Exposure to ambient air pollution and the incidence of lung cancer and breast cancer in the Ontario Population Health and Environment Cohort

Lung and female breast cancers are highly prevalent worldwide. Although the association between exposure to ambient fine particulate matter (PM_2.5) and lung cancer has been recognized, there is less evidence for associations with other common air pollutants such as nitrogen dioxide (NO₂) and ozone (O₃). Even less is known about potential associations between these pollutants and breast cancer. We conducted a population-based cohort study to investigate the associations of chronic exposure to PM_2.5, NO₂, O₃ and redox-weighted average of NO₂ and O₃ (O_x) with incident lung and breast cancer, using the Ontario Population Health and Environment Cohort (ONPHEC), which includes all long-term residents aged 35–85 years who lived in Ontario, Canada, 2001–2015. Incident lung and breast cancers were ascertained using the Ontario Cancer Registry. Annual estimates of exposures were assigned to the residential postal codes of subjects for each year during follow-up. We used Cox proportional-hazards models adjusting for personal- and neighborhood-level covariates. Our cohorts for lung and breast cancer analyses included ~4.9 million individuals and ~2.5 million women, respectively. During follow-up, 100,146 incident cases of lung cancer and 91,146 incident cases of breast cancer were diagnosed. The fully adjusted analyses showed positive associations of lung cancer incidence with PM_2.5 (hazard ratio [HR] = 1.02 [95% CI: 1.01–1.05] per 5.3 μg/m³) and NO₂ (HR = 1.05 [95% CI: 1.03–1.07] per 14 ppb). No associations with lung cancer were observed for O₃ or O_x. Relationships between PM_2.5 and NO₂ with lung cancer exhibited a sublinear shape. We did not find compelling evidence linking air pollution to breast cancer.     

The generation and analyses of a novel combination of recombinant adenovirus vaccines targeting three tumor antigens as an immunotherapeutic

Phenotypic heterogeneity of human carcinoma lesions, including heterogeneity in expression of tumor-associated antigens (TAAs), is a well-established phenomenon. Carcinoembryonic antigen (CEA), MUC1, and brachyury are diverse TAAs, each of which is expressed on a wide range of human tumors. We have previously reported on a novel adenovirus serotype 5 (Ad5) vector gene delivery platform (Ad5 [E1-, E2b-]) in which regions of the early 1 (E1), early 2 (E2b), and early 3 (E3) genes have been deleted. The unique deletions in this platform result in a dramatic decrease in late gene expression, leading to a marked reduction in host immune response to the vector. Ad5 [E1-, E2b-]-CEA vaccine (ETBX-011) has been employed in clinical studies as an active vaccine to induce immune responses to CEA in metastatic colorectal cancer patients. We report here the development of novel recombinant Ad5 [E1-, E2b-]-brachyury and-MUC1 vaccine constructs, each capable of activating antigen-specific human T cells in vitro and inducing antigen-specific CD4⁺ and CD8⁺ T cells in vaccinated mice. We also describe the use of a combination of the three vaccines (designated Tri-Ad5) of Ad5 [E1-, E2b-]-CEA, Ad5 [E1-, E2b-]-brachyury and Ad5 [E1-, E2b-]-MUC1, and demonstrate that there is minimal to no “antigenic competition” in in vitro studies of human dendritic cells, or in murine vaccination studies. The studies reported herein support the rationale for the application of Tri-Ad5 as a therapeutic modality to induce immune responses to a diverse range of human TAAs for potential clinical studies.     

Platelet-derived growth factor stimulates bone fill and rate of attachment level gain: results of a large multicenter randomized controlled trial

