While tumor immunotherapy has improved the prognosis of many patients,immunotherapy drug resistance develops in most tu-mors.Studies of new targets and therapies are needed to overcome this challenge.Growing evidence indicates that Siglecs function in im-mune checkpoints.Siglecs belong to a family of salivary acid-binding immunoglobulin-like lectins.The majority of Siglecs are immunosup-pressive transmembrane proteins that bind to sialic acid-containing glycans on glycoproteins and glycolipids.Sialoglycan-Siglec interactions contribute to tumor immune escape and are strongly correlated with poor prognosis in tumor patients.This review will discuss Siglec func-tion in immune checkpoints,and how the interaction between sialic acid and Siglecs regulates the tumor microenvironment to exert thera-peutic effects.

Background and purpose:Epithelial ovarian cancer(EOC)has a poor prognosis and is prone to developing resistance to platinum-based chemotherapy.Exosomes are currently believed to be involved in platinum resistance in ovarian cancer.This study explored the role and mechanism of exosomes on platinum resistance of ovarian cancer.Methods:Through ultracentrifugation,exosomes were isolated and analyzed using electron microscopy,particle size studies,and Western blot for detailed exosome analysis.We detected the expression levels of exosomal proteins and related signaling pathways.Exosomal protein expression profile was analyzed by proteomics.Key differential proteins were screened by intersecting with existing drug resistance datasets.Furthermore,patients diagnosed with EOC via pathological analysis at the Fudan University Shanghai Cancer Center from August 2023 to August 2024,who underwent surgery and fulfilled the eligibility requirements,were gathered to examine the link between the expression of interferon-stimulated gene 15(ISG15)in serum exosomes and resistance to platinum medication.The expression levels of related proteins in serum exosomes were quantitatively detected by enzyme-linked immunosorbent assay(ELISA).Receiver operating characteristic(ROC)curve was plotted to explore the predictive value of serum exosomal protein in ovarian cancer resistance.Results:Exosomes derived from platinum-sensitive and drug-resistant ovarian cancer cells were extracted and proteomic analysis was further performed.We identified 9 differential proteins associated with platinum-resistance and found the key molecule interferon-stimulated gene 15(ISG15).Compared with sensitive cells,the expression of ISG15 in exosomes of drug-resistant ovarian cancer cells was significantly upregulated.Exosome tracer tests showed that exosomes were successfully taken up by ovarian cancer receptor cells.After coculture with drug-resistant exosomes,the expression level of ISG15 in ovarian cancer receptor cells was increased.Knockdown ISG15 in EOC cells decreased the expression of ISG15 in exosomes,and incubation of ISG15-knockdown exosomes decreased the cell viability on the condition of platinum drugs,indicating that ISG15 in exosomes regulated platinum resistance of ovarian cancer cells.Moreover,ISG15 could regulate the expression of multidrug resistance protein 1(MDR1)through phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)/nuclear factor-kappa-light-chain-enchancer of activated B cells(NF-κB)signaling pathway.This study included a total of 87 patients.Clinical serum samples also showed that the expression of ISG15 in exosomes was higher in platinum-resistant ovarian cancer patients than in sensitive ovarian cancer patients.Using serum exosomal ISG15 as an indicator to distinguish between sensitivity and resistance,the area under ROC curve was 0.779(P＜0.05),cutoffvalue was 27.35ng/mL,sensitivity was 70.2%,and specificity was 76.4%.Conclusion:ISG15 in exosomes can regulate the expression of MDR1 in ovarian cancer cells through PI3K/AKT/NF-κB signaling pathway,and promote platinum resistance in ovarian cancer cells.

