This study aimed to develop and validate a prognostic nomogram to predict overall survival (OS) in patients with Barcelona Clinic Liver Cancer (BCLC) stage C hepatocellular carcinoma (HCC) undergoing multimodal therapy, combining transarterial chemoembolization, hepatic arterial infusion chemotherapy, tyrosine kinase inhibitors, and programmed death-1 inhibitors. A retrospective analysis included 193 patients with BCLC stage C HCC treated at Xuzhou Medical University Affiliated Hospital between February 2021 and February 2024. Patients were randomly divided into a training cohort (n = 135) and a validation cohort (n = 58). Independent prognostic factors were identified via Cox regression analysis. A nomogram was developed and evaluated using the concordance index (C-index), time-dependent receiver operating characteristic curves, calibration plots, and decision curve analysis. Risk stratification was performed using X-tile software. The median OS was 402 days. Multivariate analysis identified ALBI grade (HR [Hazard Ratio] = 10.09–19.63), maximum tumor diameter ≥ 5 cm (HR = 2.69), multiple tumors (HR = 2.59), and vascular invasion (HR = 2.74) as independent predictors of OS. The nomogram demonstrated strong discriminatory performance, with C-indices of 0.788 in the training cohort and 0.805 in the validation cohort. The time-dependent AUCs for 1-year and 1.5-year OS were 0.879 and 0.887 in the training cohort, and 0.923 and 0.832 in the validation cohort, respectively. Calibration curves showed excellent agreement between predicted and observed outcomes. Decision curve analysis supported the clinical utility of the model. Risk stratification based on the nomogram revealed significant survival differences between the low- and high-risk groups (median OS: 566 vs. 454 days; P < 0.001). This novel nomogram, integrating locoregional and systemic therapies, offers an individualized tool for prognostication in patients with BCLC stage C HCC, potentially guiding therapeutic decision-making and patient counseling.
Abstract Topic Esophageal Cancer: Adjuvant and Neo-Adjuvant Therapies Background Esophageal squamous cell carcinoma (ESCC) with synchronous primary cancers in pharynx and larynx (SPC-PL) is rare and lacks standard-of-care treatment. This study examined tumor response and survival after neoadjuvant immuno-chemotherapy (nICT) in ESCC patients with SPC-PL. Methods This retrospective single-center study analyzed 21 patients with ESCC and SPC-PL who received nICT between 2020 and 2024. Treatment response was evaluated using clinical (endoscopic and radiological) and pathological criteria. Outcomes included response rates, overall survival (OS), and progression-free survival (PFS) and laryngeal preservation rates. Results The nICT regimen induced a clinical complete response (CR) in 71.4% (15/21) of SPC-PL lesions and a pathological CR in 38.5% (5/13) of resected esophageal specimens. With a median follow-up of 28.2 months, the 2-year OS and PFS rates were 75.9% and 44.1%, respectively. Laryngeal-preserving strategies were successfully implemented in 85.7% (6/7) of patients with locally advanced SPC-PL (cT2-3N0-2) who were conventional candidates for total laryngo-pharyngectomy. No significant difference in OS or PFS was observed compared to a concurrent surgical resection cohort (n=18). Conclusion nICT showed promising efficacy in treating ESCC patients with SPC-PL, providing high rates of tumor regression and laryngeal preservation. These results support nICT as an initial treatment option for ESCC patients with SPC-PL but further validation is needed.
Vascular endothelial growth factor B (VEGFB), a member of VEGF family, shares the VEGFR1 receptor with VEGFA. VEGFB has two isoforms, VEGFB167 and VEGFB186, whose distinct biological roles remain poorly characterized. To elucidate the isoform-specific functions of VEGFB in tumorigenesis, we utilized transgenic mouse models, including VEGFB overexpression (aP2-Vegfb167, aP2-Vegfb186) and VEGFB knockout (Vegfb-/-), along with tumor cell lines (B16-F10, U14 and LLC). Our findings revealed that VEGFB167 acts as a potent promoter of tumor growth. VEGFB inactivation significantly retards tumor growth and tumor cell metastasis. Mechanistically, VEGFB deficiency alters the tumor microenvironment by shifting tumor-associated macrophages (TAMs) from a pro-tumor M2 phenotype to an anti-tumor M1 phenotype, thereby enhancing anti-tumor immunity. Notably, the impact of VEGFB on tumor growth and metastasis surpasses that of VEGFA, highlighting its potential as a promising therapeutic target. These findings establish VEGFB167 as a key regulator of tumor progression and suggest that targeting VEGFB signaling could provide novel strategies for VEGFB-sensitive cancers.
