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1.
J Forensic Sci ; 69(1): 131-138, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37888436

RESUMO

Copy-move forgeries are a conceptual sort of image retouching that involves duplicating a portion of an image and moving it to a different position within the original image, whether by modifying the duplicated part or just moving it altogether. To identify cloned portions that have been reproduced into the same digitized image, the suggested hybrid features in this article combine using the Hessian and Raw patch features on gray-level images. Using a suggested model that combines patch features built on key points detected by the Hessian detector on gray-level image, localization of duplicated and pasted portions of the manipulated image were found. After using the combined features in the matching step, the parallelism condition was applied together with the random sample consensus method to eliminate mismatches. Two databases, GRIP and the image manipulation dataset (IMD), were used for the detection and characterization, and the empirical findings show that the approach was successful in achieving an F1 score 100% for the GRIP database. Additionally, with the IMD database, it produced a 92.13% F1 score. The proposed method was also shown to be effective by obtaining high F1 scores in images where noise, JPEG compression, and scaling attacks were applied to make forgery detection difficult.

2.
Br J Haematol ; 204(3): 931-938, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38115798

RESUMO

Multiple myeloma (MM) is a haematological malignancy primarily affecting the elderly, with a striking male predilection and ethnic disparities in incidence. Familial predisposition to MM has long been recognized, but the genetic underpinnings remain elusive. This study aimed to investigate germline variants in Turkish families with recurrent MM cases. A total of 37 MM-affected families, comprising 77 individuals, were included. Targeted next-generation sequencing analysis yielded no previously reported rare variants. Whole exome sequencing analysis in 11 families identified rare disease-causing variants in various genes, some previously linked to familial MM and others not previously associated. Notably, genes involved in ubiquitination, V(D)J recombination and the PI3K/AKT/mTOR pathway were among those identified. Furthermore, a specific variant in BNIP1 (rs28199) was found in 13 patients across nine families, indicating its potential significance in MM pathogenesis. While this study sheds light on genetic variations in familial MM in Turkey, its limitations include sample size and the absence of in vivo investigations. In conclusion, familial MM likely involves a polygenic inheritance pattern with rare, disease-causing variants in various genes, emphasizing the need for international collaborative efforts to unravel the intricate genetic basis of MM and develop targeted therapies.


Assuntos
Gamopatia Monoclonal de Significância Indeterminada , Mieloma Múltiplo , Humanos , Masculino , Idoso , Gamopatia Monoclonal de Significância Indeterminada/patologia , Mieloma Múltiplo/patologia , Fosfatidilinositol 3-Quinases/genética , Turquia , Recidiva Local de Neoplasia , Células Germinativas/patologia , Predisposição Genética para Doença
3.
Diagnostics (Basel) ; 13(19)2023 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-37835884

RESUMO

Among the most serious types of cancer is skin cancer. Despite the risk of death, when caught early, the rate of survival is greater than 95%. This inspires researchers to explore methods that allow for the early detection of skin cancer that could save millions of lives. The ability to detect the early signs of skin cancer has become more urgent in light of the rising number of illnesses, the high death rate, and costly healthcare treatments. Given the gravity of these issues, experts have created a number of existing approaches for detecting skin cancer. Identifying skin cancer and whether it is benign or malignant involves detecting features of the lesions such as size, form, symmetry, color, etc. The aim of this study is to determine the most successful skin cancer detection methods by comparing the outcomes and effectiveness of the various applications that categorize benign and malignant forms of skin cancer. Descriptors such as the Local Binary Pattern (LBP), the Local Directional Number Pattern (LDN), the Pyramid of Histogram of Oriented Gradients (PHOG), the Local Directional Pattern (LDiP), and Monogenic Binary Coding (MBC) are used to extract the necessary features. Support vector machines (SVM) and XGBoost are used in the classification process. In addition, this study uses colored histogram-based features to classify the various characteristics obtained from the color images. In the experimental results, the applications implemented with the proposed color histogram-based features were observed to be more successful. Under the proposed method (the colored LDN feature obtained using the YCbCr color space with the XGBoost classifier), a 90% accuracy rate was achieved on Dataset 1, which was obtained from the Kaggle website. For the HAM10000 data set, an accuracy rate of 96.50% was achieved under a similar proposed method (the colored MBC feature obtained using the HSV color space with the XGBoost classifier).

