Reduction-responsive supramolecular hybridized paclitaxel nanoparticles for tumor treatment.

Powerful chemotherapeutics have been used to combat tumor cells, but serious adverse effects and poor therapeutic efficiency restrict their clinical performance. Herein, we developed reduction-responsive supramolecular hybridized paclitaxel nanoparticles (PTX@HOMNs) for improved tumor treatment. The nanocarrier is composed of F127 and strengthened by a disulfide bond linked organosilica network, which ensures the desirable stability during blood circulation and controlled drug release at tumor sites. The as-prepared PTX@HOMNs could effectively accumulate at tumor regions. After entering tumor cells, PTX@HOMNs can respond to intracellular glutathione, and trigger active drug release for chemotherapy. As a result, PTX@HOMNs exhibited potent antitumor activity against ovarian tumors in vitro and in vivo. Our work provides a deep insight into constructing simple and controlled drug delivery nanoplatforms for improved tumor treatment.

Truncated Lactoferricin Peptide Controls Cervical Cancer Cell Proliferation via lncRNA-NKILA/NF-κB Feedback Loop.

BACKGROUND: Lactoferricin peptide (LP) has been reported to control cancer cell proliferation. NF-κB interacting lncRNA (NKILA) is a tumor suppressor in several cancers. OBJECTIVE: We aimed to explore the potential function of the truncated LP (TLP) in the prevention of cervical cancer cell proliferation. METHODS: Bioinformatics analysis via PPA-Pred2 showed that 18-aa N-terminus of truncated lactoferricin peptide (TLP18, FKCRRWQWRMKKLGAPSI) shows higher affinity with nuclear factor kappaB (NF-κB) than LP. The effects of LP and TLP18 on cervical cancer cells SiHa and HeLa and the related mechanisms were explored by investigating NF-κB and lncRNA-NKILA. RESULTS: TLP18 shows an inhibitory rate up to 0.4-fold higher than LP on the growth of cervical cancer cells (P<0.05). NKILA siRNA promoted cell growth whether LP or TLP18 treatment (P<0.05). TLP18 treatment increases the level of lncRNA-NKILA and reduces the level of NF-κB up to 0.2-fold and 0.6-fold higher than LP (P<0.05), respectively. NKILA siRNA increased the levels of NF-κB, cleaved caspase-3, and BAX (P<0.05). TLP18 increased apoptotic cell rate up to 0.2-fold higher than LP, while NKILA siRNA inhibited cell apoptosis cell growth even LP or TLP18 treatment. CONCLUSION: Truncated Lactoferricin peptide controls cervical cancer cell proliferation via lncRNA- NKILA/NF-κB feedback loop.

Anti-tumour effects of a dual cancer-specific oncolytic adenovirus on Breast Cancer Stem cells.

Apoptin can specifically kill cancer cells but has no toxicity to normal cells. Human telomerase reverse transcriptase (hTERT) can act as a tumour-specific promoter by triggering the expression of certain genes in tumour cells. This study aims to investigate the inhibitory effects and to explore the inhibitory pathway of a dual cancer-specific recombinant adenovirus (Ad-apoptin-hTERTp-E1a, Ad-VT) on breast cancer stem cells. Breast cancer cell spheres were obtained from MCF-7 cells through serum-free suspension culture. The cell spheres were detected by flow cytometry for CD44+ CD24- cell subsets. The stemness of MCF-7-CSC cells was confirmed by in vivo tumorigenesis experiments. The inhibitory effect of the recombinant adenoviruses on MCF-7-CSC cells was evaluated by CCK-8 assay. In addition, the stemness of adenovirus-infected MCF-7-CSC cells was analysed by testing the presence of CD44+ CD24- cell subsets. The ability of the recombinant adenovirus to induce MCF-7-CSC cell apoptosis was detected by staining JC-1, TMRM and Annexin V. Our results showed that a significantly higher proportion of the CD44+ CD24- cell subsets was present in MCF-7-CSC cells with a significantly increased expression of stem cell marker proteins. The MCF-7-CSC cells, whlist exhibited a strong tumorigenic ability with a certain degree of stemness in mice, were shown to be strongly inhibited by recombinant adenovirus Ad-VT through cell apoptosis. In addition, Ad-VT was shown to exert a killing effect on BCSCs. These results provide a new theoretical basis for the future treatment of breast cancer.

