Anti-CDX2 monoclonal antibody, clone 4H0C0

Patients with KRAS mutated colorectal cancer (CRC) represent a cohort with unmet medical needs, with limited options of FDA-approved therapies. Representing 40-45% of all CRC patients, they are considered ineligible to receive anti-EGFR monoclonal antibodies that have added a significant therapeutic benefit for KRAS wild type CRC patients. Although several mouse models of CRC have been developed during the past decade, one genetically resembling the KRAS mutated CRC is yet to be established. In this study C57 BL/6 mice with truncated adenomatous polyposis coli (APC) floxed allele was crossed with heterozygous KRAS floxed outbred mice to generate an APC(f/f) KRAS(+/f) mouse colony. In another set of breeding, APC floxed mice were crossed with CDX2-Cre-ERT2 mice and selected for APC(f/f) CDX2-Cre-ERT2 after the second round of inbreeding. The final model of the disease was generated by the cross of the two parental colonies and viable APC (f/f) KRAS (+/f) CDX2-Cre-ERT2 (KPC: APC) were genotyped and characterized. The model animals were tamoxifen (TAM) induced to generate tumors. Micro-positron emission tomography (PET) scan was used to detect and measure tumor volume and standard uptake value (SUV). Hematoxylin and eosin (H&E) staining was performed to establish neoplasm and immunohistochemistry (IHC) was performed to determine histological similarities with human FFPE biopsies. The MSI/microsatellite stable (MSS) status was determined. Finally, the tumors were extensively characterized at the molecular level to establish similarities with human CRC tumors. The model KPC: APC animals are conditional mutants that developed colonic tumors upon induction with tamoxifen in a dose-dependent manner. The tumors were confirmed to be malignant within four weeks of induction by H&E staining and higher radioactive [18F] fluoro-2-deoxyglucose (FDG) uptake (SUV) in micro-PET scan. Furthermore, the tumors histologically and molecularly resembled human colorectal carcinoma. Post tumor generation, the KPC: APC animals died of cachexia and rectal bleeding. Implications: This model is an excellent preclinical platform to molecularly characterize the KRAS mutated colorectal tumors and discern appropriate therapeutic strategies to improve disease management and overall survival.

Background: In colorectal cancer (CRC) patients, pulmonary nodules are usually considered lung metastases (LM). However, approximately 10% of LM is presented as a solitary pulmonary nodule which mimics primary lung cancer (PLC). This study aims to determine the distinguishing characteristics of the two pulmonary nodule types during postoperative surveillance of CRC patients. Methods: Between March 2009 and February 2018, 47 CRC patients with pulmonary nodules from a single institution were retrospectively analyzed. They were divided into two groups, namely CRC with second PLC (CSPLC) and CRC with LM (CRCLM), and their demographic data and clinicopathological features were analyzed. Results: When pulmonary nodules are presented, multiple lesions and serum carcinoembryonic antigen (CEA) level >5 ng/mL indicated a higher probability of CRCLM (p < 0.001 and p = 0.028, respectively). A CK7(-)/CK20(+)/CDX2(+)/TTF-1(-) phenotype on immunohistochemistry (IHC) stain suggested CRCLM. Other clinicopathological features showed no significant between-group differences. The median overall survival was considerably longer in the CSPLC group (not reached) than in the CRCLM group (45.41 months, p = 0.064). Conclusions: The detection of a suspicious isolated pulmonary nodule in CRC patients warrants further workup to distinguish between SPLC and LM. Multiple lesions, serum CEA >5 ng/mL when an isolated pulmonary nodule detected, and initial TNM stage IV CRC are more likely related to LM rather than SPLC. Image-guided needle biopsy and IHC stain can reduce the probability of misdiagnosis and rule out LM. CSPLC may have a favorable prognosis owing to early detection and receiving appropriate treatment. (C) 2018 Asian Surgical Association and Taiwan Robotic Surgery Association. Publishing services by Elsevier B.V.