4.
Mol Biol Rep ; 49(6): 5473-5482, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35235154

RESUMO

BACKGROUND: Pistacia is a genus of dioecious plant species whose trees can take 4-5 years to reach the economically valuable fruit-bearing stage. The fruits have great importance as raw material in the food, healthcare, and baking industries. For that reason, the identification of individual plants in the early juvenile period for the pollination and positioning of trees is crucial for growers. The objective of this study is to develop markers for each Pistacia species that can help in screening the sex of plant seedlings before they reach the reproductive stage, without waiting for morphological characteristics to appear. METHODS AND RESULTS: Within this context, by using the power of the kompetitive allele-specific PCR (KASP) assay technology as a marker screening system, we successfully discriminated seven out of eight Pistacia species: P. atlantica, P. integerrima, P. khinjuk, P. mutica, P. terebinthus, P. vera, and P. lentiscus. We used a high-throughput DNA sequence read archive (SRA) to assemble a reference genome that was employed in our studies as a de novo bioinformatics method. Four genomic regions from SRA and three single-nucleotide polymorphism (SNP) positions from Kafkas et al. BMC Genomics 16:98, 2015) were selected and sequenced with collected plant material from predominantly the Antepfistigi Research Institute Collection Garden, and eight species were aligned intraspecifically for SNP mining. In total, 12 SNP markers were converted to KASP markers, and 5 of them (SNP-PIS-133396, SNP-PIS-167992, P-ATL-91951-565, P-INT-91951-256, P-KHI-91951-115) showed clear allelic discrimination between male and female plants. SNP-PIS-167992 and P-ATL-91951-565 were identified as the best marker assays because they showed allelic frequency differences for all individuals and for both homozygous and heterozygous characters. These markers could be the most comprehensive ones for the whole genus because they showed discriminative power for several species. CONCLUSIONS: This study is the first one to use the KASP assay for sex discrimination in Pistacia species, and it can be regarded as a precursor study for sex discrimination by KASP for plants in general.


Assuntos
Pistacia , Alelos , Sequenciamento de Nucleotídeos em Larga Escala , Pistacia/genética , Reação em Cadeia da Polimerase/métodos , Polimorfismo de Nucleotídeo Único/genética
5.
Afr Health Sci ; 22(3): 183-191, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36910358

RESUMO

Background: Cytogenetic findings are important prognostic factors in acute myeloid leukemia. Large systematic data about chromosomal characteristics of Turkish AML patients have not been reported to date. Objectives: The karyotypic profiles of 157 adult AML patients were evaluated retrospectively and compared with other reports from different populations. Methods: Cytogenetics analyses were performed on bone marrow samples using G-banding. Patients were categorized according to their cytogenetic results into four groups with the addition of a normal karyotyped group to the favorable, intermediate and adverse groups of European Leukemia Network. Results: Cytogenetic analyses were carried out successfully in 138 patients (88%). Abnormal karyotypes were found in 79 (57.2%) patients of which 13 (9.4%) were in favorable, 37 (26.8%) in intermediate and 29 (21%) in adverse groups. t(8;21) (5%) was the most common favorable abnormality while monosomal karyotypes (15.9%) in adverse group. Conclusion: This single center study is the most comprehensive study about the cytogenetic profile of acute myeloid leukemia in Turkey with comparison of other population-based studies. While there were similarities and differences with different publications, our results did not show a marked tendency to the findings of any specific geographic region.


Assuntos
Leucemia Mieloide Aguda , Humanos , Adulto , Estudos Retrospectivos , Turquia , Cariotipagem , Análise Citogenética , Prognóstico , Aberrações Cromossômicas
6.
Clin Lymphoma Myeloma Leuk ; 21(8): 549-557, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34052176