Anti-tumor effect of a dual cancer-specific recombinant adenovirus on ovarian cancer cells.

BACKGROUND: Apoptin can specifically kill cancer cells but has no toxicity to normal cells. Human telomerase reverse transcriptase (hTERT) acts as a tumor-specific promoter, triggering certain genes to replicate or express only in tumor cells, conferring specific replication and killing abilities. This study aimed at investigating the anticancer potential of the recombinant adenovirus Ad-apoptin-hTERTp-E1a (Ad-VT) in ovarian cancer treatment. METHODS: Crystal Violet staining and WST-1 assays were used to analyze the inhibitory effect of Ad-VT on ovarian cancer SKOV3 and OVCAR-3 cells. Ad-VT-induced apoptosis of ovarian cancer cells, was detected using Hoechst, Annexin V-FITC/PI, JC-1 staining. Cell migration and invasion of ovarian cancer cells were detected using cell-scratch and Transwell assays. The pGL4.51 plasmid was used to transfect and to generate SKOV3-LUC cells, that stably express luciferase. The in vivo tumor inhibition effect of Ad-VT was subsequently confirmed using a tumor-bearing nude mouse model. RESULTS: Ad-VT had a strong apoptosis-inducing effect on SKOV3 and OVCAR-3 cells, that was mainly mediated through the mitochondrial apoptotic pathway. The Ad-VT could significantly increase the inhibition of ovarian cancer cell migration and invasion. The Ad-VT also can inhibit tumor growth and reduce toxicity in vivo. CONCLUSIONS: The recombinant adenovirus, comprising the apoptin protein and the hTERTp promoter, was able to inhibit the growth of ovarian cancer cells and promote their apoptosis.

Chemovirotherapy of Lung Squamous Cell Carcinoma by Combining Oncolytic Adenovirus With Gemcitabine.

Oncolytic virotherapy is emerging as an important agent in cancer treatment. In a previous study, we designed and constructed Ad-Apoptin-hTERTp-E1a (Ad-VT), a dual cancer-selective anti-tumor recombinant adenovirus. In this study, crystal violet staining and WST-1 assays showed that Ad-VT has a significant tumor killing effect in a time and dose dependent manner. The combination of Ad-VT (10 MOI) and gemcitabine (10 nM) significantly inhibited NCI-H226 cells, but did not increase the killing effect of gemcitabine on human normal bronchial epithelial cells BEAS-2B. Hoechst, JC-1 and Annexin V experiments demonstrated that the combination of Ad-VT and gemcitabine mainly inhibited NCI-H226 cell proliferation by inducing apoptosis (mitochondrial pathway). The combination also significantly inhibited the migration and invasion abilities of NCI-H226 cells. In vivo, Ad-VT in combination with low-dose gemcitabine could effectively inhibit tumor growth and prolong survival of mice. Ad-VT has the characteristics of tumor-selective replication and killing, in vitro and in vivo. The combined application of Ad-VT and gemcitabine has a synergistic effect, which can increase the anti-tumor effect and reduce the toxicity of chemotherapy drugs, indicating that Ad-VT has a potential clinical value in the treatment of lung squamous cell carcinoma.

Recombinant adenoviruses expressing apoptin suppress the growth of MCF­7 breast cancer cells and affect cell autophagy.

