scholarly journals Polydatin Encapsulated Poly [Lactic-co-glycolic acid] Nanoformulation Counteract the 7,12-Dimethylbenz[a] Anthracene Mediated Experimental Carcinogenesis through the Inhibition of Cell Proliferation

Antioxidants ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 375 ◽  
Author(s):  
Sankaran Vijayalakshmi ◽  
Arokia Vijaya Anand Mariadoss ◽  
Vinayagam Ramachandran ◽  
Vijayakumar Shalini ◽  
Balupillai Agilan ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Phase I ◽  
Phase Ii ◽  
Glycolic Acid ◽  
Liquid Paraffin ◽  
Tumor Burden ◽  
Tumor Formation ◽  
Dimethyl Benzyl ◽  
The Status ◽  
Induced Apoptosis

In the present study, the authors have attempted to fabricate Polydatin encapsulated Poly [lactic-co-glycolic acid] (POL-PLGA-NPs) to counteract 7,12-dimethyl benzyl anthracene (DMBA) promoted buccal pouch carcinogenesis in experimental animals. The bio-formulated POL-PLGA-NPs were characterized by dynamic light scattering (DLS), Fourier transform infrared (FTIR) spectroscopy, X-ray powder diffraction (XRD) pattern analysis, and transmission electron microscope (TEM). In addition, the nano-chemopreventive potential of POL-PLGA-NPs was assessed by scrutinizing the neoplastic incidence and analyzing the status of lipid peroxidation, antioxidants, phase I, phase II detoxification status, and histopathological changes and in DMBA-treated animals. In golden Syrian hamsters, oral squamous cell carcinoma (OSCC) was generated by painting with 0.5% DMBA in liquid paraffin three times a week for 14 weeks. After 100% tumor formation was observed, high tumor volume, tumor burden, and altered levels of biochemical status were observed in the DMBA-painted hamsters. Intra-gastric administration of varying concentration of POL-PLGA-NPs (7.5, 15, and 30 mg/kg b.wt) to DMBA-treated hamsters assumedly prevents oncological incidences and restores the status of the biochemical markers. It also significantly enhances the apoptotic associated and inhibits the cancer cell proliferative markers expression (p53, Bax, Bcl-2, cleaved caspase 3, cyclin-D1). The present study reveals that POL-PLGA-NPs is a penitential candidate for nano-chemopreventive, anti-lipid peroxidative, and antioxidant potential, and also has a modulating effect on the phase I and Phase II detoxification system, which is associated with reduced cell proliferation and induced apoptosis in experimental oral carcinogenesis.

scholarly journals Effects of Combination of Anti-CTLA-4 and Anti-PD-1 on Gastric Cancer Cells Proliferation, Apoptosis and Metastasis

2018 ◽  
Vol 49 (1) ◽  
pp. 260-270 ◽  
Author(s):  
Bin Wang ◽  
Lei Qin ◽  
Mei Ren ◽  
Hao Sun
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Combination Therapy ◽  
Tumor Formation ◽  
Migration And Invasion ◽  
Signal Pathways ◽  
Mrna Levels ◽  
Mesenchymal Transition ◽  
Induced Apoptosis