RESUMO

BACKGROUND: In the era of tyrosine kinase inhibitors (TKIs), chronic myeloid leukemia (CML) patients generally live close to a normal lifespan, and the number of elderly patients with CML with comorbidities is increasing. PATIENTS AND METHODS: We retrospectively compared the efficacy and safety of frontline imatinib between elderly patients (≥60 years old) and younger patients (<60 years old) with CML. RESULTS: The study included 33 elderly and 125 younger patients. Elderly patients had significantly higher Charlson comorbidity index (CCI) scores. Efficacy and toxicity were comparable among the older patients with CCI scores of 0 and ≥1. There were significantly more hematologic adverse events (AEs) in elderly patients (P = .005). Although not significant, nonhematologic AEs were also more common in older cases (P = .056). Elderly patients had significantly higher rates of imatinib dose reduction (P < .001). Cumulative response rates were similar in both groups. Event-free survival was comparable, and overall survival (OS)-when non-CML-related deaths were censored-was also similar. In the multivariate analysis, age at diagnosis and CCI were associated with OS, and patients ≥ 60 years of age had a 5.998-times higher risk of death compared with the patients < 60 years of age (P = .011). Similarly, patients with CCI scores ≥ 2 had a 3.758-times higher risk of death compared with patients with a CCI score of 0 (P = .033). CONCLUSIONS: Upfront imatinib was generally well tolerated among elderly Turkish patients with CML with non-inferior responses and long-term outcomes when compared with younger patients. Comorbidities can be problematic in elderly patients, and today the survival of patients with CML is determined mostly by comorbidities.


Assuntos
Antineoplásicos/uso terapêutico , Mesilato de Imatinib/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Feminino , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Leucemia Mielogênica Crônica BCR-ABL Positiva/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento , Turquia/epidemiologia
7.
Turk J Med Sci ; 51(1): 348-354, 2021 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-32950049

RESUMO

Background/aim: A proliferation-inducing ligand (APRIL) has been investigated as a prognostic marker in chronic lymphocytic leukemia (CLL) patients. However, there is no cut-off level for serum APRIL (sAPRIL) levels that predict time to treatment in CLL patients. Materials and methods: Between May and December 2012, 94 consecutive CLL patients and 25 healthy controls were assessed. sAPRIL levels were measured by ELISA. Demographic data and prognostic markers were obtained from the patients' files. Treatment-naïve patients were followed up for 6.5 years for any treatment need. Results: Patients were divided into 3 groups: Treatment-naïve (n = 47), chemotherapy receiving (n = 25), and those who had received chemotherapy previously (n = 22). There was no difference in median sAPRIL levels of patients who were receiving chemotherapy at the sampling time and the healthy controls, which indicates that sAPRIL levels might be influenced by treatment. For treatment-naïve patients, the best cut-off in predicting time to treatment was found at the sAPRIL level of 2.04 ng/mL, with 78% sensitivity and 63% specificity. Time to treatment was significantly earlier in the APRIL high group (n = 27) than in the APRIL low group (n = 20) (P = 0.010, log-rank test). Conclusion: sAPRIL, a simple, promising blood test which can be measured by ELISA, will likely obtain a place in the wide range of prognostic markers in CLL. Prospective large-scale studies are required to validate and confirm the feasibility of the proposed cut-off level of 2.04 ng/mL as a predictor of time to treatment in treatment-naïve CLL patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Leucemia Linfocítica Crônica de Células B , Membro 13 da Superfamília de Ligantes de Fatores de Necrose Tumoral/sangue , Biomarcadores Tumorais/sangue , Monitoramento de Medicamentos/métodos , Feminino , Humanos , Leucemia Linfocítica Crônica de Células B/sangue , Leucemia Linfocítica Crônica de Células B/diagnóstico , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Ligantes , Masculino , Conduta do Tratamento Medicamentoso , Pessoa de Meia-Idade , Seleção de Pacientes , Valor Preditivo dos Testes , Prognóstico , Sensibilidade e Especificidade
8.
Clin Lymphoma Myeloma Leuk ; 20(8): e474-e484, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32482539

RESUMO

BACKGROUND: In countries where frontline drug approval is limited to first-generation proteasome inhibitors or immunomodulatory drugs, relapses have been both more frequent and less durable. We investigated real world data on the efficacy and safety of daratumumab monotherapy among patients with relapsed refractory multiple myeloma (RRMM) from Turkey using a prospective early access program. PATIENTS AND METHODS: A total of 42 patients with RRMM after a minimum of 3 previous lines of proteasome inhibitor/immunomodulatory drug-based treatments were included from 25 centers across Turkey. Daratumumab monotherapy was administered intravenously at a dose of 16 mg/kg weekly (cycles 1-2), on alternate weeks (cycles 3-6), and monthly thereafter. RESULTS: The median daratumumab monotherapy duration was 5.5 months (range, 0.2-28.7 months). The overall response rate was 45.2%, including 14 (33.3%) partial responses, 4 (9.5%) very good partial responses, and 1 (2.4%) complete response. The median duration of response was 4.9 months. The median progression-free survival (PFS) was 5.5 (95% confidence interval, 2.6-8.4 months) with 12- and 18-month PFS rates of 35.7% and 31.0%, respectively. The median overall survival was not reached; the 12- and 18-month overall survival rates were 64.3% and 59.5%, respectively. The depth of response had a significant effect on PFS (log-rank test, P = .026). Overall, of the 76 adverse events reported, 33 (43.4%) were grade ≥ 3; only 4 (9.52%) were grade 3 infusion-related reactions. No infusion-related reactions or adverse events led to treatment discontinuation. CONCLUSION: The present findings from our daratumumab early access program have confirmed the efficacy and safety profile of daratumumab monotherapy in heavily pretreated Turkish patients with RRMM.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Idoso , Anticorpos Monoclonais/farmacologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/patologia , Turquia
9.
Plant Signal Behav ; 14(9): 1633885, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31366277

