Hemorrhagic cystitis in gastric cancer after nanoparticle albuminbound paclitaxel:A case report

BACKGROUND The advanced first-line regimen for advanced gastric cancer is based on a combination of fluoropyrimidine and platinum and/or paclitaxel(PTX),forming a two-or three-drug regimen.Compared to conventional PTX,nanoparticle albumin-bound PTX(Nab-PTX)has better therapeutic effects and fewer adverse effects reported in studies.Nab-PTX is a great option for patients presenting with advanced gastric cancer.Herein,we highlight an adverse event(hemorrhagic cystitis)of Nab-PTX in advanced gastric cancer.CASE SUMMARY A 55-year-old male was diagnosed with lymph node metastasis after a laparo-scopic-assisted radical gastrectomy for gastric cancer that was treated by Nab-PTX and S-1(AS).On the 15th day after treatment with AS,he was diagnosed with hemorrhagic cystitis.CONCLUSION Physicians should be aware that hemorrhagic cystitis is a potential adverse event associated with Nab-PTX treatment.

Clinical implications of neutrophil-to-lymphocyte ratio and MDSC kinetics in gastric cancer patients treated with ramucirumab plus paclitaxel

Objective: We aimed to investigate the prognostic value of neutrophil-to-lymphocyte ratio(NLR) and myeloidderived suppressor cells(MDSCs) in gastric cancer patients treated with second-line ramucirumab plus paclitaxel.Methods: A total of 116 patients with advanced or metastatic gastric cancer who receive ramucirumab plus paclitaxel were prospectively enrolled. Fresh blood samples were collected before and after treatment, and flow cytometry was performed to assess the proportions of monocytic(m MDSCs) and granulocytic MDSCs(g MDSCs).Results: Median age was 58 years and 71(61.2%) patients were male. A baseline NLR≥2.94 was associated with significantly poorer progression-free survival(PFS) and overall survival(OS) vs. an NLR<2.94(P=0.011 and P=0.002, respectively). In multivariate analysis, an NLR≥2.94 was independently associated with poorer PFS[hazard ratio(HR)=1.58;95% confidence interval(95% CI): 1.01-2.49, P=0.046] and OS(HR=1.77;95% CI:1.04-3.04, P=0.036). While m MDSC counts did not significantly change following two cycles of therapy(P=0.530),g MDSC counts decreased significantly after two treatment cycles(P=0.025) but tended to increase in patients with progressive disease after two treatment cycles(P=0.098). A progressive increase in g MDSC counts(≥44%) was associated with a significantly shorter PFS and OS vs. a g MDSC count increase <44%(P=0.001 and P=0.003,respectively).Conclusions: The baseline NLR may help guide clinical decisions during ramucirumab plus paclitaxel therapy for gastric cancer. Our g MDSC kinetics data warrant further clinical validation and mechanistic investigation.

Comparison of efficacy and safety of nab-paclitaxel and oxaliplatin+S-1 and standard S-1 and oxaliplatin chemotherapy regimens for treatment of gastric cancer

BACKGROUND Gastric cancer(GC)is a relatively frequent clinical phenomenon,referring to ma-lignant tumors emerging in the gastric mucosal epithelial cells.It has a high mor-bidity and mortality rate,posing a significant threat to the health of patients.Hence,how to diagnose and treat GC has become a heated topic in this research field.AIM To discuss the effectiveness and safety of nab-paclitaxel in combination with oxaliplatin and S-1(P-SOX)for the treatment of GC,and to analyze the factors that may influence its outcomes.METHODS A total of 219 eligible patients with advanced GC,who were treated at Qinghai University Affiliated Hospital Gastrointestinal Oncology between January 2018 and March 2020,were included in the study.Among them,149 patients received SOX regimen and 70 patients received S-1 regimen.All patients underwent both preoperative and postoperative chemotherapy consisting of 2-4 cycles each,totaling 6-8 cycles,along with parallel D2 radical surgical treatment.The patients were followed up for a period of three years or until reaching the event endpoint.RESULTS The short-term and long-term efficacy of the P-SOX group was significantly higher than that of the SOX group,and the safety was manageable.Cox multivariate analysis revealed that progression-free survival was associated with perioperative chemotherapy efficacy,tumor diameter≤2cm,high differentiation,and early cTNM(T stands for invasion depth;N stands for node metastasis;M stands for distant invasion)stage.CONCLUSION In comparison to the SOX regimen,the P-SOX regimen demonstrates improved short-term and long-term efficacy with tolerable adverse reactions.It is anticipated that the P-SOX regimen will emerge as a first-line chemotherapy option for GC.Patients with GC who receive effective perioperative chemotherapy(Response Evaluation Criteria in Solid Tumors 1.1,Tumor Regression Grade),have a tumor diameter≤2cm,exhibit high degree of differentiation,and are at an early cTNM stage show better prognosis.

