Identification of miR-20a as A Potential Discerning Biomarker for Non-Invasive versus Invasive Retinoblastoma.

OBJECTIVE: Intraocular retinoblastoma (RB) is common in kids. Although the cause of this disease is a mutation in the RB1 gene, the formed cancerous mass in different patients is seen in non-invasive states, limited to the ocular cavity or in invasive states distributed to other parts of the body. Because this tumor's aggressiveness cannot be predicted early, these patients receive systemic chemotherapy with multiple drugs. Treating non-invasive and invasive tumors separately reduces chemical drug side effects. The aim of this study was to identify diagnostic biomarkers by separating miRNAs in blood serum from invasive and non-invasive RB patients. MATERIALS AND METHODS: In this experimental study, selected three gene expression omnibus (GEO) datasets. Two were related to serum and tumor tissue miRNAs, and one was related to non-invasive and invasive RB gene expression. Examined RB gene-miRNA relationships. Then, we performed real-time polymerase chain reaction (PCR) on candidate miRNAs in the Y79 cell line and patient blood samples in non-invasive and invasive retinoblastoma. RESULTS: Fourteen high-expression and 7 low-expression miRNAs resulted. MiR-181, miR-135a, miR-20a, miR-373, and miR-191 were common genes with differential genes between invasive and non-invasive retinoblastoma. Only MiR-181 was upregulated in the Y79 RB cell line. Other candidate miRNAs expressed less. Invasive retinoblastomas increased serum miR-20a and miR-191. CONCLUSION: Integrated and regular bioinformatics analyses found important miRNAs in patients' and miR-20a, miR- 191, and miR-135a can distinguish non-invasive and invasive retinoblastoma, suggesting further research.

Translating mechanisms into therapeutic strategies for immune thrombocytopenia (ITP): Lessons from clinical trials.

Immune thrombocytopenia (ITP) is an autoimmune disorder that causes a significant reduction in peripheral blood platelet count. Fortunately, due to an increased understanding of ITP, there have been significant improvements in the diagnosis and treatment of these patients. Over the past decade, there have been a variety of proven therapeutic options available for ITP patients, including intravenous immunoglobulins (IVIG), Rituximab, corticosteroids, and thrombopoietin receptor agonists (TPO-RAs). Although the effectiveness of current therapies in treating more than two-thirds of patients, still some patients do not respond well to conventional therapies or fail to achieve long-term remission. Recently, a significant advancement has been made in identifying various mechanisms involved in the pathogenesis of ITP, leading to the development of novel treatments targeting these pathways. It seems that new agents that target plasma cells, Bruton tyrosine kinase, FcRn, platelet desialylation, splenic tyrosine kinase, and classical complement pathways are opening new ways to treat ITP. In this study, we reviewed the pathophysiology of ITP and summarized updates in this population's management and treatment options. We also took a closer look at the 315 ongoing trials to investigate their progress status and compare the effectiveness of interventions. May our comprehensive view of ongoing clinical trials serve as a guiding beacon, illuminating the path towards future trials of different drugs in the treatment of ITP patients.

Proteomic-Based Discovery of Predictive Biomarkers for Drug Therapy Response and Personalized Medicine in Chronic Immune Thrombocytopenia.

Purpose: ITP is the most prevalent autoimmune blood disorder. The lack of predictive biomarkers for therapeutic response is a major challenge for physicians caring of chronic ITP patients. This study is aimed at identifying predictive biomarkers for drug therapy responses. Methods: 2D gel electrophoresis (2-DE) was performed to find differentially expressed proteins. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometer (MALDI-TOF MS) analysis was performed to identify protein spots. The Cytoscape software was employed to visualize and analyze the protein-protein interaction (PPI) network. Then, enzyme-linked immunosorbent assays (ELISA) were used to confirm the results of the proteins detected in the blood. The DAVID online software was used to explore the Gene Ontology and pathways involved in the disease. Results: Three proteins, including APOA1, GC, and TF, were identified as hub-bottlenecks and confirmed by ELISA. Enrichment analysis results showed the importance of several biological processes and pathway, such as the PPAR signaling pathway, complement and coagulation cascades, platelet activation, vitamin digestion and absorption, fat digestion and absorption, cell adhesion molecule binding, and receptor binding. Conclusion and Clinical Relevance. Our results indicate that plasma proteins (APOA1, GC, and TF) can be suitable biomarkers for the prognosis of the response to drug therapy in ITP patients.

