第791回 千葉医学会例会・第22回 麻酔科例会・第44回 千葉麻酔懇話会 9.

Correlations of plasma PIM-1 levels and clinicopathological parameters. (XLSX 11 kb

LAT2 regulates glutamine-dependent mTOR activation to promote glycolysis and chemoresistance in pancreatic cancer

Abstract Background Reprogrammed energy metabolism has become an emerging hallmark of cancer in recent years. Transporters have been reported to be amino acid sensors involved in controlling mTOR recruitment and activation, which is crucial for the growth of both normal and tumor cells. L-type amino acid transporter 2 (LAT2), encoded by the SLC7A8 gene, is a Na+-independent neutral amino acid transporter and is responsible for transporting neutral amino acids, including glutamine, which can activate mTOR. Previous studies have shown that LAT2 was overexpressed in gemcitabine-resistant pancreatic cancer cells. However, the role of LAT2 in chemoresistance in pancreatic cancer remains uncertain and elusive. Methods The effects of LAT2 on biological behaviors were analyzed. LAT2 and LDHB levels in tissues were detected, and the clinical value was evaluated. Results We demonstrated that LAT2 emerged as an oncogenic protein and could decrease the gemcitabine sensitivity of pancreatic cancer cells in vitro and in vivo. The results of a survival analysis indicated that high expression levels of both LAT2 and LDHB predicted a poor prognosis in patients with pancreatic cancer. Furthermore, we found that LAT2 could promote proliferation, inhibit apoptosis, activate glycolysis and alter glutamine metabolism to activate mTOR in vitro and in vivo. Next, we found that gemcitabine combined with an mTOR inhibitor (RAD001) could reverse the decrease in chemosensitivity caused by LAT2 overexpression in pancreatic cancer cells. Mechanistically, we demonstrated that LAT2 could regulate two glutamine-dependent positive feedback loops (the LAT2/p-mTORSer2448 loop and the glutamine/p-mTORSer2448/glutamine synthetase loop) to promote glycolysis and decrease gemcitabine (GEM) sensitivity in pancreatic cancer. Conclusion Taken together, our data reveal that LAT2 functions as an oncogenic protein and could regulate glutamine-dependent mTOR activation to promote glycolysis and decrease GEM sensitivity in pancreatic cancer. The LAT2-mTOR-LDHB pathway might be a promising therapeutic target in pancreatic cancer

MiR-10a-5p targets TFAP2C to promote gemcitabine resistance in pancreatic ductal adenocarcinoma

Abstract Background By regulating target genes, microRNAs play essential roles in carcinogenesis and drug resistance in human pancreatic ductal adenocarcinoma (PDAC). Previous studies have shown that microRNA-10a-5p (miR-10a-5p) is overexpressed in PDAC and acts as an oncogene to promote the metastatic behavior of PDAC cells. However, the role of miR-10a-5p in PDAC chemoresistance remains unclear. Methods The effects of miR-10a-5p on biological behaviors were analyzed. MiR-10a-5p and TFAP2C levels in tissues were detected, and the clinical value was evaluated. Results We found that miR-10a-5p is up-regulated in gemcitabine-resistant PDAC cells and enhances PDAC cell gemcitabine resistance in vitro and vivo. Meanwhile, we also determined that miR-10a-5p promotes the migratory and invasive ability of PDAC cells. Next, we confirmed that transcription factor activating protein 2 gamma (TFAP2C) is a target of miR-10a-5p, and TFAP2C overexpression resensitizes PDAC cells to gemcitabine, which is initiated by miR-10a-5p. Further studies revealed that TFAP2C also decreased PDAC cell migration and invasion capability. Finally, survival analysis demonstrated that high miR-10a-5p expression levels and low TFAP2C expression levels were both independent adverse prognostic factors in patients with PDAC. Conclusion Together, these results indicate that miR-10a-5p/TFAP2C may be new therapeutic target and prognostic marker in PDAC

An Integrated Interferometric Fiber Optic Sensor Using a 638 nm Semiconductor Laser for Air-Water Surface Velocity Measurements

An integrated interferometric fiber optic velocimetry sensor has been proposed and demonstrated at the central wavelength of 638 nm. The sensor is based on the principle of two laser-beams’ interference. The light signal scattered from the particles or vapor is demodulated to measure the water surface velocity and water vapor velocity. Three velocity measurement experiments are carried out to measure the velocity, and the experimental data shows that the velocity increases linearly in the range of 4 mm·s−1 to 100 mm·s−1, with a slope of linear fitting curve of 0.99777 and the R-Square of 1.00000. The velocity calculated from frequency shift fits well with the reference velocity. The maximum average relative error in the three velocity measurements is less than 2.5%. In addition, the maximum speed of 4.398 m·s−1 is confirmed in the rotating disk calibration experiment, which expands the sensor’s velocity measurement range. To solve the problem that it is difficult to directly measure the velocity of small-scale water surface flow velocity, especially from the aspect of the low velocity of air-water surface, the interferometric fiber optic sensor can be applied to the measurement of water surface velocity and wind velocity on the water surface

