The anti-proliferative effects of a frankincense extract in a window of opportunity phase ia clinical trial for patients with breast cancer.

PURPOSE: Boswellic acids, active components of frankincense, suppress tumor proliferation in vitro with a strong clinical trial safety profile in patients with inflammatory diseases. We performed a Phase Ia window of opportunity trial of Boswellia serrata (B. serrata) in patients with breast cancer to evaluate its biologic activity and safety. METHODS: Patients with invasive breast cancer were treated pre-operatively with B. Serrata (2400 mg/day PO) until the night before surgery for a median of 11 days (SD 6 days; range: 5-23 days). Paraffin-embedded sections from pretreatment diagnostic core biopsies and post-treatment surgical excisions were evaluated using a tunnel assay and immunohistochemistry staining with Ki-67 antibodies. A non-intervention retrospective control arm consisting of core and surgical tissue specimens from untreated patients was used to compare patients treated with B. Serrata. The change in proliferation and apoptosis between diagnostic core specimens and surgical specimens was compared between the control and treatment groups using a two-tailed paired t-test. RESULTS: Twenty-two patients were enrolled, of which 20 received treatment, and 18 had sufficient tissue for IHC. There was an increase in percent change in proliferation from core biopsy to surgical excision in the control group (n = 18) of 54.6 ± 21.4%. In the B. serrata-treated group there was a reduction in proliferation between core biopsy and excision (n = 18) of 13.8 ± 11.7%. This difference was statistically significant between the control and B. serrata-treated groups (p = 0.008). There was no difference in change in apoptosis. There were no serious adverse events related to the drug. CONCLUSION: Boswellia serrata inhibited breast cancer proliferation and was well-tolerated in a Phase Ia window of opportunity trial.

Laparoscopic fluorescence image-guided photothermal therapy enhances cancer diagnosis and treatment.

Endoscopy is the gold standard investigation in the diagnosis of gastrointestinal cancers and the management of early and pre-malignant lesions either by resection or ablation. Recently gold nanoparticles have shown promise in cancer diagnosis and therapeutics (theranostics). The combination of multifunctional gold nanoparticles with near infrared fluorescence endoscopy for accurate mapping of early or pre-malignant lesions can potentially enhance diagnostic efficiency while precisely directing endoscopic near infrared photothermal therapy for established cancers. The integration of endoscopy with near infrared fluorescence imaging and photothermal therapy was aided by the accumulation of our multifunctionalized PEG-GNR-Cy5.5-anti-EGFR-antibody gold nanorods within gastrointestinal tumor xenografts in BALB/c mice. Control mice (with tumors) received either gold nanorods or photothermal therapy, while study mice received both treatment modalities. Local (tumor-centric) and systemic effects were examined for 30 days. Clear endoscopic near infrared fluorescence signals were observed emanating specifically from tumor sites and these corresponded precisely to the tumor margins. Endoscopic fluorescence-guided near infrared photothermal therapy successfully induced tumor ablations in all 20 mice studied, with complete histological clearance and minimal collateral damage. Multi-source analysis from histology, electron microscopy, mass spectrometry, blood, clinical evaluation, psychosocial and weight monitoring demonstrated the inherent safety of this technology. The combination of this innovative nanotechnology with gold standard clinical practice will be of value in enhancing the early optical detection of gastrointestinal cancers and a useful adjunct for its therapy.

Point-of-care C reactive protein for the diagnosis of lower respiratory tract infection in NHS primary care: a qualitative study of barriers and facilitators to adoption.