Background and purpose:Epithelial ovarian cancer(EOC)has a poor prognosis and is prone to developing resistance to platinum-based chemotherapy.Exosomes are currently believed to be involved in platinum resistance in ovarian cancer.This study explored the role and mechanism of exosomes on platinum resistance of ovarian cancer.Methods:Through ultracentrifugation,exosomes were isolated and analyzed using electron microscopy,particle size studies,and Western blot for detailed exosome analysis.We detected the expression levels of exosomal proteins and related signaling pathways.Exosomal protein expression profile was analyzed by proteomics.Key differential proteins were screened by intersecting with existing drug resistance datasets.Furthermore,patients diagnosed with EOC via pathological analysis at the Fudan University Shanghai Cancer Center from August 2023 to August 2024,who underwent surgery and fulfilled the eligibility requirements,were gathered to examine the link between the expression of interferon-stimulated gene 15(ISG15)in serum exosomes and resistance to platinum medication.The expression levels of related proteins in serum exosomes were quantitatively detected by enzyme-linked immunosorbent assay(ELISA).Receiver operating characteristic(ROC)curve was plotted to explore the predictive value of serum exosomal protein in ovarian cancer resistance.Results:Exosomes derived from platinum-sensitive and drug-resistant ovarian cancer cells were extracted and proteomic analysis was further performed.We identified 9 differential proteins associated with platinum-resistance and found the key molecule interferon-stimulated gene 15(ISG15).Compared with sensitive cells,the expression of ISG15 in exosomes of drug-resistant ovarian cancer cells was significantly upregulated.Exosome tracer tests showed that exosomes were successfully taken up by ovarian cancer receptor cells.After coculture with drug-resistant exosomes,the expression level of ISG15 in ovarian cancer receptor cells was increased.Knockdown ISG15 in EOC cells decreased the expression of ISG15 in exosomes,and incubation of ISG15-knockdown exosomes decreased the cell viability on the condition of platinum drugs,indicating that ISG15 in exosomes regulated platinum resistance of ovarian cancer cells.Moreover,ISG15 could regulate the expression of multidrug resistance protein 1(MDR1)through phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)/nuclear factor-kappa-light-chain-enchancer of activated B cells(NF-κB)signaling pathway.This study included a total of 87 patients.Clinical serum samples also showed that the expression of ISG15 in exosomes was higher in platinum-resistant ovarian cancer patients than in sensitive ovarian cancer patients.Using serum exosomal ISG15 as an indicator to distinguish between sensitivity and resistance,the area under ROC curve was 0.779(P＜0.05),cutoffvalue was 27.35ng/mL,sensitivity was 70.2%,and specificity was 76.4%.Conclusion:ISG15 in exosomes can regulate the expression of MDR1 in ovarian cancer cells through PI3K/AKT/NF-κB signaling pathway,and promote platinum resistance in ovarian cancer cells.

While tumor immunotherapy has improved the prognosis of many patients,immunotherapy drug resistance develops in most tu-mors.Studies of new targets and therapies are needed to overcome this challenge.Growing evidence indicates that Siglecs function in im-mune checkpoints.Siglecs belong to a family of salivary acid-binding immunoglobulin-like lectins.The majority of Siglecs are immunosup-pressive transmembrane proteins that bind to sialic acid-containing glycans on glycoproteins and glycolipids.Sialoglycan-Siglec interactions contribute to tumor immune escape and are strongly correlated with poor prognosis in tumor patients.This review will discuss Siglec func-tion in immune checkpoints,and how the interaction between sialic acid and Siglecs regulates the tumor microenvironment to exert thera-peutic effects.