A human pilot study on positive electrostatic charge effects in solid tumors of the late-stage metastatic patients.

Background: Correlative interactions between electrical charges and cancer cells involve important unknown factors in cancer diagnosis and treatment. We previously reported the intrinsic suppressive effects of pure positive electrostatic charges (PEC) on the proliferation and metabolism of invasive cancer cells without any effect on normal cells in cell lines and animal models. The proposed mechanism was the suppression of pro-caspases 3 and 9 with an increase in Bax/Bcl2 ratio in exposed malignant cells and perturbation induced in the KRAS pathway of malignant cells by electrostatic charges due to the phosphate molecule electrostatic charge as the trigger of the pathway. This study aimed to examine PECs as a complementary treatment for patients with different types of solid metastatic tumors, who showed resistance to chemotherapy and radiotherapy. Methods: In this study, solid metastatic tumors of the end-stage patients (n = 41) with various types of cancers were locally exposed to PEC for at least one course of 12 days. The patient's signs and symptoms, the changes in their tumor size, and serum markers were followed up from 30 days before positive electrostatic charge treating (PECT) until 6 months after the study. Results: Entirely, 36 patients completed the related follow-ups. Significant reduction in tumor sizes and cancer-associated enzymes as well as improvement in cancer-related signs and symptoms and patients' lifestyles, without any side effects on other tissues or metabolisms of the body, were observed in more than 80% of the candidates. Conclusion: PECT induced significant cancer remission in combination with other therapies. Therefore, this non-ionizing radiation would be a beneficial complementary therapy, with no observable side effects of ionizing radiotherapy, such as post-radiation inflammation.

Complications in patients with transfusion dependent thalassemia: A descriptive cross-sectional study.

Background and Aims: One of the most common hemoglobinopathies globally related to blood transfusion and iron overload in the body is thalassemia syndrome. Increasing ferritin levels can cause severe damage to the patient's body organs. This study aims to evaluate the complications of iron overload on vital body organs in patients with transfusion-dependent beta-thalassemia. Methods: This descriptive cross-sectional study was performed in Iran University of Medical Sciences Hospitals on patients with a beta-thalassemia major with frequent blood transfusions. To evaluate the effect of iron overload on vital body organs, hematologic and blood analysis, echocardiography with measurement of pulmonary artery pressure (PAP) and ejection fraction (EF) tests, bone densitometry, and audiometric tests were performed for all patients. Results: Of the 1010 patients participating in this study, 497 (49%) were males, 513 were (51%) females aged 5-74 years, and the majority of participants (85%) were over 20 years old. This study demonstrated that increasing ferritin levels had no notable correlation with sex, cholesterol, low-density lipoprotein, parathyroid hormone, T4, and aspartate aminotransferase. However, elevating ferritin levels had significant correlations with increasing triglyceride, phosphorus, thyroid stimulating hormone, alkaline phosphatase, alanine transaminase, and PAP levels, age, hearing disorders, splenectomy, osteoporosis, and decreasing high-density lipoprotein, body mass index, calcium, and EF levels. Conclusion: Improvement in beta-thalassemia patients' survival and quality of life can be due to multidisciplinary care in a comprehensive unit through regular follow-up and early complication detection.

Angiogenesis, coagulation, and fibrinolytic markers in acute promyelocytic leukemia (NB4): An evaluation of melatonin effects.

Melatonin is a powerful biological agent that has been shown to inhibit angiogenesis and also exerts anti-inflammatory effects. It is well known that new blood vessel formation (angiogenesis) has become an urgent issue in leukemia as well as solid tumors. Acute promyelocytic leukemia (APL) is a form of liquid cancer that manifests increased angiogenesis in the bone marrow of patients. Despite high-rate curable treatment with all-trans-retinoic acid (ATRA) and recently arsenic-trioxide (ATO), early death because of hemorrhage, coagulopathy, and Disseminated intravascular coagulation (DIC) remains still a concerning issue in these patients. It is, therefore, urgent to seek treatment strategies with antiangiogenic capabilities that also diminish coagulopathy and hyperfibrinolysis in APL patients. In this study, a coculture system with human umbilical vein endothelial cells (HUVECs) and NB4 APL cells was used to investigate the direct effect of melatonin on angiogenesis and its possible action on tissue factor (TF) and tissue-type plasminogen activator-1 (TPA-1) expression. Our experiments revealed that HUVEC-induced angiogenesis by cocultured NB4 cells was suppressed when melatonin alone or in combination with ATRA was added to the incubation medium. Melatonin at concentrations of 1 mM inhibited tube formation of HUVECs and also decreased interleukin-6 secretion and VEGF mRNA expression in HUVEC and NB4 cells. Taken together, the results of this study demonstrate that melatonin inhibits accelerated angiogenesis of HUVECs and ameliorates the coagulation and fibrinolysis indices stimulated by coculturing with NB4 cells.

