AIM: To determine the effect of cis -9, trans -11-conjugated linoleic acid (c9, t11-CLA) on the cell cycle of gastric cancer cells (SGC-7901) and its possible mechanism in inhibition cancer growth. METHODS: Using cell...AIM: To determine the effect of cis -9, trans -11-conjugated linoleic acid (c9, t11-CLA) on the cell cycle of gastric cancer cells (SGC-7901) and its possible mechanism in inhibition cancer growth. METHODS: Using cell culture and immunocytochemical techniques, we examined the cell growth, DNA synthesis, expression of PCNA, cyclin A, B(1), D(1), p16(ink4a) and p21(cip/waf1) of SGC-7901 cells which were treated with various c9, t11-CLA concentrations (25, 50, 100 and 200 micromol.L(-1))of c 9, t 11-CLA for 24 and 48h, with a negative control (0.1% ethane). RESULTS: The cell growth and DNA synthesis of SGC-7901 cells were inhibited by c9, t11-CLA.SGC-7901 cells. Eight day after treatment with various concentrations of c9, t11-CLA mentioned above, the inhibition rates were 5.92%, 20.15%, 75.61% and 82.44%, respectively and inhibitory effect of c9, t11-CLA on DNA synthesis (except for 25 micromol.L, 24h) showed significantly less (3)H-TdR incorporation than that in the negative controls (P【0.05 and P【0.01). Immunocytochemical staining demonstrated that SGC-7901 cells preincubated in media supplemented with different c9, t11-CLA concentrations at various times significantly decreased the expressions of PCNA (the expression rates were 7.2-3.0%, 24h and 9.1-0.9% at 48h, respectively), Cyclin A (11.0-2.3%, 24h and 8.5-0.5%,48h), B(1) (4.8-1.8% at 24h and 5.5-0.6% at 48h)and D(1) (3.6-1.4% at 24h and 3.7%-0 at 48h) as compared with those in the negative controls(the expressions of PCNA, Cyclin A, B(1) and D(1) were 6.5% at 24h and 9.0% at 48h, 4.2% at 24h and 5.1% at 48h, 9.5% at 24h and 6.0% at 48h,respectively)(P【0.01), whereas the expressions of P16(ink4a) and P21(cip/waf1), cyclin-dependent kinases inhibitors(CDKI), were increased. CONCLUSION: The cell growth and proliferation of SGC-7901 cell is inhibited by c9, t11-CLA via blocking the cell cycle, with reduced expressions of cyclin A,B(1) and D(1) and enhanced expressions of CDKI(P16(ink4a) and p21(cip/waf1)).展开更多
Biosensors based on organic field-effect transistors(OFETs)are one of the most promising electronic devices for emerging bioanalytical applications.The selection of organic semiconductors(OSCs)is essential to improve ...Biosensors based on organic field-effect transistors(OFETs)are one of the most promising electronic devices for emerging bioanalytical applications.The selection of organic semiconductors(OSCs)is essential to improve the sensitivity and reliability of this kind of biosensors.Given the good field effect performance and tunable structures of D-A type conjugated polymers,here,we design two D-A type copolymers[P(BDT-co-DPP2T-ThC_(2))and P(BDT-co-DPP2T-Th)],which are applied as the OSC layers.With carcinoembryonic antigen antibody(anti-CEA)adsorbed onto the OSC layers as the recognition sites,OFETs based biosensors for CEA detection are developed.The experimental findings support that the attachment of ester side groups onto the polymer backbone[as for P(BDT-co-DPP2T-ThC_(2))]is favorable for improved solubility and filming properties of the polymer.The introduction of ester side groups affects molecular stacking and enhances intermolecular forces.The resultant devices show high charge mobility and antibody adsorption ability,both of which are critical for sensitive and facile detection of CEA biomarkers.The reliable determination of CEA down to the picomolar level is determined.It is expected that this kind of biosensors fabricated by D-A type conducting polymers will open new avenues toward the early diagnosis,real-time monitoring and treatment of future cancer diseases.展开更多
In order to generate an antibody against a small hapten molecule, the hapten is cross-linked with carrier protein to make it immunogenic. In this study, the hapten （ochratoxin A, OTA） was coupled to ovalbumin （OVA...In order to generate an antibody against a small hapten molecule, the hapten is cross-linked with carrier protein to make it immunogenic. In this study, the hapten （ochratoxin A, OTA） was coupled to ovalbumin （OVA） by an active ester reaction. To develop a technique for detecting the conjugation, the hapten-protein conjugate （OTA-OVA） was characterized thoroughly by immunoarray technology, ultraviolet （UV） spectroscopy and matrix-assisted laser desorption ionization time-of-flight mass spectrometry （MALDI-TOF-MS）, respectively. The molecular weight of OTA-OVA was 50 350.141 Da, and the molecular weight of OVA was 44 887.506 Da, which were determined by MALDI-TOF-MS, respectively. In OTA-OVA, the molecular coupling ratio was 13：1 by MALDI-TOF-MS while the molecular coupling ratio was 10：1 by UV. In this experiment, UV and MALDI-TOF-MS were selected as the efficient methods to evaluate the cross-linking effect and calculate the molecular coupling ratio.展开更多