Apatinib,S-1 Combined with Paclitaxel Perfusion in the Treatment of Malignant Seroperitoneum of Gastric Cancer

Objective:To analyze the effect of apatinib,S-1 combined with paclitaxel perfusion on malignant seroperitoneum of gastric cancer.Methods:From December 2019 to May 2020,172 patients with gastric cancer treated in our hospital were randomly divided into two groups:observation group and control group,86 cases each.The control group adopted the method of S-1 combined with paclitaxel perfusion therapy in the treatment of malignant seroperitoneum of gastric cancer.The observation group was given oral apatinib on the basis of S-1 combined with paclitaxel perfusion therapy,and the dosage was 500 mg/d.Results:The total effective treatment in the control group was 43.02%,while the total effective rate in the observation group was 69.77%;the drug resistance of the two groups of patients increased and the adverse reactions were low.Conclusion:Apatinib and S-1 combined with paclitaxel perfusion therapy can effectively improve the treatment effect,stabilize the patient's condition,increase the patient's drug resistance to adverse reactions,and have a good prognosis.

Short-term outcomes of albumin-bound paclitaxel (abraxane)-containing chemotherapy in patients with advanced gastric cancer: a report of 14 cases

Objective： Albumin-bound paclitaxel （abraxane, ABX） has more favorable efficacy and less toxicity than conventional taxanes. However, the data of ABX in advanced gastric cancer （AGC） treatment is unavailable. The current study was designed to summarize our experience in treating AGC patients with ABX. Methods： The clinical data of patients with AGC who had received at least one cycle of ABX-based chemotherapy in Sun Yat-sen University Cancer Center from January 10th 2010 to May 14th 2012 was retrospectively analyzed. Results： A total of 47 cycles of ABX-containing regimens, with a median of 3 cycles （range： 1-8 cycles）, were administered to 14 patients. Five （35.7%） partial responses and 6 （42.9%） stable diseases were obtained, with a disease control rate （DCR） of 78.6%. The median progression free survival （PFS） and overall survival （OS） were 3.3 and 10.8 months, respectively. Interestingly, patients in the first-line setting achieved a DCR of 100% （8/8）. Neutropenia and thrombocytopenia were the main grade 3/4 adverse events with an incidence of 50% in the whole group. However, only 25% patients （2/8） experienced grade 3 neutropenia when ABX in combination with fluoropyrJmJdines. Conclusion： The activity of ABX-based regimens as first-line therapy for patients with AGC is remarkable, and the toxicity is mild when ABX combined with fluorepyrimidines. Further prospective clinical trials of ABX-based chemotherapy as first-line treatment for AGC are strongly anticipated.

Expressions of Thymidylate Synthase, Thymidine Phosphorylase, Class Ⅲ β-tubulin, and Excision Repair Cross-complementing Group 1 Predict Response in Advanced Gastric Cancer Patients Receiving Capecitabine Plus Paclitaxel or Cisplatin