Da Chaihutang from the Treatise on Febrile Disease （Shanghanlun） has the function of harmonizing lesser Yang and discharging internal heat. It is formulated by ZHANG Zhongjing for the concurrent diseases of lesser Yang and Yang brightness and has been widely used in the treatment of digestive system diseases， especially malignant tumors. By review of the articles published in the last 20 years， this paper summarizes the application of Da Chaihutang in treating digestive system tumors from syndrome analysis， clinical research， and mechanism research. Da Chaihutang can treat the syndrome involving lesser Yang and Yang brightness in the digestive system， release interior and exterior to expel pathogen， and remove obstruction by conforming to the descending nature of the six fu-organs. In clinical practice， Da Chaihutang can directly treat digestive system malignant tumors such as liver cancer， pancreatic cancer， intestinal cancer， gastric cancer， and gallbladder cancer. In addition， it can relieve common complications of digestive system malignant tumors， such as cancerous fever， malignant obstructive jaundice， and constipation. Moreover， it can alleviate the adverse reactions caused by Western medical treatment， such as post-embolization syndrome， side effects of chemotherapy， and incomplete postoperative obstruction. Da Chaihutang is effective when used alone as it can relieve clinical symptoms， improve prognosis， and prolong survival of advanced patients and is safe and non-toxic， suitable for long-term use by tumor patients. Regarding the mechanism， Da Chaihutang can promote the apoptosis and inhibit the proliferation of tumor cells， reduce inflammation and inflammatory injury， and improve the liver function. The clear effect and mechanism confirms the anti-tumor effect of Da Chaihutang. This paper comprehensively describes the current research status of Da Chaihutang in the treatment of digestive system tumors and puts forward the deficiencies and improvement measures for the current research， aiming to provide reference for the application of this formula in treating digestive system tumors， the establishment of Chinese and Western medicine treatment schemes of tumors， and the research and development of anti-tumor drugs.

Objective:To explore the efficacy and safety of hepatic arterial infusion chemotherapy(HAIC) for unresectable hepatitis B-related intrahepatic cholangiocarcinoma(ICC).Methods:This is a retrospective controlled study. Data from 140 unresectable ICC patients who received HAIC treatment at Sun Yat-sen University Cancer Center from March 2015 to June 2023 were retrospectively collected, including 72 patients in the hepatitis B surface antigen(HBsAg)negative group (43 males and 29 females, aged (59.6±9.5)years(range: 34 to 81 years)), 68 cases in the HBsAg-positive group (48 males, 20 females, aged (53.4±11.4)years(range: 29 to 82 years)). HAIC treatment used the FOLFOX regimen combined with oxaliplatin, leucovorin,and fluorouracil. The differences in effects, prognosis,and adverse reactions between the two groups of patients after HAIC treatment were analyzed. All variables were expressed as categorical data. The χ 2 test or Fisher′s exact probability method was used to compare between groups. The Kaplan-Meier method was used to draw survival curves. The difference of survival curve between groups were compared through the Log-rank test. Results:According to the Response Evaluation Criteria in Solid Tumors(RECIST) version 1.1,the objective response rate(ORR) of the HBsAg-negative group was 23.2%(16/69),and the ORR of the HBsAg-positive group was 40.3%(25/62). The difference in ORR between the two groups was statistically significant( χ 2=4.459, P=0.035). According to the modified RECIST(mRECIST) criteria,the ORR of the HBsAg-negative group was 27.5%(19/69), and the ORR of the HBsAg-positive group was 45.2%(28/62). The difference in ORR between the two groups was statistically significant( χ 2=4.410, P=0.036). The median progression-free survival(PFS) of the HBsAg-negative group and the positive group were 7.1 months(95% CI: 5.8 to 13.2 months) and 7.3 months (95% CI: 5.7 to 10.3 months), respectively, and the median overall survival(OS) were 16.3 months (95% CI: 12.5 to 33.9 months) and 15.9 months (95% CI: 9.2 to 20.7 months) respectively. There were no statistically significant differences in PFS and OS between the two groups (both P>0.05). The main serious adverse reactions of the two groups of patients included increased AST, increased ALT, thrombocytopenia,and neutropenia. There were no statistically significant differences in various adverse reactions between the two groups after HAIC treatment (all P>0.05). Conclusion:Patients with HBsAg-positive unresectable ICC are more likely to benefit from HAIC treatment.

