Background/Aims: Bisphosphonates are increasingly recognized for their anti-neoplastic properties, which are the result of their action on the mevalonate pathway. Our primary aim was to investigate the association between bisphosphonate use and survival in patients with pancreatic cancer. Since statins also act on the mevalonate pathway, we also investigated the effect of the combined use of bisphosphonates and statins on survival. Methods: The Surveillance, Epidemiology, and End Results registry (SEER)-Medicare linked database was used to identify patients with pancreatic ductal adenocarcinoma (PDAC) between 2007 and 2015. Kaplan-Meier models were used to examine the association between survival with bisphosphonate use alone and in combination with statins within 1 year prior to the diagnosis of PDAC. Propensity score matching analysis and Cox-proportional hazard models were used to determine the association between overall survival with bisphosphonate use alone and combined with statins, after adjusting for relevant confounders, such as the Charlson comorbidity index score, stage, treatment, sociodemographic characteristics, and propensity score. Results: In total, 13,639 patients with PDAC were identified, and 1,203 (8.82%) used bisphosphonates. There was no difference in the mean survival duration between bisphosphonate users (7.27 months) and nonusers (7.25 months, p=0.61). After adjustment for confounders, bisphosphonate use was still not associated with improved survival (hazard ratio, 1.00; 95% confidence interval, 0.93 to 1.08; p=0.96). Combined bisphosphonate and statin use was also not associated with improved survival (hazard ratio, 0.97; 95% confidence interval, 0.87 to 1.07; p=0.48) after adjustment for confounders. Conclusions Our findings suggest that the use of bisphosphonates, whether alone or in combination with statins, does not confer a survival advantage in patients with PDAC.

Background/Aims: Bisphosphonates are increasingly recognized for their anti-neoplastic properties, which are the result of their action on the mevalonate pathway. Our primary aim was to investigate the association between bisphosphonate use and survival in patients with pancreatic cancer. Since statins also act on the mevalonate pathway, we also investigated the effect of the combined use of bisphosphonates and statins on survival. Methods: The Surveillance, Epidemiology, and End Results registry (SEER)-Medicare linked database was used to identify patients with pancreatic ductal adenocarcinoma (PDAC) between 2007 and 2015. Kaplan-Meier models were used to examine the association between survival with bisphosphonate use alone and in combination with statins within 1 year prior to the diagnosis of PDAC. Propensity score matching analysis and Cox-proportional hazard models were used to determine the association between overall survival with bisphosphonate use alone and combined with statins, after adjusting for relevant confounders, such as the Charlson comorbidity index score, stage, treatment, sociodemographic characteristics, and propensity score. Results: In total, 13,639 patients with PDAC were identified, and 1,203 (8.82%) used bisphosphonates. There was no difference in the mean survival duration between bisphosphonate users (7.27 months) and nonusers (7.25 months, p=0.61). After adjustment for confounders, bisphosphonate use was still not associated with improved survival (hazard ratio, 1.00; 95% confidence interval, 0.93 to 1.08; p=0.96). Combined bisphosphonate and statin use was also not associated with improved survival (hazard ratio, 0.97; 95% confidence interval, 0.87 to 1.07; p=0.48) after adjustment for confounders. Conclusions Our findings suggest that the use of bisphosphonates, whether alone or in combination with statins, does not confer a survival advantage in patients with PDAC.

Alginate-(Poly-L-Lysine)-Alginate(APA) microcapsules were prepared by Electrostatic Droplet Generator(EDG) technique and the thickness of microcapsule membrane, which was composed by polyelectrolyte complex, were studied in this paper. The theoretical formula was given for the measurement of membrane thickness of APA microcapsules by element analysis of membrane and calculation. The membrane thickness was 7-10 microns by theoretical calculation. On the other hand, the thickness of membrane was measured by SEM and optical microscopy and the results were 7 microns and 12 microns, respectively. The results showed that theoretical calculation is in good accordance with experimental determoination of mermbrane thickness and the membrane thickness of APA microcapsule is about 7-10 microns. The optical microscopy is an easy way to measure membrane thickness.
Alginates ; Capsules ; Mathematical Computing ; Membranes, Artificial ; Polylysine ; analogs & derivatives ; Spectrum Analysis

BACKGROUNDTime-intensity curves derived from microbubble destruction/refilling sequences and recorded using myocardial contrast echocardiography (MCE) can provide parameters that correlate with coronary blood flow. The response of these parameters to adenosine vasodilatation correlates with coronary flow reserve (CFR) measured by fluorescent microsphere techniques (FMT). Currently, no data exist regarding the effect of physiological variables, such as hypoxia, on the determination of CFR by MCE. The purpose of this study was to define the effects of decreases in blood partial pressure of oxygen (PO2) on CFR as measured by MCE.

