triple-negative breast cancer (tnBc) has a more aggressive phenotype and higher metastasis and recurrence rates than other breast cancer subtypes. tnBc currently lacks a transplantation model that is suitable for clinical simulations of the tumor microenvironment. intraductal injection of tumor cells into the mammary duct could mimic the occurrence and development of breast cancer. Herein, we injected 4T1 cells into the mammary ducts of BALB/C mice to build a preclinical model of tnBc and optimized the related construction method to observe the occurrence and spontaneous metastasis of tumors. We compared the effects of different cell numbers on tumorigenesis rates, times to tumorigenesis, and metastases to determine the optimal number of cells for modelling. We demonstrated that 4T1-MIND model mice injected with 20,000 cells revealed a suitable tumor formation rate and time, thus indicating a potential treatment time window after distant metastasis. We also injected 20,000 cells directly into the breast fat pad or breast duct for parallel comparison. The results still showed that the 4T1-MIND model provides sufficient treatment time for lung metastases in mice and that it is a more reliable model for early tumor development. The 4T1-MIND model requires continuous improvement and optimization. A suitable and optimized model for translational research and studies on the microenvironment in tnBc should be developed.Breast cancer is the most commonly diagnosed cancer type and the leading cause of cancer death among women worldwide 1,2 . Breast ductal carcinoma in situ (DCIS) accounts for 15%-30% of all breast cancer cases 3 . DCIS tends to break through the matrix and develop into invasive ductal carcinoma 4 . Approximately 90% of all breast cancer-related deaths are caused by metastasis 5,6 , the most frequent sites of which are the lung, bone, liver, and brain. Triple-negative breast cancer (TNBC) is remarkably heterogeneous in terms of the tumor microenvironment 7 . Preclinical models that can return the breast tumor microenvironment to its original condition play a pivotal role in studies on the pathogenesis and treatment of breast cancer. However, 23 anticancer drugs failed in clinical trials between 2007 and 2010 8 , partly because the preclinical models used to test them were inappropriate for breast cancer. These findings illustrate that the success of breast cancer research and treatment depends on the experimental animal model used.Experimental animal models of breast cancer have been widely studied. Researchers should choose different animal models based on the needs of their experimental work. Today, the most frequently used breast cancer models include spontaneous breast cancer animal models 9-11 , induced breast cancer animal models 11-15 , allograft experimental animal mammary cancer models [16][17][18][19] , xenograft breast cancer models 20-24 , distant metastasis of breast cancer models 17,25-27 and genetically engineered mouse models (GEMMs) of breast cancer [28][29][30] . Given the Pathological fe...

A closer association has been found between the microRNA-146a rs2910164 polymorphism and the risk of head and neck carcinoma in some molecular epidemiological studies. Recently two meta-analyses were performed to explore the relationship between miRNA-146a polymorphisms and the susceptibility of squamous cell carcinoma of the head and neck (SCCHN); however, they yielded conflicting results in susceptibility regarding ethnic variations. Hence, the present study was performed to explain the relationship between the miRNA-146a rs2910164 polymorphism and the risk of SCCHN development of Chinese patients. We retrieved databases and screened eligible papers up to March 10, 2017 and then we extracted the essential data. The subgroup analyses were also performed based on the tumor site, region, and genotyping means. Crude odds ratios (OR) at 95% confidence intervals (CI) were chosen to describe the strength of the association. As a result, 6 publications were included in our study which involved 8 independent case-control studies. A significant association was found between miR-146a rs2910164 polymorphisms and the risk of SCCHN in Chinese patients according to the overall data [CC+CG vs. GG: OR = 1.13; 95%CI = 1.00–1.29; CC vs. GG: OR = 1.19; 95%CI = 1.03–1.38]. According to the subgroup analysis based on tumor site, the risk of cancer was significantly increased among laryngeal cancer (dominant model: OR = 1.76, 95%CI = 1.26~2.46, P = 0.001; homozygote model: OR = 1.83, 95%CI = 1.25~2.67, P = 0.002) and nasopharyngeal carcinoma (homozygote model: OR = 1.41, 95%CI = 1.05~1.90, P = 0.022). In summary, variant alleles of miR-146a rs2910164 alleles may have an association with the increased risk of SCCHN in Chinese patients, and these associations differed based on tumor site. Further studies including a larger sample size will be necessary to clarify these results.