Objective: To evaluate the role of class III β-tubulin (TUBB3), thymidylate synthase (TS), thymidine phosphorylase (TP), and excision repair cross-complementing group 1 (ERCC1) in clinical outcome of advanced gastric cancer patients receiving capecitabine plus paclitaxel or cisplatin. Methods: The clinical data and tumor specimens from 57 advanced gastric cancer patients receiving first-line capecitabine plus paclitaxel (cohort 1, n=36) and capecitabine plus cisplatin (cohort 2, n=21) were retrospectively collected, and TUBB3, TS, TP, and ERCC1 expressions were detected by real-time quantitative PCR. The associations between expressions of biomarkers and response or survival were analyzed statistically. Results: The median age of 57 patients was 57 years (range: 27–75 years) with 38 males and 19 females. Of all patients, the response rates of patients with high TP, low TP and high TS, low TS expressions were 57.1%, 27.6% (P=0.024), and 55.2%, 28.6% (P=0.042), respectively. Among cohort 1, the response rates and median overall survivals of patients with low and high TUBB3 expressions were 61.1% vs. 33.3% (P=0.095) and 13.8 months vs. 6.6 months (P=0.019), respectively; the response rate (87.5%) of patients with low TUBB3 and high TP expressions was higher than that (14.3%) of patients with high TUBB3 and low TP expressions (P=0.01). Among cohort 2, the response rates of patients with low ERCC1 and high ERCC1 expressions were 45.5% and 20.0% respectively (P=0.361). Conclusion: TUBB3, TS and TP expressions could predict the response of advanced gastric cancer patients receiving capecitabine-based and paclitaxel-based chemotherapy. These results will be further confirmed in future large samples.

Pharmacokinetic study of paclitaxel in malignant ascites from advanced gastric cancer patients

AIM： To examine the paclitaxel concentrations in plasma and ascites after its intravenous administration in patients with ascites due to peritonitis carcinomatosa resulting from advanced gastric cancer. METHODS： Two patients with ascites due to peritonitis carcinomatosa resulting from gastric cancer were included in this study. The paclitaxel concentrations in plasma and ascites were investigated for 72 h in case 1 and 168 h in case 2 after intravenous administration. RESULTS： The paclitaxel concentration in plasma peaked immediately after administration, followed by rapid decrease below the threshold value of 0.1 μmol （85 ng/mL） within 24 h. In contrast, the paclitaxel concentration in ascites increased gradually for 24 h after administration to a level consistent with the level found in plasma. After 24 h the level of paclitaxel in ascites and plasma became similar, with the optimal level being maintained up to 72 h following administration. CONCLUSION： The concentration of paclitaxel in ascites is maintained within the optimal level for the treatment of cancer cells for up to 72 h after intravenous administration. Paclitaxel is a promising drug for the treatment of malignant ascites of gastric cancer.

Synergistic inhibitory effect of wogonin and low-dose paclitaxel on gastric cancer cells and tumor xenografts

Objective：To investigate the synergistic inhibitory effects of wogonin （WOG） and chemotherapeutic drugs on growth of gastric cancer cells and tumor xenografts.Methods：The IC50 values of WOG,cisplatin （CDDP） and paclitaxel （PTX） in four gastric cancer cell lines were determined by MTS assay.Hoechst staining and the median effect method of Chou-Talalay were used to assess the apoptosis of cells and the interaction of two drugs,respectively.BGC-823-derived xenografts in nude mice were established to investigate the effects of WOG combined with chemotherapeutic drugs in vivo.Results：WOG,CDDP and PTX inhibited the growth of BGC-823,MGC-803,MKN-45 and HGC-27 gastric cancer cells in a dose-dependent manner.WOG combined with CDDP or PTX synergistically inhibited the growth of all gastric cancer cell lines in vitro.In BGC-823,MGC-803,HGC-27 and MKN-45 cell lines,synergisms between WOG and PTX were shown when the fraction affected （Fa） values were ＜0.45,＜0.90,＜0.85 and ＜0.60.While WOG and CDDP had a synergistic inhibitory.effect when the Fa values were ＞0,＞0,＞0.65 and ＞0.10.From the results of in vivo experiments using tumor xenografts,WOG and low-dose PTX showed better efficacy than either drug alone.The inhibitory percentages of tumor weight were 61.58％,20.29％,and 22.28％ for the combination,WOG-alone,and low-dose PTX-alone groups,respectively.Notably,WOG combined with CDDP displayed very high toxicity.Conclusions：A synergistic inhibitory effect on growth was observed when WOG was combined with low-dose PTX in gastric cancer cells and tumor xenografts.These findings provide evidence for the design of a clinical trial to test the combination of WOG with low-dose PTX in human gastric cancer.

