Embedding aligned nanofibrous architectures within 3D-printed polycaprolactone scaffolds for directed cellular infiltration and tissue regeneration

Three-dimensional(3D) printing provides a promising way to fabricate biodegradable scaffolds with designer architectures for the regeneration of various tissues.However,the existing3D-printed scaffolds commonly suffer from weak cell-scaffold interactions and insufficient cell organizations due to the limited resolution of the 3D-printed features.Here,composite scaffolds with mechanically-robust frameworks and aligned nanofibrous architectures are presented and hybrid manufactured by combining techniques of 3D printing,electrospinning,and unidirectional freeze-casting.It was found that the composite scaffolds provided volume-stable environments and enabled directed cellular infiltration for tissue regeneration.In particular,the nanofibrous architectures with aligned micropores served as artificial extracellular matrix materials and improved the attachment,proliferation,and infiltration of cells.The proposed scaffolds can also support the adipogenic maturation of adipose-derived stem cells(ADSCs)in vitro.Moreover,the composite scaffolds were found to guide directed tissue infiltration and promote nearby neovascularization when implanted into a subcutaneous model of rats,and the addition of ADSCs further enhanced their adipogenic potential.The presented hybrid manufacturing strategy might provide a promising way to produce additional topological cues within 3D-printed scaffolds for better tissue regeneration.

Expression of MUC1 and its significance in hepatocellular and cholangiocarcinoma tissue

AIM： To investigate the relation between MUC1 expression, distribution, and prognosis in hepatocellular and cholangiocarcinoma （HCC and CC） and cirrhotic liver tissues, and their significance in HCC and CC diagnosis. METHODS： Expression and distribution of MUC1 were examined by immunohistochemical assay with anti-MUC1 mAb in 59 samples of HCC and 37 samples of CC, 20 samples of cirrhotic liver tissues, and 10 samples of normal liver tissues, seeking possible associations between MUC1 positive expression, distribution in HCC and CC （primary liver cancer, PLC） cases and the studied clinical data. RESULTS： Immunohistochemical analysis of MUC1 expression showed that in the 96 PLC samples, 68 （70.8%） were strong positive, and 6 （6.2%） were weak positive. Only 4 in the 20 cirrhotic liver tissues were found to be weak positive, while no expression of MUC1 was detected in normal liver tissues. Apparently, the high expression rate of MUC1 in PLC tissues was statistically significant in comparison to that in cirrhotic and normal liver tissues. The expressed MUC1 protein, stained in dark brownish or brownish-yellow particles, chiefly localized on the cancer cell membranes or in cytoplasm. In the 68 strong positive samples, 40 were detected on cell membrane and the other 28 were in cytoplasm. In addition, follow-up studies of those PLC cases demonstrated that MUC1 expression on cell membrane or in cytoplasm was closely associated with PLC prognosis. The expression of HUC1 in PLC had little statistical significance in respect of the pathological types and sizes of the tumors, but a strong relationship regarding histological differentiation, metastasis of lymph nodes, portal canal emboli, and post-operational recurrence of the carcinomas. After 3 years of tumor excision, the metastasis rate in MUC1 positive expression group （67.6%） was much higher than that in MUC1 weak expression group （33.3%） and negative expression group （31.8%）, and thus the survival rate in MUC1-positive expression group was significantly different from that in weak and negative expression groups. CONCLUSION： Expression and localization of MUC1 proteins in primary liver carcinomas （PLCs） may act as prognostic markers, and MUC1 molecules might be helpful in differential diagnosis.

The value of 18-FDG-PET for diagnosing and evaluating lymph node metastasis in primary breast cancer

Objective: To analyze the result of 18F-2-deoxy-2-fluoro-D-glucose-positron emission tomography (FDG-PET) in suspicious primary breast cancer patients and to evaluate its value for the surgery therapy. Methods: Total 36 patients suspected of breast neoplasm were enrolled into the research. The result was compared with the pathology result. The rate of missed diagnosis, the rate of mi.sdiagnosis. the sensitivity and specificity were calculated and analyzed. Results:Compared with the pathology results, the misdiagnosis rate. the rate of missed diagnosis. the sensitivity and specificity of FDG-PET for breast cancer were 0% , 36. 36%. 63. 63% and 100%, respectively. To those who had a neoplasm no more than 2 cm in diameter, the rate of missed diagnosis was as high as 41. 67%. To 33 breast cancer patients, the misdiagnosis rate, the rate of missed diagnosis, the sensitivity and specificity for lymph node metastasis were 18. 75%, 41. 18%, 58. 82% and 81. 25%, respectively. Conclusion:FDG-PET has a perfect specificity and a considerable sensitivity to the primary breast neoplasm and similar to the lymph node metastasis diagnosis. It is an ideal choice for those patients with suspected breast cancer but reluctantly to receive a vulnerarious examination.