RESUMO

Sunflower is a globally important oilseed, food, and ornamental crop. This study seeks to investigate the genotoxic effects of tissue culture parameters in sunflower calli tissues belongs to two genotypes obtained via anther culture. Anthers were pretreated with cold for 24 hours at 4°C and heat for 2 days at 35°C in the dark and plated onto media supplemented with different concentrations and combinations of 6-benzylaminopurine, 2,4-dichlorophenoxyacetic acid, α-naphthalene acetic acid and indole-3-acetic acid. Obtaining calli tissues were used to detect the DNA damage levels by Comet assay, evaluating changes on superoxide dismutase and guaiacol peroxidase activities derived from in vitro culture factors. 0.5 mg/L 2,4-dichlorophenoxyacetic acid and 2 mg/L α-naphthalene acetic acid from plant growth regulators showed acute genotoxic effect while 0.5 mg/L indole-3-acetic acid and 0.5 mg/L α-naphthalene acetic acid showed no genotoxic effect. Total protein content analysis of antioxidant enzymes revealed that although superoxide dismutase activity did not increase, Guaiacol peroxidase (GPOX) activity decreased in comparison to control. The obtained results have indicated that in vitro culture factors apparently lead to genotoxicity and oxidative stress.


Assuntos
Flores/crescimento & desenvolvimento , Helianthus/crescimento & desenvolvimento , Mutagênicos/toxicidade , Técnicas de Cultura de Tecidos , Antioxidantes/metabolismo , Ensaio Cometa , Dano ao DNA , DNA de Plantas/genética , Flores/embriologia , Genótipo , Helianthus/embriologia , Helianthus/genética , Peroxidase/metabolismo , Proteínas de Plantas/metabolismo , Solubilidade , Superóxido Dismutase/metabolismo
10.
Clin Lymphoma Myeloma Leuk ; 19(7): e377-e384, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31088736

RESUMO

BACKGROUND: In the European LeukemiaNet (ELN) 2013 recommendations, chronic myeloid leukemia (CML) patients with warning response (WR) were suggested to be monitored closely continuing with the same tyrosine kinase inhibitor (TKI). Differently, the guidelines of the National Comprehensive Cancer Network considers switching to another TKI as an option. PATIENTS AND METHODS: We retrospectively evaluated 73 CML patients receiving first-line imatinib, who were followed and managed in accordance with ELN recommendations. We compared patients with molecular WR with patients with optimal response (OR) and failure regarding short- and long-term outcomes. RESULTS: The cumulative major molecular response (MMR) rates in patients with OR were significantly higher at any time point than those achieved by the WR group. Patients with WR at 3 months had significantly inferior failure-free survival (FFS) than optimal responders, but overall survival (OS) was similar. For 6 and 12 months, the WR and OR groups had similar FFS and OS. Twenty of 23 patients with WR at 12 months achieved MMR during imatinib treatment. CONCLUSION: It takes longer to get to ELN time points with imatinib than second-generation TKIs (2GTKIs). Treatment might fail in a small proportion of the patients with WR during imatinib treatment, but close and careful monitoring and timely switching to 2GTKIs might translate into favorable outcomes. Avoiding early switch to 2GTKIs would prevent patients from experiencing potential toxicities. There is still a need for prospective comparative studies (ie, continuing imatinib treatment vs. switching to 2GTKIs) in patients with WR, to justify the validity of this response category and to explore the benefit of treatment change in these patients.


