Using NSG recipient mice improves engraftment of gastric cancer patient derived xenografts.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 70-70
Author(s):  
Sam C. Wang ◽  
Min Zhu ◽  
Ibrahim Nassour ◽  
Jeanne Shen ◽  
John C. Mansour ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Liver Metastases ◽  
Expression Profiles ◽  
Management Strategies ◽  
Axillary Lymph Node Metastasis ◽  
Post Treatment ◽  
Clinical Samples ◽  
Axillary Lymph ◽  
Nsg Mice ◽  
The One

70 Background: Previous gastric cancer (GC) patient derived xenograft (PDX) studies reported engraftment rates inversely proportional to the immunocompromised states of recipient mice (nudes 17%, scid 27%, and NOD/ scid 34%). We tested highly immunocompromised NOD scidgamma (NSG) mice, which lack mature T cells, B cells, or functional natural killer cells, as recipients for low volume biopsies and post-treatment GC samples. Methods: Consent was obtained from GC patients who were scheduled to undergo esophagogastroduodenoscopy (EGD) and diagnostic laparoscopy as part of their disease management strategies. The following amounts of tumor were coated with Matrigel and inoculated into the flanks of NSG mice: EGD biopsies ~10 mg, post-treatment samples ~100 mm3, and peritoneal metastasis biopsies ~100 mm3. Tumors were serially measured and passaged when the greatest dimension reached 1.5 cm, or if there was overlying skin necrosis. Results: The engraftment rates were: EGD biopsies 48% (13 of 27 samples), post-resection samples 58% (7 of 12), and peritoneal metastases 11% (1 of 9). Median time to first passage was 10.1 weeks (range: 8.1 to 12.4) for EGD biopsies and 22.1 weeks (9.6 to 33.0) for post-treatment samples. Two (15%) engrafted EGD mice developed liver metastases, and one (7.7%) had axillary lymph node metastasis (AxLN). Three (47%) engrafted post-treatment mice had liver metastases and two (29%) had AxLN. Histology was generally maintained through passages and metastases with some loss of mucinous components. There were no associations between engraftment rate and any evaluated clinical or pathologic characteristics, including tumor response and overall survival. The tumor from the one patient who had a complete pathologic response after NAT did not engraft. Conclusions: Using highly immunocompromised NSG mice improved engraftment rates of GC PDX, even for challenging specimens such as endoscopic biopsies and post-treatment resection samples. Peritoneal biopsies did not engraft well. Tumor histology was generally maintained through passages. Studies comparing the expression profiles of serially passaged tumors to the original clinical samples are ongoing.

scholarly journals Dynamic changes of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio predicts breast cancer prognosis

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Ju-Yeon Kim ◽  
Eun Jung Jung ◽  
Jae-Myung Kim ◽  
Han Shin Lee ◽  
Seung-Jin Kwag ◽  
...  
Keyword(s):  
Initial Treatment ◽  
Univariate Analysis ◽  
Axillary Lymph Node Metastasis ◽  
Post Treatment ◽  
Neutrophil To Lymphocyte Ratio ◽  
Cancer Prognosis ◽  
Axillary Lymph ◽  
Platelet To Lymphocyte Ratio ◽  
Free Survival ◽  
Lymphocyte Ratio

Abstract Background We aimed to identify whether neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are more useful predictors after initial intention to treat than at the time of diagnosis. Methods We collected the medical data of 533 patients. The results of the peripheral blood sampling before the primary treatments were labeled as initial cohort, and those obtained between 24 and 36 months after initial treatment were defined as the 2nd cohort. Delayed metastasis has been defined as distant metastasis 2 years after treatment, and survival outcome was estimated and compared across groups. Results Median follow-up duration was 74 months (24–162 months), and 53 patients experienced delayed metastasis. In univariate analysis, metastasis-free survival, patient age at diagnosis, tumor size, axillary lymph node metastasis, HER-2 status, initial NLR and PLR, and 2nd NLR and PLR were found to be significantly associated with delayed metastasis. However, in multivariate analysis, only the 2nd NLR and PLR were found to be significantly associated with delayed metastasis, excluding initial NLR and PLR. Metastasis-free survival was analyzed through the pattern changes of NLR or PLR. The results revealed that patients with continued low NLR and PLR values at pre- and post-treatment (low initial values and 2nd values) showed a significantly better prognosis than those with a change in value or continued high NLR and PLR. Conclusions We identified that patients with persistent high NLR and PLR after initial treatment have significant worse prognosis in terms of late metastasis. Therefore, these results suggest that NLR and PLR are more useful in predicting prognosis post-treatment.