Deep learning(DL) models can improve significantly discrimination of lymph node metastasis(LNM) of pancreatic ductal adenocarcinoma(PDAC), but have not been systematically assessed. To develop and test a transformer model utilizing dual-energy computed tomography (DECT) for predicting LNM in patients with PDAC. This retrospective study examined patients who had undergone surgical resection and had pathologically confirmed PDAC, with DECT performed between August 2016 and October 2022. Six predictive models were constructed: a DECT report model, a clinical model, 100 keV DL model, 150 keV DL model, a combined 100 + 150 keV DL model, and a model that integrated clinical information with DL-derived signatures. Multivariable logistic regression analysis was employed to develop the integrated model. The efficacy of these models was assessed by comparing their areas under the receiver operating characteristic curve (AUC) using the Delong test. Survival analysis was conducted using Kaplan-Meier curves. In brief, 223 patients (mean age, 57 years ± 11 standard deviation; 93 men) were evaluated. All patients were divided into training (n = 160) and test (n = 63) sets. Patients with LNM accounted for 96 of the 223 patients (43
Background: In the JCOG0501 study, neoadjuvant chemotherapy (NAC) failed to demonstrate survival benefits for type 4 and large type 3 gastric cancer (GC). The prognosis of these patients is still poor. We conducted this study to explore the value of NAC with non-SP regimens for type 4 and large type 3 GC in the Chinese population. Methods: We retrospectively collected data from our electronic medical record system. Patients with large type 3 or type 4 GC who underwent D2 gastrectomy and AC were included. Patients were divided into two groups based on whether they received NAC: the CSC (NAC + surgery + AC) and SC (surgery + AC) groups. The survival and perioperative outcomes for large type 3 or type 4 GC were analyzed between the CSC and SC groups, separately. Results: Between May 2009 and December 2018, 189 patients were reviewed. Among large type 3 GC, the 5-year overall survival (OS) rates for patients in the CSC and SC groups were 54.4 % and 28.0 %, respectively (P = 0.0008). Among type 4 GC, the 5-year OS rates for patients in the CSC and SC groups were 15.8 % and 24.8 %, respectively (P > 0.05). Conclusions: This study showed NAC can improve the prognosis of large type 3 GC. However, NAC did not demonstrate significant survival advantages for type 4 GC.
Glial-cell-line-derived neurotrophic factor (GDNF) is highly expressed and is involved in the malignant phenotype in glioblastomas (GBMs). However, uncovering its underlying mechanism for promoting GBM progression is still a challenging work. In this study, we found that serine protease inhibitor family E member 1 (SERPINE1) was a potential downstream gene of GDNF. Further experiments confirmed that SERPINE1 was highly expressed in GBM tissues and cells, and its levels of expression and secretion were enhanced by exogenous GDNF. SERPINE1 knockdown inhibited the migration and invasion of GBM cells promoted by GDNF. Mechanistically, GDNF increased SERPINE1 by promoting the phosphorylation of SMAD2/3. In vivo experiments demonstrated that GDNF facilitated GBM growth and the expressions of proteins related to migration and invasion via SERPINE1. Collectively, our findings revealed that GDNF upregulated SERPINE1 via the SMAD2/3-signaling pathway, thereby accelerating GBM cell migration and invasion. The present work presents a new mechanism of GDNF, supporting GBM development.
