Effect of cytokine genes in the pathogenesis and on the clinical parameters for the treatment of multiple myeloma

WOS: 000394527000002PubMed ID: 27611810In this study, we aimed to explore the association among gene variants of five cytokines, tumor necrosis factor alpha (TNF-alpha), transforming growth factor beta-1 (TGF-beta 1), interferon gamma (IFN-gamma), interleukin-6 (IL-6), and interleukin-10 (IL-10), and clinical parameters and prognosis in patients with multiple myeloma (MM) treated with novel therapeutic drugs in Turkish population for the first time except TNF-alpha. We analyzed five cytokine genes in 113 cases with MM and 113 healthy controls. Cytokine genotyping was performed by the polymerase chain reaction-sequence-specific primer method (PCR-SSP). AG genotype associated with high expression in TNF-alpha gene (-308) variant was found to be significantly higher (p = 0.019), and GG genotype associated with low expression in TNF-alpha gene (-308) variant was significantly lower in MM group as compared with controls (p = 0.012). IFN-gamma (+874) variant TT genotype was increased (p = 0.037), and AA genotype was decreased (p = 0.002) in MM group in contrast to controls. IFN-gamma (+874) T allele was higher inMMpatients compared with controls (OR = 1.985, p = 0.000), while A allele was significantly lower (OR = 0.5037, p = 0.0005). Multivariate analysis revealed that factors associated with 5-year overall survival (OS) were only IPI III (RR = 1.630, p = 0.018) and thrombocytopenia (RR = 2.207, Cox p = 0.021), while 5-year event-free survival (EFS) was associated with IPI III (RR = 1.524, p = 0.022), thrombocytopenia (RR = 2.902, p = 0.002), APSCT treatment (RR = 1.729, p = 0.035), and female gender (RR = 0.435, p = 0.002) with negative prognostic values. Our results suggested that TNF-alpha gene (-308) AG genotype and IFN-gamma (+874) TT genotype and T allele may have a role on MM, while other cytokines were not associated with the risk of MM

Wellesley College 1875-1975: A Century of Women

https://repository.wellesley.edu/wellesleyhistories/1000/thumbnail.jp

“The Lolelaplap (Marshall Islands) in Us: Sailing West to East (Ralik→Ratak) to These Our Atolls (Aelon Kein Ad) Ad Jolet Jen Anij (Our Blessed Inheritance from God)”

This paper discusses the expansion of Oceania through a Marshallese indigenous lens as a focal point. It explains that decolonizing methodologies allows reclaiming of space for mental liberation and reassurement of constitutional rights. It highlights similar occurrences of decolonization practices meeting resistance in the 21st century all while strengthening the human right argument that no human deserves any less than their fellow human brothers and sisters. It argues that an indigenous imagery can only be viewed through an indigenous lens where the researches’ level of purity is retained and unfiltered. It nevertheless argues that Marshallese ethnolinguistics reveal the same cultural practices in America, Judeo-Christianity, and Oceania thus dictating the reality that “we are the same not withstanding one stays here and one there (Bedbedjin Bedbedjen, Bedbedjinma wot Kwe)”. It further explains the importance in these similarities and how Marshallese spirituality predates introduced American Judeo-Christianity despite the latter attempting to marginalize the former. It concludes by stating that Marshallese contributions on the global stage are rooted in that culture of love (IaKwe) which is echoed by the custom(s) revealing the significance of Marshallese validation academically, spiritually, economically, & socially to prevent institutionalized discrimination. This paper ends stating that the agency to know one’s self and how one should fit in the world, is a human right in itself and Marshallese are entitled to this sense of self worth through knowing thy self by thy self where real thinking takes place in one’s own mind as we all live our own lives

Akut lösemilerde MIF Genindeki polimorfizmlerin önemi ve febril nötropenîk ataklara etkisi

