyroidism and determining the time of treatment. METHODS: Ninety patients (71 females, 19 males, age range; 27-73âyears, average age; 46) who underwent single gland excision with the diagnosis of primary hyperparathyroidism were studied. The patients were divided into 2 groups as serum Ca level <12 and serum Ca level ≥12. Age and sex of the patients, mean cell number of the gland, mean volume of the gland, serum levels of PTH, P, and histopathologic type of hyperplasia were evaluated. RESULTS: The mean cell number per cubic centimeter is 22.9 (10-220 range) million in all glands. Serum Ca level was <12 in 82 (91.1%) of the patients, and ≥12 in 8 (8.9%) cases. Mean cell number of the gland, mean volume of the gland, existence of cystic hyperplasia of the gland, serum levels of PTH and P were statistically significant between the 2 groups (Pâ<â.001, Pâ<â.001, Pâ<â.05, Pâ<â.001, Pâ<â.05 respectively). CONCLUSION: In primary hyperparathyroidism cases serum Ca level is not related to age and sex but directly related to proportionals to the cell number and volume of the gland and serum levels of PTH, inversely related to cystic hyperplasia and serum levels of P. Early surgical intervention should be planned since the serum Ca level will be high in large adenomas with a noncystic radiological appearance.