scholarly journals Quxie Capsule Inhibits Colon Tumor Growth Partially Through Foxo1-Mediated Apoptosis and Immune Modulation

2019 ◽  
Vol 18 ◽  
pp. 153473541984637 ◽  
Author(s):  
Dongmei Chen ◽  
Yufei Yang ◽  
Peiying Yang
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Immune Response ◽  
Treg Cells ◽  
Vehicle Control ◽  
Antitumor Efficacy ◽  
Th2 Cells ◽  
Control Group ◽  
Vehicle Control Group ◽  
Mouse Colon

Quxie capsule (QX), a herbal remedy used in traditional Chinese medicine, is routinely used in advanced colorectal cancer treatment in Xiyuan Hospital in Beijing, China. However, the mechanism(s) underlying the effect of QX in colorectal cancer remain unclear, which hampers the optimal use of QX for the treatment of the disease. The transcription factor forkhead box O1 (Foxo1) plays important roles in regulation of cell cycle, apoptosis, and immune response in various cancers. In this study, we examined the antitumor efficacy of QX in a mouse model of colorectal cancer and further investigated the mechanism by which QX regulated Foxo1 protein-mediated pathways. QX administered via gavage daily for 2 weeks in mice carrying CT26 mouse colon tumors resulted in significantly lower mean tumor weight (0.93 ± 0.32 g) compared with that in vehicle control-treated mice (1.57 ± 0.57 g, P <.05). Foxo1 protein expression in tumors was also higher in the QX group than that in the vehicle control group. Furthermore, QX treatment upregulated apoptotic proteins such as Fas, Bim, and cleaved caspase-3 in tumor tissue compared with those in the vehicle control group. Intriguingly, the ratios of Th1/Th2 and Th17/Treg cells and levels of T-bet protein (the key regulator of Th1 and Th2 cells) were higher while the level of Foxp3 (the key regulator of Treg cells) was lower in QX-treated mice compared to vehicle control mice, revealing that Foxo1 upregulated T-bet and downregulated Foxp3 and induced a shift in immune balance. This shift could be critical in the antitumor efficacy of QX. Furthermore, knocking down Foxo1 in human colon cancer HCT116 cells partially blocked the effect of QX-elicited antiproliferative activity. Together, these results suggest that QX exerts antitumor activity in CT26 mouse colon cancer model partially mediated by Foxo1-induced apoptosis and antitumor immune response.

A Teratological Evaluation and Postnatal Behavioral Screen of KF-868 In Rats

1985 ◽  
Vol 4 (1) ◽  
pp. 91-110 ◽  
Author(s):  
A. M. Hoberman ◽  
W. M. Weatherholtz ◽  
R. S. Durloo
Keyword(s):  
Body Weight ◽  
Vehicle Control ◽  
Female Rats ◽  
Reproductive Capacity ◽  
Control Group ◽  
Dosage Group ◽  
Vehicle Control Group ◽  
High Dosage Group ◽  
Significant Difference ◽  
Body Weights

The effects of a new experimental drug, KF-868, were investigated after administration to pregnant Sprague-Dawley rats at 0(vehicle), 0.1, 2.0, and 40.0 mg/kg per day during Days 7 through 17 of gestation by examination of term fetuses and naturally delivered offspring. Pregnant rats administered 0.1, 2.0, and 40.0 mg/kg per day gained significantly more weight during the dosage period than did the vehicle control group. Treatment-related physical signs, bloody crust on nose and stains on fur, were observed in the high dosage group. Fetal viability was significantly increased, and resorptions were significantly decreased for the mid and high dosage groups, when compared with the control group. Average fetal body weights for cesarean-delivered fetuses were less for the 40.0 mg/kg per day dosage groups than for the vehicle control group. Visceral and skeletal evaluations of fetuses revealed no difference between the control and test groups. Percent survival of pups was significantly less for the high dosage group than for the control group. Average rat body weights prior to mating for the high dosage group were generally less than for the control group. All physical and functional developmental values were comparable among the control and test groups. Evaluation of postweaning parameters of pups revealed no significant difference in sex maturation, behavior (open-field and water maze), and reproductive capacity. Average body weight gains during the 9-week growth period before mating were significantly less for the 40.0 mg/kg per day dosage group F1 generation female rats. Toxicity in fetuses and offspring was observed only at the highest dosage level. Dosage-dependent, significant increases in maternal body weight gain, as compared with control values, occurred for doses in the 3 KF-868-administered groups. These results indicate that 0.1 and 2.0 mg/kg per day dosages of KF-868 were not lethal and did not produce any adverse effects on the morphological or functional development of offspring. Toxicity was evident in offspring and fetuses of dams administered 40.0 mg/kg per day KF-868, 40,000 times as high as the daily therapeutic dose.