Assuntos
Antineoplásicos/uso terapêutico , Mesilato de Imatinib/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/mortalidade , Inibidores de Proteínas Quinases/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Feminino , Proteínas de Fusão bcr-abl/antagonistas & inibidores , Humanos , Mesilato de Imatinib/administração & dosagem , Mesilato de Imatinib/efeitos adversos , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
11.
Balkan Med J ; 35(6): 417-421, 2018 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-29966997

RESUMO

Background: Thrombotic thrombocytopenic purpura is a potentially life-threatening condition. Although the introduction of therapeutic plasma exchange has reduced mortality rates from over 90% to 10%-20%, approximately 40% of patients relapse, and outcomes may be fatal in refractory patients. There is clearly a need for additional therapeutic approaches. Aims: To describe the outcomes of relapsed/refractory thrombotic thrombocytopenic purpura patients treated with vincristine as an adjunct to therapeutic plasma exchange. Study Design: Cross-sectional study. Methods: The medical records of all relapsed/refractory patients with thrombotic thrombocytopenic purpura treated with vincristine adjunct to therapeutic plasma exchange between October 2000 and December 2016 were retrospectively reviewed. Diagnosis of thrombotic thrombocytopenic purpura was based on clinical history, physical examination, and laboratory examinations. Patient demographics, laboratory findings, initial date and duration of therapeutic plasma exchange, dosage and time of administration of vincristine, and outcomes were recorded. Results: The study included 15 patients [median age: 37 years (range: 26-65); 7 women and 8 men] with either relapsed or refractory thrombotic thrombocytopenic purpura who were treated with vincristine as an adjunct to therapeutic plasma exchange for a total of 22 episodes. Eighty-seven percent of patients achieved remissions in 20 of 22 episodes, with a median duration of remission of 29.5 months (range: 3-105). After a median follow-up of 55 months, 11 patients were alive. Vincristine was well tolerated with no safety concerns. Conclusion: Vincristine offers a reasonable option for the treatment of patients with relapsed/refractory thrombotic thrombocytopenic purpura. Further studies evaluating vincristine in the front-line setting and in the relapsed/refractory setting are needed to validate the role of vincristine in thrombotic thrombocytopenic purpura patients.


Assuntos
Troca Plasmática/métodos , Púrpura Trombocitopênica Trombótica/tratamento farmacológico , Vincristina/farmacologia , Adulto , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Turquia , Vincristina/efeitos adversos , Vincristina/uso terapêutico
12.
Open Life Sci ; 13: 319-326, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33817099

RESUMO

The effectiveness of Pl genes is known to be resistant to downy mildew (DM) disease affected by fungus Plasmopara halstedii in sunflower. In this study phenotypic analysis was performed using inoculation tests and genotypic analysis were carried out with three DM resistance genes Plarg, Pl13 and Pl8. A total of 69 simple sequence repeat markers and 241 F2 individuals derived from a cross of RHA-419 (R) x P6LC (S), RHA-419 (R) x CL (S), RHA-419 (R) x OL (S), RHA419 (R) x 9758R (S), HA-R5 (R) x P6LC (S) and HA89 (R) x P6LC (S) parental lines were used to identify resistant hybrids in sunflower. Results of SSR analysis using markers linked with downy mildew resistance genes (Plarg, Pl8 and Pl13) and downy mildew inoculation tests were evaluated together and ORS716 (for Plarg and Pl13), HA4011 (for Pl8) markers showed positive correlation with their phenotypic results. These results suggest that these markers are associated with DM resistance and they can be used successfully in marker-assisted selection for sunflower breeding programs specific for downy mildew resistance.

13.
Hematology ; 23(4): 212-220, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-28990873

RESUMO

OBJECTIVES: Newer tyrosine kinase inhibitors (TKIs) (bosutinib, ponatinib) and allogeneic hematopoietic stem cell transplantation (allo-HSCT) can be utilized as a salvage therapy in patients with chronic myeloid leukemia (CML) who failed two lines (imatinib → nilotinib or imatinib → dasatinib) of TKI therapy. However, these TKIs are not available in many countries and not all patients can undergo allo-HSCT. METHODS: In this study, CML patients who received dasatinib or nilotinib as a third-line treatment were retrospectively evaluated. RESULTS: Out of 209 patients, third-line dasatinib/nilotinib was administered in 21. During the follow-up, 16 out of 21 patients gained and/or maintained an optimal response, and 4 patients died due to progression. Seventeen patients were alive at the time of the analysis, of which 13 were still on TKI, whereas 4 patients quit treatment. DISCUSSION: In patients failing two lines of TKI, dasatinib or nilotinib can be beneficial and safely administered as a third-line treatment especially in nations with restricted resources.