scholarly journals Chemotherapy Effectiveness and Prognosis of Gastric Cancer Influenced by PTPN11 Polymorphisms

2016 ◽  
Vol 39 (4) ◽  
pp. 1537-1552 ◽  
Author(s):  
Chuanjun Zhuo ◽  
Mingjing Shao ◽  
Ce Chen ◽  
Chongguang Lin ◽  
Deguo Jiang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Fold Increase ◽  
Axillary Lymph Node Metastasis ◽  
Axillary Lymph ◽  
Nucleotide Polymorphisms ◽  
Positive Interaction ◽  
Kaplan Meier ◽  
Pcr Rflp ◽  
Differentiation Degree ◽  
H Pylori

Objective: Since gastric cancer (GC) cells exhibited higher grades of SHP-2 encoded by PTPN11 than normal cells, it would be intriguing to explore whether PTPN11 single nucleotide polymorphisms (SNPs) would influence chemotherapy effectiveness and GC prognosis among a Chinese population. Methods: Altogether 430 late-stage GC patients and 960 healthy controls matched with age and sex were incorporated. Three PTPN11 SNPs (i.e. rs7958372, rs12229892 and rs2301756) were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Chemotherapies of cisplatin and 5-fluorouracil were performed for 4 cycles. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using the logistic regression. Survival curves were plotted with Kaplan-Meier method and the COX proportional hazard model was used to analyze independent factors for GC prognosis. Results: For rs12229892, AA and GA genotypes would cause 1.60-fold increase of GC risk in comparison to homozygote GG (OR = 1.60; 95% CI = 1.23-2.07; P < 0.001). The A allele of rs2301756 was significantly associated with a decrease in the risk of GC when compared with G allele (OR = 0.81; 95% CI = 0.65-0.99; P = 0.043). Results from both 2-cycle and 4-cycle chemotherapy suggested that chemotherapy was significantly more effective for GA and AA genotypes of rs2301756 compared with homozygote GG (P < 0.001). Besides, the joint impact of rs12229892 (AA) and environmental factors (i.e. smoking, family history, intake of processed food and H .pylori infection) on GC risk was considered as positive interaction, while that of rs2301756 (AA) and the above parameters was deemed as negative interaction. Finally, differentiation degree, axillary lymph node metastasis, rs12229892 and rs2301756 appeared as independent risk factors for GC development (all P < 0.05). Conclusion: Since rs2301756 polymorphism of PTPN11 was associated with reduced risk of GC and better effects of chemotherapy on GC, it can be considered as a predictor of GC prognosis and the treatment target for GC.

scholarly journals Dynamic changes of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio predicts breast cancer prognosis

2020 ◽  
Author(s):  
Ju-Yeon Kim ◽  
Eun Jung Jung ◽  
Jae-Myung Kim ◽  
Han Shin Lee ◽  
Seung-Jin Kwag ◽  
...  
Keyword(s):  
Initial Treatment ◽  
Univariate Analysis ◽  
Axillary Lymph Node Metastasis ◽  
Post Treatment ◽  
Neutrophil To Lymphocyte Ratio ◽  
Cancer Prognosis ◽  
Axillary Lymph ◽  
Platelet To Lymphocyte Ratio ◽  
Free Survival ◽  
Lymphocyte Ratio

Abstract Background: We aimed to identify whether neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are more useful predictors after initial intention to treat than at the time of diagnosis.Methods: We collected the medical data of 533 patients. The results of the peripheral blood sampling before the primary treatments were labeled as initial cohort, and those obtained between 24 and 36 months after initial treatment were defined as the 2nd cohort. Delayed metastasis has been defined as distant metastasis 2 years after treatment, and survival outcome was estimated and compared across groups. Results: Median follow-up duration was 74 months (24–162 months), and 53 patients experienced delayed metastasis. In univariate analysis, metastasis-free survival, patient age at diagnosis, tumor size, axillary lymph node metastasis, HER-2 status, initial NLR and PLR, and 2nd NLR and PLR were found to be significantly associated with delayed metastasis. However, in multivariate analysis, only the 2nd NLR and PLR were found to be significantly associated with delayed metastasis, excluding initial NLR and PLR. Metastasis-free survival was analyzed through the pattern changes of NLR or PLR. The results revealed that patients with continued low NLR and PLR values at pre- and post-treatment (low initial values and 2nd values) showed a significantly better prognosis than those with a change in value or continued high NLR and PLR. Conclusions: We identified that patients with persistent high NLR and PLR after initial treatment have significant worse prognosis in terms of late metastasis. Therefore, these results suggest that NLR and PLR are more useful in predicting prognosis post-treatment.

