scholarly journals Prediction of Sensitivity and Efficacy of Clinical Chemotherapy Using Larval Zebrafish Patient-Derived Xenografts of Gastric Cancer

2021 ◽  
Vol 9 ◽  
Author(s):  
Jing Zhai ◽  
Jiaqi Wu ◽  
Yaohui Wang ◽  
Ruoyue Fan ◽  
Guiping Xie ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Early Stage ◽  
Locally Advanced ◽  
Human Tumor ◽  
Curative Intent ◽  
Drug Dosing ◽  
Larval Zebrafish ◽  
Locally Advanced Gastric Cancer ◽  
Gastric Cancer Patients

BackgroundPerioperative chemotherapy has been accepted as one of the most common approaches for locally advanced gastric cancer. However, the efficacy of chemotherapy varies among patients, and there is no effective method to predict the chemotherapy efficacy currently. We previously established the first larval zebrafish patient-derived xenografts (zPDXs) of gastric cancer as a platform for the translational research and personalized treatment. The objective of this study was to investigate the feasibility of screening individualized chemotherapeutics using the zPDXs.MethodsWe further optimized this zPDXs platform including administration route, drug dosing, and rhythm to develop a stable and reliable protocol for chemotherapeutics screening. Using the novel platform, we investigated the chemosensitivity of 5-fluorouracil, cisplatin, docetaxel, and doxorubicin for gastric cancer patients.ResultsWe showed that the engrafted zebrafish retained the original prominent cell components of the corresponding human tumor tissues, and we successfully obtained the results of chemosensitivity of 5-fluorouracil, cisplatin, docetaxel, and doxorubicin for 28 patients with locally advanced gastric cancer. These patients underwent radical gastrectomy for curative intent and 27 cases received postoperative adjuvant chemotherapy. We revealed that the chemosensitivity obtained from zPDXs was consistent with the clinical responses in these patients (P = 0.029). More importantly, the responder drug(s) from zPDXs used or not was the only risk factor for early-stage recurrence in these 27 patients (P = 0.003).ConclusionOur study with the largest sample size so far suggests that larval zPDXs help to predict the chemotherapeutics response and to achieve precise chemotherapy for gastric cancer.

scholarly journals A PHASE II TRIAL EXPLORING THE EXTENSIVE INTRA-OPERATIVE PERITONEAL LAVAGE (EIPL) AS A PROPHYLACTIC STRATEGY FOR PERITONEAL RECURRENCE IN LOCALLY ADVANCED GASTRIC CANCER: reporting postoperative morbidity and mortality after early closure

2015 ◽  
Vol 52 (2) ◽  
pp. 161-164 ◽  
Author(s):  
Thales Paulo BATISTA ◽  
Mário Rino MARTINS ◽  
Euclides Dias MARTINS-FILHO ◽  
Rogerio Luiz dos SANTOS
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Phase Ii ◽  
Peritoneal Lavage ◽  
Locally Advanced ◽  
Open Label ◽  
Safety And Efficacy ◽  
Intention To Treat ◽  
Locally Advanced Gastric Cancer ◽  
Gastric Cancer Patients

Background The Extensive Intraoperative Peritoneal Lavage (EIPL) has been proposed as a practical prophylactic strategy to decrease the risk of peritoneal metastasis in gastric cancer. Objective To explore the safety and efficacy of the EIPL in our locally advanced gastric cancer patients. Methods This study is an open-label, double-center, single-arm phase II clinical trial developed at two tertiary hospitals from Recife (Pernambuco, Brazil). Results The study protocol was prematurely closed due to slow accrual after only 16 patients had been recruited to participate. Eight of them were excluded of the protocol study during the laparotomy, whereas four cases were also excluded from the per-protocol analysis. Two patients had died in hospital before 30 days and six were alive with no evidence of cancer relapses after a follow-up ranging from five to 14,2 months (median of 10.6 months). In the intention-to-treat analysis, three of eight patients suffered of gastrointestinal leakages and two of them had died. On a per-protocol basis, two of four patients presented this type of postoperative complication and one of them had died. All deaths occurred as a somewhat consequence of gastrointestinal leakages. Conclusion We could not make any conclusion about the safety and efficacy of the EIPL, but the possibility of this approach might increase the rate of gastrointestinal leakage is highlighted.

scholarly journals FEATURES OF EMERGENCY SURGERY IN PATIENTS WITH LOCALLY ADVANCED GASTRIC CANCER

2020 ◽  
pp. 108-112
Author(s):  
V. V. Boyko ◽  
I. V. Krivorotko ◽  
V. A. Lazirsky
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Surgical Intervention ◽  
Locally Advanced ◽  
Postoperative Mortality ◽  
Surgical Interventions ◽  
Second Stage ◽  
Locally Advanced Gastric Cancer ◽  
Surgical Tactics ◽  
Gastric Cancer Patients

Summary. Materials and methods. The work is based on an analysis of the results of surgical treatment of 418 patients with complicated locally advanced gastric cancer. Patients are divided into two groups: comparisons — 212, and the main — 206 patients who were treated from 2006 to 2010. and from 2011 to 2015 respectively. The complications rating was: bleeding in 252 (60.3 %) patients, stenosis in 89 (21.3 %), perforation in 15 (3.5 %), and their combination in 62 (14.8 %). Results and discussion. Radical operations were performed in 212 (50.7 %) patients, in 145 (34.6 %) — palliative and symptomatic. Postoperative complications occurred in 82 patients (19.6 %), postoperative mortality was 7.2 % (30 patients). A two-stage surgical tactics has been developed, which involves the implementation of minimally invasive endoscopic and endovascular surgical interventions at the first stage with the implementation of a delayed or planned surgical intervention at the second stage. Conclusions. Urgent operations decreased from 21.7 to 6.3 %, which reduced the number of palliative and symptomatic operations from 50.4 to 18.4 %.

