Tracking human multiple myeloma xenografts in NOD-Rag-1/IL-2 receptor gamma chain-null mice with the novel biomarker AKAP-4

<p>Abstract</p> <p>Background</p> <p>Multiple myeloma (MM) is a fatal malignancy ranking second in prevalence among hematological tumors. Continuous efforts are being made to develop innovative and more effective treatments. The preclinical evaluation of new therapies relies on the use of murine models of the disease.</p> <p>Methods</p> <p>Here we describe a new MM animal model in NOD-Rag1null IL2rgnull (NRG) mice that supports the engraftment of cell lines and primary MM cells that can be tracked with the tumor antigen, AKAP-4.</p> <p>Results</p> <p>Human MM cell lines, U266 and H929, and primary MM cells were successfully engrafted in NRG mice after intravenous administration, and were found in the bone marrow, blood and spleen of tumor-challenged animals. The AKAP-4 expression pattern was similar to that of known MM markers, such as paraproteins, CD38 and CD45.</p> <p>Conclusions</p> <p>We developed for the first time a murine model allowing for the growth of both MM cell lines and primary cells in multifocal sites, thus mimicking the disease seen in patients. Additionally, we validated the use of AKAP-4 antigen to track tumor growth <it>in vivo </it>and to specifically identify MM cells in mouse tissues. We expect that our model will significantly improve the pre-clinical evaluation of new anti-myeloma therapies.</p

Eosinophilic Enteritis in Northeastern Australia - Pathology, Association with Ancylostoma-Caninum, and Implications

While eosinophilic gastroenteritis is considered a rare condition, eosinophilic enteritis without gastric involvement is quite common in northeastern Australia. We present 79 patients with biopsy-proven eosinophilic enteritis, 70 seen since 1987. In 10 patients, eosinophilic enteritis was associated with infection by single, sexually immature, adult hookworms, most positively identified as the common dog hookworm Ancylostoma caninum. An additional 22 patients (of 34 tested) had serological evidence of A. caninum exposure. The essential pathology, i.e., edema and eosinophilic infiltration of the gut wall, ascites, and regional lymphadenopathy, was identical to that seen in eosinophilic gastroenteritis. Additional, more specific features included pathological reactions centered on attached worms, mucosal alterations and ulcers considered to be hookworm bite sites, and submucosal and lymph node granulomas with central eosinophil degranulation and degradation products. Since A. caninum has an almost worldwide distribution, it is probable that A. caninum-induced eosinophilic enteritis occurs outside Australia. We show that the worm is easily overlooked in pathological specimens and that care is required to preserve worms intact for specific parasitological identification. The clinical and pathological features were similar to those seen in another human enteric helminthic zoonosis, anisakiasis. The possibility that there are yet other undiscovered intestinal zoonoses remains

Sequential assessment of bowel function and anorectal physiology after anterior resection for cancer: a prospective cohort study

Aim: to investigate changes in bowel function and anorectal physiology (ARP) after anterior resection for colorectal cancer.Methods: patients were recruited from November 2006 to September 2008. Cleveland Clinic Incontinence (CCI) scores and stool frequency were determined by patient questionnaires before surgery (t0 ) and at three (t3 ), six (t6 ), nine (t9 ) and 12 (t12 ) months after restoration of intestinal continuity. ARP measurements were recorded at t0 , t3 and t12 . Endoanal ultrasound was performed at t0 and t12 .Results: eighty-nine patients were included in the study. CCI score increased post-operatively then normalised, whereas stool frequency did not change. Patients who had neoadjuvant radiotherapy or lower anastomoses had increased incontinence and stool frequency in the post-operative period, whereas those with defunctioning stomas or open surgery had increased stool frequency alone. Maximum resting pressure, volume at first urge and maximum rectal tolerance were reduced throughout the post-operative period. Radiotherapy, lower anastomosis and defunctioning stoma (but not operative approach) altered manometric parameters post-operatively. Maximum tolerance correlated with incontinence and first urge with stool frequency. Anterior internal anal sphincter thickness decreased post-operatively.Conclusions: incontinence recovers in the first year after anterior resection. Radiotherapy, lower anastomosis, defunctioning stoma and open surgery negatively influence bowel function. ARP may be useful if bowel dysfunction persists beyond 12 months.</p