Stepwise-targeting and hypoxia-responsive liposome AMVY@NPs carrying siYAP and verteporfin for glioblastoma therapy.

BACKGROUND: The Hippo pathway is a conserved tumour suppressor signalling pathway, and its dysregulation is often associated with abnormal cell growth and tumorigenesis. We previously revealed that the transcriptional coactivator Yes-associated protein (YAP), the key effector of the Hippo pathway, is a molecular target for glioblastoma (GBM), the most common malignant brain tumour. Inhibiting YAP with small interfering RNA (siYAP) or the specific inhibitor verteporfin (VP) can diminish GBM growth to a certain degree. RESULTS: In this study, to enhance the anti-GBM effect of siYAP and VP, we designed stepwise-targeting and hypoxia-responsive liposomes (AMVY@NPs), which encapsulate hypoxia-responsive polymetronidazole-coated VP and DOTAP adsorbed siYAP, with angiopep-2 (A2) modification on the surface. AMVY@NPs exhibited excellent blood‒brain barrier crossing, GBM targeting, and hypoxia-responsive and efficient siYAP and VP release properties. By inhibiting the expression and function of YAP, AMVY@NPs synergistically inhibited both the growth and stemness of GBM in vitro. Moreover, AMVY@NPs strongly inhibited the growth of orthotopic U87 xenografts and improved the survival of tumour-bearing mice without adverse effects. CONCLUSION: Specific targeting of YAP with stepwise-targeting and hypoxia-responsive liposome AMVY@NPs carrying siYAP and VP efficiently inhibited GBM progression. This study provides a valuable drug delivery platform and creative insights for molecular targeted treatment of GBM in the future.

Reconstruction of Anterior Mandible and Mouth Floor Using the Myofascial Iliac Crest Free Flap After Tumor Resection.

The current study introduces a novel approach of anterior mandible and mouth floor reconstruction with the myofascial iliac crest free flap. A series of 4 patients who presented between May 2015 and July 2017 had benefited from this technique. The myofascial component of this flap was designed to be attached to the iliac crest, and the flap was obtained after identifying the neurovascular pedicle. We transferred the iliac crest, with an outward-oriented placement, to the mandibular defect as the base of the alveolar process. We found that the iliac crest can provide sufficient bone height and an aesthetic shape for the reconstruction of the anterior mandible. More important, we also observed that the myofascial component on the flap surface completely replaced the oral mucosa in as early as 1 month after the operation. Moreover, the proper soft tissue volume can be achieved using this approach for better functional reconstruction of the oral mucosa. No obvious scar contracture of the myofascial component was observed during the follow-up period. The myofascial iliac crest free flap could provide a suitable reconstruction method for combined oral mucosa-mandible defects.

Repair of buccal mucosa and floor of mouth defects using keystone design perforator island flap.

OBJECTIVE: To assess the feasibility of utilizing the keystone design perforator island flap (KDPIF) for the repair of small to medium-sized defects in the buccal mucosa and floor of mouth (cT1-2 stage tumor). STUDY DESIGN: We conducted a retrospective analysis of eight patients who underwent KDPIF to address oral defects at the Affiliated Hospital of Qingdao University between June 2021 and September 2022. Patient information, including medical history, defect site, flap size, operative time, hospital stay, complications, and postoperative recovery of oral function, was comprehensively evaluated. RESULTS: Eight patients (6 females and 2 males) underwent reconstruction using KDPIF. The mean operation time was 58.5 minutes (55-63 minutes), with an average length of stay of 3.5 days (3-5 days). None of the 8 cases (100%) exhibited flap splitting necrosis or infection. Moreover, no scar contracture was observed, and oral functions, including the degree of opening, type of opening, tongue mobility, speech function, and swallowing function, were successfully restored. One patient (12.5%) experienced bleeding from the incision on the first postoperative day, but following compression, hemostasis was achieved, and the incision healed well. CONCLUSIONS: KDPIF demonstrates technical feasibility and suitability for repairing small to medium-sized buccal mucosa and floor of mouth defects (cT1-2).

Knowledge of Chinese dentists on HPV, their willingness and barriers to recommend HPV vaccination to patients.

Objective: This study aimed to assess the knowledge of Chinese dentists on human papilloma virus (HPV), their willingness and factors prevention them from recommending patients for HPV vaccination, and to identify ways through which dentists can acquire HPV-related knowledge.Methods: This was a cross-sectional study based on Chinese dentists. The anonymous self-filled questionnaire method was used to collect demographic information of participants, their knowledge of HPV, willingness and barriers to recommending HPV vaccines to patients, and the strategies they can adopt to obtain HPV-related knowledge.Results: A total of 517 dentists completed the questionnaire, and 89.94% of dentists were willing to recommend HPV vaccination to patients. Participants aged 30-39 years, male dentists and dentist-in-charge had relatively lower knowledge scores than other groups. Besides, participants aged 30-39 years, working in private hospitals, and practicing in Southern China had a lower willingness to recommend HPV vaccination to patients. Recommending HPV vaccination to patients is not within the scope of practicing dentists, and concerns about the safety of the HPV vaccine were found to be the main barriers preventing its recommendation. Notably, 97.87% of dentists were eager to acquire HPV-related knowledge, and agreed for the first time to enroll in relevant educational courses.Conclusion: Chinese dentists had expressed a strong desire to recommend HPV vaccines to patients, even though their knowledge of HPV was scanty. Therefore, measures to improve their understanding of HPV vaccines and eliminate barriers suppressing their willingness to recommend HPV vaccines are urgently needed.

