An anatomic study was performed on canine cadavers to define the blood supply to the cranial sartorius muscle. The vascular supply to this muscle was found to be a single dominant pedicle branching from the femoral artery at the proximal portion of the muscle. This anatomic information was applied in designing a study to determine the feasibility of performing a cranial sartorius muscle flap in the dog. The cranial sartorius muscle was transposed to the caudal abdominal region in four dogs. The muscle flap was based on the singular vascular pedicle defined in the anatomic study. All muscle transpositions were successful on day 19 as evidenced by gross appearance and histologic examination. Grossly, the muscles were well adhered to the recipient sites and were covered by connective tissue. Histologically, the specimens were characterized by viable skeletal muscle fibers, proliferative and maturing granulation and fibrous connective tissue, and mild to moderate mononuclear inflammation. Seroma formation and infection were the two postoperative complications noted. The cranial sartorius muscle flap has potential clinical application for repair of traumatic caudal abdominal hernias and large inguinal hernias in the dog.

An anatomic study was performed on canine cadavers to define the blood supply to the caudal sartorius muscle. The vascular supply to this muscle was segmental with the saphenous artery and vein providing a distal vascular pedicle. Anastomotic channels existed between distal and proximal capillary beds within the muscle belly. This anatomic information was used to determine the feasibility of performing caudal sartorius muscle flaps in dogs. The caudal sartorius muscle was transposed to the medial tibial region in four dogs. The muscle flap was based on a singular vascular pedicle of the saphenous artery and vein. The muscle transpositions were all successful on day 14 as evidenced by gross appearance and results of histologic examination. Grossly, the muscles were well adhered to the recipient sites and were covered by connective tissue. Histologically, the specimens were characterized by viable skeletal muscle fibers, large amounts of granulation tissue, varying degrees of inflammatory response, and small foci of myocyte necrosis (2 cases). Seroma formation was a consistent postoperative complication.

Estrogen receptor positive (ER+) breast cancer accounts for 70% of all breast cancers and is primarily treated with endocrine therapy. Approximately 40% of patients on endocrine therapy will become resistant via a number of mechanisms. There is evidence that in many cases ER continues to play a central role, including mutations in ER leading to a constitutively active receptor. Estrogen receptor degraders like fulvestrant are effective in shutting down ER signaling; however, poor pharmaceutical properties limit fulvestrant clinical activity and prevent it from achieving maximum receptor blockade. We describe the discovery of SAR439859, a novel, orally bioavailable SERD that is a potent antagonist and degrader of ER both in vitro and in vivo. SAR439859 has robust activity in multiple ER+ breast cancer cell lines including cells that are resistant to tamoxifen as well as cell lines harboring ER mutants. Across a large panel of ER+ cells, SAR439859 demonstrated broad and superior ER degradation activity than most SERDs undergoing clinical testing. This leads to a profound inhibition of ER signaling, better inhibition of cell growth and results in improved in vivo efficacy. SAR439859 demonstrated tumor regression in all ER+ BC models including MCF7-ESR1 mutant-Y537S model, as well as patient-derived xenograft model that is resistant to endocrine therapies. Furthermore, SAR439859 displays limited cross-resistance with other class of SERDs. Taken together, these results suggest that SAR439859 would be of therapeutic benefit in metastatic BC setting for patients harboring wild type or mutant ER. SAR439859 is being advanced toward the clinic. Citation Format: Shomali M, Cheng J, Koundinya M, Weinstein M, Malkova N, Sun F, Hebert A, Cindachao M, Hoffman D, McManus J, Levit M, Pollard J, Vincent S, Besret L, Adrian F, Winter C, El-Ahmad Y, Halley F, Hsu K, Lager J, Garcia-Echeverria C, Bouaboula M. Identification of SAR439859, an orally bioavailable selective estrogen receptor degrader (SERD) that has strong antitumor activity in wild-type and mutant ER+ breast cancer models [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P3-04-05.

The sartorius muscle in the cat is a broad, sheet-like muscle which covers the craniomedial aspect of the thigh. The major portion of the blood supply arises from the proximal pole of the muscle. A single sartorius muscle can be positioned over the abdomen in a transverse manner along the pubis, to cover the entire (i.e., left and right sides) caudal 30% of the abdomen. It also can be extended in a cranial-to-caudal fashion where it covers approximately 80% of the length and 75% of the width of the ipsilateral abdomen. The sartorius muscle flap is easy to harvest and provides good coverage for defects of the caudal abdominal wall. This muscle flap was used successfully in two feline patients.