Emre Cecen

The time to diagnosis in childhood lymphomas and other solid tumors.

There are few reports from developing countries on the factors that influence the time to diagnosis (TD) in childhood cancer. The purpose of this study was to investigate the determinants of the TD in Turkish cancer patients.

Promoting effects of sanguinarine on apoptotic gene expression in human neuroblastoma cells.

Neuroblastoma is the most common extracranial solid tumor in children. Approximately half of the affected patients are diagnosed with high-risk poor prognosis disease, and novel therapies are needed. Sanguinarine is a benzophenanthridine alkaloid which has anti-microbial, anti-oxidant and anti-inflammatory properties. The aim of this study is whether sanguinarine has in vitro apoptotic effects and which apoptotic genes might be affected in the human neuroblastoma cell lines SH-SY5Y (N-myc negative), Kelly (N-myc positive, ALK positive), and SK- N-BE(2). Cell viability was analysed with WST-1 and apoptotic cell death rates were determined using TUNEL. After RNA isolation and cDNA conversion, expression of 84 custom array genes of apoptosis was determined. Sanguinarine caused cell death in a dose dependent manner in all neuroblastoma cell lines except SK-N-BE(2) with rates of 18% in SH-SY5Y and 21% in Kelly human neuroblastoma cells. Cisplatin caused similar apoptotic cell death rates of 16% in SH-SY5Y and 23% in Kelly cells and sanguinarine-cisplatin combinations caused the same rates (18% and 20%). Sanguinarine treatment did not affect apoptototic gene expression but decreased levels of anti-apoptotic genes NOL3 and BCL2L2 in SH-SY5Y cells. Caspase and TNF related gene expression was affected by the sanguinarine-cisplatin combination in SH-SY5Y cells. The expression of regulation of apoptotic genes were increased with sanguinarine treatment in Kelly cells. From these results, we conclude that sanguinarine is a candidate agent against neuroblastoma.

Atypical teratoid/rhabdoid tumor in an infant conceived by in vitro fertilization

BackgroundAtypical teratoid/rhabdoid tumor (ATsRT) is a rare tumor and extremely aggressive embryonal neoplasm of the central nervous system. Brain tumors in infant are suggestive of some oncogenic prenatal factors.Case presentationWe report on a case of ATRT in a 4-month-old infant conceived by in vitro fertilization (IVF). Some previous reports have raised a question about the possible relation between IVF and childhood cancer, particularly embryonal tumors.ConclusionReport of such cases may provide some evidence to identify if there is a real association between congenital tumors and IVF.

PHYLLODES TUMOR OF THE BREAST IN AN ADOLESCENT GIRL

Phyllodes tumor (PT) is an uncommon tumor in adolescent girls and young women. A case of PT in a 14-year-old girl is reported. The clinical examination showed a painless tumor that had grown during 10 months. Total excision of the mass with wide margin was performed. The diagnosis, behavior, and treatment of this rare tumor are discussed.

VENO-OCCLUSIVE DISEASE IN A CHILD WITH RHABDOMYOSARCOMA AFTER CONVENTIONAL CHEMOTHERAPY: Report of a Case and Review of the Literature

Although veno-occlusive disease of the liver is a well-known complication of high-dose chemotherapy and bone marrow transplantation, it has rarely been observed in children who receive conventional chemotherapy. Most cases in the literature consists of children with Wilms tumor. It has been very uncommon in rabdomyosarcoma patients until recently, although they commonly receive similar anticancer agents. Here the authors report a 2-year-old boy with rhabdomyosarcoma who developed veno-occlusive disease while receiving VAC (vincristine, actinomycin D, cyclophosphamide) chemotherapy regimen according to the IRS-IV protocol. The patient gradually recovered during 2 weeks with supportive treatment only.

Apoptotic Effects of Sanguinarine on the Organ of Corti 1 Cells: Comparison with Cisplatin.

OBJECTIVE Sanguinarine is an alkaloid obtained from the root of Sanguinaria canadensis and other plants from the Papaveraceae family and is well known to possess a broad range of biological functions, such as antimicrobial, antifungal, anti-inflammatory, and antineoplastic activities. We aimed to specify the in vitro effect of sanguinarine on the House Ear Institute-Organ of Corti 1 (HEI-OC1) cells and to compare this effect with the ototoxic effect of cisplatin (CDDP). MATERIALS AND METHODS We performed cell proliferation assay for determining the in vitro effect of sanguinarine alone and compared it with the effect of cisplatin. Flow cytometry annexin-V apoptosis detection was performed. RESULTS We found that sanguinarine and CDDP inhibited the cell growth in a dose-dependant manner in HEI-OC1 cells after 24 h of incubation. In sanguinarine-treated group, apoptosis was 6.6%, necrosis was 26.7%, and the cell viability was 66.7%. Further, in CDDP-treated group, apoptosis was 5.6%, necrosis was 45.4%, and the cell viability was 48.7%. According to the annexin-V apoptosis detection results, we found that sanguinarine caused 3.9% apoptosis and 1.3% necrosis, while CDDP caused 2.9% apoptosis and 20% necrosis on HEI-OC1 cells. CONCLUSION Our findings suggested that lower doses of sanguinarine are promising antineoplastic agents, which did not indicate any toxic effect on HEI-OC1 cells. Application of these data to clinical practice requires further support by in vivo studies.