BACKGROUND: Growth factors are generally accepted to be essential mediators of tissue repair via well-established mechanisms of action that include stimulatory effects on angiogenesis and cellular proliferation, ingrowth, differentiation, and matrix biosynthesis. The aim of this study was to evaluate in a large-scale, prospective, blinded, and randomized controlled clinical trial the safety and effectiveness of purified recombinant human platelet-derived growth factor (rhPDGF-BB) mixed with a synthetic beta-tricalcium phosphate (beta-TCP) matrix for the treatment of advanced periodontal osseous defects at 6 months of healing. METHODS: Eleven clinical centers enrolled 180 subjects, each requiring surgical treatment of a 4 mm or greater intrabony periodontal defect and meeting all inclusion and exclusion criteria. Subjects were randomized into one of three treatment groups: 1) beta-TCP + 0.3 mg/ml rhPDGF-BB in buffer; 2) beta-TCP + 1.0 mg/ml rhPDGF-BB in buffer; and 3) beta-TCP + buffer (active control). Safety data were assessed by the frequency and severity of adverse events. Effectiveness measurements included clinical attachment levels (CAL) and gingival recession (GR) measured clinically and linear bone growth (LBG) and percent bone fill (% BF) as assessed radiographically by an independent centralized radiology review center. The area under the curve (AUC), an assessment of the rate of healing, was also calculated for CAL measurements. The surgeons, clinical and radiographic evaluators, patients, and study sponsor were all masked with respect to treatment groups. RESULTS: CAL gain was significantly greater at 3 months for group 1 (rhPDGF 0.3 mg/ml) compared to group 3 (beta-TCP + buffer) (3.8 versus 3.3 mm; P = 0.032), although by 6 months, this finding was not statistically significant (P = 0.11). This early acceleration of CAL gain led to group 1 exhibiting a significantly greater rate of CAL gain between baseline and 6 months than group 3 as assessed by the AUC (68.4- versus 60.1-mm weeks; P = 0.033). rhPDGF (0.3 mg/ml)-treated sites also had significantly greater linear bone gain (2.6 versus 0.9 mm, respectively; P < 0.001) and percent defect fill (57% versus 18%, respectively; P < 0.001) than the sites receiving the bone substitute with buffer at 6 months. There was less GR at 3 months in group 1 compared to group 3 (P = 0.04); at 6 months, GR for group 1 remained unchanged, whereas there was a slight gain in gingival height for group 3 resulting in comparable GR. There were no serious adverse events attributable to any of the treatments. CONCLUSIONS: To our knowledge, this study is the largest prospective, randomized, triple-blinded, and controlled pivotal clinical trial reported to date assessing a putative periodontal regenerative and wound healing therapy. The study demonstrated that the use of rhPDGF-BB was safe and effective in the treatment of periodontal osseous defects. Treatment with rhPDGF-BB stimulated a significant increase in the rate of CAL gain, reduced gingival recession at 3 months post-surgery, and improved bone fill as compared to a beta-TCP bone substitute at 6 months.     

De Novo Bone Induction by Recombinant Human Bone Morphogenetic Protein-2 (rhBMP-2) in Maxillary Sinus Floor Augmentation

PURPOSE: This phase II study was designed to evaluate 2 concentrations of recombinant human bone morphogenetic protein-2 (rhBMP-2) for safety and efficacy in inducing adequate bone for endosseous dental implant in patients requiring staged maxillary sinus floor augmentation. MATERIALS AND METHODS: Patients were treated with rhBMP-2 (via an absorbable collagen sponge [ACS]), at concentrations of 0.75 mg/mL (n = 18), 1.50 mg/mL (n = 17), or with bone graft (n = 13). Bone induction was assessed by alveolar ridge height, width, and density measurements from computed tomography scans obtained before and 4 months after treatment and 6 months post-functional loading of dental implants (density only). RESULTS: Mean increases in alveolar ridge height at 4 months after treatment were similar among the groups; 11.3 mm, 9.5 mm, and 10.2 mm, respectively, in the bone graft, 0.75 mg/mL, and 1.50 mg/mL rhBMP-2/ACS treatment groups. Mean increases in alveolar ridge width (buccal to lingual) at the crest of the ridge were statistically different among the treatment groups; 4.7 mm, 2.0 mm, and 2.0 mm, respectively, in the bone graft, 0.75 mg/mL, and 1.50 mg/mL treatment groups (P 相似文献   

Pilot clinical and histologic evaluations of a two-piece zirconia implant

An investigation was conducted to evaluate the clinical and histologic results of bone and soft tissue healing around a two-piece zirconia dental implant in a human model. A healthy female patient requiring tooth replacement with dental implants received a two-piece zirconia implant together with conventional titanium implants to be implemented in a prosthesis. Clinical and radiographic evaluations at 6 months revealed stable osseointegrated zirconia and titanium dental implants. Light microscopy and backscatter scanning electron microscopic analyses confirmed the biocompatibility and achievement of osseointegration, in addition to maintenance of the crestal bone level. The findings suggest that the bone-to-implant contact with a zirconia implant surface is sufficient to provide clinical and histologic evidence of osseointegration. The biopsied two-piece zirconia dental implant with platform switching demonstrated osseointegration occlusal to the implant-abutment junction, eliminating the significance of the microgap.     

Concurrent (tandem) cervical and lumbar spinal stenosis: a 10-yr review of 54 hospitalized patients

OBJECTIVE: To determine the frequency of concurrent cervical and lumbar spinal stenosis (i.e., "tandem spinal stenosis" [TSS]) in a 10-yr review of hospital admissions. DESIGN: In a retrospective study of 460,964 hospital admissions to our 1,000-bed academic community hospital, we identified a base population of 54 patients with TSS. These patients presented with multiple complaints, including neurogenic claudication, progressive gait disturbances, and neurologic signs of both upper and lower motor neuron dysfunction, among others. Since 1964 when TSS was first described, estimates of its frequency have varied widely, ranging from a low of 5% to a high of 28%. RESULTS: Of the 54 cases of TSS identified among the 460,964 patient admissions during a 10-yr period, 36 were men and 18 were women. A total of 51 were >51 yrs of age. For all ages, the frequency rate of TSS in this series was 12 per 100,000 admissions. CONCLUSION: With TSS, the symptoms of either the cervical or the lumbar type initially predominate. Often, only after the primary pathology is treated does the secondary problem become evident. Although TSS occurred relatively infrequently in this series, its potential presence should not be overlooked.