Intra-lesion injection of activated Natural Killer (NK) cells in recurrent malignant brain tumors.

Despite multi-modal therapies for patients with malignant brain tumors, their median survival is < 2 years. Recently, NK cells have provided cancer immune surveillance through their direct natural cytotoxicity and by modulating dendritic cells to enhance the presentation of tumor antigens and regulate T-cell-mediated antitumor responses. However, the success of this treatment modality in brain tumors is unclear. The main reasons are; the brain tumor microenvironment, the NK cell preparations and administration, and the donor selection. Our previous study showed that intracranial injection of activated haploidentical NK cells resulted in the eradication of glioblastoma tumor mass in the animal model without any evidence of tumor recurrence. Therefore, in the present study, we evaluated the safety of intra-surgical cavity or intra cerebrospinal fluid (CSF) Injectionofex vivoactivated haploidentical NK cells in six patients with recurrent glioblastoma multiform (GBM) and malignant brain tumors resistance to chemo/radiotherapy. Our results indicated that activated haploidentical NK cells express activator and inhibitor markers and can kill the tumor cells. However, their cytotoxic potential on patient-derived GBM (PD-GBM) was more than that of its cell line. Also, their infusion increased the overall disease control rate by about 33.3%, with a mean survival of 400 days. Moreover, we showed that local administration of the activated haploidentical NK cells in malignant brain tumors is safe, feasible, tolerated at higher doses, and cost-effective.

Monozygotic twin cases of endometriosis with Glanzmann thrombasthenia: a case report and review of literature.

BACKGROUND: Glanzmann thrombasthenia (GT) is a rare bleeding disorder with a high prevalence in communities where consanguineous marriages are mainstream. Endometriosis is a chronic inflammatory disease, and its risk increases in women with menstrual periods of longer than six days. The phenotypic expression of endometriosis is determined by the frequency and rate of the menstrual flow, as well as genetic and environmental factors. RESULT AND CASE PRESENTATION: 14-year-old monozygotic twin sisters with GT who developed ovarian endometriosis were referred to Hazrat Rasoul Hospital due to severe dysmenorrhea. In ultrasonic examination, endometrioma cysts were reported in both patients. They both went under endometrioma cystectomy, and the bleeding was managed using antifibrinolytic drugs, followed by recombinant activated coagulation factor VII. Both were discharged after 3 days. In the ultrasound examination performed one year after the surgery, ovaries were normal in the first twin, while the second twin had a 28 × 30 hemorrhagic cyst in the left ovary. DISCUSSION AND CONCLUSION: Menstrual bleeding and genetic factors are two theories that could be related to GT and endometriosis association, and GT could be considered a risk factor for endometriosis.

Extensive genetic screening of Iranian Factor FVII-deficient individuals unraveled several novel mutations and postulated founder effects in some cases.

Background: As the most frequent congenital rare bleeding disorder that transmits in an autosomal recessive manner, factor VII (FVII) deficiency is a serious bleeding complication in populations with high rate of in-marriages. While diagnosis mainly relies on clinical and laboratory phenotypes, plasma FVII antigen and activity levels do not often correlate with symptoms' severity. Objectives: Genetic profiling of the affected individuals potentially improves our biological understanding of this complicated rare disorder. Methods: Conventional polymerase chain reaction-Sanger sequencing and whole-exome sequencing were applied for genetic profiling of F7 gene in 66 symptomatic FVII-deficient individuals from 62 independent pedigrees. Thirty-nine asymptomatic relatives of the patients were also studied. Results: Thirty different F7 pathogenic variations were identified in the studied cases of which 11 have not been reported before. The novel mutations include 5 missenses (c.715G>A, c.794T>C, c.1090C>G, c.1222C>A, c.1265T>C), 3 splicing (c.316+1G>T, c.682-2A>G, c.572-16C>G), 2 nonsenses (c.790delC, c.1248G>A), and 1 frameshift (c.1346delA). A founder effect is proposed for c.790delC that was detected in 8 independent pedigrees who were all from similar geographical regions and ethnic backgrounds. Homozygous c.790delC reduces plasma FVII activity to <1% and causes spontaneous intracranial hemorrhage in early infancy. Conclusion: From the 66 studied symptomatic FVII-deficient individuals, 58 were homozygous carriers of the identified variations. Identification of homozygotes clarifies the potential role of nucleotide variations in reducing FVII activity and their contributions to a certain phenotype. Some of those variations, such as c.1A>G, c.509G>A, c.634C>T, and c.1285G>A have only been previously reported as heterozygous.