Purpose To retrospectively analyze the clinical characteristics of patients undergoing surgical treatment for gastrointestinal stromal tumors (GISTs) in Ruijin Hospital and explore the relevant prognosis clinical factors after surgical treatment. Methods We screened out 1015 patients with GISTs diagnosed and treated during January 2010 to December 2019. We performed univariate analysis by the log-rank test and multivariate analysis by COX regression. The Kaplan–Meier method was used to estimate the disease-free survival (DFS) and overall survival (OS) of the whole group. Results All 1015 patients in the whole group received radical surgery, and the proportion of patients with high, intermediate, and low risk was 31.1%, 21.7%, and 47.3%, respectively. Among the 480 low-risk patients, surgery could achieve radical therapy; only the Ki-67 index was related to DFS and OS (DFS: p = 0.032, OS: p = 0.009) among the 140 intermediate-risk patients with tumors located in the stomach, whether received Tyrosine kinase inhibitors (TKIs) therapy did not affect the prognosis of patients (DFS: p = 0.716, OS: p = 0.848). Among the 331 high-risk patients, those with non-gastric tumors (those outside the stomach, duodenum, and small intestine, HR 1.55, 95% CI 1.19–2.00, p < 0.001), tumor diameter > 10 cm (hazard ratio, HR 2.63, 95% confidence interval, CI 2.09–4.03, p < 0.001), as well as high-risk patients with mitotic rate > 10/50 HPF (HR 2.74, 95% CI 2.00–3.76, p < 0.001), the overall prognosis was obviously worse than that of other patients. For some high-risk patients, prolonged postoperative imatinib therapy could significantly improve the survival of patients (HR 0.43, 95% CI 0.15–0.66, p < 0.001). Conclusions For the vast majority of GIST patients, surgery can be curative; but in intermediate-risk patients, the Ki-67 index and postoperative TKI treatment are closely related to prognosis. For intermediate-risk patients whose primary tumor is the stomach, the value of TKI-targeted therapy after surgery seem be not necessary in our study. However, for some high-risk patients, the prognosis of patients can be improved by appropriately prolonging the treatment time of TKI.
To investigate the efficacy, feasibility, and safety of transjugular intrahepatic portosystemic shunt (TIPS) as a treatment for patients with recurrent portal hypertension with variceal bleeding (RPHVB) who have previously undergone open splenectomy and esophagogastric devascularization (OSED). The data were retrospectively retrieved from 39 cirrhotic RPHVB patients who had undergone OSED from August 2015 to December 2020. All patients were treated with TIPS using the Viabahn stent. Out of the 39 patients included in the study, TIPS was successfully performed in 38 patients with a success rate of 97.44
The paper aimed to investigate the effect of miR186-5p on invasion and migration of breast cancer cells and its molecular mechanism. MicroRNA-186-5p was found to be low expressed in breast cancer and highly expressed in SBEM by bioinformatics analysis. After transfecting MDA-MB-231 cells with miR-186-5p inhibitor NC, miR-186-5p inhibitor, miR-186-5p mimic NC and miR-186-5p mimic, respectively. The migration and invasive ability of breast cancer cells were detected by cell scratch test and Transwell test. Moreover, after adding 740 Y-P to the miR-186-5p mimic NC group and miR-186-5p mimic group cells, SBEM and PI3K pathway-related proteins were detected by Western blotting and proliferation of the cancer cells was evaluated by monoclonal cell experiment. Meanwhile, exogenous miR-186-5p mimic in MDA-MB-231 cells significantly inhibited the expression of SBEM, p-PI3K, p-AKT and their downstream pathways, MMP1, MMP3, MMP9, CyclinD1, PCNA and CyclinB1 proteins and reduced proliferation of breast cancer cells. Furthermore, the expression of SBEM protein in the miR-186-5p mimic + 740Y-P group was significantly lower than the miR-186-5p mimic NC + 740Y-P group after adding 740 Y-P. However, there were no significant changes in the protein's levels associated with PI3K pathway and the cancer cells proliferation. These results suggest that low expression of miR-186-5p in breast cancer results in an abnormally high expression of SBEM, activation of PI3K/AKT signaling pathway, promoting migration and invasion of human breast cancer cells.