Upregulation of miR-34c after silencing E2F transcription factor 1 inhibits paclitaxel combined with cisplatin resistance in gastric cancer cells

BACKGROUND MicroRNA 34c(miR-34c)has been reported to be associated with malignant types of cancer,however,it remains unknown whether miR-34c is involved in chemoresistance in gastric cancer(GC).AIM To investigate the effect of miR-34c and its upstream transcription factor E2F1 on paclitaxel combined with cisplatin resistance in GC cells.METHODS Paired GC tissues and adjacent normal tissues were randomly sampled from 74 GC patients.miR-34c and E2F1 were detected by real-time quantitative PCR(qPCR)and Western blot.In addition,the drug resistance of GC cells to paclitaxel and cisplatin was induced by concentration gradient increasing methods,and changes in miR-34c and E2F1 during this process were measured.Furthermore,E2F1 and miR-34c overexpression or underexpression vectors were constructed and transfected into drug-resistant GC cells.MTT was employed to test the sensitivity of cells to paclitaxel combined with cisplatin,qPCR was adopted to detect the expression of miR-34c,Western blot was applied to detect the expression levels of E2F1,drug resistance-related proteins and apoptosis-related proteins,and flow cytometry was used for the determination of cell apoptosis and cell cycle status.RESULTS E2F1 was overexpressed while miR-34c was underexpressed in GC.After inducing GC cells to be resistant to paclitaxel and cisplatin,E2F1 expression increased while miR-34c expression decreased.Both silencing E2F1 and overexpressing miR-34c could increase the sensitivity of drug-resistant GC cells to paclitaxel combined with cisplatin,promote cell apoptosis and inhibit cell proliferation.Among which,silencing E2F1 could reduce the expression of drug resistance-related proteins and apoptosis-related proteins,while over-expression of miR-34c could upregulate the expression of apoptosis-related proteins without affecting the expression of MDR-1,MRP and other drug resistance-related proteins.Rescue experiments demonstrated that inhibiting miR-34c could significantly weaken the sensitization of drug resistant cells,and Si E2F1 to paclitaxel combined with cisplatin.CONCLUSION E2F1 inhibits miR-34c to promote the proliferation of GC cells and enhance the resistance to paclitaxel combined with cisplatin,and silencing E2F1 is conducive to improving the efficacy of paclitaxel combined with cisplatin in GC cells.

Molecular mechanisms of paclitaxel and NM-3 on human gastric cancer in a severe combined immune deficiency mice orthotopic implantation model

AIM: To explore the molecular mechanisms of action of paclitaxel and NM-3 on human gastric cancer in severe combined immune deficiency (SCID) mice. METHODS: Human gastric cancer cells SGC-7901 were implanted into SCID mice and mice were treated with paclitaxel and NM-3. The effects of paclitaxel and NM-3 on apoptosis of human gastric cancer cells were analyzed using flow cytometry, TUNEL assays, and DNA fragment analyses. RESULTS: Apoptosis of SGC-7901 cells was successfully induced by paclitaxel, NM-3, and the combination of paclitaxel and NM-3 24 h after injection as shown by the presence of apoptotic hypodiploid peaks on the flow cytometer before G1-S and a characteristic apoptotic band pattern in the DNA electrophoresis. The apoptotic rate detected by TUNEL assay was found to be significantly higher in the paclitaxel/NM-3 compared to the control group (38.5% ± 5.14% vs 13.2% ± 1.75%, P < 0.01). CONCLUSION: Paclitaxel in combination with NM-3 is able to induce apoptosis of the human gastric cancer cells in SCID mice effectively and synergistically.

