scholarly journals Application Research of Individualized Conditional Reprogramming System to Guide Treatment of Gastric Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Weizhu Zhao ◽  
Kai Liu ◽  
Zhikun Sun ◽  
Longgang Wang ◽  
Bing Liu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Tumor Cell ◽  
Primary Tumor ◽  
Drug Sensitivity ◽  
Malignant Tumors ◽  
Chemotherapeutic Agents ◽  
Cell Bank ◽  
Chemotherapy Drugs ◽  
Primary Tumor Cell ◽  
Cr System

BackgroundGastric cancer (GC) is one of the most common causes of malignant tumors in the world. Due to the high heterogeneity of GC and lack of specificity of available chemotherapy regimens, these tumors are prone to resistance, recurrence, and metastasis. Here, we formulated an individualized chemotherapy regimen for GC using a modified individual conditional reprogramming (i-CR) system. We established a primary tumor cell bank of GC cells and completed drug screening in order to realize individualized and accurate GC treatment.MethodsWe collected specimens from 93 surgical or gastroscopy GC cases and established a primary tumor cell bank using the i-CR system and PDX models. We also completed in vitro culture and drug sensitivity screening of the GC cells using the i-CR system. Whole-exome sequencing (WES) of the i-CR cells was performed using P0 and P5. We then chose targeted chemotherapy drugs based on the i-CR system results.ResultsOf the 72 cases that were collected from surgical specimens, 26 cases were successfully cultured with i-CR system, and of the 21 cases collected from gastroscopy specimens, seven were successfully cultured. Among these, 20 cases of the PDX model were established. SRC ± G3 had the highest culture success rate. The i-CR cells of P0 and P5 appeared to be highly conserved. According to drug sensitivity screening, we examined the predictive value of responses of GC patients to chemotherapeutic agents, especially in neoadjuvant patients.ConclusionThe i-CR system does not only represent the growth characteristics of tumors in vivo, but also provides support for clinical drug use. Drug susceptibility results were relatively consistent with clinical efficacy.

NNDR Salvage Biochemotherapy Regimens for Therapy-Refractory Leukemia and Lymphoma Patients: A Report from the Parker Hughes Cancer Center.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4715-4715
Author(s):  
Faith M. Uckun ◽  
Mireille Sarquis ◽  
Kathleen Lundell ◽  
Sandra Morar ◽  
Jan Larson ◽  
...  
Keyword(s):  
Treatment Outcome ◽  
Tumor Cell ◽  
Tumor Cells ◽  
Median Survival ◽  
Primary Tumor ◽  
Drug Sensitivity ◽  
Blast Crisis ◽  
Future Application ◽  
Cell Level ◽  
Primary Tumor Cell

Abstract We examined the activity of vinorelbine-based salvage biochemotherapy regimens NNDR-I (Vinorelbine [Navelbine] 25 mg/m2 d1, d8, Mitoxantrone [Novantrone] 10 mg/m2 d1, Dexamethasone [Decadron] 20 mg BID d1 through 7, Rituximab [Rituxan] 375 mg/m2 d1,8,15,29) and NNDR-II (Vinorelbine 25 mg/m2 d1, Mitoxantrone 10 mg/m2 d1, Dexamethasone 20 mg BID d1 through7, Rituximab 375 mg/m2 d1,8,15,22, Fludarabine 25 mg/m2 d1, d2, d3) in 26 patients with lymphohematopoietic malignancies, including 3 adult chronic myeloid leukemia (CML) patients in blast crisis, 2 adult chronic lymphocytic leukemia (CLL) patients with rapidly progressive leukemia, 10 acute lymphoblastic leukemia (ALL)(2 adults, 8 children) patients in therapy refractory relapse, and 11 adult non-Hodgkin’s lymhoma (NHL) patients (9 in relapse with progressive lymphoma). All patients completed their salvage therapy as an outpatient without infectious disease complications or hospitalizations. Of the 26 patients, 20 had objective responses, including 14 complete remissions (CR). The median survival was 1.3 (95% CI:0.5–3.9) y and the probability of survival was 53± 10% at 1 year and 37 ± 10% at 3 years (Figure 1). All 3 CML patients achieved a CR; two subsequently underwent allogeneic stem cell transplantation and remain alive free of leukemia at 4.5 y and 5.0 y, respectively, post blast crisis. One died with progressive disease at 0.7y. Both CLL patients achieved a CR and remain alive in CCR at 0.6y and 4.5y, respectively. Of the 10 ALL patients, 5 achieved a CR; of these 5, 2 died of pulmonary Aspergillosis at 0.3 y, 1 died of CMV pneumonitis at 0.7 y, 1 relapsed and died of gram negative sepsis at 1.2 y during reinduction, and 1 remains alive at 4.5 y in continued CR on maintenance chemotherapy. The median survival was 4 months. Of the 11 NHL patients, 4 achieved a CR and 5 achieved a PR. The median survival was 1.5y and 4 remain alive disease-free at 2.5y, 2.5y, 3.5y and 4.0y, respectively. Drug sensitivity profiling of primary tumor cells was performed in 14 patients: the vinorelbine sensitivity of the patients’ leukemia/lymphoma cells predicted their clinical response to the NNDR regimens. Of the 9 responders tested, 8 were vinorelbine sensitive at the primary tumor cell level. Of the 5 non-responders tested, only one was vinorelbine sensitive at the primary tumor cell level. Taken together, these findings demonstrate that patients with high risk/poor prognosis leukemias and lymphomas can achieve meaningful objective responses in an outpatient setting using vinorelbine-based salvage regimens. Future application if the drug sensitivity profiling of primary tumor cells might help tailor the NNDR regimens to those who are most likely to respond. Figure 1. Treatment Outcome of Leukemia/Lymphoma Patients receiving NNDR I/II Therapy Figure 1. Treatment Outcome of Leukemia/Lymphoma Patients receiving NNDR I/II Therapy

