Analysis of Maxillofacial Fractures Based on the Etiology in Southeast China: A 10-Year, Multi-Center Study.

BACKGROUND: The aim of this study was to explore the characteristics and correlation of maxillofacial fractures and concurrent injuries with different injury causes. METHODS: In this retrospective study, data were collected from patients treated for maxillofacial fractures in 3 oral and maxillofacial surgery departments in Southeast China, from January 2010 to December 2019. The information was obtained from clinical notes and surgical records using a standardized data collection form, and some causes of injuries were confirmed by telephone follow-ups and police records. These patients were divided into 7 groups according to the etiology: bicycle accident, electric bicycle accident, motorcycle accident, automobile accident, fall at ground level, fall from a height, and assault-related accident. Statistical tests were performed using R software (version 3.1.1), and all P-values were computed based on Chi-square tests and set at 0.05. RESULTS: During this 10-year retrospective study, a total of 1772 patients with definite causes were analyzed. The average age was approximately 35.04 years (9 months-94 years). All patients were treated with open reduction and rigidly internal fixation, and the average duration was approximately 6.51 days (range 0 day-50 days), that from the time of the injury to the time of treatment. Traffic accidents were identified as the main cause of maxillofacial fracture (57.62%; n = 1021 of 1772 cases). In different etiology groups, there were statistically significant differences in the distribution of age, sex, maxillofacial fracture type, and concurrent injuries (all P < 0.001). However, the main cause of maxillofacial injuries was falls (fall at ground level and fall from a height) in children, and the highest incidence of the cause of maxillofacial injuries was bicycle accident in adolescents. Compared with the other groups, zygomatic complex fracture was more common in the electric bicycle accident group, panfacial fracture was more common in the automobile accident group, and mandible fracture was more common in the other groups. CONCLUSION: The results of this study suggest that patients with maxillofacial fractures caused by different injuries had their own unique characteristics. These findings may assist us in avoiding misdiagnosis and treatment delays, and may make treatment plans faster.

Dual inhibition of the vascular endothelial growth factor pathway: a phase 1 trial evaluating bevacizumab and AZD2171 (cediranib) in patients with advanced solid tumors.

BACKGROUND: The current study was conducted to evaluate the safety and biological activity of dual inhibition of the vascular endothelial growth factor (VEGF) pathway with combined bevacizumab and cediranib (a VEGF receptor tyrosine kinase inhibitor). METHODS: This was a 3 + 3 dose escalation study in patients with advanced solid tumors. Cediranib was given orally daily for 21 days and bevacizumab intravenously every 2 weeks. Pharmacokinetics and correlates (nitric oxide synthase, nitrate oxide, and circulating tumor cells) were assessed. RESULTS: Fifty-one patients were treated. Dose-limiting toxicities (DLTs) (grade 3-4; graded according to the National Cancer Institute Common Terminology Criteria of Adverse Events [version 3.0]) observed included 1 patient with chest pain, 1 patient with fatigue, 2 patients with thrombocytopenia, 3 patients with hypertension (1 with intracranial hemorrhage), and 1 patient with grade 5 hemoptysis. Moreover, 2 patients presented with grade 3 intracranial bleeding beyond the DLT window. Dose level 2 (cediranib at a dose of 20 mg/day and bevacizumab at a dose of 5 mg/kg every 2 weeks) was selected as the recommended phase 2 dose (RP2D); 17 patients were treated at dose level 2 with 1 DLT and no intracranial bleeding or severe hypertension reported. Pharmacokinetics of cediranib at dose level 3 demonstrated a 46% to 77% increase in area under the curve (0-24 hours) on cycle 1 day 1 compared with historical controls. Four patients attained partial remissions: inflammatory breast cancer (-54%), basal cell carcinoma (-33%), alveolar soft part sarcoma (-33%), and synovial sarcoma (-32%). Patients with a lower circulating tumor cell count (< 30) at the predose period had a longer time to tumor progression (P = .024, log-rank test). CONCLUSIONS: Cediranib at a dose of 20 mg/day and bevacizumab at a dose of 5 mg/kg every 2 weeks was found to be the RP2D. Activity in several tumor types was noted. Central nervous system bleeding and severe hypertension were observed at doses above the RP2D.