Background/Aims: Gastric cancer (GC) is one of the most common and lethal varieties of cancers. Anticancer activities of anti-CTLA-4 and anti-PD-1 antibodies have been explored in different cancers, including GC. The study aimed to explore the role of combination therapy with anti-CTLA-4 and anti-PD-1 antibodies in GC cells, and understand the possible underlying molecular mechanism. Methods: MKN-45 and MGC-803 cells were divided into four groups, namely control, CTLA-4, PD-1, and CTLA-4&PD-1. Cell viability, cell cycle, apoptosis, migration and invasion were measured by MTT, flow cytometry, and transwell assays, respectively. Expression levels of different mRNAs and proteins associated with apoptosis, epithelial mesenchymal transition (EMT), β-catenin, MAPK, and PI3K/AKT pathways were assessed by RT-qPCR and western blot analysis, respectively. The tumor formation in vivo was examined by tumor Xenograft model assay. Results: Combination with anti-CTLA-4 and anti-PD-1 antibodies significantly suppressed cell proliferation, induced apoptosis, as well as inhibited migration, invasion, and EMT in MKN-45 and MGC-803 cells. Western blotting revealed that combination with anti-CTLA-4 and anti-PD-1 antibodies declined the activation of β-catenin, MAPK and PI3K/AKT signal pathways. Moreover, combination of anti-CTLA-4 and anti-PD-1 antibodies inhibited tumor formation in vivo. Furthermore, the mRNA levels of CTLA-4 and PD-1 were significantly decreased in si-CTLA and si-PD-1 transfected cells, and combination with si-CTLA and si-PD-1 also suppressed cell proliferation, migration, invasion, EMT and induced apoptosis in MKN-45 cells. Conclusion: Combination therapy with anti-CTLA-4 and anti-PD-1 antibodies presented the promising outcomes in GC, although further investigations are warranted.

Enicostemma littorale prevents tumor formation in 7,12-dimethylbenz(a)anthracene-induced hamster buccal pouch carcinogenesis

2015 ◽  
Vol 34 (9) ◽  
pp. 911-921 ◽  
Author(s):  
D Rajasekaran ◽  
S Manoharan ◽  
MM Prabhakar ◽  
A Manimaran
Keyword(s):  
Lipid Peroxidation ◽  
Oral Cancer ◽  
Phase I ◽  
Ethanolic Extract ◽  
Thiobarbituric Acid ◽  
Tumor Burden ◽  
Tumor Formation ◽  
Oral Carcinogenesis ◽  
Hamster Buccal Pouch ◽  
Enicostemma Littorale

Oral cancer is one of the most common malignancies worldwide, and India has recorded the highest annual incidence of oral cancer in comparison with other countries. Altered lipid peroxidation and antioxidant status along with defect in detoxification cascade have been implicated in the pathogenesis of several cancers including oral cancer. The aim of this study was to investigate the chemopreventive potential of ethanolic extract of Enicostemma littorale leaves (ElELet) in 7,12-dimethylbenz(a)anthracene (DMBA)-induced hamster buccal pouch carcinogenesis. Oral tumor was developed in the buccal pouches of male golden Syrian hamsters by painting with 0.5% DMBA three times a week for 14 weeks. We observed 100% tumor formation with increase in tumor volume and tumor burden in the hamsters treated with DMBA alone. Imbalance in phase I (cytochrome P450 and cytochrome b5) and phase II (glutathione reductase, glutathione- S-transferase, glutathione, and Deoxythymidine-diaphorase (DT)-diaphorase) detoxification agents and lipid peroxidation by-products (thiobarbituric acid reactive substances) and antioxidant (superoxide dismutase, catalase, glutathione peroxidase, and vitamins E and C) status was noticed in hamsters treated with DMBA alone. Oral administration of ElELet at a dose of 250 mg/kg body weight to hamsters treated with DMBA significantly prevented both precancerous and cancerous lesions in the oral cavity. ElELet modulated the status of phase I and II detoxification agents and antioxidants in favor of the suppression of oral carcinogenesis. This study thus suggests that E. littorale might have inhibited the oral carcinogenesis in DMBA-treated hamsters through its antioxidant potential. The present findings are also substantiated by histological studies during DMBA-induced oral carcinogenesis.

scholarly journals miR-517a is up-regulated in glioma and promotes glioma tumorigenesis in vitro and in vivo

2019 ◽  
Vol 39 (5) ◽  
Author(s):  
Cheng-li Du ◽  
Fei Peng ◽  
Ke-qin Liu
Keyword(s):  
Cell Proliferation ◽  
Glioma Cell ◽  
Migration And Invasion ◽  
Functional Assay ◽  
Normal Brain ◽  
Pathology Classification ◽  
The Status ◽  
Induced Apoptosis

