Breast cancer metastasis is the leading cause of cancer-related deaths in women worldwide. Collagen in the tumor microenvironment plays a crucial role in regulating tumor progression. We have shown that type III collagen (Col3), a component of tumor stroma, regulates myofibroblast differentiation and scar formation after cutaneous injury. During the course of these wound-healing studies, we noted that tumors developed at a higher frequency in Col3(+/-) mice compared to wild-type littermate controls. We, therefore, examined the effect of Col3 deficiency on tumor behavior, using the murine mammary carcinoma cell line 4T1. Notably, tumor volume and pulmonary metastatic burden after orthotopic injection of 4T1 cells were increased in Col3(+/-) mice compared to Col3(+/+) littermates. By using murine (4T1) and human (MDA-MB-231) breast cancer cells grown in Col3-poor and Col3-enriched microenvironments in vitro, we found that several major events of the metastatic process were suppressed by Col3, including adhesion, invasion, and migration. In addition, Col3 deficiency increased proliferation and decreased apoptosis of 4T1 cells both in vitro and in primary tumors in vivo. Mechanistically, Col3 suppresses the procarcinogenic microenvironment by regulating stromal organization, including density and alignment of fibrillar collagen and myofibroblasts. We propose that Col3 plays an important role in the tumor microenvironment by suppressing metastasis-promoting characteristics of the tumor-associated stroma.
Objective To report the incidence of short‐term incisional complications in dogs receiving intraoperative local infiltration of liposomal bupivacaine. Study design Retrospective study. Animals Client‐owned dogs (n = 218). Methods Medical records were searched for dogs whose surgical site was infiltrated with liposomal bupivacaine. Records were reviewed for complications within 20 days postoperatively. Cases were categorized by: (1) surgical wound classification (clean, clean‐contaminated, contaminated); (2) labeled versus off‐label use in orthopedic surgery – stifle surgery to address cranial cruciate ligament (CCL) disease versus other orthopedic procedures; and (3) orthopedic versus soft‐tissue surgery. Results Complications were documented in 43/218 (19.7%) records, including 27/218 (12.4%) complications that resolved spontaneously or with topical treatment. The incidence of short‐term incisional complications did not differ between surgical wound classifications (P = 0.55) or between labeled versus off‐label use in orthopedic surgery (P = 0.21). Complications seemed more common after soft‐tissue procedures (32/123; 26.0%) than orthopedic procedures (11/95; 11.6%) (P < 0.01). Conclusion Surgical wound classification or type of orthopedic procedure did not seem to influence incisional complications of infiltrated surgical sites. Complications were more common after soft‐tissue procedures than orthopedic procedures. Clinical significance Infiltration of surgical sites with liposomal bupivacaine seems safe in a broader range of orthopedic procedures than currently labeled. The results also justify further investigation in soft‐tissue surgery.
CASE DESCRIPTION A 3-year-old neutered male domestic shorthair cat with a history of urethral obstruction was evaluated at a veterinary referral center for acute onset of hunched posture and signs of discomfort on being handled. No evidence of urethral obstruction was found; signs initially responded to medical management, but the cat was presented to the primary care veterinarian < 48 hours after the initial examination with signs suggesting urethral obstruction. CLINICAL FINDINGS No urinary calculi were detected radiographically. Attempted urinary catheter placement was unsuccessful, and the cat was returned to the referral center for evaluation and treatment of suspected urethral obstruction. Hematologic evaluation revealed hyperglobulinemia and leukocytosis; the cat was febrile, its prepuce was swollen, and its urinary bladder was soft but could not be manually expressed. TREATMENT AND OUTCOME A urinary catheter was placed; urinalysis revealed hematuria, leukocyturia, and bacteriuria. Medical management included analgesic, antimicrobial, urethral antispasmodic, and IV fluid treatment. Positive-contrast cystourethrography results were equivocal for a congenital anomaly versus urethral rupture. Contrast-enhanced CT revealed a sinus communicating with the dorsal aspect of the urethra, and urethral rupture was ruled out. Partial urethral duplication was confirmed surgically; perineal urethrostomy was performed, creating an opening to the accessory urethra, and the strictured orthotopic urethra was ligated. Four weeks after surgery, the cat was doing well. CLINICAL RELEVANCE This case highlighted the importance of advanced imaging to distinguish between urethral rupture and a congenital malformation in a cat with signs of lower urinary tract disease. This approach was pivotal to appropriate diagnosis and management and a favorable outcome for the patient.
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