scholarly journals Direct effect of p,p'- DDT on mice liver

2016 ◽  
Vol 52 (2) ◽  
pp. 287-298 ◽  
Author(s):  
Bárbara Arroyo-Salgado ◽  
Jesús Olivero-Verbel ◽  
Angélica Guerrero-Castilla
Keyword(s):  
Insulin Resistance ◽  
Epidemiological Data ◽  
Vehicle Control ◽  
Sesame Oil ◽  
Pcr Analysis ◽  
Control Group ◽  
Molecular Evidence ◽  
Vehicle Control Group ◽  
Mice Liver

ABSTRACT Contact with the pesticide dichlorodiphenyltrichloroethane (p,p′-DDT) can be the cause of various harmful effects in humans, wildlife, and the environment. This pesticide is known to be persistent, lipophilic, resistant to degradation, and bioaccumulive in the environment and to be slowly released into bloodstream. Growing evidence shows that exposure to DDT is linked to type 2 diabetes mellitus. Individuals exposed to elevated levels of DDT and its metabolite have an increased prevalence of diabetes and insulin resistance. To evaluate these possible relationships, experiments were performed on eight-week-old female mice, divided into three groups (n = 10 per group): Group 1 received a vehicle-control intraperitoneal (i.p.) injection of sesame oil; Groups 2 and 3 received an i.p. dose of 50 and 100 µg/g p,p′-DDT respectively, dissolved in sesame oil. All groups were treated once daily for four days. Real-time PCR analysis of several genes was undertaken. Additionally, biochemical parameters and histopathological changes were measured. NQO1, HMOX1, NR1I3 and NR3C1 were up-regulated in DDT-exposed animals compared to the vehicle control group, while only SREBP1 was down-regulated in the 100 µg/g group. MTTP and FABP5, not previously reported for DDT exposure, but involved in regulation of fatty acid fluxes, could also function as biomarkers cross-talking between these signaling pathways. These results suggest that beyond epidemiological data, there is increasing molecular evidence that DDT may mimic different processes involved in diabetes and insulin resistance pathways.

scholarly journals Effect of the Chinese Medicine YangZheng XiaoJi on Reducing Fatigue in Mice with Orthotopic Transplantation of Colon Cancer

2019 ◽  
Vol 2019 ◽  
pp. 1-12
Author(s):  
Yanni Zhang ◽  
Zhongxin Li ◽  
Zhaolong Zhao ◽  
Wentao Kuai ◽  
Cong Wei ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Chinese Medicine ◽  
Liver Tissue ◽  
Glycogen Synthesis ◽  
Mental Fatigue ◽  
Control Group ◽  
Hepatic Glycogen ◽  
Resting Time ◽  
And Control

