Integrin αvβ6 Colonic epithelial cells Connective tissues RGD RGD binding siteAnti-integrin αvβ6 autoantibodies in UC patients RGD

Treatment with tamoxifen (TAM) increases the risk of developing endometrial cancer in women. The carcinogenic effect is thought to involve initiation and/or promotion resulting from DNA damage induced by TAM as well as its estrogenic action. To minimize this serious side-effect while increasing the anti-breast cancer potential, a new benzopyran antiestrogen, 2E-3-{4-[(7-hydroxy-2-oxo-3-phenyl-2H-chromen-4-yl)-methyl]-phenyl}-acrylic acid (SS5020), was synthesized. Unlike TAM, SS5020 exhibits no genotoxic activity to damage DNA. Furthermore, SS5020 does not present significant uterotrophic potential in rats; in contrast, the structurally related compounds, TAM, toremifene, raloxifene (RAL) and SP500263 all have uterotrophic activity. At the human equivalent molar dose of TAM (0.33 or 1.0 mg/kg), SS5020 had much stronger antitumor potential than those same antiestrogens against 7,12-dimethylbenz(a)anthracene-induced mammary carcinoma in rats. The growth of human MCF-7 breast cancer xenograft implanted into athymic nude mice was also effectively suppressed by SS5020. SS5020, lacking genotoxic and estrogenic actions, could be a safer and stronger antiestrogen alternative to TAM and RAL for breast cancer therapy and prevention.Tamoxifen (TAM; the structure in Fig. 1a) has been widely used since 1973 as an adjuvant therapy for early-stage breast cancer with positive estrogen receptors (ER) 1 and since 1998 as a prophylactic agent for women at high risk of developing this disease. 2 However, long-term administration of TAM has been associated with several adverse effects, including endometrial cancer in women. [2][3][4] The carcinogenic effect may be caused through initiation and/or promotion due to DNA damage induced by TAM as well as the drug's estrogenic action (reviewed in Refs. 5 and 6). Several groups including ours established that a-hydroxylation of TAM and its subsequent O-sulfonations are essential for DNA-adduct formation. 5,6 TAM-induced DNA adducts were detected in rodent liver 7,8 and in the endometrium of women treated with TAM. 9,10 Because TAM-DNA adducts are highly mutagenic 11 and not rapidly repaired, 12 the DNA adducts likely contribute to the initiation of endometrial cancer; in fact, K-ras mutations were detected frequently in the endometria of women treated with TAM. 13 TAM is a partial ER agonist in uterine tissue 14 ; such an estrogenic effect may also contribute to promoting endometrial cancer. 15 This drug has been listed as a human carcinogen by the International Agency for Research on Cancer. 16 Some other antiestrogens are fully or partially used for early-stage breast cancer therapy. Toremifene (TOR; Fig. 1a), a chlorinated TAM derivative, was approved in 1987 by the Food and Drug Administration (FDA) for breast cancer therapy. Although the metabolic fate of TOR is similar to that of TAM, TOR does not promote DNA adducts 8,17,18 or hepatocarcinoma in rats. 8,17 In fact, no K-ras mutations were observed in the endometria of patients receiving TOR. 13 On the contrary, a review paper 19 in ...

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OBJECTIVE To evaluate outcome of limb fracture repair in rabbits. DESIGN Retrospective case series. ANIMALS 139 client-owned rabbits with limb fractures treated between 2007 and 2015. PROCEDURES Medical records were reviewed for information on fracture location, fracture treatment, and time to fracture healing. RESULTS 25 rabbits had fractures involving the distal aspects of the limbs (ie, metacarpal or metatarsal bones, phalanges, and calcaneus or talus). Fractures were treated in 23 of these 25 rabbits (external coaptation, n = 17; external skeletal fixation, 4; and intramedullary pinning, 2) and healed in all 23, with a median healing time of 28 days (range, 20 to 45 days). One hundred ten rabbits had long bone fractures, and fractures were treated in 100 of the 110 (external skeletal fixation, n = 89; bone plating, 1; intramedullary pinning, 3; and external coaptation, 7). The percentage of fractures that healed was significantly lower for open (14/18) than for closed (26/26) tibial fractures and was significantly lower for femoral (19/26) and treated humeral (4/6) fractures than for radial (23/24) or closed tibial (26/26) fractures. Micro-CT was used to assess fracture realignment during external skeletal fixator application and to evaluate fracture healing. CONCLUSIONS AND CLINICAL RELEVANCE The prognosis for rabbits with limb fractures was good, with fractures healing in most rabbits following fracture repair (109/123). Micro-CT was useful in assessing fracture realignment and evaluating fracture healing.