scholarly journals Mechanisms of Action And Clinical Implications of MicroRNAs in the Drug Resistance of Gastric Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Ying Liu ◽  
Xiang Ao ◽  
Guoqiang Ji ◽  
Yuan Zhang ◽  
Wanpeng Yu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Drug Resistance ◽  
Molecular Mechanisms ◽  
Malignant Tumors ◽  
Life Quality ◽  
Therapeutic Targets ◽  
Chemotherapeutic Agents ◽  
Response To Chemotherapy ◽  
Novel Biomarkers ◽  
Related Proteins

Gastric cancer (GC) is one of the most common malignant tumors of digestive systems worldwide, with high recurrence and mortality. Chemotherapy is still the standard treatment option for GC and can effectively improve the survival and life quality of GC patients. However, with the emergence of drug resistance, the clinical application of chemotherapeutic agents has been seriously restricted in GC patients. Although the mechanisms of drug resistance have been broadly investigated, they are still largely unknown. MicroRNAs (miRNAs) are a large group of small non-coding RNAs (ncRNAs) widely involved in the occurrence and progression of many cancer types, including GC. An increasing amount of evidence suggests that miRNAs may play crucial roles in the development of drug resistance by regulating some drug resistance-related proteins as well as gene expression. Some also exhibit great potential as novel biomarkers for predicting drug response to chemotherapy and therapeutic targets for GC patients. In this review, we systematically summarize recent advances in miRNAs and focus on their molecular mechanisms in the development of drug resistance in GC progression. We also highlight the potential of drug resistance-related miRNAs as biomarkers and therapeutic targets for GC patients.

scholarly journals Exosomal Micro RNA-107 Reverses Chemotherapeutic Drug Resistance of Gastric Cancer Cells Through HMGA2/mTOR/P-gp Pathway

2021 ◽  
Author(s):  
Lu Jiang ◽  
Yan Zhang ◽  
Linghui Guo ◽  
Chaoyang Liu ◽  
Weihong Ren
Keyword(s):  
Gastric Cancer ◽  
Drug Resistance ◽  
Cancer Cells ◽  
Chemotherapeutic Agents ◽  
Luciferase Reporter Assay ◽  
Luciferase Reporter ◽  
Reporter Assay ◽  
Gastric Cancer Cells ◽  
Chemotherapy Drug ◽  
Chemotherapy Drugs

Abstract Background: RNA cargo in exosomes，especially microRNAs (miRNAs), play an important role in the chemotherapy drug resistance of human cancers. However, the role and mechanism of exosomal miR-107 on multidrug resistance of gastric cancer cells was still not clear. In this study, we sought to explore whether exosomal miR-107 could reverse theresistance of gastric cancer cells to the chemotherapy drugs. Methods: We extracted exosomes from sensitive (SGC-7901, MGC-803) and resistant (SGC-7901/5-FU) gastric cancer cells by ultracentrifugation and the isolated exosomes were identified using transmission electron microscopy (TEM) and dynamic light scattering analysis (DLS). The expression of miR-107 and high mobility group A2 (HMGA2) were detected by real-time quantitative PCR (RT-qPCR). MTT assay was used to investigate the effect of exosomes on gastric cancer cells growth in vitro. The uptake of exosomes by recipient cells were observed using a fluorescence microscope. The predicted target relationship between miR-107 and HMGA2 was verified by gauss-luciferase reporter assay. The expression of HMGA2, p-mTOR/mTOR, P-gp and other exosomal indicated marker proteins were detected by western blot. Results: Our results indicated that the isolated exosomes were demostrated typically cup-like lipid bilayer membrans structure. SGC-7901/5-FU cells were cross-resistant to chemotherapy drug cisplatin (DDP), and the sensitive cells-secreted exosomes drastically reversed the resistance of the resistant gastric cells to the chemotherapeutic drugs,which was verificated by exosomal inhibitor GW4896. Mechanistically, the reversal effect were mainly mediated by exosome-secreted miR-107 through downregulating the expression of targert molecular HMGA2, and inhibiting HMGA2/mTOR/P-gp pathway, which were proofed by luciferase reporter assay and rescue assay. Conclusions: These findings demonstrated that exosome-transmitted miR-107 significantly enhanced the sensitivity of resistant gastric cancer cells to chemotherapeutic agents by mediating the HMGA2/mTOR/P-gp axis and appling exosomal miR-107 may be a novel target in gastric cancers treatment.

