PURPOSE: In order to suggest optimal anticancer drugs for patient-tailored chemotherapy, we developed a colorectal cancer (CRC)-liver metastasis patient-derived tumor xenograft (PDTX) model. METHODS: Tissue obtained from a patient with CRC-liver metastasis (F0) was transplanted in a nonobese female mouse with diabetic/severe combined immune deficiency (F1) and the tumor tissue was retransplanted into nude mice (F2). When tumor volumes reached ~500 mm³, the F2 mice were randomly divided into 4 groups (n = 4/group) of doxorubicin, cisplatin, docetaxel, and nontreated control groups. The tumor tissues were investigated using H&E staining, terminal deoxynucleotidyl transferase dUTP nick end labeling assays, and immunohistochemistry. To determine where the mutant allele frequencies varied across the different passages, we isolated genomic DNA from the primary tumor, liver metastasis, and PDTX models (F1/F2). RESULTS: The physiological properties of the tumor were in accord with those of the patient's tumors. Anticancer drugs delayed tumor growth, inhibited proliferation, and caused apoptosis. Histological assessments revealed no observable heterogeneity among the intragenerational PDTX models. Target exon sequencing analysis without high-quality filter conditions revealed some genetic variations in the 83 cancer-related genes across the generations. However, when de novo mutations were defined as a total count of zero in F0 and ≥5 in F2, exactly prognostic impact of clone cancer profiling (EGFR, KRAS, BRAF, PIK3CA, NRAS, APC and TP53) were detected in the paired. CONCLUSION: A CRC liver metastasis PDTX model was established for the evaluation of chemotherapeutic efficacy. This model retained the physiological characters of the patient tumors and potentially provides a powerful means of assessing chemotherapeutic efficacy.
Animals ; Apoptosis ; Cisplatin ; Clone Cells ; Colorectal Neoplasms* ; DNA ; DNA Nucleotidylexotransferase ; Doxorubicin ; Drug Therapy* ; Exons ; Family Characteristics ; Female ; Gene Frequency ; Genetic Variation ; Heterografts* ; Humans ; Immunohistochemistry ; Liver* ; Mice ; Mice, Nude ; Neoplasm Metastasis* ; Population Characteristics ; Sequence Analysis ; Xenograft Model Antitumor Assays

PURPOSE: The purpose of the present study was to identify more useful parameters for predicting behaviors of multifocal papillary thyroid carcinoma (PTC). MATERIALS AND METHODS: We investigated dominant tumor diameter (TD), total tumor diameter (TTD), and total surface area (TSA) in tumors from 588 patients and evaluated their usefulness as parameters for assessment of tumor behaviors in multifocal PTCs. RESULTS: In 588 PTCs, tumor multifocality was found in 179 PTCs (30.4%). Multifocal tumors were significantly associated with extrathyroidal extension, lymph node metastasis, and higher tumor stage grouping (p<0.001, p<0.001, and p<0.001, respectively). The rates of nodal metastasis increased with greater TSA and TTD in PTCs. Multifocal papillary thyroid microcarcinomas (mPMCs) with TSA >3.14 cm2 had higher rates of nodal metastasis than mPMCs with TSA < or =3.14 cm2 (p=0.038); however, there was no significant difference between mPMCs with TTD >1.0 cm and with TTD < or =1.0 cm (p=0.325). In addition, nodal metastasis was more frequent in mPMCs with TSA >3.14 cm2 than in unifocal papillary thyroid microcarcinomas (uPMCs) (TD < or =1.0 cm) (p=0.002), but not overt unifocal PTCs (TD >1.0 cm) (p=0.244). CONCLUSION: Our results suggest that mPMCs with TSA >3.14 cm2 show more aggressive behavior than uPMCs and mPMCs with TSA < or =3.14 cm2. TSA could be useful in distinguishing aggressive mPMCs from favorable cases.
Adult ; Aged ; Carcinoma/*pathology/surgery ; Carcinoma, Papillary/*pathology/surgery ; Female ; Humans ; Lymph Nodes/*pathology/surgery ; Lymphatic Metastasis/*pathology ; Male ; Middle Aged ; Neoplasm Staging ; Predictive Value of Tests ; Prognosis ; Thyroid Neoplasms/*pathology/surgery ; Thyroidectomy