Berberine and palmatine inhibit the growth of human rhabdomyosarcoma cells.

A natural isoquinoline alkaloid, berberine, has been known to exhibit anti-tumor activity in various cancer cells via inducing cell cycle arrest. However, it has not been investigated whether berberine and its analogs inhibit the growth of rhabdomyosarcoma (RMS), which is the most frequent soft tissue tumor in children. The present study examined the anti-tumor effects of berberine and palmatine on expansions of three human embryonal RMS cell lines; ERMS1, KYM1, and RD. Intracellular incorporation of berberine was relatively higher than that of palmatine in every RMS cell line. Berberine significantly inhibited the cell cycle of all RMS cells at G1 phase. On the other hand, palmatine only suppressed the growth of RD cells. Both of berberine and palmatine strongly inhibited the growth of tumorsphere of RD cells in three-dimensional culture. These results indicate that berberine derivatives have the potential of anti-tumor drugs for RMS therapy.Abbreviations: ARMS: alveolar rhabdomyosarcoma; ERMS: embryonal rhabdomyosarcoma; RMS: rhabdomyosarcoma.

In vitro assessment of novel transcription inhibitors and topoisomerase poisons in rhabdomyosarcoma cell lines.

PURPOSE: Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children. Current chemotherapy regimes include the topoisomerase II poison etoposide and the transcription inhibitor actinomycin D. Poor clinical response necessitate identification of new agents to improve patient outcomes. METHODS: We assessed the in vitro cytotoxicity (MTT assay) of DNA intercalating agents in five established human RMS cell lines. These include novel classes of transcription inhibitors and topoisomerase poisons, previously shown to have potential as anti-cancer agents. RESULTS: Amongst the former agents, bisintercalating bis(9-aminoacridine-4-carboxamides) linked through the 9-position, and bis(phenazine-1-carboxamides) linked via their side chains, are compared with established transcription inhibitors. Amongst the latter, monofunctional acridine-4-carboxamides related to N-[2-(dimethylamino)ethyl]acridine-4-carboxamide, DACA, are compared with established topoisomerase poisons. CONCLUSIONS: Our findings specifically highlight the topoisomerase poison 9-amino-DACA, its 5-methylsulphone derivative, AS-DACA, and the bis(phenazine-1-carboxamide) transcription inhibitor MLN944/XR5944, currently in phase I trial, as candidates for further research into new agents for the treatment of RMS.

Alternative prognostic factors in pediatric embryonal rhabdomyosarcoma: Nm23 expression, proliferative activity and angiogenesis.

Possible clinical relevance of Nm23 expression, angiogenesis and proliferative activity were evaluated as prognostic parameters in childhood embryonal rhabdomyosarcoma (RMS). Specimens of 25 RMS cases were studied for Nm23 antigen immunohistochemically. Vascular surface density (VSD) and number of vessels per stroma (NVES) calculated by stereologic methods on labeling sections with CD34 antibody. For evaluation of proliferative activity of tumors, mitotic figures and Ki67 positive cells were investigated. All findings were searched statistically. Five patients were stage 1 (20%), two were stage 2 (8%), 15 were stage 3 (60%) and three were stage 4 (12%). The mean event free survival (EFS) was 20.8 and the mean overall survival (OS) was 25.9 months. Sixteen patients (64%) were alive and without disease. The percentage of Nm23 positivity was 52%. Log rank analysis showed Nm23 as a predictor for survival (p=0.0313). In Pearson correlation analysis, there was statistical significance between OS and presence of Nm23 expression (p=0.044). VSD was also positively related with EFS (p=0.040). Despite the present parameters in use, there is a need for new prognostic markers, especially to predict the outcome of patients. These findings suggested that Nm23 expression and VSD might be useful for follow-up in RMS.

[Embryonic rhabdomyosarcoma of the prostate. Report of a case and review of the literature]. / Rabdomiosarcoma embrionario de próstata. Aportación de un caso y revisión de la literatura.

OBJECTIVES: To report a new case of prostatic rhabdomyosarcoma in a child. METHODS: Blood analysis, urinalysis, radiologic tests (abdominal ultrasound, intravenous urography, cystography, barium enema, lower extremities X-rays), and prostatic biopsy were performed. RESULTS/CONCLUSIONS: Neoadjuvant treatment with chemotherapy and radiotherapy were started prior to intended radical prostatectomy, but the patient died before due to disease progression with dissemination.