Patient and Physician Perspectives in the Management of Immune Thrombocytopenia in Iran: Responses from the ITP World Impact Survey (I-WISh).

Data describing physicians' and patients' perspectives towards immune thrombocytopenia (ITP) management and impact of disease in Iran are limited. This ITP World Impact Survey was conducted between October 2019 and October 2020. Of the 114 patients included in the survey, 17 were aged ≤18 years. Forty-seven physicians, including 22 pediatric hematologists, participated in the survey. Fatigue and anxiety around stable platelet counts were frequent patient-reported symptoms at diagnosis and at survey completion. According to physicians, "watch-and-wait" was the preferred treatment option for mean (standard deviation) proportion of 50.1 (24.1) and 48.6 (21.8) of their adult and pediatric patients, respectively, following first diagnosis. Per adult and pediatric hematologists, the most prescribed treatments for newly diagnosed patients based on available answers were steroids (100%, n = 20/20; 89%, n = 16/18), respectively. Forty percent of adult (n = 10/25) and 38% of pediatric hematologists (n = 8/21) reported that ITP reduced patients' quality of life. Energy levels (46%, n = 52/112) and ability to concentrate on everyday activities (42%, n = 47/113) were the most affected aspects of patients' lives. This I-WISh study in Iran underlined the negative impact of ITP on patients.

Targeted chemotherapy in retinoblastoma: A step forward from patient survival to globe survival.

BACKGROUND/ OBJECTIVES: Despite being the most common intraocular malignancy in childhood, there is a substantial disparity between developing and developed countries in terms of patient and globe survival in retinoblastoma (Rb). The current study intends to determine patient and globe survival before and after the introduction of the new targeted treatment modalities in a developing country. METHODS: Medical records of 350 patients (516 eyes) with retinoblastoma referred to a tertiary referral center for Rb in Tehran, Iran, were reviewed. In order to compare patient and globe survival before and after the availability of the new treatment modalities, including intra-arterial and intravitreal chemotherapy, the patients were divided into group 1 (2001-2007) and group 2 (2008-2018) based on the calendar period of diagnosis. RESULTS: Two-hundred-twenty-three eyes of 149 patients and 293 eyes of 201 patients were categorized into groups 1 and 2, respectively. The 5-year patient survival was 97% across the current survey, and the overall survival rate was 96% in group 1 and 99% in group 2 (P = 0.08). Overall, 50% of eyes with retinoblastoma underwent enucleation, which was the primary in 63% (116/184) of the unilateral and 30% (99/322) of the bilateral cases. Primary enucleation was significantly lower in group 2 (35%) in contrast to group 1 (50%) (P < 0.001). In addition, globe survival improved significantly in the International Classification of Retinoblastoma Groups D (17% in group 1 vs. 66% in group 2, P < 0.001) and E (1% in group 1 vs. 23% in group 2 P < 0.001) during the two timelines. In enucleated eyes, despite the increased rate of prelaminar involvement in group 2 (13% vs. 2% in group 1, P = 0.003), the rate of high-risk histopathologic findings was similar between the two groups. CONCLUSION: Similar to developed countries, the application of new targeted treatment modalities, including intra-arterial and intravitreal chemotherapy, has been associated with significantly improved globe survival in Rb patients. However, it should be noted that even with the availability of these novel treatment options, the decision for on-time enucleation should not be deferred.

Neonatal Onset of Hemophagocytic Lymphohistiocytosis Due to Prenatal Varicella-Zoster Infection in a Neonate with Griscelli Syndrome Type 2.

