The MOZ-TIF2 fusion is associated with acute myeloid leukemia (AML) with inv(8)(p11q13). MOZ is a MYST family histone acetyltransferase (HAT), whereas TIF2 is a nuclear receptor coactivator that associates with CREB binding protein (CBP). Here we demonstrate that MOZ-TIF2 has transforming properties in vitro and causes AML in a murine bone marrow transplant assay. The C2HC nucleosome recognition motif of MOZ is essential for transformation, whereas MOZ HAT activity is dispensable. However, MOZ-TIF2 interaction with CBP through the TIF2 CBP interaction domain (CID) is essential for transformation. These results indicate that nucleosomal targeting by MOZ and recruitment of CBP by TIF2 are critical requirements for MOZ-TIF2 transformation and indicate that MOZ gain of function contributes to leukemogenesis.

To address the role of β1 integrins in pancreatic cancer progression, we stably knocked down β1 integrin subunit expression in human FG-RFP pancreatic cancer cells using lentiviral-based RNA interference. We then examined the effects of β1 integrin subunit knockdown on pancreatic cancer cell adhesion, migration, and proliferation on tumor microenvironment-specific ECM proteins in vitro, and on tumor progression in vivo using a clinically-relevant fluorescent orthotopic mouse model of pancreatic cancer. Knockdown of the β1 integrin subunit inhibited cell adhesion, migration, and proliferation on types I and IV collagen, fibronectin, and laminin in vitro. In vivo, knockdown of the β1 integrin subunit reduced primary tumor growth by 50% and completely inhibited spontaneously occurring metastasis. These observations indicate a critical role for the β1 integrin subunit in pancreatic cancer progression, and metastasis in particular. Our results suggest the β1 integrin subunit as a therapeutic target for the treatment of pancreatic cancer, especially in the adjuvant setting to prevent metastasis of this highly aggressive cancer.

Background We inquired if fluorescence-guided surgery (FGS) could improve surgical outcomes in fluorescent orthotopic nude mouse models of human colon cancer. Methods We established fluorescent orthotopic mouse models of human colon cancer expressing a fluorescent protein. Tumors were resected under bright light surgery (BLS) or FGS. Pre- and post-operative images with the OV-100 Small Animal Imaging System were obtained to assess extent of surgical resection. Results All mice with primary tumor which had undergone FGS had complete resection as compared to 58% of mice in the BLS group (p=0.001). FGS resulted in decreased recurrence compared to BLS (33% vs 62%, p=0.049), and lengthened disease-free median survival from 9 weeks to >36 weeks. The median overall survival increased from 16 weeks in the BLS group to 31 weeks in the FGS group. FGS resulted in a cure in 67% of mice (alive without evidence of tumor at >6 months post-surgery) compared to only 37% of mice which underwent BLS (p=0.049). Conclusions Surgical outcomes in orthotopic nude mouse models of human colon cancer were signficantly improved with FGS. The current study can be translated to the clinic by various effective methods of fluorescently labeling tumors.

Background/Aims Laparoscopy is important in staging pancreatic cancer, but false negatives remain problematic. Making tumors fluorescent has the potential to improve the accuracy of staging laparoscopy. Methodology Orthotopic and carcinomatosis models of pancreatic cancer were established with BxPC-3 human pancreatic cancer cells in nude mice. Alexa488-anti-CEA conjugates were injected via tail vein 24 hours prior to laparoscopy. Mice were examined under bright field laparoscopic (BL) and fluorescence laparoscopic (FL) modes. Outcomes measured included time to identification of primary tumor for the orthotopic model and number of metastases identified within 2 minutes for the carcinomatosis model. Results FL enabled more rapid and accurate identification and localization of primary tumors and metastases than BL. Using BL took statistically significantly longer time than FL. More metastatic lesions were detected and localized under FL compared to BL and with greater accuracy, with sensitivities of 96% vs. 40%, respectively, when compared to control. FL was sensitive enough to detect metastatic lesions <1mm. Conclusions The use of fluorescence laparoscopy with tumors labeled with fluorophore-conjugated anti-CEA antibody permits rapid detection and accurate localization of primary and metastatic pancreatic cancer in an orthotopic model. The results of the present report demonstrate the future clinical potential of fluorescence laparoscopy.

Background. Pulmonary inflammatory pseudotumor, also known as plasma cell granuloma among many other names, is widely believed to be an inflammatory or reactive lesion rather than a neoplasm, although its pathogenesis is still controversial. Methods. Cytogenetic analysis was performed on a lung mass that showed typical clinical and pathologic features of inflammatory pseudotumor. Ultrastructural and immunohistochemical studies were performed in addition to routine histologic examination. Results. Cytogenetic study of the lesion revealed clonal anomalies of t(1;2)(q21;p23) and del(4)(q27). The patient, a 30‐year‐old woman, presented with an asymptomatic but enlarging right lower lobe mass for which partial right lower lobectomy was performed. The lung mass was well circumscribed radiographically and grossly. Microscopically, it was characterized by a loosely arranged spindle cell proliferation with prominent plasma cell infiltration. Fibroblastic and myofibroblastic differentiation of the spindle cells was demonstrated by ultrastructural and immunohistochemical studies. Conclusion. To the authors' knowledge, this is the first report of clonal cytogenetic changes in a clinically and pathologically typical case of inflammatory pseudotumor in the lung. This finding suggests that pulmonary inflammatory pseudotumor might be a true neoplasm rather than a purely inflammatory or reactive lesion. Cancer 1995; 76:1545‐9.