Treatment of hepatoma with liposome-encapsulated adriamycin administered into hepatic artery of rats

AIM： To observe the therapeutic effects of liposomeencapsulated adriamycin （LADM） on hepatoma in comparison with adriamycin solution （FADM） and adriarnycin plus blank liposome （ADM ＋ BL） administered into the hepatic artery of rats. METHODS： LADM was prepared by pH gradient-driven method. Normal saline, FADM （2 mg/kg）, ADM＋BL （2 mg/kg）, and LADM （2 mg/kg） were injected via the hepatic artery in rats bearing liver W256 carcinosarcoma, which were divided into four groups randomly. The therapeutic effects were evaluated in terms of survival time, tumor enlargement ratio, and tumor necrosis degree. The difference was determined with ANOVA and Dunnett test and log rank test. RESULTS： Compared to FADM or ADM ＋ BL, LADM produced a more significant tumor inhibition （tumor volume ratio： 1.243±0.523 vs 1.883±0.708, 1.847±0.661, P 〈 0.01）, and more extensive tumor necrosis. The increased life span was prolonged significantly in rats receiving LADM compared with FADM or ADM＋BL （231.48 vs 74.66, 94.70） （P 〈 0.05）. CONCLUSION： The anticancer efficacies of adriamycin on hepatoma can be strongly improved by liposomal encapsulation through hepatic arterial administration.

Establishment of VX2 breast carcinoma model in rabbit by injecting tumor mass suspension

Objective: To establish a stable model of VX2 breast carcinoma in rabbit and select the optimal way. Methods: Thirty female New Zealand rabbits were randomly divided into 3 groups with 10 in each. Tumor cell suspensions or tumor mass suspensions were injected into breast tissues of rabbits of group A and B, respectively. Tumor blocks were surgically implanted in rabbit breasts of group C. Tumor formation rate, tumor growth rate, and tumor-bearing survival time was compared, and the histological feature of tumor was observed. Results: Models were established conveniently and successfully in rabbits received injection of tumor mass suspensions. Tumor proliferated rapidly with the biological feature of squamous cell carcinoma. Conclusion: VX2 breast carcinoma model in rabbit was established successfully. Intramammary injection of tumor mass suspension is the best method.

Bioinformatics-led design of single-chain antibody molecules targeting DNA sequences for retinoblastoma

The development of single-chain Fv antibody (scFv) by recombinant gene expression is an important milestone for cancer therapy. Single-chain antibodies are reconstructed for cancer-targeted therapy to provide good penetration into tumor tissue and to improve their pharmacokinetics in vivo, offering a clinically valuable application. The relationship needs to be analyzed that there may be some variations between the structure and function of the fusion proteins, and the relationship between the structure and function of protein molecules was obtained through analyzing relevant literature at home and abroad as well as modeling analysis. Through our analysis of the interaction region between antibody and antigen, and of the binding sites for molecular conformation, it is clear that existing antibodies need to be modified at the DNA sequence level, enhancing the biological activity of the antibodies. Based on the view that bio-molecular computer models are closely integrated with biological experiments, a bio-molecular structure-activity relationship model can be established in terms of molecular conformation, physical and chemical properties and the biological activity of single-chain antibodies. Two enlightenments are obtained from our analysis. On one hand, the structure-activity relationship is clear for new immune molecules at the gene expression level. On the other hand, a single-chain antibody molecule can be designed and optimized for the cancer-oriented treatment. In this article, we provided the theoretical and experimental basis for the development of single-chain antibodies appropriate for retinoblastoma therapy.

Local injection of liposomal adriamycin to inhibit metastatic cell proliferation in axillary nodes in rabbits bearing breast tumors

Objective: To assess the inhibitory effects of local injection of liposomal adriamycin (LADR) on the proliferation of lymph node metastases in rabbits bearing VX2 carcinoma in the mammary gland. Methods:Thirty female New Zealand white rabbits were divided into 3 groups, with 10 in each. VX2 tumor mass suspensions were injected into the breast tissues of rabbits. Treatment initiated once the axillary lymph node reached 5 mm in the maximum diameter. Group 1 received a sham treatment. Group 2 received a subcutaneous injection of LADR adjacent to tumor. Group 3 received an intravenous injection of free ADR (FADR) at the same dose and concentration to group 2. The breast tumors and axillary lymph nodes were resected after the treatment was repeated 3 times. The tumor and node sizes before and after treatment were measured. PCNA mRNA expressions in breast tumors and axillary nodes were determined using RT-PCR. Results: The mean growth ratios of lymph nodes after treatment were 3. 70, 1. 55, and 2. 89,respectively, in groups 1,2, and 3. The slowest node growth was observed in animals of group 2, with significant differences from group 1 (P<0. 001) and group 3 (P = 0. 002). The relative values of PCNA mRNA expression in lymph nodes were 0. 541, 0. 329,and 0. 450, respectively, in groups 1,2, and 3. Group 2 exhibited a significantly reduced PCNA mRNA expression in metastatic lymph node, as compared to group 1 (P<0. 001) and group 3 (P = 0. 004). Intravenous FADR injection effectively lowered the mRNA expressions of PCNA in breast tumors, which were not apparently altered after local LADR injection. Conclusion: Local injection of LADR holds a strong inhibitory effect on the proliferation of metastatic tumor cells in lymph nodes and appears to be an effective method for the treatment of lymphatic metastases of breast cancer.