Superior in vitro anticancer effect of biomimetic paclitaxel and triptolide co-delivery system in gastric cancer

As a well-known anticancer drug,paclitaxel(PTX),a first-line chemotherapeutic agent,remains unsatisfactory for gastric cancer therapy.It is reported that triptolide(TPL)could enhance the anti-gastric cancer effect of PTX.Considering the poor solubility of both drugs,we developed a red blood cell membrane-biomimetic nanosystem,an emerging tool in drug delivery,to co-load paclitaxel and triptolide(red blood cell membrane coated PTX and TPL co-loaded poly(lactic-co-glycolic acid)[PLGA]nanoparticles,RP(P/T)).The successful preparation was confirmed in terms of particle size,morphology,and surface markers assays.This biomimetic system could prolong circulation and escape immune surveillance.And these properties were verified by stability,in vitro drug release,and cellular uptake assays.Moreover,the MTT and colony formation assays demonstrated the superior anti-proliferation effect of the RP(P/T)to free drugs.The enhanced antitumor effects of RP(P/T)on migration and invasion were also evaluated by wound-healing and transwell assays.Overall,the bionic co-delivery nanoplatform with improved efficacy in vitro is a promising therapy for gastric cancer.

Impact of Oxaliplatin-Induced Neuropathy on Subsequent Paclitaxel for Advanced Gastric Cancer

Purpose: Several studies have shown that fluoropyrimidine plus oxaliplatin (SOX) is non-inferior to fluoropyrimidine plus cisplatin as first-line chemotherapy for advanced gastric cancer. We investigated retrospectively the choice of second-line regimen, along with the proportion and feasibility of paclitaxel-containing regimen, in the subsequent treatment of patients with advanced gastric cancer treated with SOX as first-line chemotherapy. Materials and Methods: We retrospectively analyzed the impact of oxaliplatin-induced neuropathy on both the choice of subsequent regimens and feasibility of subsequent chemotherapy with paclitaxel, focusing on patients with advanced gastric cancer who received S-1 plus oxaliplatin as first-line chemotherapy. Results: Twenty-seven from a total of 31 patients enrolled into the phase 2 and phase 3 study assessing S-1 plus oxaliplatin were analyzed (4 patients were deemed ineligible). Among 24 patients that had received second-line treatment, paclitaxel was not selected in 2 patients due to oxaliplatin-induced neuropathy. Paclitaxel was selected as second-line chemotherapy in 16 patients, as third-line chemotherapy in 6 patients and fourth-line chemotherapy in one patient. Severity of sensory neuropathy was grade 0/1/2/3 in 11/10/2/0 patients, respectively, immediately before treatment with paclitaxel, while the worst toxicity profile during paclitaxel treatment was grade 0/1/2/3 in 7/13/1/2 patients, respectively. Although there were no patients requiring dose reductions of paclitaxel due to neuropathy, 2 patients discontinued paclitaxel use due to grade 3 sensory neuropathy after 4 or 8 administrations of paclitaxel. Conclusion: Oxaliplatin-induced neuropathy during first-line chemotherapy may affect the choice and feasibility of subsequent chemotherapy with paclitaxel in advanced gastric cancer patients.

Pharmacokinetics of paclitaxel in a hemodialysis patient with advanced gastric cancer: A case report

We report for the first time the possibility of weekly paclitaxel chemotherapy for a patient with advanced, nonresectable gastric cancer undergoing hemodialysis. A 50-year-old man with chronic renal failure due to bilateral polycystic kidneys, who had undergone hemodialysis three times a week for 5 years, presented with hematemesis in December 2004. Based on the diagnosis of gastric cancer with lymph node metastases, surgery was performed. On the 15th postoperative day, the patient was treated with chemotherapy using paclitaxel. Paclitaxel was administered at a dose of 60 mg/m^2 as a 1 h iv infusion in 250 mL of saline. Hemodialysis was started 1 h after the completion of the paclitaxel infusion and was performed for 3 h. Paclitaxel was administered weekly on d 1, 8, and 15 on a 28-d cycle. The maximum plasma concentration of paclitaxel was 1390 μg/L. The area under the curve of paclitaxel was 4398.6 μg·h/L. Grade 2 leukopenia was encountered during the first cycle. The plasma concentrations of paclitaxel from 6 to over 24 h after the infusion were 0.01 to 0.1 μmol/L in our patient, and these concentrations have been shown to be effective on inhibiting the growth of gastric cancer cells without producing adverse side effects in the patient. The plasma concentration of paclitaxel was not influenced by hemodialysis. We conclude that the pharmacokinetics of paclitaxel is not altered in a patient with renal failure, and that weekly paclitaxel is a suitable treatment regimen for hemodialysis patients with advanced gastric cancer.

