Epidemiological Characteristics and Survival Studies of Rhabdomyosarcoma in East Egypt: A Five-Year Multicenter Study

Background. Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children, it represents 5–8% of childhood malignancies. Aim of the Work. To evaluate the epidemiological characteristics and treatment outcome in two pediatric oncology centers. Patients and Method. A retrospective analysis was performed on 41 medical records of children with RMS during 6 years period. Results. The median age of patients was 6 years with 80.4% below 10 years. Head and neck was the most common primary site. Embryonal RMS was the most frequent histopathologic subtype. Stage IV was the most frequent stage. According to IRS postsurgical grouping classification, group 4 was the most frequent group. There was a significant relationship between histopathologic subtypes of tumor and metastasis, primary site of tumor and histopathologic subtype, age, metastasis, IRS presurgical stage and IRS postsurgical group and outcome. The overall survival rate was 56.9% ± 8.4 and the failure free survival rate was 68.3% ± 7.6. Conclusion. The epidemiological characteristics of our patients are quite near to the worldwide data, apart from the higher prevalence of stage IV and group 4 with most of the primary tumor site in the extremities. CWS2002 protocol of therapy had led to improvement in the curability of the disease

Biologic Complexity in Sickle Cell Disease: Implications for Developing Targeted Therapeutics

Current therapy for sickle cell disease (SCD) is limited to supportive treatment of complications, red blood cell transfusions, hydroxyurea, and stem cell transplantation. Difficulty in the translation of mechanistically based therapies may be the result of a reductionist approach focused on individual pathways, without having demonstrated their relative contribution to SCD complications. Many pathophysiologic processes in SCD are likely to interact simultaneously to contribute to acute vaso-occlusion or chronic vasculopathy. Applying concepts of systems biology and network medicine, models were developed to show relationships between the primary defect of sickle hemoglobin (Hb S) polymerization and the outcomes of acute pain and chronic vasculopathy. Pathophysiologic processes such as inflammation and oxidative stress are downstream by-products of Hb S polymerization, transduced through secondary pathways of hemolysis and vaso-occlusion. Pain, a common clinical trials endpoint, is also complex and may be influenced by factors outside of sickle cell polymerization and vascular occlusion. Future sickle cell research needs to better address the biologic complexity of both sickle cell disease and pain. The relevance of individual pathways to important sickle cell outcomes needs to be demonstrated in vivo before investing in expensive and labor-intensive clinical trials

Increasing reactive oxygen species as a therapeutic approach to treat hereditary leiomyomatosis and renal cell carcinoma

Hereditary leiomyomatosis renal cell carcinoma (HLRCC)-associated renal tumors are aggressive and tend to metastasize early. There are currently no effective forms of therapy for patients with advanced HLRCC-associated kidney cancer. We have previously shown that HLRCC cells express a high level of reactive oxygen species (ROS). In the present study we investigated the cytotoxic-effects of increasing ROS level using bortezomib in combination with cisplatin on HLRCC cells in vitro and in an in vivo xenograft model. The cytotoxic effect of several ROS inducers on FH-deficient cells was assessed by synthetic lethality. ROS inducers had a pronounced impact on the viability of FH-deficient cells. Because of its high potency, the proteasome inhibitor bortezomib was further investigated. Bortezomib induced apoptosis in vitro in HLRCC cells and inhibited HLRCC tumor growth in vivo. Bortezomib-associated cytotoxicity was highly correlated with cellular ROS level: combining bortezomib with other ROS inducers enhanced cytotoxicity, while combining bortezomib with a ROS scavenger inhibited its cytotoxic effect. Finally, HLRCC murine xenografts were treated with bortezomib and cisplatin, another ROS inducer. This regimen induced HLRCC tumor regression in vivo. These findings suggest that increasing ROS level in HLRCC above a certain threshold can induce HLRCC-tumor cell death. Increasing tumor ROS with bortezomib in combination with cisplatin represents a novel targeted therapeutic approach to treat advanced HLRCC-associated renal tumors

Genome-wide association study of follicular lymphoma identifies a risk locus at 6p21.32

To identify susceptibility loci for non-Hodgkin lymphoma (NHL) subtypes, we conducted a three-stage genome-wide association study. We identified two variants associated with follicular lymphoma (FL) in 1,465 FL cases/6,958 controls at 6p21.32 (rs10484561, rs7755224, r(2)=1.0; combined p-values=1.12×10(-29), 2.00×10(-19)), providing further support that MHC genetic variation influences FL susceptibility. Confirmatory evidence of a previously reported association was also found between chronic lymphocytic leukemia/small lymphocytic lymphoma and rs735665 (combined p-value=4.24×10(-9))