scholarly journals Chemical hybridization of sulfasalazine and dihydroartemisinin promotes brain tumor cell death

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Annemarie Ackermann ◽  
Aysun Çapcı ◽  
Michael Buchfelder ◽  
Svetlana B. Tsogoeva ◽  
Nicolai Savaskan
Keyword(s):  
Cell Death ◽  
Tumor Cell ◽  
Cell Viability ◽  
Malignant Tumors ◽  
Glioma Cells ◽  
Chemotherapeutic Agents ◽  
Dependent Manner ◽  
Tumor Cell Death ◽  
Combinational Treatment ◽  
The Impact

AbstractGliomas are primary brain tumors with still poor prognosis for the patients despite a combination of cytoreduction via surgery followed by a radio-chemotherapy. One strategy to find effective treatment is to combine two different compounds in one hybrid molecule via linker to add to or at best potentiate their impact on malignant cells. Here, we report on the effects of a newly synthesized hybrid of sulfasalazine (SAS) and dihydroartemisinin (DHA), called AC254. In previous studies, both SAS and DHA have already proved to have anti-tumor properties themselves and to have sensitizing respectively potentiating effects on other treatments against malignant tumors. We investigated the impact of individual drugs SAS and DHA, their 1:1 combination and a novel SAS-DHA hybrid compound (AC254) on rodent and human glioma cells. In our study SAS alone showed no or only a mild effect on glioma, whereas DHA led to a significant reduction of cell viability in a dose-dependent manner. Next we compared the efficacy of the hybrid AC254 to the combinational treatment of its parent compounds SAS and DHA. The hybrid was highly efficient in combating glioma cells compared to single treatment strategies regarding cell viability and cell death. Interestingly, AC254 showed a remarkable advantage over the combinational treatment with both parent compounds in most used concentrations. In addition to its reduction of tumor cell viability and induction of cell death, the hybrid AC254 displayed changes in cell cycle and reduction of cell migration. Taken together, these results demonstrate that clinically established compounds such as SAS and DHA can be potentiated in their anti-cancer effects by chemical hybridization. Thus, this concept provides the opportunity to devise new effective chemotherapeutic agents.

scholarly journals Subversion of host defense mechanisms by murine tumors. II. Counter-influence of concomitant antitumor immunity.

1976 ◽  
Vol 143 (3) ◽  
pp. 574-584 ◽  
Author(s):  
R J North ◽  
D P Kirstein ◽  
R L Tuttle
Keyword(s):  
Tumor Cell ◽  
Host Defense ◽  
Primary Tumor ◽  
Defense Mechanisms ◽  
Antitumor Immunity ◽  
Malignant Tumors ◽  
Acquired Resistance ◽  
Antibacterial Resistance ◽  
Stages Of Growth ◽  
Murine Tumor Cells

Subcutaneous injection of murine tumor cells first resulted in a state of severely suppressed macrophage-mediated antibacterial resistance and then in a contrasting state of greatly enhanced antibacterial resistance. Whereas, the state of suppressed antibacterial resistance corresponded to a state of suppressed resistance to a tumor cell challenge, the generation of enhanced antibacterial resistance corresponded to the acquisition of concomitant antitumor immunity. It was suggested on the basis of this evidence that changes in the level of macrophage-mediated antibacterial resistance that occur during growth of the primary tumor reflected changes in the level of the host's resistance to the tumor itself. It was further suggested that the coincidental suppression of antibacterial and antitumor resistance that occurs during the initial stages of growth of the primary tumor represents the operation of a mechanism that enables the tumor to avoid destruction by macrophages. The results support the view that macrophages play an important role in native and acquired resistance to malignant tumors.

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