The objective of this study is to research polymorphisms in MIF ' gene -173 site in variable haemotological malignities and evaluate its effects on febrile neutropenic attacks after chemotherapy in acute leukemia. Single nucleotide polymorphisms (SNPs) at -173 site of the MIF gene was analysed with the PCR-RFLP method (restriction endonudease Alu I) with isolated DNA samples from 48 patients who were treated for ALL and AML and 53 healthy controls, and G and C allel frequencies were compared statistically between patients and healthy controls groups. As a result of the analyzis, it was observed that the rate of patients with GG genotypes was 70.9%, with GC genotypes 29.1%, and with CC genotypes 0%.,Association is evaluated between MIF pozitivities in acute leukemias and distribution of infections, its factors, duration of feveraldays and neutropenia. Within the GC allel group; no significant differences were observed (p;gt;0.05) in infection factors, duration of neutropenia (;lt;500/L), duration of feveral , days, fungal pnompni, blood infections and FN mortality compared to the GG allel group. In conclusion, fungal pneumonia was observed at a higher rate in the CG allel group (22%) compared to the GG allel group (11.5%); a repeat of the study with anexpended group can -yield more-information about this relationship.Bu çalışmanın amacı; Akut Lösemiler (AL)'de Makrofaj Migrasyon inhibitor Faktörü (MIF) geninin -173 bölgesine ait polimorfizmleri araştırmak ve kemoterapi sonrası gelişen febril nötropenik (FN) ataklara etkisini değerlendirmektir. Akut Myeloblastik Lösemi (AML) ve Akut Lenfoid Lösemi (ALL) tanısıyla tedavi gören 48 hasta ile 53 sağlıklı kontrolden izole edilen DNA örneklerinde MIF geni -173 bölgesine ait tek nükleotid polimorfizmleri, PCR-RFLP yöntemi ile araştırılarak, G ye C allel ve genotip dağılımları hasta ile kontrol grupları arasında karşılaştırmıştır. Analizler sonucunda GG genotipini taşıyan hastaların oranı %70.9, GC'yi taşıyanların oranı %29.1 ye CC'yi taşıyanların oranı %0 olarak saptanmıştır. Hasta ve kontrol grubunda genotip ye allel frekansları açısından anlamlı bir farklılık ile Hardy-Weinberg dengesinden bir sapma gözlenmemiştir. AL'lerde elde edilen MIF pozitifliği ile infeksiyonların dağılımı,'etkenleri, ateşli gün süresi ve nötropeni süresi arasındaki ilişki değerlendirildiğinde; GC allel grubunda, infeksiyonların etkenleri, nötropeni (500/L) süresi, ateşli gün süresi, fungal pnömoni, .: kandolaşırri infeksiyonları ve FN mörtalitesinde GG alel grubuna göre anlamlı bir farklılık saptanmamıştır (p>0.05). Sonuç olarak; Fungal - pnömoni, GC aleli taşıyan grupta, GG aleli taşıyan gruba göre (%22/ll,5) daha sık izlenmiş olup çalışma grubunun' genişletilerek tekrarlanması durumunda anlamlı bir ilişki saptanabileceği düşünülmüştür

Importance Of Polynnorphisms Of The MIF Gene At Acute Leukemia And Its Effect On Febrile Neutropenic Attacks

The objective of this study is to research polymorphisms in MIF gene -173 site in variable haemotological malignities and evaluate its effects on febrile neutropenic attacks after chemotherapy in acute leukemia, Single nucleotide polyrnorphisms (SNPs) a-173 site of the MIF gene was analysed with the PCR-RFLP method (restriction endonudease Alu I) with isolated DNA samples from 48 patients who were treated for ALL and AML and 53 healthy controls, and G and C allel frequencies were compared statistically between patients and healthy controls groups, As a result of the analyzis, it was observed that the rate of patients with GG genotypes was 70.9%, with GC genotypes 29.1%, and with CC genotypes 0%, Association is evaluated between MIF pozItivities in acute leukemias and distribution of infections, its factors, duration of feveral days and neutropenia. Within the GC allel group; no significant differences were observed (p>0.05) in infection factors, duration of neutropenia (<500/L), duration of feveral days, fungal pnomoni, blood infections and FN mortality compared to the GG allel group. In conclusion, fungal pneumonia was observed at a higher rate in the CG allel group (22%) cumpared to the GG allel group (11.5%); a repeat of the study with an expended group can yield more information about this relationship

Study for the Diagnostic Screening of Paroxysmal Nocturnal Hemoglobinuria in Older Patients with Unexplained Anemia and/or Cytopenia