A case of scirrhous gastric cancer with peritonitis carcinomatosa controlled by TS-1~ + paclitaxel for 36 mo after diagnosis

A 34-year-old female complaining of abdominal fullness was diagnosed as scirrhous gastric cancer （type 4＇） with peritonitis carcinomatosa in July 2002. A combined chemotherapy regimen was selected to control massive ascites; TS-1 80 mg/m^2 was given orally on d 1-14, 22-35, and paclitaxel 50 mg/m^2 was administered intravenously on d 1, 8, 22 and 29. After 2 courses of this regimen, the primary tumor was markedly reduced, and ascites completely vanished. Alopecia （grade 1, since d 30）, leukocytopenia （grade 2, on d 34） and anemia （grade 2, on d 34） were the only adverse events throughout the following courses. The chemotherapy was effective for 28 mo, and then it was discontinued upon the patient＇s own request, and she survived for 36 mo after diagnosis.

Gastric cancer liver metastasis will reduce the efficacy of immunotherapy

Immune checkpoint inhibitors augment the antitumor activity of T cells by inhibiting the negative regulatory pathway of T cells,leading to notable efficacy in patients with non-small cell lung cancer,melanoma,and other malignancies through immunotherapy utilization.However,secondary malignant liver tumors not only lower the liver's sensitivity to immunotherapy but also trigger systemic immune suppression,resulting in reduced overall effectiveness of immune therapy.Patients receiving immunotherapy for non-small cell lung cancer and melanoma experience reduced response rates,progression-free survival,and overall survival when secondary malignant tumors develop in the liver.Through Liu's retrospective analysis,valuable insights are provided for the future clinical management of these patients.Therefore,in patients with gastric cancer(GC),the occurrence of liver metastasis might be indicative of reduced efficacy of immuno-therapy.Overcoming liver immune tolerance mechanisms and their negative impacts allows for the potential benefits of immunotherapy in patients with GC and liver metastasis.INTRODUCTION Gastric cancer(GC)ranks among the prevalent malignancies affecting the digestive system globally.Based on the latest epidemiological data[1,2],it holds the fifth position for incidence and the fourth position for mortality among all malignant tumors.GC cases and fatalities in China make up roughly half of the worldwide figures.Earlier investigations[3]have demonstrated that the median overall survival(mOS)among advanced GC patients left untreated typically ranges from 3 to 4 months.Systemic chemotherapy recipients often experience a mOS of around one year,accompanied by a marked improvement in the quality of life among patients with advanced GC.The mainstay of treatment for advanced GC patients involves chemotherapeutic medications such as fluoropyrimidines,platinum compounds,and taxanes.However,their efficacy in tumor control is constrained by acquired resistance and primary resistance.The rise of personalized precision therapy has propelled immunotherapy into the spotlight as a crucial component of comprehensive treatment[4].By blocking the negative regulatory pathways of T cells,immune checkpoint inhibitors(ICIs)boost the anti-tumor effect of T cells.Immunotherapy has brought about significant therapeutic benefits for patients diagnosed with non-small cell lung cancer,melanoma,and related illnesses[5,6],instilling newfound hope in those with advanced GC[7].However,phase III clinical trial data[8-12]reveals that the incorporation of immunotherapy into chemotherapy regimens improves overall survival(OS)outcomes for patients with advanced GC.The liver's immune-exempt nature renders it less responsive to immunotherapy when secondary malignant tumors are present,fostering systemic immune suppression and yielding unfavorable outcomes in immune therapy[13-15].In retrospective research[16-20]pertaining to non-small cell lung cancer and melanoma,it has been observed that the presence of secondary liver malignancies may lower the response rate,progression-free survival(PFS),and OS rates in patients treated with immunotherapy,independent of factors such as tumor mutation burden and PD-L1 expression.Despite this,there is a paucity of studies examining whether the existence of secondary malignant liver tumors affects the effectiveness of immunotherapy in patients diagnosed with advanced HER-2 negative GC.