Limited clinical application of antibody-drug conjugates(ADCs)targeting tumor associated antigens(TAAs)is usually caused by on-target off-tumor side effect.Tumor-specific mutant antigens(TSMAs)only expressed in tumor ...Limited clinical application of antibody-drug conjugates(ADCs)targeting tumor associated antigens(TAAs)is usually caused by on-target off-tumor side effect.Tumor-specific mutant antigens(TSMAs)only expressed in tumor cells which are ideal targets for ADCs.In addition,intracellular somatic mutant proteins can be presented on the cell surface by human leukocyte antigen class I(HLA I)molecules forming tumor-specific peptide/HLA I complexes.KRAS G12 V mutation frequently occurred in varied cancer and was verified as a promising target for cancer therapy.In this study,we generated two TCR-mimic antibodydrug conjugates(TCRm-ADCs),2E8-MMAE and 2 A5-MMAE,targeting KRAS G12 V/HLAA*0201 complex,which mediated specific antitumor activity in vitro and in vivo without obvious toxicity.Our findings are the first time validate the strategy of TCRm-ADCs targeting intracellular TSMAs,which improves the safety of antibody-based drugs and provides novel strategy for precision medicine in cancer therapy.展开更多
Gastrointestinal(GI)cancers represent the leading cause of cancer-related mortality worldwide.Antibody drug conjugates(ADCs)are a rapidly growing new class of anti-cancer agents which may improve GI cancer patient sur...Gastrointestinal(GI)cancers represent the leading cause of cancer-related mortality worldwide.Antibody drug conjugates(ADCs)are a rapidly growing new class of anti-cancer agents which may improve GI cancer patient survival.ADCs combine tumour-antigen specific antibodies with cytotoxic drugs to deliver tumour cell specific chemotherapy.Currently,only two ADCs[brentuximab vedotin and trastuzumab emtansine(T-DM1)]have been Food and Drug Administration approved for the treatment of lymphoma and metastatic breast cancer,respectively.Clinical research evaluating ADCs in GI cancers has shown limited success.In this review,we will retrace the relevant clinical trials investigating ADCs in GI cancers,especially ADCs targeting human epidermal growth receptor 2,mesothelin,guanylyl cyclase C,carcinogenic antigen-related cell adhesion molecule 5(also known as CEACAM5)and other GI malignancy specific targets.We will review potential hurdles for their success and provide new perspective for future treatment.展开更多
基金the National Natural Science Foundation of China,No.39870661
文摘AIM: To determine the effect of cis -9, trans -11-conjugated linoleic acid (c9, t11-CLA) on the cell cycle of gastric cancer cells (SGC-7901) and its possible mechanism in inhibition cancer growth. METHODS: Using cell culture and immunocytochemical techniques, we examined the cell growth, DNA synthesis, expression of PCNA, cyclin A, B(1), D(1), p16(ink4a) and p21(cip/waf1) of SGC-7901 cells which were treated with various c9, t11-CLA concentrations (25, 50, 100 and 200 micromol.L(-1))of c 9, t 11-CLA for 24 and 48h, with a negative control (0.1% ethane). RESULTS: The cell growth and DNA synthesis of SGC-7901 cells were inhibited by c9, t11-CLA.SGC-7901 cells. Eight day after treatment with various concentrations of c9, t11-CLA mentioned above, the inhibition rates were 5.92%, 20.15%, 75.61% and 82.44%, respectively and inhibitory effect of c9, t11-CLA on DNA synthesis (except for 25 micromol.L, 24h) showed significantly less (3)H-TdR incorporation than that in the negative controls (P【0.05 and P【0.01). Immunocytochemical staining demonstrated that SGC-7901 cells preincubated in media supplemented with different c9, t11-CLA concentrations at various times significantly decreased the expressions of PCNA (the expression rates were 7.2-3.0%, 24h and 9.1-0.9% at 48h, respectively), Cyclin A (11.0-2.3%, 24h and 8.5-0.5%,48h), B(1) (4.8-1.8% at 24h and 5.5-0.6% at 48h)and D(1) (3.6-1.4% at 24h and 3.7%-0 at 48h) as compared with those in the negative controls(the expressions of PCNA, Cyclin A, B(1) and D(1) were 6.5% at 24h and 9.0% at 48h, 4.2% at 24h and 5.1% at 48h, 9.5% at 24h and 6.0% at 48h,respectively)(P【0.01), whereas the expressions of P16(ink4a) and P21(cip/waf1), cyclin-dependent kinases inhibitors(CDKI), were increased. CONCLUSION: The cell growth and proliferation of SGC-7901 cell is inhibited by c9, t11-CLA via blocking the cell cycle, with reduced expressions of cyclin A,B(1) and D(1) and enhanced expressions of CDKI(P16(ink4a) and p21(cip/waf1)).