Type 2 Griscelli syndrome (Type2 GS) is a primary inborn error of the immune system, classified in the immune dysregulation group.1,2 There are three different types of the disease, with different genetic causes responsible for the autosomal recessive inheritance pattern. Although hypopigmentation is common in all variants, neurological involvement or immunodeficiency with varying severity is seen in different types. Molecular motor protein myosin 5 an (MYo5A) [Type1GS], guanosine Triphosphate (GTP) binding protein (RAB27A) [Type2GS], and mutation in human melanophilin (MLPH) [Type 3GS] which is limited to hypopigmentation are reported as the known genetic defects in GS.3 Severe, ineffective, and uncontrolled inflammatory reactions are referred to as the pathogenesis of Hemophagocytic lymphohistiocytosis (HLH). HLH is a life-threatening condition that can be defined as either primary or secondary. Secondary causes happen in the context of autoimmunity, malignancy, spontaneous, or infections.4 Prenatal infections play an important role in causing long-term complications in the fetus. Some of them include toxoplasmosis, rubella, cytomegalovirus, herpes simplex, and other organisms including syphilis, parvovirus, and Varicella zoster, known as TORCH syndrome (5).TORCH has been well described for a long time but there are limited reports of developing HLH in the context of prenatal infections. We described a type 2GS syndrome with neonatal-onset HLH triggered by a prenatal infection.

Evaluation of immune system in patients with transfusion-dependent beta-thalassemia in Rasoul-e-Akram Hospital in 2021: A descriptive cross-sectional study.

Background and aims: Thalassemia syndromes are the most common hemoglobinopathy globally related to blood transfusion and iron overload in the body. Splenectomy, excessive iron overload, and repeated exposure to antigens in blood transfusions can cause severe damage to the patient's immune system making the patient prone to frequent infection. This study evaluates the immune system status and infection rate in beta-thalassemia major patients receiving iron chelators. Methods: This descriptive cross-sectional study was performed in Rasoul-e-Akram Hospital on patients with a beta-thalassemia major who had iron overload due to frequent blood transfusions. The percentage of lymphocyte markers was determined by flow cytometry. Serum levels of immunoglobin were measured by nephelometric assay. Also, Nitro blue tetrazolium and dihydrorhodamine assays were used to evaluate the phagocytic function. Results: Of the 106 patients participating in this study, 59 (55.7%) and 47 (44.3%) are male and female, respectively. The mean age ± SD of participants was 24.7 ± 12.1 years with 4 to 55 years. There was no significant correlation between sex, the C3 and C4 complements, the lymphocyte markers, and the immunoglobulin levels. Furthermore, all of these variables increased significantly over 30 (p < 0.05). Moreover, there was a strong positive correlation between splenectomy and IgG immunoglobulin (p < 0.001) and CD16 (p = 0.005) lymphocyte marker. Conclusion: Iron chelator agents effectively improve patients' immune system with thalassemia major. The increase in IgG and IgM immunoglobulins levels is due to frequent blood transfusions, which stimulate the immune system.

Pediatric Cancer Registry at MAHAK Pediatric Cancer Treatment and Research Center: A Single-Center Study from Iran.

Background: The childhood cancer registry in Iran is a hospital-based system and there is not any unique and national registry system for pediatric malignancies in Iran. According to the limitations and requirements, this study was designed to clarify the aspect of childhood malignancies in Iran and promote establishing the Iranian national childhood cancer registry system. Materials and Methods: This cross-sectional longitudinal study was implied on 1500 patients younger than 20-years old diagnosed with any malignancy and admitted at MAHAK Pediatric Cancer Treatment and Research Center (MPCTRC) from 2007 to 2014. Data collection was based on a validated questionnaire with three categories including demographic data, clinical data and type of malignancy, and outcomes. Collected data were analyzed using methods for qualitative and quantitative variables (P < 0.05) by SPSS software version 22. The survival rate was calculated by the Kaplan-Meyer method. Results: This study was implied on 1500 children with a mean age of 6.1 years old. The most common malignancy was acute leukemia (30.7%) followed by central nervous system tumors (27%). At the onset of starting treatment, the rate of conferring with relapse, metastasis, and secondary malignancies was 29%, 19.5%, and 1% respectively. In addition, 52 patients had bone marrow transplantation of whom, 14 cases died. Totally, 42% of patients died and the 3-years, 5-years, and 10-years overall survival rates were 67.7% ± 0.01, 60.3% ± 0.01, and 53.8% ± 0.01, respectively. Conclusion: Establishing a population-based pediatric cancer registry in Iran is necessary and will be useful for improving the survival rate of mentioned patients.