Abstract miR-517a has been reported to act as an oncogenic miRNA in human hepatocellular carcinoma and lung cancer. However, the roles and underlying molecular mechanism of miR-517a in glioma remain unclear. In the present study, the expression of miR-517a in clinical glioma tissues and glioma cell lines was examined by quantitative real-time PCR (qRT-PCR). Transfected with knockdown or forced expression of miR-517a, the effects of miR-517a on cell proliferation, migration, and invasion were detected through in vitro and in vivo tumorigenesis assays. Here, we report that miR-517a expression was up-regulated in glioma tissues when compared with normal brain tissues, and up-regulation of miR-517a level is tightly correlated with the status of pathology classification of glioma. A functional assay found that overexpression of miR-517a in glioma cells markedly promoted or suppressed cell proliferation, colony formation, migration and invasion, respectively. Moreover, we revealed that the knockdown of miR-517a dramatically suppressed glioma cell growth, migration, and invasion in vitro and in vivo. Furthermore, we found that knockdown of miR-517a significantly induced apoptosis. Therefore, miR–517a acts an oncogenic miRNA that promotes tumor progression in glioma, and thus may become a promising therapeutic candidate for glioma.

Phase I study of concurrent motexafin gadolinium (MGd) with radiation therapy for children with newly diagnosed brain stem gliomas (BSG): A Children’s Oncology Group study

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 9014-9014
Author(s):  
K. Bradley ◽  
M. Mehta ◽  
P. Adamson ◽  
M. Ames ◽  
R. Jakacki ◽  
...  
Keyword(s):  
Phase I ◽  
Phase Ii ◽  
Maximum Tolerated Dose ◽  
Volume Of Distribution ◽  
Newly Diagnosed ◽  
Motexafin Gadolinium ◽  
Mri Scans ◽  
Recommended Phase Ii Dose ◽  
Induced Apoptosis ◽  
Involved Field

9014 Background: MGd, a radiosensitizer that selectively accumulates in tumors, generates reactive oxygen species intracellularly. In preclinical experiments, MGd enhances RT-induced apoptosis. Methods: A multi-institutional Phase I dose escalation and pharmacokinetic (PK) study was performed in children with newly diagnosed BSG to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT) of MGd administered i.v. 2 to 5 hours prior to involved field radiotherapy (RT) (1.8 Gy/day, total 54 Gy). Cohort 1 received MGd, 1.7 mg/kg/dose M-F × 3 wks and cohort 2 received the same dose M, W and F × 6 wks. The 6 subsequent cohorts of 3 to 6 pts received MGd M-F × 6 weeks at doses of 1.9, 3.4, 4.4, 5.5, 7.1 and 9.2 mg/kg/dose. Serum for PK analysis, and MRI scans (MGd is detectable by MR), were obtained for analysis of drug accumulation and responses. Results: 44 pts (42 fully evaluable for toxicity) with a median age of 6 years (range 2–20) were enrolled. At the 9.2 mg/kg/dose, 2/2 pts experienced DLT. During subsequent expansion of the 7.1 and 5.5 mg/kg/dose cohorts, DLTs, including transaminitis, hypertension and urticaria, were observed in 2/5 and 2/6 pts. At the MTD of 4.4 mg/kg/dose, 1/6 pts had reversible grade 3 serum transaminase elevations. PK analysis showed biphasic elimination with a terminal t 1/2 of 6.4 h. At the MTD, serum MGd concentrations were >250 ng/ml for 24 h. Serum clearance and steady-state volume of distribution were 0.0243 L/h/kg and 0.162 L/kg. MRI for intra-tumoral MGd distribution is ongoing. One patient had a CR and 4 had a PR. The estimated median survival is 10.3 months (95% confidence interval: 8.1 months-11.5 months). Conclusions: The recommended phase II dose of MGd for children with BSG is 4.4 mg/kg/d administered M-F × 6 weeks with involved field RT. A COG phase II trial is planned. [Table: see text]

Bewegungstherapie und körperliche Aktivität bei Patienten mit Herzinsuffizienz

Praxis ◽  
2018 ◽  
Vol 107 (17-18) ◽  
pp. 951-958 ◽  
Author(s):  
Matthias Wilhelm
Keyword(s):  
Phase I ◽  
Phase Ii ◽  
Körperliche Aktivität ◽  
Phase Iii