METHODSStudies were performed in 9 closed chest swine. Low-energy, real-time MCE was performed with commercial instruments in short axis view at papillary muscle level while infusing BR1 at 30 ml/h. High-energy ultrasound bursts (referred to as FLASH frames) destroyed the bubbles every 15 cardiac cycles, and resultant time-intensity curves derived from these sequences were fitted to the exponential function y = A [1-e(-bt)] + c, from which the rate of signal rise (b) was obtained. CFR was calculated as the ratio of b values after adenosine infusion to baseline and was obtained during the control period and after decreasing blood PO2 by giving nitrogen via a respirator to create artificial hypoxic conditions. CFR was independently determined by FMT.

RESULTSNitrogen led to significant decreases in mean PO2, from (120.6 +/- 18.9) mmHg to (51.8 +/- 15.9) mmHg (P < 0.01). Adenosine produced a similar increase in CFR (2.5 fold vs 3.1 fold) as assessed by MCE and FMT during the control period. The decrease in PO2 post nitrogen resulted in a slight increase in values at rest: 0.46 +/- 0.15 to 0.53 +/- 0.18 for b and (1.39 +/- 0.66) ml x min(-1) x g(-1) to (1.72 +/- 0.30) ml x min(-1) x g(-1) for myocardial blood flow (MBF) (both P < 0.05). In addition, values decreased in response to adenosine using both techniques: 1.05 +/- 0.35 to 0.82 +/- 0.27 for b and (4.30 +/- 3.16) ml x min(-1) x g(-1) to (3.93 +/- 1.27) ml x min(-1) x g(-1) for MBF (both P < 0.05). Thus, CFR was markedly reduced under hypoxic conditions, to 1.4 by MCE (P < 0.05 compared with the baseline), and to 2.5 by FMT (P > 0.05 compared with the baseline).

CONCLUSIONSCFR values diminish under hypoxic conditions according to both MCE and FMT. The reductions in CFR involve both an increase in resting values and a decrease in post adenosine measurements, as determined by both techniques. The reduction in CFR under hypoxia is slightly greater using MCE than using FMT. Physiological variables, such as hypoxia, must be taken into consideration when assessing CFR by MCE.

Adenosine ; pharmacology ; Animals ; Coronary Circulation ; Echocardiography ; Hypoxia ; diagnostic imaging ; physiopathology ; Microspheres ; Swine

2-Methoxy-1,4-naphthoquinone (MNQ) has been shown to cause cytotoxic towards various cancer cell lines. This study is designed to investigate the regulatory effect of MNQ on the key cancer genes in mitogen-activated protein kinase, phosphoinositide 3-kinase, and nuclear factor кB signaling pathways. The expression levels of the genes were compared at different time point using polymerase chain reaction arrays and Ingenuity Pathway Analysis was performed to identify gene networks that are most significant to key cancer genes. A total of 43 differentially expressed genes were identified with 21 up-regulated and 22 down-regulated genes. Up-regulated genes were involved in apoptosis, cell cycle and act as tumor suppressor while down-regulated genes were involved in anti-apoptosis, angiogenesis, cell cycle and act as transcription factor as well as proto-oncogenes. MNQ exhibited multiple regulatory effects on the cancer key genes that targeting at cell proliferation, cell differentiation, cell transformation, apoptosis, reduce inflammatory responses, inhibits angiogenesis and metastasis.

BACKGROUND: Tissue expansion is an effective and valuable technique for the reconstruction of large skin lesions and scars. This study aimed to evaluate the applicability and safety of a newly designed skin expanding bioreactor system for maximizing the graft area and minimizing the donor site area. METHODS: A computer-controlled biaxial skin bioreactor system was used to expand skin in two directions while the culture media was changed daily. The aim was to achieve an expansion speed that enabled the skin to reach twice its original area in two weeks or less. Skin expansion and subsequent grafting were performed for 10 patients, and each patient was followed for 6 months postoperatively for clinical evaluation. Scar evaluation was performed through visual assessment and by using photos. RESULTS: The average skin expansion rate was 10.54%+/-6.25%; take rate, 88.89%+/-11.39%; and contraction rate, 4.2%+/-2.28% after 6 months. Evaluation of the donor and recipient sites by medical specialists resulted in an average score of 3.5 (out of a potential maximum of 5) at 3 months, and 3.9 at 6 months. The average score for patient satisfaction of the donor site was 6.2 (out of a potential maximum of 10), and an average score of 5.2 was noted for the recipient site. Histological examination performed before and after the skin expansion revealed an increase in porosity of the dermal layer. CONCLUSIONS: This study confirmed the safety and applicability of the in vitro skin bioreactor, and further studies are needed to develop methods for increasing the skin expansion rate.
Bioreactors* ; Cicatrix ; Culture Media ; Humans ; Patient Satisfaction ; Porosity ; Skin Transplantation ; Skin* ; Specialization ; Tissue Donors ; Tissue Expansion ; Transplants