Assuntos
Dasatinibe/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Pirimidinas/uso terapêutico , Adulto , Idoso , Feminino , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
14.
Turk J Haematol ; 34(4): 291-299, 2017 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-29199176

RESUMO

OBJECTIVE: In this study, we retrospectively analyzed the clinical outcome, treatment responses, infectious complications, and survival rates of 71 hairy cell leukemia (HCL) cases. MATERIALS AND METHODS: Sixty-seven patients received a first-line treatment and 2-chlorodeoxyadenosine (cladribine-2-CdA) was administered in 31 cases, 19 patients received interferon-alpha (INF-α), splenectomy was performed in 16 cases, and rituximab was used in one. RESULTS: Although the highest overall response rate (ORR) was observed in patients receiving 2-CdA upfront, ORRs were comparable in the 2-CdA, INF-α, and splenectomy subgroups. Relapse rates were significantly lower in patients who received first-line 2-CdA. The progression-free survival (PFS) rate with 2-CdA was significantly higher than in patients with INF-α and splenectomy, but we found similar overall survival rates with all three upfront treatment modalities. Infections including tuberculosis were a major problem. CONCLUSION: Although purine analogues have improved the ORRs and PFS, there is still much progress to make with regard to overall survival and relapsed/refractory disease in patients with HCL.


Assuntos
Antineoplásicos/uso terapêutico , Cladribina/uso terapêutico , Fatores Imunológicos/uso terapêutico , Interferon-alfa/uso terapêutico , Leucemia de Células Pilosas/terapia , Esplenectomia , Adulto , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Leucemia de Células Pilosas/tratamento farmacológico , Leucemia de Células Pilosas/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Esplenectomia/métodos , Resultado do Tratamento
15.
Clin Lymphoma Myeloma Leuk ; 17(12): 804-811, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28847475

RESUMO

BACKGROUND: The molecular response at 3 months of the original imatinib (OI) in patients with chronic myeloid leukemia has prognostic significance; however, this has never been tested for generic imatinib (GI). PATIENTS AND METHODS: We evaluated the BCR-ABL1 [international reporting scale (IS)] transcript levels at 3 and 6 months to determine whether an early molecular response (EMR) had a prognostic effect on the outcome among chronic myeloid leukemia patients receiving GI. Ninety patients were divided into 2 groups, according to the imatinib they received, as OI (group A) and GI (group B). RESULTS: Two groups were equally balanced for age, gender, Sokal risk score, and optimal response. The 2 groups did not differ in achieving an EMR at 3 months, and patients with EMR at 3 months had significantly superior complete cytogenetic response and major molecular response rates compared with patients who did not achieve an EMR in both groups. The percentage of an optimal response [BCR-ABL1 (IS), < 1%] and a warning response [BCR-ABL1 (IS), 1%-10%] at 6 months was 93% and 95% for groups A and B, respectively (P = .553). Patients with an optimal response (OR) at both 3 and 6 months had significantly superior event-free survival rates compared with patients without an OR in groups A and B. CONCLUSION: The results of the present study have demonstrated most probably for the first time that an OR at 3 and 6 months in patients receiving either first-line GI and OI is clearly associated with greater response and event-free survival rates. Prospective randomized trials with larger numbers of patients and longer follow-up periods are needed to address the effect of EMR in patients receiving GI.


Assuntos
Medicamentos Genéricos/uso terapêutico , Proteínas de Fusão bcr-abl/genética , Mesilato de Imatinib/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Regulação Leucêmica da Expressão Gênica/efeitos dos fármacos , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Masculino , Pessoa de Meia-Idade , Inibidores de Proteínas Quinases/uso terapêutico , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
16.
Turk J Haematol ; 34(3): 233-238, 2017 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-28270368

