HIGH DOSE ORAL BUSULFAN and INTRAVENOUS MELPHALAN AS CONDITIONING THERAPY for AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANT (HSCT) for the TREATMENT of PEDIATRIC SOLID TUMORS

Universidade Federal de São Paulo, Inst Oncol Pediat, GRAACC, São Paulo, BrazilUniversidade Federal de São Paulo, Inst Oncol Pediat, GRAACC, São Paulo, BrazilWeb of Scienc

Clinical characteristics of small functioning adrenocortical tumors in children

Twenty of 67 children registered on the International Registry of Childhood Adrenocortical Tumors between May 1988 and December 1994 had small adrenocortical tumors (defined for this study as measuring less than or equal to 200 cm(3) and/or weighing less than or equal to 100 g). We reviewed the records of these 20 patients to characterize the clinical and pathologic findings and outcomes of children with small adrenocortical tumors. Median patient age was 2 years (range, 4 months to 5 years). There was only one boy. All had clinical signs of virilization, and seven had signs or symptoms of Cushing syndrome. A median 5.5 months (range, 1-40 months) had elapsed between the first signs of endocrine dysfunction and diagnosis. All tumors were surgically resected. Tumor volume was 3.3-195 cm(3) (median, 38.7 cm(3)), and weight was 3.7-100 g (median, 36 g). Tumor samples were histologically reviewed in 18 cases. Eight were adenomas, and 10 were carcinomas (6 low grade and 4 high grade). Pathology records described tumor with diagnostic features of adrenocortical carcinoma in two patients. One patient received mitotane for 8 months after surgery. Only one patient had recurrent disease, which was detected 6 months after diagnosis and proved rapidly fatal. Another has been lost to follow-up. the remaining 18 patients are alive with no evidence of disease at a median 2.3 years (range, 6 months to 6.1 years) after diagnosis. Our data suggest that children with small adrenocortical tumors have an excellent prognosis with surgery as the sole therapy regardless of tumor histiotype. (C) 1997 Wiley-Liss, Inc.ST JUDE CHILDRENS RES HOSP, DEPT HEMATOL ONCOL, RCR, MEMPHIS, TN 38105 USAST JUDE CHILDRENS RES HOSP, DEPT SURG, MEMPHIS, TN 38105 USAST JUDE CHILDRENS RES HOSP, INT OUTREACH PROGRAM, MEMPHIS, TN 38105 USAUNIV FED PARANA, DEPT PEDIAT, BR-80060000 CURITIBA, PARANA, BRAZILUNIV São Paulo, BR-05508 São Paulo, BRAZILESCOLA PAULISTA MED, São Paulo, BRAZILUNIV TENNESSEE, DEPT PATHOL, MEMPHIS, TN USAUNIV TENNESSEE, DEPT PEDIAT, MEMPHIS, TN USACOLL MED, MEMPHIS, TN USAESCOLA PAULISTA MED, São Paulo, BRAZILWeb of Scienc

Does the less aggressive multimodal approach of treating bladder-prostate rhabdomyosarcoma preserve bladder function?

Purpose: the treatment of bladder-prostate rhabdomyosarcoma has evolved into multimodal therapy, including chemotherapy, radiotherapy and organ sparing surgery with bladder preservation. We investigated bladder function in children who underwent multimodal therapy at our institution and retained the original bladder for at least 6 months after treatment ended.Materials and Methods: We evaluated 8 children with bladder-prostate rhabdomyosarcoma treated at our institution between 1999 and 2003 according to inclusion criteria. All patients underwent history, physical examination and urodynamic study at least 6 months after completion of treatment (range 6 to 39 months).Results: All patients were treated following the same chemotherapy and radiotherapy scheme. Three patients (37.5%) were asymptomatic and had normal urodynamic studies, and 1 had only dysuria (this patient later underwent continent urinary diversion with transverse colon). the 4 remaining patients had urological complaints, and the urodynamic findings were reduced bladder capacity in 4, overactivity plus sensory urgency in 2, sensory urgency only in 1 and suprapubic pain during filling in 1.Conclusions: Among 8 patients 3 had normal urinary function and 4 had minor tolerable alterations. Cystectomy and urinary diversion were later necessary in only 1 patient due to disabling dysuria. the fact that the original functioning bladder was preserved in 7 of 8 patients suggests the feasibility of multimodal therapy. Long-term followup will still be necessary for definite conclusions, since we recognize that the deleterious effects, mainly of radiotherapy, may take longer to become evident.Universidade Federal de São Paulo, Dept Urol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Urol, São Paulo, BrazilWeb of Scienc

Feasability of peripheral blood stem cell (PBSC) collections in children with stage IV neuroblastoma after >= 6 cycles of chemotherapy

UNIFESP, Pediat Oncol Inst, GRAACC, Sao Paulo, BrazilUNIFESP, Pediat Oncol Inst, GRAACC, Sao Paulo, BrazilWeb of Scienc

Calmodulin-Dependent Kinase II Mediates Vascular Smooth Muscle Cell Proliferation and Is Potentiated by Extracellular Signal Regulated Kinase

Vascular smooth muscle cell (VSMC) proliferation contributes to vascular remodeling in atherosclerosis and hypertension. Calcium-dependent signaling through calcium/calmodulin-dependent kinase II (CaMKII) and ERK1/2 activation plays an important role in the regulation of VSMC proliferation by agents such as α-adrenergic receptor agonists. Nevertheless, how the CaMKII and ERK pathways interact in VSMCs has yet to be characterized. The aim of the present study was to clarify this interaction in response to α1-adrenergic receptor-mediated VSMC proliferation. We discovered that phenylephrine stimulation resulted in complex formation between CaMKII and ERK in a manner that facilitated phosphorylation of both protein kinases. To assess the effects of CaMKII/ERK association on VSMC proliferation, we inhibited endogenous CaMKII either pharmacologically or by adenoviral-mediated gene transfer of a kinase-inactive CaMKII mutant. Inhibition of CaMKII activation but not CaMKII autonomous activity significantly decreased formation of the CaMKII/ERK complex. On the contrary, the expression of constitutively active CaMKII enhanced VSMC growth and CaMKII/ERK association. In addressing the mechanism of this effect, we found that CaMKII could not directly phosphorylate ERK but instead enhanced Raf1 activation. By contrast, ERK interaction with CaMKII facilitated CaMKII phosphorylation and promoted its nuclear localization. Our results reveal a critical role for CaMKII in VSMC proliferation and imply that CaMKII facilitates assembly of the Raf/MEK/ERK complex and that ERK enhances CaMKII activation and influences its subcellular localization