OBJECTIVES: Point-of-care (POC) C reactive protein (CRP) is incorporated in National Institute of Health and Care Excellence (NICE) guidelines for the diagnosis of pneumonia, reduces antibiotic prescribing and is cost effective. AIM: To determine the barriers and facilitators to adoption of POC CRP testing in National Health Service (NHS) primary care for the diagnosis of lower respiratory tract infection. DESIGN: The study followed a qualitative methodology based on grounded theory. The study was undertaken in 2 stages. Stage 1 consisted of semistructured interviews with 8 clinicians from Europe and the UK who use the test in routine practice, and focused on their subjective experience in the challenges of implementing POC CRP testing. Stage 2 was a multidisciplinary-facilitated workshop with NHS stakeholders to discuss barriers to adoption, impact of adoption and potential adoption scenarios. Emergent theme analysis was undertaken. PARTICIPANTS: Participants included general practitioners (including those with commissioning experience), biochemists, pharmacists, clinical laboratory scientists and industry representatives from the UK and abroad. RESULTS: Barriers to the implementation of POC CRP exist, but successful adoption has been demonstrated abroad. Analysis highlighted 7 themes: reimbursement and incentivisation, quality control and training, laboratory services, practitioner attitudes and experiences, effects on clinic flow and workload, use in pharmacy and gaps in evidence. CONCLUSIONS: Successful adoption models from the UK and abroad demonstrate a distinctive pattern and involve collaboration with central laboratory services. Incorporating antimicrobial stewardship into quality improvement frameworks may incentivise adoption. Further research is needed to develop scaling-up strategies to address the resourcing, clinical governance and economic impact of widespread NHS implementation.

Application of gold nanoparticles for gastrointestinal cancer theranostics: A systematic review.

Gold nanoparticles (GNPs) are readily synthesised structures that absorb light strongly to generate thermal energy which induces photothermal destruction of malignant tissue. This review examines the efficacy, potential challenges and toxicity from in vitro and in vivo applications of GNPs in oesophageal, gastric and colon cancers. A systematic literature search of Medline, Embase, Web of Science and Cochrane databases was performed using PRISMA guidelines. Two hundred and eighty-four papers were reviewed with sixteen studies meeting the inclusion criteria. The application of GNPs in eleven in vivo rodent studies with GI adenocarcinoma demonstrated excellent therapeutic outcomes but poor corroboration in terms of the cancer cells used, photothermal irradiation regimes, fluorophores and types of nanoparticles. There is compelling evidence of the translational potential of GNPs to be complimentary to surgery and feasible in the photothermal therapy of GI cancer but reproducibility and standardisation require development prior to GI cancer clinical trials. FROM THE CLINICAL EDITOR: Gold nanoparticles are one of the most potentially useful nanoparticles. This is especially true in cancer therapeutics because of their photothermal properties. In this comprehensive article, the authors reviewed the application and efficacy of gold nanoparticles in both the diagnosis and treatment of GI cancers. This review should provide a stimulus for researchers to further develop and translate these nanoparticles into future clinical trials.

Stress management training for surgeons-a randomized, controlled, intervention study.

BACKGROUND: Stress and coping influence performance. In this study, we evaluate a novel stress management intervention for surgeons. METHODS: A randomized control group design was used. Sixteen surgeons were allocated to either the intervention or control group. The intervention group received training on coping strategies, mental rehearsal, and relaxation. Performance measures were obtained during simulated operations and included objective-structured assessment of technical skill, observational teamwork assessment for surgery, and end product assessment rated by experts. Stress was assessed using the state-trait-anxiety-inventory, observer rating, coefficient of heart rate variability (C_HRV), and salivary cortisol. The number of applied surgical coping strategies (number of coping strategies [NC]) was assessed using a questionnaire. A t test for paired samples investigated any within-subject changes, and multiple linear regression analysis explored between-subject effects. Interviews explored surgeons' perceptions of the intervention. RESULTS: The intervention group showed enhanced observational teamwork assessment for surgery performance (t = -2.767, P < 0.05), and increased coping skills (t = -4.690, P < 0.01), and reduced stress reflected inheart rate variability (t = -4.008, P < 0.01). No significant changes were identified in the control group. Linear regression analysis confirmed a significant effect on NC (ß = -0.739, P < 0.01). Qualitative data analysis revealed improved technical skills, decision making, and confidence. CONCLUSIONS: The intervention had beneficial effects on coping, stress, and nontechnical skills during simulated surgery.