IL-6 as a Biomarker for Therapeutic Resistance in Metastatic HR+, HER2- Breast Cancers

https://openworks.mdanderson.org/sumexp21/1184/thumbnail.jp

Primary Breast Sarcoma: A Retrospective Single Institution Study of Clinicopathologic Features, Treatment and Prognosis

https://openworks.mdanderson.org/sumexp22/1030/thumbnail.jp

Estimation of Carbon Sequestration by Combining Remote Sensing and Net Ecosystem Exchange Data for Northern Mixed-Grass Prairie and Sagebrush–Steppe Ecosystems

Carbon sequestration was estimated a northern mixed-grass prairie site and a sagebrush–steppe site in southeastern Wyoming using an approach that integrates remote sensing, CO2 flux measurements, and meteorological data. Net ecosystem exchange (NEE) of CO2 was measured using aircraft and ground flux techniques and was linearly related to absorbed photosynthetically active radiation (APAR). The slope of this relationship is the radiation use efficiency (ε = 0.51 g C/MJ APAR); there were no significant differences in the regression coefficients between the two sites. Furthermore, ecosystem chamber measurements of total respiration in 1998 and 1999 were used to develop a functional relationship with daily average temperature; the Q10 of the relationship was 2.2. Using the Advanced Very High Resolution radiometer. Normalized Difference Vegetation Index and meteorological data, annual gross primary production and respiration were calculated from 1995 to 1999 for the two sites. Overall, the sagebrush– steppe site was a net carbon sink, whereas the northern mixed-grass prairie site was in carbon balance. There was no significant relationship between NEE and APAR for a coniferous forest site, indicating this method for scaling up CO2 flux data may be only applicable to rangeland ecosystems. The combination of remote sensing with data from CO2 flux networks can be used to estimate carbon sequestration regionally in rangeland ecosystems

Evaluation of sensitivity to endocrine herapy index (SET2,3) for response to neoadjuvant endocrine therapy and longer-term breast cancer patient outcomes (Alliance Z1031)

PURPOSE: To evaluate prediction of response and event-free survival (EFS) following neoadjuvant endocrine therapy by SET2,3 index of nonproliferation gene expression related to estrogen and progesterone receptors adjusted for baseline prognosis. EXPERIMENTAL DESIGN: A correlative study was conducted of SET2,3 measured from gene expression profiles of diagnostic tumor (Agilent microarrays) in 379 women with cStage II-III breast cancer from the American College of Surgeons Oncology Group Z1031 neoadjuvant aromatase inhibitor trial SET2,3 was dichotomized using the previously published cutoff. Fisher exact test was used to assess the association between SET2,3 and low proliferation at week 2-4 [Ki67 ≤ 10% or complete cell-cycle arrest (CCCA; Ki67 ≤ 2.7%)] and PEPI-0 rate in cohort B, and the association between SET2,3 and ypStage 0/I in all patients. Cox models were used to assess EFS with respect to SET2,3 excluding cohort B patients who switched to chemotherapy. RESULTS: Patients with high SET2,3 had higher rate of pharmacodynamic response than patients with low SET2,3 (Ki67 ≤ 10% in 88.2% vs. 56.9%, P \u3c 0.0001; CCCA in 50.0% vs. 26.2%, P = 0.0054), but rate of ypStage 0/I (24.0% vs. 20.4%, P = 0.4580) or PEPI = 0 (28.4% vs. 20.6%, P = 0.3419) was not different. Patients with high SET2,3 had longer EFS than patients with low SET2,3 (HR, 0.52, 95% confidence interval: 0.34-0.80; P = 0.0026). CONCLUSIONS: This exploratory analysis of Z1031 data demonstrated a higher rate of pharmacodynamic suppression of proliferation and longer EFS in high SET2,3 disease relative to low SET2,3 disease. The ypStage 0/I rate and PEPI = 0 rate were similar with respect to SET2,3

Successes, challenges and lessons learned: Community-engaged research with South Carolina's Gullah population