scholarly journals Neoadjuvant therapy for locally advanced gastric cancer patients. A population pharmacodynamic modeling

PLoS ONE ◽  
2019 ◽  
Vol 14 (5) ◽  
pp. e0215970 ◽  
Author(s):  
Patricia Martin-Romano ◽  
Belén P. Solans ◽  
David Cano ◽  
Jose Carlos Subtil ◽  
Ana Chopitea ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Neoadjuvant Therapy ◽  
Advanced Gastric Cancer ◽  
Cancer Patients ◽  
Locally Advanced ◽  
Pharmacodynamic Modeling ◽  
Locally Advanced Gastric Cancer ◽  
Gastric Cancer Patients

Randomized trial of adjuvant chemotherapy with mitomycin plus ftorafur versus mitomycin alone in resected locally advanced gastric cancer.

1998 ◽  
Vol 16 (3) ◽  
pp. 1036-1039 ◽  
Author(s):  
J J Grau ◽  
J Estapé ◽  
J Fuster ◽  
X Filella ◽  
J Visa ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Adjuvant Chemotherapy ◽  
Advanced Gastric Cancer ◽  
Early Stage ◽  
Locally Advanced ◽  
Survival Rates ◽  
Group Versus ◽  
Node Negative ◽  
Treatment Groups ◽  
Locally Advanced Gastric Cancer

PURPOSE We performed a clinical trial to determine whether postoperative adjuvant chemotherapy with two drugs versus one drug could prolong survival. PATIENTS AND METHODS From 1985 to 1996, 85 patients with completely resected locally advanced gastric cancer were enrolled. The subjects were randomized into two treatment groups, as follows: mitomycin (MMC) 10 to 20 mg/m2 intravenously (i.v.) on day 1 every 6 weeks plus ftorafur (FT) 500 mg/m2/d for 36 consecutive days; or MMC alone, 10 to 20 mg/m2 i.v. every 6 weeks. All courses were repeated four times. RESULTS After a median follow-up duration of 62 months, the overall 5-year survival rates were 67% for the MMC-FT group versus 44% for the MMC group (P = .04). Subgroup analysis to compare survival curves using the method of Mantel-Cox showed survival rates significantly in favor of the MMC-FT group in the subsets of patients with node-negative disease (P = .01) and those whose disease was stage IB or II (P = .008). CONCLUSION Significantly better survival results were observed for MMC-FT versus MMC alone. Subset analysis suggest a strong benefit in patients with node-negative and early-stage resected gastric cancer.

Helicobacter pylori infection as an independent prognostic factor for locally advanced gastric cancer with curative resection

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4562-4562
Author(s):  
S. Kang ◽  
Y. Hwang ◽  
H. Lee ◽  
S. Jeong ◽  
J. Choi ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Advanced Gastric Cancer ◽  
Curative Resection ◽  
Locally Advanced ◽  
Infection Status ◽  
Type Iv ◽  
Locally Advanced Gastric Cancer ◽  
Gastric Cancer Patients

4562 Background: A few studies reported the association between helicobacter pylori (HP) infection and better overall survival (OS) in resected gastric cancer patients (pts). Methods: We investigated the HP infection status and its association with clinicopathologic characteristics in 210 locally advanced gastric cancer patients (stage IB: 18, II: 61, IIIA: 62, IIIB: 31, IV: 38) who underwent adjuvant chemotherapy (CTX) after curative resection (≥D2 dissection). HP infection status in hematoxlin and eosin stained peritumoral tissue was graded according to the updated Sydney System and categorized as HP(-) (normal or mild infection) and HP(+) (moderate or marked infection) (Am J Surg Pathol 20:1161, 1996). Twenty-two pts received 5-FU, doxorubicin (DOX) CTX (5- FU 500 mg/m2 weekly for 36 wks, DOX 40 mg/m2 q 3 weeks x 12) with or without OK432, while 188 pts underwent 5-FU, mitomycin-C (MMC), and polysaccharide-K (PSK) CTX (5-FU 500 mg/m2 weekly for 24 wks, MMC 8 mg/m2 q 6 wks x 4, PSK 3 g/day for 16 wks) (Br J Cancer 84:186, 2001, Hepatogastroenterol 54:290, 2007). Results: The median follow-up duration of survivors was 125 (107–155) months. HP (-) was significantly correlated with Bormann type IV, larger tumor size (>5.5cm),and stage IIIB. In univariate analysis, patients with HP(-) (104 pts) demonstrated significantly poor 10-year OS compared with those with HP (+) (106 pts) (15.9% vs. 87.7%, p<0.0001). HP(-) was associated with poor outcome in all stages except stage IB (p=0.075). In multivariate analysis, HP(-) was the most significant independent prognostic factor of poor OS (hazard ratio 9.646, 95% CI 5.407–17.206, p<0.0001) followed by advanced stage (p=0.032), Bormann type IV (p=0.037) and old age (p=0.015). Conclusions: HP infection status seems to have strong prognostic significance in locally advanced gastric cancer. HP (-) pts may need intensified adjuvant treatment and careful follow-up. No significant financial relationships to disclose.

Sign in / Sign up

Export Citation Format

Share Document