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.

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.

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.

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.

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.

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.

The design and fabrication of nanoengineered platinum needles with laser welded carbon nanotubes (CNTs) for the electrochemical biosensing of cancer lymph nodes.

A new biosensor for detecting cancer involved sentinel lymph nodes has been developed via the electrochemical tracing of fatty acid oxidation as a distinct metabolism of malignant cells invading lymph nodes (LNs). The system included integrated platinum needle electrodes that were decorated by carbon nanotubes (as hydrophobic agents) through laser-assisted nanowelding. It was applied to record the dielectric spectroscopy data from LN contents via electrochemical impedance spectroscopy. The system was applied for dielectric spectroscopy of LN contents via electrochemical impedance approach. The reduced lipid content of involved LNs, due to fat metabolism by invasive cancer cells, would decrease the charge transfer resistance (RCT) of the LNs with respect to their normal counterparts. Multi-walled carbon nanotubes (MWCNTs) with superhydrophobic properties were used to enhance the interaction of Pt needle electrodes with the lipidic contents of lymph nodes. This is the first time that a fatty acid metabolism-based sensing approach has been introduced to detect involved LNs. Moreover, a novel electrode decorating method was applied to enhance the interfacial contact of this lipid detection probe (LDP). In order to avoid doubt about the biocompatibility of ferrocyanide, [Fe(CN)6]4- and ferricyanide, [Fe(CN)6]3-, a biocompatible injectable metal ion-based material, ferric carboxymaltose, was selected and applied as the electrolyte for the first time. Rabbit LNs were tested using the LDP in the animal model phase. The system was then used in vitro on 122 dissected human LNs in the operating room. Calibration of the results showed an excellent match between the dielectric response of the LDP (known as charge transfer resistance (RCT)) and the final pathological diagnoses. The LDP may have a promising future after further clinical investigations for intra-operative distinction between normal and cancerous LNs.

Retinoblastoma presentation, treatment and outcome in a large referral centre in Tehran: a 10-year retrospective analysis.

BACKGROUND/OBJECTIVES: Early diagnosis, care and treatment of retinoblastoma is a challengeable issue for Iranian health system. This study was designed and conducted in a referral multidisciplinary centre in the capital city of Iran to evaluate management, care, prognosis and survival rates of paediatric patients with retinoblastoma. METHODS: In this retrospective study, a total number of 309 patients younger than 15 years, diagnosed with retinoblastoma, who referred for diagnosis and treatment to MAHAK's Pediatric Cancer Treatment and Research Center (MPCTRC) from 2007 to 2017 were evaluated. All data were analyzed via SPSS version 22 software in regard of parametric and non-parametric data. Survival rates were analyzed using the Kaplan-Meyer method. RESULTS: The mean age of patients was 20 months and the majority of patients (77%) had leukocoria as a common clinical symptom at the time of diagnosis. Primary treatment methods were systemic chemotherapy (94%), laser (35%) and primary enucleation (28%). Relapses occurred in nearly 42% of cases, and the median time from diagnosis to the first relapse was 9 months. At the time analyzing the data, 11% of patients died. Patients' 5-year OS and RFS rates were 79.6% and 41.5%, respectively. CONCLUSION: Comparing results with other conducted studies identifies that the recurrence rate was high in our considered patients. Also, OS and RFS rates in our study were not as considerable as other reports. Screening methods, updating protocols and follow-up of patients may lead to improvements in survival rates of patients with retinoblastoma.

Apoptotic effect of berberine via Bcl-2, ROR1, and mir-21 in patients with B-chronic lymphocytic leukemia.

Berberine is a natural isoquinoline alkaloid that has been shown to inhibit the proliferation and induce apoptosis in a wide variety of tumor cells. However, the action mechanism of berberine in CLL cells is unknown. The previous study has shown that berberine leads to reduced viability and elevated levels of apoptosis in PBMCs of CLL patients. CLL cells are characterized by remarkable expression of Bcl-2 and ROR1 which leads to activation and survival and increases disease progression in patients. High-level expression of miR-21 in patients with CLL is associated with a higher risk of death. Here we investigated the anticancer effects of berberine upon peripheral blood mononuclear cells (PBMCs) of CLL patients. To evaluate the expression of anti-apoptotic proteins and ROR1 using flow cytometry and western blot, PBMCs were treated with 25 µM of berberine for 24 hr. The expression levels of mir-21 were evaluated by real-time PCR. Examination of treated cells demonstrated that berberine decreased Bcl-2 and ROR1 levels. Although western blot results did not show any change in Bax as a pro-apoptotic protein, an increased Bax/Bcl-2 ratio indicated that mitochondrial pathway is involved in berberine-induced apoptosis of CLL cells. Interestingly, berberine could reduce the expression of miR-21 in comparison to the untreated group. Our findings describe some of the molecular mechanisms of berberine by decreasing Bcl-2, ROR1, and mir-21 which may be considered as a novel apoptosis inducer in CLL cells.

Flow cytometric Immunophenotyping and Hematological Findings at Diagnosis and Relapse of Pediatric Acute Lymphoblastic Leukemia Patients.

BACKGROUND: Acute lymphoblastic leukemia (ALL) is a common pediatric leukemia caused by lymphoid precursor proliferation. We analyzed immunophenotyping and hematological findings, as the risk of relapse, of pediatric ALL patients at diagnosis and relapse. METHODS: Peripheral blood and bone marrow samples of 30 pediatric ALL patients were collected at diagnosis and at relapse. The latter was evaluated for immunophenotyping and cytochemical staining (Periodic Acid Schiff stain (PAS)), while hematological findings were assessed in the former one. RESULTS: The percentage of PAS-positive patients, TdT, and CD4 expression were significantly higher at diagnosis than relapse (p = 0.027, 0.004, and 0.043, respectively), whereas the platelet/lymphocyte ratio (PLR) and neutrophil/lymphocyte ratio were significantly lower at diagnosis (p = 0.004 and 0.032, respectively). There were correla-tions between immunophenotyping and hematology data, including: a) a negative correlation between CD4 expression with blast percentage (r = -0.927, p = 0.003) and hemoglobin level (r = -0.991, p < 0.001) at diagnosis and TdT expression with platelet count (r = -0.441, p = 0.017) at relapse, and b) a positive correlation between CD3 expression with PLR (r = 0.367, p = 0.046) at relapse. CONCLUSIONS: Results suggest that changes in immunophenotyping and hematology findings could be applied as relapse prognostic factors in ALL.