Weekly paclitaxel and S-1 combination chemotherapy for advanced gastric cancer

Objective:There remains no standard first-line chemotherapeutic regimen for advanced gastric cancer (AGC).The aim of this study was to evaluate the efficacy and safety of combination regimen with weekly paclitaxel and S-1 as a first-line chemotherapy for AGC. Methods:Forty-six patients with AGC were included in this study. Paclitaxel was administered weekly at a dose of 60 mg/m2 on days 1, 8 and 15, S-1 was administered orally twice daily at 80 mg/m2/day for 2 weeks. The regimen was repeated every four weeks. Results:The results showed that the overall response rate was 45.7%, with 3 patients achieved complete response and 18 patients had a partial response, the disease control rate was 76.1%. The median progress free survival was 7.2 months 95% confidence interval (CI):6.3-8.1 months and the median overall survival was 11.6 months (95% CI:10.6-12.6 months) after treatment with paclitaxel and S-1. Neutropenia occurred in 25 patients (54.3%) and grade 3/4 neutropenia was observed in 8 patients (17.4%), gastrointestinal reactions were the most common non-hematologic toxicities, while severe gastrointestinal toxicities were uncommon. Conclusion:The regimen of weekly paclitaxel and S-1 demonstrated activity and acceptable toxicity for AGC as a first-line chemotherapy.

Trial of the correlation between cytochrome oxidase CYP3A4 with the susceptibility of paclitaxel-based regimen for advanced gastric cancer

Objective: The aim of the study was to investigate the relationship between susceptibility of paclitaxel-based regimen and gene polymorphisms of cytochrome oxidase CYP3A4 for advanced gastric cancer. Methods: Peripheral venous blood sample of 53 advanced gastric cancer patients were enrolled to test the mutation of CYP3A4 gene by denaturing high performance liquid chromatography(DHPLC) and DNA sequencing. The relation between the efficacy of paclitaxel-based regimen and CYP3A4 gene polymorphisms was further analyzed. Results: DHPLC indicated that among the 53 patients, 21 cases showed biomodal type(mutation) and 32 cases were of unimodal type(wild-type). Sequencing results showed that the deletion mutation was found at the 27 th basic group of C in exon 10 of CYP3A4 gene. The response rate(RR) and disease control rate(DCR) of wild-type group were 40.6% and 84.4%, while in mutation group they were 33.3% and 85.7%, respectively, with no significances between the two groups(P > 0.05). Of all 53 cases, the median progression-free survival(PFS) was 6.5 months(95% CI: 3.576–9.424 months), and the median overall survival(OS) was 11.0 months(95% CI: 6.955–15.045 months). The median PFS and OS in wild-type group had no differences compared with those in mutation group(7.0 months vs. 7.0 months, P > 0.05; 10.0 months vs. 14.0 months, P > 0.05). Between wild-type and mutation groups, the median PFS of patients applied with oxaliplatin containing regimen and the median OS in patients applied with/without oxaliplatin had no significant differences(P > 0.05), while the median PFS in patients received non-oxaliplatin regime had statistical differences(P = 0.024). The median PFS and OS in patients receiving 3-drug or 2-drug regimes had no correlation with CYP3A4 gene polymorphisms. The adverse effects in the two groups were mild, mainly in grades 1–2. The common adverse effects were anorexia, nausea/vomiting and leucopenia. Conclusion: Deletion mutation was located in the 27 th basic group of C in exon 10 of CYP3A4 gene. Paclitaxel-based regime has a trend to prolong the OS of advanced gastric cancer with mutation type.