Pilomatricoma in children: a frequently misdiagnosed superficial tumor.

Pilomatricomas are the most common superficial tumors in children, but they are frequently misdiagnosed preoperatively. There are some characteristic features of pilomatricomas that can help clinicians differentiate it from other tumors. The authors report 3 children with head and neck pilomatricomas, one with multiple tumors. They emphasize some clinical features that may help in differential diagnosis to avoid unnecessary investigations before surgical removal.

Coexisting of Wilms Tumor and Ganglioneuroblastoma in a Child

Synchronous occurrences of multiple primary cancers in children are very rare. Wilms tumor (WT) and peripheral neuroblastic tumors (pNTs) rarely present together. We report here the simultaneous occurrence of WT and ganglioneuroblastoma in a child. A previously healthy a 3-year-old girl was admitted to pediatric nephrology department of our center with a complaint of macroscopic hematuria. She had a large, nontender, firm, left-sided abdominal mass found in an otherwise normal child on physical examination. Magnetic resonance imaging revealed a complex cystic, solid mass measuring 13 × 10 cm in the left kidney and a right homogenous solid adrenal tumor measuring 2.1 cm in largest diameter (Figure 1A, B). Left renal vein and inferior vena cava were free of tumor infiltration. Metastatic work-up including chest x-ray and bone marrow aspiration showed no distant metastatic disease. The urine vanillylmandelic acid, plasma cortisol, and progesterone levels were normal. Wilms tumor, clear cell sarcoma, teratoid tumors, mesoblastic nephroma for renal tumor, peripheral neuroblastic tumors, and adrenal incidentalomas for adrenal mass were considered for differential diagnosis. A radical left nephrectomy with complete excision of the renal mass and complete right adrenalectomy were performed. The left adrenal mass was not removed to preserve adrenal function. The histological diagnosis of the renal mass was stage I WT with favorable histology (Figure 1C). Predominant histological pattern was of blastemal type and no features of anaplasia were evident. Histological examination of the adrenal tumor revealed ganglioneuroblastoma-intermixed (GNB-I) (Figure 1D). Patient received postoperative chemotherapy according to Stage I National WT Protocol (vincristine 1.4 mg/m2 weekly, for 10 weeks, then on the 1st and 5th days, with 6 weeks’ interval, for 3 times; actinomycin D 0.015 mg/kg/day, days 1–5, with 6 weeks’ interval, up to 24 weeks). She has been in complete remission for 3 years. The synchronous occurrence of WT and a pNT has been previously described in an infant with Fanconi anemia [1], a child with Fanconi anemia and VACTERL (abnor-

Stromal-predominant mesenchymal hamartoma of the liver with elevated serum alpha-fetoprotein level.

Mesenchymal hamartoma of the liver (MHL) is an uncommon, benign, tumor-like lesion and is usually diagnosed in the first 2 years of life. Its pathogenesis remains unclear. Treatment of choice is radical excision. The authors report a case of solid stromal predominant MHL in a 12-month-old male infant who also had an elevated serum α-fetoprotein level. He also had hypospadias, which might represent a spectrum of developmental anomalies. It usually presents as an asymptomatic mass, however, as in the reported case, it may cause several complications due to the compression of surrounding structures. He was successfully treated with total excision of the pedunculated large tumor without any complication.

Comparison of Cisplatin with Lipoplatin in Terms of Ototoxicity

OBJECTIVE Cisplatin (CDDP) is an anti-neoplastic agent that has been used in treatments of both pediatric and adult cancers. It has many side effects, such as ototoxicity, nephrotoxicity, and neurotoxicity. Lipoplatin (LIPO) is a nanomolecule with 110 nm diameter and composed of lipids and CDDP. In this study, we aimed to compare the toxic effects of LIPO with CDDP in the cochlear cells with anti-tumoral doses determined in neuroblastoma cells. MATERIALS AND METHODS House Ear Institute Organ Corti 1 (HEI-OC1), MYC-N amplified KELLY, and MYC-N non-amplified SH-SY5Y human neuroblastoma cells were used in this study. Firstly, anti-tumoral lethal dose 50 (LD50) of LIPO and CDDP were determined using the WST-1 assay in both neuroblastoma cells. Then anti-tumoral doses of CDDP and LIPO were applied on HEI-OC1 cells for evaluating the toxic effects. The apoptotic cell death was measured using flow cytometric analysis of annexin-V/7-amino-actinomycin (7-AAD) and cell cycle tests. RESULTS LIPO or CDDP inhibited cell viability in a dose- and time-dependent manner in both neuroblastoma and HEI-OC1 cells. LD50 values were selected as 20 mM for CDDP and 750 mM for LIPO in neuroblastoma cells. After the 48-hour incubation, KELLY cells treated with 20 mM CDDP and 750 mM LIPO had a 53% viability; SH-SY5Y cells treated 20 mM CDDP and 750 mM LIPO had a 45% and 58% viability, respectively; and HEI-OC1 cells treated with 20 mM CDDP and 750 mM LIPO had a 65% and 82% viability, respectively. CONCLUSION LIPO showed less toxic effects in the HEI-OC1 cells compared to CDDP at anti-tumoral doses.