Thoughts on Social Media in Hematology-Oncology

Background: Triple-Negative Breast Cancers (TNBC) overexpress a large number of genes compared to other breast cancer subtypes and these genes represent potential therapeutic targets.

Methods: We identified genes overexpressed in TNBC compared in public gene expression data sets and performed an siRNA screen with 4 distinct constructs against each of 681 overexpressed genes in 18 breast cancer cell lines. The top tier hits were assessed in functional and mechanistic studies to validate their role in the growth and survival of TNBC cells in vitro and in vivo.

Results: Low density Lipoprotein Receptor-Related Protein 8 (LRP8) and Very Low-Density Lipoprotein Receptor (VLDLR) was the top two ranked hits based on 3 of 4 siRNAs showing, significant and preferential growth inhibition in TNBC cell lines. Apolipoprotein E isoform 4 (ApoE4), and to a lesser extent rellin, which are ligands of both LRP8 and VLDLR stimulated the growth of TNBC cells in vitro in a receptor-dependent manner. Suppression of LRP8 or VLDLR expression or exposure to a ligand inhibitor, RAP abolished this ligandinduced proliferation. Metabolic profiling (with GC/MS and LC/MSMS) and reverse phase protein arrays (n=230 antibodies/201 proteins) revealed that ApoE4 stimulation rescued TNBC cells from serum-starvation, induced up-regulation of genes involved in lipid biosynthesis and increased protein expression of genes involved in the MAPK/ERK and DNA repair pathways.

Conclusion: LRP8 is overexpressed in TNBC and promotes cell growth and survival under nutrient depleted conditions through stimulating lipid biosynthetic pathways. Inhibitors of LRP8/VLDLR signaling represent potential new therapeutic targets for TNBC.

Warfarin, the vitamin K antagonist, was the only one oral anticoagulant available over the last six decades for clinical use. Recently, though there has been an introduction of Newer Oral Anti Coagulants (NOACs) such as dabigatron, rivaraxoban, apixaban and edoxaban. These NOACs have changed the landscape for prophylaxis and treatment of Venous Thrombo Embolism (VTE) and non valvular atrial fibrillation

Glycogen Synthase Kinase-3β (GSK-3β) is a key component of a complex array of cellular processes. Several mechanisms are involved in controlling its activity, including phosphorylation, protein complex formation and sub cellular distribution. Aberrant GSK-3β action has been implicated in many diseases and disorders, such as cancer, heart disease, metabolic and neurological disorders. More recently, GSK-3β has been identified as a crucial regulator of the balance between pro and anti-inflammatory cytokine production. This review will highlight the immunological importance of GSK-3β and the latest discoveries that led to the identification of a new central role of GSK-3β in tumor immunity.

Background: Helicobacter pylori is endemic in Egypt and present a main cause of gastrointestinal bleeding.

Aim: this study is to evaluate the prevalence of H.pylori infection in hemophilic patients, and to assess its impact on gastrointestinal bleeding associated with this infection in such patients.

Methods: we prospectively investigated the prevalence of H.pylori infection in 40 Egyptian patients with Hemophilia -A, -B and VonWillebrand syndrome and 20 normal male subjects was included. Every patient and control subject in the study was tested one time for H.pylori stool antigen by ELISA. All patients and control subjects were tested for occult blood using Guaiac-based fecal occult blood test. Results: Twenty eight out of 40 patients (70%) are H. pylori positive; and 12 out of 20 controls (60%) are H. pylori positive. The odds ratio is ‎1.55, 95% CI (0.6162 to 3.9269), ‎Significance level P=0.3497. Among 28 H.pylori positive patients, 5 patients (17.9 %) tested positive for occult blood. Among the 12 H.pylori positive subjects ‎ in the‎ control group, only one tested positive for occult blood (8.3%). Odds ratio for Occult bleeding in H pylori positive patients and control was 2.39: P=0.4504. None of the H.pylori negative patients or control subjects had a positive occult blood disease. Conclusion: patients with hemophilia, H. pylori should not be considered as an important cause of GI bleeding. The recurrence of the infection and GI bleeding could be prevented with eradication of H.pylori. Screening tests for H. pylori would not be needed in patients with hemophilia in endemic areas.

Background: Many parameters are included to determine the risk stratification of Acute Lymphoblastic Leukemia (ALL), Philadelphia Chromosome (Ph)/BCR-ABL–positive (ALL) is the largest genetically defined subtype in adult ALL with poor outcome. Here, we detected IL-2Rα (CD25) in patients with ALL and explored its diagnostic and prognostic value.