Objective To analyze the therapeutic effect of uterine artery embolisation (UAE) in patients with cesarean section pregnancy (CSP) delivered by cesarean section and the effect on serum human chorionic gonadotrophin (β-HCG) levels and reproductive function. Methods In total 142 patients with CSP, The control group (n = 71) received Methotrexate (MTX) with ultrasound monitoring after admission and the research group (n = 71) was treated with UAE on basic of the control group. The two groups were compared in terms of treatment outcome, intraoperative bleeding, bed activity, vaginal bleeding and length of hospital stay, and serum follicle stimulating hormone (FSH), oestradiol (E2), luteinising hormone (LH) and β-HCG levels at 1 month postoperatively. The clinical symptoms (normalization of β-HCG and return of menstruation) and clinical outcomes (normal pregnancy, recurrent scar pregnancy) were compared between the two groups, as well as the occurrence of post-operative complications in both groups. Results Compared with the control group, the research group had a higher overall near-term effective rate, a lower recurrence rate of CSP in pregnancy, and a lower complication rate (P < 0.05); meanwhile, the time to get out of bed, postoperative vaginal bleeding, length of hospital stay, normalization of serum β-HCG, and return to menstruation were shorter in the research group than in the control group (P < 0.05); In addition, serum FSH, E2, LH and β-HCG levels improved better in the research group compared with the control group 1 month after surgery (P < 0.05). Conclusion The treatment of CSP patients with UAE can reduce the amount of intraoperative bleeding and the duration of vaginal bleeding, promote the improvement of patients' clinical symptoms, have less impact on the disruption of patients' sex hormone balance, reduce patients' surgical risks to a greater extent, preserve patients' normal fertility, and have better application.
Background:Neoadjuvant intraperitoneal and systemic chemotherapy (NIPS) has shown promising results in gastric cancer (GC) with peritoneal metastasis. However, clinical practice experience of NIPS is still lacking in China. In this study, we investigate the efficacy and safety of NIPS in Chinese patients. Methods:Eligible patients received NIPS every 3 weeks. Gastrectomy was performed for patients who met the criteria of conversion surgery. The primary end point was 1-year overall survival (OS) rate. Secondary end points were the response rate, toxic effects, conversion surgery outcomes and median survival time (MST). Results:Sixty-seven patients were enrolled. The primary endpoint was achieved with 1-year OS rate reached 67.2% (95% CI, 56.8%-79.4%). Conversion surgery was performed in 42 patients (62.9%), and R0 resection was achieved in 23 patients (54.8%) with the MST of 31.3 months (95% CI, 24.3-38.3). And the MST was 19.3 months (95% CI, 16.4-22.2) for all patients. Toxicity and surgical complications were well-tolerated. Moreover, sex, R0 resection, pathological nodal stage and tumor regression grade (TRG) were independent prognostic factors for patients who underwent conversion surgery. Conclusion:The NIPS is effective and safe in treating GC patients with peritoneal metastasis. Male patients, patients who underwent R0 resection, patients with ypN0-1 or TRG 1 after conversion surgery are more likely to benefit from the NIPS. Clinical Trial Registration:http://www.chictr.org.cn/, identifier https://clinicaltrials.gov/ ().
Background: Neoadjuvant chemotherapy (NAC) plays an important role in the therapeutic strategy of locally advanced gastric cancer (LAGC). However, the response of LAGC after NAC varies among different patients. The objective response after NAC has proven to be an excellent indicator for benefiting from NAC, yet effective predictors of objective response are still lacking. The present study aimed to identify potential predictors of objective response in LAGC patients treated with NAC. Methods: Clinicopathological data from 267 patients with LAGC who received NAC and met the inclusion criteria between July 2009 and December 2018 were retrospectively reviewed. Patients were randomly divided into the training and test sets at a 2:1 ratio. Univariate analysis was used to investigate whether any factors were correlated with objective response in the training set. Multivariate logistic regression analysis was applied to find independent predictors. A risk score model was then constructed based on the independent predictors, and its performance in predicting objective response was validated in the test set. Results: Univariate analysis found that gender, age, short axis diameter of the largest regional lymph node (LNmax), serum total protein content, CEA detection value, tumor location, tumor differentiation, signet ring cell carcinoma component and Borrmann type were potential predictors for objective response. In multivariate logistic regression analysis, gender, LNmax and signet ring cell carcinoma component were independent predictors for objective response. Based on independent predictors, we developed a prediction model for objective response. Conclusions: We found gender, LNmax and signet ring cell carcinoma component were independent predictors for objective response. The prediction model is a good tool to predict the objective response for LAGC patients treated with NAC, which can be applied to guide clinical practice.
