The two standard treatment options in children with craniopharyngioma are primary surgery and sub-total resection followed by radiotherapy. In certain subgroups of patients such as those with large tumors and hypothalamic extension, primary surgery is associated with a high incidence of complications and high failure rates. We recommend utilization of an individualized risk-based treatment approach, that attempts to maximize cure rates without compromising long-term functional outcome in children with craniopharyngiomas.
BACKGROUNDThe treatment options of breast conservation therapy (BCT) and immediate reconstruction for patients with carcinoma of the breast have not been adopted widely. The objectives of this study were to determine how often a second opinion on the local therapy of breast carcinoma changed patient management and to identify factors predictive of remaining at the second‐opinion site for therapy.METHODSTwo hundred thirty‐one patients with intraductal carcinoma or Stage I and II breast carcinoma were reviewed retrospectively. At the time of the second opinion, patients completed a questionnaire regarding their initial surgical opinion and the reason for seeking consultation.RESULTSOnly 46% of patients had a complete discussion of treatment options prior to the second opinion. The second opinion changed management in 54 patients (20.3%). The most common finding was eligibility for BCT in patients who were offered only mastectomy. Definitive local therapy occurred at the second‐opinion site in 65.8% of patients. The only predictors of remaining at the second‐opinion site were insurance type (P = 0.008) and the patient's perception that options were not discussed at the initial opinion (P < 0.001).CONCLUSIONSSecond opinions provide useful information to patients and may change the management of their disease. They result in significant patient capture for an institution. Cancer 2002;94:889–94. © 2002 American Cancer Society.DOI 10.1002/cncr.10318
BACKGROUND In the absence of medical contraindications, survival after undergoing breast‐conserving therapy (BCT), mastectomy (M), and mastectomy with immediate reconstruction (MIR) is equal. The authors studied demographic factors to identify the variables that differed significantly among women making different surgical choices. METHODS Women with ductal carcinoma in situ or clinical Stage I or II breast carcinoma with no contraindications for BCT or MIR who were treated between 1995 and 1998 were identified from a prospectively collected data base. Demographic and tumor factors were compared using the Fisher exact test. RESULTS There were 578 women with 586 tumors who did not have contraindications for BCT or MIR. Among this group, 85.2% of women chose BCT, 9.2% of women chose M, and 5.6% of women chose MIR. Women undergoing M alone were older and were more likely to have Stage II carcinoma compared with women undergoing BCT. Patients undergoing M or MIR were more likely to have had a prior breast biopsy compared with patients who chose BCT. Marital status and employment approached significance (P = 0.06); however, a family history of breast carcinoma was not a predictor of treatment choice. CONCLUSIONS The current findings suggest a need for patient education strategies that emphasize the lack of influence of age and prior breast biopsy on the use of BCT. Differences in demographic variables may reflect true variations in patient preference among groups, emphasizing the need to address the spectrum of treatment options with patients. Cancer 2002;95:1185–90. © 2002 American Cancer Society. DOI 10.1002/cncr.10824
Introduction. We report the construction of a homology model of the human E2F1-DP1 transcription factor complex with DNA to be used as a tool for design of drugs targeted to the promoter of this oncogene based on interference of transcription factor binding. Using shape-based docking and force field calculations, we investigate the development of novel penetratin-based (PED) peptides, obtained by phage display, (E2F1 mimics) as potential binders to the major groove of GC-rich regions of DNA. Computational Procedures. The homology model of E2F1-DP1 complex with DNA was built using the Modeller (9v5) program. We used the DNA binding domains of the E2F1 and DP1 sequences (NCBI accession #'s AAC50719 and NP009042 respectively), and the x-ray crystal structure of the E2F4-DP2 complex with DNA (1CF7.pdb) as the primary template. The DNA from the crystal structure was modeled in place using the default spatial constraints in Modeller. The PED based peptide models were built using the x-ray crystal structure of the antennapedia homeodomain-DNA complex (9ANT.pdb) as a template. The alignment is shown below (The penetratin portion is shown in bold and the variable portion is in italics.). _aln.pos 10 20 30 40 50 60 9antA RQTYTRYQTLELEKEFHFNRYLTRRRRIEIAHALSLTERQIKIWFQNRRMKWKK—–EN brt1 ————————————–RQIKIWFQNRRMKWKKHHHRLSH _consrvd **************** The PatchDock program was used to dock the peptides to the DNA structure from 1CF7.pdb based on shape complementarity. The best shape scoring major-groove binding orientation was selected and refined via energy minimization using the Amber ff99SB force field. Interaction energy scores were computed from the non-bonded energy terms of the Amber force field (Eint = ∑ Evdw + ∑ Eelec). Data Summary. The HHHRLSH sequence is predicted to form a more stable complex compared to the GGGALSA sequence. The PED-HHHRLSH peptide was shown to have potent activity against several cancer cell lines (Xie, et al. AACR 2009). In the case of the HHHRLSH sequence, the model predicts enhanced stability in going from L-Arg (−646.0 kcal/mol) to D-Arg (−688.0 kcal/mol). Conclusions. The α3 helix of E2F1 composed of KRRIYDITNVLEGI binds to the major groove of GC-rich DNA. The PED-HHHRLSH peptide complex with DNA (−646.0 kcal/mol) has similar interaction energy to that of the E2F1-DNA complex (−653.0 kcal/mol), is a stable α-helical structure, and is a potential E2F1 mimic. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2673.
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