Double role of depression in gastric cancer:As a causative factor and as consequence

In this editorial we comment on the article“Hotspots and frontiers of the rela-tionship between gastric cancer and depression:A bibliometric study”.Gastric cancer(GC)is a common malignancy in the digestive system with increased mortality and morbidity rates globally.Standard treatments,such as gastrectomy,negatively impact patients'quality of life and beyond the physical strain,GC patients face psychological challenges,including anxiety and depression.The prevalence of depression can be as high as 57%,among gastrointestinal cancer patients.Due to the advancements in treatment effectiveness and increased 5-year overall survival rates,attention has shifted to managing psychological effects.However,the significance of managing the depression doesn’t lie solely in the need for a better psychological status.Depression leads to chronic stress acti-vating the sympathetic nervous system and the hypothalamus-pituitary-adrenal axis,leading release of catecholamines inducing tumor proliferation,migration,and metastasis,contributing to GC progression.The dysregulation of neurotrans-mitters and the involvement of various signaling pathways underscore the complex interplay between depression and GC.Comprehensive strategies are required to address the psychological aspects of GC,including region-specific interventions and increased monitoring for depression.Understanding the intricate relationship between depression and GC progression is essential for developing effective therapeutic strategies and improving overall outcomes for patients facing this complex disease.In this Editorial we delve into double role of depression in the pathogenesis of GC and as a complication of it.

Success rate of current human-derived gastric cancer organoids establishment and influencing factors:A systematic review and meta-analysis

BACKGROUND Human-derived gastric cancer organoids(GCOs)are widely used in gastric cancer research;however,the culture success rate is generally low.AIM To explore the potential influencing factors,and the literature on successful culture rates of GCOs was reviewed using meta-analysis.METHODS PubMed,Web of Science,and EMBASE were searched for studies.Two trained researchers selected the studies and extracted data.STATA 17.0 software was used for meta-analysis of the incidence of each outcome event.The adjusted Methodological Index for Non-Randomized Studies scale was used to assess the quality of the included studies.Funnel plots and Egger’s test were used to detect publication bias.Subgroup analyses were conducted for sex,tissue source,histo-logical classification,and the pathological tumor-node-metastasis(pTNM)cancer staging system.RESULTS Eight studies with a pooled success rate of 66.6%were included.GCOs derived from women and men had success rates of 67%and 46.7%,respectively.GCOs from surgery or biopsy/endoscopic submucosal dissection showed success rates of 70.9%and 53.7%,respectively.GCOs of poorly-differentiated,moderately-differentiated and signet-ring cell cancer showed success rates of 64.6%,31%,and 32.7%,respectively.GCOs with pTNM stages I-II and III-IV showed success rates of 38.3%and 65.2%,respectively.Y-27632 and non-Y-27632 use showed success rates of 58.2%and 70%,respectively.GCOs generated with collagenase were more successful than those constructed with Liberase TH and TrypLE(72.1%vs 71%,respectively).EDTA digestion showed a 50%lower success rate than other methods(P=0.04).CONCLUSION GCO establishment rate is low and varies by sex,tissue source,histological type,and pTNM stage.Omitting Y-27632,and using Liberase TH,TrypLE,or collagenase yields greater success than EDTA.

Streptococcus anginosus in the development and treatment of precancerous lesions of gastric cancer

The microbiota is strongly association with cancer.Studies have shown significant differences in the gastric microbiota between patients with gastric cancer(GC)patients and noncancer patients,suggesting that the microbiota may play a role in the development of GC.Although Helicobacter pylori(H.pylori)infection is widely recognized as a primary risk factor for GC,recent studies based on microbiota sequencing technology have revealed that non-H.pylori microbes also have a significant impact on GC.A recent study discovered that Streptococcus anginosus(S.anginosus)is more prevalent in the gastric mucosa of patients with GC than in that of those without GC.S.anginosus infection can spontaneously induce chronic gastritis,mural cell atrophy,mucoid chemotaxis,and heterotrophic hyperplasia,which promote the development of precancerous lesions of GC(PLGC).S.anginosus also disrupts the gastric barrier function,promotes the proliferation of GC cells,and inhibits apoptosis.However,S.anginosus is underrepresented in the literature.Recent reports suggest that it may cause precancerous lesions,indicating its emerging pathogenicity.Modern novel molecular diagnostic techniques,such as polymerase chain reaction,genetic testing,and Ultrasensitive Chromosomal Aneuploidy Detection,can be used to gastric precancerous lesions via microbial markers.Therefore,we present a concise summary of the relationship between S.anginosus and PLGC.Our aim was to further investigate new methods of preventing and treating PLGC by exploring the pathogenicity of S.anginosus on PLGC.