ER can be detected in routine tissue sections processed with antigen retrieval and ER1D5, and can be relied upon to provide accurate prognostic information regarding response to endocrine therapies in breast cancer patients.
This paper describes a phantom-based feasibility study for a potential in vivo determination of zinc in prostate, which could bring about improved diagnosis of prostate cancer. An x-ray fluorescence topographic technique was developed, which will permit determination of the Zn content in the prostate through the rectum, namely behind a 2-3 mm thick layer of the rectal wall. The topographic approach, together with a reconstruction method developed here, minimizes the interference of Zn from non-prostatic tissue. The phantom studies show that it will be possible to determine Zn in a prostatic compartment behind a few mm thick layer of tissue using a specially designed transrectal probe. Such a probe is currently under development in our laboratories.
7530 Background: About 40-50% of older patients (pts) with AML attain complete remission (CR) with induction chemotherapy (IC) but relapse is common.Effective, well-tolerated maintenance treatment (Tx) is needed for older pts in remission who are not eligible for hematopoietic stem cell transplant (HSCT). CC-486 is an oral hypomethylating agent that allows for extended dosing schedules ( >7 days [d]/cycle) to sustain therapeutic activity. In the phase III placebo (PBO)-controlled QUAZAR AML-001 trial (NCT01757535), CC-486 maintenance therapy in pts with AML in first remission following IC produced significant improvements in overall and relapse-free survival. Here we report safety and tolerability findings among pt subgroups defined by age at study entry. Methods: Eligible pts were ≥ 55 yrs of age, with de novo or secondary AML, intermediate or poor risk cytogenetics, and ECOG PS ≤ 3; had achieved first CR or CRi after IC ± consolidation; and were not candidates for HSCT. Within 4 mo of CR/CRi, pts were randomized 1:1 to CC-486 300 mg or PBO QD on d 1–14 of repeated 28d Tx cycles. Safety was assessed across 3 age subgroups (≥ 55 to < 65, ≥ 65 to < 75, and ≥ 75 yrs) in pts who received ≥ 1 dose of study drug. Adverse events (AEs) were coded using MedDRA v. 22.0 and graded by NCI-CTCAE v. 4.0. Results: 469 pts ( >99% of all enrolled pts) were evaluable for safety (CC-486 n = 236; PBO n = 233). Median age was 68 yrs (range 55-86). Age distribution was similar between the two Tx arms (Table). Between Tx arms, AE rates within each age stratum were similar to rates in the overall study population. The most common AEs (any grade) with CC-486 were GI events, which were more frequent than in the PBO arm across age groups. Within the CC-486 arm, AE rates were generally consistent across age groups, except for constipation, which was > 20% more frequent in pts aged ≥ 75 yrs, and thrombocytopenia, which was ≥ 20% less frequent in this group (Table). Overall, 13% and 4% of pts in the CC-486 and PBO groups discontinued Tx due to AEs. Conclusions: In QUAZAR AML-001, CC-486 was generally well tolerated in all age groups, including elderly pts aged ≥ 75 yrs. Clinical trial information: NCT01757535 . [Table: see text]
Background Intraductal Papillary Mucinous Neoplasms (IPMNs) are one of the 3 known curable precursor lesions (IPMN, MCN (Mucinous Cystic Neoplasm), and PanIN (Pancreatic Intraepithelial Neoplasm)) of invasive pancreatic ductal adenocarcinoma, an almost uniformly fatal disease. Methods To advance the study of the biological features of IPMNs, we attempted in vivo and in vitro growth of selected IPMNs, based on the hypothesis that IPMNs could be grown in the most severely immunodeficient mice. We examined fourteen cases by implanting them into nude, severe combined immunodeficient (SCID), and NOD/SCID/IL2Rγnull (NOG) mice, in addition to direct culture, to generate tumor xenografts and cell lines. Results Thirteen tumors were implanted into the 3 types of mice, including 10 tumors implanted into the triple immunodeficient NOG mice, where the majority (8 of 10) grew including 5 IPMNs lacking invasive components. One of the explanted IPMNs, with an associated invasive carcinoma, was successfully established as a cell line. Growth in soft agar, growth in mice and homozygous deletion of P16/cdkn2a confirmed its tumorigenicity. The expression of cytokeratin confirmed the epithelial differentiation of the cell line, and DNA fingerprinting confirmed its human origin. Future directions Isolating cell lines from IPMNs and their invasion counterparts should be valuable to identify gene mutations critical to IPMN carcinogenesis, and permit drug screening to identify compounds that cause regression of those lesions. 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 4173.
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