WOS: 000581034500007PubMed: 32902222Background: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired hematopoietic stem cell disease that may lead to weakness and death of patients, if unrecognized and untreated. Although consensus guidelines were reviewed recently for the diagnostic screening of PNH with multi-parameter flow cytometry (FCM), until now, no study has investigated the efficiency of such clinical indications in older patients. Methods: Overall, 20 centers participated in the study and a total of 1,689 patients were included, 313 of whom were at geriatric age and 1,376 were aged 18 - 64 years. We evaluated the efficiency of consensus clinical indications for PNH testing using FCM in peripheral blood samples and compared the results of older patients and patients aged 18 - 64 years. Results: PNH clones were detected positive in 7/313 (2.2%) of the older patients. Five (74.4%) of the patients with PNH clones had aplastic anemia, 1 had unexplained cytopenia, and 1 patient had myelodysplastic syndrome (MDS) with refractory anemia. PNH clones were not detected in any older patients who were screened for unexplained thrombosis, Coombs (-) hemolytic anemia, hemoglobinuria, and others (e.g., elevated lactate dehydrogenase (LDH), splenomegaly). We detected PNH clones in 55/1376 (4%) samples of the patients aged under 65 years. Forty-two (76.4%) patients with PNH clones had aplastic anemia, 2 patients had Coombs (-) hemolytic anemia, 3 patients had unexplained cytopenia, 1 patient had MDS with refractory anemia, 1 patient had hemoglobinuria, and 6 (10.9%) had others (e.g., elevated LDH, splenomegaly). PNH clones were not detected in any patients who were screened for unexplained thrombosis. There was no statistical difference between the geriatric population and patients aged 18 - 64 years in terms of clinical indications for PNH screening with FCM (p = 0.49). Conclusions: Our results showed that the current clinical indications for PNH screening with FCM were also efficient in older patients. We suggest that older patients with unexplained anemia, myelodysplastic syndrome with refractory anemia, and unexplained cytopenia should be screened for PNH with FCM to identify patients who would benefit from treatment

The Relationship of Frequency and Intensity of Bleeding with Hemophilic Arthropathy in Hemophilia Patients, Radiological Assesment and Socio-Economic Impacts of the Arthropathy

Hemophilic arthropathy is the most common complication of hemophilia, and the most important element for follow-up and treatment of hemophilia. In this study, hemophilic arthropathy was evaluated for bleeding, radiological assessment, and physical examination. Besides, socio-economic outcomes of hemophilic arthropathy and its impacts on quality of life were also investigated. Forty male patients diagnosed with hemophilia in the Hematology Unit of Gaziantep University Medical Faculty were included in the study. Of the 40 patients, 34 had hemophilia A and 6 had hemophilia B; 20 (50%) had severe, 8 (20%) had moderate and 12(30%) had mild hemophilia. According to our data collected in this study, there was a close relationship between hemophilic arthropathy and factor level. It was detected that the factor level and frequency of bleeding (p < 0.05), functional assessment of joints (p < 0.05) and scores of radiological assessment (p < 0.05) was negatively correlated. Frequency of joint bleeding during one-year period had a significantly positive correlation with functional assessment of joints (p < 0.01) and scores of radiological assessment (p < 0.01). It was observed that quality of life impaired in advanced arthropathy patients whose physical examination and radiological assessment scores were high among those who had more frequent bleedings. In addition, with increased frequency of bleeding, factor consumption and treatment costs are also increasing. Hemophilic arthropathy is a serious disease that imposes a large economic burden on patients and society. The full treatment of the disease may only be possible if the treatment is started at an early age and during this period it is crucially important to prevent joint blpedings, rehabilitate disabilities, and to introduce patients into society

Effect of the uncoupling protein-2 (UCP-2) and nuclear receptor subfamily 3 group C member 1 (NR3C1) genes on treatment efficacy and survival in patients with multiple myeloma: a single-center study

Objective Studies on the genetic background of patients with multiple myeloma (MM) have been increasing; two important factors considered in such works are uncoupling protein-2 (UCP-2) and nuclear receptor subfamily 3 group C member 1 (NR3C1). We aim to reveal the association of MM with NR3C1 and UCP-2 gene polymorphisms. In this prospective study, 200 patients diagnosed between January 2009 and 2018 and 200 healthy individuals were included. For patients who had undergone autologous stem cell transplantation and control subjects, we statistically compared the CC, GC, and GG genotypes and the C and G alleles of the NR3C1 gene, as well as the AA, AG, and GG genotypes and the A and G alleles of the UCP-2 gene. Results While the AA genotype was significantly more common in the MM group (p = 0.001), the GG genotype was significantly more common in the control group (p = 0.016). Overall survival was found to be significantly shorter in patients with the UCP-2 GG genotype (p = 0.034). It was also found that having the GG genotype of the UCP-2 gene was a 2.48-fold risk factor for mortality. The fact that overall survival is significantly shorter in MM patients with the UCP-2 GG genotype and its definition as a risk factor for mortality have been put forward for the first time in the literature