Ocular Manifestations of Newly Diagnosed Acute Leukemia Patients.

Purpose: To present primary ocular manifestations in acute leukemia. Methods: This cross-sectional descriptive hospital-based study evaluated all newly diagnosed leukemia patients of three referral hospitals of Tehran University of Medical Sciences in 2015-2016 and Mahak Hospital in Tehran in 2017. Exclusion criteria included the patients with the previous history of chemotherapy, cases of relapsing disease, and the patients with a history of ocular disease or other systemic conditions with ophthalmic manifestations. Results: A total of 85 patients (170 eyes) were evaluated in our study, including 29 children (34.1%) and 43 females (50.6%). The mean patient age was 37.84 ± 11.91 years in the adult group and 6.28 ± 4.70 years in the pediatric category. Ophthalmic involvement was seen in 27 patients (31.8%), including 6 pediatric patients (20.7%) and 21 adult patients (37.5%). Two patients (2.3%) had direct infiltration by leukemic cells and 76 patients (89.41%) of patients were asymptomatic. There was a correlation between ophthalmic involvement and platelet count and hemoglobin level. In patients with ocular signs, higher mortality rates were observed. Conclusions: At the time of diagnosis in acute leukemia patients, complete ophthalmic evaluation including dilated fundus examination is suggested as ocular involvement in these patients is common and sometimes asymptomatic. Ophthalmic involvement in leukemic patients should be identified in a timely manner, particularly in individuals with low platelet counts and hemoglobin levels, due to the potential prognostic relevance.

Inhibition of Skp2 enhances doxorubicin-induced cell death in B cell precursor acute lymphoblastic leukemia.

S-phase kinase-associated protein 2 (Skp2) is a well-defined component of the Skp2-Culin1-F-box (SCF) E3 ubiquitin ligase complex, which is involved in cell cycle progression and considered a prognostic marker in cancers. Overexpression of Skp2 is frequently observed in patients with acute lymphoblastic leukemia (ALL). Inhibition of this protein may be a valuable strategy to induce apoptosis in malignant cells. Less well known is the effect of Skp2 inhibition on the potentiation of the chemotherapeutic-induced cell death in B cell precursor acute lymphoblastic leukemia (BCP-ALL). Our results demonstrated that inhibition of the Skp2 using SZL P1-41, not only resulted in caspase-mediated apoptosis but also potentiated doxorubicin-induced apoptosis in BCP-ALL cell lines (NALM-6 and SUP-B15). SZL P1-41 in combination with doxorubicin altered cell cycle distribution and the level of cyclins and cyclin-dependent kinases in BCP-ALL cells. DNA damage response genes were also upregulated in presence of the doxorubicin and SZL P1-41 in both cell lines. In conclusion, our results indicated that inhibition of Skp2 either alone or in a combination with doxorubicin may hold promise in the future treatment of BCP-ALL.

Study of Glutathione S-transferase-P1 in cancer blood plasma after extraction by affinity magnetic nanoparticles and monitoring by MALDI-TOF, IM-Q-TOF and LC-ESI-Q-TOF MS.

Glutathione S-transferase P1 (GST-P1) is considered as a detoxification enzyme and can be upregulated in several cancers. Therefore, qualification and/or quantification of GST-P1 in biological fluids can be noteworthy in cancer diagnostic and/or prognostic methods. Whereas costly immunoassays methods are routinely used for clinical analysis, long analysis time per sample is still considered as their disadvantages. To create a fast, efficient, and economical GST-P1 qualification and/or quantification technique, we developed an affinity magnetic nanoparticle-MS method. In proposed method there is no need for any pretreatment for reducing the complexity of sample and depletion of high abundant proteins that are used in routinely immunoassays methods. After enrichment of GST-P1 from blood plasma samples by affinity magnetic nanoparticle (without any pretreatment), the final eluent was analyzed using MALDI-TOF, IM-Q-TOF and LC-ESI-Q-TOF MS. For the first time this study demonstrates the suitability of affinity magnetic nanoparticle-MS method for qualification/quantification of GST-P1 from acute lymphoblastic leukemia blood plasma samples with the limit-of-detection 0.0094 ppm in less than 5 h. Our finding showed that in these blood plasma samples the level of GST-P1 can be up to six times more than healthy children.