Background. Fatigue is a common, distressing, and persistent symptom for patients with malignant tumor including colorectal cancer (CRC). Although studies of cancer-related fatigue (CRF) have sprung out in recent years, the pathophysiological mechanisms that induce CRF remain unclear, and effective therapeutic interventions have yet to be established. Methods. To investigate the effect of the traditional Chinese medicine YangZheng XiaoJi (YZXJ) on CRF, we constructed orthotopic colon cancer mice, randomly divided into YZXJ group and control (NS) group. Physical or mental fatigue was respectively assessed by swimming exhaustion time or suspension tail resting time. At the end of the experiment, serum was collected to measure the expression level of inflammatory factors by ELISA and feces to microbiota changes by 16s rDNA, and hepatic glycogen content was detected via the anthrone method. Result. The nutritional status of the YZXJ group was better than that of the control group, and there was no statistical difference in tumor weight. The swimming exhaustion times of YZXJ group and control group were (162.80 ± 14.67) s and (117.60 ± 13.42, P < 0.05) s, respectively; the suspension tail resting time of YZXJ group was shorter than that of the control group (49.85 ± 4.56) s and (68.83 ± 7.26) s, P < 0.05)). Serum levels of IL-1β and IL-6 in YZXJ group were significantly lower than the control group (P < 0.05). Liver glycogen in YZXJ group was (5.18 ± 3.11) mg/g liver tissue, which was significantly higher than that in control group (2.95 ± 2.06) mg/g liver tissue (P < 0.05). At phylum level, increased abundance of Bacteroidetes, Verrucomicrobia, Actinobacteria, and Cyanobacteria and decreased Proteobacteria in YZXJ group emerged as the top differences between the two groups, and the Firmicutes/Bacteroidetes ratio was decreased in YZXJ group compared to the control group. At genus level, the abundance of Parabacteroides, unidentified Saprospiraceae, and Elizabethkingia which all belong to phylum Bacteroidetes were increased, while Arcobacter, Marinobacter, Alkanindiges, Sulfuricurvum, Haliangium, and Thiobacillus in phylum Proteobacteria were decreased after YZXJ intervention. YZXJ can also increase Pirellula, Microbacterium, and Alpinimonas and decrease Rubrobacter and Iamia. Conclusion. YZXJ may reduce the physical and mental fatigue caused by colorectal cancer by inhibiting inflammatory reaction, promoting hepatic glycogen synthesis, and changing the composition of intestinal microbiota.

scholarly journals Relevance of Regulatory T Cells during Colorectal Cancer Development

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1888 ◽  
Author(s):  
Jonadab E. Olguín ◽  
Itzel Medina-Andrade ◽  
Tonathiu Rodríguez ◽  
Miriam Rodríguez-Sosa ◽  
Luis I. Terrazas
Keyword(s):  
Colorectal Cancer ◽  
Immune Response ◽  
T Cells ◽  
Regulatory T Cells ◽  
Tumor Development ◽  
Treg Cells ◽  
Different Types ◽  
Inflammatory Profile ◽  
The Many ◽  
Effector Immune Response

In recent years, there has been a significant increase in the study of own and foreign human factors favoring the development of different types of cancer, including genetic and environmental ones. However, the fact that the immune response plays a fundamental role in the development of immunity and susceptibility to colorectal cancer (CRC) is much stronger. Among the many cell populations of the immune system that participate in restricting or favoring CRC development, regulatory T cells (Treg) play a major role in orchestrating immunomodulation during CRC. In this review, we established concrete evidence supporting the fact that Treg cells have an important role in the promotion of tumor development during CRC, mediating an increasing suppressive capacity which controls the effector immune response, and generating protection for tumors. Furthermore, Treg cells go through a process called “phenotypic plasticity”, where they co-express transcription factors that promote an inflammatory profile. We reunited evidence that describes the interaction between the different effector populations of the immune response and its modulation by Treg cells adapted to the tumor microenvironment, including the mechanisms used by Treg cells to suppress the protective immune response, as well as the different subpopulations of Treg cells participating in tumor progression, generating susceptibility during CRC development. Finally, we discussed whether Treg cells might or might not be a therapeutic target for an effective reduction in the morbidity and mortality caused by CRC.