BACKGROUND: Gastric cancer (GC) patients with peritoneal metastasis usually have extremely poor prognosis. Intraperitoneal infusion of paclitaxel (PTX) provides an effective treatment, but relapse and PTX-resistance are unavoidable disadvantages, and it is difficult to monitor the occurrence of PTX-resistance. OBJECTIVE: The aim of this study was to explore novel autoantibodies in the ascites of individuals with relapsed PTX-resistant GC with peritoneal metastasis. METHODS: Ascites samples were collected before PTX infusion and after the relapse in 3 GC patients. To determine the expression of significantly changed proteins, we performed autoantibody profiling with immunome protein microarrays and tandem mass tag (TMT) quantitative proteomics, and then, the overlapping proteins were selected. RESULTS: Thirty-eight autoantibodies that were differentially expressed between the ascites in the untreated group and relapsed PTX-resistant group were identified. For confirmation of the results, TMT quantitative proteomics was performed, and 842 dysregulated proteins were identified. Four proteins, TPM3, EFHD2, KRT19 and vimentin, overlapped between these two assays. CONCLUSIONS: Our results first revealed that TPM3, EFHD2, KRT19 and vimentin were novel autoantibodies in the ascites of relapsed PTX-resistant GC patients. These autoantibodies may be used as potential biomarkers to monitor the occurrence of PTX-resistance.
Background Preoperative chemotherapy (PCT) has been considered an important treatment for advanced gastric cancer (AGC). The tumor regression grade (TRG) system is an effective tool for the assessment of patient responses to PCT. Pathological complete response (TRG = 0) of the primary tumor is an excellent predictor of better prognosis. However, which patients could achieve pathological complete response (TRG = 0) after chemotherapy is still unknown. The study aimed to find predictors of TRG = 0 in AGC. Methods A total of 304 patients with advanced gastric cancer from July 2009 to November 2018 were enrolled retrospectively. All patients were randomly assigned (2:1) to training and internal validation groups. In addition, 124 AGC patients receiving PCT from December 2018 to June 2020 were included prospectively in the external validation cohort. A prediction model for TRG = 0 was established based on four predictors in the training group and was validated in the internal and external validation groups. Results Through univariate and multivariate analyses, we found that CA199, CA724, tumor differentiation and short axis of the largest regional lymph node (LNmax) were independent predictors of TRG = 0. Based on the four predictors, we established a prediction model for TRG = 0. The AUC values of the prediction model in the training, internal and external validation groups were 0.84, 0.73 and 0.82, respectively. Conclusions We found that CA199, CA724, tumor differentiation and LNmax were associated with pathological response in advanced gastric cancer. The prediction model could provide guidance for clinical work.
Background Neoadjuvant fluorouracil plus leucovorin, oxaliplatin, and docetaxel (FLOT) has shown significant benefits for gastric cancer patients. However, it has not been well accepted in Asian countries. We conducted a prospective study on the safety and feasibility of the FLOT regimen in Chinese patients. Methods Patients with adenocarcinoma of the stomach or esophagogastric junction received four cycles of neoadjuvant chemotherapy (NAC) and four cycles of adjuvant chemotherapy (AC) with the FLOT regimen. The completion status of chemotherapy, adverse events, postoperative morbidities, and pathological tumor regression were analyzed. The 2-year overall survival (OS) and relapse-free survival are presented. Results Altogether, 10 patients were enrolled, and all patients completed four cycles of neoadjuvant chemotherapy. There were no severe hematological adverse events (grade 3 or above), except for a case of grade 3 anemia. All 10 patients underwent radical gastrectomy. Nine patients had R0 resection, and three patients had complete or subtotal pathological tumor regression. Nine patients completed four cycles of adjuvant chemotherapy, but only one patient completed the full dose of adjuvant chemotherapy. The dose of adjuvant chemotherapy was reduced by 25% or less in the other patients. The median follow-up time was 23.13 months, eight patients achieved the overall survival endpoint, and seven patients had relapse-free survival for this period. Two patients died of disease progression. Conclusions Our study demonstrates that the neoadjuvant FLOT regimen is safe and effective for Chinese patients. Dose adjustment is necessary for adjuvant chemotherapy. The pathological regression and survival rates need reevaluation in a larger cohort. The trial is registered with ClinicalTrials.gov (number NCT03646591).