Objective:To explore the efficacy and safety of hepatic arterial infusion chemotherapy(HAIC) for unresectable hepatitis B-related intrahepatic cholangiocarcinoma(ICC).Methods:This is a retrospective controlled study. Data from 140 unresectable ICC patients who received HAIC treatment at Sun Yat-sen University Cancer Center from March 2015 to June 2023 were retrospectively collected, including 72 patients in the hepatitis B surface antigen(HBsAg)negative group (43 males and 29 females, aged (59.6±9.5)years(range: 34 to 81 years)), 68 cases in the HBsAg-positive group (48 males, 20 females, aged (53.4±11.4)years(range: 29 to 82 years)). HAIC treatment used the FOLFOX regimen combined with oxaliplatin, leucovorin,and fluorouracil. The differences in effects, prognosis,and adverse reactions between the two groups of patients after HAIC treatment were analyzed. All variables were expressed as categorical data. The χ 2 test or Fisher′s exact probability method was used to compare between groups. The Kaplan-Meier method was used to draw survival curves. The difference of survival curve between groups were compared through the Log-rank test. Results:According to the Response Evaluation Criteria in Solid Tumors(RECIST) version 1.1,the objective response rate(ORR) of the HBsAg-negative group was 23.2%(16/69),and the ORR of the HBsAg-positive group was 40.3%(25/62). The difference in ORR between the two groups was statistically significant( χ 2=4.459, P=0.035). According to the modified RECIST(mRECIST) criteria,the ORR of the HBsAg-negative group was 27.5%(19/69), and the ORR of the HBsAg-positive group was 45.2%(28/62). The difference in ORR between the two groups was statistically significant( χ 2=4.410, P=0.036). The median progression-free survival(PFS) of the HBsAg-negative group and the positive group were 7.1 months(95% CI: 5.8 to 13.2 months) and 7.3 months (95% CI: 5.7 to 10.3 months), respectively, and the median overall survival(OS) were 16.3 months (95% CI: 12.5 to 33.9 months) and 15.9 months (95% CI: 9.2 to 20.7 months) respectively. There were no statistically significant differences in PFS and OS between the two groups (both P>0.05). The main serious adverse reactions of the two groups of patients included increased AST, increased ALT, thrombocytopenia,and neutropenia. There were no statistically significant differences in various adverse reactions between the two groups after HAIC treatment (all P>0.05). Conclusion:Patients with HBsAg-positive unresectable ICC are more likely to benefit from HAIC treatment.

Objective To explore the effect of a new organ preservation solution with HOE642 on the apoptosis of the donor lung from a modified lung transplantation model of rabbits.Methods 24 male rabbits were divided into two groups [low potassium dextran (LPD) group and HOE group],established rabbit models for next 2-h reperfusion using LPD solution or new organ preservation solution.Detected the levles of apoptosis index and caspase-3,the expression of Fas/Fas-L and Bcl-2/Bax.Results Compared with LPD group,HOE group revealed significant lower level of apoptosis index and caspase-3 (P＜0.05),lower expression of Fas/Fas-L and Bax,and higher expression of Bcl-2 (P＜0.05).Conclusion The potential donor lung protective mechanism offered by the new organ preservation solution with HOE642 might be the inhibition of apoptosis via both intrinsic and extrinsic pathways.

Poly (N-isopropylacrylamide) (PNIPAAm), a temperature-responsive polymer, can be potentially applied to replace enzymes or cell scrapers to recover attached cells. Taking full advantage of this unique function of PNIPAAm, cells can be protected from enzymatic hydrolysis and mechanical treatment, thereby to provide ideal seed cells with high quality for biomedical fields. In this review we describe the method to facilitate cell effective adhesion and rapid detachment on thermoresponsive two dimensional surfaces, including selecting special substrate, introducing hydrophilic group, adjusting reactant ratio, controlling polymer thickness/density, providing appropriate external force, so as to effectively improve adherent cell adaptability to thermoresponsive surfaces, depress the risk of bacterial contamination and reduce the effect of low-temperature treatment on the cells. The three dimensional cell culture systems involved in temperature-sensitive microcarriers, scaffolds and gels were briefly discussed. The application based on the platforms for cell culture was also presented.
Acrylic Resins ; Cell Adhesion ; Cell Culture Techniques ; Temperature