Engaging communities is highly recommended in the conduct of health research among vulnerable populations. The strength of community-engaged research is well documented and is recognised as a useful approach for eliminating health disparities and improving health equity. In this article, five interdisciplinary teams from the Medical University of South Carolina present their involvement with community-engaged research with a unique population of Gullah African Americans residing in rural South Carolina. Their work has been integrated with the nine established principles of community-engaged research: establishing clear goals, becoming knowledgeable about the community, establishing relationships, developing community self-determination, partnering with the community, maintaining respect, mobilising community assets, releasing control, and maintaining community collaboration. In partnership with a Citizen Advisory Committee, developed at the inception of the first community-engaged research project, the academic researchers have been able to build on relationships and trust with this population to sustain partnerships and to meet major research objectives over a 20-year period. Challenges observed include structural inequality, organisational and cultural issues, and lack of resources for building sustainable research infrastructure. Lessons learned during this process include the necessity for clearly articulated and shared goals, knowledge about the community culture, and embedding the cultural context within research approaches. Keywords: Engaged health research, vulnerable populations, longterm collaboration, South Carolina 'Gullah' communitie

LMW-E/CDK2 Deregulates Acinar Morphogenesis, Induces Tumorigenesis, and Associates with the Activated b-Raf-ERK1/2-mTOR Pathway in Breast Cancer Patients

Elastase-mediated cleavage of cyclin E generates low molecular weight cyclin E (LMW-E) isoforms exhibiting enhanced CDK2–associated kinase activity and resistance to inhibition by CDK inhibitors p21 and p27. Approximately 27% of breast cancers express high LMW-E protein levels, which significantly correlates with poor survival. The objective of this study was to identify the signaling pathway(s) deregulated by LMW-E expression in breast cancer patients and to identify pharmaceutical agents to effectively target this pathway. Ectopic LMW-E expression in nontumorigenic human mammary epithelial cells (hMECs) was sufficient to generate xenografts with greater tumorigenic potential than full-length cyclin E, and the tumorigenicity was augmented by in vivo passaging. However, cyclin E mutants unable to interact with CDK2 protected hMECs from tumor development. When hMECs were cultured on Matrigel, LMW-E mediated aberrant acinar morphogenesis, including enlargement of acinar structures and formation of multi-acinar complexes, as denoted by reduced BIM and elevated Ki67 expression. Similarly, inducible expression of LMW-E in transgenic mice generated hyper-proliferative terminal end buds resulting in enhanced mammary tumor development. Reverse-phase protein array assay of 276 breast tumor patient samples and cells cultured on monolayer and in three-dimensional Matrigel demonstrated that, in terms of protein expression profile, hMECs cultured in Matrigel more closely resembled patient tissues than did cells cultured on monolayer. Additionally, the b-Raf-ERK1/2-mTOR pathway was activated in LMW-E–expressing patient samples, and activation of this pathway was associated with poor disease-specific survival. Combination treatment using roscovitine (CDK inhibitor) plus either rapamycin (mTOR inhibitor) or sorafenib (a pan kinase inhibitor targeting b-Raf) effectively prevented aberrant acinar formation in LMW-E–expressing cells by inducing G1/S cell cycle arrest. LMW-E requires CDK2–associated kinase activity to induce mammary tumor formation by disrupting acinar development. The b-Raf-ERK1/2-mTOR signaling pathway is aberrantly activated in breast cancer and can be suppressed by combination treatment with roscovitine plus either rapamycin or sorafenib

Patterns of Local-Regional Management Following Neoadjuvant Chemotherapy in Breast Cancer: Results From ACOSOG Z1071 (Alliance)

AXXXXX ZXXXX was a prospective trial evaluating the false negative rate of sentinel node (SLN) surgery after neoadjuvant chemotherapy (NAC) in breast cancer patients with initial node-positive disease. Radiation therapy (RT) decisions were at the discretion of treating physicians, providing an opportunity to evaluate variability in practice patterns following NAC