Background: Head and neck fibrosarcoma is a rare malignant tumor, accounting for about 1% of all head and neck tumors. It can also occur in the jaw bone, for which surgical resection is the main treatment but the recurrence rate is high and the prognosis is usually poor. Due to the lack of models mimicking the biological characteristics of the tumor, there is little progress in the research of the pathogenesis and treatment of fibrosarcoma. Therefore, there is an urgent need to explore a high-fidelity model that can reflect the biological characteristics of fibrosarcoma for the sake of improving the therapeutic outcome and prognosis, and preventing recurrence. Patient-derived xenografts (PDX) may more accurately reflect the human disease, and is an attractive platform to study disease biology and develop treatments and biomarkers. In this study we describe the establishment of jaw fibrosarcoma PDX models and compare PDX tumors to those of human origin. Methods: Tumor biopsies from a patient with jaw fibrosarcoma were implanted in immunodeficient mice. Primary and PDX tumors were characterized extensively by histology, immunohistochemistry and humanized identification. Based on the finding of our previous preliminary research that plumbagin had an anti-tumor effect against head and neck cancer, we used this model in the present study to evaluate the anti-tumor effect of plumbagin on jaw fibrosarcoma. Results: The established PDX model maintained the histological and immunohistochemical characteristics of the primary tumor. Plumbagin significantly inhibited the tumor growth in the jaw fibrosarcoma PDX model. Conclusion: We successfully established a PDX model of jaw fibrosarcoma and demonstrated that this PDX model preserved the important molecular characteristics of the human primary tumor, thus providing a powerful tool for treatment research and new drug development of jaw fibrosarcoma. In addition, plumbagin was found to have an inhibitory effect on the growth of PDX modeled jaw fibrosarcoma, which provides a preliminary research basis for its clinical application.

Background Orthotopic models of lung cancer have been widely utilized, and the purpose of this study was to demonstrate the viability of our proposed modified modeling approach. Methods A total of 50 female BALB/c mice were implanted with 1×1×1 mm fragments of a tumor sample into the left lung lobe. After 2 months of observation, the mice were humanely euthanized through CO 2 inhalation. The macroscopic specimens were photographed, and the most representative neoplastic lesions were collected for histological analysis. Small-animal positron emission tomography/computed tomography (PET/CT) scans were conducted on 6 randomly selected mice. Results Local tumor formation, ipsilateral thoracic tissue infiltration, the contralateral chest wall, right lung metastases, and distant kidney metastases were observed in these models. Overall, the tumor development and metastasis rates were 60.86% (28/46) and 57.14% (16/28), respectively. The 3 mice that had a small-animal PET/CT scan developed a local tumor, but no distant metastases were observed. Conclusions This modified method was deemed reliable, reproducible, minimally invasive, straightforward, and comprehensible; it might serve as the foundation for developing patient-derived orthotopic xenografts of lung cancer.

Objective: The efficacy of anlotinib as a treatment for head-and-neck squamous cell carcinoma (HNSCC) has been little explored. Here, we used patient-derived xenografts (PDXs) to this end.Methods: Fresh tumor tissues of HNSCC patients were screened in terms of in vitro drug sensitivity using the MTT assay. Patient PDXs were used to confirm the anti-tumor effects of anlotinib in vivo. After the medication regimen was complete, the tumor volume changes in mice were calculated. Apoptosis was measured using the TUNEL assay. The cell proliferation and apoptosis levels of PDXs yielded data on the utility of anlotinib treatment in vivo.Results: Anlotinib suppressed the in vitro proliferation of nine tumor tissues by an average of 51.05 ± 13.74%. Anlotinib also significantly inhibited the growth of three PDXs in mice (tumor growth inhibition 79.02%). The expression levels of Ki-67 and proliferating cell nuclear antigen after anlotinib treatment were significantly lower than those in the controls. The negative and positive controls exhibited no and some apoptosis, respectively, whereas the anlotinib group evidenced extensive apoptosis.Conclusion: Anlotinib suppressed HNSCC growth in vitro and in vivo (by inhibiting cell proliferation and promoting apoptosis), suggesting that anlotinib can potentially treat HNSCC.