Patients and methods : Thirty ALL patients were recruited in Egypt , newly diagnosed with ages above 18 years old, after informed consent they invited to perform CD25 marker using Coulter EPICSXL, PCR for BCR – ABL fusion gene and Fluorescence in Situ Hybridization (FISH) were also performed along with CBC, LDH, Uric acid, CT scan allover and testicular ultrasonography.

Results: (70%) of patients were males while (30%) were females with no statistically significant difference as correlated with CD25, 13 (43. 33%) patients had positive CD25 , recurrent infections had occurred in 8 patients (26. 67%) with no significant correlation with CD25 (P = 0. 361), 16(53. 33%) patients suffered from fever, while 5 (16. 67%) experienced bleeding with no significant correlation among them with CD 25 (P> 0.05 in both). FISH cytology and PCR were positive in 11 (36.67%) patients. There was highly statistically significant correlation among CD25 and FISH and PCR for BCR-ABL, LDH, total leucocytic count with (P value <0.001). We showed that CD25 measurements compare favorably with other ALL prognostic criteria.

Conclusion: (CD25) expression was corresponding to Philadelphia chromosome. IL-2R α (CD25) is proved to be a valuable marker for monitoring ALL patients, an important parameter for prognosis and follow-up of ALL patients

Hemophagocytic Lymphohistiocytosis (HLH) is a rare and life threatening syndrome caused by excessive and dis-regulated immune activation. It can present as a primary sporadic disorder or be secondary to a trigger disrupting the immune homeostasis, such as auto-immune disorders, malignancies and mainly infections. It is usually of low suspicion index, and has variable presentations lacking specific pathognomonic clinical or laboratory signs. HLH is a medical emergency, and is associated with poor prognosis in most of the cases. An early diagnosis and initiation of appropriate treatment may change the outcome. Here I present a review of the literature concerning HLH, and one related pathologically similar disorder, the Macrophage Activation Syndrome (MAS), emphasizing on the clinical presentation, associated etiologies, diagnosis, treatment and prognosis, thus making the clinicians more aware of this fatal syndrome in order to decrease the related mortality.

Osteosarcoma more frequently occurs in children and adolescents, at the position of knee-joint and proximal humerus.

Background: Multiple myeloma (MM) is characterized by clonal expansion of plasma cell in the bone marrow and production of monoclonal immunoglobulin, with bone destruction, renal failure and suppression of the normal hematopoiesis. Identification of clinical factors and laboratory diagnosis is important to characterize the stage of the disease and estimate survival.

Objective: To identify clinical and laboratory diagnosis of patients with multiple myeloma treated at HEMOPE - Foundation of Hematology and Hematology of Pernambuco.

Methods: This was an observational, transversal study with secondary data obtained from medical records. A descriptive analysis of clinical and laboratory features and prognostic factors of 112 patients diagnosed with multiple myeloma was conducted from January 2010 to December 2014.

Results: The median age was 65 years, of these 49.1% were male and 50.9% female. The most common clinical manifestations were: bone pain (70.5%), weight loss (25%) and weakness (23.2%). Anemia has been observed at diagnosis in 75% of patients and hypercalcemia in 15.2%. Regarding the staging system at diagnosis, 94 (83.9%) patients were classified as stage III Durie-Salmon and 32 (28.6%) patients in stage II of the International Staging System (ISS).

Conclusion: Our found in this study were similar to previous reported in the literature. A good characterization of the patient’s diagnosis and the use of accurate diagnostic methods are the ideal approach for better risk classification, therapeutic choice and follow-up of patients with MM.

Cauda Equina Syndrome (CES) is a rare complication of Multiple Myeloma (MM) that is a clonal plasma cell disorders. We presented a case who newly diagnosed MM which complicated with cauda equina involvement. A 51-year-old woman admitted to our hospital because of weakness and low back pain. Neurological examination demonstrated sphincter dysfunction, decreased Achilles tendon reflexes, frust hemiparesia, reflected CES. Laboratory analysis was revealed anemia, hipergammaglobulinemia and monoclonal peak in the protein electrophoresis. Magnetic resonance imaging (MRI) of the spine showed multiple vertebral compression fractures and marked contrast enhancement of the cauda equina region. The patient was diagnosed MM with bone marrow biopsy. After VAD treatment, MRI showed disappearance of infiltration. Although, there are some case reports with cauda equina involvement in myeloma patient, we could not find any case presenting with CES in newly diagnosed MM. This rare complication should be remembered in myeloma patients who presented symptoms of CES.

Autologous Stem Cell Transplantation (ASCT) is the preferred treatment for the management of multiple myeloma after initial 4-6 months of induction treatment.