Raya Saab

Comparing children and adults with synovial sarcoma in the surveillance, epidemiology, and end results program, 1983 to 2005: An analysis of 1268 patients

Synovial sarcoma (SS) is a typical soft tissue sarcoma subtype crosswise between the pediatric and the adult age groups. Less satisfactory overall outcome has been recorded in adult series.

Pharmacologic inhibition of cyclin-dependent kinase 4/6 activity arrests proliferation in myoblasts and rhabdomyosarcoma-derived cells

Myoblast cell cycle exit and differentiation are mediated in part by down-regulation of cyclin D1 and associated cyclin-dependent kinase (Cdk) activity. Because rhabdomyosarcoma may represent a malignant tumor composed of myoblast-like cells failing to exit the cell cycle and differentiate, we considered whether excess Cdk activity might contribute to this biology. Cyclin D–dependent Cdk4 and Cdk6 were expressed in most of a panel of six human rhabdomyosarcoma-derived cell lines. Cdk4 was expressed in 73% of alveolar and embryonal rhabdomyosarcoma tumors evaluated using a human tissue microarray. When challenged to differentiate by mitogen deprivation in vitro, mouse C2C12 myoblasts arrested in G1 phase of the cell cycle, whereas four in the panel of rhabdomyosarcoma cell lines failed to do so. C2C12 myoblasts maintained in mitogen-rich media and exposed to a Cdk4/Cdk6 inhibitor PD 0332991 accumulated in G1 cell cycle phase. Similar treatment of rhabdomyosarcoma cell lines caused G1 arrest and prevented cell accumulation in vitro, and it delayed growth of rhabdomyosarcoma xenografts in vivo. Consistent with a role for Cdk4/Cdk6 activity as a regulator of myogenic differentiation, we observed that PD 0332991 exposure promoted morphologic changes and enhanced the expression of muscle-specific proteins in cultured myoblasts and in the Rh30 cell line. Our findings support the concept that pharmacologic inhibition of Cdk4/Cdk6 may represent a useful therapeutic strategy to control cell proliferation and possibly promote myogenic differentiation in rhabdomyosarcoma. [Mol Cancer Ther 2006;5(5):1299–308]

Efficacy of intravenous immunoglobulin in Landau-Kleffner syndrome.

We administered 2 gm/kg of intravenous gamma globulin (IVIG) to each of five consecutive patients with Landau-Kleffner syndrome, over 4 days. We compared the 1-month baseline to that following IVIG using a severity score assessing speech, comprehension, behavior, seizures, and electroencephalography. There was a significant drop in this score after IVIG (P = 0.025). Two patients had a dramatic response to IVIG, with complete resolution of symptoms. This finding suggests that IVIG has at least some efficacy for the therapy of Landau-Kleffner syndrome.

Successful use of intravenous immunoglobulin as initial monotherapy in Landau-Kleffner syndrome.

Summary: Purpose: There is a need for new and more effective therapies for Landau‐Kleffner syndrome. In this article we present the first case in which a patient with Landau‐Kleffner syndrome was given intravenous immunoglobulin (IVIG) as his first and only therapy and responded to it.

Myogenesis and Rhabdomyosarcoma: The Jekyll and Hyde of Skeletal Muscle

Rhabdomyosarcoma, a neoplasm composed of skeletal myoblast-like cells, represents the most common soft tissue sarcoma in children. The application of intensive chemotherapeutics and refined surgical and radiation therapy approaches have improved survival for children with localized disease over the past 3 decades; however, these approaches have not improved the dismal outcome for children with metastatic and recurrent rhabdomyosarcoma. Elegant studies have defined the molecular mechanisms driving skeletal muscle lineage commitment and differentiation, and the machinery that couples differentiation with irreversible cell proliferation arrest. Further, detailed molecular analyses indicate that rhabdomyosarcoma cells have lost the capacity to fully differentiate when challenged to do so in experimental models. We review the intersection of normal skeletal muscle developmental biology and the molecular genetic defects in rhabdomyosarcoma with the underlying premise that understanding how the differentiation process has gone awry will lead to new treatment strategies aimed at promoting myogenic differentiation and concomitant cell cycle arrest.

Seven‐year experience of using Repiphysis® expandable prosthesis in children with bone tumors

Results of the use of the non‐invasive expandable endoprosthetic device Repiphysis® in limb salvage surgery for skeletally immature children with bone cancer have been promising.