Mass Spectrometry: A Powerful Method for Monitoring Various Type of Leukemia, Especially MALDI-TOF in Leukemia's Proteomics Studies Review.

Recent success in studying the proteome, as a source of biomarkers, has completely changed our understanding of leukemia (blood cancer). The identification of differentially expressed proteins, such as relapse and drug resistance proteins involved in leukemia by using various ionization sources and mass analyzers of mass spectrometry techniques, has helped scientists find better diagnosis, prognosis, and treatment strategies. With the aid of this powerful analytical technique, we can investigate the qualification/quantification of proteins, protein-protein interactions, post-translational modifications, and find the correlation between proteins and their genes with the hope of finding the missing parts of the successful therapy puzzle. In this review, we followed different MS sources and analyzers which used for monitoring various type of leukemia, then focused on MALDI-TOF MS as a quick and reliable method for studying proteins. Due to several review published for other techniques, the present review is the first work in this field. Also, by classifying more than 400 proteins, we have found 42 proteins are involved in two or three different stages of leukemia. Finally, we have suggested six specific biomarkers for AML, one for ALL, three biomarkers with a role in the etiology of leukemia and 13 markers with the potential for further studies.

Molecular Investigation of Human Cytomegalovirus and Epstein-Barr virus in Glioblastoma Brain Tumor: A Case-Control Study in Iran

Background: Glioblastoma multiforme is the most invasive and lethal form of brain cancer with unclear etiology. Our study aimed to investigate the molecular prevalence of human cytomegalovirus (HCMV) and Epstein-Barr virus (EBV) infections in patients with glioblastoma multiforme (GBM). Methods: This case-control study was conducted on 42 FFPE brain tumor samples from GBM patients and 42 brain autopsies from subjects without neurological disorders. The presence of EBV and HCMV DNA was determined, using PCR and nested-PCR assays, respectively. Results: HCMV DNA was detected in 3 out of 42 (7.1%) of GBM samples and was absent from the control group (p = 0.07). Importantly, EBV DNA was detected in 9 out of 42 (21.4%) brain tissue specimens of GBM subjects, but again in none of the control group (p = 0.001). Conclusion: Our findings indicate that infection with EBV is associated with GBM.

Positive electrostatic therapy of metastatic tumors: selective induction of apoptosis in cancer cells by pure charges.

BACKGROUND: We discovered that pure positive electrostatic charges (PECs) have an intrinsic suppressive effect on the proliferation and metabolism of invasive cancer cells (cell lines and animal models) without affecting normal tissues. METHODS: We interacted normal and cancer cell lines and animal tumors with PECs by connecting a charged patch to cancer cells and animal tumors. many biochemical, molecular and radiological assays were carried out on PEC treated and control samples. RESULTS: Correlative interactions between electrostatic charges and cancer cells contain critical unknown factors that influence cancer diagnosis and treatment. Different types of cell analyses prove PEC-based apoptosis induction in malignant cell lines. Flowcytometry and viability assay depict selective destructive effects of PEC on malignant breast cancer cells. Additionally, strong patterns of pyknotic apoptosis, as well as downregulation of proliferative-associated proteins (Ki67, CD31, and HIF-1α), were observed in histopathological and immunohistochemical patterns of treated mouse malignant tumors, respectively. Quantitative real-time polymerase chain reaction results demonstrate up/down-regulated apoptotic/proliferative transcriptomes (P21, P27, P53/CD34, integrin α5, vascular endothelial growth factor, and vascular endothelial growth factor receptor) in treated animal tumors. Expression of propidium iodide in confocal microscopy images of treated malignant tissues was another indication of the destructive effects of PECs on such cells. Significant tumor size reduction and prognosis improvement were seen in over 95% of treated mouse models with no adverse effects on normal tissues. CONCLUSION: We discovered that pure positive electrostatic charges (PECs) have an intrinsic suppressive effect on the proliferation and metabolism of invasive cancer cells (cell lines and animal models) without affecting normal tissues. The findings were statistically and observationally significant when compared to radio/chemotherapy-treated mouse models. As a result, this nonionizing radiation may be used as a practical complementary approach with no discernible side effects after passing future human model studies.