Adjuvant chemotherapy with uracil-tegafur (UFT) for stage III colorectal cancer: Final results of randomized trials by the National Surgical Adjuvant Study of Colorectal Cancer (NSAS-CC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4049-4049 ◽  
Author(s):  
T. Hamaguchi ◽  
K. Shirao ◽  
Y. Moriya ◽  
S. Yoshida ◽  
S. Kodaira ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Rectal Cancer ◽  
Colon Cancer ◽  
Adjuvant Chemotherapy ◽  
Hazard Ratio ◽  
Stage Iii ◽  
Control Group ◽  
Significant Difference ◽  
Resected Stage

4049 Background: In the latter 1990s, no consensus was reached as to whether adjuvant chemotherapy was standard treatment for completely resected stage III colorectal cancer in Japan. At that time, we started two randomized controlled trials to clarify the role of adjuvant chemotherapy of stage III colon and rectal cancer in the same time. Methods: Patients with completely resected stage III cancer of the colon or rectum (PS, 0 to 2; age, 20 to 75 years; no other adjuvant therapy) were eligible for these trials. Patients were registered within 6 weeks after surgery and were randomly assigned to receive surgery alone (control group) or surgery followed by treatment with UFT (400 mg/m2/day), given for 5 consecutive days per week for 1 year (UFT group). The target number of patients was 500 for colon cancer and 400 for rectal cancer (hazard ratio = 0.67, one-sided a= 0.05, β= 0.2). The primary endpoint was relapse-free survival (RFS), and the secondary end point was overall survival (OS). Results: Between October 1996 and April 2001, a total of 334 patients with colon cancer and 276 with rectal cancer were enrolled. Four ineligible patients were excluded; data from the remaining 332 patients with colon cancer and 274 with rectal cancer were analyzed. The patients’ characteristics were similar in the groups. Analysis of the results of follow-up until March 2006, at least 5 years after surgery in all patients (median follow-up period, 6.2 years), showed no significant difference in RFS or OS in colon cancer. In rectal cancer, however, RFS and OS were significantly better in the UFT group than in the control group. The only grade 4 toxicity was diarrhea, occurring in 1 patient with colon cancer and 1 patient with rectal cancer. Conclusions: Postoperative adjuvant chemotherapy with UFT is well tolerated and improved RFS and OS in patients with stage III rectal cancer. In colon cancer, the expected benefits were not obtained (hazard ratio = 0.67). [Table: see text] No significant financial relationships to disclose.

scholarly journals The expression and Clinical Significance of miRNA-135a and Bach1 in colorectal cancer

2021 ◽  
Author(s):  
Yang zhi Jiang ◽  
Qing Guo Tao ◽  
fei yan Zhu
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Clinical Information ◽  
Control Group ◽  
Tumor Control ◽  
Cancer Tissue ◽  
Expression Levels ◽  
Real Time Quantitative Pcr ◽  
Normal Tissues ◽  
Cancer Tissues

BACKGROUND AIM To explore the correlation between the expression of miRNA-135a and Bach1 in colorectal cancer tissue and the patient's clinical information.  Methods   60 patients with colorectal carcinoma were treated as a control group. Real-time quantitative PCR assays and immunohistochemistry method were performed to detect the expression of miRNA-135a and Bach1 in 60 colorectal carcinomas and adjacent normal tissues, and the clinical and pathological classifications had also been investigated. The SPSS 19.00 software was used. All data represented mean±SD of three independent experiments. P&lt;0.05 was considered statistically significant. Results  miRNA-135a expression levels increased significantly in the colon cancer tissues compared with the non-tumor control tissues(P&lt;0.01). miRNA-135a expression levels were higher in stage III/IV than in stage I/II colon cancer patients. The expression level of Bach1 in colorectal cancer was significantly lower(P&lt;0.01). Bach1 and miRNA-135a were negatively correlated.  Conclusions:  The levels of miRNA-135a and Bach1 were opposite, the over-expression of miRNA-135a might downregulated the expression of Bach1, which might be involved in the pathogenesis of colorectal cancer.

scholarly journals BSM1 Polymorphism Association in Vitamin D Receptor Genes with the Occurrence of Colorectal Cancer in Palembang, Indonesia