Zusammenfassung. Herzinsuffizienz ist ein klinisches Syndrom mit unterschiedlichen Ätiologien und Phänotypen. Die überwachte Bewegungstherapie und individuelle körperliche Aktivität ist bei allen Formen eine Klasse-IA-Empfehlung in aktuellen Leitlinien. Eine Bewegungstherapie kann unmittelbar nach Stabilisierung einer akuten Herzinsuffizienz im Spital begonnen werden (Phase I). Sie kann nach Entlassung in einem stationären oder ambulanten Präventions- und Rehabilitationsprogramm fortgesetzt werden (Phase II). Typische Elemente sind Ausdauer-, Kraft- und Atemtraining. Die Kosten werden von der Krankenversicherung für drei bis sechs Monate übernommen. In erfahrenen Zentren können auch Patienten mit implantierten Defibrillatoren oder linksventrikulären Unterstützungssystemen trainieren. Wichtiges Ziel der Phase II ist neben muskulärer Rekonditionierung auch die Steigerung der Gesundheitskompetenz, um die Langzeit-Adhärenz bezüglich körperlicher Aktivität zu verbessern. In Phase III bieten Herzgruppen Unterstützung.

Panax Notoginseng Saponins Promote Cell Death and Chemosensitivity in Pancreatic Cancer through the Apoptosis and Autophagy Pathways

2020 ◽  
Vol 20 ◽  
Author(s):  
Li-Chao Yao ◽  
Lun Wu ◽  
Wei Wang ◽  
Lu-Lu Zhai ◽  
Lin Ye ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Panax Notoginseng ◽  
Panax Notoginseng Saponins ◽  
Transwell Assay ◽  
Pancreatic Cancer Cells ◽  
New Strategy ◽  
Induced Apoptosis ◽  
Promote Cell Death

Background:: Panax Notoginseng Saponins (PNS) is used as traditional Chinese medicine for ischemic stroke and cardiovascular disease, it has been proven to possess anticancer activity recently. Objective:: In this study, we aimed to explore the anticancer curative effect and potential mechanisms of PNS in pancreatic cancer cells. Methods:: Pancreatic cancer Miapaca2 and PANC-1 cells were treated with PNS and Gemcitabine (Gem), respectively. Then the cell viability was assessed by CCK-8 assay, cell proliferation was tested by colony formation assay and EdU cell proliferation assay, cell migration and invasiveness were tested by wound healing assay and transwell assay respectively, and cell apoptosis was detected by flow cytometry. Finally, we detected the expression levels of proteins related to migration, apoptosis and autophagy through Western blotting. Results:: PNS not only inhibited the proliferation, migration, invasion and autophagy of Miapaca2 and PANC-1 cells, but also induced apoptosis and promoted chemosensitivity of pancreatic cancer cells to Gem. Conclusion:: PNS may exhibit cytotoxicity and increase chemosensitivity of pancreatic cancer cells to Gem by inhibiting autophagy and inducing apoptosis, providing a new strategy and potential treatment option for pancreatic cancer.

How to Make COVID-19 Contact Tracing Apps work: Insights from Behavioral Economics (Preprint)

2021 ◽  
Author(s):  
Ian Ayres ◽  
Alessandro Romano ◽  
Chiara Sotis
Keyword(s):  
Phase I ◽  
Phase Ii ◽  
Network Effects ◽  
Risky Behaviors ◽  
Contact Tracing ◽  
Risk Compensation ◽  
Main Function ◽  
Double Blind ◽  
Compensation Theory ◽  
Pros And Cons