Autophagy and apoptosis both promote cell death; however, the relationship between them is subtle, and they mutually promote and antagonize each other. Apoptin can induce apoptosis of various tumor cells; however, tumor cell death is not only caused by apoptosis. Whether apoptin affects tumor cell autophagy is poorly understood. Therefore, the present study aimed to explore the potential mechanisms underlying the effects of apoptin using recombinant adenoviruses expressing apoptin. Reverse transcription­quantitative polymerase chain reaction, immunoblotting, flow cytometry, fluorescence microscopy and proteomics analyses revealed that apoptin could induce autophagy in MCF­7 breast cancer cells. The results also suggested that apoptin affected autophagy in a time­ and dose­dependent manner. During the early stage of apoptin stimulation (6 and 12 h), the expression levels of autophagy pathway­associated proteins, including Beclin­1, microtubule­associated protein 1A/1B­light chain 3, autophagy­related 4B cysteine peptidase and autophagy­related 5, were significantly increased, suggesting that apoptin promoted the upregulation of autophagy in MCF­7 cells. Conversely, after 12 h of apoptin stimulation, the expression levels of apoptosis­associated proteins were decreased, thus suggesting that apoptosis may be inhibited. Therefore, it was hypothesized that apoptin may enhance autophagy and inhibit apoptosis in MCF­7 cells at the early stage. In conclusion, apoptin­induced cell death may involve both autophagy and apoptosis. The induction of autophagy may inhibit apoptosis, whereas apoptosis may inhibit autophagy; however, occasionally both pathways operate at the same time and involve apoptin. This apoptin­associated selection between tumor cell survival and death may provide a potential therapeutic strategy for breast cancer.

Synergistic antitumor effect of the combination of a dual cancer-specific oncolytic adenovirus and cisplatin on lung cancer cells.

The effect of the combination of a recombinant adenovirus (ATV) expressing a specific apoptin protein and cisplatin on human lung cancer cells (A549 cells) was determined. The inhibitory effects of ATV and cisplatin, ATV alone, or cisplatin alone on the migration and invasion of A549 cells were evaluated in vitro using cell proliferation, wound healing, Transwell migration and Matrigel invasion assays. The tumor inhibition effect on A549 cells in vivo was assessed by observing the tumor growth and survival rate of nude mice with subcutaneous tumor xenografts grown from implanted A549 cells after treatment with ATV, cisplatin, or ATV combined with cisplatin. The proliferation (P<0.01), migration (P<0.01), and invasion (P<0.01) on A549 cells was suppressed significantly by ATV, cisplatin, and ATV and cisplatin, in a dose- and time-dependent manner. The inhibition of tumor growth in transplanted nude mice in the ATV combined with cisplatin group was significantly higher than that displayed in the other groups, and the survival rate of the combined treatment group was significantly higher than that of the group treated with cisplatin alone. The results indicated that the combined application of ATV and cisplatin could reduce toxicity and showed a synergistic effect in reducing tumor growth and increasing survival. Thus, there is a potential research value in treating tumors using the combination of ATV and cisplatin, which provides a foundation for future preclinical studies on this antitumor treatment.

Misdiagnosis of aggressive fibromatosis of the abdominal wall: A case report and literature review.

RATIONALE: Aggressive fibromatosis (AF) of abdominal wall is also called desmoid tumor, ligament tumor, fibrous tissue tumor hyperplasia, tendon membrane fibroma or soft tissue ligament fibroma, etc. Aggressive fibromatosis of abdominal wall was first described by MacFarlane in 1832, and it was named for the first time by Muller according to its general appearance and texture in 1838. This disease has been mistaken for a benign lesions for a long time because when the cells were examined by pathology often show normal mitosis, and distant metastases are not found clinically, but actually the disease is locally invasive and shows a local invasive growth. So it is a rare low-grade malignant soft tissue tumor. At present, the main treatment for the disease is operation, and radiotherapy and hormone therapy have a certain effect, but these therapies are not ideal. PATIENT CONCERNS: A 32-year-old woman, who underwent cesarean section three years ago came to the hospital for finding a mass on abdominal wall for half a month. DIAGNOSES: Mass of abdominal wall. INTERVENTIONS: Underwent surgery. OUTCOMES: Pathology: The lesion is aggressive fibromatosis of abdominal wall (ligament tumor of abdominal wall). LESSONS: We discussed the particularity of its clinical characteristics, treatment strategies and prognosis combined with literature review, and we think the surgeons need to pay high attention to this disease and make more patients get timely, correct and reasonable treatment, so as to improve the quality of life.