2020 ◽  
Vol 55 (6) ◽  
Author(s):  
M. Alsen Arlan ◽  
Sarup Singh ◽  
Efman E.U. Manawan ◽  
M. Hafidh Komar ◽  
Irsan Saleh
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Vitamin D ◽  
Cancer Patients ◽  
Vitamin D Receptor ◽  
Protective Factor ◽  
Control Group ◽  
Exact Test ◽  
Cancer Occurrence ◽  
Colorectal Cancer Patients

This paper analyzed the association between Bsm1 polymorphism in vitamin D receptor genes with colorectal cancer patients in Palembang, Indonesia. This case control study was conducted from June 2019 to December 2019. The genotype was analyzed using polymerase chain reaction-restriction fragment length polymorphism with the Bsm1 restriction enzyme. Findings showed the distribution of BB-Bb-bb genotype among colorectal cancer patients was 18.6%:26.7%:4.7%, whereas the distribution in a control group was 0%:43%:7%. The distribution of B and b alleles in colorectal cancer patients was 32%:18% compared to the control group’s distribution of 21.5%:28.5%. A statistical analysis of Fisher's exact test was conducted to examine the association of polymorphism with colorectal cancer occurrence. Findings demonstrated that there is a significant association was found between Bsm1 polymorphism of vitamin D receptor genes and colorectal cancer occurrences among patients in Palembang, Indonesia. Detailed analysis revealed that rs1544410 in the genotype BB might be a causal factor for colon cancer occurrence. Allele B on the other hand was reported to be the protective factor against colon cancer.

scholarly journals Research of dynamics of immune response indicators in patients with infectious mononucleosis caused by Epstein-Barr virus

2019 ◽  
Keyword(s):  
Immune Response ◽  
Monoclonal Antibodies ◽  
Infectious Mononucleosis ◽  
Structural Characteristics ◽  
Peripheral Blood Lymphocytes ◽  
Th2 Cells ◽  
Simultaneous Increase ◽  
Control Group ◽  
Barr Virus ◽  
Immune Parameters

Objective. The article is devoted to the study of the content of the main immune parameters in patients with infectious mononucleosis (IM) in the dynamics of the disease. Materials and methods. A clinical examination of IM patients (n = 60) and patients of the control group (n = 20) included the study of complaints, epidemiological history, history of disease and life, objective examination, standard instrumental and laboratory studies in dynamics, detection of EBV DNA in saliva and blood serum, and a comprehensive analysis of immune parameters. The main subpopulations of peripheral blood lymphocytes (CD3 +; CD4 +; CD8 +; CD16 +; CD8 + CD28 +; CD8 + CD28-; CD20 +; CD25 +) were determined by flow laser cytometry on a FACS-Calibur apparatus (USA) using monoclonal antibodies. For identification of INF-γ (Th1-cells), IL-4 (Th2-cells) in the cytoplasm of T-lymphocytes, monoclonal antibodies INF-γ-PC-5, IL-4-PE (eBioscience, Beckman Caulter, R & D System) were used. Results. A comprehensive study of the state of the subpopulations of reacting immune cells revealed significant violations of cellular parts of the immune response compared to the control group. It was established that the immune response in patients with IM during the height of the disease is characterized by an imbalance in the cell link (as evidenced by an increase in the content of CD3+, CD4+, and a simultaneous increase in the content of CD16+, CD25+). In the period of convalescence, violations have been identified that will persist without reaching the levels of the control group in a larger number of IM patients. Conclusion. The results obtained indicate significant changes in the structural characteristics of the cellular immunity system and the multidirectional immune response in IM. The progressive character of changes in immune parameters in IM indicates the formation of a secondary cellular immune imbalance, a change in the balance of immunoregulatory mediators towards the Th2 link during the formation of protracted and chronic forms of EBV-infection.

scholarly journals In Vitro and In Vivo Characterization of Tebipenem (TBP), an Orally Active Carbapenem, against Biothreat Pathogens

2021 ◽  
Author(s):  
Nicholas P. Clayton ◽  
Akash Jain ◽  
Stephanie A. Halasohoris ◽  
Lisa M. Pysz ◽  
Sanae Lembirik ◽  
...  
Keyword(s):  
Survival Rates ◽  
Multidrug Resistant ◽  
Positive Control ◽  
Vehicle Control ◽  
Control Group ◽  
Post Challenge ◽  
Vehicle Control Group ◽  
Tebipenem Pivoxil