基金supported by the National Natural Science Foundation of China(Nos.22275068,21975178)the Open Project of the State Key Laboratory of Supramolecular Structure and Materials,China.
文摘Biosensors based on organic field-effect transistors(OFETs)are one of the most promising electronic devices for emerging bioanalytical applications.The selection of organic semiconductors(OSCs)is essential to improve the sensitivity and reliability of this kind of biosensors.Given the good field effect performance and tunable structures of D-A type conjugated polymers,here,we design two D-A type copolymers[P(BDT-co-DPP2T-ThC_(2))and P(BDT-co-DPP2T-Th)],which are applied as the OSC layers.With carcinoembryonic antigen antibody(anti-CEA)adsorbed onto the OSC layers as the recognition sites,OFETs based biosensors for CEA detection are developed.The experimental findings support that the attachment of ester side groups onto the polymer backbone[as for P(BDT-co-DPP2T-ThC_(2))]is favorable for improved solubility and filming properties of the polymer.The introduction of ester side groups affects molecular stacking and enhances intermolecular forces.The resultant devices show high charge mobility and antibody adsorption ability,both of which are critical for sensitive and facile detection of CEA biomarkers.The reliable determination of CEA down to the picomolar level is determined.It is expected that this kind of biosensors fabricated by D-A type conducting polymers will open new avenues toward the early diagnosis,real-time monitoring and treatment of future cancer diseases.
基金supported by the National High-Technology Research and Development Program of China (2007AA10Z429)the Stabling and Introducing Talents Fund Program of Anhui Agricultural University, China (WD2011-17)
文摘In order to generate an antibody against a small hapten molecule, the hapten is cross-linked with carrier protein to make it immunogenic. In this study, the hapten （ochratoxin A, OTA） was coupled to ovalbumin （OVA） by an active ester reaction. To develop a technique for detecting the conjugation, the hapten-protein conjugate （OTA-OVA） was characterized thoroughly by immunoarray technology, ultraviolet （UV） spectroscopy and matrix-assisted laser desorption ionization time-of-flight mass spectrometry （MALDI-TOF-MS）, respectively. The molecular weight of OTA-OVA was 50 350.141 Da, and the molecular weight of OVA was 44 887.506 Da, which were determined by MALDI-TOF-MS, respectively. In OTA-OVA, the molecular coupling ratio was 13：1 by MALDI-TOF-MS while the molecular coupling ratio was 10：1 by UV. In this experiment, UV and MALDI-TOF-MS were selected as the efficient methods to evaluate the cross-linking effect and calculate the molecular coupling ratio.
基金supported by the National Key Research and Development Program of China‘Precision Medicine Research’(Grant No.2017YFC0908602)the State Key Program of National Natural Science of China(Grant No.81430081)National Key R&D Program of China(No.2017YFE0102200)。
文摘Limited clinical application of antibody-drug conjugates(ADCs)targeting tumor associated antigens(TAAs)is usually caused by on-target off-tumor side effect.Tumor-specific mutant antigens(TSMAs)only expressed in tumor cells which are ideal targets for ADCs.In addition,intracellular somatic mutant proteins can be presented on the cell surface by human leukocyte antigen class I(HLA I)molecules forming tumor-specific peptide/HLA I complexes.KRAS G12 V mutation frequently occurred in varied cancer and was verified as a promising target for cancer therapy.In this study,we generated two TCR-mimic antibodydrug conjugates(TCRm-ADCs),2E8-MMAE and 2 A5-MMAE,targeting KRAS G12 V/HLAA*0201 complex,which mediated specific antitumor activity in vitro and in vivo without obvious toxicity.Our findings are the first time validate the strategy of TCRm-ADCs targeting intracellular TSMAs,which improves the safety of antibody-based drugs and provides novel strategy for precision medicine in cancer therapy.
文摘Gastrointestinal(GI)cancers represent the leading cause of cancer-related mortality worldwide.Antibody drug conjugates(ADCs)are a rapidly growing new class of anti-cancer agents which may improve GI cancer patient survival.ADCs combine tumour-antigen specific antibodies with cytotoxic drugs to deliver tumour cell specific chemotherapy.Currently,only two ADCs[brentuximab vedotin and trastuzumab emtansine(T-DM1)]have been Food and Drug Administration approved for the treatment of lymphoma and metastatic breast cancer,respectively.Clinical research evaluating ADCs in GI cancers has shown limited success.In this review,we will retrace the relevant clinical trials investigating ADCs in GI cancers,especially ADCs targeting human epidermal growth receptor 2,mesothelin,guanylyl cyclase C,carcinogenic antigen-related cell adhesion molecule 5(also known as CEACAM5)and other GI malignancy specific targets.We will review potential hurdles for their success and provide new perspective for future treatment.