Hypoxia-Responsive Lipid-Polymer Nanoparticle-Combined Imaging-Guided Surgery and Multitherapy Strategies for Glioma.

Glioma is the most prevalent type of malignant brain tumor and is usually very aggressive. Because of the high invasiveness and aggressive proliferative growth of glioma, it is difficult to resect completely or cure with surgery. Residual glioma cells are a primary cause of postoperative recurrence. Herein, we describe a hypoxia-responsive lipid polymer nanoparticle (LN) for fluorescence-guided surgery, chemotherapy, photodynamic therapy (PDT), and photothermal therapy (PTT) combination multitherapy strategies targeting glioma. The hypoxia-responsive LN [LN (DOX + ICG)] contains a hypoxia-responsive component poly(nitroimidazole)25 [P-(Nis)25], the glioma-targeting peptide angiopep-2 (A2), indocyanine green (ICG), and doxorubicin (DOX). LN (DOX + ICG) comprises four distinct functional components: (1) A2: A2 modified nanoparticles effectively target gliomas, enhancing drug concentration in gliomas; (2) P-(Nis)25: (i) the hydrophobic component of LN (DOX + ICG) with hypoxia responsive ability to encapsulate DOX and ICG; (ii) allows rapid release of DOX from LN (DOX + ICG) after 808 nm laser irradiation; (3) ICG: (i) ICG allows imaging-guided surgery, combining PDT and PTT therapies; (ii) upon irradiation with an 808 nm laser, ICG creates a hypoxic environment; (4) DOX inhibits glioma growth. This work demonstrates that LN (DOX + ICG) might provide a novel clinical approach to preventing post-surgical recurrence of glioma.

[Comparative study on using multiple kinds of sternocleidomastoid flaps or free flaps to repair defects in oral cancer surgery].

PURPOSE: To compare the outcomes of using multiple kinds of sternocleidomastoid flap or free flaps to repair defects after oral cancer surgery. METHODS: Twenty-eight cases using sternocleidomastoid flaps and 30 cases using free flaps were included in this study. Operation was performed in 58 patients with oral cavity cancer. The basic and surgical informations, and postoperative function were analyzed between two groups with SPSS 22.0 software package. RESULTS: The tumor size mostly belonged to T1-T2, and the primary sites were the tongue, lower gingiva, floor of mouth, base of tongue or oropharynx in patients undergoing sternocleidomastoid flaps, whose average age was higher, surgical time was shorter, systemic diseases was more serious, and surgical cost, hospital stay, tracheotomy rate was less than patients undergoing free flaps (P<0.05). Patients in the two groups had similar oral function after surgery (P>0.05). CONCLUSIONS: Selection of sternocleidomastoid flaps or free flaps for repairing oral cancer defects is dependent on a variety of factors such as the age of patients, the size and location of tumor, metastasis of cervical lymph nodes and the general conditions. Sternocleidomastoid flap is a good choice for patients with advanced ages, small size of lesions (T1-T2) and concomitant systemic diseases.

Self-assembled angiopep-2 modified lipid-poly (hypoxic radiosensitized polyprodrug) nanoparticles delivery TMZ for glioma synergistic TMZ and RT therapy.

The addition of temozolomide (TMZ) to radiotherapy (RT) improves survival of patients with glioblastoma (GBM). However, TMZ + RT causes excess toxicity in patients. In this study, we prepared angiopep-2 (A2) modified lipid-poly (hypoxic radiosensitized polyprodrug) nanoparticles for TMZ delivery (A2-P(MIs)25/TMZ) to achieve synergistic effects against glioma. This A2-P(MIs)25/TMZ display highly promising advantages: (1) a hydrophobic P-(MIs)25 core where poorly water-soluble TMZ can be encapsulated; (2) nitro groups of the hydrophobic P-(MIs)25 core that are converted into hydrophilic amino groups (P(NH2s)25) under low oxygen conditions to mimic the oxygen-increased sensitization to RT; (3) a lipid monolayer at the interface of the core and the shell to modify the A2 (a specific ligand for low-density lipoprotein receptor-related protein-1 (LRP-1), which are expressed in the blood-brain barrier (BBB) and human glioma cells), thereby enhancing the drug encapsulation efficiency in glioma. These nanoparticles appear as a promising and robust nanoplatforms for TMZ and hypoxic cell radiosensitization delivery.