BACKGROUND Due to network effects, Contact Tracing Apps (CTAs) are only effective if many people download them. However, the response to CTAs has been tepid. For example, in France less than 2 million people (roughly 3% of the population) downloaded the CTA. Consequently, CTAs need to be fundamentally rethought to increase their effectiveness. OBJECTIVE This study aimed to show that CTAs can still play a key role in containing the pandemic, provided that they take into account insights from behavioral sciences. Moreover, we study whether emphasizing the virtues of CTA to induce people to download them makes app users engage in more risky behaviors (risk compensation theory) and whether feedback on a user’s behavior affects future behaviors. METHODS We perform a double-blind online experiment (n=1500) divided in two phases. In Phase I respondents are randomly assigned to one of three different groups: Pros of the app, Pros and Cons of the app and Control I. Respondents in the Pros group were shown information on the advantages of CTAs. Participants in the Pros and Cons group were shown information on both the advantages and the problems that characterize CTAs. Last, respondents in the Control I group were not given any information on CTAs. All participants are then asked how worried they are about the pandemic, how likely they are to download the app, and on how they intend to behave (e.g. attend small and large gathering, wear a mask, etc.). A week later we carried out Phase II. Participants in Phase II were randomly assigned to different in-app notifications in which they were informed on how much risk they were taking compared to the average user. We then ask participants their intentions for future behaviors to investigate whether these notifications were effective in making respondents more prudent. RESULTS All 1500 participants completed phase I of the experiment, whereas 1303 (86.9%) completed also phase 2. The main findings are: i) informing people on the pros of the app make them less worried about the pandemic (p=.004), ii) informing people about both the pros and the cons of the app makes them more likely to download the app (p=.07); iii) carefully devised in-app notification induce people to state that they will: attend less large gatherings (p= .05) and less small gatherings (p= .001), see less people at risk (p=.004), that they stay more at home (p=.006) and wear more often the mask (p=.09). We do not find support for the risk-compensation theory. CONCLUSIONS we suggest that CTAs should be re-framed as Behavioral Feedback Apps (BFAs). The main function of BFAs would be providing users with information on how to minimize the risk of contracting COVID-19, e.g. to provide information on how crowded a store is likely to be at a given time of the day. Moreover, the BFA could have a rating system that allows users to flag stores that do not respect safety norms, such as mandating customers to wear a mask or not respecting social distancing. These functions can inform the behavior of app users, thus playing a key role in containing the spread of the virus even if a small percentage of people download the BFA. While effective contact tracing is impossible when only 3% of the population downloads the app, less risk taking by small portions of the population can produce large benefits. BFAs can be programmed so that users can also activate a tracing function akin to the one currently carried out by CTAs. Making contact tracing an ancillary, opt-in function might facilitate a wider acceptance of BFAs.

scholarly journals The Effect of Hispidulin, a Flavonoid from Salvia plebeia, on Human Nasopharyngeal Carcinoma CNE-2Z Cell Proliferation, Migration, Invasion, and Apoptosis

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1604
Author(s):  
Yiqun Dai ◽  
Xiaolong Sun ◽  
Bohan Li ◽  
Hui Ma ◽  
Pingping Wu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Nasopharyngeal Carcinoma ◽  
Migration And Invasion ◽  
Dependent Manner ◽  
Etoh Extract ◽  
Tumor Drug Resistance ◽  
Diphenyltetrazolium Bromide ◽  
Scratch Wound ◽  
Low Toxicity ◽  
Induced Apoptosis

Nasopharyngeal carcinoma (NPC) is a common malignant head and neck tumor. Drug resistance and distant metastasis are the predominant cause of treatment failure in NPC patients. Hispidulin is a flavonoid extracted from the bioassay-guided separation of the EtOH extract of Salvia plebeia with strong anti-proliferative activity in nasopharyngeal carcinoma cells (CNE-2Z). In this study, the effects of hispidulin on proliferation, invasion, migration, and apoptosis were investigated in CNE-2Z cells. The [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (MTT) assay and the colony formation assay revealed that hispidulin could inhibit CNE-2Z cell proliferation. Hispidulin (25, 50, 100 μM) also induced apoptosis in a dose-dependent manner in CNE-2Z cells. The expression of Akt was reduced, and the expression of the ratio of Bax/Bcl-2 was increased. In addition, scratch wound and transwell assays proved that hispidulin (6.25, 12.5, 25 μM) could inhibited the migration and invasion in CNE-2Z cells. The expressions of HIF-1α, MMP-9, and MMP-2 were decreased, while the MMPs inhibitor TIMP1 was enhanced by hispidulin. Moreover, hispidulin exhibited potent suppression tumor growth and low toxicity in CNE-2Z cancer-bearing mice at a dosage of 20 mg/kg/day. Thus, hispidulin appears to be a potentially effective agent for NPC treatment.