Background For gastric cancer (GC) with extensive lymph node metastasis (bulky N2 and/or para-aortic lymph node metastases), there is no standard therapy worldwide. In Japan, preoperative chemotherapy (PCT) followed by D2 gastrectomy plus para-aortic lymph node dissection (PAND) is considered the standard treatment for these patients. However, in China, the standard operation for GC patients with only bulky N2 metastases was D2 gastrectomy. Besides, after PCT, whether doing PAND improves survival or not is debatable for GC patients with para-aortic lymph node (PAN) metastases. Therefore, we conducted this study to investigate whether D2 lymphadenectomy alone is suitable for these patients after PCT. Methods We retrospectively collected data on patients from our electronic medical record system. GC patients with bulky N2 and/or PAN metastases who underwent D2 lymphadenectomy alone after PCT were enrolled. The survival outcomes and chemotherapy responses were analyzed and compared with the results of the JCOG0405 study. Results From May 2009 to December 2017, a total of 83 patients met all eligibility criteria and were enrolled. The median survival duration for all patients was 40.0 months. The 3-year and 5-year OS rates for all patients were 50.3% and 45.6%, respectively. For patients with only bulky N2 metastasis, the 3-year and 5-year OS rates were 77.1% and 71.6%, respectively, which were similar to the results of the JCOG0405 study (82.7% and 73.4%). For patients with only PAN metastases, the 3-year and 5-year OS rates were 50.0% and 50.0%, respectively, which seemed to be lower than those of the JCOG0405 study (64.3% and 57.1%). For patients with bulky N2 and PAN metastases, the 3-year and 5-year OS rates were 7.4% and 0.0%, respectively, which were lower than those of the JCOG0405 study (20.0% and 20.0%). Conclusion The results of our study suggest that D2 lymphadenectomy alone is suitable for GC patients with only bulky N2 metastasis after PCT. However, D2 lymphadenectomy alone perhaps is not suitable for patients with bulky N2 and PAN metastases after PCT.
Background For locally advanced gastric cancer (LAGC) with serosal invasion (cT4NxM0), adjuvant chemotherapy (AC) after D2 gastrectomy is the standard therapy in Asia. However, perioperative chemotherapy (PCT) combined with D2 gastrectomy is mostly suggested in Europe and America. As a part of PCT, the value of neoadjuvant chemotherapy (NAC) is unclear. We investigated whether NAC could further improve survival and other outcomes for these patients. Methods Patients with cT4NxM0 gastric cancer who underwent D2 gastrectomy were analyzed. The patients were divided into two groups based on whether they received NAC: the neoadjuvant chemotherapy (NAC) and direct surgery (S) groups. After propensity score matching (1:1 ratio), survival and perioperative outcomes were analyzed between the two groups. Results A total of 902 patients met all the eligibility criteria and were enrolled. After propensity score matching, 221 matched pairs of patients were identified. The median overall survival (OS) and disease-free survival (DFS) of all patients were 75.10 and 43.67 months, respectively. The median OS of patients in the NAC and S groups were undefined and 29.80 months, respectively (P<0.0001). The median DFS of patients in the NAC and S groups were undefined and 22.60 months (P<0.0001). There were no significant differences in the radical degrees of operation between the two groups (P=0.07). However, there were significant differences in postoperative hospital stay (P<0.001) and complications (P=0.037) between the two groups. Conclusion This study suggested NAC can further improve prognosis and prevent recurrence in LAGC (cT4NxM0) patients. NAC is feasible and safe for LAGC (cT4NxM0) patients, and does not increase the risk of perioperative surgery.