RESUMO

OBJECTIVE: Multiple myeloma patients who are relapsed or refractory to both proteasome inhibitors (PIs) and immunomodulatory drugs (IMiDs) have been reported to have poor outcomes. Bendamustine has been reported to have an antitumor effect in newly diagnosed as well as relapsed/refractory multiple myeloma (RRMM). The aim of this retrospective study was to evaluate the efficacy of bendamustine therapy in heavily pretreated MM patients who were refractory to PIs and IMiDs. MATERIALS AND METHODS: Nineteen RRMM patients treated either with bendamustine and steroids (n=13) or a combination of bendamustine with novel drugs (n=6) were included. The median number of previous treatment lines was 5 (minimum-maximum: 3-8) and median time from diagnosis was 6 years (minimum-maximum: 1-16). All of the patients were resistant to at least one of the IMiDs and one of the PIs. Bendamustine was given at doses ranging from 90 mg/m2 to 120 mg/m2 on days 1 and 2 of 28-day cycles. RESULTS: A median of 2 (minimum-maximum: 1-8) treatment cycles was administered per patient. The toxicity of bendamustine was mild and mostly of hematological origin. No complete remission was achieved. There was partial remission and stable disease in 21% and 11% of the patients, respectively. Sixty-eight percent of patients had progressive disease. The median progression-free survival and overall survival was 2 and 4 months, respectively. CONCLUSION: Bendamustine therapy was well tolerated but showed limited anti-myeloma activity in heavily pretreated patients who were refractory to IMiDs and PIs.


Assuntos
Cloridrato de Bendamustina/administração & dosagem , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/mortalidade , Inibidores de Proteassoma/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Taxa de Sobrevida
17.
Nucl Med Commun ; 38(1): 76-83, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27775994

RESUMO

OBJECTIVE: In this observational pilot study, we aimed to evaluate the role of gallium-68-labelled DOTA-TATE (Ga-TATE) PET/computed tomography (CT) scanning in patients with multiple myeloma (MM), considering previous promising results obtained from conventional somatostatin receptor scintigraphy with In pentetreotide. MATERIALS AND METHODS: Twenty-one patients with a diagnosis of MM were prospectively included in this study: eight patients were referred for initial staging and 13 patients for restaging purpose. Both fluorine-18 fluorodeoxyglucose (F-FDG) and TATE PET/CT scanning were performed in all patients. RESULTS: All patients had one or more PET-positive lesion on either F-FDG or TATE scans. Six patients had an additional diffusely increased bone marrow activity on F-FDG scans, five of whom also had a concordant bone marrow appearance on TATE scans. Each PET set (either F-FDG or TATE) was positive in 19 patients. There was a discordant result in four (19%) patients between F-FDG and TATE scans. F-FDG scans showed 112 lesions (86 TATE-positive; 26 TATE-negative) in 19 patients, whereas TATE scans showed 108 lesions (86 F-FDG-positive; 22 F-FDG-negative) in 19 patients. No significant difference was found between the two modalities in terms of lesion numbers detected (P=0.67). However, the presence of diffuse bone marrow uptake of TATE seems to be a predicting factor for the overall survival (P=0.033, hazard ratio: 15.2 and 95% confidence interval: 1.2-185.5). CONCLUSION: TATE PET/CT seems to be an alternative imaging modality and may play a complementary role in MM management, at least by providing a different pathobiological insight into the disease.


Assuntos
Mieloma Múltiplo/diagnóstico por imagem , Compostos Organometálicos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Adulto , Idoso , Feminino , Radioisótopos de Flúor , Fluordesoxiglucose F18 , Radioisótopos de Gálio , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/estatística & dados numéricos , Estudos Prospectivos , Compostos Radiofarmacêuticos
18.
Biochem Genet ; 54(5): 619-35, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27246402

RESUMO

In this study, the patterns of genetic variation and phylogenetic relationships of mastic tree (Pistacia lentiscus L.) genotypes including 12 males and 12 females were evaluated using SSR, RAPD, ISSR, and ITS markers yielding 40, 703, 929 alleles, and 260-292 base pairs for ITS1 region, respectively. The average number of alleles produced from SSR, RAPD, and ISSR primers were 5.7, 14, and 18, respectively. The grouping pattern obtained from Bayesian clustering method based on each marker dataset was produced. Principal component analyses (PCA) of molecular data was investigated and neighbor joining dendrograms were subsequently created. Overall, the results indicated that ISSR and RAPD markers were the most powerful to differentiate the genotypes in comparison with other types of molecular markers used in this study. The ISSR results indicated that male and female genotypes were distinctly separated from each other. In this frame, M9 (Alaçati) and M10 (Mesta Sakiz Adasi-Chios) were the closest genotypes and while F11 (Seferihisar) and F12 (Bornova/Gökdere) genotypes fall into same cluster and showing closer genetic relation. The RAPD pattern indicated that M8 (Urla) and M10 (Mesta Sakiz Adasi-Chios), and F10 (Mesta Sakiz Adasi-Chios) and F11 (Seferihisar) genotypes were the closest male and female genotypes, respectively.


