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Open Access Publications from the University of California

About

The Department of Orthopaedic Surgery at UCSF provides expert treatment for all aspects of musculoskeletal injuries including inpatient and outpatient surgical care, rehabilitation, and orthotics and prosthetics. Our physicians have specific training and experience in a broad range of orthopaedic specialties such as sports medicine, trauma, joint replacement, pediatrics, oncology, spine, shoulder and elbow, foot and ankle, and hand. The Department is internationally recognized for its work in patient care, education, and research. Our basic and translational research programs focus on cartilage and disc regeneration, fracture healing, molecular and stem cell biology, bioengineering, and musculoskeletal development.

Department of Orthopaedic Surgery

There are 298 publications in this collection, published between 1980 and 2021.
Open Access Policy Deposits (298)

Subchondral insufficiency fractures of the femoral head: associated imaging findings and predictors of clinical progression.

OBJECTIVES:To characterize the morphology and imaging findings of femoral head subchondral insufficiency fractures (SIF), and to investigate clinical outcomes in relation to imaging findings. METHODS:Fifty-one patients with hip/pelvis magnetic resonance (MR) images and typical SIF characteristics were identified and reviewed by two radiologists. Thirty-five patients had follow-up documentation allowing assessment of clinical outcome. Subgroup comparisons were performed using regression models adjusted for age and body mass index. RESULTS:SIF were frequently associated with cartilage loss (35/47, 74.5 %), effusion (33/42, 78.6 %), synovitis (29/44, 66 %), and bone marrow oedema pattern (BMEP) (average cross-sectional area 885.7 ± 730.2 mm(2)). Total hip arthroplasty (THA) was required in 16/35 patients, at an average of 6 months post-MRI. Compared to the THA cohort, the non-THA group had significantly (p < 0.05) smaller overlying cartilage defect size (10 mm vs. 29 mm), smaller band length ratio and fracture diameters, and greater incidence of parallel fracture morphology (p < 0.05). Male gender and increased age were significantly associated with progression, p < 0.05. CONCLUSIONS:SIF were associated with synovitis, cartilage loss, effusion, and BMEP. Male gender and increased age had a significant association with progression to THA, as did band length ratio, fracture diameter, cartilage defect size, and fracture deformity/morphology. KEY POINTS:• Femoral head subchondral insufficiency fractures (SIF) frequently require total hip arthroplasty (THA). • SIF frequently coexist with synovitis, cartilage loss, and bone marrow oedema pattern. • SIF cartilage defect size, band length ratio, and fracture diameter/morphology can predict progression risk.

LGR5 in breast cancer and ductal carcinoma in situ: a diagnostic and prognostic biomarker and a therapeutic target.

Background

Novel biomarkers are required to discern between breast tumors that should be targeted for treatment from those that would never become clinically apparent and/or life threatening for patients. Moreover, therapeutics that specifically target breast cancer (BC) cells with tumor-initiating capacity to prevent recurrence are an unmet need. We investigated the clinical importance of LGR5 in BC and ductal carcinoma in situ (DCIS) to explore LGR5 as a biomarker and a therapeutic target.

Methods

We stained BC (n = 401) and DCIS (n = 119) tissue microarrays with an antibody against LGR5. We examined an LGR5 knockdown ER- cell line that was orthotopically transplanted and used for in vitro colony assays. We also determined the tumor-initiating role of Lgr5 in lineage-tracing experiments. Lastly, we transplanted ER- patient-derived xenografts into mice that were subsequently treated with a LGR5 antibody drug conjugate (anti-LGR5-ADC).

Results

LGR5 expression correlated with small tumor size, lower grade, lymph node negativity, and ER-positivity. ER+ patients with LGR5high tumors rarely had recurrence, while high-grade ER- patients with LGR5high expression recurred and died due to BC more often. Intriguingly, all the DCIS patients who later died of BC had LGR5-positive tumors. Colony assays and xenograft experiments substantiated a role for LGR5 in ER- tumor initiation and subsequent growth, which was further validated by lineage-tracing experiments in ER- /triple-negative BC mouse models. Importantly, by utilizing LGR5high patient-derived xenografts, we showed that anti-LGR5-ADC should be considered as a therapeutic for high-grade ER- BC.

Conclusion

LGR5 has distinct roles in ER- vs. ER+ BC with potential clinical applicability as a biomarker to identify patients in need of therapy and could serve as a therapeutic target for high-grade ER- BC.

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