Myogenesis and Rhabdomyosarcoma

Rhabdomyosarcoma, a neoplasm composed of skeletal myoblast-like cells, represents the most common soft tissue sarcoma in children. The application of intensive chemotherapeutics and refined surgical and radiation therapy approaches have improved survival for children with localized disease over the past 3 decades; however, these approaches have not improved the dismal outcome for children with metastatic and recurrent rhabdomyosarcoma. Elegant studies have defined the molecular mechanisms driving skeletal muscle lineage commitment and differentiation, and the machinery that couples differentiation with irreversible cell proliferation arrest. Further, detailed molecular analyses indicate that rhabdomyosarcoma cells have lost the capacity to fully differentiate when challenged to do so in experimental models. We review the intersection of normal skeletal muscle developmental biology and the molecular genetic defects in rhabdomyosarcoma with the underlying premise that understanding how the differentiation process has gone awry will lead to new treatment strategies aimed at promoting myogenic differentiation and concomitant cell cycle arrest.

Epidemiology and management options for colorectal cancer in children.

Colorectal carcinoma (CRC), although primarily a disease of adulthood, accounts for 2% of malignancies in adolescents and has been reported in children as young as 9 months of age. Our knowledge of CRC in pediatrics is based on a handful of case series and case reports. Apart from one small clinical trial, there has been a lack of prospective clinical studies in this age group. Based on these published reports, most CRC in children is sporadic, but it can also arise in the setting of predisposing conditions, such as gastrointestinal polyposis syndromes, nonpolyposis familial cancer syndromes, and inflammatory bowel disease. Despite some similarities to adult disease, CRC in childhood may be intrinsically different biologically, because it differs from adult-onset CRC in several respects. Childhood CRC tends to be diagnosed at an advanced stage, is largely of mucinous histology, and (probably because of these features) tends to have a poorer outcome. As a result of its rarity in children and the lack of prospective pediatric studies, recommendations for therapy are primarily extrapolated from adult clinical trials. A review of pediatric case series in the English literature emphasizes the prognostic significance of stage of disease, as well as extent of surgical resection. As in adults, early detection is critical in an effort to capture the disease at less advanced stages. Complete surgical resection with aggressive lymph node dissection is essential for cure, and neoadjuvant chemotherapy may be used in an effort to render unresectable lesions resectable. Active agents in adults with CRC include fluorouracil, folinic acid (leucovorin), oxaliplatin, and irinotecan. Furthermore, newer targeted therapeutic agents, such as bevacizumab and cetuximab, have added additional efficacy to the standard chemotherapy backbone. Collaborative multi-institutional pediatric clinical trials are needed to evaluate the prognosis, optimal treatment response, and the basic biology of childhood onset CRC.

Senescence and pre-malignancy: how do tumors progress?

Cellular senescence is a tumor suppressor response that has been observed both in vitro and in vivo, and features of senescence have been documented in various human premalignant lesions, including melanoma, colon and lung adenoma, prostatic intraepithelial neoplasia, and others. The fact that a subset of these lesions eventually progress to malignant invasive tumors suggests that premalignant cells can either bypass or escape the senescent response. Much work has been done to understand the mechanisms underlying such progression, but it remains unclear whether tumors progress by evasion of senescence induction, or by disruption of senescence maintenance, or whether both mechanisms can occur in human cancer development. This review presents the current evidence for mechanisms of senescence evasion and reversion, and discusses what has been learnt about this process using in vitro and in vivo experimental systems. As we learn more about the key signaling effectors of senescence, the hope is that appropriate targets will be identified for preservation and/or re-induction of senescence in human tumors. Such knowledge may also find application in better estimation of risks of cancer progression in individual premalignant lesions, which will lead to more accurate allocation of appropriate treatment options for such patients.

Bereaved Parental Evaluation of the Quality of a Palliative Care Program in Lebanon

Palliative care (PC) is important in Pediatric Oncology as more than 20% of children with cancer still die despite modern treatment. As a significant number of children reside in countries with limited resources; more research in PC is needed there. This study aimed at evaluating the quality of care provided to children with cancer at the Childrens Cancer Center of Lebanon (CCCL) during their last month of life as perceived by the bereaved parents.