Assuntos
DNA de Plantas/genética , Pistacia/genética , Polimorfismo Genético , Análise do Polimorfismo de Comprimento de Fragmentos Amplificados/métodos , Frequência do Gene , Marcadores Genéticos , Filogenia , Análise de Componente Principal
19.
Biochem Genet ; 54(4): 421-437, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27048293

RESUMO

Bread wheat (Triticum aestivum L.) gene pool was analyzed with 117 microsatellite markers scattered throughout A, B, and D genomes. Ninety microsatellite markers were giving 1620 polymorphic alleles in 55 different bread wheat genotypes. These genotypes were found to be divided into three subgroups based on Bayesian model and Principal component analysis. The highest polymorphism information content value for the markers resides on A genome was estimated for wmc262 marker located on 4A chromosome with the polymorphism information content value of 0.960. The highest polymorphism information content value (0.954) among the markers known to be located on B genome was realized for wmc44 marker located on 1B chromosome. The highest polymorphism information content value for the markers specific to D genome was found in gwm174 marker located on 5D chromosome with the polymorphism information content value of 0.948. The presence of linkage disequilibrium between 81 pairwise SSR markers reside on the same chromosome was tested and very limited linkage disequilibrium was observed. The results confirmed that the most distant genotype pairs were as follows Ceyhan-99-Behoth 6, Gerek 79-Douma 40989, and Karahan-99-Douma 48114.


Assuntos
Mapeamento Cromossômico/métodos , Desequilíbrio de Ligação , Triticum/genética , Teorema de Bayes , Cromossomos de Plantas/genética , Variação Genética , Genoma de Planta , Repetições de Microssatélites
20.
J Clin Pathol ; 69(9): 810-6, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26811428

RESUMO

AIMS: Before the era of tyrosine kinase inhibitors (TKIs), the presence of bone marrow fibrosis (MF) in patients with chronic myeloid leukaemia (CML) has been established as a poor prognostic factor. The aim of the present study was to evaluate the effects of imatinib treatment on MF and the prognostic significance of MF at this new era of CML therapy. METHODS: The study cohort consisted of 135 patients with CML who were exposed to imatinib. The grades of MF pre and post imatinib together with cytogenetic and molecular responses were evaluated. RESULTS: Severe MF (grade II-III) was observed in 44 (33%) patients prior to imatinib therapy, and in 8 (8%) after 12 months of imatinib treatment (p=0.001). The complete cytogenetic response (CCyR) rates at 12 months did not differ according to the pre-imatinib MF grades, and CCyR rates in patients with grades 0, I, II and III MF were 36/47 (76.5%), 26/33 (78.7%), 12/23 (52.1%) and 7/10 (70%), respectively (p=0.127). There was no significant difference between patients with or without CCyR at 12 months of imatinib regarding grades of MF (p=0.785). The distribution of the major molecular response rates at 18 months according to pre-treatment grades of MF were determined as grade 0 in 38/45 (84.4%), grade I in 21/28 (75%), grade II in 14/21 (66.6%) and grade III in 7/10 (70%) (p=0.112). There was no significant difference in overall survival rates between initial MF mild (grade 0-I) and severe (grade II-III) groups (p=0.278). CONCLUSIONS: According to our findings, MF regresses with imatinib therapy over time, and the MF grades at diagnosis do not have a negative impact on the responses to imatinib treatment. Therefore, the adverse prognostic impact of the MF among patients with CML seems to disappear in the era of the TKIs.


Assuntos
Antineoplásicos/uso terapêutico , Medula Óssea/efeitos dos fármacos , Fibrose/tratamento farmacológico , Mesilato de Imatinib/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Reticulina/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/farmacologia , Medula Óssea/metabolismo , Medula Óssea/patologia , Feminino , Fibrose/metabolismo , Fibrose/patologia , Humanos , Mesilato de Imatinib/farmacologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/metabolismo , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Resultado do Tratamento , Adulto Jovem
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