Bacillus anthracis and Yersinia pestis, causative pathogens for anthrax and plague, respectively, along with Burkholderia mallei and B. pseudomallei are potential bioterrorism threats. Tebipenem pivoxil hydrobromide (TBP HBr, formerly SPR994), is an orally available prodrug of tebipenem, a carbapenem with activity versus multidrug-resistant (MDR) gram-negative pathogens, including quinolone-resistant and extended-spectrum-β-lactamase-producing Enterobacterales. We evaluated the in vitro activity and in vivo efficacy of tebipenem against biothreat pathogens. Tebipenem was active in vitro against 30-strain diversity sets of B. anthracis, Y. pestis, B. mallei, and B. pseudomallei with minimum inhibitory concentration (MIC) values of 0.001 – 0.008 μg/ml for B. anthracis, ≤0.0005 – 0.03 μg/ml for Y. pestis, 0.25 – 1 μg/ml for B. mallei, and 1 – 4 μg/ml for B. pseudomallei. In a B. anthracis murine model, all control animals died within 52 h post challenge. The survival rates in the groups treated with tebipenem were 75% and 73% when dosed at 12 h and 24 h post challenge, respectively. The survival rates in the positive control groups treated with ciprofloxacin were 75% and when dosed 12 h and 25% when dosed 24 h post challenge, respectively. Survival rates were significantly (p=0.0009) greater in tebipenem groups treated at 12 h and 24 h post challenge and in the ciprofloxacin group 12 h post-challenge vs. the vehicle-control group. For Y. pestis, survival rates for all animals in the tebipenem and ciprofloxacin groups were significantly (p<0.0001) greater than the vehicle-control group. These results support further development of tebipenem for treating biothreat pathogens.

scholarly journals The effect of Lactobacillus johnsonii Ncc533 (La1) on the balance of Th1/Th2 cells in BALB/c mice

2011 ◽  
Vol 34 (4) ◽  
pp. 254 ◽  
Author(s):  
Junli Yang ◽  
Wen Li ◽  
Ruopeng Sun ◽  
Baomin Li
Keyword(s):  
Flow Cytometry ◽  
Immune Response ◽  
Serum Levels ◽  
Treated Group ◽  
Specific Ige ◽  
Th2 Cells ◽  
Control Group ◽  
Lactobacillus Johnsonii ◽  
Asthma Model ◽  
Ifn Γ

Purpose: To determine the effect of Lactobacillus johnsonii Ncc533 (La1) on Th1/Th2 balance, the production of IL-4 and IFN-γ by splenocytes was evaluated following its administration to mice from newborn to adult. Changes in IL-4 and IFN-γ expression and serum levels of OVA-specific-IgE were then investigated in an asthma model. Methods: Using flow cytometry (FCM) and ELISA, the percentage of IL-4 and IFN-γ expressing splenocytes and serum levels of OVA-specific-IgE were measured in different groups of mice. Results: The percentages of IL-4 and IFN-γ expressing splenocytes in the offspring and in the adults of the La1-treated group were not significantly different when compared with the water-treated group. In the asthma model, the percentages of IL-4 expressing cells and the serum levels of OVA-specific-IgE in the La1-treated and water-treated group were significantly increased compared with those in the control group. The percentage of IFN-γ expressing cells was significantly lower in the La1-treated and water-treated groups. The percentage of IL-4 expressing cells and the serum levels of OVA-specific-IgE in the La1-treated group were significantly lower compared with those in the water-treated group, whereas the percentage of IFN-γ expressing cells was significantly higher. Conclusion: Administration of La1 had no effect on the immune system from the neonate to the adult in the normal mice. It did, however, significantly alter the percentages of IL-4 or IFN-γ expressing CD4+ T lymphocytes in the asthma model, suggesting that administration of La1 might regulate the immune response.

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