Surgery and metastases of stomach cancer in liver

2020 ◽  
pp. 21-24
Author(s):  
F. M. Dzhuraev ◽  
S. L. Gutorov ◽  
E. I. Borisova ◽  
G. G. Khakimova
Keyword(s):  
Gastric Cancer ◽  
Liver Metastases ◽  
Lymphovascular Invasion ◽  
Peritoneal Dissemination ◽  
Surgical Removal ◽  
Relapse Free Survival ◽  
Cancer Markers ◽  
Free Survival ◽  
The Poor ◽  
Isolated Liver

Liver metastases of gastric cancer determine the poor prognosis. Until now The expediency of their surgical removal has been controversial. However, according to a number of studies, the removal of potentially operable isolated liver metastases allows a significant increase of overall and relapse-free survival in some cases. The review is dedicated to the analysis of prognostic factors that allow selecting patients for surgical removal of liver metastases of gastric cancer. The main criteria are: effective perioperative chemotherapy; stage under T4, N0, absence of lymphovascular invasion, absence of peritoneal dissemination, number less than 3, size up to 4 cm, localization of metastases in one lobe, low level of cancer markers CA 19-9 and CEA.

scholarly journals Long-Term Survival of Two Patients with Liver Metastases from Advanced Gastric Cancer Treated with Radiofrequency Ablation and Chemotherapy

2021 ◽  
pp. 67-72
Author(s):  
Sung Jin Oh
Keyword(s):  
Gastric Cancer ◽  
Radiofrequency Ablation ◽  
Liver Metastases ◽  
Advanced Gastric Cancer ◽  
Systemic Chemotherapy ◽  
Subtotal Gastrectomy ◽  
Hepatic Metastases ◽  
Term Survival ◽  
Long Term Survival

Liver metastasis from gastric cancer has a very poor prognosis. Herein, we present two cases of liver metastases (synchronous and metachronous) from advanced gastric cancer. In the first case, the patient underwent radical subtotal gastrectomy. Liver metastases occurred 6 months after surgery while the patient was receiving adjuvant chemotherapy, but two hepatic tumors were successfully removed by radiofrequency ablation (RFA). In the second case, liver metastases occurred 15 months after surgery for gastric cancer. The patient also received RFA for one hepatic tumor, and other suspicious metastatic tumors were treated with systemic chemotherapy. Although these case presentations are limited for the efficacy of RFA treatment with systemic chemotherapy for hepatic metastases from gastric cancer, our findings showed long-term survival (overall survival for 108 and 67 months, respectively) of the affected patients, without recurrence. Therefore, we suggest that RFA treatment with systemic chemotherapy could be an effective alternative treatment modality for hepatic metastases from gastric cancer.

scholarly journals LncRNA CRNDE attenuates chemoresistance in gastric cancer via SRSF6-regulated alternative splicing of PICALM

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Feifei Zhang ◽  
Hui Wang ◽  
Jiang Yu ◽  
Xueqing Yao ◽  
Shibin Yang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Alternative Splicing ◽  
Noncoding Rna ◽  
De Novo ◽  
Acquired Resistance ◽  
Genetic Alterations ◽  
Clinical Samples ◽  
Autophagy Flux ◽  
Resistance To Chemotherapy

AbstractDe novo and acquired resistance, which are mainly mediated by genetic alterations, are barriers to effective routine chemotherapy. However, the mechanisms underlying gastric cancer (GC) resistance to chemotherapy are still unclear. We showed that the long noncoding RNA CRNDE was related to the chemosensitivity of GC in clinical samples and a PDX model. CRNDE was decreased and inhibited autophagy flux in chemoresistant GC cells. CRNDE directly bound to splicing protein SRSF6 to reduce its protein stability and thus regulate alternative splicing (AS) events. We determined that SRSF6 regulated the PICALM exon 14 skip splice variant and triggered a significant S-to-L isoform switch, which contributed to the expression of the long isoform of PICALM (encoding PICALML). Collectively, our findings reveal the key role of CRNDE in autophagy regulation, highlighting the significance of CRNDE as a potential prognostic marker and therapeutic target against chemoresistance in GC.

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