Additional file 2: of MiR-10a-5p targets TFAP2C to promote gemcitabine resistance in pancreatic ductal adenocarcinoma

Figure S2. TFAP2C does not influence cell proliferation or the cell cycle. (A) TFAP2C overexpression in the AsPC-1 cell line had a trend of suppressing cell proliferation, but proliferation was not significantly different between the overexpressing cells and control cells. (B) TFAP2C knockdown in the T3M4 cell line had a trend of promoting cell proliferation, but proliferation was not significantly different between the knockdown cells and control cells. (C) TFAP2C overexpression in the AsPC-1 cell line had a trend of reducing the G1-S transition of the cell cycle, but this transition rate was not significantly different between the overexpressing cells and control cells. (D) TFAP2C knockdown in the T3M4 cell line had a trend of accelerating the G1-S transition of the cell cycle, but this transition rate was not significantly different between the knockdown cells and control cells. The data are presented as the means ± SD (Student’s t-test; *, P < 0.05). (PNG 406 kb

Additional file 1: of MiR-10a-5p targets TFAP2C to promote gemcitabine resistance in pancreatic ductal adenocarcinoma

Figure S1. MiR-10a-5p does not influence cell proliferation, cell apoptosis or the cell cycle. (A) MiR-10a-5p overexpression in the T3M4 cell line had a trend of promoting cell proliferation, but proliferation was not significantly different between the overexpressing cells and control cells. (B) MiR-10a-5p overexpression in the T3M4 cell line had a trend of decreasing gemcitabine-induced cell apoptosis, but apoptosis was not significantly different between the overexpressing cells and control cells. (C) MiR-10a-5p knockdown in the Su86.86 cell line had a trend of suppressing cell proliferation, but proliferation was not significantly different between the knockdown cells and control cells. (D) MiR-10a-5p knockdown in the Su86.86 cell line had a trend of promoting gemcitabine-induced cell apoptosis, but apoptosis was not significantly different between the knockdown cells and control cells. (E) MiR-10a-5p overexpression in the T3M4 cell line had a trend of accelerating the S-G2 transition of the cell cycle, but this transition rate was not significantly different between the overexpressing cells and control cells. (F) MiR-10a-5p knockdown in the Su86.86 cell line reduced the S-G2 transition of the cell cycle. The data are presented as the means ± SD (Student’s t-test; *, P < 0.05). (PNG 994 kb

Additional file 3: Table S2. of PIM-1 contributes to the malignancy of pancreatic cancer and displays diagnostic and prognostic value

Univariate and multivariable analyses of factors predictive of poor overall survival in patients with pancreatic cancer (tissues). (XLSX 12 kb

Efficacy of acupuncture as an adjunctive treatment to patients with stable COPD: a multicenter, randomized, sham-controlled trial protocol

Abstract Background Chronic obstructive pulmonary disease (COPD) is a common respiratory disease and the third leading cause of death worldwide. Previous evidence has shown that acupuncture may be an effective complementary alternative therapy for stable COPD. However, large-sample, rigorously designed long-term follow-up studies still need to be completed. Notably, the relationship between the frequency of acupuncture and clinical efficacy in studies on acupuncture for stable COPD still needs further validation. This study aims to evaluate the efficacy and safety of acupuncture for stable COPD and further investigate the dose–effect relationship of acupuncture. Methods/design This is a multicenter, randomized, controlled trial that uses central randomization to randomly allocate 550 participants in a 1:1:1:1:1 ratio to once a week acupuncture group, twice a week acupuncture group, three times a week acupuncture group, sham acupuncture group and waiting-list control group. The sham acupuncture group will receive placebo acupuncture treatments three times per week, and the waiting-list control group will not receive any form of acupuncture intervention. The study consists of a 2-week baseline, 12-week of treatment, and 52-week of follow-up. Patients with COPD between 40 to 80 years old who have received stable Western medication within the previous 3 months and have had at least 1 moderate or severe acute exacerbation within the past 1 year will be included in the study. Basic treatment will remain the same for all participants. The primary outcome is the proportion of responders at week 12. Secondary outcomes include the proportion of responders at week 64, change in the St. George's Respiratory Questionnaire (SGRQ) Scale, change in the Modified-Medical Research Council (mMRC) Scale, change in the COPD Assessment Test (CAT) Scale, change in the Lung Function Screening Indicators (LFSI), change in the 6-min walk distance (6-MWD), change in Short-Form 36 Health Survey (SF-36) Scale, the number of moderate and severe acute exacerbations and adverse event rate during the follow-up period. Discussion This study will provide robust evidence on whether acupuncture is safe and effective for treating stable COPD. Meanwhile, comparing the differences in efficacy between different acupuncture frequencies will further promote the optimization of acupuncture for stable COPD. Trial registration This study was registered in the Chinese Clinical Trial Registry (ChiCTR2200058757), on April 16, 2022