Background Cervical cancer is a world-wide problem that requires transformative therapeutic strategies. We have previously developed patient-derived orthotopic xenograft (PDOX) nude-mouse models of this disease. In the present report, we demonstrate that the standard drug, cisplatinum (CDDP), is highly-effective while the new, highly-touted agent, nab-paclitaxel (NAB-PTX) is ineffective. Materials and Methods Cervical PDOX tumors were grown on the cervix of nude mice for 4 weeks after surgical orthotopic implantation (SOI). Tumors were treated with CDDP or NAB-PTX. Results H&E staining demonstrated that the PDOX tumor recapitulated the original patient tumor. CDDP was highly-effective. One tumor that was treated with CDDP completely regressed. CDDP-treated tumors were smaller (tumor volume ratio: 0.42±0.36) than the control group (tumor volume ratio: 3.47±1.66) (p<0.01). In contrast, NAB-PTX did not show significant efficacy on the cervical cancer PDOX model (tumor volume ratio: 2.85±1.45) (p=0.47). CDDP-treated tumor weight (50±50 mg) was significantly less than control (238±114 mg) (p<0.01). NAB-PTX-treated tumors were not reduced in weight (246±136 mg) compared to control (p=0.91). There were no significant differences in mouse body weight between groups. Histological evaluation demonstrated that CDDP-treated tumors were fibrotic with scattered squamous cell nests compared to control or NAB-PTX-treated tumors. Conclusion The results of the present study demonstrate the power of PDOX models of cervical cancer to distinguish efficacy of potential therapeutics for individual patients with this disease.

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Background/Aim: Matrix-producing breast carcinoma (MPBC) is a rare and usually aggressive triplenegative breast cancer (TNBC). In the present report, we determined the drug sensitivity for a triple-negative MPBC using a patient-derived orthotopic xenograft (PDOX) model. Materials and Methods: The PDOX model was established in the left 2 nd mammary by surgical orthotopic implantation (SOI). MPBC PDOX models were randomized into 4 groups (6 mice per group) when the tumor volume became 80 mm 3 : G1, control group; G2, cisplatinum group [intraperitoneal (i.p.) injection, weekly, for 2 weeks]; G3, paclitaxel group (i.p., weekly, for 2 weeks); G4, eribulin group [intravenous (i.v.) injection, weekly, for 2 weeks]. All mice were sacrificed on day 15. Tumor volume and body weight were measured one time per week. Results: The MPBC PDOX model was resistant to cisplatinum (p=0.800). Paclitaxel suppressed tumor growth compared to the control group (p=0.009). However, only eribulin regressed the tumor (p=0.001). Conclusion: Eribulin has clinical potential for triple-negative MPBC patients.Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer (1, 2). TNBC is defined by a lack of estrogen receptor (ER), progesterone receptor (PgR), as well as lack of amplification of human epidermal growth factor receptor 2 (HER-2) (1, 2). Approximately 15-20% of all diagnosed breast cancer cases are TNBC (1, 2). TNBCs often become resistant to standard chemotherapy used against them. Therefore, clinical outcomes for patients with metastatic TNBC (mTNBC) indicate a poor prognosis (3).Matrix-producing breast carcinoma (MPBC) is a rare and specialized histological type of metaplastic carcinoma (4). MPBC is usually TNBC. MPBC is an invasive breast carcinoma with direct transition to a cartilaginous or osseous matrix having no intervening spindle-cell component (5,6). Therefore, this tumor should be initially treated with chemotherapy. Although 2475This article is freely accessible online.

Background/Aim: The discovery of the nude mouse model enabled the experimental growth of humanpatient tumors. However, the low establishment rate of tumors in nude and other immunodeficient strains of mice has limited wide-spread clinical use. Materials and Methods: In order to increase the establishment rate of surgical specimens of patient tumors, we transplanted tumors to nude mice subcutaneously along with large amounts of surrounding tissue of the tumor. Results: The new transplantation method increased the establishment rate in nude mice to 66% compared to the old method of implanting the surgical tumor specimen with surrounding tissue removed (14%). High stage and presence of metastasis in the patient donor are positively correlated to tumor engraftment in nude mice. Conclusion: The new method can potentially allow most cancer patients who undergo surgery or biopsy to have their own mouse model for drug-sensitivity testing.Cancer-drug sensitivity depends on the individual characteristics of the patient's tumor. Therefore, cancer chemotherapy needs to be individualized (1, 2). Rygaard was the first to successfully transplant and grow surgical cancer specimens in nude mice in 1969 (3). The surgical specimens were transplanted subcutaneously in the nude mice. Laboratories in the United States, Europe, China and Japan adopted this method and it is in use today under the term patient-derived xenograft (PDX) (4). However, since the time of Rygaard, there has not been a significant increase in the establishment frequency of human tumors in nude and other immune-deficient mice, which has inhibited the use of PDX models for individualized cancer therapy. The standard implantation technique is to first remove the surrounding tissue from the surgical cancer specimen. In the present report we describe a novel approach of co-implanting the tumor along with large amounts of surrounding tissue into a pocket made in the subcutaneous space of nude mice. The new method greatly increased the establishment frequency of patient tumors in nude mice, that should enable its widespread clinical use. Materials and MethodsAthymic nude mice (AntiCancer Japan Inc, Narita, Japan) were used for tumor implantation. All procedures followed ethical procedures for use of experimental animals. All patients provided written informed consent for implantation of their tumors in nude 3241 This article is freely accessible online.