scholarly journals Analysis of the ex-vivo transformation of semen, saliva and urine as they dry out using ATR-FTIR spectroscopy and chemometric approach

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tanurup Das ◽  
Abhimanyu Harshey ◽  
Ankit Srivastava ◽  
Kriti Nigam ◽  
Vijay Kumar Yadav ◽  
...  
Keyword(s):  
Phase I ◽  
Phase Ii ◽  
Ex Vivo ◽  
Body Fluids ◽  
Biochemical Changes ◽  
Partial Least Square ◽  
The Body ◽  
Slow Phase ◽  
Time Since Deposition ◽  
Dry Out

AbstractThe ex-vivo biochemical changes of different body fluids also referred as aging of fluids are potential marker for the estimation of Time since deposition. Infrared spectroscopy has great potential to reveal the biochemical changes in these fluids as previously reported by several researchers. The present study is focused to analyze the spectral changes in the ATR-FTIR spectra of three body fluids, commonly encountered in violent crimes i.e., semen, saliva, and urine as they dry out. The whole analytical timeline is divided into relatively slow phase I due to the major contribution of water and faster Phase II due to significant evaporation of water. Two spectral regions i.e., 3200–3400 cm−1 and 1600–1000 cm−1 are the major contributors to the spectra of these fluids. Several peaks in the spectral region between 1600 and 1000 cm−1 showed highly significant regression equation with a higher coefficient of determination values in Phase II in contrary to the slow passing Phase I. Principal component and Partial Least Square Regression analysis are the two chemometric tool used to estimate the time since deposition of the aforesaid fluids as they dry out. Additionally, this study potentially estimates the time since deposition of an offense from the aging of the body fluids at the early stages after its occurrence as well as works as the precursor for further studies on an extended timeframe.

scholarly journals Detoxification of the tricyclic antidepressant opipramol and its analog – IS-noh by UGT enzymes before and after activation by phase I enzymes in rat liver microsomes

2021 ◽  
Author(s):  
Anna Mieszkowska ◽  
Koleta Hemine ◽  
Anna Skwierawska ◽  
Ewa Augustin ◽  
Zofia Mazerska
Keyword(s):  
Phase I ◽  
Rat Liver ◽  
Phase Ii ◽  
Oxidation Product ◽  
Liver Microsomes ◽  
Correct Selection ◽  
Rat Liver Microsomes ◽  
Recombinant Enzymes ◽  
Data Set ◽  
Phase I Enzymes

AbstractThe present studies were carried out to evaluate the simultaneous one-pot metabolism of opipramol (IS-opi) and analog (IS-noh) by phase I and phase II enzymes present in rat liver microsomes (RLM) as an alternative to separate testing with recombinant enzymes. This approach allows for more time-saving and cost-effective screening of the metabolism of newly discovered drugs. We also considered that the lack of results for phase II, including UGT, often creates problems in correct selection of valuable compounds. Moreover, microsomes data set is richer in the contest and provides medical scientist to determine also the susceptibility of drugs to undergo phase I and then phase II. In the present work, we have shown that IS-noh was metabolized in vitro by phase I enzymes to the oxidation product, which was next transformed with UGTs to glucuronide. The results showed also that the previously known oxidation product of opipramol was changed to previously no reported glucuronidation product by UDP-glucuronosyltransferases. In addition, unlike IS-noh, opipramol did not prove to be the substrate for UGTs. Therefore, tricyclic antidepressants depending on the structure can trigger a different response after contact with UGT enzymes. Some will metabolize directly with UGTs, others only after activation by phase I enzymes.

Sign in / Sign up

Export Citation Format

Share Document