Antigen binding of human IgG Fabs mediate ERK-associated proliferation of human breast cancer cells.

Serum-circulating antibody can be linked to poor outcomes in some cancer patients. To investigate the role of human antibodies in regulating tumor cell growth, we constructed a recombinant cDNA expression library of human IgG Fab from a patient with breast cancer. Clones were screened from the library with breast tumor cell lysate. Sequence analysis of the clones showed somatic hypermutations when compared to their closest VH/VL germ-line genes. Initial characterizations focused on five clones. All tested clones displayed stronger binding to antigen derived from primary breast cancers and established breast cancer cell lines than to normal breast tissues. In vitro functional studies showed that four out of five tested clones could stimulate the growth of MDA-MB-231 breast cancer cell lines, and one out of five was able to promote MCF-7 cell growth as well. Involvement of ERK2 pathway was observed. By 1H-NMR spectra and Western blot analysis, it was evident that two tested antibody Fabs are capable of interacting with sialic acid. Our study suggests a possible role for human antibody in promoting tumor cell growth by direct binding of IgG Fab to breast tumor antigen. Such studies prompt speculation regarding the role of serum antibodies in mediating tumor growth as well as their contribution to disease progression.

Tumor lysate-specific cytotoxic T lymphocytes in multiple myeloma: promising effector cells for immunotherapy.

The idiotype protein, secreted by myeloma plasma cells, is a tumor-specific but weak antigen. Idiotype-based immunotherapy has been explored in myeloma patients with disappointing results. It is conceivable that myeloma cells contain a multitude of tumor antigens that can more effectively stimulate antitumor T cells. To explore the possibility of using whole myeloma cells as a source of tumor antigens for immunotherapy, the current study was undertaken to generate and examine the function of myeloma-specific cytotoxic T lymphocytes (CTLs) by using dendritic cells (DCs) pulsed with myeloma cell lysates as stimulating cells. After repeated stimulation, specific CTL lines, containing CD4(+) and CD8(+) T cells, were generated from myeloma patients. Our results show that these T cells not only recognized and lysed autologous myeloma protein-pulsed DCs, they also killed autologous primary myeloma cells. Occasionally, CTLs responded to autologous idiotype-pulsed DCs and to allogeneic primary myeloma cells. No cytolytic activity, however, was detected against autologous lymphocytes including B cells, suggesting that the T cells acted specifically against myeloma cells. Cytotoxicity against target cells was major histocompatibility complex class 1 and, to a lesser extent, class 2 restricted and was dependent mainly on the perforin-mediated pathway. CTLs secreted predominantly interferon-gamma and tumor necrosis factor-alpha on antigenic stimulation, indicating a type 1 T-cell subset. These findings represent the first demonstration that tumor cell lysate-primed CTLs kill only myeloma cells, not autologous lymphocytes. This provides a rationale for myeloma cell-based immunotherapy in multiple myeloma.

Malignancy: Idiotypic Immune Targeting of Multiple Myeloma.

Immunotherapy of malignant diseases remains a major therapeutic challenge. In multiple myeloma, interests have been focussed primarily on the targeting of the idiotypic protein since it represents one of the few tumor specific antigens. Various vaccination strategies have been employed, including the use of naked protein, protein conjugated to Keyhole Limpet Hemocyanin and, most recently, vaccine delivered via dendritic cells. Studies so far indicate the feasibility of inducing potentially beneficial idiotype-specific immune responses in the autologous hosts. However, the antitumor responses produced by the vaccines have been generally modest and sup-optimal. Further work is therefore ongoing to optimize the antitumor responses by including cytokines in the vaccination schedule. In addition, the development of a polyvalent vaccine is also being explored. The next few years should prove interesting and crucial in bringing effective and reliable immunotherapeutic strategies to the clinics.