Background: The evidence of combining neoadjuvant chemotherapy with targeted therapy for patients with locally advanced gastric cancer is inadequate. We conducted a single-arm phase II trial to evaluate the efficacy and safety of S-1, oxaliplatin and apatinib (SOXA) in patients with locally advanced gastric adenocarcinoma. Methods: Treatment-naive patients received three preoperative cycles of S-1 (80-120 mg/day on days 1-14) and oxaliplatin (130 mg/m(2) on day 1) and two cycles of apatinib (500 mg/day for 21 days) at 3-week intervals, followed by surgery. The primary end-point was pathologic response rate (pRR). This trial is registered at ChiCTR.gov.cn: ChiCTR-OPC-16010061. Results: Of 29 patients included, median age was 60 (range, 43-73) years; 20 (69.0%) were male. The pRR was 89.7% (95% confidence interval [CI], 72.7%-97.8%; 26 of 29 patients; P < 0.001) with 28 patients treated with surgery. All 29 patients were available for preoperative response evaluation, achieving an objective response rate of 79.3% (95% CI, 60.3% -92.0%) and a disease control rate of 96.6% (95% CI, 82.2%-99.9%). The margin-free resection rate was 96.6% (95% CI, 82.2%-99.9%). The pathologic complete response rate was 13.8% (95%CI, 1.2% -26.3%). Downstaging of overall TNM stage was observed in 16(55.2%) patients. During neoadjuvant therapy, 10 ( 34.5%) patients had grade >= III adverse events. No treatment- related death occurred. Surgery-related complications were observed in 12 of 28 (42.9%) patients. Conclusion: SOXA followed by surgery in patients with locally advanced gastric adenocarcinoma showed favourable activity and manageable safety. A randomised controlled trial in locally advanced gastric or oesophagogastric junction adenocarcinoma is ongoing (Clinical-Trials.gov:NCT04208347). (C) 2020 The Authors. Published by Elsevier Ltd. This is an open access
AbstractBackgroundNeoadjuvant fluorouracil plus leucovorin, oxaliplatin, and docetaxel (FLOT) has shown significant benefits for gastric cancer patients. However, it has not been well accepted in Asian countries. We conducted a prospective study on the safety and feasibility of FLOT regimen in Chinese patients.MethodsPatients with adenocarcinoma of the stomach or esophagogastric junction received 4 cycles of neoadjuvant chemotherapy (NAC) and 4 cycles of adjuvant chemotherapy (AC) with the FLOT regimen. The completion status of chemotherapy, adverse events, postoperative morbidities and pathological tumor regression were analyzed. The two-year overall survival (OS) and relapse-free survival are presented.ResultsAltogether, 10 patients were enrolled, and all patients completed 4 cycles of neoadjuvant chemotherapy. There were no severe hematological adverse events (grade 3 or above), except for a case of grade 3 anemia. All 10 patients underwent radical gastrectomy. Nine patients had R0 resection, and 3 patients had complete or subtotal pathological tumor regression. Nine patients completed 4 cycles of adjuvant chemotherapy, but only one patient completed the full dose of adjuvant chemotherapy. The dose of adjuvant chemotherapy was reduced by 25% or less in the other patients. The median follow-up time was 23.13 months, 8 patients achieved the overall survival endpoint, and 7 patients had relapse-free survival for this period. Two patients died of disease progression.ConclusionsOur study demonstrates that the neoadjuvant FLOT regimen is safe and effective for Chinese patients. Dose adjustment is necessary for adjuvant chemotherapy. The pathological regression and survival rates need reevaluation in a larger cohort.The trial is registered with ClinicalTrials.gov (number NCT03646591).
To optimize the experimental conditions of MTT colorimetric assay for HSS bioactivity in vitro, we studied the optimal combination of the major conditions of the MTT assay by orthogonal test and other experiments, and compared HSS bioactivity in vitro measured by the improved MTT protocol and published MTT assay at serial protein doses. Results showed that the absorbance value (A value) of the MTT assay directly correlated with the number of human hepatoma cell lines SMMC7721. The result of orthogonal test was the number of 5×104 SMMC7721 cells/ml, culture period 6 h before adding HSS, concentration of HSS 100 ?g/ml, incubation time with HSS 36 h. Additionally, several experiments demonstrated the optimal combination of other conditions was 50 ?g MTT, incubation time for MTT 6 h, DMSO was used to dissolve the MTT formazan crystals and measured with ELISA scanner at 570 nm. The result of determining HSS bio-activity in vitro by optimized MTT protocol showed that sHSS bio-activity increased with the growth of protein dose, but decreased when it beyond a certain dose. The optimized MTT protocol was a sensitive, convenient and stable quantitative method to evaluate HSS bio-activity.